On April 29, 2025 Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, reported data in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting, held April 25-30, 2025, in Chicago, IL (Press release, TONIX Pharmaceuticals, APR 29, 2025, View Source [SID1234652325]). A copy of the Company’s presentation is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. The presentation titled, "TFF2-mediated CXCR4 partial agonism outperforms CXCR4 antagonism in reducing murine gastric cancer by suppressing PMN-MDSC generation," demonstrated positive data in gastric cancer animal models. In the AACR (Free AACR Whitepaper) presentation, a fusion protein of murine trefoil factor family member 2- murine serum albumin (mTFF2-MSA) was studied. Tonix is developing human TFF2-human serum albumin (hTFF2-HAS) as TNX-1700.

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"The combination therapy of mTFF2-MSA with anti-PD1 treatment shows promise in reducing immunosuppression in the tumor microenvironment (TME) in animal models," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "We are excited to develop TNX-1700 (TFF2-HAS) as the lead program in our immuno-oncology pipeline, by testing potential dosing strategies, and establishing potential clinical biomarkers through preclinical models."

Immunosuppressive neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a major component in solid tumors that significantly hinder anti-tumor activity1,2. Despite being short-lived, their continuous replenishment from the bone marrow sustains their potent immunosuppression in the TME3. Stromal cells in the TME promote immunosuppression by recruiting MDSCs via secretion of CXCL12. Trefoil Factor 2 (TFF2), a secreted peptide of the trefoil factor family, has displayed activity as a partial agonist of CXCR44,5. Data presented in the poster demonstrated that TFF2-MSA selectively reduces immunosuppressive neutrophils and cancer-driven granulopoiesis. Treatment with TFF2-MSA, in combination with an anti-PD1 antibody, induced robust anti-tumoral CD8+ T cell responses, inhibiting tumor invasion. TFF2 reduction correlated with elevated PMN-MDSCs in gastric cancer patients, highlighting the potential negative correlation between TFF2 and PMN-MDSCs levels.

About Trefoil Factor Family Member 2 (TFF2)

Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 (rTFF2-HSA) for the treatment of gastric and colon cancers under a license from Columbia University. The inventor of the core technology at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8+ T cells. He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-life in vivo and was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth. Dr. Wang proposed the concept of employing rTFF2 in combination with other therapies in cancer prevention and early treatment.

On April 29, 2025 Ensoma, a genomic medicines company advancing the future of medicine through one-time, in vivo therapies designed to precisely and durably engineer the hematopoietic system to treat chronic diseases, reported it will present preclinical data and manufacturing advancements at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 28th Annual Meeting, hosted May 13-17 in New Orleans (Press release, Ensoma, APR 29, 2025, View Source [SID1234652342]).

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The company’s poster presentations will highlight key programs that leverage its in vivo HSC engineering platform. Ensoma combines a unique delivery system with an advanced gene engineering toolkit, offering the potential for durable, transformative therapies to address chronic diseases, improve patient access and significantly reduce treatment burden. The platform uses virus-like particles (VLPs) that preferentially bind to HSCs, efficiently deliver DNA to the nucleus and de-target the liver. With a 35-kilobase cargo capacity, these VLPs carry a diverse range of genomic engineering constructs, including control elements that enable specific cargo expression in targeted cells, from single base edits to large multi-gene insertions.

"We look forward to presenting preclinical data at ASGCT (Free ASGCT Whitepaper) that underscore the potential of our in vivo HSC engineering platform to address complex genetic disorders and cancer," said Robert Peters, Ph.D., chief scientific officer of Ensoma. "Exciting new findings from our non-human primate studies reinforce the precision and effectiveness of our VLPs, showcasing their ability to safely deliver genetic therapies with targeted biodistribution and expression. With this strong progress, Ensoma remains on track to initiate our first clinical trial in the second half of 2025—marking a major step toward bringing this groundbreaking therapy to patients."

"Building on this momentum, our novel adenovirus production process is a significant milestone for Ensoma, ensuring the scalable and high-quality production of VLPs needed for clinical trials," said Dan Leblanc, chief technology officer of Ensoma. "This robust suspension manufacturing process is delivering consistent product yield and quality to support the clinical use of EN-374 for the treatment of X-CGD. It’s incredibly rewarding to see our platform move closer to delivering potentially transformative therapies to patients."

Poster Presentations at ASGCT (Free ASGCT Whitepaper) 28th Annual Meeting:

Title: In Vivo Engineering of Hematopoietic Stem Cells with Virus-like Particles to Generate Multi-Lineage CAR Immune Cell Therapy for Cancer (1783)
Poster Presentation Time/Date: 5:30-7:30 p.m. CT, Thursday, May 15
Location: Poster Hall I2
Presenter: Chirayu Chokshi, Ph.D., Ensoma

Data Summary: Ensoma will present updated data from its preclinical HER2 CAR program. An HSC-targeted VLP encoding lineage-specific regulatory elements to direct CAR expression resulted in robust generation of HSC-derived CAR-M, NK and T cells in vivo. This lineage-restricted, multi-cellular CAR therapy mediated tumor control and microenvironment remodeling, supporting Ensoma’s technology as a highly differentiated approach to addressing solid tumors.

