CN-122028927-A - Method for treating inflammatory bowel disease

Abstract

Provided herein are methods of treating inflammatory bowel disease. Also provided are methods of preparing EOM613 and pharmaceutical compositions comprising EOM 613.

Inventors

• S. Z. Hirschman
• TARAPOREWALA IRACH B.
• E Goldberger

Assignees

• EOM制药有限公司

Dates

Publication Date

20260512

Application Date

20240830

Priority Date

20230901

Claims (20)

1. 1. A method of treating Inflammatory Bowel Disease (IBD) in a subject, comprising administering to the subject a therapeutically effective amount of EOM613.
2. 2. The method of claim 1, wherein the IBD is crohn's disease, ulcerative colitis, or indeterminate colitis.
3. 3. The method of claim 1, wherein treating a subject reduces the frequency or severity of one or more IBD symptoms in the subject.
4. 4. The method of claim 3, wherein the one or more IBD symptoms comprise one or more of rectal bleeding, abdominal distension, diarrhea, multiple daily bowel movements, fatigue, weight loss, and abdominal pain or cramps.
5. 5. The method of claim 1, further comprising selecting a subject with IBD for treatment.
6. 6. The method of claim 5, wherein the subject has active IBD or is in remission after diagnosis of IBD.
7. 7. The method of claim 1, wherein the therapeutically effective amount of EOM613 is administered parenterally, topically, inhaled, or systemically.
8. 8. The method of claim 7, wherein the therapeutically effective amount of EOM613 is administered parenterally.
9. 9. The method of claim 1, wherein the therapeutically effective amount of EOM613 is administered subcutaneously.
10. 10. The method of claim 5, wherein the administering comprises administering to the subject EOM613 from about 1 ml to about 4 ml once or twice daily.
11. 11. The method of claim 10, wherein the administering comprises administering to the subject: i) Administering EOM613 of about 1.5 ml to about 2.5 ml twice daily, or Ii) twice daily EOM613 of about 2 ml.
12. 12. The method of claim 5, wherein the administering comprises daily administration of from about 1 microliter to about 200 microliters of EOM613 per kilogram of body weight to the subject.
13. 13. The method of claim 5, wherein the administering comprises daily administration of from about 10 microliters to about 150 microliters of EOM613 per kilogram of body weight to the subject.
14. 14. The method of claim 5, wherein the administering comprises daily administration of about 20 microliters to about 100 microliters of EOM613 per kilogram of body weight to the subject.
15. 15. The method of claim 5, wherein EOM613 is administered: i) At least 1 week; ii) at least 2 weeks; iii) 1 to 12 weeks, or Iv) 2 to 8 weeks.
16. 16. The method of claim 1, further comprising administering a second IBD therapeutic agent to the subject.
17. 17. The method of claim 1, wherein the subject is a human.
18. 18. The method of claim 1, wherein the subject has an elevated level of one or more of C-reactive protein, IL-6, IL-12, TNF-a, IL-23, miR-223, and procalcitonin; Optionally, wherein administration of the therapeutically effective amount of EOM613 reduces the subject's elevated level to undetectable or normal levels.
19. 19. A method of treating Inflammatory Bowel Disease (IBD), comprising: A subject suffering from IBD is selected for treatment, 2 Ml of EOM613 was parenterally administered twice daily to a subject to treat the IBD.
20. 20. The method of any one of the preceding claims, wherein EOM613 is prepared by a method comprising the steps of: i) Suspending 35% to 50% casein, 15% to 40% beef peptone, 10% to 25% RNA, 1% to 10% BSA and 5% to 25% sodium hydroxide on a dry weight basis (w/w) in distilled water to obtain a suspension; ii) autoclave treatment of the suspension; iii) After autoclave treatment, the suspension is cooled to 3 ℃ to 8 ℃ for at least 12 hours; iv) after cooling, the suspension is filtered, thereby obtaining a filtered solution; v) adjusting the filtered solution: a) To a total nitrogen content of 1.65 mg/ml to 2.10 mg/ml, and B) To the physiological pH value, the pH value is adjusted to be equal to the physiological pH value, Thereby obtaining a conditioned solution; vii) filtering the conditioned solution, thereby obtaining a final filtrate; viii) sterilizing the final filtrate to produce EOM613.

