Zalunfiban for use in the treatment of thrombotic disorder in patients with renal impairment

Abstract

The present disclosure relates to methods for treating or preventing a thrombotic disorder in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof, wherein the subject has renal impairment.

Description

METHODS FOR THE ADMINISTRATION OF ZALUNFIBAN CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority under 35 U.S.C. § 119(e) to U.S. Provisional Application Number 63 / 671,460, filed July 15, 2024, titled METHODS FOR THE ADMINISTRATION OF ZALUNFIBAN, the contents of which are incorporated herewith by reference in their entirety. BACKGROUND OF THE INVENTION

[0002] A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. Worldwide, about 15.9 million myocardial infarctions occurred in 2015 in developed countries, and more than 3 million people had an ST elevation MI (STEMI). Of the people who die from MI, about half die within an hour of their first symptoms, and before they can reach the hospital. There is a direct relationship between the amount of time a heart artery is closed and the severity of the heart attack and odds of survival. Therefore, pre-hospital treatment is critical. In the past 40 years, in-hospital STEMI mortality has declined dramatically, but pre-hospital mortality remains unchanged.

[0003] Oral P2Y12 antagonists administered along with aspirin at the first point of medical care, for example, in an ambulance, are not effective because these agents require several hours to achieve maximal effect in STEMI. Early intravenous administration of glycoprotein IIb / IIIa inhibitors (GPI) improves clinical outcomes but requires an initial bolus administration followed by continuous infusion.

[0004] Since transportation to a care facility such as a hospital can take longer than an hour, there is an urgent need for a rapidly-acting therapy that can be administered to MI patients to achieve high- grade inhibition of platelet function before they reach the care facility. Additionally, in order to reduce the risk of bleeding, it is desirable that the antiplatelet effect of the rapid-onset therapy diminish as the effects of commonly co-administered oral P2Y12 antagonists, such as current standard-of-care therapies, reach their maximal effects.

[0005] Moreover, current small molecule GPIs such as eptifibatide and tirofiban are both substantially excreted unchanged in the urine, necessitating dose adjustments in patients with renal impairment. However, dose adjustments during emergency situations such as MI can pose a challenge, as a medical professional needs to assess whether there is renal impairment, which is made more difficult if the patient is non-responsive or outside a hospital setting (e.g., in an ambulance). SUMMARY OF THE INVENTION

[0006] Zalunfiban (RUC-4) is an inhibitor of the platelet αIIbβ3 receptor (i.e., glycoprotein IIb / IIIa) and is described in United States patent number 9,303,044, which is incorporated herein by reference.C1519.70003WO00 1 / 69 #14198807v1Mechanistically, zalunfiban is believed to inhibit ligand binding to αIIbβ3 by binding to both the αIIb and β3 subunits and displacing the Mg2+ metal from the ion-dependent adhesion site (MIDAS) required for ligand binding; this locks the β3 subunit of the receptor in its inactive conformation. This may reduce the likelihood of thrombocytopenia, because data indicate that much of the thrombocytopenia caused by the current αIIbβ3 antagonists (i.e., glycoprotein IIb / IIIa inhibitors) is due to the presence of antibodies that bind to conformations of the receptor induced by the binding of the drugs. Thrombocytopenia is one of the potentially dangerous side effects of all current agents (~0.5-2%). Zalunfiban may also exhibit enhanced efficacy relative to blood thinners such as eptifibatide and tirofiban, which induce a high-affinity binding conformation that may result in ligand binding and platelet aggregation as the drug levels decline.

[0007] Zalunfiban is being developed for prehospital STEMI treatment. The present disclosure stems from the unexpected discoveries that zalunfiban is rapidly metabolized in humans to Des-Gly zalunfiban, which has minimal antiplatelet activity and is excreted via renal and hepatic routes, and that only very small amounts of unchanged zalunfiban are excreted in urine. Thus, the inventors posit that zalunfiban may be suitable for administration to patients with impaired renal function without renal function-based dose adjustment.

[0008] Accordingly, in one aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein: the subject has renal impairment, and the therapeutically effective amount is the same amount that would be administered to a subject in need thereof with normal renal function.

[0009] In another aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof, the method comprising: administering to the subject in need thereof a first dose comprising a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; subsequently determining that the subject has renal impairment; and administering to the subject in need thereof a second dose comprising the same therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof.

[0010] In another aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein the method does not produce a zalunfiban Cmaxgreater than 1.7 times the zalunfiban Cmaxproduced in a subject with normal renal function.C1519.70003WO00 2 / 69 #14198807v1

[0011] In another aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein the method does not produce a zalunfiban AUC0-t greater than 1.7 times the zalunfiban AUC0-tproduced in a subject with normal renal function.

[0012] In another aspect, provided herein is, in a method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof, the improvement comprising; administering the same amount of zalunfiban, or pharmaceutically acceptable salt thereof, to the subject in need thereof with renal impairment that would be administered to a subject in need thereof with normal renal function.

[0013] It should be appreciated that the foregoing concepts, and the additional concepts discussed below, may be arranged in any suitable combination, as the present disclosure is not limited in this respect. Further, other advantages and novel features of the present disclosure will become apparent from the following detailed description of various non-limiting embodiments when considered in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG.1 shows the mean cumulative percent recovery in urine and feces following a single subcutaneous dose of 9.5 mg / 5 µCi [14C]-zalunfiban.

[0015] FIG.2 shows concentrations of zalunfiban and total14C in whole blood following a single subcutaneous dose of 9.5 mg / 5 µCi [14C]-zalunfiban.

[0016] FIG.3 shows cumulative mean dose recovery of zalunfiban, des-gly-zalunfiban, and total radioactivity, by analyte and route of elimination. Collection times: zalunfiban and des-gly-zalunfiban urine (0-48 hour), feces (0-192 hour), total radioactivity (0-240 hour).

[0017] FIG.4 shows metabolic conversion of zalunfiban to des-gly-zalunfiban. DEFINITIONS

[0018] Unless otherwise specified, the terms “administer,” “administering,” or “administration” refers to implanting, absorbing, ingesting, injecting, inhaling, or otherwise introducing a compound described herein, or a composition thereof, in or on a subject.

[0019] The terms “condition,” “disease,” and “disorder” may be used interchangeably.

[0020] An “effective amount” of a compound, or a pharmaceutically acceptable salt thereof, described herein refers to an amount sufficient to elicit the desired biological response. An effective amount of a compound described herein may vary depending on such factors as the desired biologicalC1519.70003WO00 3 / 69 #14198807v1endpoint, severity of side effects, disease, or disorder, the identity, pharmacokinetics, and pharmacodynamics of the particular compound, the condition being treated, the mode, route, and desired or required frequency of administration, the species, age and health or general condition of the subject. In certain embodiments, an effective amount is a therapeutically effective amount. In certain embodiments, an effective amount is a prophylactic treatment. In certain embodiments, an effective amount is the amount of a compound described herein in a single dose. In certain embodiments, an effective amount is the combined amounts of a compound described herein in multiple doses. In certain embodiments, the desired dosage is delivered three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage is delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations).

[0021] “Pharmaceutically acceptable” means that which is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable and includes that which is acceptable for veterinary use as well as human pharmaceutical use.

[0022] As used herein, the term “salt” refers to any and all salts, and encompasses pharmaceutically acceptable salts. Salts include ionic compounds that result from the neutralization reaction of an acid and a base. A salt is composed of one or more cations (positively charged ions) and one or more anions (negative ions) so that the salt is electrically neutral (without a net charge). For instance, a salt may be composed of a dication (an ion with +2 charge) and two anions, each with a –1 charge, wherein the anions are the same or different. References to a salt of a compound (e.g., zalunfiban), can refer to a single salt of the compound, or a mixture of salts of the compound. Salts of the compounds of the present disclosure include those derived from inorganic and organic acids and bases. Examples of acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2–hydroxy–ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2–naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3–phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, hippurate, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N+(C1–4alkyl)4salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further salts includeC1519.70003WO00 4 / 69 #14198807v1ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate.

[0023] The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and non-human animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2- hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N+(C1-4 alkyl)4−salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate.

[0024] A “subject” to which administration is contemplated refers to a human (i.e., male or female of any age group, e.g., pediatric subject (e.g., infant, child, or adolescent) or adult subject (e.g., young adult, middle-aged adult, or senior adult)) or non-human animal. In certain embodiments, the non- human animal is a mammal (e.g., primate (e.g., cynomolgus monkey or rhesus monkey), commercially relevant mammal (e.g., cattle, pig, horse, sheep, goat, cat, or dog), or bird (e.g., commercially relevant bird, such as chicken, duck, goose, or turkey)). In certain embodiments, the non-human animal is a fish, reptile, or amphibian. The non-human animal may be a male or female at any stage of development. The non-human animal may be a transgenic animal or genetically engineered animal. The term “patient” refers to a human subject in need of treatment of a disease.C1519.70003WO00 5 / 69 #14198807v1

[0025] The terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, or inhibiting the progress of a disease or condition described herein. In some embodiments, treatment may be administered after one or more signs or symptoms of the disease have developed or have been observed. In other embodiments, treatment may be administered in the absence of signs or symptoms of the disease. For example, treatment may be administered to a susceptible subject prior to the onset of symptoms (e.g., in light of a history of symptoms and / or in light of exposure to a pathogen). Treatment may also be continued after symptoms have resolved, for example, to delay or prevent recurrence.

[0026] The term “prevent,” “preventing,” or “prevention” refers to a prophylactic treatment of a subject who is not and was not with a disease but is at risk of developing the disease or who was with a disease, is not with the disease, but is at risk of regression of the disease. In certain embodiments, the subject is at a higher risk of developing the disease or at a higher risk of regression of the disease than an average healthy member of a population.

[0027] A “prophylactically effective amount” of a compound described herein is an amount sufficient to prevent a condition, or one or more symptoms associated with the condition or prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the condition. The term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent.

[0028] The term “about X,” where X is a number or percentage, refers to a number or percentage that is between 99.5% and 100.5%, between 99% and 101%, between 98% and 102%, between 97% and 103%, between 96% and 104%, between 95% and 105%, between 92% and 108%, or between 90% and 110%, inclusive, of X.

[0029] The terms “zalunfiban,” “Zalunfiban,” and “RUC-4” refer to 2-amino-N-(5-(5-oxo-7- (piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl)pyridin-3-yl)acetamide:.

[0030] The terms “Des-Gly zalunfiban” and “Des-Gly Zalunfiban” refer to 2-(5-aminopyridin-3-yl)- 7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one:.C1519.70003WO00 6 / 69 #14198807v1DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

[0031] Because of the difficulties associated with determining renal status at the first point of medical care, there is a need for small molecule GPIs, the dosing of which is not dependent on renal function, and methods of use thereof. Such small molecule GPIs and methods would allow for the use during medical emergencies (e.g., treating an MI patient) without concern for the patient’s level of renal sufficiency. Although other small molecule GPIs exist (e.g., eptifibatide and tirofiban), they require dosage adjustment in patients with renal impairment. But particularly during medical emergencies such as MI, there are significant complications associated with improper dosing of a small molecule GPI (e.g., excessive bleeding), but the patient must be treated quickly to prevent death.

[0032] Zalunfiban is being developed for prehospital STEMI treatment. The present disclosure stems from the unexpected discoveries that zalunfiban is rapidly metabolized in humans to Des-Gly zalunfiban, which has minimal antiplatelet activity and is excreted via renal and hepatic routes, and that only very small amounts of unchanged zalunfiban are excreted in urine. Thus, the inventors posit that zalunfiban is suitable for administration to patients with impaired renal function without renal function-based dose adjustment, unlike other small molecule GPIs. This is a significant improvement over existing small molecule GPIs, as may allow for the treatment of patients with impaired renal function (e.g., patients with renal insufficiency or who are receiving dialysis) during medical emergencies without the risks associated with the existing small molecule GPIs (e.g., increased risk of excessive bleeding if dosed improperly, or increased risk of death if not administered soon enough).

[0033] The aspects described herein are not limited to specific embodiments, systems, compositions, methods, or configurations, and as such can, of course, vary. The terminology used herein is for the purpose of describing particular aspects only and, unless specifically defined herein, is not intended to be limiting.

[0034] In one aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein: the subject has renal impairment, and the therapeutically effective amount is the same amount that would be administered to a subject in need thereof with normal renal function.

[0035] In another aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof, the method comprising: administering to the subject in need thereof a first dose comprising a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; subsequently determining that the subject has renal impairment; and administering to the subject in need thereof a second dose comprising the same therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof.C1519.70003WO00 7 / 69 #14198807v1

[0036] In another aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein the method does not produce a zalunfiban Cmax greater than 1.7 times the zalunfiban Cmaxproduced in a subject with normal renal function.

[0037] In another aspect, provided herein is a method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein the method does not produce a zalunfiban AUC0-t greater than 1.7 times the zalunfiban AUC0-t produced in a subject with normal renal function.

[0038] In another aspect, provided herein is, in a method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof, the improvement comprising; administering the same amount of zalunfiban, or pharmaceutically acceptable salt thereof, to the subject in need thereof with renal impairment that would be administered to a subject in need thereof with normal renal function.

[0039] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is administered in the form of a pharmaceutical composition comprising the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, and one or more carriers, diluents, or excipients. Dosage

[0040] As generally used herein, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is defined in terms of the amount of zalunfiban in free (i.e., non-salt) form (also referred to as “zalunfiban free base”). When a numerical criterion modifying the term “therapeutically effective amount” is recited, that numerical criterion refers to the amount of zalunfiban free base, rather than the amount of a pharmaceutically acceptable salt of zalunfiban. For the avoidance of doubt, as an example, a recited therapeutically effective amount of between about 0.09 mg / kg and about 0.15 mg / kg of zalunfiban, or a pharmaceutically acceptable salt thereof, refers to a range of between about 0.09 mg / kg and about 0.15 mg / kg of zalunfiban free base, which would correspond to a range of, e.g., between about 0.104 mg / kg and about 0.173 mg / kg of zalunfiban monoacetate. As an additional example, a recited therapeutically effective amount of between about 6.0 mg and about 12.0 mg of zalunfiban, or a pharmaceutically acceptable salt thereof, refers to aC1519.70003WO00 8 / 69 #14198807v1range of between about 6.0 mg and about 12.0 mg of zalunfiban free base, which would correspond to a range of, e.g., between about 6.93 mg and about 13.86 mg of zalunfiban monoacetate.

[0041] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.01 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.07 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.075 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.08 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.10 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.11 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.15 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.20 mg / kg and about 0.30 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.25 mg / kg and about 0.30 mg / kg.

[0042] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.01 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.07 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.075 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.08 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.10 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.11 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeuticallyC1519.70003WO00 9 / 69 #14198807v1effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.15 mg / kg and about 0.25 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.20 mg / kg and about 0.25 mg / kg.

[0043] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.01 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.07 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.075 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.08 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.10 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.11 mg / kg and about 0.20 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.15 mg / kg and about 0.20 mg / kg.

[0044] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.01 mg / kg and about 0.15 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / kg and about 0.15 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.07 mg / kg and about 0.15 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.075 mg / kg and about 0.15 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.08 mg / kg and about 0.15 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.15 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.10 mg / kg and about 0.15 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.11 mg / kg and about 0.15 mg / kg.C1519.70003WO00 10 / 69 #14198807v1

[0045] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.01 mg / kg and about 0.13 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / kg and about 0.13 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.07 mg / kg and about 0.13 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.075 mg / kg and about 0.13 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.08 mg / kg and about 0.13 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.13 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.10 mg / kg and about 0.13 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.11 mg / kg and about 0.13 mg / kg.

