Sonnet BioTherapeutics Holdings, Inc. announced that a Phase 1b/2a clinical trial of SON-1010 (IL12-FHAB) in combination with Roche's anti-PD-L1 checkpoint inhibitor, atezolizumab (Tecentriq®?), has been approved to begin in Australia. The approval by the Bellberry HREC was based on scientific and ethical review of trial documentation, which included the successful completion of a study of SON-1010 monotherapy (SB102) in healthy volunteers (NCT05408572) and demonstration of continued safety in the first-in-human (FIH) dose-escalation trial in cancer (SB101). The latter is a study of patients with advanced solid tumors that will now focus on platinum-resistant ovarian cancer (PROC) in the USA (NCT05352750).

The new study (SB221), which will also focus on the treatment of PROC (NCT05756907), consists of a dose-escalation phase in Part 1 and a randomized comparison of the combination versus SON-1010 mon therapy or the standard of care (SOC) in Part 2. Importantly, SB221 is expected to show proof-of-concept (POC) with SON-1010 for PROC, as well as augmenting the foundational work underway with the Sonnet bifunctional molecules, SON-1210 and SON-1410. SON-1010 is a proprietary version of recombinant human Interleukin 12 (IL-12), configured using the FHAB technology that targets tumor and lymphatic tissue, that provides a mechanism for dose sparing due to its extended PK properties. The extension of PK with the FHAB platform may improve the safety and efficacy profile of IL-12, an effect that can be complemented using a variety of potent immunomodulators that will be linked to the molecule in a bispecific construct in subsequent programs. Atezolizumab is an immune checkpoint inhibitor approved for the treatment of some of the most aggressive and difficult-to-treat forms of cancer.

The characteristics of ovarian cancer present a unique opportunity to assess the combination of these two agents in an indication that persists as a large unmet medical need. Interleukin-12 has been shown to orchestrate a robust immuneresponse to many cancers and pathogens in patients, as well as in healthy volunteers, but the dosing strategy has been an elusive challenge for over two decades. Sonnet's initial Phase 1 studies with SON-1010 have provided many clues to help improve the dose levels and intervals.

Given the types of proteinsinduced, gynecological cancers are particularly relevant for this approach.