Description

Method for treating inflammatory bowel disease Cross Reference to Related Applications The present application claims priority from U.S. provisional application No. 63/536,325 filed on 1 month 9 of 2023, which is incorporated herein by reference in its entirety. Technical Field The present application relates to methods of treating inflammatory bowel disease such as Crohn's disease or ulcerative colitis. Background Inflammatory Bowel Disease (IBD) is a disease characterized by chronic inflammation of the gastrointestinal tract. Types of IBD include crohn's disease, ulcerative colitis, and indeterminate colitis. The main symptoms include persistent diarrhea (lasting more than 4 weeks), abdominal pain, hematochezia or hematochezia with mucus, fatigue and weight loss. IBD varies in severity from mild to severe disease, which can lead to life threatening complications. Currently available treatments are either poorly tolerated or not durable. Patient response to existing IBD therapies may decrease over time until the therapy fails. Thus, alternative methods of treating IBD are urgently needed. Disclosure of Invention Disclosed herein are methods of treating Inflammatory Bowel Disease (IBD) in a subject comprising administering to the subject a therapeutically effective amount of EOM613. In certain aspects, the IBD is crohn's disease. In certain aspects, the EOM613 treatment may reduce one or more IBD symptoms, such as rectal bleeding, abdominal distension, diarrhea, multiple daily bowel movements, fatigue, weight loss, and abdominal pain or cramps. Subjects with IBD may be selected for treatment. In certain aspects, the subject has active IBD, or is in remission after diagnosis of IBD. The method may further comprise administering a second IBD therapeutic agent, such as infliximab, adalimumab (adalibumab), pezilimumab (certolizumab pegol), li Shengji bezumab (risankizumab), vedelizumab (vedozilumib), wu Sinu mab (ustekinumab), wu Pati nii (upadacitimib), aminosalicylate (aminosalicylates) (e.g., sulfasalazine (ulfasalazine), mesalamine (mesalamine), or oxalazine (olsalazine)), mercaptopurine (mercaptopurine), or methotrexate (methotrexate). Also disclosed are methods of preparing EOM613 and pharmaceutical compositions comprising EOM613. The above and other objects, features and advantages of the present invention will become more apparent from the following detailed description. Detailed Description I. introduction to the invention In 2015, the american center for disease control and prevention (CDC) estimated that 1.3% of american adults were diagnosed with crohn's disease or ulcerative colitis. The prevalence of the elderly population in the united states has increased significantly between 2000 and 2018 (see Fang Xu et al Morbidity and Mortality Weekly (19): 698-701, 2021). The etiology of IBD is driven primarily by the release of pro-inflammatory cytokines by gastrointestinal macrophages (see, e.g., sanchez-Munoz et al, world J gastroentol. 14 (27): 4280-4288, 2008). The major cytokines involved in inducing IBD symptoms are TNF- α and IL-23, and thus, based on antibodies directed against these cytokines, a variety of therapeutic agents have been developed. TNF-alpha inhibitor-like biological agents that were approved for the treatment of IBD symptoms include infliximab (Remicade), adalimumab (trimipromycin (Humira)) and pezilizumab (simenda (Cimizia)). IL-23 blocking antibodies included Li Shengji bead mab (Xikangyu (Skyrizi cube)). Other agents for clinical treatment of IBD include the intestinal targeted α4- β integrin inhibitor vedelizumab (anguyou (Entyvio b)), and Wu Sinu mab (bendazol (Stelara b)). All of these monoclonal biologics are administered intravenously and many have serious adverse side effects including increased risk of infection (including upper respiratory and urinary tract infections), nausea, headache and joint pain. In addition, allergic reactions may occur and these drugs may harm fetal health, so pregnant women should be avoided. Non-biological agents for the treatment of IBD include aminosalicylates such as sulfasalazine, mesalamine or olsalazine. However, these treatments are best for IBD involving the lower colon segment rather than the small intestine. Immunomodulators, such as mercaptopurine or methotrexate, are sometimes used to induce remission, but may damage the liver and pancreas. It is common for existing IBD therapies (such as those discussed above) to fail treatment, that the patient is unable to tolerate the treatment, or that the patient develops tolerance over time, ultimately leading to failure of the therapy. Furthermore, despite advances in the treatment of IBD using antibodies directed against IL-23 and TNF-a cytokines, treatment failures remain commonplace. Typically, 50% to 60% of patients initially respond to these therapies with an improvement in symptoms or markers of inflammation. Of these patients, only about 20% to 30% were able to achieve remission, wher