Method and use of kdm1a inhibitor for treatment of behavioral changes

Description

1 / 58 METHOD AND USE OF KDM1A INHIBITOR FOR THE TREATMENT OF BEHAVIORAL DISORDERS Divided from BR112020000827-3, deposited on 03 / 08 / 2018 Field

[0001] The present invention relates to methods for treating behavioral disorders. Background

[0002] Behavioral changes, such as social withdrawal or aggressive behavior, are highly prevalent in today's society and are viewed by physicians as a medical condition in their own right. Yet, the treatment of behavioral changes remains a medical challenge. Currently, there are no approved drugs that specifically target the treatment of social withdrawal, aggressive behavior, or other behavioral changes. In addition, many of the existing medications being used to treat behavioral changes can cause severe side effects; for example, many antipsychotic drugs (also known as neuroleptics or major tranquilizers) used to treat aggressive behavior and other behavioral changes cause sedation.

[0003] Thus, there is a strong and unmet need for new and improved drugs for the treatment of behavioral disorders, particularly drugs acting via novel mechanisms of action that allow them to specifically treat behavioral disorders and / or exhibiting a more favorable side effect profile than current treatments. The present invention addresses these and other needs. Summary of the Invention

[0004] The invention provides new methods for treating alterations Petition 870260063781, dated 06 / 29 / 2026, p. 10 / 149 2 / 58 behavioral disorders through the use of KDM1A inhibitors. Thus, the present invention provides a KDM1A inhibitor for use in the treatment of a behavioral disorder. The present invention further provides a method for treating a behavioral disorder in a patient (preferably a human), comprising administering to the patient a therapeutically effective amount of a KDM1A inhibitor. The present invention further provides use of a KDM1A inhibitor for the manufacture of a medicament for the treatment of a behavioral disorder.

[0005] The present invention further provides use of a KDM1A inhibitor for the treatment of a behavioral disorder. In some forms, the behavioral disorder is a social behavioral disorder. In some forms, the behavioral disorder is aggression or social withdrawal.

[0006] In preferred embodiments, the KDM1A inhibitor is 5((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol2-amine, or a pharmaceutically acceptable salt or solvate thereof. Brief Description of the Drawings

[0007] Figure 1 shows the effect of treatment with the KDM1A inhibitor Compound 1 (as defined below and in Example 1) on aggressive behavior in the resident intruder test in male SAMP8 mice, as assessed by the total number of attacks, as described in more detail in Example 3. Means and standard error of the mean (SEM) are shown. * p < 0.05; ** p < 0.01.

[0008] Figure 2 shows the effect of treatment with Compound 1 on aggressive behavior in the resident intruder test in male SAMP8 mice, as assessed by the number of grasping attacks, as described in more detail in Example 3. Means and SEMs are shown. **p < 0.01; ***p < 0.001.

[0009] Figure 3 shows the treatment effect with Compound 1 Petition 870260063781, dated 06 / 29 / 2026, page 11 / 149 3 / 58 on social avoidance in the resident intruder test in the rat isolation model, as assessed by time without social interaction (measured in seconds), as described in more detail in Example 4. Means and SEMs are shown. *p < 0.05; **p < 0.01.

[0010] Figure 4 shows the effect of Compound 1 on social avoidance in the resident intruder test in the rat isolation model, as assessed by the number of avoidances, as described in more detail in Example 4. Means and SEMs are shown. *p < 0.05; ***p < 0.001.

[0011] Figure 5 shows the decomposed effect 1 on social interaction behavior in the three-chamber test (TCT), as assessed by the time spent in each of the Object chamber and Mouse chamber (measured in seconds), as described in more detail in Example 5. Means and SEMs are shown. *** p < 0.001.

[0012] Figure 6 shows the effect of Compound 1 on social interaction behavior in the TCT, as assessed by the time spent directly exploring the new mice (measured in seconds), as described in more detail in Example 5. Means and SEMs are shown. ***p, 0.001. Detailed Description of the Invention

[0013] The present invention is based on the finding that KDM1A inhibitors are useful as therapeutic agents for the treatment of behavioral disorders, as explained in more detail below and illustrated in the examples.

[0014] Similarly, the present invention provides a KDM1A inhibitor for use in the treatment of a behavioral disorder. The present invention further provides a method for treating a behavioral disorder in a patient (preferably a human), comprising administering to the patient a therapeutically effective amount of a KDM1A inhibitor. The present Petition 870260063781, dated 06 / 29 / 2026, page 12 / 149 4 / 58 invention further provides the use of a KDM1A inhibitor for the manufacture of a drug for the treatment of a behavioral disorder.

[0015] The present invention further provides the use of a KDM1A inhibitor for the treatment of a behavioral disorder. According to the present invention, a behavioral disorder refers, in particular, to an alteration, disturbance, dysfunction, aberration, disorder or the like affecting a subject's behavior, including, for example, and without limitation, behavioral changes induced by or associated with genetic or epigenetic variations, behavioral changes associated with a disease, behavioral changes induced by drug therapy, behavioral changes induced by acute and / or chronic drug abuse, or behavioral changes induced by an adverse social environment (e.g., abandonment or neglect during childhood, traumatic experiences such as military operations or sexual assault during adulthood) among others.Behavioral changes according to the present invention do not include changes in cognitive function (e.g., memory impairment) or mood (e.g., anxiety).

[0016] In some modalities, behavioral change is a change in social behavior. In particular, this refers to an alteration, disturbance, dysfunction, aberration, disorder, or the like affecting a subject's social behavior for whatever reason, including, for example, and without limitation, changes in social behavior (e.g., changes in social interaction or aggression) induced by or associated with genetic or epigenetic variations, changes in social behavior (e.g., changes in social interaction or aggression) associated with a disease, changes in social behavior (e.g., changes in social interaction or aggression) associated with a disease, changes in social behavior (e.g., changes in social interaction or aggression) associated with a disease. Petition 870260063781, dated 06 / 29 / 2026, p. 13 / 149 5 / 58 of social interaction or aggressiveness) induced by drug therapy, changes in social behavior (e.g., changes in social interaction or aggressiveness) induced by acute and / or chronic drug abuse, or changes in social behavior (e.g., changes in social interaction or aggressiveness) induced by an adverse social environment (e.g., abandonment or neglect during childhood, traumatic experiences such as military maneuvers or sexual assault during adulthood), among others. Examples of changes in social behavior according to the invention include, without limitation, social withdrawal, aggressiveness, or apathy, among others.

[0017] The present invention also relates to a KDM1A inhibitor for use in the treatment of a behavioral disorder, a behavioral dysfunction, a behavioral aberration, or a behavioral disorder, particularly a social behavioral disorder, a social behavioral dysfunction, a social behavioral aberration, or a social behavioral disorder. Similarly, the invention also provides a method for treating a behavioral disorder, a behavioral dysfunction, a behavioral aberration, or a behavioral disorder (particularly a social behavioral disorder, a social behavioral dysfunction, a social behavioral aberration, or a social behavioral disorder) in a patient (preferably a human), the method comprising administering to the patient a therapeutically effective amount of a KDM1A inhibitor.Social behavior disorder, social behavior dysfunction, social behavior aberration, or social behavior disorder can include, in particular, social withdrawal, aggressiveness, or apathy. Additionally, any of the conditions mentioned previously may be present. Petition 870260063781, dated 06 / 29 / 2026, page 14 / 149 6 / 58 can be, for example, (i) induced by or associated with genetic or epigenetic variations, (ii) associated with a disease, (iii) induced by drug therapy, (iv) induced by acute and / or chronic drug abuse, or (v) induced by an adverse social environment, as also described in more detail below.

[0018] Social withdrawal according to the present invention in particular refers to an abnormal, pathological or inappropriate lack of social interaction and / or reduced extent of social interaction (including social avoidance) for members of a social species such as humans, particularly a condition in which an individual is withdrawing from social and interindividual relationships through consistent (across situations and over time) displays of solitary behavior in the presence of others, often accompanied by indifference or withdrawal. In this sense, social withdrawal (which may also be referred to as passive withdrawal) is seen to arise from internal factors, with the individual choosing, for one reason or another, not to interact with others.Social withdrawal according to the invention does not include active social isolation, used to represent a lack of social interaction attributed to external factors, for example, the method by which an individual remains alone because his / her peer does not wish to interact with him / her (i.e., the individual is isolated by others). Non-limiting examples of social withdrawal to be addressed according to the present invention include social withdrawal induced by, or associated with, genetic or epigenetic variations (including, for example, COMT), social withdrawal associated with a disease (including, for example, autism, spectrum disorder (ASD, such as, for example, autism or Asperger's syndrome), avoidance personality disorder (AvPD), schizophrenia (including, for example, schizotypal and / or delusional disorder), a mood disorder (including, for example, major depressive disorder, dysthymic disorder, or other depressive disorders). Petition 870260063781, dated 06 / 29 / 2026, page 15 / 149 7 / 58 bipolar disorder), drug addiction, post-traumatic stress disorder (PTSD), dementia (including, for example, Alzheimer's disease), paranoid personality disorder, depressive personality disorder, schizoaffective disorder, traumatic brain injury (TBI), or an eating disorder (including, for example, bulimia nervosa), drug therapy-induced social withdrawal, social withdrawal induced by acute and / or chronic drug abuse (including, for example, dependence syndrome), or social withdrawal induced by an adverse social environment (for example, abandonment or neglect during childhood, traumatic experiences such as military maneuvers or sexual assault during adulthood), among others.

[0019] According to the present invention, aggressiveness refers, in particular, to any type of improper or pathological, abnormal, aggressive or violent behavior, hostility or agitation, for example, physical or verbal, including interpersonal aggressiveness (i.e., towards other subjects) and / or intrapersonal aggressiveness (i.e., self-aggression).Non-limiting examples of aggression to be addressed according to the invention include, without limitation, aggression induced by or associated with genetic or epigenetic variations (including, for example, Trisomy 21, GABRA2, MAOA, SLC6A4, CHMP2B, VPS13A, PLA2G6, TBP, HTT, ANK3, EHMT1, MYCN, CASK, HDAC4, MLL / KMT2A, TCF4, CNTNAP2, NRXN1, ATN1, CTNNB1, MED12, KDM5C / JARID1C, CUL4B, SYN1, UBE2A, SMARCA2, HCFC1, HERC2, NDP, PAK3, ATP13A2, SPAST, NSD1, STAMBP, HPRT1, DJ1, TARDBP, MAPT or AVPR1A), aggression associated with a disease (including, for example, Alzheimer's disease). (AD), Huntington's disease (HD), Lewy body dementia (LBD), Parkinson's disease (PD), schizophrenia (SZ), bipolar disorder (BPD), depression (DS), traumatic brain injury (TBI), REM sleep behavior disorder (RBD), dementia, dentatorubral-pallidoluysian atrophy. Petition 870260063781, dated 06 / 29 / 2026, page 16 / 149 8 / 58 (DRPLA), Tourette Syndrome (GTS), a conduct disorder (including, for example, unsocialized conduct disorder, socialized conduct disorder, or oppositional defiant disorder), drug addiction, a stress-related disorder (including, for example, post-traumatic stress disorder), autism spectrum disorder (ASD), borderline personality disorder, or adult attention deficit hyperactivity disorder), drug therapy-induced aggression, toxin-induced aggression (e.g., trimethyltine), diet deficit-induced aggression (e.g., Zn), sleep deprivation-induced aggression, or aggression induced by an adverse social environment (e.g., abandonment or neglect during childhood, traumatic experiences such as military operation or sexual assault during adulthood), among others.The illnesses listed above are examples of illnesses in the context of social withdrawal associated with an illness, or in the context of aggression associated with an illness; similarly, they are examples of an illness in the context of a behavioral change associated with an illness, as well as in the context of a social behavioral change associated with an illness.

[0020] In some modalities, the change in behavior is social withdrawal.

