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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On April 25, 2025 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, reported that its Phase 1/2 clinical trial of NDI-219216, the company’s investigational non-covalent Werner syndrome helicase (WRN) inhibitor, is actively enrolling and dosing patients with advanced solid tumors (Press release, Nimbus Therapeutics, APR 25, 2025, View Source [SID1234652169]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The initiation of this clinical trial marks an important milestone in advancing our novel WRN inhibitor program," said Anita Scheuber, M.D., Ph.D., Senior Vice President, Therapeutic Head, Oncology at Nimbus. "We are excited to be evaluating NDI-219216 in patients with advanced disease, who currently have limited treatment options when they experience disease progression on standard of care therapies. The trial is actively enrolling across multiple clinical sites, and we look forward to generating important additional safety and efficacy data as we advance this promising candidate through clinical development."

The Phase 1/2 clinical trial (NCT06898450) is an open-label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced cancer. The study will be conducted in three parts: Part A (dose escalation), Part B (dose optimization), and Part C (dose expansion).

Nimbus presented promising preclinical data on NDI-219216 (previously NTX-452) at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in October 2024. The data demonstrate that NDI-219216 is a potent and selective WRN inhibitor with significant tumor regression and sustained complete responses observed at low doses in MSI-H tumor models refractory to immunotherapy and chemotherapy.

The company will present new findings comparing covalent versus non-covalent WRN inhibition mechanisms and demonstrating NDI-219216’s superior efficacy across multiple preclinical MSI-H tumor models compared with other clinical-stage WRN inhibitors in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 25-30, 2025 in Chicago. The poster entitled "NDI-219216: a non-covalent, potent, selective and highly efficacious WRN inhibitor with best-in-class potential for the treatment of MSI-H tumors" highlights key preclinical findings related to NDI-219216, including:

Demonstration of activity against a potential resistance mutation at Cysteine 727 that could significantly reduce the efficacy of covalent WRN inhibitors
Robust tumor regression across multiple MSI-H tumor models, including those that are refractory to existing standard of care agents
Superior efficacy at lower doses and in less responsive MSI-H tumor models compared to other clinical-stage WRN inhibitors
"The data we are presenting at AACR (Free AACR Whitepaper) 2025 highlight several important features of our non-covalent WRN inhibitor," said Peter J. Tummino, Ph.D., President of Research and Development at Nimbus. "NDI-219216 has the potential for more durable target engagement than covalent inhibitors and maintains potency against potential resistance mutations. Its superior efficacy across multiple MSI-H tumor models, including those less sensitive to other WRN inhibitors and those refractory to current therapies, reinforces our belief that NDI-219216 represents a best-in-class opportunity with broad potential across multiple MSI-H tumor types with significant unmet need."

About NDI-219216

NDI-219216 is a highly potent and selective non-covalent investigational inhibitor of Werner syndrome helicase (WRN) activity being developed for the treatment of MSI-H tumors. WRN is a DNA helicase required for DNA replication and DNA repair and is a validated synthetic lethal target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of deficient mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric, and endometrial cancers. In preclinical studies, treatment with NDI-219216 exhibited robust antitumor activity across multiple cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) MSI-H tumor models, including models for colorectal, gastric, and endometrial cancers.

On April 25, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that it will present new data from studies evaluating two of its internally developed, next-generation, investigational oncology therapies that it has global rights to, ZL-6201, a novel leucine-rich repeat-containing protein 15 (LRRC15) antibody-drug conjugate (ADC) targeting multiple solid tumors, and ZL-1222, an innovative anti-PD-1/ interleukin-12 (IL-12) immunocytokine for cancer immunotherapy, during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, Illinois this week (Press release, Zai Laboratory, APR 25, 2025, View Source [SID1234652168]). The data provide strong evidence supporting continued evaluation of both investigational therapies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The latest findings that will be presented at AACR (Free AACR Whitepaper) 2025 demonstrate impressive potential for the continued advancement of these next-generation oncology therapies," said Linda Liu, Ph.D., Senior Vice President, Biologics Discovery, Zai Lab. "We look forward to continuing our evaluation of these therapies that may provide the opportunity to broaden treatment options for patients who have been unresponsive or resistant to current treatments across a broad range of cancer types."

ZL-6201 is a potential first- and best-in-class ADC with high affinity and specificity for LRRC15, an appealing target for cancer therapy due to its overexpression in multiple solid tumor types such as sarcoma, glioblastoma and melanoma. The compound was designed with a novel ADC technology platform called TMALIN, which leverages the tumor microenvironment to overcome challenges associated with first-generation ADC therapies, including off-target payload toxicity.

Findings to be presented at AACR (Free AACR Whitepaper) 2025 on Tuesday, April 29, demonstrate that ZL-6201 efficiently internalizes within and kills tumor cells, while also exhibiting a strong bystander killing effect in the tumor microenvironment where the target is often expressed. In multiple in vitro and in vivo pre-clinical studies, treatment with ZL-6201 effectively suppressed the growth of established tumors. Based on these findings, Zai Lab plans to initiate Investigational New Drug (IND)-enabling studies of ZL-6201 as a potential treatment for patients with sarcoma and other LRRC15-positive solid tumors, such as breast cancer and other malignancies, in 2025.

ZL-1222 is a PD-1 targeted, next-generation IL-12 immunocytokine designed to leverage the anti-tumor potential of IL-12 while lowering the associated systemic toxicity. Previous preclinical studies have demonstrated that IL-12 can have dramatic anti-tumor activity. However, in clinical investigations, systemic administration of IL-12 has been associated with a narrow therapeutic index with severe adverse events.

Findings from preclinical studies to be presented Monday, April 28, at AACR (Free AACR Whitepaper) 2025 suggest that ZL-1222, through precisely tailored IL-12 activity and PD-1 targeting, demonstrate potent anti-tumor activity in both anti-PD-1 sensitive and resistant tumor models, with improved systemic safety. These results indicate its potential to benefit patients who are unresponsive or resistant to the current immuno-oncology therapies.

"At Zai Lab we are building a robust portfolio of potential first- and best-in-class oncology therapies to expand treatment options for patients around the world," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "Findings from our preclinical studies of ZL-6201 and ZL-1222 demonstrate our commitment to identifying innovative approaches that address limitations associated with first-generation therapies. These include the ability to deliver higher concentrations of cytotoxic agents and limit off-target toxicity, in order to deliver meaningful treatment options for patients with a range of cancer types."

Details regarding the Zai Lab poster presentations at AACR (Free AACR Whitepaper) 2025 are as follows:

Title: Discovery and characterization of a novel LRRC15-targeting antibody-drug conjugate (ADC) for the treatment of solid tumors
Presenter: Bing Wan, Ph.D., Executive Director, Biology, Zai Lab
Session Title: New and Emerging Cancer Drug Targets
Date/Time: Tuesday, April 29, 2025, from 9:00 a.m. – 12:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 17
Poster Board Number: 23
Published Abstract Number: 4266

Title: Cis-delivery of a potency-reduced IL-12 via an anti-PD-1 single-chain antibody exhibits potent anti-tumor activity
Presenter: Linda Liu, Ph.D., Senior Vice President, Biologics Discovery, Zai Lab
Session Title: Late-Breaking Research: Clinical Research 1
Date/Time: Monday, April 28, 2025, from 2:00 p.m. – 5:00 p.m. CT
Location: McCormick Place Convention Center, Poster Section 53
Poster Board Number: 1
Published Abstract Number: LB204