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.

On April 25, 2025 Azitra, Inc. (NYSE American: AZTR), a clinical stage biopharmaceutical company focused on developing innovative therapies for precision dermatology, reported that an abstract detailing the Phase 1/2 clinical trial of ATR04-484 in EGFR inhibitor ("EGFRi")-associated rash has been accepted for presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held May 30-June 3, 2025 in Chicago (Press release, Azitra, APR 25, 2025, View Source [SID1234652138]).

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"We look forward to presenting an update on the ATR-04 program at ASCO (Free ASCO Whitepaper) as we plan to dose the first patient in the first half of 2025," said Francisco Salva, CEO of Azitra. "ASCO is widely regarded as the most prestigious cancer research conference in the world, and we are eager to educate leaders in the oncology community on the potential of ATR04-484 to treat the unique dermatologic toxicities that often accompany EGFRi treatments, which can hamper treatment efforts and cause significant physical and psychological discomfort for patients."

ATR04-484 is a live biotherapeutic product candidate including an isolated, naturally derived Staphylococcus epidermidis strain that was engineered to be safe by deleting an antibiotic resistance gene and engineering auxotrophy to control the growth of ATR04-484. ATR04-484 is in development for EGFRi-associated skin rash, which is associated with the suppression of skin immunity by EGFR inhibitors and subsequent inflammation, often accompanied by elevated levels of IL-36γ and S. aureus. Azitra has received Fast Track designation from the FDA for EGFRi associated rash and has initiated a Phase 1/2 clinical study in patients with EGFRi rash with the first patient expected to be dosed in the first half of 2025.

EGFR inhibitors are a class of cancer drugs that target and block the activity of the EGFR protein, which plays a crucial role in cell growth and survival. They are primarily used to treat certain types of cancer, including non-small cell lung cancer (NSCLC) and colorectal cancer.

The full ASCO (Free ASCO Whitepaper) abstracts will be available on May 22, 2025, after 5 p.m. ET. Abstract titles are available at: View Source

On April 25, 2025 Autolus Therapeutics plc (Nasdaq: AUTL), an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation programmed T cell therapies and candidates, reported that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorisation for AUCATZYL (obecabtagene autoleucel) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-ALL) (Press release, Autolus, APR 25, 2025, View Source [SID1234652154]).

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"Having treated a number of patients with AUCATZYL as part of the FELIX clinical trial, I am delighted that we have moved closer to eligible relapsed/refractory B-ALL patients being able to access AUCATZYL," said Dr. Claire Roddie, MD, PhD, FRCPath, Lead investigator of the FELIX study and Associate Professor of Haematology at the University College London (UCL) Cancer Institute. "We now look forward to NICE completing its assessment of the medicine to potentially make it an option for eligible patients on the NHS."

"AUCATZYL was designed to address an unmet need for eligible adult r/r B-ALL patients and it is satisfying that is has been licensed in the country where it was created," said Dr. Martin Pule, Chief Scientific Officer and Founder of Autolus.

"Continuing our momentum, this MHRA license is a significant milestone for Autolus as a company. With our scientific expertise, operations and manufacturing based in the UK, this is an important achievement for our company," said Dr. Christian Itin, Chief Executive Officer of Autolus. "We want to thank all the patients and investigators at the UK trial centres for their contributions towards this license, as well as the foundational work by our partners at UCL and our internal team."

Obecabtagene autoleucel is an autologous CD19 CAR T cell therapy with a proprietary CD19 CAR, invented by a team led by Dr. Martin Pule, at University College London, along with collaborators at Great Ormond Street Hospital and University College London Hospital. The CAR is designed to have a "fast-off" rate which mimics physiological T-cell receptor interactions2.

The MHRA authorisation of AUCATZYL was based on the results of the FELIX study, an open-label, multi centre, single arm study in adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, the results of which were published in the New England Journal of Medicine in November 20242. Of the 153 r/r B-ALL patients enrolled in the FELIX study, 127 (83.0%) received at least one obecabtagene autoleucel infusion and were evaluable. In the pivotal cohort of patients, (cohort IIA (n=94)), the Complete Response/Complete Response with Incomplete Haematological Recovery (CR/CRi) for patients who received at least one infusion of obecabtagene autoleucel was 76.6%. Median response duration for all infused patients was 21.2 months. Median event-free survival (EFS) was 11.9 months and the estimated 6- and 12-month event-free survival rates were 65.4% and 49.5%, respectively. The most common non-laboratory Grade 3 or higher adverse reactions were infections-pathogen unspecified (32%), febrile neutropenia (24%) and bacterial infectious disorders (11%). Cytokine release syndrome developed in 87 of the 127 patients (68.5%), with events of grade 3 or higher in three patients (2.4%). Immune effector cell-associated neurotoxicity syndrome developed in 29 of the 127 patients (22.8%), with grade 3 or higher occurring in nine patients (7%).

For further information regarding obecabtagene autoleucel, the Summary of Product Characteristics (SPC), including a full list of side effects and adverse reactions, is available here.

Autolus submitted obecabtagene autoleucel for appraisal by the National Institute for Health and Care Excellence (NICE)3 in Q4 2024 and is working with NICE and the NHS to potentially achieve access for eligible patients in England. NICE provides guidance to the NHS in England on the clinical and cost-effectiveness of medicines, treatments, and technologies based on a rigorous process of evidence review and consultation with professionals and patients.