[0046] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / kg and about 0.30 mg / kg, between about 0.07 mg / kg and about 0.25 mg / kg, between about 0.075 mg / kg and about 0.15 mg / kg, between about 0.09 mg / kg and about 0.15 mg / kg, between about 0.10 mg / kg and about 0.15 mg / kg, or between about 0.09 mg / kg and about 0.13 mg / kg.

[0047] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.07 mg / kg and about 0.08 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.08 mg / kg and about 0.09 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.10 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.10 mg / kg and about 0.11 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.11 mg / kg and about 0.12 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.12 mg / kg and about 0.13 mg / kg.

[0048] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.07 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.075 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.08 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is aboutC1519.70003WO00 11 / 69 #14198807v10.085 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.09 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.095 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.10 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.11 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.12 mg / kg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.13 mg / kg.

[0049] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 8.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 9.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 11.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 13.0 mg and about 15.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 14.0 mg and about 15.0 mg.

[0050] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable saltC1519.70003WO00 12 / 69 #14198807v1thereof, is between about 8.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 9.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 11.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12.0 mg and about 14.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 13.0 mg and about 14.0 mg.

[0051] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 8.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 9.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 11.0 mg and about 13.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12.0 mg and about 13.0 mg.

[0052] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 12.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 12.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 12.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 12.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 8.0 mg and about 12.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 9.0 mg and about 12.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10.0 mg and about 12.0 mg. In certainC1519.70003WO00 13 / 69 #14198807v1embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 11.0 mg and about 12.0 mg.

[0053] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 11.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 11.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 11.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 11.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 8.0 mg and about 11.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 9.0 mg and about 11.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10.0 mg and about 11.0 mg.

[0054] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 10.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 10.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 10.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 10.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 8.0 mg and about 10.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 9.0 mg and about 10.0 mg.

[0055] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 9.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 9.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 9.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 9.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 8.0 mg and about 9.0 mg.

[0056] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 8.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable saltC1519.70003WO00 14 / 69 #14198807v1thereof, is between about 5.0 mg and about 8.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 8.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 7.0 mg and about 8.0 mg.

[0057] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 7.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 7.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 7.0 mg.

[0058] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 6.0 mg. In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 6.0 mg.

[0059] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 5.0 mg.

[0060] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 15.0 mg, between about 5.0 mg and about 13.0 mg, or between about 8.0 mg and about 10.0 mg.

[0061] In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a free base form of zalunfiban.

[0062] In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a pharmaceutically acceptable salt of zalunfiban.

[0063] In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of an acetate salt of zalunfiban. In certain embodiments, the acetate salt of zalunfiban is a monoacetate salt. In certain embodiments, the acetate salt of zalunfiban is a diacetate salt.

[0064] In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a hydrochloride salt of zalunfiban. In certain embodiments, the hydrochloride salt of zalunfiban is a monohydrochloride salt. In certain embodiments, the hydrochloride salt of zalunfiban is a dihydrochloride salt.

[0065] In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a mixed acetate and hydrochloride salt of zalunfiban. In certain embodiments, the mixed acetate and hydrochloride salt of zalunfiban is a mixed monoacetate and monohydrochloride salt.

[0066] In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a mixture of pharmaceutically acceptable salts of zalunfiban. InC1519.70003WO00 15 / 69 #14198807v1certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a mixture of acetate and hydrochloride salts of zalunfiban. In certain embodiments, the method comprises administering to the subject in need thereof a therapeutically effective amount of a mixture of monoacetate and monohydrochloride salts of zalunfiban. Dose Selection

[0067] Several factors are considered in connection with dose selection. It is necessary to consistently achieve high grade inhibition of platelet aggregation (e.g., at least 75% or at least 80%) within 15 minutes of administration. It is necessary to minimize the risk of bleeding, particularly in persons of low body weight (e.g., elderly women) who have the highest risk of bleeding. It is also desirable for zalunfiban to persist, e.g., maintain at least 50% inhibition of platelet function, for up to 120 minutes.

[0068] However, the determination of antiplatelet effect attributable to zalunfiban may be confounded by the presence of other antiplatelet agents, such as aspirin, ticagrelor, and αIIbβ3 antagonists other than zalunfiban. Therefore, an assay is required that can differentiate the effects of zalunfiban from those of other antiplatelet agents.

[0069] Light transmission aggregometry (LTA) is considered the gold standard assay to assess the potency of antiplatelet agents, such as Zalunfiban, because of its association with clinical outcomes. Activators such as ADP, iso-TRAP, and Arachidonic Acid (AA) can be used to assess the differential effects of various platelet inhibitors. Zalunfiban dramatically inhibits ADP and AA, whereas aspirin does not significantly inhibit ADP or iso-TRAP induced LTA, and ticagrelor (and other P2Y12 inhibitors) inhibits the ADP induced LTA to various degrees, and slightly inhibits iso-TRAP induced LTA (depending on the dose administered). Addition of ADP + PAR-4 activating peptide completely inhibits the inhibition of platelet aggregation by P2Y12 inhibitors.

[0070] LTA may be difficult to perform during STEMI, as patients are being transported in an ambulance, or are being treated with percutaneous coronary intervention (PCI) in a cardiac catheterization laboratory away from the clinical lab. LTA requires significant manipulation of a blood sample and addition of reagents. As an alternative, rapid platelet function assays like VerifyNow can be used directly, using a blood sample without any manipulation. See, e.g., Joseph A. Jakubowski et al., Platelets, December 2011; 22(8): 619–625.

[0071] VerifyNow (VN) assays (Instrumentation Laboratories, Bedford, MA) are whole-blood, cartridge-based, and automated, and produce results within 15 minutes of blood draw. They are based on the agglutination of fibrinogen-coated beads by platelets activated by different agonists. Commercially available VN assays are designed to study the antiplatelet effects of aspirin (VN Aspirin cartridge; arachidonic acid activator) or P2Y12 antagonists (VN PRUTest cartridge and VN P2Y12 cartridge; ADP+PGE1 activator / inhibitor combination). The modified thrombin receptorC1519.70003WO00 16 / 69 #14198807v1activating peptide (iso-TRAP) is included in a separate reaction chamber (in addition to the ADP+PGE1 reaction chamber) in both the PRUTest and P2Y12 cartridges, and the P2Y12 cartridges further include a ‘BASE channel’ reaction chamber in which a PAR-1 activating peptide( iso-TRAP) at higher concentrations is combined with a PAR-4 activating peptide (PAR-4 AP) to achieve potent activation that can overcome the effects of P2Y12 antagonists.

[0072] VerifyNow ADP+PGE1, iso-TRAP, and base channel assays may be used to report zalunfiban-mediated inhibition in near real-time. VN assays can be used to help deconvolute antiplatelet effects of αIIbβ3 antagonists versus P2Y12 antagonists. Zalunfiban dramatically inhibits all 3 VN assays, whereas aspirin does not inhibit the assays, and ticagrelor dramatically inhibits the ADP+PGE1 assay, slightly inhibits the iso-TRAP assay, and does not inhibit the base channel assay. The BASE channel assay can be used to monitor the pharmacodynamic effects of zalunfiban independent of any P2Y12 inhibitors. Patient Populations

[0073] The term “level of renal sufficiency” refers to the level of renal (kidney) function in an individual. The levels of renal sufficiency in an individual include: no renal impairment, mild renal impairment, moderate renal impairment, severe renal impairment and end stage renal disease (ESRD).

[0074] The term “renal impairment” includes mild renal impairment, moderate renal impairment, severe renal impairment and end stage renal disease (ESRD).

[0075] The terms a “subject having renal impairment,” a “subject in need thereof having renal impairment,” a “renally impaired subject,” and the like refer to a subject having mild renal impairment, moderate renal impairment, or severe renal impairment, or a subject having end-stage renal disease (ESRD).

[0076] Different thresholds or cutoffs can be used to determine the level of renal sufficiency in an individual depending on the technique used and the interpretation of the health care practitioner. Several variables can be considered when determining the level of renal sufficiency in an individual including, for example, whether an individual is obese, the individual's race, the individual's gender, and the individual's age. Recommendations regarding classification of renal sufficiency are known in the art. These recommendations may change over time as newer techniques or better equations are used to more accurately determine renal function in an individual. For example, a patient with mild to moderate renal impairment may have a creatinine clearance rate of 30-90 mL / min. On the other hand, a patient with severe renal impairment may have a creatinine clearance rate of <30 mL / min.

[0077] In certain embodiments, the Cockcroft-Gault equation is used to determine the renal status of the subject. In certain embodiments, the subject with severe renal impairment has a creatinine clearance rate of 15 to 29 mL / minute using the Cockcroft-Gault equation. In certain embodiments, the subject with mild, moderate or severe renal impairment has a creatinine clearance rate of 15 to 90 mL / minute using the Cockcroft-Gault equation. In certain embodiments, the subject with mild orC1519.70003WO00 17 / 69 #14198807v1moderate renal impairment has a creatinine clearance rate of 30 to 90 mL / minute using the Cockcroft- Gault equation. The Cockcroft-Gault equation is CrCL={[(140−Age)×WT] / Scr} where CrCL is creatinine clearance (ml / min), age is in years, WT is actual body weight (kg), and Scr is serum creatinine (mg / dl); for female subjects the value is multiplied by a factor of 0.85.

[0078] In certain embodiments, the subject's serum creatinine concentration is used to determine the level of renal sufficiency of the subject. In certain embodiments, the subject with severe renal impairment has an approximate serum creatinine concentration of: less than 4.9 mg / dL for an 18-20 year old man, less than 3.5 mg / dL for an 18-20 year old woman, less than 4.5 mg / dL for a 21-30 year old man, less than 3.2 mg / dL for a 21-30 year old woman, less than 4.1 mg / dL for a 31-40 year old man, less than 2.9 mg / dL for a 31-40 year old woman, less than 2.7 mg / dL for a 41-50 year old woman, less than 3.3 mg / dL for a 51-60 year old man, less than 2.4 mg / dL for a 51-60 year old woman, less than 3.0 mg / dL for a man over 60 years old, or less than 2.0 mg / dL for a woman over 60 years old.

[0079] In certain embodiments, the renal status of the subject may be determined by measuring the “estimated glomerular filtration rate” or “eGFR” of the individual. The eGFR in mL / min / 1.73 m2is calculated by the Modification of Diet in Renal Disease [MDRD] equation: (eGFR in mL / min) / 1.73 m2=175×(serum creatinine in mg / dL)−1.154×Age−0.203×0.742 (if female)×1.212 (if black).

[0080] Further details regarding the calculation of the eGFR may be found in, e.g., Levey A S, Coresh J, Greene T, Marsh J, Stevens L A, Kusek J W, Van Lente F: Chronic Kidney Disease Epidemiology Collaboration. Expressing the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate with Standardized Serum Creatinine Values. Ann Intern Med.2009;150(9):604-12.

[0081] Renal impairment status based on Food and Drug Administration (FDA) guidance is as follows: Normal (i.e., no renal impairment): eGFR ≥ 90 mL / min / 1.73 m2; Mild renal impairment: eGFR 60-89 mL / min / 1.73 m2(i.e., ≥ 60 mL / min / 1.73 m2and < 90 mL / min / 1.73 m2); Moderate renal impairment: eGFR 30-59 mL / min / 1.73 m2(i.e., ≥ 30 mL / min / 1.73 m2and < 60 mL / min / 1.73 m2); Severe renal impairment: eGFR 15-29 mL / min / 1.73 m2(i.e., ≥ 15 mL / min / 1.73 m2and < 30 mL / min / 1.73 m2) and not on hemodialysis; End-stage renal disease (ESRD): eGFR < 15 mL / min / 1.73 m2and not on hemodialysis or on hemodialysis. See Pharmacokinetics in Patients with Impaired Renal Function—Study Design, Data Analysis, and Impact on Dosing Guidance for Industry. U.S. Department of Health and Human Services Food andC1519.70003WO00 18 / 69 #14198807v1Drug Administration Center for Drug Evaluation and Research (CDER) March 2024 Clinical Pharmacology.

[0082] In certain embodiments, the subject has mild renal impairment. In certain embodiments, the subject has mild renal impairment and is not on chronic dialysis. In certain embodiments, the subject has a creatinine clearance of ≥ 60 mL / min and < 90 mL / min. In certain embodiments, the subject has an estimated glomerular filtration rate (eGFR) of ≥ 60 mL / min / 1.73 m2and < 90 mL / min / 1.73 m2.

[0083] In certain embodiments, the subject has moderate renal impairment. In certain embodiments, the subject has moderate renal impairment and is not on chronic dialysis. In certain embodiments, the subject has a creatinine clearance of ≥ 30 mL / min and < 60 mL / min. In certain embodiments, the subject has an estimated glomerular filtration rate (eGFR) of ≥ 30 mL / min / 1.73 m2and < 60 mL / min / 1.73 m2.

[0084] In certain embodiments, the subject has severe renal impairment. In certain embodiments, the subject has severe renal impairment and is not on chronic dialysis. In certain embodiments, the subject has a creatinine clearance of ≥ 15 mL / min and < 30 mL / min. In certain embodiments, the subject has an estimated glomerular filtration rate (eGFR) of ≥ 15 mL / min / 1.73 m2and < 30 mL / min / 1.73 m2.

[0085] In certain embodiments, the subject has end-stage renal disease (ESRD). In certain embodiments, the subject has ESRD and is not on chronic dialysis. In certain embodiments, the subject has ESRD and is on chronic dialysis. In certain embodiments, the subject has a creatinine clearance of < 15 mL / min. In certain embodiments, the subject has an estimated glomerular filtration rate (eGFR) of < 15 mL / min / 1.73 m2.

[0086] In certain embodiments, the subject has a high risk of bleeding. In certain embodiments, the subject has a low body weight. In certain embodiments, the subject has a high risk of bleeding and a low body weight. In certain embodiments, the subject is an elderly person. In certain embodiments, the subject is an elderly woman.

[0087] In certain embodiments, an exposure of zalunfiban and its metabolite Des-Gly zalunfiban in the subject with renal impairment is substantially similar to an exposure of zalunfiban and its metabolite Des-Gly zalunfiban in the subject with normal renal function.

[0088] In certain embodiments, the zalunfiban does not undergo primary renal clearance.