[0021] In some modalities, the behavioral change is social withdrawal associated with an illness. In some modalities, said illness is a CNS illness. In some modalities, said CNS illness is an autism spectrum disorder (ASD, such as, for example, autism or Asperger's syndrome), avoidant personality disorder (AVPD), schizophrenia (including, for example, a schizotypal and / or delusional disorder), a mood disorder (including, for example, major depressive disorder, dysthymic disorder, or bipolar disorder), drug addiction, tension disorder Petition 870260063781, dated 06 / 29 / 2026, page 17 / 149 9 / 58 post-traumatic stress disorder (PTSD), dementia (including, for example, Alzheimer's disease), paranoid personality disorder, depressive personality disorder, schizoaffective disorder, bipolar disorder, or an eating disorder (including, for example, bulimia nervosa).

[0022] In some modalities, the behavioral change is aggression associated with a disease. In some modalities, said disease is a CNS disease. In some modalities, said CNS disease is AD, HD, DLB, PD, SZ, BPD, DS, TBI, RBD, dementia, DRPLA, GTS, a conduct disorder (e.g., unsocialized conduct disorder, socialized conduct disorder, or oppositional defiant disorder), drug addiction, a stress-related disorder (including, for example, post-traumatic stress disorder), ASD, borderline personality disorder, or adult attention deficit hyperactivity disorder. In a preferred modality, the disease is AD. However, the disease may also be different from AD.For example, the illness may be HD, DLB, PD, SZ, BPD, DS, TBI, RBD, dementia, DRPLA, GTS, a conduct disorder (e.g., unsocialized conduct disorder, socialized conduct disorder, or oppositional defiant disorder), drug addiction, a stress-related disorder (including, for example, post-traumatic stress disorder), ASD, borderline personality disorder, or adult attention deficit hyperactivity disorder.

[0023] In some modalities, the behavioral change is apathy.

[0024] In the treatment methods and therapeutic uses as described herein, any KDM1A inhibitor may in principle be used, including the KDM1A inhibitors as described in more detail below. However, it is preferred that the KDM1A inhibitor for use in the methods and uses of the invention be the compound 5-((((1R,2S)-2-(4(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a Petition 870260063781, dated 06 / 29 / 2026, p. 18 / 149 10 / 58 its pharmaceutically acceptable salt or solvate, and it is particularly preferred that the KDM1A inhibitor be the compound 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine (in non-salt form). This compound is also referred to herein (including in Examples and Figures) as Compound 1 or Comp. 1. The names 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, Compound 1 or Comp. 1 are used interchangeably herein.

[0025] Similarly, the present invention provides 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of a behavioral disorder.

[0026] The present invention further provides a method for treating a behavioral disorder in a patient (preferably a human), comprising administering to the patient a therapeutically effective amount of 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt or solvate thereof.

[0027] The present invention further provides the use of 5-((((1R,2S)-2(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for the treatment of a behavioral disorder.

[0028] The present invention further provides the use of 5-((((1R,2S)-2(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt or solvate thereof, for the treatment of a behavioral disorder.

[0029] In some modalities, the change in behavior is a change in social behavior.

[0030] In some modalities, the change in behavior is Petition 870260063781, dated 06 / 29 / 2026, page 19 / 149 11 / 58 social distancing.

[0031] In some modalities, the behavioral change is aggressiveness.

[0032] In some modalities, the behavioral change is apathy.

[0033] Preferably, the KDM1A inhibitor for use in the treatment methods and uses described herein, for example, the compound 5((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine (or a pharmaceutically acceptable salt or solvate thereof), is administered orally. Exemplary formulations that can be administered via perioral ingestion are further described in more detail below.

[0034] As explained above, in preferred embodiments the present invention provides the compound 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of a behavioral disorder. Similarly, the invention relates to the compound 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine as a free base (in non-salt form) for use in the treatment of a behavioral disorder and, furthermore, the invention also relates to a pharmaceutically acceptable salt or solvate of 5-((((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine for use in the treatment of a behavioral disorder.

[0035] As illustrated in the Examples, it has been surprisingly verified in the context of the present invention that KDM1A inhibitors, such as Compound 1, provide potent therapeutic effects in animal models of behavioral disorders (human). In particular, the beneficial effects of KDM1A inhibitors have been observed on different types of behavioral disorders. Petition 870260063781, dated 06 / 29 / 2026, page 20 / 149 12 / 58 ment, particularly aggressiveness, social withdrawal, and other changes in social behavior.

[0036] As illustrated in more detail in Example 3 and Figures 1 and 2, KDM1A inhibitors such as Compound 1 have been found to be effective in treating aggression. To test the effects of a compound of interest such as Compound 1 on aggression, an animal model (e.g., a rodent model) is selected where animals treated with the vehicle are known to develop, or are identified as exhibiting, altered (increased) aggressive behavior compared to control animals, as assessed using a well-established method for measuring aggressive behavior, and then it is evaluated whether treatment of said aggressive animals with the compound reduces their aggressive behavior compared to animals treated with the vehicle, or even restores the aggressive behavior to the (normal) levels of the control animals.Aggressive animal behavior can be assessed using any standard method for evaluating aggressive behavior parameters, such as, for example, the intruder-resident (RI) test, which can be performed, for example, as described in more detail in Example 3.1. As an example of an appropriate animal model for testing aggression, male SAMP8 mice can be used, using male SAMR1 mice as a control. As illustrated in Example 3 and in Figures 1 and 2, vehicle-treated male SAMP8 mice exhibited significantly increased aggressive behavior compared to the control SAMR1 strain, as shown by a significantly increased number of total attacks and especially grappling attacks. Treatment of male SAMP8 mice with a KDM1A inhibitor (particularly Compound 1) drastically reduces their aggression, as illustrated in Figures 1 and 2 through the number of attacks (both, ata. Petition 870260063781, dated 06 / 29 / 2026, page 21 / 149 13 / 58 total queues and grappling attacks), which are restored in SAMP6 mice treated with Compound 1 to SAMR1 levels. Treatment with the KDM1A inhibitor Compound 1 is thus able to correct the altered aggressive behavior of SAMP8 mice, supporting the use of KDM1A inhibitors to treat aggression and related behavioral changes.

[0037] In addition to exerting therapeutic effects on aggression, KDM1A inhibitors such as Compound 1 are also useful for treating other behavioral disorders such as social withdrawal, as illustrated in Example 4 and Figures 3 and 4. Although mice are highly territorial, rats are known as a more gregarious species and are thus a particularly appropriate species for assessing social interaction behavior and particularly social withdrawal. An appropriate model for assessing social withdrawal is the rat isolation-backing model. In this model, rats are isolated after weaning and deprived of the normal environment that preconditions their social behavior. Isolation at this stage of rat development leads to behavioral changes, particularly a lack of interest in social interactions (social avoidance) in the adult animal, which can be used as a model for human social withdrawal.Social behavior of animals in this model can then be assessed using any standard method for such assessment known in the art, such as the intruder-resident test. As illustrated in Example 4 and Figures 3 and 4, social avoidance parameters are greatly increased in isolated rats treated with vehicle compared to non-isolated rats treated with vehicle, as reflected by the time without social interaction (Figure 3) and the number of avoidances (Figure 4). Treatment with the KDM1A inhibitor Compound 1 greatly reduces social avoidance in isolated rats, as illustrated in Figure 3 through a dependent reduction. Petition 870260063781, dated 06 / 29 / 2026, page 22 / 149 14 / 58 of the dose during the time without social interaction in isolated rats, and in Figure 4 through a reduction in the number of avoidances, which was greatly increased in isolated rats treated with vehicle and was restored to normal (i.e., to levels of non-isolated rats) through treatment with the KDM1A inhibitor Compound 1. Treatment with a KDM1A inhibitor is able to improve or correct social avoidance, supporting the use of KDM1A inhibitors to treat social withdrawal and related social behavior disorders.

[0038] The usefulness of KDM1A inhibitors for treating social behavior disorders is further illustrated in Example 5 and Figures 5 and 6, using another widely used social behavior test, the Three-Chamber Test (TCT). The TCT is a commonly used method for measuring social behavior in mice and is useful for evaluating the effects of a compound to treat social interaction disorders, using animals exhibiting innate or acquired deficits in social behavior. In the TCT test, as explained in more detail in Example 5, after adaptation to the three-chamber arena, a mouse is released into the middle chamber and allowed to explore the other compartments. In the adjacent 'mouse' compartment, a docile stimulus mouse is situated in a wire mesh container, while in the other adjacent compartment a similar container is located without the stimulus mouse (object compartment).The propensity to approach or avoid the compartment with the stimulus mouse provides a measure of sociability. As illustrated in Example 5 and Figures 5 and 6, treatment with a KDM1A inhibitor such as Compound 1 is able to restore social interaction behavior / sociability in subjects exhibiting social interaction alterations. As described in Example 5, unlike the control strain, SAMR1, female SAMP8 mice do not show a preference for the mouse chamber over the object chamber and size. Petition 870260063781, dated 06 / 29 / 2026, page 23 / 149 15 / 58 also spend less time exploring the new mouse, thus showing deficits in social behavior. Treatment of female SAMP8 mice with the KDM1A inhibitor Compound 1 completely restores the social interaction behavior / sociability of SAMP8 mice to SAMR1 levels, as shown by restoration of preference for the socialization chamber (mouse chamber) (see Figure 5) and time spent exploring a new mouse (see Figure 6). Importantly, the therapeutic effects of KDM1A inhibitors as Compound 1 in the treatment of behavioral disorders are obtainable without producing sedative effects, as illustrated in Examples 3 and 4 using standard assays to measure sedative or anxiolytic effects such as the Open Field and Elevated Plus Maze tests. Sedation is a serious side effect of many drugs currently used to treat behavioral disorders.For example, antipsychotic drugs used to treat aggression generally cause strong sedation. KDM1A inhibitors, and particularly Compound 1, are therefore highly advantageous over current treatments in that they can be used to treat behavioral disorders without causing sedative side effects. KDM1A inhibitors

[0039] As used herein, a KDM1A inhibitor is a compound that inhibits KDM1A, particularly human KDM1A. All types of KDM1A inhibitors can be used in the methods and uses according to the invention. Preferably, the KDM1A inhibitor to be used in the methods and uses according to the invention is a small molecule. Both irreversible and reversible KDM1A inhibitors have been reported and can be used according to the present invention. Irreversible KDM1A inhibitors exert their inhibitory activity by becoming covalently linked to the FAD cofactor within the active site. Petition 870260063781, dated 06 / 29 / 2026, page 24 / 149 16 / 58 of KDM1A and are generically based on a 2-cyclopropyl amino moiety such as a 2-(hetero)aryl cyclopropyl amino moiety. Reversible inhibitors of KDM1A have also been shown.

[0040] Non-limiting examples of KDM1A inhibitors that can be used according to the present invention are shown in, for example, WO2010 / 043721, WO2010 / 084160, WO2011 / 035941, WO2011 / 042217, WO2011 / 131697, WO2012 / 013727, WO2012 / 013728, WO2012 / 045883, WO2013 / 057320, WO2013 / 057322, WO2010 / 143582, US2010-0324147, WO2011 / 022489, WO2011 / 131576, WO2012 / 034116, WO2012 / 135113, WO2013 / 022047, WO2013 / 025805, WO2014 / 058071, WO2014 / 084298, WO2014 / 086790, WO2014 / 164867, WO2014 / 205213, WO2015 / 021128, WO2015 / 031564, US2015-0065434, WO2007 / 021839, WO2008 / 127734, WO2015 / 089192, CN104119280, CN103961340, CN103893163, CN103319466, CN103054869, WO2015 / 123408, WO2015 / 123424, WO2015 / 123437, WO2015 / 123465, WO2015 / 156417, WO2015 / 181380, WO2016 / 123387, WO2016 / 130952, WO2016 / 172496, WO2016 / 177656, WO2017 / 027678, CN106045862, WO2012 / 071469, WO2013 / 033688, WO2014 / 085613, WO2015 / 120281, WO2015 / 134973, WO2015 / 168466, WO2015 / 200843, WO2016 / 003917, WO2016 / 004105, WO2016 / 007722, WO2016 / 007727, WO2016 / 007731,WO2016 / 007736, WO2016 / 034946, WO2016 / 037005, WO2016 / 161282, WO2017 / 004519, WO2017 / 027678, WO2017 / 079476, WO2017 / 079670, WO2017 / 090756, WO2017 / 109061, WO2017 / 116558, WO2017 / 114497, CN106432248, CN106478639, CN106831489, CN106928235, CN105985265, WO2017 / 149463, WO2017 / 157322, WO2017 / 195216, WO2017 / 198780, WO2017 / 215464, WO2018 / 081342, WO2018 / 081343, US2017-0283397, as well as, Petition 870260063781, dated 06 / 29 / 2026, page 25 / 149 17 / 58 Petition 870260063781, dated 06 / 29 / 2026, page 26 / 149 18 / 58 Petition 870260063781, dated 06 / 29 / 2026, page 27 / 149 19 / 58

[0041] including any of its optically active stereoisomers, or any of its pharmaceutically acceptable salts or solvates. Any of the compounds shown above comprising a 1,2-substituted cyclopropyl ring may be used in the form of the corresponding trans isomer (where the two substituents on the cyclopropyl ring are in trans configuration), or in the form of any of the respective specific trans isomers (where the two substituents on the cyclopropyl ring have the same absolute configuration as shown in the drawn structure; or where the two substituents on the cyclopropyl ring each have the opposite absolute configuration as shown in the drawn structure).

