On April 28, 2025 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotechnology company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to enhancing survival for patients with cancer through immune modulation, reported new preclinical data for MaaT034, the Company’s next generation product, showing compelling anti-tumor efficacy results in germ-free mice at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, Illinois, taking place from April 25 to 30, 2025 (Press release, MaaT Pharma, APR 28, 2025, View Source [SID1234652236]).

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MaaT Pharma has built a versatile platform combining two complementary approaches. The first one leverages a GMP-compliant approach to produce standardized donor-derived therapies (MaaT013, MaaT033) using pooled donations, proven to restore a rich and diverse gut microbiome for patients with severe dysbiosis and currently in late-stage of clinical evaluation (Phases 2 and 3). In parallel, the Company is advancing a next-generation, AI-driven co-culture technology to develop a donor-independent synthetic microbiome ecosystem at large industrial scale targeting indication-specific diseases. MaaT034, the first-in-class co-cultured product, aims to optimize intestinal microbiome functions and to improve patient responses to immunotherapy in combination with Immune Checkpoint Inhibitors.

Below are the key results presented at AACR (Free AACR Whitepaper) for MaaT034:

Metagenomic analysis shows that MaaT034 reproduces the microbial functions of MaaT013 – the Company’s lead asset, currently evaluated in the randomized Phase 2 PICASSO trial in combination with immune checkpoint inhibitors (ICI), ipilimumab (Yervoy) and nivolumab (Opdivo) for unresectable or metastatic melanoma.
MaaT034 improves DC-mediated T cell activation and potentiates anti-tumor effects mediated by anti-PD-1 checkpoint blockade in vitro.
70% of MaaT034 microbial species engraft in mice, ensuring an enduring presence of beneficial bacteria in the gut environment.
MaaT034 increases the production of key microbial-derived metabolites such as short-chain fatty acids in germ-free mice. This translates into an improved gastrointestinal physiology as evidenced by gut mucosal restoration.
MaaT034 optimizes anti-PD1 mediated activity in tumor-bearing, germ-free mice. While anti-PD1 alone reduced tumor growth by 10%, the combination of anti-PD1 and MaaT034 resulted in a 83.7% tumor growth reduction (compared to a 24.2% reduction when using a single strain of Akkermansia muciniphila bacteria). These results demonstrate that improved tumor control is achieved with anti-PD1 in combination with MaaT034, as compared to PD-1 alone or in combination with a reference single bacterial strain.
"These positive data in tumor-bearing mice demonstrate the significant potential of MaaT034 as a microbiome ecosystem therapy candidate and provide a robust basis for the progression of this therapy into clinical development for solid tumors. We look forward to further evaluating the potential benefits of MaaT034 in the next phases of our research," said Gianfranco Pittari, MD PhD, Chief Medical Officer, MaaT Pharma.

Upcoming conferences participation

May 5-6, 2025 – Swiss Biotech Day, Basel
May 13, 2025 – Forum Midcaps Gilbert Dupont, Paris
June 12-15 – European Hematology Association (EHA) (Free EHA Whitepaper) Congress, Milan, IT
June 16-19, 2025 – Bio International Convention, Boston, MA – Company Presentation
June 18-19, 2025 – Portzamparc Conference Mid & Small Caps 2025, Paris
September 25, 2025 – KBC Healthcare Conference, Brussels
About MaaT034

MaaT034, currently in preclinical development, is a next-generation donor-independent full ecosystem synthetic microbiome therapy, dedicated to improving patient responses to immunotherapy in combination with Immune Checkpoint Inhibitors. Developed using the Company’s co-culturing proprietary MET-C platform, MaaT034 is optimized for large-scale production in oncology. Previous presented preclinical data showed that MaaT034 produced key metabolites, recognized as promoting gut barrier restoration and modulating immune responses, such as Short-Chain Fatty Acids (SCFA), secondary bile acids, and tryptophan derivatives. These data support the role of MaaT034 in gut barrier repair and in T cell reactivation either in combination with anti-PD1 or with anti-PD-L1. By enhancing gut barrier repair and modulating immune responses, MaaT034 is expected to complement the action of these immunotherapeutic agents, potentially improving their efficacy in treating solid tumors cancer.