[0089] In certain embodiments, the method produces a zalunfiban Cmaxof between about 92 ng / mL and about 152 ng / mL, between about 92 ng / mL and about 146 ng / mL, between about 92 ng / mL and about 140 ng / mL, between about 92 ng / mL and about 134 ng / mL, between about 92 ng / mL and about 128 ng / mL, between about 92 ng / mL and about 122 ng / mL, between about 92 ng / mL and about 116 ng / mL, between about 92 ng / mL and about 110 ng / mL, between about 92 ng / mL and about 104 ng / mL, between about 92 ng / mL and about 98 ng / mL, between about 98 ng / mL and about 152 ng / mL, between about 98 ng / mL and about 146 ng / mL, between about 98 ng / mL and about 140 ng / mL, between about 98 ng / mL and about 134 ng / mL, between about 98 ng / mL and about 128 ng / mL,C1519.70003WO00 19 / 69 #14198807v1between about 98 ng / mL and about 122 ng / mL, between about 98 ng / mL and about 116 ng / mL, between about 98 ng / mL and about 110 ng / mL, between about 98 ng / mL and about 104 ng / mL, between about 104 ng / mL and about 152 ng / mL, between about 104 ng / mL and about 146 ng / mL, between about 104 ng / mL and about 140 ng / mL, between about 104 ng / mL and about 134 ng / mL, between about 104 ng / mL and about 128 ng / mL, between about 104 ng / mL and about 122 ng / mL, between about 104 ng / mL and about 116 ng / mL, between about 104 ng / mL and about 110 ng / mL, between about 110 ng / mL and about 152 ng / mL, between about 110 ng / mL and about 146 ng / mL, between about 110 ng / mL and about 140 ng / mL, between about 110 ng / mL and about 134 ng / mL, between about 110 ng / mL and about 128 ng / mL, between about 110 ng / mL and about 122 ng / mL, between about 110 ng / mL and about 116 ng / mL, between about 116 ng / mL and about 152 ng / mL, between about 116 ng / mL and about 146 ng / mL, between about 116 ng / mL and about 140 ng / mL, between about 116 ng / mL and about 134 ng / mL, between about 116 ng / mL and about 128 ng / mL, between about 116 ng / mL and about 122 ng / mL, between about 122 ng / mL and about 152 ng / mL, between about 122 ng / mL and about 146 ng / mL, between about 122 ng / mL and about 140 ng / mL, between about 122 ng / mL and about 134 ng / mL, between about 122 ng / mL and about 128 ng / mL, between about 128 ng / mL and about 152 ng / mL, between about 128 ng / mL and about 146 ng / mL, between about 128 ng / mL and about 140 ng / mL, between about 128 ng / mL and about 134 ng / mL, between about 134 ng / mL and about 152 ng / mL, between about 134 ng / mL and about 146 ng / mL, between about 134 ng / mL and about 140 ng / mL, between about 140 ng / mL and about 152 ng / mL, between about 140 ng / mL and about 146 ng / mL, or between about 146 ng / mL and about 152 ng / mL in the subject. In certain embodiments, the method produces a zalunfiban Cmax of between about 75 ng / mL and about 152 ng / mL, between about 80 ng / mL and about 152 ng / mL, between about 85 ng / mL and about 152 ng / mL, or between about 90 ng / mL and about 152 ng / mL in the subject.

[0090] In certain embodiments, the method produces a zalunfiban Cmax of between about 92 ng / mL and about 152 ng / mL, between about 98 ng / mL and about 152 ng / mL, between about 92 ng / mL and about 146 ng / mL, or between about 98 ng / mL and about 146 ng / mL in the subject. In certain embodiments, the method produces a zalunfiban Cmax of between about 92 ng / mL and about 152 ng / mL or between about 98 ng / mL and about 146 ng / mL in the subject. In certain embodiments, the method produces a zalunfiban Cmaxof between about 92 ng / mL and about 152 ng / mL in the subject. In certain embodiments, the method produces a zalunfiban Cmaxof between about 98 ng / mL and about 146 ng / mL in the subject. In certain embodiments, the method produces a zalunfiban Cmaxof between about 92 ng / mL and about 146 ng / mL in the subject. In certain embodiments, the method produces a zalunfiban Cmaxof between about 98 ng / mL and about 152 ng / mL in the subject.

[0091] In certain embodiments, the method does not produce a zalunfiban Cmaxgreater than 1.2 times the zalunfiban Cmaxproduced in the subject with normal renal function. In certain embodiments, the method does not produce a zalunfiban Cmaxgreater than 1.3 times the zalunfiban Cmaxproduced in the subject with normal renal function. In certain embodiments, the method does not produce aC1519.70003WO00 20 / 69 #14198807v1zalunfiban Cmaxgreater than 1.4 times the zalunfiban Cmaxproduced in the subject with normal renal function. In certain embodiments, the method does not produce a zalunfiban Cmaxgreater than 1.5 times the zalunfiban Cmaxproduced in the subject with normal renal function. In certain embodiments, the method does not produce a zalunfiban Cmaxgreater than 1.6 times the zalunfiban Cmax produced in the subject with normal renal function.

[0092] In certain embodiments, the method produces a zalunfiban AUC0-tof between about 110 ng*hr / mL and about 180 ng*hr / mL, between about 110 ng*hr / mL and about 175 ng*hr / mL, between about 110 ng*hr / mL and about 173 ng*hr / mL, between about 110 ng*hr / mL and about 170 ng*hr / mL, between about 110 ng*hr / mL and about 165 ng*hr / mL, between about 110 ng*hr / mL and about 160 ng*hr / mL, between about 110 ng*hr / mL and about 155 ng*hr / mL, between about 110 ng*hr / mL and about 150 ng*hr / mL, between about 110 ng*hr / mL and about 145 ng*hr / mL, between about 110 ng*hr / mL and about 140 ng*hr / mL, between about 110 ng*hr / mL and about 135 ng*hr / mL, between about 110 ng*hr / mL and about 130 ng*hr / mL, between about 110 ng*hr / mL and about 125 ng*hr / mL, between about 110 ng*hr / mL and about 120 ng*hr / mL, between about 110 ng*hr / mL and about 115 ng*hr / mL, about 115 ng*hr / mL and about 180 ng*hr / mL, between about 115 ng*hr / mL and about 175 ng*hr / mL, between about 115 ng*hr / mL and about 173 ng*hr / mL, between about 115 ng*hr / mL and about 170 ng*hr / mL, between about 115 ng*hr / mL and about 165 ng*hr / mL, between about 115 ng*hr / mL and about 160 ng*hr / mL, between about 115 ng*hr / mL and about 155 ng*hr / mL, between about 115 ng*hr / mL and about 150 ng*hr / mL, between about 115 ng*hr / mL and about 145 ng*hr / mL, between about 115 ng*hr / mL and about 140 ng*hr / mL, between about 115 ng*hr / mL and about 135 ng*hr / mL, between about 115 ng*hr / mL and about 130 ng*hr / mL, between about 115 ng*hr / mL and about 125 ng*hr / mL, between about 115 ng*hr / mL and about 120 ng*hr / mL, about 120 ng*hr / mL and about 180 ng*hr / mL, between about 120 ng*hr / mL and about 175 ng*hr / mL, between about 120 ng*hr / mL and about 173 ng*hr / mL, between about 120 ng*hr / mL and about 170 ng*hr / mL, between about 120 ng*hr / mL and about 165 ng*hr / mL, between about 120 ng*hr / mL and about 160 ng*hr / mL, between about 120 ng*hr / mL and about 155 ng*hr / mL, between about 120 ng*hr / mL and about 150 ng*hr / mL, between about 120 ng*hr / mL and about 145 ng*hr / mL, between about 120 ng*hr / mL and about 140 ng*hr / mL, between about 120 ng*hr / mL and about 135 ng*hr / mL, between about 120 ng*hr / mL and about 130 ng*hr / mL, between about 120 ng*hr / mL and about 125 ng*hr / mL, about 125 ng*hr / mL and about 180 ng*hr / mL, between about 125 ng*hr / mL and about 175 ng*hr / mL, between about 125 ng*hr / mL and about 173 ng*hr / mL, between about 125 ng*hr / mL and about 170 ng*hr / mL, between about 125 ng*hr / mL and about 165 ng*hr / mL, between about 125 ng*hr / mL and about 160 ng*hr / mL, between about 125 ng*hr / mL and about 155 ng*hr / mL, between about 125 ng*hr / mL and about 150 ng*hr / mL, between about 125 ng*hr / mL and about 145 ng*hr / mL, between about 125 ng*hr / mL and about 140 ng*hr / mL, between about 125 ng*hr / mL and about 135 ng*hr / mL, between about 125 ng*hr / mL and about 130 ng*hr / mL, about 130 ng*hr / mL and about 180 ng*hr / mL, between about 130 ng*hr / mLC1519.70003WO00 21 / 69 #14198807v1and about 175 ng*hr / mL, between about 130 ng*hr / mL and about 173 ng*hr / mL, between about 130 ng*hr / mL and about 170 ng*hr / mL, between about 130 ng*hr / mL and about 165 ng*hr / mL, between about 130 ng*hr / mL and about 160 ng*hr / mL, between about 130 ng*hr / mL and about 155 ng*hr / mL, between about 130 ng*hr / mL and about 150 ng*hr / mL, between about 130 ng*hr / mL and about 145 ng*hr / mL, between about 130 ng*hr / mL and about 140 ng*hr / mL, between about 130 ng*hr / mL and about 135 ng*hr / mL, about 135 ng*hr / mL and about 180 ng*hr / mL, between about 135 ng*hr / mL and about 175 ng*hr / mL, between about 135 ng*hr / mL and about 173 ng*hr / mL, between about 135 ng*hr / mL and about 170 ng*hr / mL, between about 135 ng*hr / mL and about 165 ng*hr / mL, between about 135 ng*hr / mL and about 160 ng*hr / mL, between about 135 ng*hr / mL and about 155 ng*hr / mL, between about 135 ng*hr / mL and about 150 ng*hr / mL, between about 135 ng*hr / mL and about 145 ng*hr / mL, between about 135 ng*hr / mL and about 140 ng*hr / mL, about 140 ng*hr / mL and about 180 ng*hr / mL, between about 140 ng*hr / mL and about 175 ng*hr / mL, between about 140 ng*hr / mL and about 173 ng*hr / mL, between about 140 ng*hr / mL and about 170 ng*hr / mL, between about 140 ng*hr / mL and about 165 ng*hr / mL, between about 140 ng*hr / mL and about 160 ng*hr / mL, between about 140 ng*hr / mL and about 155 ng*hr / mL, between about 140 ng*hr / mL and about 150 ng*hr / mL, between about 140 ng*hr / mL and about 145 ng*hr / mL, about 145 ng*hr / mL and about 180 ng*hr / mL, between about 145 ng*hr / mL and about 175 ng*hr / mL, between about 145 ng*hr / mL and about 173 ng*hr / mL, between about 145 ng*hr / mL and about 170 ng*hr / mL, between about 145 ng*hr / mL and about 165 ng*hr / mL, between about 145 ng*hr / mL and about 160 ng*hr / mL, between about 145 ng*hr / mL and about 155 ng*hr / mL, between about 145 ng*hr / mL and about 150 ng*hr / mL, about 150 ng*hr / mL and about 180 ng*hr / mL, between about 150 ng*hr / mL and about 175 ng*hr / mL, between about 150 ng*hr / mL and about 173 ng*hr / mL, between about 150 ng*hr / mL and about 170 ng*hr / mL, between about 150 ng*hr / mL and about 165 ng*hr / mL, between about 150 ng*hr / mL and about 160 ng*hr / mL, between about 150 ng*hr / mL and about 155 ng*hr / mL, about 155 ng*hr / mL and about 180 ng*hr / mL, between about 155 ng*hr / mL and about 175 ng*hr / mL, between about 155 ng*hr / mL and about 173 ng*hr / mL, between about 155 ng*hr / mL and about 170 ng*hr / mL, between about 155 ng*hr / mL and about 165 ng*hr / mL, between about 155 ng*hr / mL and about 160 ng*hr / mL, about 160 ng*hr / mL and about 180 ng*hr / mL, between about 160 ng*hr / mL and about 175 ng*hr / mL, between about 160 ng*hr / mL and about 173 ng*hr / mL, between about 160 ng*hr / mL and about 170 ng*hr / mL, between about 160 ng*hr / mL and about 165 ng*hr / mL, about 165 ng*hr / mL and about 180 ng*hr / mL, between about 165 ng*hr / mL and about 175 ng*hr / mL, between about 165 ng*hr / mL and about 173 ng*hr / mL, between about 165 ng*hr / mL and about 170 ng*hr / mL, about 170 ng*hr / mL and about 180 ng*hr / mL, between about 170 ng*hr / mL and about 175 ng*hr / mL, between about 170 ng*hr / mL and about 173 ng*hr / mL, about 173 ng*hr / mL and about 180 ng*hr / mL, between about 173 ng*hr / mL and about 175 ng*hr / mL, or between about 175 ng*hr / mL and about 180 ng*hr / mL in the subject. In certain embodiments, the method produces a zalunfiban AUC0-tof between about 80 ng*hr / mL and about 180C1519.70003WO00 22 / 69 #14198807v1ng*hr / mL, between about 85 ng*hr / mL and about 180 ng*hr / mL, between about 90 ng*hr / mL and about 180 ng*hr / mL, between about 95 ng*hr / mL and about 180 ng*hr / mL, between about 100 ng*hr / mL and about 180 ng*hr / mL, or between about 105 ng*hr / mL and about 180 ng*hr / mL in the subject.

[0093] In certain embodiments, the method produces a zalunfiban AUC0-t of between about 110 ng*hr / mL and about 180 ng*hr / mL, between about 115 ng*hr / mL and about 180 ng*hr / mL, between about 110 ng*hr / mL and about 173 ng*hr / mL, or between about 115 ng*hr / mL and about 173 ng*hr / mL in the subject. In certain embodiments, the method produces a zalunfiban AUC0-t of between about 110 ng*hr / mL and about 180 ng*hr / mL or between about 115 ng*hr / mL and about 173 ng*hr / mL in the subject. In certain embodiments, the method produces a zalunfiban AUC0-t of between about 110 ng*hr / mL and about 180 ng*hr / mL in the subject. In certain embodiments, the method produces a zalunfiban AUC0-t of between about 115 ng*hr / mL and about 180 ng*hr / mL in the subject. In certain embodiments, the method produces a zalunfiban AUC0-t of between about 110 ng*hr / mL and about 173 ng*hr / mL in the subject. In certain embodiments, the method produces a zalunfiban AUC0-t of between about 115 ng*hr / mL and about 173 ng*hr / mL in the subject.

[0094] In certain embodiments, the method does not produce a zalunfiban AUC0-t greater than 1.7 times the zalunfiban AUC0-t produced in the subject with normal renal function. In certain embodiments, the method does not produce a zalunfiban AUC0-t greater than 1.3 times the zalunfiban AUC0-t produced in the subject with normal renal function. In certain embodiments, the method does not produce a zalunfiban AUC0-t greater than 1.4 times the zalunfiban AUC0-t produced in the subject with normal renal function. In certain embodiments, the method does not produce a zalunfiban AUC0- t greater than 1.5 times the zalunfiban AUC0-t produced in the subject with normal renal function. In certain embodiments, the method does not produce a zalunfiban AUC0-t greater than 1.6 times the zalunfiban AUC0-t produced in the subject with normal renal function.

