On April 25, 2025 Radiant Biotherapeutics, a preclinical biotechnology company developing an antibody platform to deliver first-in-class transformative therapies for patients facing life-changing disease, reported the presentation of a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25-30, 2025 in Chicago (Press release, Radiant Biotherapeutics, APR 25, 2025, View Source [SID1234652174]). The presentation describes the company’s Multabody platform, a novel approach to stimulating key targets in immunotherapy that have remained out of reach due to toxicity or lack of response.

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Details on the poster presentation are below:

Presentation Title: Multabodies: A next-generation approach for cancer immunotherapy and 4-1BB agonist therapy
Abstract Number: 2889/28
Session Date and Time: April 28th 2:00-5:00 p.m.
Presenter: Joanne Hulme, Ph.D.

On April 25, 2025 Onchilles Pharma, a private biotech company pioneering next-generation cytotoxic therapeutics that harness the ELANE pathway, reported the presentation of new preclinical data for its lead drug candidate, N17350, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 ("AACR") (Press release, Onchilles Pharma, APR 25, 2025, View Source [SID1234652173]). The presentation highlights N17350’s superior and selective tumor-killing ability compared to standard-of-care chemotherapies in ovarian cancer models, including chemotherapy-resistant tumors, derived from patients.

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This data builds on the growing body of evidence supporting N17350’s novel mechanism of action and its potential to become a next-generation cytotoxic therapeutic. Unlike traditional chemotherapies, which indiscriminately damage both cancer and healthy immune cells, N17350 leverages elevated levels of histone H1 isoforms found in cancer cells to selectively kill tumors while sparing healthy cells. The results show that N17350 maintains its efficacy across various tumor types and treatment histories.

"We are excited to share this compelling data at AACR (Free AACR Whitepaper), which further reinforces the potential of N17350 to address unmet needs across cancers, with the potential to make a significant impact in chemotherapy-resistant disease," said Lev Becker, Ph.D., Founder and Chief Scientific Officer of Onchilles Pharma. "These results demonstrate the strength of leveraging the ELANE pathway to therapeutically target tumor heterogeneity and overcome limitations of current cytotoxic therapies."

Highlights from the AACR (Free AACR Whitepaper) Presentation Include:

Broad Efficacy: N17350 was effective in killing cancer cells derived from treatment-naïve, neoadjuvant chemotherapy-treated (NACT), and recurrent ovarian tumors.
Selective Cytotoxicity: While standard chemotherapies were equally toxic to both cancer and immune cells, N17350 preserved immune cell viability while inducing immunogenic cell death in cancer cells.
In Vivo Superiority: In cell-derived xenograft (CDX) models from ovarian cancer patients, N17350 outperformed carboplatin in inducing tumor regression.
No Resistance: N17350 maintains potency following repeat dosing and effectively kills chemotherapy-resistant cancer cells.
"These new data exemplify the power of the ELANE pathway, and we believe therapeutics such as N17350 could represent a fundamentally new class of cancer treatments," said Court R. Turner, J.D., Co-Founder and Chief Executive Officer of Onchilles Pharma. "We remain focused on translating these compelling preclinical results into clinical benefit as we prepare to enter the clinic later this year."

N17350 is currently advancing toward first-in-human clinical trials, with an initial focus on skin, head and neck, triple-negative breast, and lung cancers. These new data support its continued development and highlight its promise as a differentiated cytotoxic modality with potential applications across a broad range of solid tumors.

The AACR (Free AACR Whitepaper) poster presentation, titled "N17350 outperforms cytotoxic agents in killing tumors of treatment-naïve and chemotherapy-treated ovarian carcinoma patients," will be available in Poster Section 21 (Poster Board Number: 30, Presentation Number: 861) from 2pm to 5pm CT on Monday, April 28th. The poster will also be available to meeting attendees via the AACR (Free AACR Whitepaper) virtual platform beginning at 1pm ET today.

On April 25, 2025 Talus Bioscience, a technology-enabled therapeutics company, reported new preclinical data from programs targeting transcription factors in chordoma, non-small cell lung cancer, and advanced prostate cancer (Press release, Talus Bioscience, APR 25, 2025, View Source [SID1234652172]). The data, presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held April 25-30, support Talus Bio’s first-in-class approach to target previously undruggable transcription factors using regulome-scale discovery in live human cells.

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"We built our platform to systematically address transcription factors, a target class long considered out of reach for small-molecule therapeutics," said Alex Federation, PhD, CEO and Co-Founder of Talus Bio. "The data we’re presenting at AACR (Free AACR Whitepaper) show that the approach is working. Our platform has already logged over 50 million protein-compound interactions this year. These results validate our strategy in two difficult oncology indications. Our Brachyury molecules are on track for candidate nomination, and new compounds targeting NONO and AR-V7 show real promise for metastatic castration-resistant prostate cancer. We now have a repeatable model for discovering tractable starting points across transcription factor targets once thought undruggable."

