On April 30, 2025 Domain Therapeutics ("Domain" or "the Company"), the GPCR experts harnessing deep receptor biology to develop breakthrough treatments for patients, reported new clinical and preclinical data for its key oncology programs DT-9081 and DT-7012, and preclinical insights on its PAR2 biased NAM program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago, USA (Press release, Domain Therapeutics, APR 30, 2025, View Source [SID1234652379]).

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The presentations underscore Domain’s commitment to redefining cancer therapy and the potential of GPCRs to modulate the tumor microenvironment (TME) and enhance anti-tumor immunity. Details on the poster presentations are highlighted below:

Poster presentation #7450 titled "Clinical PK, PD and safety analysis of a phase I clinical trial of DT-9081, an EP4R-antagonist, for RP2D determination in patients with advanced solid tumors", details Phase I clinical trial results for DT-9081, a novel EP4 receptor antagonist. The findings outline DT-9081’s promising potential to inhibit tumor growth and enhance immune response in patients with advanced solid tumors. Administered orally once daily, DT-9081 has demonstrated:

Sustained EP4R target engagement as shown by cytokine release measurements and dose-proportional pharmacokinetics (PK) exposure with the best target coverage profile reported at the dose of 600 mg
An acceptable safety profile with no dose-limiting toxicities (DLT) observed at the highest doses (400 mg and 600 mg). In addition, one-third of patients achieved stable disease after two cycles of treatment
The comprehensive evaluation of safety, tolerability, and PK/pharmacodynamics (PD) profile of DT-9081 allowed to select 600 mg as the RP2D for further clinical development in advanced solid tumors.

Poster presentation #7080 titled "Comprehensive Characterization of DT-7012, a Differentiated CCR8-Depleting Antibody for the Treatment of Solid Tumors", details preclinical and benchmark data highlighting the sophisticated profile of DT-7012, a Treg depleting anti-CCR8 monoclonal antibody. The study highlighted that DT-7012:

Demonstrates a broad pattern of CCR8 binding, high affinity to CCR8, and potent effector functions, enabling effective targeting and selective depletion of CCR8+ Tregs in patient samples
Exhibits high specificity for CCR8, avoiding depletion of circulating immune cells and presenting a favorable safety profile
Maintains functional efficacy, preserving antagonistic activities (ADCC/ADCP) even under high concentrations of the CCR8 ligand CCL1 and effectively blocking CCL1-induced receptor internalization
The highly differentiated and competitive properties of DT-7012 differentiate it from other clinical anti-CCR8 candidates, positioning it as a promising therapeutic solution to overcome immune evasion mechanisms and enhance anti-tumor immune responses in solid tumors. These preclinical findings support the advancement of DT-7012 into Phase I/II trials, anticipated to start in 2025.

Poster presentation #6157, titled "PAR2 inhibitors reduce resistance to immunotherapy against cancer", details the groundbreaking research in collaboration with Prof. John Stagg, demonstrating the promising potential of its PAR2 biased NAM in overcoming resistance to immune checkpoint blockade (ICB) and addressing T cell dysfunction in cancer. The preclinical findings revealed that PAR2 biased NAM:

Synergizes with anti-PD1 therapy, turning macrophage phenotype and cytokine profile toward a pro-inflammatory TME
Promotes antigen-presenting cells and T cells, facilitating robust antitumoral responses
This research provides critical insights into the mechanisms of PAR2 inhibition, positioning Domain’s PAR2 biased NAM program as a transformative therapeutic approach to overcome tumor resistance to ICB and restore effective immune control.

Stephan Schann, Chief Scientific Officer of Domain Therapeutics, said: "The exciting data presented at AACR (Free AACR Whitepaper) 2025 further validates our unique and differentiated drug discovery and development approach, built on our proprietary platform and deep expertise in GPCR biology. These findings underscore the transformative potential of our compounds to address significant unmet medical needs and illustrate our commitment to provide better treatments for patients, a goal that is profoundly important to us."

Prof. John Stagg, Principal Investigator at the Centre Hospitalier de l’Université de Montréal (CHUM), Canada and Member of Domain Therapeutics’ Scientific Advisory Board, commented: "This collaboration with Domain Therapeutics, a unique GPCR company, highlights the importance of tackling challenging targets like PAR2. The comprehensive research presented at AACR (Free AACR Whitepaper) 2025, which explores PAR2’s role in the tumor microenvironment, demonstrates its potential to combat resistance mechanisms and improve treatment efficacy, paving the way for new advancements in immuno-oncology."

On April 30, 2025 Genocury Biotech reported groundbreaking clinical data from its noval in vivo CD19 CAR-T therapy in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), a notoriously aggressive blood cancer (Press release, Shenzhen Genocury Biotech, APR 30, 2025, View Source [SID1234652399]). In an investigator-initiated trial (IIT) led by the Hematology Department at Tongji Hospital, a heavily pretreated relapsed/refractory (R/R) patient with advanced DLBCL achieved complete remission (CR) after 1 month of the in vivo CAR-T treatment, with durable response sustained over three months. Notably, the treatment eliminated the need for lymphodepletion, a standard yet toxic preconditioning step in traditional CAR-T protocols.