[0042] Further non-limiting examples of KDM1A inhibitors to be used in accordance with the present invention are shown, for example, in K Taeko et al, Bioorg Med Chem Lett 2015, 25(9):1925-8. doi: 10.1016 / j.bmcl.2015.03.030. Epub 2015 Mar 20, PMID: 25827526; S Valente et al, Eur J Med Chem. 2015, 94:163-74. doi: 10.1016 / j.ejmech.2015.02.060. Epub 2015 Mar 3, PMID:25768700; MN Ahmed Khan et al Med. Chem. Commun., 2015,6, 407-412, DOI: 10.1039 / C4MD00330F epub 29 Sep 2014; M Pieroni et al, Eur J Med Chem. 2015 ;92:377-386. doi: 10.1016 / j.ejmech.2014.12.032. Epub 2015 Jan 7. PMID:25585008; V Rodriguez et al, Med. Chem. Commun., 2015,6, 665-670 DOI: 10.1039 / C4MD00507D, Epub 23 Dec 2014; P Vianello et al, Eur J Med Chem. 2014, 86:352-63. doi: 10.1016 / j.ejmech.2014.08.068. Epub 2014 Aug 27; DP Mold et al, Med. Res. Rev., 2015,35:586-618. doi:10.1002 / med.21334, epub 24-Nov2014; LY Ma et al, 2015, 58(4):1705-16. doi: 10.1021 / acs.jmedchem. 5b00037.Epub 2015 Feb 6; SL Nowotarski et al, 2015, 23(7):1601-12. doi: 10.1016 / j.bmc.2015.01.049. Epub 2015 Feb 7. PMID:25725609; CJ Kutz et al Medchemcomm. 2014, 5(12):1863-1870 PMID: 25580204; C Zhou et al, Chemical Biology & Drug Design,2015,. Petition 870260063781, 06 / 29 / 2026, pág. 28 / 149 20 / 58 85(6):659-671. doi:10.1111 / cbdd.12461, epub 22-Dec-2014; P Prusevich et al, ACS Chem Biol. 2014, 9(6):1284-93. doi: 10.1021 / cb500018s. Epub 2014 Apr 7; B Dulla et al, Org Biomol Chem 2013,11, 3103-3107, doi: 10.1039 / c3ob40217g; JR Hitchin et al, MedChemCommun,2013, 4, 1513-1522 DOI: 10.1039 / c3md00226h; and Y Zhou et al, Biorg Med Chem Lett, 2015, online publication 20-Jun-2015, doi:10.1016 / j.bmcl.2015.06.054.

[0043] Irreversible KDM1A inhibitors that can be used in the methods / uses of the invention include, without limitation, any of the compounds shown in: WO2010 / 043721, WO2010 / 084160, WO2011 / 035941, WO2011 / 042217, WO2011 / 131697, WO2012 / 013727, WO2012 / 013728, WO2012 / 045883, WO2013 / 057320, WO2013 / 057322, WO2010 / 143582, US2010-0324147, WO2011 / 131576, WO2012 / 135113, WO2013 / 022047, WO2014 / 058071, WO2014 / 084298, WO2014 / 086790, WO2014 / 164867, WO2015 / 021128; WO2015 / 123408, WO2015 / 123424, WO2015 / 123437, WO2015 / 123465, WO2015 / 156417, WO2015 / 181380, WO2016 / 123387, WO2016 / 130952, WO2016 / 172496, WO2016 / 177656, WO2017 / 027678, CN106045862, WO2014 / 164867 WO2017 / 027678, WO2017 / 079476, WO2017 / 109061, WO2017 / 116558, WO2017 / 114497, CN106831489; K Taeko et al, Bioorg Med Chem Lett. 2015, 25(9): 1925-8. doi: 10.1016 / j.bmcl.2015.03.030. Epub 2015 Mar 20, PMID: 25827526; S Valente et al, Eur J Med Chem. 2015, 94:163-74. doi: 10.1016 / j.ejmech.2015.02.060.Epub 2015 Mar 3, PMID:25768700; MN Ahmed Khan et al Med. Chem. Commun., 2015,6, 407-412, DOI: 10.1039 / C4MD00330F epub 29 Sep 2014; M Pieroni et al, Eur J Med Chem. 2015 ;92:377-386. doi: 10.1016 / j.ejmech.2014.12.032. Epub 2015 Jan 7. PMID:25585008; V Rodriguez et al, Med. Chem. Commun., 2015,6, 665-670 DOI: 10.1039 / C4MD00507D, Epub 23 Dec 2014; or P Vianello et al, Eur J Med Chem. 2014, 86:352-63. doi: 10.1016 / j.ejmech.2014.08.068. Epub 2014 Aug 27, assim como. Petition 870260063781, of 29 / 06 / 2026, p. 29 / 149 21 / 58 Petition 870260063781, of 29 / 06 / 2026, p. 30 / 149 22 / 58

[0044] including any of its optically active stereoisomers; or any of its pharmaceutically acceptable salts or solvates. Any of the compounds shown above comprising a 1,2-substituted cyclopropyl ring may be used in the form of the corresponding trans isomer (where the two substituents on the cyclopropyl ring are in trans configuration), or in the form of any of the respective specific trans isomers (where the two substituents on the cyclopropyl ring have the same absolute configuration as shown in the drawn structure; or where the two substituents on the cyclopropyl ring each have the opposite absolute configuration as shown in the drawn structure).

[0045] Reversible KDM1A inhibitors that can be used Petition 870260063781, dated 06 / 29 / 2026, p. 31 / 149 23 / 58 in the methods I uses of the invention include, without limitation, any of the compounds shown in WO2007 / 021839, WO2008 / 127734, WO2011 / 022489, WO2012 / 034116, WO2012 / 071469, WO2013 / 025805, US2015 / 0065434, WO2013 / 033688, CN103054869, CN103319466, WO2014 / 085613, CN103893163A, CN103961340, WO2014 / 205213, WO2015 / 031564, WO2015 / 089192, WO2015 / 120281, WO2015 / 134973, WO2015 / 168466, WO2015 / 200843, WO2016 / 003917, WO2016 / 004105, WO2016 / 007722, WO2016 / 007727, WO2016 / 007731, WO2016 / 007736, WO2016 / 034946, WO2016 / 037005, WO2016 / 161282, WO2017 / 004519, WO2017 / 079670, WO2017 / 090756, CN106432248, CN106478639, CN 106928235, as well as

[0046] including any of its optically active stereoisomers, or any of its pharmaceutically acceptable salts or solvates. In some embodiments, in the methods and uses according to the invention, the KDM1A inhibitor is an irreversible KDM1A inhibitor, preferably a 2-(hetero)aryl cyclopropyl amino KDM1A inhibitor. As used herein, a 2-(hetero)aryl cyclopropyl amino KDM1A inhibitor or a 2-(hetero)aryl cyclopropyl amino compound means a KDM1A inhibitor whose chemical structure comprises a subcutaneous cyclopropyl ring. Petition 870260063781, dated 06 / 29 / 2026, p. 32 / 149 24 / 58 substituted at position 1 with an amino group, which is optionally substituted, and substituted at position 2 with an aryl or heteroaryl group (where the aryl or heteroaryl group is optionally substituted).

[0047] The ability of a compound to inhibit KDM1A can be tested in vitro using any method for determining KDM1A inhibition known in the art, for example, the method shown in Example 2.

[0048] A particularly preferred KDM1A inhibitor for use in the methods and uses according to the invention is 5-((((1R,2S)-2-(4-benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt or solvate thereof.