[0095] In certain embodiments, the method produces a zalunfiban Tmax of between about 5 minutes and about 50 minutes, between about 5 minutes and about 45 minutes, between about 5 minutes and about 40 minutes, between about 5 minutes and about 35 minutes, between about 5 minutes and about 30 minutes, between about 5 minutes and about 25 minutes, between about 5 minutes and about 20 minutes, between about 5 minutes and about 15 minutes, between about 5 minutes and about 10 minutes, between about 10 minutes and about 50 minutes, between about 10 minutes and about 45 minutes, between about 10 minutes and about 40 minutes, between about 10 minutes and about 35 minutes, between about 10 minutes and about 30 minutes, between about 10 minutes and about 25 minutes, between about 10 minutes and about 20 minutes, between about 10 minutes and about 15 minutes, between about 15 minutes and about 50 minutes, between about 15 minutes and about 45 minutes, between about 15 minutes and about 40 minutes, between about 15 minutes and about 35 minutes, between about 15 minutes and about 30 minutes, between about 15 minutes and about 25 minutes, between about 15 minutes and about 20 minutes, between about 20 minutes and about 50C1519.70003WO00 23 / 69 #14198807v1minutes, between about 20 minutes and about 45 minutes, between about 20 minutes and about 40 minutes, between about 20 minutes and about 35 minutes, between about 20 minutes and about 30 minutes, between about 20 minutes and about 25 minutes, between about 25 minutes and about 50 minutes, between about 25 minutes and about 45 minutes, between about 25 minutes and about 40 minutes, between about 25 minutes and about 35 minutes, between about 25 minutes and about 30 minutes, between about 30 minutes and about 50 minutes, between about 30 minutes and about 45 minutes, between about 30 minutes and about 40 minutes, between about 30 minutes and about 35 minutes, between about 35 minutes and about 50 minutes, between about 35 minutes and about 45 minutes, between about 35 minutes and about 40 minutes, between about 40 minutes and about 50 minutes, between about 40 minutes and about 45 minutes, or between about 45 minutes and about 50 minutes in the subject.

[0096] In certain embodiments, the method produces a zalunfiban Tmax of between about 5 minutes and about 50 minutes, between about 10 minutes and about 40 minutes, between about 15 minutes and about 35 minutes, or between about 20 minutes and about 30 minutes in the subject. In certain embodiments, the method produces a zalunfiban Tmax of between about 5 minutes and about 50 minutes or between about 10 minutes and about 40 minutes in the subject. In certain embodiments, the method produces a zalunfiban Tmax of between about 5 minutes and about 50 minutes in the subject. In certain embodiments, the method produces a zalunfiban Tmax of between about 10 minutes and about 40 minutes in the subject. In certain embodiments, the method produces a zalunfiban Tmax of between about 15 minutes and about 35 minutes in the subject. In certain embodiments, the method produces a zalunfiban Tmax of between about 20 minutes and about 30 minutes in the subject.

[0097] In certain embodiments, the subject has a history of coronary artery disease. In certain embodiments, the subject has stable coronary artery disease. In certain embodiments, the subject has no history of coronary artery disease.

[0098] In certain embodiments, the subject is being administered (or is self-administering) another pharmacological therapy at the time of onset of symptoms of the thrombotic disorder. In certain embodiments, the other pharmacological therapy comprises one or more of aspirin, warfarin, a statin, and a P2Y12 inhibitor. In certain embodiments, the other pharmacological therapy comprises aspirin. In certain embodiments, the other pharmacological therapy comprises warfarin. In certain embodiments, the other pharmacological therapy comprises a statin. In certain embodiments, the other pharmacological therapy comprises a P2Y12 inhibitor. In certain embodiments, the P2Y12 inhibitor is ticagelor, prasugrel, or clopidogrel. In certain embodiments, the P2Y12 inhibitor is ticagelor. In certain embodiments, the P2Y12 inhibitor is prasugrel. In certain embodiments, the P2Y12 inhibitor is clopidogrel.

[0099] In certain embodiments, the subject has been administered aspirin. In certain embodiments, the administration of the aspirin is prior to the onset of symptoms. In certain embodiments, the administration of the aspirin is after the onset of symptoms but prior to administration of theC1519.70003WO00 24 / 69 #14198807v1zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the administration of the aspirin is after the onset of symptoms and after administration of the zalunfiban, or pharmaceutically acceptable salt thereof. Thrombotic Disorders

[0100] In certain embodiments, the thrombotic disorder is myocardial infarction (MI), ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), acute coronary syndrome (ACS), stroke, unstable angina, or macrovascular or microvascular thrombosis. In certain embodiments, the thrombotic disorder is myocardial infarction (MI), ST-segment elevation myocardial infarction (STEMI), or non-ST-segment elevation myocardial infarction (NSTEMI). In certain embodiments, the thrombotic disorder is myocardial infarction (MI) or ST-segment elevation myocardial infarction (STEMI).

[0101] In certain embodiments, the thrombotic disorder is myocardial infarction (MI). In certain embodiments, the thrombotic disorder is ST-segment elevation myocardial infarction (STEMI), also referred to as ST-elevated myocardial infarction. In certain embodiments, the thrombotic disorder is non-ST-segment elevation myocardial infarction (NSTEMI). In certain embodiments, the thrombotic disorder is acute coronary syndrome (ACS). In certain embodiments, the thrombotic disorder is stroke. In certain embodiments, the thrombotic disorder is unstable angina. In certain embodiments, the thrombotic disorder is macrovascular or microvascular thrombosis. In certain embodiments, the thrombotic disorder is macrovascular or microvascular thrombosis caused by a diverse group of inciting events and affecting one or more organs or implanted or extracorporeal artificial materials, for example, retina, kidney, heart valve, vascular shunt or fistula, left-ventricular assist device, or intravascular cerebral coiled wire used to treat aneurysms.

[0102] In certain embodiments, the diagnosis of ST-segment elevation is established by characteristic ECG findings. Pharmaceutical Compositions

[0103] In certain embodiments, the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is administered in the form of a pharmaceutical composition comprising the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, and one or more carriers, diluents, or excipients. In certain embodiments, the pharmaceutical composition is a solution, a suspension, or an emulsion. In certain embodiments, the pharmaceutical composition is a solution. In certain embodiments, the pharmaceutical composition is a microemulsion. In certain embodiments, the pharmaceutical composition is a suspension. In certain embodiments, the pharmaceutical composition is an emulsion. In certain embodiments, the pharmaceutical composition is a gel. In certain embodiments, the pharmaceutical composition is a slurry.C1519.70003WO00 25 / 69 #14198807v1

[0104] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a free base form of zalunfiban.

[0105] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a pharmaceutically acceptable salt of zalunfiban.

[0106] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of an acetate salt of zalunfiban. In certain embodiments, the acetate salt of zalunfiban is a monoacetate salt. In certain embodiments, the acetate salt of zalunfiban is a diacetate salt.

[0107] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a hydrochloride salt of zalunfiban. In certain embodiments, the hydrochloride salt of zalunfiban is a monohydrochloride salt. In certain embodiments, the hydrochloride salt of zalunfiban is a dihydrochloride salt.

[0108] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a mixed acetate and hydrochloride salt of zalunfiban. In certain embodiments, the mixed acetate and hydrochloride salt of zalunfiban is a mixed monoacetate and monohydrochloride salt.

[0109] In certain embodiments, the pharmaceutical composition comprises a mixture of pharmaceutically acceptable salts of zalunfiban. In certain embodiments, the pharmaceutical composition comprises a mixture of acetate and hydrochloride salts of zalunfiban. In certain embodiments, the pharmaceutical composition comprises a mixture of monoacetate and monohydrochloride salts of zalunfiban.

[0110] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of zalunfiban, and acetic acid. In certain embodiments, the compositions comprise an additional acid, which may act as a solubilizer, pH adjustor, or stabilizer. In certain embodiments, the additional acid is one or more of a pharmaceutically acceptable organic acid and / or a pharmaceutically acceptable inorganic acid.

[0111] In certain embodiments, the molar ratio of zalunfiban to acetic acid is in the range of about 1:0.2 to about 1:2.5. In certain embodiments, the molar ratio of zalunfiban to acetic acid is in the range of about 1:0.4 to about 1:2.4. In certain embodiments, the molar ratio of zalunfiban to acetic acid is in the range of about 1:0.2 to about 1:3.5.

[0112] In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:0.25. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:0.5. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:1. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:2. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:2.5. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:3. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:3.5.

[0113] In certain embodiments, the solution further comprises one or more of acetic acid, hydrochloric acid, citric acid, glycerin, and water.C1519.70003WO00 26 / 69 #14198807v1

[0114] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of zalunfiban, acetic acid, and hydrochloric acid. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:2.4, about 1:2.2, about 1:2, about 1:1.9, about 1:1.8, about 1:1.6, about 1:1.4, about 1:1.2, about 1:1, about 1:0.8, about 1:0.6, or about 1:0.4.

[0115] In certain embodiments, the pharmaceutical composition comprises a therapeutically effective amount of zalunfiban, acetic acid, hydrochloric acid, and citric acid. In certain embodiments, the molar ratio of zalunfiban to acetic acid is about 1:2.4, about 1:2.2, about 1:2, about 1:1.9, about 1:1.8, about 1:1.6, about 1:1.4, about 1:1.2, about 1:1, about 1:0.8, about 1:0.6, or about 1:0.4.

[0116] In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL and about 20 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL and about 15 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL and about 10 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 3 mg / mL and about 8 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 3 mg / mL and about 7 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 3 mg / mL and about 6 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 4 mg / mL and about 8 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 4 mg / mL and about 7 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 4 mg / mL and about 6 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 5 mg / mL and about 8 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 5 mg / mL and about 7 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 5 mg / mL and about 6 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 10 mg / mL and about 20 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 10 mg / mL and about 15 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises between about 15 mg / mL and about 20 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 1 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 2 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 3 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 4 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 5 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 6 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 7 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 8 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 9 mg / mL of acetic acid. In certainC1519.70003WO00 27 / 69 #14198807v1embodiments, the pharmaceutical composition comprises about 10 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 11 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 12 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 13 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 14 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 15 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 16 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 17 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 18 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 19 mg / mL of acetic acid. In certain embodiments, the pharmaceutical composition comprises about 20 mg / mL of acetic acid.

[0117] In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL and about 10 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 3 mg / mL and about 8 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 5 mg / mL and about 8 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 3 mg / mL and about 5 mg / mL of citric acid. In certain particular embodiments, the pharmaceutical composition comprises between about 0 mg / mL and about 3 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL and about 3 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL and about 2 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 2 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 1.35 mg / mL of citric acid. In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL of citric acid.

[0118] In certain embodiments, the pharmaceutical composition is a solution comprising water. In certain embodiments, the solution comprises a pH. The pH can refer to the pH of a ready to use solution or the pH of a lyophilized formulation after reconstitution. In certain embodiments, the pH is between about 4.0 and about 9.0. In certain embodiments, the pH is between about 4.0 and about 8.0. In certain embodiments, the pH is between about 6.0 and about 9.0. In certain embodiments, the pH is between about 7.0 and about 9.0. In certain embodiments, the pH is between about 8.0 and about 9.0. In certain embodiments, the pH is between about 4.0 and about 9.0, between about 4.0 and about 8.0, between about 6.0 and about 9.0, between about 7.0 and about 9.0, or between about 8.0 and about 9.0, and the solution is a reconstituted lyophilized formulation. In certain embodiments, the pH is between about 4.0 and about 6.0. In certain embodiments, the solution has a pH of between about 4.25 and about 6.0. In certain embodiments, the pH is between about 4.0 and about 5.0. In certain embodiments, the pH is between about 4.25 and about 4.75. In certain embodiments, the pH is between about 4.5 and about 5.5. In certain embodiments, the pH is between about 4.75 and aboutC1519.70003WO00 28 / 69 #14198807v15.25. In certain embodiments, the pH is between about 4.5 and about 5.0. In certain embodiments, the pH is between about 4.0 and about 6.0, between about 4.25 and about 6.0, between about 4.0 and about 5.0, between about 4.25 and about 4.75, between about 4.5 and about 5.5, between about 4.75 and about 5.25, or between about 4.5 and about 5.0, and the solution is a ready to use solution.

[0119] In certain embodiments, the pharmaceutical composition is a solution and the total chloride ion concentration in the pharmaceutical composition is ≤35 mM. In certain particular embodiments, the total chloride ion concentration is between about 5 mM and about 35 mM, between about 10 mM and about 30 mM, between about 15 mM and about 25 mM, between about 20 mM and about 35 mM, or between about 25 mM and about 35 mM. In certain embodiments, the solution comprises an additional pharmaceutically acceptable solvent. In certain embodiments, the pharmaceutical composition is a solution in a solvent comprising water and another pharmaceutically acceptable solvent.

[0120] In certain embodiments, the pharmaceutical composition is a solution of zalunfiban and acetic acid in water, further comprising an additional acid that is not hydrochloric acid. In certain embodiments, the concentration of the additional acid is ≤35 mM. In certain particular embodiments, the concentration of the additional acid is between about 5 mM and about 35 mM, between about 10 mM and about 30 mM, between about 15 mM and about 25 mM, between about 20 mM and about 35 mM, or between about 25 mM and about 35 mM.

[0121] In certain embodiments, the pharmaceutical composition is a solution comprising water having an osmolality of ≥200 mmol / L. In certain particular embodiments, the osmolality is between about 200 mmol / L and about 250 mmol / L, between about 250 mmol / L and about 300 mmol / L, between about 300 mmol / L and about 350 mmol / L, or between about 350 mmol / L and about 400 mmol / L. In certain embodiments, the pharmaceutical composition further comprises one or more osmotic agents, including, but not limited to salts and polyols (including, e.g., sugars).

[0122] In certain embodiments, the pharmaceutical composition comprising zalunfiban, or a pharmaceutically acceptable salt thereof, is a solution. In certain embodiments, the concentration of zalunfiban or the pharmaceutically acceptable salt thereof (in the solution) is between about 0.01 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 15 mg / mL and about 100 mg / mL. In certain embodiments,C1519.70003WO00 29 / 69 #14198807v1the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 18 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 20 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 30 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 40 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 50 mg / mL and about 100 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 15 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 18 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 20 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 30 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 40 mg / mL and about 50 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 15 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 18 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 20 mg / mL and about 25 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 22 mg / mL. InC1519.70003WO00 30 / 69 #14198807v1certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12 mg / mL and about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 15 mg / mL and about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 18 mg / mL and about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 20 mg / mL and about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12 mg / mL and about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 15 mg / mL and about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 18 mg / mL and about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 18 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 18 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 18 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 18 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12 mg / mL and about 18 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 15 mg / mL and about 18 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 15 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 15 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 15 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 15 mg / mL. In certain embodiments, the concentrationC1519.70003WO00 31 / 69 #14198807v1of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 12 mg / mL and about 15 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 12 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 12 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 12 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 10 mg / mL and about 12 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / mL and about 10 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.1 mg / mL and about 10 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 1 mg / mL and about 10 mg / mL.

[0123] In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is between about 10 mg / mL and about 20 mg / mL, between about 12 mg / mL and about 20 mg / mL, between about 15 mg / mL and about 20 mg / mL, between about 12 mg / mL and about 22 mg / mL, between about 15 mg / mL and about 22 mg / mL, between about 18 mg / mL and about 22 mg / mL, between about 12 mg / mL and about 25 mg / mL, between about 15 mg / mL and about 25 mg / mL, or between about 18 mg / mL and about 25 mg / mL.

[0124] In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 10 mg / mL, about 11 mg / mL, about 12 mg / mL, about 13 mg / mL, about 14 mg / mL, about 15mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 21 mg / mL, about 22 mg / mL, about 23 mg / mL, about 24 mg / mL, or about 25 mg / mL.

[0125] In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 10 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 11 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 12 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 13 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 14 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 15mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 16 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 17 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 18 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 19C1519.70003WO00 32 / 69 #14198807v1mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 20 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 21 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 22 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 23 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 24 mg / mL. In certain embodiments, the concentration of zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is about 25 mg / mL.

