Abstract 7181: Low dose interleukin-6 (SON-080) for neuropathies: Toxicology and clinical plans

Abstract

Abstract Neuropathies are conditions in which peripheral nerves degenerate, resulting in sensory and motor symptoms that can profoundly affect the patients’ quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is induced by most antineoplastic agents, affecting cancer patients during or following completion of treatment. Neuropathy-specific pain medication is most often inefficient against pain, can cause major side effects that limit their use, do not address non-pain related symptoms, and do not stop CIPN progression. Most evidence suggests that physical exercise is the most efficient approach to reduce neuropathy symptoms and potentially, progression. Other publications have causally linked exercise, through the ability of contracting muscles to release low levels of interleukin-6 into the bloodstream thereby activating several metabolic and physiological pathways that help regenerate muscle and nerve tissue, affect glucose homeostasis, increase lipolysis, improve microvascular blood flow and reduce inflammation. Preclinical disease models of CIPN and diabetic peripheral neuropathy (DPN) have confirmed that IL-6 administered at low doses is capable of stimulating peripheral nerve growth, thereby ameliorating motor and sensory functions and normalizing the associated pain or sensation disturbance of neuropathy. The maximum tolerated (MTD) dose of recombinant human IL-6 (rhIL-6) has been established as a treatment for thrombocytopenia in hundreds of cancer patients using the drug product that was produced in the 1990’s (Process A) dosed intravenously (IV) or subcutaneously (SC). We have developed a cGMP compliant version of rhIL-6 (SON-080) using a state-of-the-art process (Process B) that meets current regulatory guidelines for cell lines and processes. An analytical comparison of SON-080 with Process A rhIL-6 concluded that both drugs are highly comparable for at least 14 different key physicochemical characteristics. Therefore, we expect similar in vivo behavior with Process B material as compared with the Process A molecule. In order to support clinical plans for the safety and toxicity of rhIL-6, a dose range and schedule of administration that matches the current clinical protocol was performed in a cynomolgus monkey primate toxicology model. Under these conditions, SON-080 was found safe and well tolerated with a No Adverse Effect Levels (NOAEL) of 30µg/kg, the highest dose tested. On this basis, a fully controlled Phase 1b/2a clinical study, SB211, is ongoing to evaluate safety, tolerability, and efficacy of subcutaneous SON-080 dosage and administration schedule that targets an exposure mirroring the endogenous release levels elicited by moderate to heavy exercise. Confirmation of safety in the first portion of the trial will pave the way for efficacy evaluation with the objective to provide CIPN patients with a novel, safe, and effective treatment for painful neuropathies. Citation Format: Susan Dexter, Gael Hedou, Richard T. Kenney, Darrel J. Rezac, Pankaj Mohan. Low dose interleukin-6 (SON-080) for neuropathies: Toxicology and clinical plans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7181.