Title: Novel In Vivo Gene Therapy Approach to Hematopoietic Stem Cell (HSC) Engineering Creates Durable HSC-Derived Neutrophils to Treat X-Linked Chronic Granulomatous Disease (1780)
Poster Presentation Time/Date: 5:30-7:30 p.m. CT, Thursday, May 15

Location: Poster Hall I2

Presenter: Sravya Kattula, Ph.D., Ensoma

Data Summary: Ensoma will present updated preclinical data from its X-CGD program with EN-374, which highlights the use of its VLP platform to efficiently modify HSCs in vivo and restore neutrophil function. In this preclinical study in a CGD mouse model, EN-374 provided durable gene correction in neutrophils to restore CYBB protein expression and activity. This study sets the foundation for Ensoma’s in vivo HSC gene therapy to reach the clinic and be applied to a range of genetic disorders that thus far have only been addressed with ex vivo gene therapies.

Title: Acute Safety and Biodistribution Profile of Hematopoietic Stem Cell (HSC) Targeting Virus-like Particles Based on Helper-dependent Adenovirus Serotype 5/35++ in Non-human Primates (1779)
Poster Presentation Time/Date: 5:30-7:30 p.m. CT, Thursday, May 15
Location: Poster Hall I2
Presenter: Patrick Au, Ph.D., Ensoma

Data Summary: Ensoma will present data from a non-human primate study evaluating the safety, biodistribution and transgene expression profiles of its HSC-targeting VLPs. Results showed favorable tolerability without any clinical signs of toxicity and a well-characterized biodistribution, supporting the continued development of Ensoma’s VLP-based platform as a safe and effective solution for in vivo HSC engineering.

Title: Development and Scale-up of a Novel Adenovirus Production Process (2016)
Poster Presentation Time/Date: 6:00-7:30 p.m. CT, Tuesday, May 13
Location: Poster Hall I2
Presenter: Chapman Wright, Ph.D., Ensoma

Data Summary: Ensoma will present the establishment of a novel, serum-free suspension manufacturing process for large-scale, high-efficiency VLP manufacturing. The presentation will address adaptation of an adherent cell line to a serum-free suspension cell culture, followed by a design-of-experiment strategy for efficient development of a clinical-scale production process.

On April 29, 2025 CytoDyn Inc. (OTCQB: CYDY) ("CytoDyn" or the "Company"), a biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, reported that the Company will be presenting a poster at the upcoming European Society for Medical Oncology’s ("ESMO") Breast Cancer meeting, following its promising survival observations among patients with metastatic triple-negative breast cancer ("mTNBC") treated with leronlimab (Press release, CytoDyn, APR 29, 2025, View Source [SID1234652305]). The conference will take place on May 14-17, 2025, in Munich, Germany, and CytoDyn’s presentation is scheduled for May 15, 2025.

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As announced in February 2025, a review of patients treated with leronlimab during CytoDyn’s prior clinical trials in oncology revealed observed survival rates at 12, 24, and 36 months that compare favorably to expected outcomes with currently approved therapies. The Company has also now confirmed survival outcomes in a group of patients with mTNBC and four prior lines of treatment who are alive more than 48 months after receiving leronlimab. This includes four patients who currently identify as having no evidence of ongoing disease and a fifth patient who is alive with stable disease. CytoDyn has already initiated a follow-up protocol to continue to monitor these surviving patients into the future.

"We look forward to sharing details on the progress we have made advancing our clinical development pipeline for leronlimab in oncology," said Dr. Lalezari. "We are also excited to share information about the apparent mechanism of action in long-term surviving patients that we see as a potentially paradigm-shifting development in solid tumor oncology."

Dr. Lalezari will be joined at the conference by Dr. Richard Pestell, MD, PhD, AO, Lead Consultant in Preclinical and Clinical Oncology, who will present during the poster display session in Hall B0 on Thursday, May 15 from 12:00-12:45PM CEST. Several other CytoDyn key opinion leaders will also be attending the conference.

On April 29, 2025 VerImmune, Inc. ("VerImmune"), a biotechnology company developing innovative Virus-inspired Particle (ViP) modalities, reported it has been awarded a ~$470,000 USD research grant (MRP Idea Award) from the U.S. Department of Defense (DoD) Melanoma Research Program (MRP), managed by the office of Congressionally Directed Medical Research Programs (CDMRP) (Press release, VerImmune, APR 29, 2025, View Source [SID1234652326]).

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The award will support the development of novel candidates based on VerImmune’s ViP technology for the treatment of advanced or rare melanoma cancers.

The MRP received 136 compliant applications and recommended funding for only nine, placing VerImmune’s application in the top 6.6% of submissions.

