Marengo Therapeutics, Inc.

Ipsen has announced that it will be gaining exclusive global rights to Biomunex Pharmaceuticals’ pre-clinical T cell engager (TCE) in a deal worth up to $610m, marking an expansion to the company’s immuno-oncology pipeline. BMX-502 is a bispecific antibody that engages and activates a subset of cytotoxic T cells called MAIT cells and targets the GPC3 tumour antigen to kill cancer cells. GPC3 is highly expressed across several cancer types, including melanoma and hepatocellular carcinoma, while MAIT cells are present throughout the body, particularly in mucosal and barrier tissues. MAIT engagers have the potential to provide a “more robust therapeutic window” compared to classical pan-TCEs in specific tumour types and are expected to overcome limitations associated with the therapies, such as cytokine release syndrome, according to Ipsen. Following Biomunex’s completion of the Investigational New Drug (IND)-enabling package for BMX-502, Ipsen will assume responsibility for phase 1 preparation activities, including submission of the IND application, and all subsequent clinical-development and global commercialisation. In exchange, Biomunex will be eligible for up to $610m, including an undisclosed upfront fee, development, regulatory and commercial milestones, in addition to tiered global royalties on sales. Mary Jane Hinrichs, senior vice president and head of early development at Ipsen, said: “This new MAIT-engager programme will complement our existing TCE portfolio as we harness the next-generation of TCEs to overcome treatment challenges, including dose-limiting toxicity, to bring transformational new medicines to people living with solid tumours around the world.” Also commenting on the agreement, Pierre-Emmanuel Gerard, founder, president and chief executive officer of Biomunex, said: “We are convinced that our MAIT engagers will represent a new step forward in the development of disruptive immuno-therapies for the treatment of cancer. We look forward to initiating and supporting the development of BMX-502 alongside Ipsen.” The deal comes six months after Ipsen expanded its ongoing oncology research partnership with Marengo Therapeutics to include Marengo’s TCE platform. The new agreement, worth up to $1.2bn, centres around Marengo’s TriSTAR platform, which offers the potential to produce candidates able to overcome the effects of poor T cell quality and T cell exhaustion that may limit the activity of traditional TCEs targeting difficult-to-treat ‘cold’ tumours.

Ipsen has inked yet another licensing deal in an effort to bolster its cancer pipeline, this time for a preclinical T cell engager developed by another Paris-based drugmaker. The French pharma company is committing up to $610 million in upfront and milestone payments, as well as tiered royalties on sales, for global rights to Biomunex’s BMX-502. The biotech, which also has an office in Cambridge, MA, will complete IND-enabling activities for the candidate, with Ipsen taking over for Phase 1 and beyond, according to a Tuesday release . Ipsen has made at least five cancer deals this year, which is part of a broader push to expand its pipeline in three core therapeutic areas that also include rare diseases and neuroscience. “The number of deals that we did this year is roughly the number of deals that we should expect to see next year,” chief business officer Philippe Lopes-Fernandes told Endpoints News in an interview. “This year, we’ve definitely done more in oncology, but it might be the opposite next year.” Ipsen plans to continue with bolt-on licensing deals but also scout for later-stage targets that could merit an acquisition, Lopes-Fernandes said. BMX-502 is a bispecific antibody that “engages and activates” a type of T cell called mucosal-associated invariant T (MAIT), while also targeting the GPC3 antigen, which is expressed in multiple tumors, according to Ipsen. MAIT cells are more “enriched” in some areas of the body, such as mucosal and barrier tissues, and targeting them specifically could avoid some of the setbacks that come with pan T cell engagers, such as cytokine release syndrome. “We have other T cell engagers, bispecific and trispecific [that are partnered] with Marengo [Therapeutics], but this is a different approach and it complements quite nicely,” Lopes-Fernandes said. In June, the company expanded a 2022 deal with Marengo to add two trispecific antibody candidates. The Biomunex and Marengo deals add to a spate of oncology deals Ipsen has forged this year. In April, the drugmaker bagged exclusive rights to Sutro Biopharma’s ROR1-targeting ADC for solid tumors as part of a pact featuring $90 million in near-term payments. In July, Ipsen picked up the rights to another ADC from China’s Foreseen Biotechnology for up to $1.03 billion in upfront payments, milestones and tiered royalties. It also paid $111 million upfront for the ex-US rights to a medicine for pediatric low-grade glioma called Ojemda that was developed by Day One Biopharmaceuticals.

