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Marengo Presents Expanded Clinical Monotherapy Activity of Invikafusp Alfa in Multiple PD-1 Resistant Tumors as a Clinical Plenary Oral at AACR 2025

On April 29, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy, reported new clinical and translational data from the ongoing STARt-001 Phase 1/2 trial of invikafusp alfa (STAR0602), presented as a clinical plenary oral session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Marengo Therapeutics, APR 29, 2025, View Source [SID1234652333]).

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The presentation highlights strong evidence of meaningful clinical activity, robust immune activation in vivo, and a well-characterized safety profile, further supporting the momentum behind the ongoing Phase 2 study as well as the value proposition for developing invikafusp as monotherapy in PD1 resistant TMB-H cancers.

"Today’s data represent a major step forward for Marengo and for the field of IO to advance a new class of cancer immunotherapy: Immune Activation Inducers (IAI)," said Zhen Su, M.D., M.B.A., Chief Executive Officer of Marengo Therapeutics. "Invikafusp alfa’s ability to selectively activate and expand a key T cell subset to drive meaningful anti-tumor responses across a range of PD-1 resistant tumors gives us confidence in our precision T cell activation approach. The emerging clinical signals in both colorectal and lung cancers further underscore invikafusp’s pan-tumor potential and justify our focused expansion into these high-need indications."

"Colorectal cancer is less sensitive to immunotherapy except in a very small percentage of MSI-H tumors. The field has seen few, if any, immunotherapy agents achieve single-agent activity in PD-1 resistant colorectal cancer," said Josep Tabernero, M.D., Director of Vall d’Hebron Institute of Oncology (VHIO). "The clinical signals observed with invikafusp alfa in both CRC and other tumor types are highly encouraging and warrant further clinical investigation to fully realize the clinical potential of this novel T cell agonist approach."

Invikafusp alfa is Marengo’s first-in-class dual T cell agonist, designed with a bi-specific antibody format to selectively engage and activate the Vβ6 and Vβ10 subsets of T cells in vivo, promoting durable anti-tumor immunity.

Updated Findings from the STARt-001 Clinical Plenary Presentation:

Clinically meaningful anti-tumor activity as monotherapy in anti-PD(L)1-resistant tumors at the recommended Phase 2 dose (RP2D) of 0.08 mg/kg:
61% disease control rate in heavily pretreated, PD-1 resistant tumors dosed at 0.08 or 0.12 mg/kg
52% tumor regression rate observed across multiple tumor types, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), cervical, squamous cell carcinoma of the head and neck (SCCHN), and melanoma
Objective responses in colorectal cancer and NSCLC:
3 responders out of 10 TMB-high metastatic CRC patients (across RAS wild-type, RAS mutant, and MSI-H subtypes)
1 additional responder with 73% tumor regression out of 2 anti-PD(L)1-resistant TMB-high NSCLC patients
Mechanism of Action and Translational Insights:
Invikafusp promoted potent, selective expansion of peripheral CD8+ Vβ6/Vβ10 T cells, which acquired a novel "memory-like effector" phenotype in both blood and tumor tissue
Expanded and activated Vβ T cells in post treatment tumor tissues consistent with enhanced anti-tumor function
Safety Profile:
Consistent with a selective T cell activation mechanism
Adverse events were generally transient and manageable with supportive care
Based on these early clinical and preclinical findings, the U.S. Food and Drug Administration has granted Fast Track Designation to invikafusp alfa for the treatment of patients with TMB-high colorectal cancer.

The Phase 2 portion of the STARt-002 trial is actively enrolling patients across multiple tumor types, including TMB-H metastatic colorectal cancer, MSI-H and TMB-H tissue-agnostic solid tumors.

NEUVOGEN Announces Poster Presentation at the American Association of Cancer Research Annual Meeting

On April 29, 2025 NEUVOGEN, Inc. ("NEUVOGEN THERAPEUTICS" or "NEUVOGEN"), a San Diego based biotechnology company, reported that it will present data that its next generation whole tumor cell vaccine (NGEN-143) activates T cells that recognize a diverse antigen repertoire (Press release, NEUVOGEN, APR 29, 2025, View Source [SID1234652332]).

