Sonnet BioTherapeutics Completes Phase 1 Enrollment for SON-1010 in Solid Tumor Treatment

Sonnet BioTherapeutics Holdings, Inc., a clinical-stage company focused on developing immunotherapeutic drugs, recently completed enrollment and initiated dosing in its Phase 1 SB101 clinical trial of SON-1010. This trial targets adult patients with advanced solid tumors, and the company expects to present initial safety data by the fourth quarter of 2024.

SON-1010, Sonnet's proprietary version of recombinant human interleukin-12 (rhIL-12), is designed using the Fully Human Albumin Binding (FHAB) platform. This platform enhances the half-life and activity of IL-12 by binding it to native albumin in serum, effectively targeting the tumor microenvironment by binding to gp60 and Secreted Protein Acidic and Rich in Cysteine (SPARC).

The SB101 clinical trial is an open-label, adaptive-design, dose-escalation study. It aims to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of SON-1010 in patients with advanced solid tumors. The primary goals are to evaluate safety and tolerability and to establish the maximum tolerated dose (MTD) of SON-1010. The study enrolled 24 participants, and safety reviews were conducted at each dose escalation step by the Safety Review Committee. The trial employs a 'desensitizing' initial dose to utilize the known tachyphylaxis of rhIL-12, minimizing toxicity and allowing higher maintenance doses. To date, no dose-limiting toxicities have been observed, with most adverse events being mild and transient.

SON-1010 has shown promise, particularly in one patient with progressive endometrial sarcoma who experienced stable disease for nearly two years. Her ascites resolved, and tumors shrank, although she did not achieve a partial response according to RECIST criteria. Cytokine analysis revealed a controlled induction of interferon gamma (IFNγ) peaking at 24-48 hours and returning to baseline within 2-4 weeks, with a small increase in IL-10 and minimal or no signals for other cytokines like IL-1β, IL-6, IL-8, and TNFα. There was no evidence of cytokine release syndrome at the administered doses.

SON-1010 is designed to deliver IL-12 to tumor tissue, transforming 'cold' tumors 'hot' by stimulating IFNγ, which activates both innate and adaptive immune responses and increases PD-L1 production on tumor cells. This mechanism holds potential for treating various cancers, including non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers.

The SB101 Phase 1 trial seeks to evaluate the safety of multiple ascending doses of SON-1010 in cancer patients across several U.S. sites. The study follows a standard 3+3 oncology design in at least five cohorts to establish the MTD using subcutaneous injections every 3-4 weeks. Besides safety and tolerability, secondary endpoints of the trial include measuring PK, PD, immunogenicity, and anti-tumor activity. This study will lay the groundwork for future combinations with other immunotherapies and the development of bispecific candidates using the FHAB platform.

Sonnet BioTherapeutics Holdings, Inc. leverages its FHAB technology to develop targeted biologic drugs with improved safety and efficacy. The platform uses a fully human single-chain antibody fragment that binds human serum albumin, enhancing drug delivery to tumor and lymphatic tissues. Sonnet's lead program, SON-1010, is under evaluation for the treatment of solid tumors and ovarian cancer. The company is also progressing its second program, SON-1210, in collaboration with the Sarcoma Oncology Center, and SON-080 for Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Diabetic Peripheral Neuropathy (DPN).