Talus Bio’s technology profiles the regulome, providing a quantitative readout of active transcription factors and other DNA-bound regulators in live, unmodified human cells. The platform can measure over 10,000 regulomes per month and is being deployed to discover and optimize small molecules that modulate transcription factor activity in their native context.

Data presented at AACR (Free AACR Whitepaper) on lead drug candidates highlight the strength of this approach. By combining high-throughput transcription factor profiling with AI-guided chemistry, Talus Bio is accelerating the discovery of modulators for transcription factor targets.

Presentation Highlights

Poster 4036 / 2: Selective inhibition of the transcription factor Brachyury in chordoma and non-small cell lung cancer

Preclinical data presented by Gaelle Mercenne at AACR (Free AACR Whitepaper) showcase the ability of a novel covalent small molecule, TAL61, to effectively modulate Brachyury activity in patient-derived xenograft (PDX) models of chordoma:

TAL61 demonstrated significant efficacy in reducing tumor burden in PDX chordoma models with durable tumor suppression post-treatment
TAL61 exhibited low toxicity and high tolerability with daily dosing
Additionally, TAL61 decreased tumor burden by more than 50% in in vivo models of Brachyury-positive non-small cell lung cancer (NSCLC)
Poster 6991 / 20: Targeting NONO as a therapeutic strategy for metastatic castration-resistant prostate cancer (CRPC)

Preclinical data presented by Brian McEllin support an emerging modality targeting NONO to disrupt both AR and ARv7 transcription as an emerging treatment for metastatic castration-resistant prostate cancer:

A targeted search of Talus Bio’s proprietary compound database identified covalent small molecules for lead optimization
Compound treatment reduced mRNA and protein levels of AR and ARv7 in prostate cancer cells
Active compounds show abrogate AR and ARv7 gene expression programs in castration-resistant prostate cancer models
Poster 4496 / 7: Small molecule inhibition of previously "undruggable" transcription factors with AI-guided functional proteomics

Data presented by Alex Federation at AACR (Free AACR Whitepaper) highlight the regulome sequencing platform as a drug discovery engine for previously intractable transcription factors:

The assay provides a quantitative, time-resolved readout of drug-induced changes in transcription factor activity, capturing protein:genome interactions for thousands of proteins simultaneously
This approach enables small molecule screening in physiologically relevant contexts, where transcription factors fold, assemble, and function as they do in human disease
AI-guided hit discovery using this technology has enabled discovery and optimization for inhibitors of Brachyury, AR-V7, and STAT3
Talus Bio’s foundational AI model has helped identify over 30 tractable compounds against validated transcription factor targets in cancer and other diseases. The company is actively pursuing co-development opportunities with partners to accelerate these discoveries into the clinic. Connect with the team to learn more about partnerships and collaborations.

On April 25, 2025 CDR-Life reported the presentation of data for its novel T cell engager (TCE) programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago (Press release, CDR-Life, APR 25, 2025, View Source [SID1234652171]). The presentations showcase the company’s proprietary M-gager platform-derived TCE candidates, with a focus on CDR404, currently in Phase 1 clinical trials for MAGE-A4-positive solid tumors.

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"The data presented at AACR (Free AACR Whitepaper) highlight the potential advantages of our antibody-based approach to T cell engagement against highly tumor-specific targets," said Christian Leisner, PhD, Chief Executive Officer of CDR-Life. "CDR404 demonstrated superior potency and durability in preclinical models, which align with the encouraging early signals we’re seeing in our ongoing Phase 1 trial."

Key Findings for CDR404 in MAGE-A4-Positive Tumors (Abstract #3494)
The poster, "Durable and potent in vitro T cell activity with repeated exposure to CDR404, a potential best-in-class T cell engager targeting MAGE-A4" demonstrated several advantages of CDR404 compared to a TCR-based TCE:

Superior Potency and Durability: CDR404 showed more potent killing of MAGE-A4-positive cancer cell lines across multiple indications, even at low effector-to-target cell ratios which mimic a "cold" tumor environment, compared to a TCR-based competitor
Enhanced T Cell Fitness: After multiple rounds of serial killing, T cells exposed to CDR404 maintained significantly better fitness, with lower levels of crucial T cell exhaustion markers compared to the TCR-based approach
Favorable Cytokine Profile: CDR404 demonstrated a more favorable cytokine release profile, potentially offering safety advantages in the clinical setting
Effective Across Multiple Cancer Types: CDR404 showed strong activity against MAGE-A4-positive tumor cells from different cancer types, including lung adenocarcinoma and squamous cell carcinoma, and melanomas
The data presented in the poster align well with early emerging data from the ongoing Phase 1 trial of CDR404 (NCT06402201). CDR404 has shown clear signals of immunological activity and preliminary evidence of anti-tumor activity, including at the pharmacokinetic model-derived starting dose. Use of this innovative model created an elevator to a higher starting dose, potentially shortening overall trial duration by enabling a starting dose closer to the efficacious dosing range while maintaining patient safety. Dose escalation is ongoing and patient data from the early stages of the Phase 1 trial will be reported later this year.