"These findings support that NGEN-143 can deliver an unprecedented breadth of targets and activate cytotoxic T cells, as compared to other currently available cancer vaccines, making NGEN-143 a better potential option for patients" said Todd Binder, Chief Executive Officer of NEUVOGEN. "Our dedicated team is eager to bring this new cancer vaccine forward to treat patients with non-small cell lung cancer (NSCLC)."

Key Findings:

In a fully human in vitro system, NGEN-143 expands effector T cells against a broad repertoire of both tumor-associated antigens and common shared neo-antigens across a wide range of HLA types.

NGEN-143 activates polyfunctional, cytotoxic T cells; the response is dominated by CD8+ cells without any evidence of antigenic competition. CD4+ T cell responses are skewed toward CD4+ Th1 cells over CD4+ Th2 cells.

NGEN-143 activated T cells efficiently kill human tumor cells in a caspase-3 dependent manner.

In the ‘immune warm’ CT26 mouse tumor model, vaccine abrogates or slows tumor growth – durable protection against rechallenge supports efficient induction of immune memory; vaccine + αPD1 improved survival over αPD1 monotherapy.

In the ‘immune cold’ B16F10 mouse tumor model, our vaccine approach inhibits tumor growth and prolongs survival; vaccine + αPD1 improved survival.
Bernadette Ferraro, Ph.D., NEUVOGEN’s Vice President, Immuno-oncology, is scheduled to present "An optimized off-the-shelf whole tumor cell vaccine activates T cells that recognize a diverse antigen repertoire with potential to provide meaningful clinical benefit to patients with NSCLC," at AACR (Free AACR Whitepaper) on Tuesday, April 29 from 2:00 – 5:00 PM CT. A copy of the poster will be made available for download at neuvogen.com/our-science after the meeting concludes.

Innovent Announces First Patient Dosed in Phase 1 Study of IBI3020, Global First-in-class Dual Payload CEACAM5 ADC, in Patients with Advanced Malignancies

On April 29, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported completion of the first patient dosing for IBI3020, its first-in-class dual-payload CEACAM5 ADC, in Phase 1 clinical trial for the treatment of patients with advanced solid tumors (Press release, Innovent Biologics, APR 29, 2025, View Source;in-patients-with-advanced-malignancies-302441146.html [SID1234652331]). IBI3020 is the first dual-payload ADC developed from Innovent’s proprietary DuetTx dual-payload ADC platform and the first dual-payload ADC globally known in the same class to complete the first-in-human dosing.

The study is an open-label, multi-regional Phase 1 study evaluating the safety, tolerability, and preliminary efficacy of IBI3020 in participants with advanced solid tumors, as well as determining the recommended Phase 2 dose (RP2D). The study has received IND approval in the U.S. recently and will be conducted in both China and the U.S.

As a global first-in-class ADC candidate, IBI3020 is generated from Innovent’s proprietary DuetTx dual-payload ADC platform. The internationalization of the CEACAM5-dependent ADC occurs after IBI3020 selectively binds to CEACAM5-expressing tumor cells, followed by lysosomal degradation. This process releases two types of cytotoxic payloads, leading to cell killing of tumor cells.

In preclinical studies, IBI3020 has demonstrated robust antitumor activity across various tumor-bearing pharmacology models, with a notable bystander killing effect. Additionally, IBI3020 has shown favorable safety characteristics in preclinical models, with an overall manageable safety profile.

