Sonnet BioTherapeutics Updates SON-1010 Clinical Data and Dose-Escalation Target

Sonnet BioTherapeutics Holdings, Inc., a clinical-stage company focused on developing immunotherapeutic drugs, has announced a significant milestone in its ongoing clinical trials for SON-1010. The company's proprietary version of recombinant human interleukin-12 (rhIL-12) has shown promising results in both safety and efficacy during its Phase 1 clinical trials.

SON-1010, developed using Sonnet's Fully Human Albumin Binding (FHAB®) platform, has been designed to extend the half-life and activity of IL-12 by binding to native albumin in the serum and targeting the tumor microenvironment (TME). This unique configuration aims to enhance the drug's therapeutic potential.

The company's active clinical trials include SB101 and SB221. SB101 is a Phase 1 multiple-ascending dose (MAD) trial involving adult patients with advanced solid tumors. The trial, which began in the second quarter of 2022, is currently enrolling its sixth dose cohort. SB221, which started in the fourth quarter of 2023, is a Phase 1b/2a trial that explores the combination of SON-1010 with atezolizumab, targeting platinum-resistant ovarian cancer (PROC). This trial is now enrolling its fourth dose cohort. A previous study, SB102, was a Phase 1 single-ascending dose (SAD) trial conducted in healthy volunteers, and its results were recently published.

The safety of SON-1010 has been rigorously reviewed by Safety Review Committees at each stage of dose escalation in both active cancer trials. These trials employ a 'desensitizing' first dose to leverage the known tachyphylaxis with rhIL-12, minimizing toxicity and enabling higher maintenance doses. To date, no dose-limiting toxicities or related serious adverse events have been observed. Most adverse events reported have been mild and transient, with no evidence of cytokine release syndrome. Among the 25 cancer patients dosed and evaluable for follow-up, 15 (60%) exhibited stable disease at their first follow-up scan, and 8 of these were progressing at the study's commencement. At the four-month mark, 35% of evaluable patients continued to show clinical benefit.

Dr. Richard Kenney, Chief Medical Officer at Sonnet, highlighted the progress made with SON-1010. The data from the SB102 study provided clean pharmacokinetic (PK) and pharmacodynamic (PD) analyses, aiding in the simulation of multiple doses. This modeling supports the FHAB mechanism targeting tumor tissue. The combination of SON-1010 with atezolizumab could potentially enhance the conversion of ‘cold’ tumors to ‘hot,’ thereby increasing PD-L1 expression in the TME.

One notable case involved a patient with progressive endometrial sarcoma who achieved stable disease for nearly two years under SON-1010 monotherapy. Cytokine analysis revealed controlled and prolonged induction of interferon gamma (IFNγ), peaking at 24 to 48 hours post-dose and returning to baseline within 2 to 4 weeks. There was minimal induction of other cytokines, indicating no risk of cytokine release syndrome.

Dr. Robert Wenham from Moffitt Cancer Center emphasized the significance of these findings, noting that the FHAB platform's ability to extend the drug's half-life and concentrate it in the TME marks a significant advancement. The company plans to add groups in both studies to evaluate higher maintenance doses of SON-1010.

Dr. Pankaj Mohan, Sonnet's Founder and CEO, expressed satisfaction with the safety and tolerability of SON-1010 at higher doses. He highlighted the potential of the FHAB platform to make IL-12 safer and more effective by prolonging its half-life and concentrating it in the tumor. Given the long battle many patients face with their cancers, any observed tumor shrinkage is both challenging to achieve and promising.

In summary, Sonnet BioTherapeutics is making noteworthy strides in the development of SON-1010, showing encouraging safety and efficacy profiles. The company is poised to continue exploring the potential of this innovative drug, particularly in combination with atezolizumab, to address significant unmet medical needs in cancer treatment.