On April 28, 2025 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that the first patients have been dosed in KOMET-015, a Phase 1 clinical trial of ziftomenib, the Company’s potent and selective, oral investigational menin inhibitor, in patients with advanced gastrointestinal stromal tumors (GIST) after imatinib failure (Press release, Kura Oncology, APR 28, 2025, View Source [SID1234652234]).

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"Building on compelling clinical activity of ziftomenib in patients with NPM1-mutant and KMT2A-rearranged AML, we are committed to evaluating the full therapeutic potential of menin inhibitors for the treatment of cancer," said Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology. "Approximately 4,000 to 6,000 new cases of GIST are diagnosed each year in the U.S., and advanced GIST patients have limited treatment options. Our preclinical data demonstrate the combination of ziftomenib and imatinib provides robust and durable antitumor activity in both imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST patient-derived xenograft models, and we look forward to seeing whether the combination offers potential to transform the treatment paradigm."

In preclinical studies, the data demonstrates the combination exerts antitumor activity via a synthetic lethal mechanism through which ziftomenib epigenetically targets a vulnerability of GIST tumors actively induced by even ineffective tyrosine kinase inhibitor (TKI) treatments. Sixty percent of patients develop resistance to imatinib, the frontline standard of care for GIST, within two years, and ziftomenib has the potential to delay the onset of or overcome that resistance in these patients.

"This study is an important step in developing new combination treatments to potentially improve outcomes for patients with advanced gastrointestinal stromal tumors, a disease indication for which new therapeutic options are needed," said Mrinal Gounder, M.D., Sarcoma Oncologist & Early Phase Drug Development Specialist at Memorial Sloan Kettering Cancer Center. "KOMET-015 builds upon the promising preclinical data observed with ziftomenib in combination with imatinib in GIST models and we look forward to evaluating the investigational drug candidate and its potential to transform the treatment landscape."

"Until now, most approaches to treating gastrointestinal stromal tumors rely on targeted KIT inhibition via tyrosine kinase inhibitors such as imatinib, however most patients eventually progress due to acquired secondary KIT mutations highlighting the need for new treatment options," said Shreyaskumar Patel, M.D., Center Medical Director, Sarcoma Center, at The University of Texas MD Anderson Cancer Center. "We are highly encouraged by the substantial preclinical data generated to date supporting the combination for ziftomenib in combination with KIT inhibitors in advanced GIST, and the dosing of the first patients marks an important milestone to address the meaningful unmet need for these patients."

The KOMET-015 Phase 1a/1b, open-label, dose-escalation trial is designed to evaluate the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib in adults with GIST who have documented disease progression while currently on or previously treated with imatinib. Upon completion of the dose-escalation portion of the trial, expansion cohorts are planned to further assess the safety, tolerability, and clinical activity of ziftomenib. The primary objectives include evaluation of safety and tolerability and determination of the recommended Phase 2 dose, and key secondary endpoints include clinical benefit, overall response rate (ORR), progression free survival (PFS), duration of response, and overall survival (OS).

Currently, there are no other clinical trials evaluating the combination of a menin inhibitor with standards of care for the treatment of GIST. For more information regarding the KOMET-015 trial, please visit www.clinicaltrials.gov (identifier: NCT06655246).

About GIST

Gastrointestinal stromal tumors (GIST) are the most common form of sarcoma, and are characterized as KIT-dependent solid tumors, with an estimated 4,000 to 6,000 new cases diagnosed in the U.S. each year. Despite the successful disease control achieved with imatinib in advanced GIST patients, most patients eventually progress due to acquired secondary KIT mutations. TKIs such as sunitinib target imatinib-resistant genotypes and are approved in later lines, but response rates and long-term outcomes are modest, so new therapeutic options are needed.

About Ziftomenib

Ziftomenib is a once daily, oral investigational menin inhibitor currently in development for the treatment of genetically defined AML and GIST patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) from the FDA for the treatment of relapsed/refractory (R/R) NPM1-mutant (NPM1-m) AML based on data from Kura’s KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at www.kuraoncology.com/clinical-trials/#ziftomenib.