ALL is an aggressive type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. In the UK there are approximately 7654 new cases of ALL diagnosed every year. In frontline treatment for adult B-ALL, up to 50% of patients will ultimately relapse5. Survival rates remain very poor in adult patients with r/r ALL, with median overall survival of eight months with conventional treatments6, and the standard-of-care treatment can trigger severe toxicities.

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 Baylink Biosciences reported data from its Antibody Drug Conjugate portfolio at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL (Press release, Baylink Biosciences, APR 25, 2025, View Source [SID1234652139]). The data presented for BLB-101, an antibody drug conjugate targeting Claudin 6 and 9 delivering exatecan, represents a potential best-in-class profile. In addition, Baylink presented data demonstrating its novel next-generation ADC linker technology is able to overcome key challenges in ADC development.

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"The data presented today at AACR (Free AACR Whitepaper) provides strong evidence of BLB-101’s best-in-class profile. We believe BLB-101 is the only ADC with dual targeting of Claudin 6 and 9, with the ability to impact heterogenous tumors and benefit more patients with ovarian and other CLDN6/9+ tumor types. We plan to file an IND for this exciting candidate in 2026," said Alice Chen, PhD, Chief Scientific Officer and Founder of Baylink. "In addition, our scientists presented data at the meeting showcasing our innovative linker technology which has been designed to overcome a number of key challenges in the ADC field. In particular, our linker technology enables the delivery of new payload classes such as degraders and the delivery of two modalities in a dual payload ADC format, approaches that we believe will help to overcome resistance to chemotherapy, a significant unmet need."

Presentation Highlights

Preclinical evaluation of BLB-101, a topoisomerase-inhibitor-based anti-CLDN6/9 antibody-drug conjugate featuring a proprietary hydrophilic linker

Poster number：1578

Session Date and Time: April 28, 2025, 9:00 AM – 12:00 PM

BLB-101 is an antibody drug conjugate designed to target Claudin 6/9 and deliver the topoisomerase 1 inhibitor, exatecan in a highly efficient manner with a drug to antibody ratio of 8. Claudin 6 (CLDN6) is a tight junction protein that is highly expressed in various human cancers, including ovarian cancer, endometrial cancer, and non-small cell lung cancer (NSCLC), but is absent in normal adult tissues. Claudin 9 (CLDN9), which shares high homology with CLDN6, exhibits a similar expression pattern—being nearly undetectable in normal tissues but upregulated in ovarian and endometrial cancers. The compelling preclinical activity profile supports BLB-101 development for Claudin 6/9 positive tumors. An investigational new drug submission is planned for 2026.

Key Results:

We successfully identified a high-affinity antibody, 2D5S, that specifically binds to CLDN6 and CLDN9 while avoiding interaction with other Claudin family members. BLB-101 is an antibody-drug conjugate (ADC) candidate that incorporates 2D5S (CLDN6/9 Ab) and the topoisomerase I inhibitor, exatecan as payload, along with our proprietary hydrophilic linker, BL001. BLB-101 demonstrates excellent biological activity, favorable in vivo pharmacokinetics (PK), and excellent developability. It exhibits strong cytotoxic effects across multiple antigen-positive cancer cell lines. In xenograft models expressing CLDN6 or CLDN9, BLB-101 achieved tumor elimination at low doses. Additionally, BLB-101 was well tolerated in non-human primates. Collectively, these findings provide strong support for the continued clinical development of BLB-101.

• 2D5S Ab binds with high affinity to CLDN6 and CLDN9 while sparing other claudin

family members.

• 2D5S demonstrates stronger internalization compared to a benchmark antibody.

• BLB-101 is a DAR8 ADC featuring a topoisomerase 1-inhibitor-based payload with a

proprietary hydrophilic linker, BL001.

• BLB-101 exhibits strong in vitro cytotoxic and bystander killing effects.

• In xenograft models, BLB-101 treatment resulted in robust tumor elimination at dose as low as 1 mg/kg.

• BLB-101 demonstrated outstanding plasma stability and favorable PK in cynomolgus monkey.

• BLB-101 is well-tolerated in cynomolgus monkeys up to 40 mg/kg, suggesting an

extended therapeutic window.

A linker platform for antibody drug conjugates (ADCs): expanding the therapeutic window

Poster number：7463

Session Date and Time: April 30, 2025, 9:00 AM – 12:00 PM

Key Results:

Our novel linker designs offer significant advantages, with features that could expand the therapeutic window of current ADCs by improving their hydrophilicity and stability, and reducing off–target effects while maintaining efficacy. The linkers have been applied to several projects with the frontrunner project scheduled to enter a phase 1clinical trial in 2026. We are also expanding the utility of this class of linkers to enable innovative design of dual–payload–ADC and Degrader–Antibody–Conjugates.

• Baylink’s proprietary linker BL001 improves hydrophilicity and stability of ADC

• BL001 linker reduced non-specific uptake of ADC into non-cancerous cells via macropinocytosis

• BL001 linker utilized in a trastuzumab exatecan ADC showed superior antitumor effect to GGFG based ADC delivering Dxd.

• BL001 linker utilized in BLB-101 candidate showed excellent PK and tolerability in cynomolgus monkeys, predicting an enhanced therapeutic index.

Copies of the poster presentations will be available on the Baylink Biosciences website at www.Baylinkbio.com/blog following the AACR (Free AACR Whitepaper) meeting.