• First-in-human results from the STARt-001 Phase 1/2 clinical trial demonstrate selective activation of Vβ6/Vβ10 T cells expands functional effector and memory populations, generating single-agent antitumor activity in heavily pretreated, checkpoint-resistant solid tumors
• Peer-reviewed findings establish the human biological foundation for invikafusp alfa and validate Marengo’s STAR, TriSTAR and MSTAR precision immunotherapy platforms

CAMBRIDGE, Mass., Oct. 23, 2026 /PRNewswire/ — Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering precision immunotherapies for oncology and inflammation and immunology (I&I), today announced the publication in Nature Medicine of results from STARt-001, the first-in-human Phase 1/2 clinical trial of invikafusp alfa in patients with advanced, heavily pretreated solid tumors. The publication represents the first clinical demonstration that germline-encoded (sequences of DNA naturally present in the body from birth) Vβ T-cell subsets can be selectively activated and expanded as a therapeutic approach in oncology. In patients whose tumors were mostly resistant to prior immune checkpoint blockade (ICB), invikafusp alfa expanded functional effector and memory Vβ6/Vβ10 T cells and generated single-agent antitumor activity across multiple tumor types.

The article titled “Bispecific dual T cell agonist invikafusp alfa in solid tumors: the Phase 1/2 START-001 trial,” reports findings from the completed Phase 1 dose-escalation and initial Phase 2 expansion cohorts. The results demonstrate a manageable safety profile, selective peripheral and intratumoral expansion of Vβ6/Vβ10 T cells, objective responses across multiple difficult-to-treat tumor types and the establishment of a recommended Phase 2 dose.

“These data provide encouraging clinical evidence that selected Vβ6/Vβ10 T-cell populations can be activated and expanded in patients with advanced cancer,” said Lillian L. Siu, M.D., Senior Medical Oncologist at UHN’s Princess Margaret Cancer Centre and co-lead author of the publication. “The alignment of target engagement, functional T-cell expansion, a manageable safety profile and objective responses across several refractory tumor types provides a rationale for further investigation of this approach and its potential antitumour activity.”

Key findings reported in the publication include:

• Completion of Phase 1 dose escalation without reaching a maximum tolerated dose and selection of a recommended Phase 2 dose based on integrated safety, pharmacodynamic and antitumor activity data.
• Selective, dose-dependent expansion of peripheral and intratumoral functional effector and memory Vβ6/Vβ10 T cells, providing evidence of target engagement and the intended biological mechanism.
• Confirmed objective responses in heavily pretreated patients with immune checkpoint blockade-resistant tumors, including microsatellite-stable (MSS) colorectal cancer and PD-L1-negative non-small cell lung cancer, settings that have historically shown limited responsiveness to checkpoint inhibition.
• A manageable safety profile consistent with invikafusp alfa’s mechanism of action, with cytokine release syndrome primarily low grade and no treatment-related deaths, no treatment-related non-laboratory Grade 4 adverse events and no cases of immune effector cell-associated neurotoxicity syndrome (ICANS).

“Publication of these data in Nature Medicine marks the breakthrough moment at which a novel scientific concept becomes a clinically demonstrated therapeutic approach,” said Zhen Su, M.D., President and Chief Executive Officer of Marengo Therapeutics. “For the first time, we show that selected germline Vβ T-cell populations can be activated and expanded in cancer patients, generating antitumor activity across biologically distinct, PD-1-resistant tumors. Invikafusp alfa represents the first clinical application of this biology, and these findings provide proof of concept in humans for our broader platform to activate, redirect or deplete selected T-cell populations. As we present updated Phase 2 results at ESMO today and advance our next-generation IO-ADC strategy, we are applying this biology with precision tailored to the right tumor, the right patient and the right therapeutic solution.”

Invikafusp alfa is the lead clinical asset from Marengo’s Vβ-directed platform. Vβ6/Vβ10 T cells are a germline-encoded population expressed consistently across multiple tumor types, regardless of patient age or sex, and enriched among tumor-infiltrating lymphocytes (TILs). Invikafusp alfa therefore has a target that does not depend on any single tumor-specific mutation or antigen. By demonstrating that a selected germline-encoded Vβ subset can be therapeutically modulated in humans, the Nature Medicine publication provides the biological foundation for three complementary approaches: selective activation through STAR, tumor-directed redirection through TriSTAR and selective depletion through MSTAR.

Marengo will also present interim Phase 2 results from STARt-002, the first clinical study to combine a Vβ6-selective T-cell agonist with an antibody-drug conjugate in triple-negative and HR-positive/HER2-negative metastatic breast cancer at the SITC 2026 Annual Meeting. Further analyses are also ongoing, with additional clinical data expected in 2027.

Dr. Lillian Siu serves as a scientific advisor to Marengo Therapeutics and holds equity in the company. UHN conducts clinical research supported by Marengo Therapeutics.

About Invikafusp Alfa (STAR0602)

Invikafusp alfa (STAR0602), the lead candidate from Marengo’s STAR™ platform, is a first-in-class, bispecific dual T-cell agonist. It is designed to selectively activate a common Vβ T-cell subset found in all cancers by combining a non-clonal mode of TCR activation with a T-cell co-stimulatory signal in a single molecule. This approach promotes the expansion of clonally diverse, effector memory Vβ T cells, enhancing antitumor immunity and enabling durable tumor clearance. Invikafusp alfa was designed to restore and amplify antitumor immunity in patients who have progressed on, or are insensitive to, prior immune checkpoint blockade.

About the STARt-001 Clinical Study

STARt-001 is a global Phase 1/2 trial evaluating invikafusp alfa monotherapy in patients with advanced, antigen-rich solid tumors that are refractory or resistant to PD-1–directed therapy. The Phase 2 portion uses biomarker-enriched cohorts, including TMB-H and MSI-H, to assess activity across multiple tumor types and help identify patients most likely to benefit. For more information, visit ClinicalTrials.gov (NCT05592626). STARt-001 Phase 2 expansion is ongoing to further investigate invikafusp alfa for the treatment of ICB-resistant tumors.

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 autoimmune diseases. With a passionate team of dedicated scientists experienced in immunology and oncology, and three proprietary platforms: Selective T Cell Activation Repertoire (STAR), Trispecific T Cell Engager (TriSTAR) and T cell Depletor (MSTAR), Marengo is working to selectively target the right T cells in the right patients to create a world in which everyone’s immune system can defeat cancer and autoimmune diseases. To learn more, visit marengotx.com.

Contacts:

Media | Peg Rusconi | peg.rusconi@deerfieldgroup.com
Investors | Anne Marie Fields | annemarie.fields@precisionaq.com

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SOURCE Marengo Therapeutics