On April 28, 2025 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta (γδ) T cell therapies for cancer and autoimmune diseases, reported new preclinical data from its innovative γδ T cell engager (γδ-TCE) platform. The data will be presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 30, 2025 (Press release, In8bio, APR 28, 2025, View Source [SID1234652233]). The data showed that IN8bio’s new γδ-TCE platform demonstrated potent and consistent cancer-killing activity across targets in leukemia models, while avoiding the secretion of cytokines that drive the dangerous side effects seen with other TCE based immune therapies.

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Unlike traditional TCEs that rely on CD3 to activate all T cells in the body – often triggering excessive inflammatory responses, potential T cell exhaustion and other serious side effects – IN8bio’s next-gen platform is designed to specifically activate only γδ T cells, a small but powerful subset of immune cells. These cells can naturally detect, phagocytose (eat) and kill tumors cells without needing to be "trained" to recognize specific targets. The platform’s lead molecules, INB-619 (targeting CD19) and INB-633 (targeting CD33), were able to eliminate cancer cells in preclinical studies with minimal release of inflammatory cytokines. This potentially offers a lower risk of cytokine release syndrome (CRS) or the neurotoxicity that can impact 60-75% of patients treated with conventional CD3 TCEs.

William Ho, CEO and co-founder of IN8bio, commented, "Our INB-600 TCE platform combines the natural tumor-fighting abilities of γδ T cells with bispecific engagers to generate a more precise and powerful way to mobilize the immune system against cancer cells. These early results in leukemia models are exciting, and we believe this technology can eventually be applied to other hard-to-treat cancers, and even certain autoimmune diseases."

Key highlights from the in vitro studies:

INB-619 and INB-633 both triggered strong and specific, linear dose-related killing of leukemia cells (ALL and AML) at low picomolar concentrations.
Both molecules activated and expanded two key γδ T cell subsets (Vδ1+ and Vδ2+), which is critical since most cancer patients have reduced numbers of these cells.
Both molecules promoted activation and degranulation, with dose-related increases in the expression of cellular markers indicating a transition to a powerful cancer-cell killing phenotype.
Importantly, they did so with minimal, if any, changes in dangerous cytokines, such as IL-6, IL-10, and IL-17a – markers that are often linked to cytokine release syndrome (CRS) and other treatment-related toxicities.
Because this new off-the-shelf platform can drive γδ T cell expansion without the need for genetic engineering, it has the potential to offer a more scalable and flexible approach to building next-generation immunotherapies.

IN8bio continues to expand its γδ T cell therapeutic pipeline beyond genetically engineered and drug-resistant cellular therapies and is exploring various disease indications and any opportunities for partnership with the INB-600 platform. This preclinical data reinforces the company’s differentiated strategy to build modular and scalable therapeutic approaches to leverage the power of γδ T cells to target malignancies with increased precision and reduced toxicity.

The AACR (Free AACR Whitepaper) 2025 poster is available on the investor section of the company’s website at View Source

On April 28, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported it has signed an exclusive patent license agreement with NYU Langone Health related to the drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid) (Press release, Genprex, APR 28, 2025, View Source [SID1234652232]). The therapy is under investigation as a potential treatment for mesothelioma. The subject patent is co-owned by Genprex and NYU Langone Health, and the license provides Genprex with patent exclusivity.

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"We are pleased to expand our robust oncology franchise, intellectual property portfolio and research program for REQORSA to continue exploring how it may serve as a therapeutic treatment for some of the most difficult to treat cancers and diseases," said Thomas Gallagher, Senior Vice President of Intellectual Property and Licensing. "We believe REQORSA has the potential to treat mesothelioma, and this license agreement positions Genprex to expand its clinical development pipeline with future clinical studies that are within the scope of the licensed patent."

Expression of TUSC2 is downregulated in 84% of mesotheliomas. TUSC2 is the tumor suppressor gene used in REQORSA. Research collaborators at NYU presented positive preclinical data from a study of REQORSA for the treatment of mesothelioma at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics.

In this study, four Malignant Pleural Mesothelioma (MPM) cell lines and tert-transformed mesothelial LP9 cells were treated with REQORSA and control liposomes for 48h. Treated cells were then evaluated for TUSC2 expression by semi quantitative RT-PCR, Western blot analysis, and functional assays including cell proliferation, invasion, and apoptosis.