[0126] In certain embodiments, the pharmaceutical composition comprises between about 10 mg / mL and about 20 mg / mL, between about 12 mg / mL and about 20 mg / mL, between about 15 mg / mL and about 20 mg / mL, between about 12 mg / mL and about 22 mg / mL, between about 15 mg / mL and about 22 mg / mL, between about 18 mg / mL and about 22 mg / mL, between about 12 mg / mL and about 25 mg / mL, between about 15 mg / mL and about 25 mg / mL, or between about 18 mg / mL and about 25 mg / mL of zalunfiban, or pharmaceutically acceptable salt thereof; and between about 4 mg / mL and about 8 mg / mL, between about 4 mg / mL and about 7 mg / mL, between about 4 mg / mL and about 6 mg / mL, between about 5 mg / mL and about 7 mg / mL of acetic acid, or between about 5 mg / mL and about 6 mg / mL of acetic acid; and the pH of the solution is between about 4.0 and about 6.0, between about 4.5 and about 5.5, or between about 4.75 and about 5.25

[0127] In certain embodiments, the pharmaceutical composition comprises between about 15 mg / mL and about 25 mg / mL of zalunfiban, or pharmaceutically acceptable salt thereof; and between about 4 mg / mL and about 7 mg / mL of acetic acid; and the pH of the solution is between about 4.0 and about 6.0.

[0128] In certain embodiments, the pharmaceutical composition comprises between about 15 mg / mL and about 20 mg / mL of zalunfiban, or pharmaceutically acceptable salt thereof; and between about 5 mg / mL and about 6 mg / mL of acetic acid; and the pH of the solution is between about 4.75 and about 5.25.

[0129] In certain embodiments, the pharmaceutical composition further comprises a polyol. In certain embodiments, the polyol is glycerin, i.e., glycerol. In certain embodiments, the polyol is propylene glycol. In certain embodiments, the pharmaceutical composition comprises between about 1 mg / mL and about 50 mg / mL polyol. In certain embodiments, the pharmaceutical composition comprises between about 10 mg / mL and about 30 mg / mL polyol. In certain embodiments, the pharmaceutical composition comprises between about 10 mg / mL and about 20 mg / mL polyol. In certain embodiments, the pharmaceutical composition comprises between about 12 mg / mL and about 18 mg / mL polyol.

[0130] In certain embodiments, the polyol is a sugar. In certain embodiments, the polyol is a sugar. In certain embodiments, the sugar is a non-reducing sugar. In certain embodiments, the sugar isC1519.70003WO00 33 / 69 #14198807v1sucrose, trehalose, or mannitol. In certain embodiments, the sugar is sucrose. In certain embodiments, the sugar is mannitol. In certain embodiments, the sugar is trehalose. In certain embodiments, the polyol is sucrose.

[0131] In certain embodiments, the molar ratio of zalunfiban to the sugar is between about 2:1 and about 1:2. In certain embodiments, the molar ratio is between about 2:1 and about 1:1. In certain embodiments, the molar ratio is between about 1.5:1 and about 1:1.

[0132] In certain embodiments, the pharmaceutical composition further comprises one or more additional agents, such as a buffering agent, a tonicity agent, a stabilizing agent, or a solubilizing agent.

[0133] In certain embodiments, the solution is intended for lyophilization. In certain embodiments, the solution is a reconstituted lyophile, wherein the lyophile is as described herein. In certain embodiments, the reconstituted lyophile further comprises sodium chloride.

[0134] In certain embodiments, the composition is a solid lyophile.

[0135] In certain embodiments, the solution is a reconstituted lyophilized formulation.

[0136] In certain embodiments, the reconstituted lyophilized formulation comprises one or more of acetic acid, a polyol, and water. In certain embodiments, the reconstituted lyophilized formulation comprises acetic acid. In certain embodiments, the reconstituted lyophilized formulation comprises a polyol. In certain embodiments, the reconstituted lyophilized formulation comprises water. In certain embodiments, the reconstituted lyophilized formulation comprises acetic acid, a polyol, and water. In certain embodiments, the reconstituted lyophilized formulation comprises one or more of acetic acid, sucrose, and water. In certain embodiments, the reconstituted lyophilized formulation comprises acetic acid. In certain embodiments, the reconstituted lyophilized formulation comprises sucrose. In certain embodiments, the reconstituted lyophilized formulation comprises water. In certain embodiments, the reconstituted lyophilized formulation comprises acetic acid, sucrose, and water.

[0137] In certain embodiments, the reconstituted lyophilized formulation is prepared by reconstituting a solid lyophile. In certain embodiments, the solid lyophile comprises one or more of acetic acid and a polyol. In certain embodiments, the solid lyophile comprises acetic acid. In certain embodiments, the solid lyophile comprises a polyol. In certain embodiments, the solid lyophile comprises acetic acid and a polyol. In certain embodiments, the solid lyophile comprises one or more of acetic acid and sucrose. In certain embodiments, the solid lyophile comprises acetic acid. In certain embodiments, the solid lyophile comprises sucrose. In certain embodiments, the solid lyophile comprises acetic acid and sucrose.

[0138] In certain embodiments, the solid lyophile is prepared by lyophilizing a pre-lyophilization solution comprising one or more of acetic acid, a polyol, and water. In certain embodiments, the pre- lyophilization solution comprises acetic acid. In certain embodiments, the pre-lyophilization solution comprises a polyol. In certain embodiments, the pre-lyophilization solution comprises water. In certain embodiments, the pre-lyophilization solution comprises acetic acid, a polyol, and water. InC1519.70003WO00 34 / 69 #14198807v1certain embodiments, the solid lyophile is prepared by lyophilizing a pre-lyophilization solution comprising one or more of acetic acid, sucrose, and water. In certain embodiments, the pre- lyophilization solution comprises acetic acid. In certain embodiments, the pre-lyophilization solution comprises sucrose. In certain embodiments, the pre-lyophilization solution comprises water. In certain embodiments, the pre-lyophilization solution comprises acetic acid, sucrose, and water.

[0139] In certain embodiments, the solid lyophile comprises the following components:

[0140] In certain embodiments, the pre-lyophilization solution comprises the following components:

[0141] Other excipients are known in the art. Such excipients include bulking agents, buffering agents, tonicity modifiers, antimicrobial agents, and solubilizing agents.. See also, A. Baheti, et al. J. Excipients and Food Chem.1 (1) 2010.

[0142] In certain embodiments, the composition is a spray-dried solid. In certain embodiments, the composition is a micronized solid.

[0143] Tables 1 and 2 show various formulations and their stabilities. In certain embodiments, the pharmaceutical composition is a formulation shown in Table 1. In certain embodiments, the pharmaceutical composition is a formulation shown in Table 2. Table 1. Formulations and StabilitiesC1519.70003WO00 35 / 69 #14198807v1Table 2. Formulations and Stabilities

[0144] In certain particular embodiments, the pharmaceutical composition comprises the following components per milliliter of water:(2) Formulation 2 (pH of 4.75±0.1)(3) Formulation 3 (pH of 4.75±0.1)C1519.70003WO00 36 / 69 #14198807v1(4) Formulation 4 (pH of 5.0±0.1)(5) Formulation 5 (pH of 4.75±0.1)(6) Formulation 6 (pH of 4.5±0.1)or (7) Formulation 7 (pH of 4.25±0.1)

[0145] Tables 3 and 4 show zalunfiban drug product formulations. In certain particular embodiments, the pharmaceutical composition is a formulation shown in Table 3. In certain particular embodiments, the pharmaceutical composition is a formulation shown in Table 4.C1519.70003WO00 37 / 69 #14198807v1Table 3. Quantitative Composition of the Zalunfiban Solution for Injection Drug ProductTable 4. Quantitative Composition of the Zalunfiban 110 mg / vial Lyophilized Drug ProductNF = national formulary; USP = United States Pharmacopeia; qs = quantum satis, amount which is enough; wt% = weight percentage1Adjusted for purity of drug substance2Removed during the drying process Administration

[0146] In certain embodiments, zalunfiban, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein, is administered to the subject by injection. In certain embodiments, the injection is intramuscular injection. In certain embodiments, the injection is subcutaneous injection. In certain embodiments, the site of injection includes the arm, leg, thigh, back, buttocks, and abdomen. In certain embodiments, administration by injection is performed using a pre-filled syringe, pen, or auto-injector. In certain embodiments, administration is self- administration by auto-injector.

[0147] In certain embodiments, the volume of the injection is 2 mL or less. In certain embodiments, the volume of the injection is 1 mL or less. In certain embodiments, the volume of the injection isC1519.70003WO00 38 / 69 #14198807v1about 0.9 mL, about 0.8 mL, about 0.7 mL, about 0.6 mL, about 0.5 mL, about 0.4 mL, about 0.3 mL, about 0.2 mL, or about 0.1 mL.

[0148] In certain embodiments, administration of zalunfiban, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein, results in minimal injection site reaction (e.g., bruising, bleeding, swelling, and discomfort) in the subject at t=0, t=1 hour, t=1 day, t=3 days, or t=1 month post injection. In certain embodiments, the administration results in an injection site reaction that resolves in 30 days or less, e.g., within 25, 20, 15, 10, or 5 days.

[0149] In certain embodiments, the methods disclosed herein comprise a single administration (e.g., injection). In certain embodiments, the methods disclosed herein comprise multiple administrations (e.g., injections). For example, certain embodiments comprise administering a first dose of zalunfiban, or a pharmaceutically acceptable salt thereof, or composition thereof, and optionally a second dose. A second dose is administered if such administration is desirable, advantageous, or necessary.

[0150] In certain embodiments, the dosage of a subsequent (e.g., second) administration is the same dose as the dosage of the first administration. In certain embodiments, the dosage of a subsequent (e.g., second) administration is different from the dosage of the first administration. Representative dosages, formulations, and concentrations are described herein.

[0151] In certain embodiments, the subject experiences one or more symptoms of the thrombotic disorder, and zalunfiban or a pharmaceutically acceptable salt thereof is administered within 6 hours of the onset of symptoms or the demonstration of ECG findings diagnostic of MI. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 5 hours of the onset of symptoms. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 4 hours of the onset of symptoms. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 3 hours of the onset of symptoms. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 2 hours of the onset of symptoms. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 1 hour of the onset of symptoms. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 30 minutes of the onset of symptoms. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 15 minutes of the onset of symptoms.

[0152] In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 15 minutes to 6 hours of the onset of symptoms. In certain embodiments, zalunfiban or a pharmaceutically acceptable salt thereof is administered within 30 minutes to 6 hours of the onset of symptoms.

[0153] In certain embodiments, the symptoms are selected from chest pain or discomfort, shortness of breath, dizziness or light-headedness, nausea or vomiting, diaphoresis, palpitations, and anxiety or dread.C1519.70003WO00 39 / 69 #14198807v1

[0154] In certain embodiments, the subject experiences one or more symptoms of the thrombotic disorder, and the zalunfiban, or pharmaceutically acceptable salt thereof, is administered within 30 minutes to 6 hours of the onset of symptoms.

[0155] In certain embodiments, the subject experiences one or more symptoms of the thrombotic disorder, wherein the thrombotic disorder is STEMI; and the symptoms are selected from chest pain or discomfort, shortness of breath, dizziness or light-headedness, nausea or vomiting, diaphoresis, palpitations, and anxiety or dread.

[0156] In certain embodiments, the subject experiences one or more symptoms of the thrombotic disorder, wherein the thrombotic disorder is STEMI; the symptoms are selected from chest pain or discomfort, shortness of breath, dizziness or light-headedness, nausea or vomiting, diaphoresis, palpitations, and anxiety or dread; and the zalunfiban, or pharmaceutically acceptable salt thereof, is administered within 30 minutes to 6 hours of the onset of symptoms. Clinical Objectives

[0157] In certain embodiments, treating comprises restoring coronary artery blood flow. In certain embodiments, treating comprises at least partially restoring coronary artery blood flow. For example, coronary artery blood flow may be restored by about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100%.

[0158] In certain embodiments, treating comprises restoring, at least partially restoring, or maintaining coronary artery blood flow.

[0159] In certain embodiments, treating comprises achieving an improvement of Thrombolysis in Myocardial Infarction (TIMI) Frame Count, TIMI Flow Grade, or TIMI Myocardial Perfusion Grade in the subject. In certain embodiments, the improvement is relative to a placebo. Placebo refers to the absence of any treatment, or comparison to a treatment that has no biological effect. In certain embodiments, the improvement is achieved within 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

[0160] In certain embodiments, a TIMI Frame Count reduction of at least 5 is achieved within 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

[0161] In certain embodiments, treating comprises achieving and / or maintaining in the subject a stable platelet count. In certain embodiments, the platelet count does not change by more than 10%, 20%, or 30%.

[0162] In certain embodiments, treating comprises achieving ≥75% inhibition of platelet aggregation in the subject. In certain embodiments, achieving ≥75% inhibition of platelet aggregation in the subject is achieved within 5-90, 5-60, 5-50, 5-40, 5-30, 10-90, 10-60, 10-50, 10-40, or 10-30 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥75% inhibition of platelet aggregation in the subject is achieved within about 15 minutes following administration of the zalunfiban, or pharmaceutically acceptable saltC1519.70003WO00 40 / 69 #14198807v1thereof. In certain embodiments, achieving ≥75% inhibition of platelet aggregation is achieved within 5-50 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥75% inhibition of platelet aggregation is achieved within 10-40 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥75% inhibition of platelet aggregation is achieved from about 5 minutes until about 50 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥75% inhibition of platelet aggregation is achieved from about 10 minutes until about 40 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥75% inhibition of platelet aggregation is achieved from about 5 minutes until about 35 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

[0163] In certain embodiments, treating comprises achieving ≥80% inhibition of platelet aggregation in the subject. In certain embodiments, achieving ≥80% inhibition of platelet aggregation in the subject is achieved within 5-90, 5-60, 5-50, 5-40, 5-30, 10-90, 10-60, 10-50, 10-40, or 10-30 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥80% inhibition of platelet aggregation in the subject is achieved within about 15 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥80% inhibition of platelet aggregation is achieved within 5-50 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥80% inhibition of platelet aggregation is achieved within 10-40 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥80% inhibition of platelet aggregation is achieved from about 5 minutes until about 50 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥80% inhibition of platelet aggregation is achieved from about 10 minutes until about 40 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, achieving ≥80% inhibition of platelet aggregation is achieved from about 5 minutes until about 35 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

[0164] In certain embodiments, treating comprises achieving improved ST deviation resolution in the subject. In certain embodiments, the ST deviation resolution in the subject is ≥ 70% compared to baseline. In certain embodiments, the ST deviation resolution is measured relative to placebo. In certain embodiments, the ST deviation resolution in the subject is ≥ 75% compared to baseline. In certain embodiments, the ST deviation resolution in the subject is ≥ 80% compared to baseline. In certain embodiments, the ST deviation resolution in the subject is ≥ 85% compared to baseline. In certain embodiments, the ST deviation resolution in the subject is ≥ 90% compared to baseline. In certain embodiments, ST deviation resolution in the subject is achieved within about 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.C1519.70003WO00 41 / 69 #14198807v1

[0165] In certain embodiments, treating comprises achieving a reduction in residual ST deviation in the subject. In certain embodiments, the reduction is measured relative to placebo. In certain embodiments, a reduction in residual ST deviation in the subject is achieved following a single administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, a reduction in residual ST deviation in the subject is achieved within about 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

[0166] In certain embodiments, treating comprises achieving a reduction in all-cause mortality and / or cardiovascular mortality versus placebo at 12 months.