Professor Yu Jinming, Shandong Cancer Hospital, stated:" Carcinoembryonic antigen (CEA), also known as CEACAM5, is a glycosylphosphatidylinositol-anchored cell-surface glycoprotein involved in cell adhesion, invasion, and metastasis of cancer cells. There is a significant clinical need for effective therapies in advanced colorectal cancer, non-squamous lung cancer, gastric cancer, pancreatic cancer, and others. CEACAM5 is overexpressed in these solid tumors but shows limited expression in healthy tissues, making it a potentially safe and promising therapeutic target. The dual payload of IBI3020 consists of two types of payloads that have been clinically validated. This dual-payload design has demonstrated enhanced tumor-killing effects in preclinical studies. We look forward to observing the clinical profiles and potential breakthrough of IBI3020 in terms of safety, tolerability, and efficacy in clinical trials."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to announce the successful dosing of the first patient dose with IBI3020. We will continue to advance the global development of IBI3020, aiming to offer better treatment options for patients with advanced solid tumors. Innovent possesses innovative ADC technology platforms with independent intellectual property rights. Multiple ADC molecules have clinically validated their differentiated competitiveness. IBI3020, Innovent’s first dual-payload ADC, has successfully entered clinical trials and is the first dual-payload ADC globally known in the same class to complete the first-in-human dosing, marking a breakthrough in Innovent’s ADC technology. We will continue our "IO+ADC" strategy, focusing on next-generation innovations with global potential to benefit cancer patients worldwide."

About IBI3020

IBI3020 is a global first-in-class ADC candidate developed from Innovent’s proprietary DuetTx dual-payload ADC platform. The CEACAM5 dependent ADC internalization occurs after IBI3020 selectively binds to the CEACAM5-expressing tumor cells, followed by the lysosomal degradation. This process releases two types of cytotoxic payloads, leading to tumor cell killing.

The multi-regional Phase 1 study of IBI3020, initiated in China, assesses the safety, tolerability, and preliminary efficacy of IBI3020 in patients with advanced solid tumors and aims to determine the recommended Phase 2 dose (RP2D). The study has also received IND approval in the U.S. recently and will be conducted in China and the U.S.

aTyr Pharma Presents Preclinical Data for NRP2-Targeting Antibody ATYR2810 at the American Association for Cancer Research (AACR) Annual Meeting 2025

On April 29, 2025 aTyr Pharma, Inc. (Nasdaq: ATYR) ("aTyr" or the "Company"), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, reported that the Company will present a poster featuring preclinical data for ATYR2810, a monoclonal antibody targeting neuropilin-2 (NRP2), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, which is being held April 25 – 30, 2025, in Chicago, IL (Press release, aTyr Pharma, APR 29, 2025, View Source [SID1234652330]).

"Aggressive cancers like glioblastoma multiforme (GBM) continue to show drug resistance, and the efficacy of current immunotherapies may be limited due to immunosuppressive myeloid cells in the tumor microenvironment that contribute to drug resistance. We are pleased to see that ATYR2810 appears to combat drug resistance mechanisms, and we are particularly encouraged by its ability to increase survival and improve the effectiveness of checkpoint inhibitors in a GBM model," said Leslie A. Nangle, Ph.D., Vice President, Research, at aTyr. "These findings, which were generated as part of our ongoing research collaboration with Dr. Michael Lim and Stanford Medicine, demonstrate the role of NRP2 in maintaining the immunosuppressive tumor microenvironment and suggest that blocking NRP2 may offer a new approach to treating GBM, both as a monotherapy and in combination with anti-PD-1 therapies."

Details of the poster presentation appear below. The poster will be available on the aTyr website once presented.

Title: Immunosuppressive myeloid cells can be modulated with NRP2-targeting antibody ATYR2810 leading to enhanced anti-tumor immunity
Authors: Christoph Burkart, Clara Polizzi, John Choi, Max Pastenes, Alison Barber, Michael Lim, Leslie Nangle. aTyr Pharma, San Diego. Department of Neurosurgery, Stanford School of Medicine, Stanford.
Session: Antibodies and Antibody-Drug Conjugates
Poster Number: 27
Date and Time: Tuesday, April 29, 2025 from 9:00AM – 12:00PM CT
Location: Poster Board Section 36, McCormick Place Convention Center, Chicago, IL