The researchers demonstrated that REQORSA treatment resulted in a significant decrease in cell proliferation, cell invasion, and a significant increase in cell apoptosis in all four MPM cell lines. Data also demonstrated potent tumor suppressive activity of the TUSC2 gene delivered by REQORSA, and thus, its re-expression could serve as a potential therapeutic strategy for the treatment of MPM.

In 2024, Genprex announced the formation of its Mesothelioma Clinical Advisory Board to support the Company’s preclinical mesothelioma oncology program. The Board is comprised of four world-renown researchers from major research institutions specializing in the treatment of mesothelioma.

According to the Centers for Disease Control and Prevention, mesothelioma is a cancer that forms in the thin tissue that lines many internal organs, called the mesothelium. The most common kind of mesothelioma forms in the tissue around the lungs, called the pleura. This is called pleural mesothelioma, which accounts for 80-90% of all mesothelioma diagnoses. Approximately 3,000 new cases of mesothelioma are diagnosed each year in the U.S., and there are approximately 2,500 mesothelioma-related deaths each year in the U.S. The life expectancy for pleural mesothelioma is 18 months, and the 3-year survival rate with treatment for pleural mesothelioma is 23%.

About Reqorsa Gene Therapy

REQORSA (quaratusugene ozeplasmid) consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.

On April 28, 2025 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported new data underscoring the ability of cancer vaccine EVX-01 to drive a targeted and robust immune response (Press release, Evaxion Biotech, APR 28, 2025, View Source [SID1234652230]). Designed with Evaxion’s AI-Immunology platform, EVX-01 is a personalized cancer vaccine currently being evaluated as a treatment for advanced melanoma (skin cancer).

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New immune data from the ongoing phase 2 trial with EVX-01 will be presented at a poster session tomorrow at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in Chicago. The data demonstrates that 80% of EVX-01 vaccine targets triggered a tumor-specific immune response.

In earlier interim analyses presented at the ASCO (Free ASCO Whitepaper) and ESMO (Free ESMO Whitepaper) 2024 meetings, a vaccine target hit rate of 71% and 79%, respectively, was demonstrated. Now, with more long-term patient samples analyzed, we’ve improved this hit rate to 80%, reinforcing the potential of EVX-01 as a new and effective treatment for a broad range of solid tumors.

"We are excited to report yet another positive set of data for our lead vaccine candidate EVX-01. Its ability to trigger an immune response is unprecedented compared to what has been reported by others. We are further encouraged by the data showing this response to be strong and long-lasting and increasing with additional booster immunizations. The data package for EVX-01 gets stronger and stronger and we are eagerly anticipating the two-year clinical readout," says Birgitte Rønø, CSO of Evaxion.

The trial previously yielded strong interim one-year clinical data and remains on track for readout of two-year clinical data in the second half of 2025. Additionally, the trial has been extended with a third year, allowing for a more comprehensive assessment of the full potential of EVX-01.

The phase 2 trial investigates EVX-01 in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with advanced melanoma (skin cancer). Each patient enrolled in the trial has received a unique vaccine designed and manufactured based on their individual biology. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

AACR presentation details:

Abstract title: T-cell immunogenicity and biomarker profiling in advanced melanoma patients receiving the personalized vaccine EVX-01 in combination with pembrolizumab
Abstract#: 4538
Poster#: 9
Session (category): Immune responses to therapies including chemotherapy and radiotherapy (Clinical research)
Location: Poster section 28
Date/Time: April 29, 2025, at 9am-12pm CST/16-19 CET
Presenter: Mads Lausen Nielsen, PhD, Project Manager at Evaxion

About EVX-01
EVX-01 is a personalized peptide-based cancer vaccine intended for first-line treatment of multiple advanced solid cancers. It is Evaxion’s lead clinical asset.

EVX-01 is designed with our AI-Immunology platform and is tailored to target the unique tumor profile and immune characteristics of each patient. It engages the patient’s immune system to fight off cancer by mounting a targeted response against tumors.

In clinical trials, EVX-01 has demonstrated 69% and 67% Overall Response Rates in patients with advanced melanoma. Further, significant correlations between clinical responses and AI-Immunology predictions have been observed, underlining the predictive power of the platform.