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.

On April 28, 2025 Edgewood Oncology, a clinical-stage biotechnology company focused on delivering BTX-A51 to patients with hematologic malignancies and genetically-defined solid tumors, reported the presentation of new preclinical data presented by Dana-Farber Cancer Institute and Hebrew University-Hadassah Medical School in support of an ongoing investigator-sponsored Phase 1 study of BTX-A51 in liposarcoma (LPS) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30, 2025, in Chicago (Press release, Edgewood Oncology, APR 28, 2025, View Source [SID1234652229]).

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BTX-A51 is a first-in-class, small molecule kinase inhibitor that co-targets casein kinase 1 alpha (CK1a) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9), three master regulators of cancer cell survival and transcriptional control.

The presentation, "Therapeutic potential of combined targeting of casein kinase 1 alpha (CK1a) and CDK7/9 with the inhibitor BTX-A51 in human liposarcomas," highlights new mechanistic and efficacy data in patient-derived cell lines and xenograft models. One of the most significant findings from the presentation is that CK1a is an essential gene for the growth of liposarcomas based on genome-scale RNAi perturbation analysis. The study also used RNAi knockdown and targeted small molecules to confirm that inhibition of CK1a, CDK7, and CDK9 has synergistic impacts on LPS cell survival. As a single agent, BTX-A51 blocked MDM2 and induced P53 expression, stimulating potent apoptosis in LPS models while significantly inhibiting tumor growth in patient-derived xenografts at well tolerated dose levels.

"Well-differentiated and dedifferentiated liposarcomas (WD/DDLPS) remain among the most challenging soft tissue sarcomas to treat," said Geoffrey I. Shapiro, M.D., Ph.D., Professor of Medicine, Harvard Medical School, and director of the Early Drug Development Center at Dana-Farber Cancer Institute. "This study identifies novel, targetable vulnerabilities in LPS and offers a compelling justification for the clinical evaluation of BTX-A51 in this patient population."

BTX-A51 is currently being evaluated in an open-label, investigator-sponsored Phase 1 pilot study at Dana-Farber Cancer Institute in patients with metastatic and/or recurrent liposarcomas characterized by Murine Double Minute Clone 2 (MDM2) amplifications. Additional details about the study can be found at clinicaltrials.gov under the identifier NCT06414434.

"These findings strengthen the rationale for BTX-A51’s mechanism of action and support its potential across a spectrum of genetically defined cancers," said David N. Cook, Ph.D., Chief Executive Officer of Edgewood Oncology. "We’re encouraged by the strength of these preclinical findings, which further support the ongoing clinical advancement of BTX-A51."

Additional Details about the Study
Through computational and experimental methods, including DepMap screening, siRNA silencing, and small-molecule inhibitor profiling, the study confirmed that CK1α, CDK7, and CDK9 are essential for LPS survival. CK1a knockdown by itself was shown to be toxic to LPS cell lines and CDK9 inhibition alone suppressed LPS cell growth and induced apoptosis by downregulating MDM2 and activating p53. When CK1α depletion and CDK9 inhibition were combined, the potency of the individual approaches was amplified. In addition, combining CDK7 and CDK9 inhibitors synergistically inhibited LPS cell lines. These observations led to the evaluation of BTX-A51, which inhibits all three kinases with nanomolar potency. BTX-A51 robustly reduced MDM2 expression and induced expression of p53 and PUMA. The compound also lowered MCL1 expression and sensitized cells to apoptotic signaling through BIM and PUMA, as confirmed by BH3 profiling. In vivo studies in two LPS PDX models demonstrated that BTX-A51 is well tolerated and inhibits tumor growth under clinically relevant dosing conditions.

On April 28, 2025 Delcath Systems, Inc. (NASDAQ: DCTH), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported that the U.S. Food and Drug Administration (FDA) has completed its 30-day review of the Company’s Investigational New Drug (IND) application for a Phase 2 clinical trial evaluating HEPZATO in combination with standard of care (SOC) for liver-dominant metastatic breast cancer (mBC) (Press release, Delcath Systems, APR 28, 2025, View Source [SID1234652228]). With the FDA’s review complete, Delcath is now cleared to initiate patient enrollment in the U.S.

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The Phase 2 trial will evaluate the safety and efficacy of HEPZATO in combination with SOC versus SOC alone in patients with liver-dominant HER2-negative mBC following the failure of previous treatments. The SOC options will be the physician’s choice of eribulin, vinorelbine or capecitabine. Approximately 90 patients will be enrolled in this randomized, controlled trial. The study will take place at more than 20 sites across the United States and Europe, with patient enrollment expected to begin in the fourth quarter of 2025. The trial’s primary endpoint, hepatic progression-free survival, is anticipated to be announced by the end of 2028, while results for overall survival, a secondary endpoint, are expected in 2029.

Company management estimates that approximately 7,000 patients annually in the United States are affected by HER2-negative metastatic breast cancer with liver metastases and are candidates for third line treatment. This population includes patients with a significant burden of liver metastases, which are likely to be the primary cause of mortality. By focusing on this demographic, Delcath intends to offer a novel therapeutic option to those patients with limited treatment alternatives.

"This randomized Phase 2 trial marks an important milestone as we expand the clinical investigation of HEPZATO into patients with liver-dominant metastatic breast cancer," said Gerard Michel, Chief Executive Officer of Delcath Systems, Inc. "We are excited to bring new hope to patient populations in indications beyond metastatic uveal melanoma and to further demonstrate the potential of HEPZATO to address unmet needs in oncology. This study underscores our commitment to broadening the applications of HEPZATO and the underlying hepatic delivery system, positioning us as a platform technology that can offer directed treatment options for a variety of liver-dominant cancers."