[0167] In certain embodiments, treating comprises achieving an improvement composite of all cause death, recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR), or blinded bail-out use of intravenous (IV) αIIbβ3 antagonists or IV P2Y12 antagonist in the subject following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, treating comprises achieving an improvement composite of all cause death, recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR), or blinded bail-out use of intravenous (IV) αIIbβ3 antagonists or IV P2Y12 antagonist in the subject up to a month following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the determination is made versus placebo up to 1 month post-PCI / angiography relative to placebo.

[0168] In certain embodiments, treating comprises achieving reduced acute stent thrombosis in the subject up to 24 hours following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the reduced stent thrombosis is measured versus placebo.

[0169] In certain embodiments, treating comprises achieving reduced heart failure, directly or indirectly, for several years following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the reduction is measured versus placebo. This effect can be predicted by measurement of B-type-natriuretic protein (BNP), specifically measuring N-terminal pro-B-Type natriuretic protein measured within about 1 day following the administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

[0170] In certain embodiments, treating comprises achieving no occurrence of death in the subject within 30 days following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the no occurrence of death is measured versus placebo.

[0171] In certain embodiments, treating comprises achieving no occurrence of stroke in the subject within 30 days following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the no occurrence of stroke is measured versus placebo.C1519.70003WO00 42 / 69 #14198807v1

[0172] In certain embodiments, treating comprises achieving no recurrence of myocardial infarction (MI) in the subject within 30 days following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the no recurrence of myocardial infarction is measured versus placebo.

[0173] In certain embodiments, treating comprises achieving no occurrence of acute stent thrombosis in the subject up to 24 hours following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the no occurrence of acute stent thrombosis is measured versus placebo.

[0174] In certain embodiments, treating comprises achieving no new onset of heart failure or rehospitalization for heart failure within 30 days following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the no new onset of heart failure or rehospitalization for heart failure is measured versus placebo.

[0175] In certain embodiments, treating comprises achieving peak high-sensitive cardiac troponin T (hs-cTnT) less than ten times an upper limit of normal at 24 hours following administration (e.g., a single subcutaneous injection) of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the peak hs-CTnT is measured versus placebo. Combinations

[0176] In certain embodiments, the methods described herein further comprise administering to the subject an additional therapeutic compound (e.g., one or more additional therapeutic compounds).

[0177] In certain embodiments, the additional therapeutic compound is a blood thinner. In certain embodiments, the additional therapeutic compound is heparin.

[0178] In certain embodiments, the additional therapeutic compound is a P2Y12 inhibitor (e.g., ticagelor, prasugrel, or clopidogrel). In certain embodiments, the additional therapeutic compound is ticagelor. In certain embodiments, the additional therapeutic compound is prasugrel. In certain embodiments, the additional therapeutic compound is clopidogrel.

[0179] In certain embodiments, the additional therapeutic compound is aspirin.

[0180] In certain embodiments, the additional therapeutic compound is selected from cangrelor, warfarin, enoxaparin, fondaparinux, dalteparin, bivalirudin, hirudin, rivaroxaban, dabigatran, apixaban, and edoxaban.

[0181] In certain embodiments, the methods described herein further comprise administering to the subject a blood thinner and a P2Y12 inhibitor (e.g., ticagelor, prasugrel, or clopidogrel). In certain embodiments, the methods described herein further comprise administering to the subject heparin and a P2Y12 inhibitor (e.g., ticagelor, prasugrel, or clopidogrel). In certain embodiments, the methods described herein further comprise administering to the subject aspirin and heparin. In certain embodiments, the methods described herein further comprise administering to the subject aspirin and a P2Y12 inhibitor (e.g., ticagelor, prasugrel, or clopidogrel).C1519.70003WO00 43 / 69 #14198807v1

[0182] In certain embodiments, the additional therapeutic agent is administered to the subject prior to administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In certain embodiments, the additional therapeutic agent is administered to the subject following administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In certain embodiments, the additional therapeutic agent is administered to the subject concurrently with the administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein.

[0183] In certain embodiments, the subject has been administered aspirin. In certain embodiments, the administration of the aspirin is prior to the onset of symptoms. In certain embodiments, the administration of the aspirin is prior to the onset of symptoms, or after the onset of symptoms but prior to administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the administration of the aspirin is after the onset of symptoms but prior to administration of the zalunfiban, or pharmaceutically acceptable salt thereof. In certain embodiments, the administration of the aspirin is after the onset of symptoms and after administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

[0184] In certain embodiments, the subject has been administered a P2Y12 inhibitor. In certain embodiments, the administration of the P2Y12 inhibitor is prior to the onset of symptoms, or after the onset of symptoms, but prior to administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In certain embodiments, the administration of the P2Y12 inhibitor is prior to the onset of symptoms. In certain embodiments, the administration of the P2Y12 inhibitor is after the onset of symptoms, but prior to administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In certain embodiments, the administration of the P2Y12 inhibitor is after the onset of symptoms, and after administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein.

[0185] In certain embodiments, the subject has been administered aspirin and a P2Y12 inhibitor. In certain embodiments, the subject has been administered aspirin and a P2Y12 inhibitor prior to the onset of symptoms, or after the onset of symptoms, but prior to administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In certain embodiments, the subject has been administered aspirin and a P2Y12 inhibitor prior to the onset of symptoms. In certain embodiments, the subject has been administered aspirin and a P2Y12 inhibitor after the onset of symptoms, but prior to administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In certain embodiments, the subject has been administered aspirin and a P2Y12 inhibitor after the onset of symptoms, and after administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein.C1519.70003WO00 44 / 69 #14198807v1

[0186] In certain embodiments, the subject is administered a P2Y12 inhibitor at the same time as administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In certain embodiments, the subject is administered a P2Y12 inhibitor after the administration of zalunfiban or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. EXAMPLES

[0187] In order that the present disclosure may be more fully understood, the following examples are set forth. The synthetic and biological examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting in their scope. Example 1: Phase I Clinical Study Rationale

[0188] A human radiolabeled mass balance study is the single most direct method to obtain quantitative and comprehensive information about the absorption, distribution, metabolism, and excretion (ADME) of a drug. It can also help define the overall pathways of drug metabolism and excretion, as well as identify and quantify circulating metabolites. It can also provide information on which metabolites should be structurally characterized, and whether renal or hepatic studies or drug interaction studies should be considered. See Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance Studies Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) July 2024 Clinical Pharmacology. The key safety, regulatory, and clinical pharmacology findings that can be derived from a well designed mass balance study are provided below: 1. Generate whole blood concentration versus time profiles of total radioactivity, parent drug, and metabolites of interest, to identify pharmacokinetic analytes of interest. 2. Obtain pharmacokinetic parameters of total radioactivity, parent drug, and metabolites of interest. 3. Obtain cumulative percentage of administered dose radioactivity recovered in urine, feces, and combined over time. 4. Identify primary metabolic and elimination pathways, where more than 80% of radioactivity is recovered in excreta. 5. Identify metabolite(s), including structural characterization of metabolites representing more than 10% of total drug exposure in plasma / whole blood. 6. Construct a proposed biotransformation scheme based upon the structurally identified metabolites and routes of elimination.C1519.70003WO00 45 / 69 #14198807v17. Determine the percentage of systemically available parent drug and active metabolite(s) eliminated by the kidney. If this is 30% or more, this indicates the drug is substantially eliminated by the kidney. 8. Determine the percentage of parent drug and active metabolite(s) eliminated by the liver. If this is 20% or more of the absorbed drug, this indicates drug is substantially eliminated by the liver. Study Design

[0189] An open-label, single-dose, phase 1 study of zalunfiban was conducted to assess the absorption, distribution, metabolism and excretion of zalunfiban. A single subcutaneous (SC) injection of 9.5 mg / 5 µCi [14C]-zalunfiban in 0.5 mL was administered to eight healthy male participants with normal renal function in a fed state, with water. Suitable SC injection sites included the upper arm or abdomen, in a location that did not interfere with study procedures. The injection site was required to be free of skin lesions, scars, tattoos, and bony prominences and had to be readily visible for monitoring. The injection was administered at a 45 to 90-degree angle to a pinched region of the skin. Following injection, a bandage was placed over the injection site. The bandage was later collected and tested for IP leakage.

[0190] Blood, urine, and fecal samples were collected at predetermined time points up to 240 hours for pharmacokinetics (PK), total reactivity, and metabolite assessments. Blood samples were collected pre-dose (-60 minutes); 5, 10, 15, 30 and 45 minutes; and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Blood samples were taken via an indwelling IV catheter or by direct venipuncture into designated blood collection tubes. Study samples were diluted immediately after blood collection at a ratio of 1:4 using prechilled 30% acetonitrile, then separated into storage tubes and immediately frozen at -80 ℃. During screening, 1.0 mL aliquots of urine were collected from urinalysis samples and used for a background14C measurement. Following admission, urine was collected pre-dose, and then post-dose over the following collection time intervals: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144- 168, 168-192, 192-216, and 216-240 hours. During each interval, individual urine samples were collected, and retained samples harvested, processed, and stored. Individual urine samples were then pooled in 3,000 mL collection containers. From each container 4.5 mL and 12 mL aliquots were obtained for14C analysis and metabolite profiling and identification, respectively. Individual bowel movements were collected in labeled containers and stored at 2-8 ℃. These were pooled into containers as per the following collection intervals: pre-dose and post-dose 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216 and 216-240 hours. Samples were harvested, processed, and stored. Approximately 4.5 mL of homogenate was retained for14C analysis and 12 mL retained for metabolite profiling and identification.C1519.70003WO00 46 / 69 #14198807v1

[0191] Each subject was required to meet all of the following criteria to be eligible for study enrollment: 1. Capable of understanding the written informed consent form (ICF), willingly provide valid, signed written informed consent and willing and able to comply with the schedule, requirements and restrictions of the study. 2. Healthy adult males between 18.0 and 55.0 years of age (inclusive) at the time of Screening. 3. Body weight 73-99 kg at Screening. 4. Considered to be in good health by the Investigator, as determined by medical history, physical examination, VS measurements, 12-lead ECG and clinical laboratory test results. 5. Male subjects with female sexual partner(s) were permitted to be enrolled if the male: a. was documented to be surgically sterile (i.e., successfully vasectomized), or b. agreed to use 2 methods of highly effective contraception (eg, condom plus spermicide) and female partner’s use of a reliable form of contraception during intercourse for the duration of the study, and for at least 90 days after receiving study drug and agrees to refrain from sperm donation from the time of Screening through 90 days post dose. 6. Negative serology results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) and human immunodeficiency virus antibody (HIV Ab). 7. Non-smoker (with no use of other tobacco or nicotine containing products, in any form), as documented by history (no nicotine within 6 months prior to Screening) and a negative cotinine test at Screening and Admission. 8. Negative results for drugs of abuse and alcohol at Screening and Admission. 9. Content of14C in urine, whole blood and / or plasma (per Investigator discretion) samples obtained at Screening does not significantly exceed the general environmental background 14C level. At present, background level of14C is 104 percent Modern Carbon (pMC) or approximately 20 pMC if subject to radiodilution with sodium benzoate (SB) carbon carrier. To be eligible for study enrollment, subjects were required to have ≤ 30 pMC in a urine sample analyzed with SB carbon carrier and / or ≤ 50 pMC for a plasma sample analyzed with SB carbon carrier. 10. Willing to comply with Pharmaron’s COVID-19 policies.

[0192] Subjects meeting any of the following criteria were ineligible for study enrollment: 1. History or presence of any condition (e.g., chronic diarrhea) or prior surgery (e.g., gastric bypass) that, in the opinion of the Investigator, poses a significant risk to subject safety and / or achievement of study objectives. 2. Clinically significant abnormal medical history, or any abnormal findings on physical examination, VS, ECG or laboratory tests at Screening, Admission or pre dose on Day 1 that,C1519.70003WO00 47 / 69 #14198807v1in the opinion of the Investigator, could jeopardize achieving the study objectives and / or compromise the subject’s safety. 3. History of cancer that has not been in complete remission for > 5 years (except basal cell skin cancer or squamous cell skin cancer with a history of curative treatment and no recurrence for > 1 year prior to Screening), as judged by the Investigator. 4. Acute illness within 14 days prior to study drug administration on Day 1, unless mild in severity and enrollment is approved by both the Investigator and Sponsor’s medical representative. 5. History of COVID symptoms or positive COVID test within 2 weeks prior to admission date. 6. Any history of serious allergic drug reactions. 7. History or presence of alcohol or drug abuse within 2 years prior to Screening. 8. Recent history of incomplete bladder emptying with voiding or awakening more than once at night to void. 9. Usual habit of < 1 or > 3 bowel movements per day. 10. Exposure to radiation for therapeutic or diagnostic reasons (except dental X rays and plain X rays of the thorax and bony skeleton) within the past 12 months prior to study drug administration on Day 1, or worker occupationally exposed to radiation. 11. Participation in another clinical study in which a 14C labeled drug was administered within 1 year prior to Admission. 12. Administration of another investigational medication within 30 days (or 5 half-lives, whichever is longer) prior to study drug administration. 13. Participation in an investigational device study within 30 days prior to study drug administration. 14. Any ECG abnormality considered to be clinically significant by the Investigator. 15. QTcB interval (QT interval corrected for heart rate per Bazett’s formula) > 450 msec at Screening, Admission or pre dose on Day 1. 16. Family history of long QT syndrome or of unexplained sudden death in a first-degree relative under 50 years of age. 17. Documented congenital or acquired long QT syndrome. 18. Glomerular filtration rate (GFR) ≤90 mL / min / 1.73 m2, as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation. 19. Presence of clinically significant hypertension, defined as systolic blood pressure (SBP) > 145 mmHg and / or diastolic blood pressure (DBP) > 90 mmHg, at Screening or Admission. 20. Presence of clinically significant hypotension, defined as SBP < 90 mmHg and / or DBP < 50 mmHg, at Screening or Admission.C1519.70003WO00 48 / 69 #14198807v121. Loss or donation of blood (approximately 500 mL or greater) within 60 days prior to study drug administration on Day 1; donation of bone marrow or peripheral stem cells within 90 days prior to study drug administration on Day 1; or donation of plasma within 30 days prior to study drug administration on Day 1. 22. Excessive consumption of alcohol, defined as > 3 alcoholic beverages per day (12 ounces of beer [354 mL], 5 ounces of wine [148 mL] or 1.5 ounces of distilled spirits [44 mL] is approximately equivalent to 1 alcoholic beverage). 23. Excessive consumption of coffee, tea, cola or other caffeinated beverages; excessive consumption is defined as > 6 servings per day (1 serving contains approximately 120 mg caffeine). 24. Venous access considered inadequate for PK sample collection; history or evidence of adverse symptoms associated with phlebotomy or blood donation. 25. Employee or family member of the Investigator, study site personnel or Sponsor. 26. Use / consumption of any medications or substances listed as prohibited in Section 9.2.3. 27. Any other reason that, in the opinion of the Investigator, would render the subject unsuitable for study enrollment. Analysis

[0193] Total reactivity analysis: Whole blood, urine, and feces samples were analyzed for total14C radioactivity by liquid scintillation counting (LSC) and / or by accelerator mass spectrometry (AMS). When total radioactivity concentrations were above the limit of quantification, total radioactivity analysis was performed using two liquid scintillation counters, a TriCarb 3180 TR / SL and a TriCarb 5110 TR (Perkin Elmer, Waltham MA). If the concentration was below the limit of quantification (BLOQ), samples were analyzed by Accelerator Mass Spectrometry (AMS). Whole blood samples were analyzed using AMS. Urine sample analysis was performed using liquid scintillation. Each sample was counted for at least 10 min or until the 2% terminator was reached. Homogenized feces samples were combusted in a Perkin Elmer, Model 307 sample oxidizer (Perkin Elmer, Waltham MA). The CO2 produced was trapped in a Carbosorb / Permafluor 2:1 v / v (Perkin Elmer, Waltham MA) to determine total carbon content and the14C:12C ratio and then analyzed by AMS. A carbon content correction based upon pre-dose whole blood samples and urine samples was applied to all post dose samples. As the carbon content of homogenized feces can be variable, all homogenized feces samples were analyzed by C,H,N using a Thermo Scientific FlashSmart elemental analyzer (Waltham, MA). Urea standards were used to calibrate and normalize the C,H,N, and the carbon content of each sample was determined.

