Benzinga | Aug 30, 2021 04:02PM EDT

Sonnet Announces Completion Of Discovery Phase For Its Next Preclinical Pipeline Candidate (SON-1410)

Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a biopharmaceutical company developing innovative targeted biologic drugs, announced today that it has selected a novel development candidate after completing comparative studies in a mouse melanoma model. The candidate represents Sonnet's second bispecific compound integrating Interleukin 12 (IL-12) with the company's Fully Human Albumin Binding (FHAB) platform. The target indications for SON-1410 will be melanoma and renal cancers.

Pankaj Mohan, Ph.D., Sonnet founder and CEO, commented, "Following our recently completed $30 million financing, we are excited to have identified this latest bispecific candidate, which is scheduled to enter the next stages of its development during the fourth quarter of 2021, with the objective of filing an IND in the second half of 2022. Our Scientific Advisory Board is very encouraged by these latest data and by the opportunity to further expand our work with IL-18 and IL-12, as we continue the buildout of our immuno-oncology pipeline."

IL18-FHAB-IL12 showed statistically significant tumor size reduction in a mouse melanoma study compared with the placebo, as well as a dose response. The data demonstrated:

Day 0, Single Dose Day 8 Tumor Volume (mm3 +/ Day 8 Percentage TumorTest Article - SEM), N=8 Shrinkage Tumor @ 100 mm3

Placebo NA 1747 +/- 301 -

IL18-FHAB-IL12 1 ug 918 +/- 130 47%

IL18-FHAB-IL12 5 ug 619 +/- 141 65%

A separate mouse study was also performed comparing the selected version of IL18-FHAB-IL12 with two other candidates, GMCSF-FHAB-IL18 and GMCSF-FHAB-IL12. The comparison data indicated significantly greater reduction in tumor volume, along with higher Interferon Gamma levels and immune cell responses (NK, NKT, Th1, and cytotoxic CD8 T cells) using IL18-FHAB-IL12, compared with GMCSF-FHAB-IL12 or GMCSF-FHAB-IL18. Based on this study, SON-1410 (IL18-FHAB-IL12) will replace SON-2014 (GMCSF-FHAB-IL18) as a development program.

The data was reviewed by Sonnet's Scientific Advisory Board, composed of leading oncology specialists from MD Anderson Cancer Center, Fox Chase Cancer Center, UMDNJ-Robert Wood Johnson Medical School/Cancer Institute of New Jersey, and Moffitt Cancer Center, Tampa, Florida.

Sonnet Chief Scientific Officer and Co-Founder, John K. Cini, Ph.D., said, "I am excited about IL18-FHAB-IL12 becoming our second bispecific candidate that utilizes IL-12. There appears to be synergy between these interleukins, as IL-18 upregulates the IL-12 receptor and IL-12 upregulates the IL-18 receptor. IL-18 also appears to increase chemokines CXCL9 and CXCL10. SON-1410 has the potential to make a cold tumor immunologically hot. Used with a checkpoint inhibitor, SON-1410 could synergistically enhance clinical efficacy. Bispecific assets on the FHAB platform offer targeted delivery to tumors and an extended half-life, potentially improving the therapeutic index for safety and tolerability with enhanced efficacy."

Richard T. Kenney, M.D., Sonnet's Chief Medical Officer, added, "The decision to move the SON-1410 construct forward is an important one for Sonnet, as we continue our search for novel, bispecific combinations with profound anticancer properties. IL-18 is a member of the IL-1 superfamily of cytokines that activates Th1 cells when combined with IL-12, as well as stimulating natural killer (NK) cells. The mouse data we generated demonstrate that SON-1410 represents a molecule that may harness IL-18 as a potentially effective therapeutic tool for oncologists."

Sonnet is initiating the manufacturing process for SON-1410 with cell line and process development, which will be followed by manufacturing for a toxicology study, with the intention of filing an IND during the second half of 2022.