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Clinical Breakthrough: Redefining Safety, Efficacy, and Speed

Key trial findings:

1. Rapid and Deep Response:

A relapsed DLBCL male patient achieved complete hematological remission (CR) within 28 days following a single dose of Genocury’s CD19 in vivo CAR-T without lymphodepletion. Flow cytometric analysis revealed significant CAR-T cell expansion kinetics, with sustained therapeutic efficacy confirmed through 90-day follow-up monitoring.

2. Unprecedented Safety Profile:

Unlike conventional CAR-T, which carries a ~50% risk of cytokine release syndrome (CRS) and neurotoxicity, this novel therapeutic approach demonstrated complete absence of:

Cytokine release syndrome (CRS)
Immune effector cell-associated neurotoxicity syndrome (ICANS)
Lymphodepletion-related complications – typically associated with increased infection risk- further underscores the therapy’s safety profile.
Reimagining CAR-T: In Vivo Engineering Breakthroughs

Genocury’s in vivo CAR-T platform overcomes two critical roadblocks in current CAR-T therapy:

Eliminates Ex Vivo Manipulation: Traditional CAR-T requires 3-4 week vein-to-vein timeline by harvesting, modifying, and expanding a patient’s T cells outside the body, and $400K price tag stems from this time-consuming process. Genocury’s proprietary in vivo CAR-T vector delivers CAR payload directly into circulating T cells in vivo, enabling functional CAR-T generation.
Lymphodepletion-Free Protocol: Current protocols require the harsh preconditioning chemotherapy for immune reset – a leading cause of hospitalization. Genocury’s lymphodepletion-free approach reduces treatment-related complications and logistical burdens, as well as enabling significant CAR-T cell expansion.
Statement from Prof. Jia Wei , M.D., Ph.D.

PI (principal investigator), Tongji Hospital Hematology Department (Wuhan)
"In this groundbreaking case, we observed the patient treated with Genocury’s CD19 in vivo CAR-T achieved complete remission through 90-day follow-up – achieved without any lymphodepletion, which fundamentally challenges current cellular therapy dogma" said Dr. Jia Wei, "This therapy combines the benefits of autologous CAR-T with the accessibility of universal therapies, potentially ending the era of unaffordable cancer treatments. This could democratize access to CAR-T globally, we are very excited to advance this paradigm-shifting approach."

On April 30, 2025 Endevica Bio, a privately held company developing first-in-class peptide drug candidates, reported the dose administration for the first patient in a Phase 2 trial for its experimental drug TCMCB07 (B07) to prevent weight loss in cancer patients undergoing chemotherapy (Press release, Endevica Bio, APR 30, 2025, View Source [SID1234652383]).

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The trial, being conducted in partnership with WuXi Clinical, will include 20 sites and 100 patients who are diagnosed with stage 4 metastatic colorectal cancer.

In the trial, patients are dosed with B07 as they begin chemotherapy and during the first several rounds of chemotherapy. The primary endpoint is preventing weight loss, which can lead to a debilitating condition called cachexia, a life-threatening wasting syndrome associated with chronic diseases, including cancer.

"This marks an important milestone in our commitment in developing a potentially life changing treatment for cachexia," said Russell Potterfield, Chief Executive Officer and Executive Chair of Endevica. "Each trial brings us closer to offering a viable solution for this debilitating disease, and we remain dedicated to making a lasting impact on the lives of those affected."

"We are incredibly excited to have our first patient dosed with B07 in individuals diagnosed with metastatic colorectal cancer who are undergoing chemotherapy," said Dr. Daniel Marks, Chief Medical and Scientific Officer of Endevica Bio. "Since there is no FDA approved therapeutic for cancer cachexia, this trial is a crucial step to provide a therapy for an area of huge unmet clinical need, and we look forward to the results."

In 2024, Endevica Bio completed its Phase 1 clinical trial with preliminary findings supporting its strong safety and efficacy. Last November, the Journal of Clinical Investigation, showed that B07 improved the appetite and preserved lean mass and fat mass in rodent models of cancer and its associated combination chemotherapy. This same study showed the strong potential of B07 to alleviate chemotherapy-induced anorexia and weight loss for millions of patients worldwide.

About TCMCB07
TCMCB07 is a melanocortin‐3/4 antagonist peptide candidate in clinical development for the treatment of cachexia. It is designed to be a first-in-class peptide drug with the ability to cross the blood-brain barrier and act on previously inaccessible target receptors to modulate the body’s behavioral and metabolic response to chronic illness. Pre-clinical animal trial results show significant lean muscle mass retention (e.g., a reversal of the cachectic condition) during administration of the drug. The results are consistent in cachexia arising from many different types of chronic disease.

