On February 1, 2021 Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs, reported that it has successfully completed a non-human primate (NHP) repeat-dose study of SON-1010, a proprietary fully human Interleukin 12 (IL-12) therapeutic candidate configured using Sonnet’s Fully Human Albumin Binding (FHAB) platform (Press release, Sonnet BioTherapeutics, FEB 1, 2021, View Source [SID1234576687]). The FHAB technology targets tumor tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of immunomodulatory cytokines.

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The objectives of the study were to evaluate the toxicity of SON-1010 in a repeat dose regimen at two different doses and to gather critical data for the design of further IND-enabling safety and toxicity studies. The study included both intravenous and subcutaneous routes of administration with a total of two doses given 14 days apart. The high dosage rate utilized in this study was greater than 50 times the anticipated clinical level of exposure to patients.

Study results included:

Repeat dosing by intravenous and subcutaneous routes of administration were tolerated at both dose levels examined. As is typically observed with IL-12 administration, the white blood cell count dropped, and liver enzymes (ALT and AST) were elevated. These were transient effects that returned to baseline within 7 days following the second dose.
SON-1010-related changes in the physiological observations, body weight, pathology, cytokines and immunophenotyping were seen, all of which were consistent with those on-target effects previously observed in single dose studies.
A significant increase in Interferon-γ levels, a key pleiotropic cytokine associated with anti-tumor activity, was observed following the initial dose of SON-1010 with lower Interferon-γ levels observed following the second dose. This trend follows the published data from other studies of IL-12 in both humans and NHPs.
Pharmacokinetic analysis indicated a mean serum half-life of approximately 40 hours for animals administered SON-1010 via subcutaneous injection. This is consistent with data from the previously conducted dose escalation phase of the study, which demonstrates a substantial improvement in half-life compared to the 13-19-hour half-life of naked, recombinant human IL-12.
Pankaj Mohan, Ph.D., Sonnet founder and CEO, commented, "Taken in combination with our recent single dose toxicology results, these repeat dose data further reinforce our confidence in the SON-1010 safety and efficacy profile as we look forward to initiating the Phase 1 clinical development program later this year."

Sonnet used these data to inform the design of the ongoing GLP toxicity studies in preparation for IND submission. Additionally, the Company has developed a, continuous manufacturing platform consisting of an industry standard mammalian cell (Chinese Hamster Ovary or CHO) host cell line coupled with an intensified perfusion process that allows for rapid scale-up and commercial manufacturing, using state-of-the-art processes and technologies. The mammalian cell culture system enables glycosylation, thereby reducing the risk of immunogenicity.

Susan Dexter, Sonnet’s Chief Technology Officer added, "We have established an intensified, continuous manufacturing process, as compared with an industry standard fed batch process, to enhance productivity and improve the yield of difficult-to-express cytokines. We believe that the ability to manufacture SON-1010 as a single genetic sequence will enable scale up and optimize product quality. A lyophilization formulation provides stability and refrigerated cold chain simplicity."