[0049] Other KDM1A inhibitors that may be used in the methods and uses of the invention include: (trans)-N1-((1R,2S)-2-phenylcyclopropyl)cyclohexane-1,4-diamine; (cis)-N1-((1S,2R)-2-phenylcyclopropyl)cyclohexane-1,4-diamine; (trans)-N1-((1S,2R)-2-phenylcyclopropyl)cyclohexane-1,4-diamine; (cis)-N1-((1R,2S)-2-phenylcyclopropyl)cyclohexane-1,4-diamine; N1-((trans)-2-(thiazol-5-yl) cyclopropyl) cyclohexane-1,4-diamine; N1-((trans)-2-(pyridin-3-yl)cyclopropyl)cyclohexane-1,4-diamine; N1-((trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropyl)cyclohexane-1,4-diamine; N1-((trans)-2-(3'-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropyl)cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-(benzyloxy) phenyl) cyclo propyl hexane-1,4-diamine; 4-(((trans)-2-(6-(3-(trifluoromethyl) phenyl) pyridin-3-yl) cyclopropyl) amino) cyclo-hexanol; 4-(((trans)-2-(6-(3-(trifluoromethyl) phenyl) pyridin-3-yl) cyclopropyl) amino) cyclo-hexane carboxamide; N-(4-(((trans)-2-(6-(3-(trifluoromethyl) phenyl) pyridin-3-yl) cyclopropyl) ami Petition 870260063781, 06 / 29 / 2026, pág. 33 / 149 25 / 58 no) ciclo-hexil) acetamide; N-4-(((trans)-2-(6-(3-(trifluoromethyl) phenyl) pyridin-3-yl) cyclopropyl) amino) cyclo-hexyl)) methane sulfonamida; (R)-1-(4-(((trans)-2-phenyl cyclopropyl) amino) cyclo-hexyl) pyrrolidine-3-amine; N1-((trans)-2-(4'-chloro-[1,1'-biphenyl]-4-yl)cyclopropyl)cyclo-hexane-1,4-diamine; N1-((trans)-2-(3'-chloro-[1,1'-biphenyl-4-yl)cyclopropyl)cyclo-hexane-1,4-diamine; 4'-((trans)-2-((4-aminocyclo-hexyl) amino)cyclopropyl)-[1,1-biphenyl]-3-ol; N-(4'-((trans)-2-((4-amino cyclo-hexyl) amino) cyclo propyl)-[1,1'-biphenyl]-3yl) methane sulfonamide; N1-((ttrans)-2-(4-((2-fluor benyl) oxy) phenyl) cyclopropyl) cyclo-hexane-1,4diamine; N1-((trans)-2-(4-((3-fluor benzyl) oxy) phenyl) cyclopropyl) cyclo-hexano1,4-diamine; N1-((trans)-2-(4-((4-fluor benzyl) oxy) phenyl) cyclopropyl) cyclo-hexano1,4-diamine; N1-methyl-N4-((trans)-2-phenyl cyclopropyl) cyclo-hexane-1,4-diamine; N1-methyl-N4-((trans)-2-(3'-(trifluoromethyl)-[1,1']-biphenyl]-4-yl)cyclopropyl)cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-(benzyloxy)phenyl) cyclopropyl)-N4-methyl cyclo-hexano1,4-diamine; N1-((trans)-2-phenylcyclopropyl)cyclobutane-1,3-diamine; N1-((trans)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl) cyclopropyl) cyclobutane-1,3-diamine; N1-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)cyclobutane-1,3-diamine; N1-((trans)-2-phenylcyclopropyl)-2,3-dihydro-1H-indene-1,3-diamine; N1 -((trans)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)-2,3-dihydro-1H-indene-1,3-diamine; Petition 870260063781, dated 06 / 29 / 2026, p. 34 / 149 26 / 58 N1-((trans)-2-(4-(benzyloxy)phenyl)propylcyclo)-2,3-dihydro-1H-indene1,3-diamine; N1-((trans)-2-fluoro-2-phenylcyclopropyl)cyclohexane-1,4-diamine; N1-((1S,2S)-2-fluoro-2-phenylcyclopropyl)cyclohexane-1,4-diamine; N1-((1R,2S)-2-fluoro-2-phenylcyclopropyl)cyclohexane-1,4-diamine; 1-methyl-N4-((trans)-2-phenyl cyclopropyl) cyclohexane-1,4-diamine; 4-(amino methyl)-N-((trans)-2-phenyl cyclopropyl) cyclohexanamine; N1-((trans)-2-phenylcyclopropyl)cyclohexane-1,3-diamine; N1-((cis)-2-phenylcyclopropyl)cyclohexane-1,4-diamine; (4-(((trans)-2-phenylcyclopropyl)amino)cyclohexyl) t-butyl carbamate; 1-ethyl-3-(4-(((trans)-2-phenylcyclopropyl)amino)cyclohexyl) urea; 4-morpholino-N-((trans)-2-phenyl cyclopropyl) cyclohexanamine; N1-((trans)-2-(4-bromophenyl)cyclopropyl)cyclohexane-1,4-diamine; N1-(2-(o-tolyl)cyclopropyl)cyclohexane-1,4-diamine; N1-(2-(4-(trifluoromethyl) phenyl) cyclopropyl) cyclohexane-1,4-diamine; N1-(2-(4-methoxyphenyl)cyclopropyl)cyclohexane-1,4-diamine; 4-(2-((4-amino cyclohexyl) amino) cyclopropyl) phenol; N1-(2-(2-fluorophenyl)cyclopropyl)cyclohexane-1,4-diamine; N1-(2-(3,4-difluorophenyl)cyclopropyl)cyclohexane-1,4-diamine; N1-(2-(naphthalen-2-yl)cyclopropyl)cyclo-hexane-1,4-diamine; N1-(2-methyl-2-phenyl cyclopropyl)cyclo-hexane-1,4-diamine; (R)-1-(4-(((trans)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)amino)cyclo-hexyl)pyrrolidine-3-amine; (cis)-N1-((1S,2R)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)cyclo-hexane-1,4-diamine; (trans)-N1-((1S,2R)-2-(3'-(trifluoromethyl)-[1, 1 '-biphenyl]-4-yl)cyclopropyl)cyclo-hexane-1,4-diamine; (cis)-N1-((1R,2S)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)cyclo-hexane-1,4-diamine; (trans)-N 1 ​​-((1 R,2S)-2-(3'-(trifluoromethyl)-[1, 1 '-biphenyl]-4-yl)cyclopropyl) Petition 870260063781, 06 / 29 / 2026, pág. 35 / 149 27 / 58 cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-cyclo propyl phenyl) cyclo propyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-(pyridin-3-yl) phenyl) cyclopropyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-(1H-indazol-6-yl) phenyl)cyclopropyl)cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-(1H-pyrazol-5-yl)phenyl)cyclopropyl)cyclo-hexane-1,4-diamine; 3-(5-((trans-2-((4-amino cyclo-hexyl) amino) cyclopropyl) thiophen-2-yl) phenol; 3-(5-((trans)-2-((4-aminocyclo-hexyl) amino)cyclopropyl)thiazol-2-yl)phenol; 3-(5-((trans)-2-((4-amino cyclo-hexyl) amino) cyclopropyl) pyridin-2-yl) 5-methoxy benzonitrile; 5-(5-((trans)-2-((4-aminocyclo-hexyl) amino)cyclopropyl)pyridin-2-yl)-2methyl phenol; N-(4'-((trans)-2-((4-aminocyclo-hexyl) amino)cyclopropyl)-6-methoxy[1,1'-biphenyl]-3-yl) methane sulfonamida; N-(3-(5-((trans)-2-((4-amino cyclo-hexyl) amino) cyclo propyl) thiazol-2-yl) phenyl)-2-cyano benzene sulfonamide; N-(4'-((trans)-2-((4-aminocyclo-hexyl) amino)cyclopropyl)-[1,1'-biphenyl]-3yl)-2-cyanobenzene sulfonamida; 6-amino-N-(4'-((trans)-2-((4-amino cyclo-hexyl) amino) cyclopropyl)-[1,1'biphenyl]-3-yl) pyridino-3-sulfonamida; N-(4'-((trans)-2-((4-amino cyclo-hexyl) amino) cyclo propyl)-[1,1'-biphenyl]-3yl) piperazino-1-sulfonamide; N1-((cis)-2-fluor-2-phenyl cyclo propyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-((3-(piperazin-1-yl) benzyl) óxi) phenyl) cyclopropyl) cyclohexane-1,4-diamine; N1-((trans)-2-(4-(pyridn-3-yl methoxy)phenyl)cyclopropyl)cyclo-hexane-1,4diamine; Petition 870260063781, 06 / 29 / 2026, pág. 36 / 149 28 / 58 N1-((trans)-2-(6-((3-methyl benzyl) amino) pyridin-3-yl) cyclopropyl) cyclohexane-1,4-diamine; 3-((5-((trans)-2-((4-amino cyclo-hexyl) amino) cyclopropyl) pyridin-2-yl) amino) benzonitrilate; N1-((trans)-2-(naphthalen-2-yl) cyclopropyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-(o-tolyl) cyclopropyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-(trifluoromethyl)phenyl)cyclopropyl)cyclo-hexane-1,4-diamine; N1-((trans)-2-(4-methoxy phenyl) cyclo propyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-(2-fluor phenyl) cyclo propyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-(3,4-difluor phenyl) cyclo propyl) cyclo-hexane-1,4-diamine; N1-((trans)-2-methyl-2-phenylcyclopropyl)cyclohexane-1,4-diamine; (cis)-N1-((1S,2R)-2-(pyridin-3-yl)cyclopropyl)cyclohexane-1,4-diamine; (trans)-N1-((1R,2S)-2-(pyridin-3-yl) cyclopropyl) cyclo-hexane-1,4-diamine; (cis)-N1-((1R,2S)-2-(pyridin-3-yl) cyclopropyl) cyclo-hexane-1,4-diamine; (tans)-N1-((1S,2R)-2-(pyridin-3-yl) cyclopropyl) cyclo-hexane-1,4-diamine; (cis)-N1-((1S,2R)-2-phenyl propyl cycle) butane-1,3-diamine cycle; (trans)-N1-((1R,2S)-2-phenyl propyl cycle) butane-1,3-diamine cycle; (cis)-N1-((1R,2S)-2-phenyl propyl cycle) butane-1,3-diamine cycle; (trans)-N1-((1R,2S)-2-phenyl propyl cycle) butane-1,3-diamine cycle; (cis)-N1-((1S,2R)-2-(3,4-difluorophenyl) cyclopropyl) cyclo-hexane-1,4-diamine; (trans)-N1-((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)cyclo-hexane-1,4diamine; (cis)-N1-((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)cyclo-hexane-1,4-diamine; (trans)-N1-((1S,2R)-2-(3,4-difluorophenyl) cyclopropyl) cyclo-hexane-1,4diamine; (cis)-N1-((1S,2R)-2-(naphthalen-2-yl) cyclopropyl) cyclo-hexane-1,4-dia Petition 870260063781, 06 / 29 / 2026, pág. 37 / 149 29 / 58 mina; (trans)-N1-((1R,2S)-2-(naphthalen-2-yl) cyclopropyl) cyclo-hexane-1,4-diamine; (cis)-N1-((1R,2S)-2-(naphthalen-2-yl) cyclopropyl) cyclo-hexane-1,4-diamine; (trans)-N1-((1S,2R)-2-(naphthalen-2-yl) cyclopropyl) cyclo-hexane-1,4-diamine; (cis)-N1-((1S,2R)-2-(4-(1H-pyrazol-5-yl)phenyl)cyclopropyl)cyclo-hexano1,4-diamine; (trans)-N1-((1R,2S)-2-(4-(1H-pyrazol-5-yl) phenyl)cyclopropyl)cyclo-hexane-1,4-diamine; (cis)-N1-((1R,2S)-2-(4-(1H-pyrazol-5-yl) phenyl)cyclopropyl)cyclo-hexane1,4-diamine; (trans)-N1-((1S,2R)-2-(4-(1H-pyrazol-5-yl)phenyl)cyclopropyl)cyclo-hexane-1,4-diamine; N-(4'-((1R,2S)-2-(((cis)-4-aminocyclo-hexyl) amino)cyclopropyl)-[1,1'biphenyl]-3-yl)piperazino-1-asulfonamida; N-(4'-((1S,2R)-2-(((trans)-4-aminocyclo-hexyl) amino)cyclopropyl)-[1,1'biphenyl]-3-yl) piperazino-1-sulfonamida; N-(4'-((1S,2R)-2-(((cis)-4-amino cyclo-hexyl) amino) cyclo