Sonnet BioTherapeutics (NASDAQ: SONN) has announced the publication of discovery and development data for its lead drug candidate, SON-1010, in Frontiers in Immunology, detailing the mechanism of action of its albumin-binding (FHAB) technology combined with IL-12 for improved cancer treatment delivery. The publication underscores the potential of SON-1010 to enhance therapeutic efficacy while minimizing toxicity.
FHAB Technology for Enhanced Drug Delivery
The research highlights the identification of molecules that bind to serum albumin across multiple species and pH ranges, leading to an extended half-life and improved tumor targeting. This is crucial as traditional IL-12 therapies have faced limitations due to their short circulating half-life and systemic toxicities. Patents for FHAB and SON-1010 have been issued in major markets, including the US, China, and Japan, expiring between 2038 and 2039, providing a substantial exclusivity window for commercialization.
Pankaj Mohan, Ph.D., Founder and CEO of Sonnet, stated, "This work lays the foundation for all of the products on our platform that are designed to safely extend the half-life of cytokines and deliver them to the tumor, where they can convert the immunological response from ‘cold’ to ‘hot’ and potentially realize the promise of immunotherapy."
Clinical Trials and Future Development
The company is currently conducting a Phase 1 clinical trial of SON-1010 for advanced solid tumors, with safety data expected in Q4 2024 (NCT05352750). Additionally, SON-1010 is being evaluated in a Phase 1/2a study in combination with Roche's atezolizumab for Platinum-Resistant Ovarian Cancer (PROC). This collaboration aims to address the unmet need in patients with ovarian cancer who have developed resistance to platinum-based chemotherapies.
John Cini, Ph.D. Co-Founder and CSO of Sonnet, added, "We believe we have addressed these issues with our discovered platform, having utilized a molecule that can be applied in any solid tumor type that concentrates albumin, such as sarcoma, gynecologic, and gastrointestinal cancers. We intend to explore new compounds as well, as funds become available."
Addressing Limitations of IL-12 Therapy
IL-12 and related compounds have been extensively studied in cancer and immunotherapy, but recombinant interleukins have had limited clinical success due to their short circulating half-life, inefficient tumor microenvironment (TME) targeting, and requirement for frequent dosing, often leading to substantial systemic toxicities. Sonnet's FHAB platform aims to overcome these limitations by improving cytokine delivery and reducing toxicity.
The extensive discovery program included identifying strongly binding molecules that bind tightly over a 5.8 to 7.2 pH range and do not interfere with the normal physiology of albumin to bind the neonatal Fc receptor (FcRn). This resulted in prolonged half-life in serum and binding to SPARC/GP60, which allows albumin to target the tumor microenvironment (TME).