[0194] Quantification in whole blood, urine, feces: Whole blood samples were analyzed for zalunfiban and Des-Gly zalunfiban using a Sciex (AB Sciex, Framingham, MA) 5500 liquid chromatography tandem mass spectrometry (LC-MS / MS) using a validated analytical method andC1519.70003WO00 49 / 69 #14198807v1zalunfiban and Des-Gly zalunfiban reference standards provided by CeleCor Therapeutics. Zalunfiban and Des-Gly zalunfiban concentrations below 5 and 25 ng / mL respectively were considered BLOQ. Sample acceptance criteria and analytical procedures were in compliance with FDA Good Laboratory Practice regulations and ICH Good Clinical Practice guidelines.

[0195] Pharmacokinetics: Whenever possible, pharmacokinetic (PK) parameters were calculated for each study subject based on whole blood concentrations of zalunfiban as well as whole blood, urine and feces total radioactivity. Zalunfiban and whole blood radioactivity concentrations were used to calculate PK parameters using standard noncompartmental analysis (NCA) methods using Phoenix WinNonlin software (Phoenix, Princeton, NJ). All statistical programming and tables, figures and listings were carried out using SAS 9.4 (SAS Institute, Inc., Cary, NC).

[0196] Mass Balance: Whenever possible, PK parameters were calculated based on the urine and feces concentrations of total radioactivity and the cumulative amount excreted (Ae0-t).

[0197] Metabolite Profiling and Identification: Whole blood, urine and feces metabolite profiling were performed and metabolite identification conducted, as appropriate. Whole blood, feces, and urine radiochromatograms were generated for each sample by collecting high performance liquid chromatography (HPLC) fractions using Agilent 1290 and Agilent 1260 systems (Agilent, Santa Clara, CA), followed by AMS. AMS data were imported into LAURA V6 (LabLogic, Sheffield, UK) to generate radiochromatograms, and regions of interest were quantified and provisionally identified where possible. Assignment of parent and metabolites was made by matching retention times, using liquid chromatography ultraviolet chromatography (LC-UV).

[0198] LC-MS-MS systems: Whole blood, urine, and feces samples were analyzed using high resolution LC-MS / MS. A single whole blood sample was analyzed from the all participants, cross- participant, pool combining samples from hours 0-144 hour. A single urine sample was analyzed from all participants, cross-participant, pool combining samples from 0-48 hours. A single feces sample from a cross-participant pool combining samples from 0-192 hours was analyzed.

[0199] In vitro testing for inhibition of platelet aggregation: Ten mL of whole blood was collected from healthy human donors via venipuncture and treated with an anticoagulant (D-phenylalanyl- prolyl-arginyl chloromethyl ketone). From this, platelet-rich plasma (PRP) was prepared by centrifuging whole blood at room temperature at 650 x g for 4 minutes. PRP was removed and standardized to a uniform platelet concentration of 3.0 x 105 / μL, using platelet poor plasma as a diluent, where necessary. Compounds were tested for inhibition of platelet aggregation via incubation with PRP for 20 minutes at 22 ℃ followed by the addition of 25 μl of 50 μM adenosine diphosphate, to initiate aggregation. Platelet aggregation was measured using an aggregometer (PAP-8E C / N 106075; Bio / Data Corp, Horsham PA). For each compound, a range of concentrations was tested to produce a single fitted curve, and the Levenberg-Marquardt approach was used to calculate IC50values.C1519.70003WO00 50 / 69 #14198807v1

[0200] Safety: Safety endpoints for this study included: adverse events (AEs), clinical laboratory abnormalities, vital sign measurement, 12-lead ECG abnormalities, physical examination findings, use of concomitant medications and unscheduled assessments as needed for management of AEs. Vital signs (blood pressure, heart rate, body temperature, respiratory rate) were measured at screening, admission, pre-dose, post-dose at 1, 4, 8, hours, and in the morning on study days 2-11. Safety laboratory tests included serum chemistry, hematology, coagulation, and urinalysis, and were performed at screening, admission, and on study days 1, 4, and 11. On day 1, additional platelet counts were performed post-dose at 2, 6, and 12 hours. Following SC administration, the injection site was observed for bruising and / or hematoma. Participants were continuously monitored for adverse events (AEs) and new use of medication(s). During the study, AEs were collected from the time of informed consent to the last time the participant was seen. Any AE that occurred after the start of study drug administration was considered a treatment-emergent AE (TEAE). The investigator or designee assessed the severity of all AEs using the toxicity grading scale in National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. These scales assign a grade of 1 through 5 to indicate the severity of AEs.

[0201] Materials: [14C]-zalunfiban stock material was manufactured by Pharmaron, UK, The Old Glassworks, Nettleford Road, Cardiff, CF245JQ, UK and supplied as a solid. Unlabeled zalunfiban was manufactured by University of Iowa Pharmaceuticals,115 S Grand Ave Suite G20, Iowa City, IA 52242, USA. Study Results

[0202] Zalunfiban was well-tolerated in all participants, with no dose-limiting toxicities observed. There were no observed clinically significant changes in clinical laboratory tests, vital signs or ECGs. There were no serious TEAEs, TEAEs leading to study discontinuation, or deaths in the study.

[0203] Zalunfiban was detectable in whole blood within 5 minutes post-injection. Four of eight participants had their last measurable whole blood zalunfiban concentrations at 4 h post-dose, 3 of 8 participants had their last measurable whole blood concentrations at 3 h post-dose, and one participant had a last measurable concentration at 2.5 h post-dose (FIG.2). After a single SC dose of [14C]- zalunfiban at a nominal specific activity of 9.5 mg / 5 μCi, urine was the primary route of excretion (FIG.1). Median Tmaxradioactivity and whole blood zalunfiban values were 0.50 and 0.25 hours.

[0204] Whole blood analysis: Whole blood zalunfiban concentrations reached a peak by approximately 0.25 hours (median) and thereafter declined with a mean (SD) terminal T1 / 2of 0.96 (0.33) hours. The mean (SD) Cmaxof zalunfiban was 95.23 (11.52) ng / mL, mean (SD) AUC0-lastwas 109 (19.6) h*ng / mL, and mean (SD) AUC0-infwas 118 (19.5) h*ng / mL. (50.0) L (Table 5). As with zalunfiban, whole blood radioactivity was detected in all participants at the 5 minute post-dose blood sample. Peak whole blood radioactivity occurred at 0.50 hours (median) and thereafter declined in an apparent biphasic manner, with an overall mean (SD) terminal T1 / 2of 98.32 (31.35) hours. The meanC1519.70003WO00 51 / 69 #14198807v1(SD) Cmaxof whole blood total radioactivity was 165 (16.1) ngEq / mL, mean (SD) AUC0-lastwas 705 (81.6) h*ngEq / mL, and mean (SD) AUC0-infwas 782 (102) h*ngEq / mL (Table 6). Mean whole blood zalunfiban / total radioactivity expressed as a percentage was 35.6% for AUC0-4and 15.1% for AUC0-inf(Table 7). Table 5. Whole blood zalunfiban PK parameters in the PK population.Table 6. Whole blood total radioactivity PK parameters in the PK population.Table 7. Whole blood zalunfiban / total radioactivity in the PK population.

[0205] Metabolite profiling and excretion: In whole blood extracts, only 2 peaks with more than 5% of total radioactivity were seen in the radiochromatograms from the AUC0-144cross-pooled sample. Zalunfiban whole blood radioactivity exceeded blood concentration levels of zalunfiban, indicating the presence of metabolites. The major identified metabolite was Des-Gly zalunfiban, which has <1% of the antiplatelet activity of zalunfiban. Zalunfiban and Des-Gly zalunfibanC1519.70003WO00 52 / 69 #14198807v1accounted for 46.9% and 24.4% of the total circulating radioactivity over 144 hours, respectively. Each component peak of the remaining circulating radioactivity accounted for <5% of the total.

[0206] In urine extracts there were 2 peaks with more than 5% of total radioactivity. Based on LC- UV retention times, Des-Gly zalunfiban was the major radioactive component in urine, accounting for 64.1% of the 0-48 hr crossparticipant pooled sample and equivalent to 52.98% of the dose excreted over 48 hours. Zalunfiban accounted for 1.59 % of total radioactivity, equivalent to only 1.31% of dose excreted (FIG.3).

[0207] In the feces extracts there were 6 peaks with more than 5% of total radioactivity. Based on LC-UV retention times, Des-Gly zalunfiban was identified as the major radioactive component, accounting for 20.8% of the total radioactivity identified in the 0-192 h sample, equivalent to 2.87% of the dose excreted. Zalunfiban accounted for 0.173% of total radioactivity, equivalent to 0.0239% of the dose. By 240 hours, cumulative percentages of recovered14C ranged from 94.6-98.1%, cumulative urinary14C recovery ranged from 77.1% to 86.6%, and cumulative fecal recovery ranged from 10.7% to 18.5%. Most of the excretion had taken place by the 144-hour post-dose timepoint. Urine was the major route of14C recovery (FIG.3).

[0208] Reviewing the cumulative recovered radioactivity (%) vs time profile for urine, feces, and total radioactivity, shows that on average more than 80% of the radioactivity was recovered by 48 hours, with the majority of14C in urine. Excretion of smaller amounts in feces was delayed, and this accounts for most excretion past 48 hours (FIG.1).

[0209] Metabolite identification and parent drug conversion: Plasma, urine, and feces samples were analyzed with the objective of identifying radioactive regions representing 10% or more of the circulating radioactivity in whole blood (“AUC” pool) or accounting for 10% or more of the administered radioactivity / dose in urine and feces. No single radioactive region in feces accounted for greater than 10% of the administered radioactivity / dose; therefore, no formal metabolite identification was performed. Based upon this, the proposed metabolic pathway of zalunfiban involves a single step, the removal of glycine to form Des-Gly zalunfiban (FIG.4). This inactive metabolite is then primarily excreted in the urine, with lesser amounts excreted in the feces.

[0210] Antiplatelet activity of Des-Gly zalunfiban: The IC50for platelet aggregation of Des-Gly zalunfiban was 25.5 ±3.5 μM, whereas the IC50for zalunfiban was 0.112 μM, indicating that Des-Gly zalunfiban has < 0.05% of the antiplatelet activity of Zalunfiban. Since Des-Gly zalunfiban was not detected in whole blood at concentrations above the lower quantification limit of 25 ng / mL, it is considered to be an inactive metabolite.

[0211] Discussion: Zalunfiban rapidly reaches peak concentrations after subcutaneous injection. It is primarily metabolized to the inactive Des-Gly zalunfiban metabolite, the only metabolite to exceed the threshold of 10% of total radioactivity whole blood AUC0-144, in cross-pooled samples. Zalunfiban is excreted via renal and hepatic routes, with over 80% of the total dose recovered in urine and feces by 48 hours. Zalunfiban was not detectable in whole blood after at 3.5 hours (median) andC1519.70003WO00 53 / 69 #14198807v1it comprised only 1.31% of the dose excreted in the urine over 48 hours, and 0.0239% of the dose detected in the feces (0-192 hours). With the low urinary recovery of unchanged zalunfiban, its rapid metabolism to Des-Gly zalunfiban, and minimal antiplatelet activity of Des-Gly zalunfiban, the inventors posit that zalunfiban is suitable for patients with impaired renal function without dosage adjustment. INCORPORATION BY REFERENCE

[0212] The present application refers to various issued patent, published patent applications, scientific journal articles, and other publications, all of which are incorporated herein by reference. The details of one or more embodiments of the invention are set forth herein. Other features, objects, and advantages of the invention will be apparent from the Detailed Description, the Figures, the Examples, and the Claims. EQUIVALENTS AND SCOPE

[0213] In the articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Embodiments or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[0214] Furthermore, the disclosure encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claims that is dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is / are referred to as comprising particular elements and / or features, certain embodiments of the disclosure or aspects of the disclosure consist, or consist essentially of, such elements and / or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms “comprising” and “containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub–range within theC1519.70003WO00 54 / 69 #14198807v1stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

[0215] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the embodiments. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any embodiment, for any reason, whether or not related to the existence of prior art.

[0216] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended embodiments. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.C1519.70003WO00 55 / 69 #14198807v1

Claims

CLAIMS What is claimed is:

1. A method of treating or preventing a thrombotic disorder in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein: the subject has renal impairment, and the therapeutically effective amount is the same amount that would be administered to a subject in need thereof with normal renal function.

2. A method of treating or preventing a thrombotic disorder in a subject in need thereof, the method comprising: administering to the subject in need thereof a first dose comprising a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; subsequently determining that the subject has renal impairment; and administering to the subject in need thereof a second dose comprising the same therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof.

3. A method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein the method does not produce a zalunfiban Cmax greater than 1.7 times the zalunfiban Cmax produced in a subject with normal renal function.

4. The method of claim 3, wherein the method does not produce a zalunfiban Cmax greater than 1.6 times the zalunfiban Cmax produced in the subject with normal renal function.

5. The method of claim 3 or claim 4, wherein the method does not produce a zalunfiban Cmaxgreater than 1.5 times the zalunfiban Cmaxproduced in the subject with normal renal function.

6. The method of any one of claims 3-5, wherein the method does not produce a zalunfiban Cmaxgreater than 1.4 times the zalunfiban Cmaxproduced in the subject with normal renal function.

7. The method of any one of claims 3-6, wherein the method does not produce a zalunfiban Cmaxgreater than 1.3 times the zalunfiban Cmaxproduced in the subject with normal renal function.C1519.70003WO00 56 / 69 #14198807v18. The method of any one of claims 3-7, wherein the method does not produce a zalunfiban Cmaxgreater than 1.2 times the zalunfiban Cmaxproduced in the subject with normal renal function.

9. A method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof; wherein the method does not produce a zalunfiban AUC0-tgreater than 1.7 times the zalunfiban AUC0-t produced in a subject with normal renal function.

10. The method of claim 9, wherein the method does not produce a zalunfiban AUC0-t greater than 1.6 times the zalunfiban AUC0-t produced in the subject with normal renal function.

11. The method of claim 9 or claim 10, wherein the method does not produce a zalunfiban AUC0-t greater than 1.5 times the zalunfiban AUC0-t produced in the subject with normal renal function.

12. The method of any one of claims 9-11, wherein the method does not produce a zalunfiban AUC0-t greater than 1.4 times the zalunfiban AUC0-t produced in the subject with normal renal function.