propyl)-[1,1'biphenyl]-3-yl) piperazino-1-sulfonamide; N-(4'-((1R,2S)-2-(((trans)-4-aminocyclo-hexyl) amino)cyclopropyl)-[1,1'biphenyl]-3-yl) piperazino-1-sulfonamida; (cis)-N1-((1S,2R)-2-(4-((2-fluorobenzyl) oxy)phenyl) cyclopropyl) cyclo-hexane-1,4-diamine; (trans)-N1-((1R,2S)-2-(4-((2-fluorobenzyl) oxy) phenyl) cyclopropyl) cyclohexane-1,4-diamine; (cis)-N1-((1R,2S)-2-(4-((2-fluorobenzyl)oxy)phenyl)cyclopropyl)cyclohexane-1,4-diamine; (trans)-N1-((1S,2R)-2-(4-((2-fluorobenzyl) oxy) phenyl) propyl cycle) cyclohe Petition 870260063781, dated 06 / 29 / 2026, page 38 / 149 30 / 58 xane-1,4-diamine; N-((trans)-2-phenyl cyclopropyl) piperidin-4-amine; N-((1S,2R)-2-phenyl cyclopropyl) piperidin-4-amine; N-((1R,2S)-2 phenylcyclopropyl)piperidin-4-amine; N-((trans)-2-(4-benzyloxy)phenyl)cyclopropyl)piperidin-4-amine; N-((trans)-2-(6-(3-(trifluoromethyl) phenyl) pyridin-3-yl) cyclopropyl) tetrahydro-2H-pyran-4-amine; N-((trans)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine; N-((trans)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine; N-((trans)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)piperidine-4amine; N-((trans)-2-phenyl cyclopropyl) piperidin-3-amine; N-((trans)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)piperidine-3amine; N-((trans)-2-(4-(benzyloxy) phenyl) cyclo propyl) piperidin-3-amine; N-((trans)-2-phenyl cyclopropyl) pyrrolidin-3-amine; N-((trans)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)pyrrolidine-3amine; N-((trans)-2-(4-(benzyloxy) phenyl) cyclo propyl) pyrrolidine-3-amine; N-((trans)-2-phenyl cyclopropyl) azetidine-3-amine; N-((trans)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl) azetidine-3amine; N-((trans)-2-(4-(benzyloxy) phenyl) cyclo propyl) azetidine-3-amine; N-((trans)-2-phenyl cyclopropyl) azepan-3-amine; N-((trans)-2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine; N-((trans)-2-phenylcyclopropyl)-3-aza bicyclo[3.2.1] octan-8-amina; N-((trans)-2-phenylcyclopropyl)decadro quinolin-4-amina; N-((trans)-2-phenyl cyclo propyl)-1,2,3,4-tetra-hydro quinolin-4-amina; N-((trans)-2-fenil cyclo propyl)-3-aza spiro[5.5] undecan-9-amina; N-((trans)-2-fenil cyclo propyl)-2-aza spiro[4.5] decan-8-amina; Petition 870260063781, of 29 / 06 / 2026, p. 39 / 149 31 / 58 N-((trans)-2-fenil cyclo propyl)-2,3-di-hidro spiro [indeno-1,4'-piperidin]3-amina; N-((1S,2R)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amina; N-((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amina; N-((1S,2R)-2-(piridin-3-yl)cyclopropyl)piperidin-4-amina; N-((1R,2S)-2-(piridin-3-yl)cyclopropyl)piperidin-4-amina; N-((1S,2S)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amina; N-((1R,2R)-2-(thiazol-5-yl)cyclopropyl)piperidine-4-amine; N-((1S,2R)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)piperidin4-amine; N-((1R,2S)-2-(3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)cyclopropyl)piperidin4-amine; N-((trans)-2-phenyl cyclopropyl)-7-aza spiro[3,5] nonan-2-amine; N-(2-(o-tolyl) cyclopropyl) piperidin-4-amine; N-(2-(2-fluorophenyl) cyclopropyl) piperidin-4-amine; N-(2-(3,4-difluorophenyl) cyclopropyl) piperidin-4-amine; N-(2-(4-methoxy phenyl) propyl cyclo) piperidin-4-amine; N-(2-(naphthalen-2-yl)cyclopropyl)piperidine-4-amine; N-(2-methyl-2-phenyl cyclopropyl) piperidin-4-amine; N-(6-methoxy-4'-((trans)-2-(piperidin-4-yl amino)cyclopropyl)-[1,T-biphenyl]3-yl) methane sulfonamida; N-(4'-((trans)-2-(piperidin-4-yl amino)cyclopropyl)-[1,1'-biphenyl]-3-yl) propane-2-sulfonamida; 1-(metil sulfonil)-N-((trans)-2-fenil cyclo propyl) piperidin-4-amina; 1-(4-(((tritans)-2-(4-bromo phenyl)cyclopropyl)amino)piperidin-1-yl)ethanona; 4-(((trans)-2-(4-bromo phenyl)cyclopropyl)amino)piperidino-1-carboxamida; N-((trans)-2-(4-bromofenil) ciclo propyl) tetra-hidro-2H-piran-4-amina; 2,2,6,6-tetra metil-N-((trans)-2-fenil cyclo propyl) piperidin-4-amina; Petition 870260063781, of 29 / 06 / 2026, p. 40 / 149 32 / 58 1-methyl-N-((trans)-2-phenyl cyclo propyl)piperidin-4-amina; 1-isopropyl-N-((trans)-2-phenyl cyclo propyl)piperidin-4-amina; N-((trans)-2-phenyl cyclo propyl)-1-(2,2,2-trifluoro ethyl)piperidin-4-amina; N-((trans)-2-phenyl cyclo propyl)-1-(pyridin-4-yl)piperidin-4-amina; 1,1- dioxid de 4-(((trans)-2-(4-bromo phenyl) cyclo propyl) amino) tetrahydro-2H-thiopyrano; N-((trans)-2-fluor-2-phenylcyclopropyl)piperidin-4-amina; N-((1S,2S)-2-fluor-2-phenyl cyclopropyl) piperidin-4-amine; N-((1R,2R)-2-fluor-2-phenyl cyclopropyl) piperidin-4-amine; N-((trans)-2-(naphthalene-2-yl) cyclo propyl) piperidin-4-amine; N-((trans)-2-methyl-2-phenyl cyclopropyl) piperidin-4-amine; N-((trans)-2-(o-tolyl) cyclo propyl) piperidin-4-amine; N-((trans)-2-(2-fluor phenyl) cyclo propyl) piperidin-4-amine; N-((trans)-2-(3,4-difluorophenyl) cyclo propyl) piperidin-4-amine; N-((trans)-2-(4-methoxy phenyl) cyclo propyl) piperidin-4-amine; (trans)-2-phenyl-N-(piperidin-4-yl methyl)cyclopropanamine; (trans)-2-phenyl-N-(2-(piperidin-4-yl) ethyl)cyclopropanamine; (trans)-2-phenyl-N-(2-(tetra-hidro-2H-pyran-4-yl) ethyl) propanamine cycle; (trans)-2-(4'-chloro-[1,1'-biphenyl]-4-yl)-N-(2-(tetra-hidro-2H-pyran-4-yl) ethyl) propanamine cycle; (trans)-N-(piperidin-4-yl methyl)-2-(pyridin-3-yl)cyclopropanamine; (trans)-N-(piperidine-4-yl methyl)-2-(thiazol-5-yl) propanamine cycle; (trans)-N-(piperidine-4-yl methyl)-2-(3'-(trifluoromethyl)-[1, 1 '-biphenyl]-4-yl) cyclic propanamine; (trans)-2-(4-(benzyloxy) phenyl)-N-(piperidin-4-yl methyl) propanamine cycle; (trans)-N-(2-(piperidin-4-yl) ethyl)-2-(pyridin-3-yl) propanamine cycle; (trans)-N-(2-(piperidin-4-yl) ethyl)-2-(thiazol-5-yl) propanamine cycle; (trans)-N-(2-(piperidin-4-yl) ethyl)-2-(3′-(trifluoromethyl)-[1, 1′-biphenyl]-4-yl) propanamine cycle; (trans)-2-(4-(benzyloxy) phenyl)-N-(2-(piperidin-4-yl) ethyl) propanam cycle Petition 870260063781, dated 6 / 29 / 2026, p. 41 / 149 33 / 58; (1S,2R)-2-phenyl-N-(piperidin-4-yl methyl) propanamine cycle; (1R,2S)-2-phenyl-N-(piperidin-4-yl methyl) propanamine cycle; (1S,2R)-2-phenyl-N-(2-(piperidin-4-yl) ethyl) propanamine cycle; (1R,2S)-2-phenyl-N-(2-(piperidin-4-yl) ethyl)cyclopropanamine; (1S,2R)-N-(piperidin-4-yl methyl)-2-(pyridin-3-yl) cyclopropanamine; (1R,2S)-N-(piperidin-4-yl methyl)-2-(pyridin-3-yl) cyclopropanamine; (1S,2S)-N -(piperidin-4-yl methyl)-2-(thiazol-5-yl) cyclopropanamine; (1R,2R)-N-(piperidin-4-yl methyl)-2-(thiazol-5-yl) cyclopropanamine; (1S,2R)-N-(piperidn-4-yl methyl)-2-(3'-(trifluoromethyl)-[1, 1 '-biphenyl]-4-yl)cyclopropanamine; (1 R,2S)-N-(piperidin-4-yl methyl)-2-(3'-(trifluoromethyl)-[1, 1 '-biphenyl]-4-yl)cyclopropanamine; (1S,2R)-2-(4-(benzyloxy) phenyl)-N-(piperidin-4-yl methyl) propanamine cyclo; (1R,2S)-2-(4-(benzyloxy) phenyl)-N-(piperidin-4-yl methyl) propanamine cyclo; (1S,2R)-N-(2-(piperidin-4-yl) ethyl)-2-(pyridin-3-yl) cyclopropanamine; (1R,2S)-N-(2-(piperidin-4-yl) ethyl)-2-(pyridin-3-yl) cyclopropanamine; (1S,2S)-N -(2-(piperidin-4-yl) ethyl)-2-(thiazol-5-yl) propanamine cycle; (1R,2R)-N-(2-(piperidin-4-yl) ethyl)-2-(thiazol-5-yl) propanamine cycle; (1S,2R)-N-(2-(piperidin-4-yl) ethyl)-2-(3′-trifluoromethyl)-[1, 1′-biphenyl]-4-yl) propanamine cycle; (1 R,2S)-N-(2-piperidine-4-yl) ethyl)-2-(3'-(trifluoromethyl)-[1, 1 '-biphenyl]-4-yl) propanamine cycle; (1S,2R)-2-(4-(benzyloxy) phenyl)-N-(2-piperidin-4-yl) ethyl) propanamine cycle; (1R,2S)-2-(4-(benzyloxy) phenyl)-N-(2-(piperidin-4-yl) ethyl) propanamine cycle; (trans)-2-phenyl-N-(pyrrolidin-3-yl methoxy) propanamine cycle; (trans)-2-(4-((2-fluorine benzyl) oxy) phenyl)-N-(piperidin-4-yl methyl) propanamine cycle; Petition 870260063781, dated 6 / 29 / 2026, p. 42 / 149 34 / 58 (trans)-N-(azetidin-3-yl methyl)-2-phenyl cyclic propanamine; (trans)-2-(4-cycle propyl phenyl)-N-(piperidin-4-yl methyl) cyclopropanamine; (trans)-N-(piperidin-4-yl methyl)-2-(4-pyridin-3-yl) phenyl) propanamine cycle; (trans)-2-(4-(1H-pyrazol-5-yl) phenyl)-N-(piperidin-4-yl methyl) propanamine cycle; (trans)-2-(naphthalen-2-yl)-N-(piperidine-4-yl methyl) propanamine cycle; 2-methyl-2-phenyl-N-(piperidin-4-yl methyl) propanamine cycle; (trans)-2-methyl-2-phenyl-N-(piperidine-4-yl methyl) propanamine cycle; (trans)-2-(4-(benzyloxy) phenyl)-N-((1-methyl piperidine-4-yl) methyl) propanamine cycle; Acid 4-((4-(((((1R,2S)-2-phenyl cyclic propyl) amino) methyl) piperidin-1-yl)methyl)benzoic acid; Acid 1-((4-(methoxy methyl)-4-((((1R,2S)-2-phenyl cyclic propyl amino) methyl) piperidin-1-yl) methyl) carboxylic butane cycle; N-[(2S)-5-{[(1R,2S)-2-(4-fluorine phenyl) propyl cycle] amino}-1-(4-methyl piperazine-1-yl)-1-oxo pentane-2-yl]-4-(1 H-1,2,3-triazol-1-yl) benzamide; 4-[2-(4-amino piperidin-1-yl)-5-(3-fluoro-4-methoxy phenyl)-1-methyl-6-oxo-1,6- Petition 870260063781, dated 06 / 29 / 2026, page 43 / 149 35 / 58 including any optically active stereoisomer thereof, or a pharmaceutically acceptable salt or solvate thereof. Pharmaceutical Formulations

