Sonnet BioTherapeutics Announces A Publication Demonstrating Safety And Tolerability Of SON-1010 In Healthy Volunteers

Author: Happy Mohamed | February 29, 2024 05:25pm

Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs for cancer, announced today the publication of clinical data on SON-1010 in Frontiers in Immunology. SON-1010, Sonnet's lead proprietary monofunctional compound, combines the company's fully-human albumin-binding (FHAB) construct with single-chain interleukin 12 (IL‑12). The paper, entitled "A phase I trial of SON-1010, a tumor-targeted, interleukin-12-linked, albumin-binding cytokine, shows favorable pharmacokinetics, pharmacodynamics, and safety in healthy volunteers", demonstrated safety and tolerability up to 300 ng/kg as a single ascending dose. In the B16F10 melanoma model, a single dose of SON-1010 results in a marked reduction of tumor growth that was concomitant with increased IFNg, along with augmented immune cell numbers and activity in the tumor microenvironment (TME). The study of SON‑1010 in healthy volunteers, called SB102 (NCT05408572), was first announced in July 2022 and was done in parallel with the ongoing SB101 study in cancer patients (NCT05352750). The results from SB102 provide the initial ‘desensitizing dose' for further dose escalation of the maintenance dose in SB101, to establish the maximum tolerated dose for this molecule.

"The publication of these data is an important milestone for Sonnet that provides additional scientific validation of our FHAB technology." said Pankaj Mohan, Ph.D., Founder and CEO of Sonnet. "The SB102 study was designed to elucidate the PK and PD of SON-1010 in normal, healthy volunteers, and shows that the drug is safe in the dose range tested, while also providing an appreciably extended half-life. When combined with checkpoint inhibitors, we hypothesize that the targeted immune enhancing components of the SON-1010 mechanism have the potential to turn cold tumors hot. We also believe that our pipeline, which includes compounds with bifunctional combinations of Interleukins 15 and 18, could potentially prove useful in combination with cell-based therapies. We are diligently pursuing these applications, as well."

While doses above 100 ng/kg were tolerated, participants generally experienced more treatment-emergent adverse effects (TEAEs) than those receiving the lowest dose of 50 ng/kg. All TEAEs were transient and were consistent with published experience using recombinant IL‑12. More precise pharmacokinetic (PK) and pharmacodynamic (PD) data can be obtained using this non-genotoxic cancer therapy in healthy individuals, without a background of immunosuppression. PK analysis showed two-compartment elimination in SB102 with a mean half-life of 104 hours, compared with one-compartment elimination in SB101, which correlated with prolonged but controlled and dose-related increases in IFNg. This is evidence for target-mediated drug disposition (TMDD), which implies delivery to and retention of SON-1010 in tumor tissue. There were minimal responses with other cytokines and no evidence of cytokine release syndrome.

"IL-12 has been studied in healthy volunteers in the past and has shown great promise in animal models of cancer treatment for decades, yet developmental progress in human trials has typically been hindered by toxicity before the therapeutic dose can be reached." said Richard Kenney, M.D., Sonnet's Chief Medical Officer. "Extending the PK by binding to the neonatal Fc receptor (FcRn), combined with targeting retention in the TME through binding to gp60 and SPARC, contributes to TME localization of SON-1010. This may be the key to enhancing the therapeutic window and inducing successful immune responses in the TME, as the PD will also be extended to allow better activation of immune cell penetration and replacement of immune inhibitors."

The manuscript can be accessed through the following link:

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1362775/full

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