Novel cancer treatments with il-2 conjugates

HK40138671APending Publication Date: 2026-10-09ASCENDIS PHARMA ONCOLOGY DIV AS
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Patent Information

Application Number
HK62026126526
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-10-19
Filing Date
2026-07-23
Publication Date
2026-10-09
Estimated Expiration
2044-05-07

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Abstract

The present invention relates to an IL-2 conjugate or a pharmaceutically acceptable salt thereof for use in the treatment of cancer, wherein the IL-2 conjugate is administered in a dose ranging from 80 µg IL-2 / kg to 160 µg IL-2 / kg and wherein the IL-2 conjugate is of formula (I); and to related aspects.
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Description

Abstract This invention relates to IL-2 conjugates or pharmaceutically acceptable salts thereof for the treatment of cancer, wherein the IL-2 conjugates are administered in a dose range of 80 µg IL-2 / kg to 160 µg IL-2 / kg, and wherein the IL-2 conjugates have formula (I); the invention also relates to related aspects.

Claims

Ascendis Pharma Oncology Division A / S CPX74830PC 08 May 2024 Claims 1. An IL-2 conjugate or a pharmaceutically acceptable salt thereof for use in the treatment of cancer, wherein the IL-2 conjugate is administered in a dose ranging from 80 µg IL-2 / kg to 160 µg IL-2 / kg and wherein the IL-2 conjugate is of formula (I) (I), wherein -D is -D’-Mmod, wherein -D’- is an IL-2 moiety; -Mmodis a first polymeric moiety that is stably conjugated to a side chain of an amino acid residue of -D’-; -L1- is a linker moiety covalently and reversibly attached to -D’-; -L2- is absent or a spacer moiety; and -Z is a second polymeric moiety.

2. The IL-2 conjugate for use of claim 1, wherein the dose ranges from 100 µg IL-2 / kg to 140 µg IL-2 / kg.

3. The IL-2 conjugate for use of claim 1 or 2, wherein the dose ranges from 110 µg IL-2 / kg to 130 µg IL-2 / kg.

4. The IL-2 conjugate for use of any one of claims 1 to 3, wherein the dose is about 120 µg IL-2 / kg.

5. The IL-2 conjugate for use of any one of claims 1 to 4, wherein the dose is 120 µg IL-2 / kg.

6. The IL-2 conjugate for use of any one of claims 1 to 5, wherein the dose is administered multiple times.

7. The IL-2 conjugate for use of any one of claims 1 to 6, wherein the interval between two consecutive administrations ranges from two to eight weeks.

8. The IL-2 conjugate for use of any one of claims 1 to 7, wherein the interval between two consecutive administrations is three weeks.

9. The IL-2 conjugate for use of any one of claims 1 to 7, wherein the interval between two consecutive administrations is six weeks.

10. The IL-2 conjugate for use of any one of claims 1 to 6, wherein the IL-2 conjugate is administered at a frequency dependent on disease progression.Ascendis Pharma Oncology Division A / S CPX74830PC 08 May 2024 11. The IL-2 conjugate for use of any one of claims 1 to 5, wherein the dose is administered once.

12. The IL-2 conjugate for use of any one of claims 1 to 11, wherein the treatment starts directly on diagnosis of the cancer.

13. The IL-2 conjugate for use of any one of claims 1 to 12, wherein the treatment is a first line of treatment.

14. The IL-2 conjugate for use of any one of claims 1 to 12, wherein the treatment is the second, third or further line of treatment.

15. The IL-2 conjugate for use of any one of claims 1 to 14, wherein the IL-2 conjugate is administered via external application, injection or infusion, including intraarticular, periarticular, intradermal, subcutaneous, intramuscular, intravenous, intraosseous, intraperitoneal, intrathecal, intracapsular, intraorbital, intravitreal, intratympanic, intravesical, intracardiac, transtracheal, subcuticular, subcapsular, subarachnoid, intraspinal, intraventricular, intrasternal injection and infusion; direct delivery to the brain via an implanted device allowing delivery of the IL-2 conjugate to brain tissue or brain fluids (e.g., Ommaya Reservoir), direct intracerebroventricular injection or infusion, injection or infusion into brain or brain associated regions, injection into the subchoroidal space, retro-orbital injection or ocular instillation.

16. The IL-2 conjugate for use of any one of claims 1 to 15, wherein the IL-2 conjugate is administered intravenously.

17. A method of synthesizing an IL-2 conjugate, wherein the method comprises the steps of a) providing a)i. at least one reagent of formula (XII)Ascendis Pharma Oncology Division A / S CPX74830PC 08 May 2024 wherein p1, p2, p3, p4 are independently of each other an integer ranging from 110 to 345, from 140 to 315, from 170 to 285, from 195 to 255, from 200 to 250, from 210 to 250 or from 220 to 240; a)ii. a mixture of about 30% (v / v) acetonitrile in water; and a)iii. a solution comprising D’-Mmod, wherein -D’- has the amino acid sequence of SEQ ID NO:4, and -Mmodhas the structure of (A-1d) or (A-1e)wherein the dashed line marked with the asterisk indicates attachment to the sulfur atom of the side chain of the cysteine at position 38; b1 is 2 or 3; b2 is 2 or 3; and b3 ranges from 90 to 140, from 95 to 135 or from 100 to 125; b) mixing the at least one reagent of step a)i. with the mixture of step a)ii.; c) mixing the mixture of step b) with the solution of step a)iii., wherein the molar ratio of the reagent of formula (XII) and D’-Mmod is ranging from 4:1 to 1:1; d) incubating the mixture of step c) for 1 to 5 hours at a temperature ranging from 10°C to 20°C to obtain the IL-2 conjugate of formula (I); and e) optionally, purifying the IL-2 conjugate of formula (I) from the incubated mixture of step d).

18. A method of treating or delaying progression of cancer in a patient, comprising: (a) measuring the level of sCD25 in a biological sample obtained from the patient after administration of at least one dose ranging from 80 µg IL2 / kg to 160 µg IL- 2 / kg of the IL-2 conjugate of formula (I) to the patient; and / or (b) measuring the level and / or proliferation of CD8+ T cells in a biological sample obtained from the patient after administration of at least one dose ranging from 80 µg IL2 / kg to 160 µg IL-2 / kg of the IL-2 conjugate of formula (I) to the patient;Ascendis Pharma Oncology Division A / S CPX74830PC 08 May 2024 (c) comparing the level from step (a) and / or the level and / or proliferation from step (b) to a reference; wherein an increased level of sCD25 and / or increased level and / or proliferation of CD8+ T cells compared to the reference indicates that the patient is likely to benefit from the treatment with the IL-2 conjugate of formula (I); and (d) if the patient has i) an increased level of sCD25 compared to the reference, administering to the patient one or more additional dose ranging from 80 µg IL2 / kg to 160 µg IL- 2 / kg of the IL-2 conjugate of formula (I); and / or ii) an increased level and / or proliferation of CD8+ T cells compared to the reference, administering to the patient one or more additional dose ranging from 80 µg IL2 / kg to 160 µg IL-2 / kg of the IL-2 conjugate of formula (I).