[0050] Although it is possible that a KDM1A inhibitor, for example, Compound 1, could be administered for use in therapy directly as such, it is typically administered in the form of a pharmaceutical composition, which comprises the compound as the active pharmaceutical ingredient along with one or more pharmaceutically acceptable excipients or carriers. Any reference herein to the KDM1A inhibitor includes a reference to the compound as such, i.e., the corresponding compound in non-salt form (e.g., as a free base) or in the form of any of its pharmaceutically acceptable salts or solvates. Petition 870260063781, dated 06 / 29 / 2026, page 44 / 149 36 / 58 acceptable, as well as a reference to a pharmaceutical composition comprising said compound and one or more pharmaceutically acceptable excipients or vehicles.

[0051] The KDM1A inhibitor can be administered by any means that accomplishes the intended purpose. Examples include administration via oral, parenteral (including, for example, intravenous, subcutaneous, or intracerebral), or topical routes.

[0052] For oral release, the compound may be incorporated into a formulation that includes pharmaceutically acceptable carriers such as binders (e.g., gelatin, cellulose, tragacanth gum), excipients (e.g., starch, lactose), lubricants (e.g., magnesium stearate, silicon dioxide), disintegrating agents (e.g., alginate, Primogel, and corn starch), and sweetening or flavoring agents (e.g., glucose, sucrose, saccharin, methyl salicylate, and mint). The formulation may be orally released, for example, in the form of gelatin-enclosed capsules or tablets. Capsules and tablets may be prepared using any conventional techniques. Capsules and tablets may also be coated with various coatings known in the art for modification of aromas, flavors, colors, and shapes of the capsules and tablets. In addition, liquid carriers such as fatty oil may also be included in capsules.Suitable oral formulations may also be in the form of suspensions, syrups, chewing gum, wafers, elixirs, and the like. If desired, conventional agents for modifying aromas, flavors, colors, and shapes of special forms may also be included. In addition, for convenient administration via enteral feeding tube in patients unable to swallow, the active compounds may be dissolved in an acceptable lipophilic vegetable oil vehicle such as olive oil, corn oil, and safflower oil. Petition 870260063781, dated 06 / 29 / 2026, page 45 / 149 37 / 58

[0053] The compound can also be administered parenterally in the form of a solution or suspension, or in lyophilized form capable of conversion into a solution or suspension before use. In such formulations, pharmaceutically acceptable diluents or vehicles such as sterile water and physiological saline buffer may be used. Other conventional solvents, pH buffers, stabilizers, antibacterial agents, surfactants, and antioxidants may all be included. For example, useful components include sodium chloride buffers, acetates, citrates, or phosphates, glycerin, dextrose, fixed oils, methylparabens, polyethylene glycol, propylene glycol, sodium bisulfate, benzyl alcohol, ascorbic acid, and the like. Parenteral formulations may be stored in any containers such as vials and ampoules.

[0054] For topical administration, the compound may be formulated as lotions, creams, ointments, gels, sprays, pastes, pulses, suspensions, drops, and aerosols. Thus, one or more thickening, humectant, and stabilizing agents may be included in the formulations. Examples of such agents include, but are not limited to, polyethylene glycol, sorbitol, xanthan gum, petrolatum, beeswax, or mineral oil, lanolin, squalene, and the like. A special form of topical administration is delivery via a transdermal patch. Methods for preparing transdermal patches are shown, for example, in Brown, et al. (1988) Ann. Rev. Med. 39:221-229, which is incorporated herein by reference.

[0055] Subcutaneous implantation for sustained release of the compound may also be an appropriate delivery route. This links surgical procedures to implantation of an active compound in any appropriate formulation into a subcutaneous space, for example, under the anterior abdominal wall. See, for example, Wilson et al. (1984) J. Clin. Psych. 45:242-247. Hydrogels may be Petition 870260063781, dated 06 / 29 / 2026, p. 46 / 149 38 / 58 used as a vehicle for the sustained release of active compounds. Hydrogels are generically known in the art. They are typically manufactured by crosslinking high molecular weight biocompatible polymers into a network, which swells in water to form a gel-like material. Preferably, hydrogels are biodegradable or bioabsorbable. For the purposes of this invention, hydrogels manufactured from polyethylene glycols, collagen, or poly(glycolic-co-L-lactic acid) may be useful. See, for example, Phillips et al. (1984) J. Pharmaceut. Sci., 73:1718-1720.

[0056] The compound can also be conjugated to a non-peptidic, non-immunogenic, water-soluble high molecular weight polymer to form a polymer conjugate. For example, the compound can be covalently linked to polyethylene glycol to form a conjugate. Typically, such a conjugate exhibits improved solubility, stability, and reduced toxicity and immunogenicity. Thus, when administered to a patient, the compound in the conjugate may have a longer half-life in the body and exhibit better efficacy. See generically Burnham (1994) Am. J. Hosp. Pharm. 15:210-218. PEGylated proteins are currently being used in protein replacement therapies and for other therapeutic uses. For example, PEGylated interferon (PEG-INTRON A) is clinically used to treat Hepatitis B. PEGylated adenosine deaminase (ADAGEN) is being used to treat severe combined immunodeficiency disease (SCIDS).PEGylated L-asparaginase (ONCAPSPAR) is being used to treat acute lymphoblastic leukemia (ALL). It is preferred that the covalent bond between the polymer and the active compound and / or the polymer itself be hydrolytically degradable under physiological conditions. Such conjugates, known as prodrugs, can readily release the active compound within the body. Controlled release of an active compound can also be achieved through incorporation. Petition 870260063781, dated 06 / 29 / 2026, page 47 / 149 39 / 58 active ingredient in microcapsules, nanocapsules, or hydrogels generically known in the art. Other pharmaceutically acceptable prodrugs of the compound include, but are not limited to, esters, carbonates, thiocarbonates, N-acyl derivatives, N-acyl alkyl derivatives, quaternary amine derivatives, N-Mannich bases, Schiff bases, amino acid conjugates, phosphate esters, metal salts, and sulfonate esters.

[0057] Liposomes can also be used as vehicles for the active compound. Liposomes are micelles made of various lipids such as cholesterol, phospholipids, fatty acids, and their derivatives. Various modified lipids can also be used. Liposomes can reduce the toxicity of active compounds and increase their stability. Methods for preparing liposome suspensions containing active ingredients are generally known in the art. See, for example, US Patent No. 4522 811; Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, NY (1976).

[0058] Pharmaceutical compositions, such as oral and parenteral compositions, may be formulated in unit dosage forms for ease of administration and uniformity of dosage. As used herein, unit dosage forms refer to physically discrete units suitable as unit dosages for administration to subjects, each unit containing a predetermined amount of active ingredient calculated to produce the desired therapeutic effect, in association with one or more appropriate pharmaceutical vehicles.

[0059] In therapeutic applications, pharmaceutical compositions are to be administered in a manner appropriate to the disease being treated, as determined by those skilled in medical techniques. An appropriate dose and appropriate duration and frequency Petition 870260063781, dated 06 / 29 / 2026, pp. 48 / 149 40 / 58 The dosage regimen will be determined by factors such as the patient's condition, the type and severity of the disease, the particular form of the active ingredient, the method of administration, among others. In general, an appropriate dose and administration regimen provides the pharmaceutical composition in a sufficient quantity to provide therapeutic benefit, for example, an improved clinical outcome, such as more frequent partial or complete remissions, or longer total and / or disease-free survival, or decreased symptom severity, or any other objectively identifiable improvement as noted by the physician. Effective doses can generally be evaluated or extrapolated using experimental models such as dose-response curves derived from animal model or in vitro testing systems such as those illustrated in the Examples.The pharmaceutical compositions of the invention may be included in a container, packaging, or dispenser along with instructions for administration.

[0060] KDM1A inhibitors, such as Compound 1, have been found to be orally active and effective in treating behavioral disorders when administered orally, as also illustrated in Examples 3 and 4. Similarly, it is preferred that the KDM1A inhibitor (e.g., Compound 1) be administered via the oral route for the treatment of a behavioral disorder.

[0061] The present invention also encompasses the use of KDM1A inhibitors, where one or more atoms are replaced by a specific isotope of the corresponding atom. For example, the invention encompasses the use of a KDM1A inhibitor in which one or more hydrogen atoms (or, for example, all hydrogen atoms) are replaced by deuterium atoms (i.e., 2H; also referred to as D). Similarly, the invention also encompasses inhibitors of Petition 870260063781, dated 06 / 29 / 2026, pp. 49 / 149 41 / 58 KDM1A inhibitors that are enriched in deuterium. Naturally occurring hydrogen is an isotopic mixture comprising about 99.98 mol % of hydrogen-1(1H) and about 0.0156 mol % of deuterium (2H or D). The deuterium content at one or more hydrogen positions in a KDM1A inhibitor can be increased using known deuteration techniques. For example, a KDM1A inhibitor or a reagent or precursor to be used in the synthesis of the KDM1A inhibitor can be subjected to an H / D exchange reaction using, for example, heavy water (D2O). Further appropriate deuteration techniques are described in: Atzrodt J et al., Bioorg Med Chem, 20(18), 5658-5667, 2012; William JS et al., Journal of Labelled Compounds and Radiopharmaceuticals, 53(11-12), 635-644, 2010; Modvig A et al., J Org Chem, 79, 58615868, 2014. Deuterium content can be determined, for example, using mass spectrometry or NMR spectroscopy.Unless specifically indicated otherwise, it is preferred that the KDM1A inhibitor to be used according to the present invention not be enriched in deuterium. Similarly, the presence of naturally occurring hydrogen atoms or 1H hydrogen atoms in the KDM1A inhibitor is preferred. In general, it is preferred that none of the atoms in the KDM1A inhibitor to be used according to the invention be substituted by specific isotopes. The KDM1A inhibitor or the pharmaceutical composition comprising the KDM1A inhibitor to be used according to the present invention may be administered as monotherapy (e.g., without concomitant administration of any other therapeutic agents, or without concomitant administration of any other therapeutic agents against the same behavioral disorder that is to be treated with the KDM1A inhibitor).Similarly, the KDM1A inhibitor or the pharmaceutical composition comprising the KDM1A inhibitor may be used in the monotherapy treatment of a behavioral disorder (e.g., Petition 870260063781, dated 06 / 29 / 2026, page 50 / 149 42 / 58 without administration of any other therapeutic agents against the same behavioral disorder until treatment with the KDM1A inhibitor is terminated). However, the KDM1A inhibitor or the pharmaceutical composition comprising the KDM1A inhibitor may also be administered in combination with one or more other therapeutic agents. If the KDM1A inhibitor is used in combination with a second therapeutic agent active against the same behavioral disorder, the dose of each compound may differ from that when the corresponding compound is used alone; in particular, a lower dose of each compound may be used.The combination of the KDM1A inhibitor with one or more additional therapeutic agents may comprise the simultaneous / concomitant administration of the KDM1A inhibitor and the additional therapeutic agent(s) (either in a single pharmaceutical formulation or in separate pharmaceutical formulations), or the sequential / separate administration of the KDM1A inhibitor and the additional therapeutic agent(s). If administration is sequential, both the KDM1A inhibitor and one or more additional therapeutic agents may be administered first. If administration is simultaneous, the one or more additional therapeutic agents may be included in the same pharmaceutical formulation as the KDM1A inhibitor, or they may be administered in one or more different (separate) pharmaceutical formulations (which may be administered via the same or different routes of administration). Definitions

[0062] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains.

[0063] The following definitions apply throughout this document. Petition 870260063781, dated 06 / 29 / 2026, page 51 / 149 43 / 58 descriptive report and claims, unless specifically stated otherwise.

[0064] A patient or subject for the purposes of the present invention includes both humans and other animals, particularly mammals, and other organisms. Thus, the methods and uses of the invention are applicable to both human therapy and veterinary applications. In a preferred aspect the subject or patient is a mammal, and in the most preferred aspect the subject or patient is human.

[0065] The term abnormal indicates a deviation from the normal, average, or expected.

[0066] The term improper indicates that something is at odds with societal standards and / or expectations.

[0067] The term pathological indicates that something, for example, a phenomenon or condition, constitutes a disease state or is altered or caused by or related to a disease.

[0068] The terms treatment, treating, and the like are used herein to generically mean obtaining a desired pharmacological and / or physiological effect. The effect may be prophylactic in terms of completely or partially preventing a disease (here, a behavioral change) or its symptom and / or may be therapeutic in terms of partially or completely curing or improving a disease (i.e., a behavioral change) and / or a symptom or adverse effect attributed to the disease or partially or completely preventing the progression of a disease and / or a symptom or adverse effect attributed to the disease. The term treatment as used herein covers any treatment of a disease (i.e., a behavioral change) in a patient and includes, without limitation, any one or more of the following: (a) prevention of a behavioral change in a patient who may be predisposed to / at risk of developing a behavioral change; (b) delaying Petition 870260063781, dated 06 / 29 / 2026, page 52 / 149 44 / 58 onset of behavioral change; (c) inhibition of behavioral change, that is, preventing, delaying, or slowing down its development / progression; or (d) relief of behavioral change, that is, causing regression (complete or partial), correction, or relief of the behavioral change. The present invention specifically and distinctly relates to each of these treatment forms.

