On May 10, 2021 Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a biopharmaceutical company developing innovative targeted biologic drugs, reported that it has completed a successful preclinical nonhuman primate (NHP) GLP repeat-dose study of SON-1010, a proprietary version of Interleukin 12 (IL-12) configured using Sonnet’s Fully Human Albumin Binding (FHAB) platform (Press release, Sonnet BioTherapeutics, MAY 10, 2021, View Source [SID1234579590]). The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The objectives of the study were to evaluate the toxicity of SON-1010 in NHP using a subcutaneous, repeat-dose regimen at three different dose levels versus untreated controls and to evaluate the potential reversibility of any adverse findings.
Pankaj Mohan, Ph.D., Sonnet founder and CEO, commented, "This GLP study was an important milestone to support an IND with the FDA. SON-1010 has now accrued, along with previous non-GLP data, a significant NHP toxicology dataset. The NHP data continues to demonstrate that SON-1010 appears to be safe and is eliciting the expected immune responses that we believe could position this as an effective treatment for multiple types of cancer."
Study results included:
The No Observed Adverse Event Level (NOAEL) following repeated administration was more than 50 times the anticipated equivalent human clinical dose in NHP with no evidence of cytokine release syndrome.
Pharmacokinetic (PK) analysis of serum samples confirmed an enhanced profile of IL12-FHAB over recombinant human IL-12, with a half-life around 40 hours in NHP.
A significant increase in Interferon-γ, a key pleiotropic cytokine associated with anti-tumor mechanisms, was observed following dosing with IL12-FHAB.
SON-1010 related changes in clinical observations, body weight, clinical pathology, cytokines, and immunophenotyping were seen, all of which were consistent with on-target effects previously observed in nonhuman primates.
By Day 38 all study subjects recovered to baseline (pre-study) values.
Repeat dosing administration was tolerated at all dose levels examined.
Richard T. Kenney, M.D., Chief Medical Officer, commented, "Interleukin-12 is a key immunomodulator that bridges innate and adaptive immunity, but showed toxicity in the first human trials over two decades ago. Careful subcutaneous administration of IL-12 has been shown to be a safe dosing approach, even in healthy volunteers. Given that IL12-FHAB has an extended half-life, tolerable doses can be given at longer dosing intervals. SON-1010 has IL-12 attached to a proprietary fully human albumin binding construct, which provides the longer half-life and targeting capability that may be needed to treat tumors. The NHP data suggests that our candidate will be well tolerated. We believe that this novel approach can lead to an effective treatment regimen for multiple types of cancer".
Sonnet’s cell-based manufacturing platform coupled with an intensified perfusion process using state-of-the-art technologies allows rapid scale-up for future commercial manufacturing. Our mammalian cell culture system enables glycosylation, thereby reducing the risk of inducing immunogenicity with IL12-FHAB. We are on track for providing GMP material for initiation of the clinical trial in 2H 2021.