The poster presents preclinical research evaluating the use of ATYR2810 in syngeneic tumor models including the orthotopic CT-2A mouse model of GBM, which has a high prevalence of myeloid-derived suppressor cells that exhibit enriched expression of NRP2 and promote an immunosuppressive tumor microenvironment. The findings demonstrate that ATYR2810 when used as a single agent enhanced anti-tumor immunity and resulted in a significant increase in overall survival. Additionally, when combined with an anti-PD-1 agent, ATYR2810 further increased survival and reduced tumor size. These findings suggest that modulating NRP2 may offer a new approach to reversing the immunosuppressive function of myeloid cells in the tumor microenvironment.

Affimed Shows Higher Exposure of AFM24 is Associated with Significantly Higher Response Rates and Progression-Free Survival in Refractory NSCLC Patients at AACR Annual Meeting

On April 29, 2025 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported findings on an exposure-outcome analysis of its innate cell engager (ICE) AFM24, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) in a poster session at the 2025 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Affimed, APR 29, 2025, View Source [SID1234652329]).

The analysis is based on post-hoc exposure-response data from 72 NSCLC patients treated with 480 mg of AFM24 monotherapy or a combination of AFM24 with atezolizumab. For all patients, trough levels over time were used to calculate the patient’s mean exposure to AFM24. Patients were then split into high and low AFM24 exposure groups for the analysis using the respective median as a cut-off.

Key Findings from the Exposure-Response Analysis

Objective Response Rate (ORR): 33.3% in the high-exposure group vs. 5.6% in the low-exposure group (p=0.0059)
Disease Control Rate (DCR): 83.3% vs. 58.3% (p=0.0367)
Median Progression-Free Survival (mPFS): 7.33 vs. 2.86 months
Overall Survival (OS): Not yet mature in the high-exposure group vs. 13 months in the low-exposure group
A quartile analysis further confirmed the exposure-efficacy relationship, showing a stepwise increase in ORR from 0% in the lowest quartile to 50% in the highest. Subgroup analysis of 55 patients treated with AFM24 plus atezolizumab showed consistent results: 37.04% ORR in the high-exposure group vs. 7.14% in the low group. Importantly, higher exposure was not associated with an increased rate of more serious or severe adverse events.

"Advanced NSCLC is a devastating disease and remains an area of high unmet need," said Andreas Harstrick, MD, Chief Medical Officer of Affimed. "These findings strengthen our clinical rationale for dose optimization and highlight the potential of AFM24 – particularly in combination with atezolizumab – as a novel, chemotherapy-free, immunotherapy-based treatment approach. Importantly, the data suggest that achieving higher drug exposure early in treatment may prevent rapid disease progression."

Further Development

Pharmacokinetic (PK) modeling indicates that a 720 mg weekly dose of AFM24—previously established as safe—achieves target exposure levels by the second week of treatment that correspond to the high exposure group in the post-hoc analysis. Based on these findings, Affimed will include the 720 mg dose moving forward to optimize clinical benefit and reduce early progression risk.

"These data provide compelling evidence that higher exposure may translate to better outcomes in patients with advanced NSCLC," Dr. Harstrick added. "With dose optimization in hand, we are positioned to advance AFM24 in its potential to deliver durable benefit in a difficult-to-treat patient population."

Conclusions

The data show a strong correlation between exposure and clinical outcome with a significantly increased risk for early tumor progression in the low exposure group. PK modeling suggests that a dose of 720 mg AFM24 weekly will result in exposure levels exceeding the cutoff for the high exposure group as early as week two. The 720 mg dose, which has already been established as safe in the phase 1 trial, will be used in future AFM24 studies.

More details about the programs for the AACR (Free AACR Whitepaper) Annual Meeting 2025 are available online at AACR (Free AACR Whitepaper) Annual Meeting 2025 | Meetings | AACR (Free AACR Whitepaper).

About AFM24
AFM24 is a tetravalent, bispecific ICE that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.