[0069] As used herein, the term therapeutically effective amount refers to the amount sufficient to produce a desired biological effect (e.g., a therapeutic effect) in a subject. Similarly, a therapeutically effective amount of a compound may be an amount that is sufficient to treat a disease, and / or delay the onset or progression of a disease, and / or alleviate one or more symptoms of the disease, when administered to a subject suffering from or susceptible to that disease.

[0070] As used herein, a pharmaceutically acceptable salt is intended to mean a salt that retains the biological efficacy of the free acids and / or bases of the specified compound and that is not biologically or otherwise undesirable. A compound may possess functional groups that are sufficiently acidic, sufficiently basic, or both, and likewise react with any of a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt.Pharmaceutically acceptable salts include those salts prepared by reacting a compound of the invention, for example, Compound 1, with a mineral or organic acid, such as hydrochlorides, hydrobromides, sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrophosphates, dihydrophosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, nitrates, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, etc. Petition 870260063781, dated 06 / 29 / 2026, page 53 / 149 45 / 58 leates, butyne-1,4-dioates, hexyne-1,6-dioates. Benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, xylene sulfonates, phenyl acetates, phenyl propionates, phenyl butyrates, citrates, lactates, gamma-hydroxybutyrates, glycolates, tartrates, methane sulfonates, ethane sulfonates, propane sulfonates, benzene sulfonates, toluene sulfonates, trifluoromethane sulfonates, ethane sulfonates, propane sulfonates, benzene sulfonates, toluene sulfonates, trifluoromethane sulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates, mandelates, pyruvates, stearates, ascorbates, or salicylates.When a compound carries an acidic moiety, its appropriate pharmaceutically acceptable salts may include alkali metal salts, for example, sodium or potassium salts; alkaline earth metal salts, for example, calcium or magnesium salts; and salts formed with appropriate organic ligands such as ammonia, alkyl amines, hydroxyalkyl amines, lysine, arginine, N-methylglycamine, procaine, and the like. Pharmaceutically acceptable salts are well known in the art.

[0071] As used herein, a pharmaceutically acceptable solvate refers to a complex of variable stoichiometry formed by a solute and a pharmaceutically acceptable solvent such as water, ethanol and the like. A complex with water is known as a hydrate. It is to be understood that the invention encompasses pharmaceutically acceptable solvates of any KDM1A inhibitors in non-salt form and also in the form of a pharmaceutically acceptable salt thereof.

[0072] As used herein, a pharmaceutically acceptable vehicle or pharmaceutically acceptable excipient refers to non-API substances (API refers to Active Pharmaceutical Ingredient) such as disintegrants, binders, fillers, and lubricants used in pharmaceutical formulations. They are generic Petition 870260063781, dated 06 / 29 / 2026, page 54 / 149 46 / 58 are safe for administration to humans according to established government standards, including those promulgated by the United States Food and Drug Administration and / or the European Medicines Agency. Pharmaceutically acceptable vehicles or excipients are well known to those skilled in the art.

[0073] As used herein, a small molecule refers to an organic compound with a molecular weight below 900 daltons, preferably below 500 daltons. Molecular weight is the mass of a molecule and is calculated as the sum of the atomic weights of each constituent element multiplied by the number of atoms of that element in the molecular formula.

[0074] As used herein, the term comprising (or includes, contains, or containing), unless explicitly stated otherwise or contradicted by the text, has the meaning of containing, inter alia, that is, containing, even among optional elements, .... In addition, this term also includes the more restricted meanings of consisting essentially of and consisting of. For example, the term A comprising B and C has the meaning of A containing, inter alia, B and C, where A may still contain optional elements (for example, A containing B, C and D may also be included), but this term also includes the meaning of A consisting essentially of B and C and the meaning of A consisting of B and C (that is, no other component besides B and C is included in A).

[0075] As used herein, unless explicitly indicated otherwise or contradicted by context, the terms a, an and the are used interchangeably with one or more and at least one. Thus, for example, a composition comprising a KDM1A inhibitor may be interpreted as referring to a composition comprising one or more KDM1A inhibitors. Examples Petition 870260063781, dated 06 / 29 / 2026, page 55 / 149 47 / 58

[0076] The following examples illustrate various aspects of the invention. The examples, of course, should be understood as merely illustrative of only certain embodiments of the invention and not constituting limitations on the scope of the invention. Results are also presented and described in the Figures and Figure captions. Example 1: Materials

[0077] Compound 1 (or Com. 1) is the compound 5-((((1R,2S)-2-(4(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, also known as (-) 5-((((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, and whose chemical structure is shown below.

[0078] This compound can be obtained as shown in WO2012 / 013728. Example 2: In vitro KDM1A inhibition assay

[0079] The inhibitory activity of a compound against KDM1A can be determined using the method described below.

[0080] Recombinant human KDM1A protein (GenBank accession no. NM_015013, amino acid end-158 with N-terminal GST label, MW: 103 kDa) was used.

[0081] Serial 3-fold dilutions of a test compound ranging from 30 μM to 1 nM were pre-incubated for 15 minutes with recombinant human KDM1A enzyme (BPS Bioscience, Ref. 50100) on ice in assay buffer (50 mM sodium phosphate pH 7.4). Each inhibitor concentration was tested in duplicate. The enzymatic reaction was initiated by the addition of dimethyl H3K4 peptide substrate (Anaspec, Ref. 63677) to the KDM1A appKM. After 30 minutes of incubation at 37°C Petition 870260063781, dated 06 / 29 / 2026, page 56 / 149 48 / 58 Amplex Red reagent and horseradish peroxidase (HRP) solution were added to detect H2O2 formed in the enzymatic reaction, following the recommendations provided by the supplier (Invitrogen). The mixture was incubated for 5 minutes at room temperature in the dark, and the conversion of Amplex Red reagent to the highly fluorescent resorufin was analyzed using a Tecan Infinite F200 fluorescence microplate reader (α excitation = 540 nm, α emission = 590 nm). The maximum KDM1A demethylase activity was obtained in the absence of inhibitor and corrected for background fluorescence in the absence of KDM1A. The IC50 value for each inhibitor was calculated using GraphPad Prism5 logic support from a minimum of two independent experiments.

[0082] Compound 1 is a KDM1A inhibitor, as shown by an average IC50 value of 101 + / - 40 nM obtained in the KDM1A assay described herein. Example 3: Evaluation of the effect of KDM1A inhibitors on aggressive behavior.

[0083] The effect of the KDM1A inhibitor, Compound 1, on aggressive behavior was evaluated in male SAMP8 mice using the resident-intruder (RI) test. The RI test is a standardized method for measuring social behavior, particularly aggressive behavior in a semi-natural setting. 3.1 Method

[0084] SAM mouse models were developed from AKR / J mouse strains by Kyoto University. The SAMP8 litter showed severe senescence and was selected for further propagation and examination of these characteristics. The SAMR1 litter showed normal aging and was selected as a senescence-resistant strain.

[0085] In this study, male SAMP8 animals were treated both Petition 870260063781, dated 06 / 29 / 2026, page 57 / 149 49 / 58 mice received vehicle (n = 52), 0.32 (n = 8), or 0.96 (n = 8) mg / kg / day of Compound 1 for 5 weeks starting at 5 months of age and then underwent the RI test. Vehicle (1.8% 2-hydroxypropyl-β-cyclodextrin, SigmaAldrich, Spain) or Compound 1 was administered in drinking water. SAMR1 mice with vehicle were included as a control (n = 6). All drugs were administered via drinking water and diluted in vehicle. Drug concentration was calculated weekly based on body weight and corrected for drinking water consumption.

[0086] The resident-intruder (RI) test was conducted as follows: the test subject (resident) was kept in its residence cage without changes to sleeping accommodation for one week. On the test day, a significantly younger and smaller subject (intruder; 90-day-old C57BL6 mouse) was introduced into the resident's residence cage. The session (20 minutes) was video-recorded, and the test subject's social interaction (tested parameters: social interaction and rearing) and aggressive behavior (tested parameters: lateral threats, grasping attacks, hold-down behavior, and total attacks as the sum of all three measured aggressive behavior parameters) were analyzed by an experimenter blinded to the treatment.

[0087] Statistical Analyses: SAMR1 and SAMP8 vehicle groups were compared by t-test. Among the SAMP8 groups, different treatments were compared by one-way ANOVA with post-hoc SNK and Dunnett analyses. 3.2 Results

[0088] When the aggressive behavior of SAMP8 mice was compared to that of SAMR1 mice in the RI test, the total number of attacks, and especially grappling attacks, was significantly increased in vehicle-treated SAMP8 mice. Petition 870260063781, dated 06 / 29 / 2026, page 58 / 149 50 / 58 in relation to vehicle-treated SAMR1 mice, as shown in Figures 1 and 2, indicating that male SAMP8 mice exhibit altered (increased) aggressive behavior compared to the SAMR1 reference strain. Treatment of SAMP8 mice with Compound 1 decreased the number of attacks in SAMP8 mice to SAMR1 levels, as shown in Figures 1 and 2. Compound 1 thus drastically reduced aggressiveness in SAMP8 mice, correcting the altered aggressive behavior of said animals.

[0089] SAMP8 mice treated with vehicle show no significant differences from SAMR1 mice treated with vehicle in time spent in social interaction. No significant difference was observed in the number of rearings in SAMP8 mice treated with vehicle versus SAMR1, nor does treatment with Compound 1 affect this reading in SAMP8 mice. 3.3 The effects of KDM1A inhibitors on aggressive behavior are not due to sedation.

[0090] To confirm that the effects of Compound 1 on aggressive behavior in male SAMP8 mice were due to a direct effect of the compound on the animals' aggressiveness and not caused by a potential sedative effect of the compound, the effects of Compound 1 on anxiety and locomotor activity in male SAMP8 mice were studied using the open field (OF) and elevated plus maze (EPM) tests, as described below. 3.3.1 Method

[0091] Animals (n = 8 / group) were treated from 5 months of age with vehicle, 0.32 or 0.96 mg / kg / day Compound 1, and by 7 months of treatment they were sequentially subjected to the OF and EPM tests at one-week intervals. Vehicle (1.8% 2-hydroxypropyl-βcyclodextrin, Sigma-Aldrich, Spain) or KDM1A inhibitor (Com Petition 870260063781, dated 06 / 29 / 2026, page 59 / 149 51 / 58 mice (position 1) were administered in drinking water. SAMR1 mice treated with vehicle were included as a control (n = 8). All drugs were administered via drinking water and diluted in vehicle. Drug concentration was calculated weekly as a function of body weight and corrected for drinking water consumption.

[0092] The OF and EPM tests were performed as follows:

[0093] Open Field (OF): A 50 x 50 cm white plastic arena with 25 cm high walls was used to analyze spontaneous exploratory behavior. The floor of the apparatus was divided into 25 equal squares. The movements of each animal were recorded for 5 minutes. Locomotor activity was analyzed by video tracking over the captured images using SMART (v3.0, PanLab, SLU, Spain).

[0094] Elevated Plus Maze (EPM): The EPM consisted of four arms at right angles to each other connected to a central square and held elevated 50 cm above the floor. Two of the opposite arms had high walls (enclosed arms, 30 x 5 x 15 cm), while the other two were open arms (30 x 5 x 0 cm). The animal was placed face down on the closed arm, and its movements were video recorded for 5 minutes and analyzed by video tracking using SMART (v3.0, PanLab, SLU, Spain).

[0095] Statistical Analyses: SAMR1 and SAMP8 vehicle groups were compared by t-test. Among the SAMP8 groups, different treatments were compared by one-way ANOVA with posthoc SNK and Dunnett analyses. 3.3.2 Results

[0096] No significant difference was observed between vehicle-treated SAMR1 mice and vehicle-treated SAMP8 mice in the OF test, nor did treatment with Compound 1 significantly affect Petition 870260063781, dated 06 / 29 / 2026, page 60 / 149 52 / 58 locomotor activity or time spent in the center zone. SAMP8 mice spend significantly more time in the open arms of the EPM compared to SAMR1 mice, but this behavior was not significantly modified by Compound 1. Therefore, Compound 1 has no anxiolytic or sedative activity in SAMP8 mice.