On April 30, 2025 J INTS BIO, a company specializing in anticancer and orphan drugs, reported its research findings for the next-generation EGFR-TKI therapeutic ‘JIN-A02’ (clinical Phase 1/2 results) and the ovarian cancer treatment candidate ‘JIN-001’ (preclinical results) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025, held in Chicago from April 25 to 30 (Press release, J INTS BIO, APR 30, 2025, View Source [SID1234652400]). In this presentation, J INTS BIO demonstrated its innovative drug development capabilities on a global stage, attracting significant attention from both academia and the industry.

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‘JIN-A02’: New Hope for Overcoming Resistance – 4th Generation EGFR-TKI Clinical Results

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases worldwide, and among these, EGFR mutations are considered a major therapeutic target. JIN-A02, introduced at AACR (Free AACR Whitepaper) 2025, showed outstanding therapeutic efficacy in patients who developed resistance to existing third-generation EGFR-TKIs. In particular, JIN-A02 demonstrated remarkable antitumor activity in patients with EGFR C797S mutation—currently a mutation for which no approved targeted therapies exist—thus opening a new avenue for treatment options.

In the clinical trial, a patient in the 300 mg cohort showed complete clearance of circulating tumor DNA (ctDNA) harboring either the C797S or Ex19del mutation, and ctDNA carrying the T790M mutation was reduced by over 90%. Clinically, a partial response (PR) was observed, with tumor size reductions of up to 39.7%, and notable shrinkage of intracranial metastatic lesions. These findings are particularly important for NSCLC patients, in whom brain metastases are common. Furthermore, no dose-limiting toxicities (DLTs) or serious adverse events were observed up to the 300 mg dose, highlighting the excellent safety profile of JIN-A02. This safety profile is expected to be particularly beneficial for patients requiring long-term treatment and combination therapies.

Currently, JIN-A02 is undergoing multinational clinical trials in Korea, the United States, Thailand, and other countries, and it is being closely watched as a potential groundbreaking treatment option for EGFR-mutant NSCLC patients.

‘JIN-001’: An Innovative New Drug Targeting Refractory Ovarian Cancer

Also presented was ‘JIN-001,’ J INTS BIO’s second-generation synthetic HSP90 inhibitor, developed as a new strategy to overcome resistance to existing ovarian cancer treatments. Ovarian cancer remains one of the deadliest gynecological malignancies, as it is often diagnosed at an advanced stage when effective treatment options are extremely limited.

The preclinical study demonstrated that JIN-001, when combined with the chemotherapeutic agent cisplatin, significantly enhanced tumor suppression compared to cisplatin alone. Notably, even at low concentrations (≤0.1 μM), JIN-001 enhanced the antitumor activity of cisplatin against both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells, compared to cisplatin alone. Moreover, the combination therapy significantly reduced the expression of key signaling proteins related to cisplatin resistance, contributing to a sustained antitumor effect.

Based on these promising results, J INTS BIO is planning additional preclinical studies and aims to rapidly advance JIN-001 into clinical trials, with the goal of establishing a new standard of care for the treatment of refractory and multidrug-resistant ovarian cancer.

Led by the presentation at AACR (Free AACR Whitepaper) 2025, J INTS BIO aims to further strengthen its competitiveness in the global oncology market and solidify its position as a frontrunner in next-generation anticancer drug development. The company also outlined its vision to continue delivering innovative therapies through ongoing research and development efforts, offering new hope to cancer patients worldwide.

On April 30, 2025 FORE Biotherapeutics, a registration stage biotherapeutics company dedicated to developing targeted therapies to treat patients with cancer, reported that a plixorafenib abstract has been selected for poster presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper), taking place May 30-June 3, 2025 in Chicago (Press release, Fore Biotherapeutics, APR 30, 2025, View Source [SID1234652384]).

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At ASCO (Free ASCO Whitepaper) 2025, Karisa Schreck, M.D., Ph.D., from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, will present a trials-in-progress poster highlighting the study design of the global registration-intended FORTE Master Protocol, which includes four sub-protocol baskets evaluating plixorafenib in distinct patient populations. The three monotherapy indications currently under evaluation are BRAF V600 Recurrent Primary Central Nervous System Tumors, Rare BRAF V600 Mutated Solid Tumors and Solid Tumors with BRAF Fusions.

Poster Presentation Details:

Title: FORTE: A phase 2 master protocol assessing plixorafenib for BRAF-altered cancers
Poster Session: Central Nervous System Tumors
Date and Time: Saturday, May 31, 2025, 9:00 a.m. – 12:00 p.m. CT
Abstract Number: TPS2091
Presenter: Karisa Schreck, M.D., Ph.D., Johns Hopkins University