CAMBRIDGE, MA, USA I November 9, 2024 I Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision T cell activation, today announced encouraging initial Phase 1 clinical data from its lead program, invikafusp alfa (STAR0602), during a late-breaking oral presentation at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting taking place in Houston, Texas. This is the first public disclosure of results from the ongoing STARt-001 Phase 1/2 trial (NCT05592626), evaluating invikafusp alfa as monotherapy in biomarker-enriched (TMB-H, MSI-H/dMMR or virally associated) patients with advanced anti-PD-1 resistant, or refractory solid tumors. Phase 1 data from STARt-001 trial demonstrate early anti-tumor activity, including initial signals of clinical benefit in heavily pre-treated, anti-PD-1 resistant cancer patients. Invikafusp alfa also showed a manageable safety profile consistent with its novel mechanism of action, further supporting its potential as a treatment option across a range of high tumor mutational burden (TMB-H) cancers or virally associated malignancies. “Having completed Phase 1 and commenced the Phase 2 dose expansion cohorts of STARt-001, Marengo is thrilled to share initial clinical findings that validate our novel selective dual T cell agonist platform,” said Zhen Su, M.D., MBA, Chief Executive Officer of Marengo Therapeutics. “The single agent activity observed in Phase 1, especially in PD-1 resistant cold tumors such as colorectal cancer is a critical milestone, and we look forward to further exploring the potential of STAR0602 to become a next-generation backbone IO therapy across a range of tumor types.” Additional highlights from the Phase 1 findings include: “The first-in-human data suggest that this novel approach to selectively activate and expand Vβ T cell subsets may hold promise for treating patients with advanced solid tumors,” said Dr. James L. Gulley, Co-Director of the Center for Immuno-Oncology and Clinical Director of the National Cancer Institute. “The observed unique Vβ T cell biology in humans and selective expansion of Vβ6/Vβ10 across a range of solid tumors, combined with the initial anti-tumor activity, particularly in heavily pre-treated anti-PD-1 resistant cancer patients with TMB-H colorectal cancer, are encouraging signs. The differentiated clinical profile supports further investigation of this unique mechanism of action in the next phase of clinical trials for high unmet medical needs in anti-PD-1 resistant tumors.” Taken together, the data presented from the STARt-001 study underscore invikafusp alfa’s potential as a novel therapeutic option for patients with advanced, PD-1-resistant solid tumors. Marengo has initiated the Phase 2 dose expansion and expects to share initial results in 2H 2025. Late-breaking oral presentation details: About Marengo Therapeutics Marengo Therapeutics, Inc, a clinical-stage biotech company, develops novel TCR-targeting antibodies that selectively modulate common and disease-specific T cell subsets of the germline TCR repertoire to provide lifelong protection against cancer and other diseases. With a passionate team of dedicated scientists experienced in immunology and oncology, Marengo’s proprietary Selective T Cell Activation Repertoire (STAR) platform leverages an extensive biological understanding of T cell function and receptor signaling to create a world in which everyone’s immune system can defeat cancer. To learn more, visit marengotx.com. About STAR ™ Platform Marengo’s STAR ™ Platform is a multi-specific antibody-fusion platform derived from Marengo’s proprietary library of antibodies targeting germline-encoded variable Vβ regions of the TCR fused to different T cell co-stimulatory moieties. Combining a novel non-clonal mode of TCR activation with a T cell co-stimulator in the same molecule, promotes a distinct mechanism of action that promotes durable anti-tumor Vβ T cell responses. About invikafusp alfa (STAR0602) Invikafusp alfa (STAR0602) is Marengo’s lead program, the first T cell activator generated from Marengo’s STAR platform; a library of antibodies targeting non-clonal variable Vβ regions of the TCR fused to different co-stimulatory moieties. STAR0602 selectively targets a common Vβ T cell subset present in all cancers and, by combining a novel non-clonal mode of TCR activation with a T cell co-stimulator in the same molecule, promotes expansion of a new population of clonally enriched, effector memory Vβ T cells that turbo-charge tumor immune responses and promote durable clearance of tumors. STAR0602 has undergone extensive preclinical testing and is currently being studied in a Phase 1/2 clinical trial. About the STARt-001 STARt-001 is a Phase 1/2 clinical trial evaluating the safety, tolerability, and preliminary clinical activity of invikafusp alfa (STAR0602) as a single agent in biomarker selected patients with advanced antigen-rich solid tumors including PD-1 refractory and rare tumors. This open-label, multi-center trial consists 2 of two parts: Phase 1 dose escalation and Phase 2 dose expansion. For more information, please visit clinicaltrials.gov (trial identifier: NCT05592626). For patients interested in enrolling in this study at NCI, please contact NCI’s toll-free number 1800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the website https://trials.cancer.gov and/or email NCIMO_referrals@mail.nih.gov . SOURCE: Marengo Therapeutics