[0097] In summary, the data and results obtained in Example 3 show that the KDM1A inhibitor, Compound 1, administered at doses that are well tolerated by mice for long-term treatment, drastically reduced aggression, but it does not function as a sedative or anxiolytic drug in SAMP8 mice. Example 3 thus supports the verification that KDM1A inhibitors, particularly Compound 1, can be used to treat behavioral disorders such as aggression without causing sedation.

[0098] Using the protocol described here in Example 3, the effects of improving behavior change (including, for example, effects of improving aggression) can be verified with other KDM1A inhibitors. Example 4: Evaluation of the effect of KDM1A inhibitors on social withdrawal.

[0099] Although mice are highly territorial, rats are known as a more gregarious species. To further characterize the therapeutic effects of KDM1A inhibitors as Compound 1 for the treatment of behavioral disorders, the effect of Compound 1 on social withdrawal, another type of behavioral disorder, was evaluated in rats using the rat isolation rearing model.

[00100] In this model, rats are isolated after weaning on postnatal day 21 (PND21) and deprived of the normal environment that preconditions them. Petition 870260063781, dated 06 / 29 / 2026, page 61 / 149 53 / 58 their social behavior. Isolation at this stage of rat development can lead to behavioral changes, particularly a lack of interest in social interactions, which can be used as a model for human social withdrawal. 4.1 Method

[00101] Just after weaning (postnatal days 21-23), 48 male Sprague-Dawley rats were divided into two groups: Control (non-isolated; n = 12), kept 3-4 animals per cage; Isolated (n = 36), 1 animal per cage. Starting on postnatal day 61 (PND), adult isolated male rats were treated with vehicle, Compound 1 at 0.16 mg / kg / day or Compound 1 at 0.48 mg / kg / day (n = 12 / group) for 5 weeks. Control animals were treated with vehicle. The route of administration was drinking water and the vehicle 2-hydroxypropyl-β-cyclodextrin 1.8%. Drug concentration was adjusted weekly based on body weight and water consumption. During the last week of treatment, all animals were tested on the RI (PND94) to assess their social behavior and, on a different day, on the EPM test (PND87-88) to assess anxiety behavior.

[00102] The resident-intruder (RI) test was conducted following a protocol similar to that described for mice in Example 3 above, as follows: in summary, the test subject (resident) was kept in its residence cage without changes to sleeping accommodations for one week. On the test day (PND94), a significantly younger and smaller subject (intruder, 50-day-old Sprague-Dawley rat) was introduced into the resident's residence cage. The session was video-recorded for 15 minutes, and the test subject's social interaction (measured parameters: active and passive social interaction, avoidance, and time without social interaction) and aggressive behavior were analyzed by an experimenter blinded to the treatment.

[00103] The elevated plus maze (EPM) test was performed following Petition 870260063781, dated 06 / 29 / 2026, page 62 / 149 54 / 58 A protocol similar to that described for mice in Example 3 above was used, as follows: the EPM consisted of four arms at right angles to each other connected to a central square and held elevated 50 cm above the floor. Two of the opposite arms had high walls (enclosed arms, 46.5 x 12 x 42 cm), while the other two were open arms (46.5 x 12 x 0.3 cm). The animal was placed facing an enclosed arm, and its movements were video-recorded for 5 minutes and analyzed by video tracking using SMART (v2.5.21, PanLab, SLU, Spain).

[00104] Statistical Analyses: Non-isolated and isolated vehicle groups were compared by t-test. Among the isolated groups, different drug treatments were compared by one-way ANOVA with post-hoc SNK and Dunnett analyses. 4.2 Results

[00105] The RI test as performed does not reveal aggressive behavior in rats, nor does isolation significantly affect active or passive social interaction. However, social avoidance parameters were greatly increased in isolated rats treated with vehicle compared to non-isolated rats treated with vehicle, as assessed by time without social interaction (Figure 3) and the number of avoidances (Figure 4). Time without social interaction in isolated rats was reduced dose-dependently through treatment with Compound 1, and the number of avoidances, which was greatly increased in isolated rats, was restored to normal (i.e., to levels of non-isolated rats) through treatment with Compound 1 (see Figures 3 and 4).

[00106] In the EPM test, no difference was observed between isolated rats treated with vehicle vs. non-isolated rats treated with vehicle. Compound 1 does not produce any significant effect on anxiety or locomotor activity in rats as assessed in the EPM, indicating Petition 870260063781, dated 06 / 29 / 2026, page 63 / 149 55 / 58 that the beneficial effects produced by Compound 1 on the social avoidance parameters measured in the RI test are not due to a sedative effect of the drug.

[00107] In summary, the data and results obtained in Example 4 show that the KDM1A inhibitor, Compound 1, administered at doses that are well tolerated by rats for long-term treatment, corrected behavioral changes, particularly social avoidance, in rats after weaning without causing sedation. Example 4 thus further supports the verification that KDM1A inhibitors, particularly Compound 1, can be used for the (non-sedative) treatment of behavioral changes, including social avoidance.

[00108] Using the protocol described here in Example 4, the effects of improving behavior change (including, for example, social withdrawal) can be verified with other KDM1A inhibitors. Example 5: Evaluation of the effect of KDM1A inhibitors using the three-chamber test (TCT) in mice.

[00109] The KDM1A inhibitor, Compound 1, was further tested in an additional animal model for social behavior alterations, the three-chamber test (TCT). The TCT is a commonly used method for measuring social behavior in mice and can be used to evaluate the effects of a compound to treat social interaction alterations using animals exhibiting innate or acquired deficits in social behavior.

[00110] In this test, after adaptation to the three-chamber arena, a mouse is released into the middle chamber and allowed to explore the other compartments. In the adjacent 'mouse' compartment, a docile stimulus mouse is situated in a wire mesh container, while in the other adjacent compartment a similar container is located without a stimulus mouse (compartment Petition 870260063781, dated 06 / 29 / 2026, page 64 / 149 56 / 58 object). The tendency to approach or avoid the compartment with the stimulus mouse provides a measure of social interaction behavior / sociability. Wild-type mice prefer social interaction and spend more time in the mouse compartment compared to the object compartment. 5.1 Method

[00111] In this study, 8-month-old female SAMP8 mice were treated with vehicle (n = 9) or 0.96 mg / kg / day of Compound 1 (n = 12) for 4 months and then subjected to TCT. Vehicle (2-hydroxypropyl-e-cyclodextrin 1.8%, Sigma-Aldrich, Spain) or Compound 1 (diluted in vehicle) were administered in drinking water. Vehicle-treated SAMR1 mice were included as a control (n = 11). Drug concentration was calculated weekly as a function of body weight and corrected for drinking water consumption.

[00112] The TCT was performed in a transparent Plexiglas box with three identical consecutive chambers (15 x 15 x 20 cm) with two identical small metal cages placed in both side chambers. Adjacent chambers were connected, and animals were free to move from one to the other. The test subject (female SAMR1 or SAMP8 mice) was allowed to explore the apparatus for 5 minutes. This habituation time was monitored to avoid animals showing preference for one of the chambers. Then, a new female mouse was introduced into one of the metal cages (Mouse Chamber) while the other cage remained empty (Object Chamber). The time spent in each chamber and the direct exploration time of the new mouse were measured during a total observation time of 10 minutes.

[00113] Statistical Analysis: The t-test was used to assess the significance of the difference in exploration of new mice for the Petition 870260063781, dated 06 / 29 / 2026, p. 65 / 149 57 / 58 SAMP8 mice compared to SAMR1 mice and Compound 1-treated mice compared to Vehicle-treated SAMP8 mice. Two-way ANOVA was used to assess the significance of chamber preference. ***: p < 0.001. 5.2 Results

[00114] The results obtained in this test are shown in Figures 5 and 6. As shown in Figure 5, vehicle-treated female SAMR1 mice spend more time in the Mouse chamber compared to the Object chamber. Unlike control SAMR1 animals, vehicle-treated female SAMP8 mice did not show a preference for the Mouse chamber over the Object chamber (see Figure 5) and also spent less time exploring the new mouse compared to SAMR1 mice (see Figure 6), thus showing deficits in social behavior. Treatment of female SAMP8 mice with the KDM1A inhibitor, Compound 1, restored the preference for the socialization chamber (mouse chamber) (Figure 5) and the time spent exploring a new mouse (Figure 6) from SAMP8 mice to SAMR1 levels. Compound 1 thus completely corrected the changes / lack of social interaction in SAMP8 mice.

[00115] The results obtained in Example 5 still show that KDM1A inhibitors as Compound 1 can be used for the (non-sedative) treatment of social behavior disorders.

[00116] Using the protocol described here in Example 5, the effects of improving social behavior change can be verified with other KDM1A inhibitors.

[00117] All publications, patents and patent applications cited herein are hereby incorporated by reference in their entirety.

[00118] Publications, patents and patent applications mentioned Petition 870260063781, dated 06 / 29 / 2026, page 66 / 149 Figures 58 / 58 in the descriptive report are provided solely for their disclosure prior to the filing date of this patent application. Nothing herein is to be construed as an admission that they are prior art to the present patent application.

[00119] Although the invention has been described in connection with its specific embodiments, it will be understood that it is capable of further modifications and this patent application is intended to cover any variations, uses or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as they come within known or customary practice within the art to which the invention belongs and as they can be applied to the essential features shown above and as follows in the claims set forth. Petition 870260063781, dated 06 / 29 / 2026, page 67 / 149

Claims

1 / 2 CLAIMS 1. Use of a KDM1A inhibitor, which is 5-((((1R,2S)-2-(4(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine, or a pharmaceutically acceptable salt or solvate thereof, characterized in that it is for the manufacture of a medicament for the treatment of a behavioral disorder, wherein the behavioral disorder is social withdrawal associated with a disorder selected from autism spectrum disorder, schizophrenia, and post-traumatic stress disorder, or wherein the behavioral disorder is aggression associated with a disorder selected from borderline personality disorder, autism spectrum disorder, adult attention deficit hyperactivity disorder, schizophrenia, and post-traumatic stress disorder.

2. Use, according to claim 1, characterized in that the behavioral change is social withdrawal associated with a disease selected from autism spectrum disorder, schizophrenia, and post-traumatic stress disorder.

3. Use, according to claim 1 or 2, characterized in that the behavioral change is social withdrawal associated with autism spectrum disorder.

4. Use, according to claim 1 or 2, characterized in that the behavioral change is social withdrawal associated with schizophrenia.

5. Use, according to claim 1 or 2, characterized in that the behavioral change is social withdrawal associated with post-traumatic stress disorder.

6. Use, according to claim 1, characterized in that the behavioral change is aggressiveness associated with a disease selected from borderline personality disorder, autism spectrum disorder, adult attention deficit hyperactivity disorder, schizophrenia, and post-traumatic stress disorder.

7. Use, according to claim 1 or 6, characterized in that the behavioral change is aggressiveness associated with borderline personality disorder.

8. Use, according to claim 1 or 6, characterized in that the behavioral change is aggressiveness associated with autism spectrum disorder.

9. Use, according to claim 1 or 6, characterized in that the behavioral change is aggressiveness associated with schizophrenia.

10. Use, according to claim 1 or 6, characterized in that the behavioral change is aggressiveness associated with post-traumatic stress disorder.

11. Use, according to any one of claims 1 to 10, characterized in that the medicament is formulated to be administered to a human patient.

12. Use, according to any one of claims 1 to 11, characterized in that the KDM1A inhibitor is 5-((((1R,2S)-2(4-(benzyloxy)phenyl)cyclopropyl)amino)methyl)-1,3,4-oxadiazol-2-amine.

13. Use, according to any one of claims 1 to 12, characterized in that the medicament is formulated for oral administration.

14. A method for treating a behavioral disorder in a patient, characterized by the fact that it comprises administering a therapeutically effective amount of a KDM1A inhibitor.

15. Method, according to claim 14, characterized in that the behavioral change is social withdrawal or aggressiveness. Petition 870260063781, dated 06 / 29 / 2026, pp. 69 / 149

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