- Compelling data with STAR0602 demonstrate potent single-agent anti-tumor activity in PD-1 refractory solid tumor models
- Distinct mechanism of action through expansion of a subset of Vβ T cells with a novel memory phenotype that promotes long-lasting de novo antitumor immune responses
- STAR0602 is expected to start Phase 1/2 clinical trial (START-001) in Q4 2022
CAMBRIDGE, Mass., October 28, 2022 /PRNewswire/ — Marengo Therapeutics, Inc., a pioneering novel therapeutics company targeting the T cell receptor Vβ chain (TCR Vβ) to selectively activate the right T cell subsets to fight cancer, today presented first preclinical proof-of-concept data on STAR0602, its novel TCR agonist antibody, in the 34e EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA) at Barcelona, Spain. The data presented showed potent anti-tumor activity of STAR0602 in a range of solid tumor models, including those refractory to checkpoint inhibitors like PD-1/PD-L1.
The plenary oral presentation was given by james gulleyMD, Ph.D., Co-Director of the Center for Immuno-Oncology (CIO), Deputy Director of the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), and Acting Clinical Director of the NCI.
“STAR0602 offers an entirely novel mechanism of selective T-cell activation that increases both the quantity and quality of T-cell responses to tumor via a mechanism distinct from checkpoint inhibitors,” said Zhen Su, MD, MBA, Chairman and CEO of Marengo. “These results strongly suggest that our lead asset has the potential to become a next-generation IO core treatment against a range of solid tumors representing a new therapeutic strategy for patients.”
“We are excited to share the first data from our STAR0602 program,” added Andrew Bayliffe, Ph.D., scientific director of Marengo. “These studies show that our selective T-cell Vβ activators access a novel T-cell immunology that has the potential to fundamentally reshape the adaptive immune response to solid tumors and install long-term tumor immunity.”
In a range of refractory murine syngeneic solid tumor models, mSTAR0602 monotherapy (the murine surrogate for STAR0602) at moderate doses either eradicated tumors or resulted in substantial regressions – long-term durable effects. The mice cured with mSTAR0602 also showed long-term protection against the novel tumor challenge. This anti-tumor activity has been shown to depend on the accumulation of a specific subset of Vβ T cells in tumors that adopt a novel effector memory phenotype and a striking increase in TCR diversity. The expansion of these memory effector Vβ T cells was accompanied by a reduction of exhausted T cells and regulatory T cells. A similar potent expansion of human TILs and tumor destruction has been observed in primary syngeneic human ex vivo tumor models derived from multiple patient samples. The anti-tumor activity of STAR0602 in these ex vivo human tumor models was superior to that of pembrolizumab when tested in parallel at therapeutic concentrations.
Additional details on the presentation are outlined below:
- Title: STAR0602, a novel TCR agonist antibody, demonstrates potent anti-tumor activity in refractory solid tumor models through the expansion of a novel subset of polyclonal effector memory T cells
- Abstract number: ENA22-0183
- Session day/time: friday october 28; 12:40 p.m. CET
- Venue: Barcelona International Congress Center, Barcelona, Spain
- Presenter: james gulleyMD, Ph.D.
- Research Highlights:
- Studies in non-human primates and patient organoids were conducted to confirm translation of the STAR0602 target immunology to support planned human clinical trials.
- The START-001 clinical study will evaluate the safety, tolerability, and preliminary clinical activity of STAR0602 as a single agent in patients with advanced antigen-rich solid tumors, including PD-1 refractory patients. This open-label, multicenter Phase 1/2 study consists of two parts: Phase 1 dose escalation and Phase 2 dose expansion. For more information, please visit clinicaltrials.gov (trial ID: NCT05592626)
About Marengo Therapeutics
Marengo Therapeutics, Inc, an ATP company, is a pioneer in first-class therapies that activate the right immune response to promote lifelong protection against cancer. With a passionate team of dedicated and experienced scientists in immunology and oncology, Marengo’s proprietary Selective T Cell Activation Repertoire (STAR) platform is based on a deep biological understanding of T cell function and signaling. receptors to create a world in which everyone’s immune system can defeat cancer. To learn more, visit marengotx.com.
STAR0602 is the company’s lead program, the first T-cell enhancer generated by Marengo’s STAR platform, a multi-species fusion protein library that targets specific TCR Vβ variants fused to different co-stimulatory moieties generating potent T-cell enhancers The unique feature of this platform is to fine tune the T cell response in selected T cell subsets to generate endogenous, highly functional and anti-cancer T cells for solid tumors. STAR0602, is a fusion protein that binds to a specific region of TCR Vβ and delivers a unique activation signal to the same T cell, leading to selective expansion of targeted T cell subclones. This molecule has shown remarkable single agent activity in a wide range of preclinical models.
SOURCE Marengo Therapeutic