"Receiving this award from such a highly competitive pool clearly demonstrates the innovation and groundbreaking work we are doing at VerImmune to develop therapies for patients with unmet medical needs," said Joshua Wang, Founder and CEO of VerImmune, Inc. "We are committed to advancing our ViP platform to address critical healthcare challenges and look forward to utilizing this funding to drive our efforts in melanoma and other cancers."

On April 29, 2025 Cellworks Group Inc., a leader in Personalized Therapy Decision Support and Best-in-Class PTRS, reported compelling results from a new study demonstrating the ability of the Cellworks Platform to identify patients with high microsatellite instability (MSI-H) who may not respond to immune checkpoint inhibitors (ICIs), despite MSI-H status (Press release, Cellworks, APR 29, 2025, View Source [SID1234652343]). Results from the study were showcased in a poster presentation titled, Use of Biosimulation to Predict Immune Checkpoint Inhibitor Resistance in Patients with High Microsatellite Instability as part of the AACR (Free AACR Whitepaper) Annual Meeting 2025 taking place April 25-30, 2025 at the McCormick Place Convention Center in Chicago.

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While immune checkpoint inhibitors (ICIs) such as pembrolizumab are considered a standard-of-care for MSI-H cancers, MSI-H status alone is not a definitive predictor of treatment success. In this study, Cellworks applied its unique mechanistic Computational Biology Model (CBM) to biosimulate patient-specific responses to ICIs. The computational biosimulation process in the study uncovered molecular signatures of resistance in MSI-H patients who were predicted to have poor response to ICIs, providing a deeper understanding of why some MSI-H patients fail to benefit from immunotherapy.

Key Findings

Efficacy Scores Significantly Higher in MSI-H Patients. MSI-H patients demonstrated significantly higher pembrolizumab efficacy scores compared to microsatellite stable (MSS) patients in both STAD (average ES: 20.5 vs. 3.2, p < 0.001) and CRC (average ES: 13.4 vs. 2.4, p < 0.001).
Large Subset of MSI-H Patients Predicted to Have Low ICI Response. Despite being MSI-H, 59% of STAD and 81% of CRC patients were identified as low pembrolizumab responders.
Molecular Drivers of Resistance Identified. In MSI-H patients classified as low pembrolizumab responders, higher rates of NOTCH2, EGFR, and EZH2 amplifications, along with TP53 loss-of-function mutations, were identified. In MSI-H/ES-L CRC patients, MYC amplification was significantly enriched (p < 0.05).
"These findings highlight the power of using patient-specific drug response methods to move beyond MSI-H status and identify critical molecular drivers of immune checkpoint inhibitor resistance," said Dr. James Wingrove, Chief Development Officer at Cellworks and presenting author of the study. "By identifying patients unlikely to respond to ICIs, we can help oncologists personalize treatment strategies and improve outcomes for MSI-H patients who may otherwise receive ineffective therapies."

"This study demonstrates the importance of looking beyond MSI status to understand immune checkpoint inhibitor resistance at a molecular level," said Dr. Michael Castro, Chief Medical Officer at Cellworks. "Our biosimulation revealed that MSI-H patients with low predicted response to pembrolizumab frequently harbored alterations such as NOTCH2, EGFR, and EZH2 amplifications, as well as TP53 loss-of-function mutations in STAD, and MYC amplifications in CRC. Identifying these resistance-associated biomarkers can help guide clinicians in selecting more effective, personalized treatment strategies for MSI-H patients who may not benefit from ICIs alone."

Study Design

Cellworks developed a mechanistic Computational Biology Model (CBM) that can be personalized based on a patient’s tumor-based genomic profile, revealing signaling pathway dysregulation and patient-specific drug response. Output from the model was used to identify MSI-H patients who may have a poorer response to ICIs. Computational biosimulation was performed using real-world retrospective cohorts of 423 STAD patients and 534 CRC patients (TCGA). MSI measurements were provided by TCGA. Efficacy scores based on biosimulated composite cell growth in response to disease and therapy were generated on all patients for pembrolizumab. Molecular rationales for ICI resistance were identified for MSI-H patients with low pembrolizumab efficacy scores.

The Cellworks Platform

The Cellworks Platform performs computational biosimulation of protein-protein interactions, enabling in silico modeling of tumor behavior using comprehensive genomic data. This allows for the evaluation of how personalized treatment strategies interact with the patient’s unique tumor network. Multi-omic data from an individual patient or cohort is used as input to the in silico Cellworks Computational Biology Model (CBM) to generate a personalized or cohort-specific disease model.

The CBM is a highly curated mechanistic network of 6,000+ human genes, 30,000 molecular species and 600,000 molecular interactions. This model along with associated drug models are used to biosimulate the impact of specific compounds or combinations of drugs on the patient or cohort and produce therapy response predictions, which are statistically modeled to produce a qualitative therapy response score for a specific therapy. The Cellworks CBM has been tested and applied against various clinical datasets with results provided in over 125 presentations and publications with global collaborators.