Sonnet BioTherapeutics Reports Phase 1 SON-1010 Monotherapy Dose Escalation Safety Data

Sonnet BioTherapeutics Holdings, Inc. recently unveiled promising results from their Phase 1 SB101 clinical trial, evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SON-1010 in adult patients with advanced solid tumors. SON-1010, a proprietary recombinant human interleukin-12 (rhIL-12), has been genetically fused with Sonnet’s Fully Human Albumin Binding (FHAB®) platform, which aims to extend the half-life and bioactivity of the IL-12 component by binding to native albumin in serum and targeting the tumor microenvironment.

The trial has so far enrolled 24 patients, and the primary outcomes are focused on ensuring the safety and tolerability of SON-1010 while establishing the Maximum Tolerated Dose (MTD). The MTD was determined to be 1200 ng/kg, with no dose-limiting toxicities or cytokine release syndrome observed at any dosing level. Of the 24 patients treated to date, 48% exhibited stable disease (SD) at four months post-initiation, including one patient at the MTD who showed a partial response (PR) with a 45% reduction in tumor size according to RESIST criteria.

Dr. Richard Kenney, Sonnet’s Chief Medical Officer, expressed optimism about the safety data, particularly considering the historical safety concerns associated with rhIL-12 in early human trials. The unique biodistribution and albumin-binding profile of SON-1010 appear to contribute to its minimal toxicity and effective delivery to the tumor microenvironment. The robust yet controlled IFNγ response is seen as crucial for anti-tumor activity, and the observed partial response in the highest dose cohort suggests potential synergy with checkpoint inhibitors or chemotherapy.

Sonnet’s trial strategy included a desensitizing first dose of 300 ng/kg to exploit the known tachyphylaxis of rhIL-12, aiming to reduce toxicity and permit higher maintenance doses. Adverse events (AEs) were generally mild and transient, typical for a Phase 1 oncology trial. Importantly, no serious adverse events (SAEs) related to the treatment were reported.

The trial's final cohort, receiving the 1200 ng/kg dose, was expanded to six patients to better assess PK and PD at the MTD. Out of the 24 patients treated, 71% had stable disease at the first follow-up CT, including patients who were progressing at the study's start. The patient with clear cell sarcoma in the highest dose cohort demonstrated a partial response, with a significant reduction in tumor size.

Pankaj Mohan, Ph.D., Sonnet’s Founder and CEO, highlighted the significance of these results, marking the completion of dose escalation in their first trial with SON-1010. He noted that the safety profile of this extended PK version of IL-12 aligns with expectations, and the data supports the potential for tumor targeting in humans. Dr. Mohan also mentioned ongoing efforts to seek partnerships to support further development of SON-1010.

Additionally, SON-1010 is under evaluation in a Phase 1b/2a dose-escalation and proof-of-concept study (SB221) in collaboration with Genentech, targeting platinum-resistant ovarian cancer. Updates on safety at the MTD for this trial are anticipated in Q1 2025.

SON-1010 links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3, designed to bind albumin at normal and acidic pH levels typical of the tumor microenvironment. This targeting technology aims to improve the safety and efficacy profile of IL-12 by focusing on tumor and lymphatic tissues, making it relevant for cancers like non-small cell lung cancer, melanoma, and sarcoma, among others. SON-1010 is intended to activate local immune responses, converting ‘cold’ tumors into ‘hot’ ones by stimulating IFNγ and increasing PD-L1 production on tumor cells.

Sonnet’s Phase 1 SB101 trial, conducted across multiple U.S. sites, is designed to determine the safety of ascending doses of SON-1010 in cancer patients using a standard 3+3 oncology design. The study aims to establish the MTD through subcutaneous injections administered every three to four weeks, assessing safety, PK, PD, immunogenicity, and anti-tumor activity. This trial will form the basis for potential combinations with other immunotherapies and future bispecific candidates developed using the FHAB platform.

Sonnet BioTherapeutics continues to focus on developing targeted biologic drugs for oncology through their proprietary FHAB platform, aiming to optimize the therapeutic window for immune-modulating biologic drugs by specifically targeting tumor and lymphatic tissues.