13. The method of any one of claims 9-12, wherein the method does not produce a zalunfiban AUC0-t greater than 1.3 times the zalunfiban AUC0-t produced in the subject with normal renal function.

14. The method of any one of claims 9-13, wherein the method does not produce a zalunfiban AUC0-t greater than 1.2 times the zalunfiban AUC0-t produced in the subject with normal renal function.

15. In a method of treating or preventing a thrombotic disorder in a subject in need thereof having renal impairment, the method comprising administering to the subject in need thereof a therapeutically effective amount of zalunfiban, or a pharmaceutically acceptable salt thereof, the improvement comprising: administering the same amount of zalunfiban, or pharmaceutically acceptable salt thereof, to the subject in need thereof with renal impairment that would be administered to a subject in need thereof with normal renal function.C1519.70003WO00 57 / 69 #14198807v116. The method of any one of claims 1-15, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.05 mg / kg and about 0.30 mg / kg.

17. The method of any one of claims 1-16, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.07 mg / kg and about 0.25 mg / kg.

18. The method of any one of claims 1-17, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.075 mg / kg and about 0.15 mg / kg.

19. The method of any one of claims 1-18, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.15 mg / kg.

20. The method of any one of claims 1-19, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.10 mg / kg and about 0.15 mg / kg.

21. The method of any one of claims 1-20, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 0.09 mg / kg and about 0.13 mg / kg.

22. The method of any one of claims 1-21, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is about 0.11 mg / kg or about 0.13 mg / kg.

23. The method of any one of claims 1-22, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 4.0 mg and about 15.0 mg.

24. The method of any one of claims 1-23, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 5.0 mg and about 13.0 mg.

25. The method of any one of claims 1-24, wherein the therapeutically effective amount of zalunfiban, or pharmaceutically acceptable salt thereof, is between about 6.0 mg and about 12.0 mg.C1519.70003WO00 58 / 69 #14198807v126. The method of any one of claims 1-25, comprising administering to the subject in need thereof a therapeutically effective amount of a free base form of zalunfiban.

27. The method of any one of claims 1-26, comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutically acceptable salt of zalunfiban.

28. The method of any one of claims 1-27, comprising administering to the subject in need thereof a therapeutically effective amount of a mixture of pharmaceutically acceptable salts of zalunfiban.

29. The method of any one of claims 1-28, comprising administering to the subject in need thereof a therapeutically effective amount of an acetate salt of zalunfiban.

30. The method of any one of claims 1-29, comprising administering to the subject in need thereof a therapeutically effective amount of a hydrochloride salt of zalunfiban.

31. The method of any one of claims 1-30, wherein the subject has mild renal impairment, moderate renal impairment, severe renal impairment, or end stage renal disease (ESRD).

32. The method of any one of claims 1-31, wherein the subject has mild renal impairment.

33. The method of any one of claims 1-32, wherein the subject has a creatinine clearance of ≥ 60 mL / min and < 90 mL / min.

34. The method of any one of claims 1-33, wherein the subject has an estimated glomerular filtration rate (eGFR) of ≥ 60 mL / min / 1.73 m2and < 90 mL / min / 1.73 m2.

35. The method of any one of claims 1-31, wherein the subject has moderate renal impairment.

36. The method of any one of claims 1-31 or 35, wherein the subject has a creatinine clearance of ≥ 30 mL / min and < 60 mL / min.

37. The method of any one of claims 1-31, 35, or 36, wherein the subject has an estimated glomerular filtration rate (eGFR) of ≥ 30 mL / min / 1.73 m2and < 60 mL / min / 1.73 m2.

38. The method of any one of claims 1-31, wherein the subject has severe renal impairment.C1519.70003WO00 59 / 69 #14198807v139. The method of any one of claims 1-31 or 38, wherein the subject has a creatinine clearance of ≥ 15 mL / min and < 30 mL / min.

40. The method of any one of claims 1-31, 38, or 39, wherein the subject has an estimated glomerular filtration rate (eGFR) of ≥ 15 mL / min / 1.73 m2and < 30 mL / min / 1.73 m2.

41. The method of any one of claims 1-31, wherein the subject has end-stage renal disease (ESRD).

42. The method of any one of claims 1-31 or 41, wherein the subject has a creatinine clearance of < 15 mL / min.

43. The method of any one of claims 1-31, 41, or 42, wherein the subject has an estimated glomerular filtration rate (eGFR) of < 15 mL / min / 1.73 m2.

44. The method of any one of claims 1-43, wherein the subject has a high risk of bleeding.

45. The method of any one of claims 1-44, wherein the subject has a low body weight.

46. The method of any one of claims 1-45, wherein the subject is an elderly person.

47. The method of any one of claims 1-46, wherein the subject is an elderly woman.

48. The method of any one of claims 1-47, wherein the subject is a dialysis patient.

49. The method of any one of claims 1-48, wherein an exposure of zalunfiban and its metabolite Des-Gly zalunfiban in the subject with renal impairment is substantially similar to an exposure of zalunfiban and its metabolite Des-Gly zalunfiban in the subject with normal renal function.

50. The method of any one of claims 1-49, wherein the method produces a zalunfiban Cmaxof between about 92 ng / mL and about 152 ng / mL in the subject.

51. The method of any one of claims 1-50, wherein the method produces a zalunfiban Cmaxof between about 98 ng / mL and about 146 ng / mL in the subject.C1519.70003WO00 60 / 69 #14198807v152. The method of any one of claims 1-51, wherein the method produces an AUC0-tof between about 110 ng*hr / mL and about 180 ng*hr / mL in the subject.

53. The method of any one of claims 1-52, wherein the method produces an AUC0-tof between about 115 ng*hr / mL and about 173 ng*hr / mL in the subject.

54. The method of any one of claims 1-53, wherein the method produces a zalunfiban Tmaxof between about 5 minutes and about 50 minutes in the subject.

55. The method of any one of claims 1-54, wherein the method produces a zalunfiban Tmax of between about 10 minutes and about 40 minutes in the subject.

56. The method of any one of claims 1-55, wherein the zalunfiban does not undergo primary renal clearance.

57. The method of any one of claims 1-56, wherein the thrombotic disorder is myocardial infarction.

58. The method of any one of claims 1-57, wherein the thrombotic disorder is ST-segment elevation myocardial infarction (STEMI).

59. The method of any one of claims 1-58, wherein the zalunfiban, or pharmaceutically acceptable salt thereof, is administered by injection.

60. The method of claim 59, wherein the injection is intramuscular injection.

61. The method of claim 59, wherein the injection is subcutaneous injection.

62. The method of claim 59, wherein the injection is a single subcutaneous injection.

63. The method of any one of claims 1-61, wherein the zalunfiban, or pharmaceutically acceptable salt thereof, is administered in the form of a pharmaceutical composition further comprising one or more carriers, diluents, or excipients.

64. The method of any one of claims 1-63, wherein the zalunfiban, or pharmaceutically acceptable salt thereof, is administered in the form of a solution, suspension, or emulsion.C1519.70003WO00 61 / 69 #14198807v165. The method of any one of claims 1-64, wherein the zalunfiban, or pharmaceutically acceptable salt thereof, is administered in the form of a solution.

66. The method of claim 64 or claim 65, wherein a concentration of the zalunfiban, or pharmaceutically acceptable salt thereof, in the solution is between about 0.01 mg / mL and about 100 mg / mL.

67. The method of claim 66, wherein the concentration is about 10 mg / mL, about 11 mg / mL, about 12 mg / mL, about 13 mg / mL, about 14 mg / mL, about 15mg / mL, about 16 mg / mL, about 17 mg / mL, about 18 mg / mL, about 19 mg / mL, about 20 mg / mL, about 21 mg / mL, about 22 mg / mL, about 23 mg / mL, about 24 mg / mL, or about 25 mg / mL.

68. The method of any one of claims 62-67, wherein the solution further comprises one or more of acetic acid, hydrochloric acid, citric acid, glycerin, and water.

69. The method of any one of claims 64-68, wherein the pH of the solution is between about 4.0 and about 9.

0.

70. The method of any one of claims 64-69, wherein the pH of the solution is between about 4.0 and about 6.

0.

71. The method of any one of claims 64-70, wherein the pH of the solution is between about 4.5 and about 5.

5.

72. The method of any one of claims 64-71, wherein the pH of the solution is between about 4.75 and about 5.

25.

73. The method of any one of claims 64-69, wherein the pH of the solution is between about 7.0 and about 9.

0.

74. The method of any one of claims 64-72, wherein the solution comprises the following components per milliliter of water:wherein the composition has a pH of 5.0±0.1.C1519.70003WO00 62 / 69 #14198807v175. The method of any one of claims 64-72, wherein the solution comprises the following components per milliliter of water:wherein the composition has a pH of 4.75±0.

1.

76. The method of any one of claims 64-72, wherein the solution comprises the following components per milliliter of water:wherein the composition has a pH of 4.75±0.

1.

77. The method of any one of claims 64-72, wherein the solution comprises the following components per milliliter of water:wherein the composition has a pH of 5.0±0.

1.

78. The method of any one of claims 64-72, wherein the solution comprises the following components per milliliter of water:wherein the composition has a pH of 4.75±0.

1.

79. The method of any one of claims 64-72, wherein the solution comprises the following components per milliliter of water:wherein the composition has a pH of 4.5±0.1.C1519.70003WO00 63 / 69 #14198807v180. The method of any one of claims 64-72, wherein the solution comprises the following components per milliliter of water:wherein the composition has a pH of 4.25±0.

1.

81. The method of any one of claims 64-69 or 73, wherein the solution is a reconstituted lyophilized formulation.

82. The method of claim 81, wherein the reconstituted lyophilized formulation comprises one or more of acetic acid, a polyol, and water.

83. The method of claim 81 or 82, wherein the reconstituted lyophilized formulation is prepared by reconstituting a solid lyophile.

84. The method of claim 83, wherein the solid lyophile comprises one or more of acetic acid and a polyol.

85. The method of claim 83 or 84, wherein the solid lyophile is prepared by lyophilizing a pre- lyophilization solution comprising one or more of acetic acid, a polyol, and water.

86. The method of any one of claims 82-85, wherein the polyol is sucrose.

87. The method of any one of claims 83-86, wherein the solid lyophile comprises the following components:

88. The method of any one of claims 85-87, wherein the pre-lyophilization solution comprises the following components:C1519.70003WO00 64 / 69 #14198807v189. The method of any one of claims 1-88, wherein administration of the zalunfiban, or pharmaceutically acceptable salt thereof, results in minimal injection site reaction in the subject at t=0, t=1 hour, t=1 day, t=3 days, or t=1 month post injection.

90. The method of any one of claims 1-89, wherein the subject experiences one or more symptoms of the thrombotic disorder, and the zalunfiban, or pharmaceutically acceptable salt thereof, is administered within 30 minutes to 6 hours of the onset of symptoms.

91. The method of claim 90, wherein the thrombotic disorder is STEMI, and the symptoms are selected from chest pain or discomfort, shortness of breath, dizziness or light-headedness, nausea or vomiting, diaphoresis, palpitations, and anxiety or dread.

92. The method of any one of claims 1-91, wherein treating comprises at least partially restoring, or maintaining, coronary artery blood flow.

93. The method of any one of claims 1-92, wherein treating comprises achieving an improvement of Thrombolysis in Myocardial Infarction (TIMI) Frame Count or TIMI flow, preferably within 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

94. The method of claim 93, wherein treating comprises achieving an improvement of TIMI Frame Count or TIMI flow of at least 5, preferably within 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

95. The method of any one of claims 1-94, wherein treating comprises maintaining a stable platelet count, preferably within 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

96. The method of any one of claims 1-95, wherein treating comprises achieving ≥75% inhibition of platelet aggregation, preferably within 5-90 minutes (e.g., 15 minutes) following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

97. The method of any one of claims 1-96, wherein treating comprises achieving ≥80% inhibition of platelet aggregation, preferably within 5-90 minutes (e.g., 15 minutes) following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.C1519.70003WO00 65 / 69 #14198807v198. The method of claim 96 or claim 97, wherein the maximum level of inhibition of platelet aggregation is achieved within 5-50 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

99. The method of any one of claims 96-98, wherein the maximum level of inhibition of platelet aggregation is achieved within 10-40 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

100. The method of claim 96 or claim 97, wherein the maximum level of inhibition of platelet aggregation is maintained from about 5 minutes until about 50 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

101. The method of any one of claims 96, 97, or 100, wherein the maximum level of inhibition of platelet aggregation is maintained from about 10 minutes until about 40 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

102. The method of any one of claims 96, 97, or 100, wherein the maximum level of inhibition of platelet aggregation is maintained from about 5 minutes until about 35 minutes following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

103. The method of any one of claims 1-102, wherein treating comprises achieving improved ST deviation resolution (≥ 70% compared to baseline), preferably within 1-5 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

104. The method of any one of claims 1-103, wherein treating comprises achieving a reduction in residual ST deviation after a single subcutaneous injection.

105. The method of any one of claims 1-104, wherein treating comprises achieving an improvement composite of all cause death, recurrent myocardial infarction (MI), urgent target vessel revascularization (TVR) or blinded bail-out use of intravenous (IV) αIIbβ3 antagonists or IV P2Y12 antagonist after a single subcutaneous injection.

106. The method of any one of claims 1-105, wherein treating comprises achieving reduced acute stent thrombosis after a single subcutaneous injection.C1519.70003WO00 66 / 69 #14198807v1107. The method of any one of claims 1-106, wherein treating comprises achieving no occurrence of death in the subject within 30 days following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

108. The method of any one of claims 1-107, wherein treating comprises achieving no occurrence of stroke in the subject within 30 days following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

109. The method of any one of claims 1-108, wherein treating comprises achieving no recurrence of myocardial infarction (MI) in the subject within 30 days following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

110. The method of any one of claims 1-109, wherein treating comprises achieving no acute stent thrombosis in the subject up to 24 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

111. The method of any one of claims 1-110, wherein treating comprises achieving no new onset heart failure or rehospitalization for heart failure in the subject within 30 days following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

112. The method of any one of claims 1-111, wherein treating comprises achieving peak high- sensitive cardiac troponin T (hs-cTnT) less than ten times an upper limit of normal at 24 hours following administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

113. The method of any one of claims 1 or 3-112, further comprising administering a second dose of zalunfiban, or pharmaceutically acceptable salt thereof.

114. The method of any one of claims 1-113, further comprising administering to the subject a P2Y12 inhibitor.

115. The method of any one of claims 1-114, further comprising administering to the subject aspirin.

116. The method of any one of claims 1-115, further comprising administering to the subject heparin.C1519.70003WO00 67 / 69 #14198807v1117. The method of any one of claims 114-116, wherein the P2Y12 inhibitor is ticagelor, prasugrel, or clopidogrel.

118. The method of any one of claims 1-117, wherein the subject has been administered aspirin.

119. The method of claim 118, wherein the administration of the aspirin is prior to the onset of symptoms.

120. The method of claim 118, wherein the administration of the aspirin is after the onset of symptoms but prior to administration of the zalunfiban, or pharmaceutically acceptable salt thereof.

121. The method of any one of claims 1-120, wherein the subject has a history of coronary artery disease.

122. The method of any one of claims 1-121, wherein the subject has stable coronary artery disease.C1519.70003WO00 68 / 69 #14198807v1

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