Second T Cell Engager for KK-LC-1-Positive Tumors (Abstract #3493)
In the poster, "A novel T cell engager antibody for the treatment of HLA-A01/KK-LC-1-positive tumors," CDR-Life presented data on CDR505, a novel antibody-based TCE targeting the Kita-Kyushu lung cancer antigen-1 (KK-LC-1) presented on HLA-A01:01.

Key findings for CDR505 included:

Potent and Selective: CDR505 demonstrated potent and selective killing of KK-LC-1-positive cancer cells.
Preferential T Cell Activation: The molecule showed preferential activation of CD8+ T cells, confirming the intended mechanism of action.
High Target Specificity: CDR505 exhibited high specificity for the KK-LC-1 peptide/HLA-A*01:01 complex, demonstrating low risk for off-target binding.
Desirable Pharmaceutical Properties: The molecule demonstrated excellent manufacturability, solubility and stability characteristics, supporting its feasibility for subcutaneous formulation.
Broad Patient Potential
Both TCE candidates have the potential to address significant patient populations:

CDR404 targets MAGE-A4-positive tumors in HLA-A02:01-positive patients. MAGE-A4 is expressed in up to 63% of ovarian cancers, 62% of head and neck cancers and 52% of squamous lung cancers.
CDR505 is the only TCE in development targeting KK-LC-1-positive tumors in HLA-A*01:01-positive patients. KK-LC-1 is expressed in 75% of colorectal and gastric carcinoma cancers and 60% of pancreatic ductal adenocarcinoma cancers.
"With CDR505, we’re breaking new ground in targeting previously inaccessible cancer antigens through our innovative M-gager platform," added Dr. Leisner. "This first-in-class molecule demonstrates how we’re tackling difficult targets with precision, particularly in tumor types where traditional approaches have shown limited success. The widespread expression of KK-LC-1 across gastrointestinal cancers positions CDR505 to potentially address some of medicine’s most challenging malignancies with a novel immunotherapeutic approach."

On April 25, 2025 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported the acceptance of two abstracts for mini-oral presentation and the acceptance of four abstracts for poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 25-30, 2025, in Chicago, Illinois (Press release, Repare Therapeutics, APR 25, 2025, View Source [SID1234652170]).

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Mini-Oral Presentation Details:
Title: Efficacy and safety of the combination PKMYT1-inhibitor lunresertib and ATR-inhibitor camonsertib in patients with ovarian and endometrial cancers: Phase I MYTHIC study (NCT04855656)
Presenter: Alison M. Schram, MD, Memorial Sloan Kettering Cancer Center
Session: Innovative Approaches to Key Molecular Targets
Session Date and Time: Tuesday, April 29 from 2:30-4:30 p.m. CT
Location: Room S406 (Vista Ballroom)
Abstract Number: CT262

Title: The PLK4 inhibitor RP-1664 drives centriole modulation and single agent tumor regressions in preclinical neuroblastoma models
Presenter: John M. Maris, MD, Children’s Hospital of Philadelphia
Session: Advancing the Science of Childhood Cancers: From Bench to Bedside
Session Date and Time: Sunday, April 27 from 3:00-5:00 p.m. CT
Location: Room E353 C
Abstract Number: 1201

Poster Presentation Details:

Title: A dual mechanism of sensitivity to PLK4 inhibition by RP-1664 in neuroblastoma
Presenter: Michal Zimmermann, PhD, Repare Therapeutics
Session: Cell Cycle Effects of Anticancer Drugs
Session Date and Time: Sunday, April 27 from 2:00-5:00 p.m. CT
Location: Poster Section 17
Poster Number: 9
Abstract Number: 365

Title: RP-1664: A potent and selective PLK4 inhibitor causing tumor regressions in TRIM37-high xenograft models of solid tumors
Presenter: Anne Roulston, PhD, Repare Therapeutics
Session: Kinase and Phosphatase Inhibitors 1
Session Date and Time: Monday, April 28 from 9:00 a.m-12:00 p.m. CT
Location: Poster Section 21
Poster Number: 9
Abstract Number: 1734

Title: Pan-cancer analysis of TRIM37 copy-number and development of fit-for-screening in situ hybridization tools
Presenter: Isabel Soria-Bretones, PhD, Repare Therapeutics
Session: Diagnostic Biomarkers 2
Session Date and Time: Sunday, April 27 from 2:00-5:00 p.m. CT
Location: Poster Section 31
Poster Number: 2
Abstract Number: 717

Title: Targeting CCNE1 amplification in gastric cancer
Presenter: Sung Joo Jang, Columbia University Irving Medical Center
Session: Protein Kinases and Phosphatases as Targets for Therapy
Session Date and Time: Wednesday, April 30 from 9:00 a.m.-12:00 p.m. CT
Location: Poster Section 24
Poster Number: 4
Abstract Number: 6942

A copy of each poster presentation is available on the Scientific Resources page of the Repare Therapeutics website and a copy of each mini-oral presentation will be available on the Scientific Resources page of the Repare Therapeutics website at the start of each mini-oral session.