On July 22, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, and Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui), a global pharmaceutical company focused on scientific and technological innovation, reported the publication of an abstract for an oral presentation on IDE849 (SHR-4849) at the IASLC 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (WCLC), taking place September 6-9, 2025 in Barcelona, Spain (Press release, Ideaya Biosciences, JUL 22, 2025, View Source [SID1234654472]). The presentation will cover efficacy and safety results in SCLC from the Phase 1 trial Hengrui is conducting in China for IDE849 (SHR-4849), a potential first-in-class delta-like ligand 3 (DLL3)-targeting Topoisomerase-1 (TOP1) payload antibody drug conjugate (ADC). DLL3 is upregulated across multiple solid tumor types where significant unmet need remains, including SCLC, neuroendocrine tumors (NETs), non-small cell lung cancer (NSCLC) and melanoma.

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IDEAYA will also have a poster presentation with data from a second published abstract providing combination mechanism and pre-clinical synergy data between TOP1-payload based ADCs and IDE161, the company’s proprietary, potentially first-in-class PARG inhibitor. This combination has the potential to enhance the durability of TOP1-payload based ADCs, including IDE849 and IDE034, IDEAYA’s B7H3/PTK7 bispecific TOP1 ADC, and aligns with the company’s clinical development strategy of evaluating rational combinations, where appropriate, to drive improved clinical outcomes for patients with cancer.

"We are excited to have the first-in-human Phase 1 clinical efficacy and safety data presented by our partner Hengrui for IDE849 (SHR-4849) in SCLC patients at the WCLC 2025, as IDEAYA rapidly advances the global development of IDE849," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. "IDE849 represents a potential first-in-class DLL3-TOP1 ADC, and we look forward to evaluating its clinical potential as both a monotherapy agent in SCLC and NET patients, as well as in combination with immunotherapy and our Phase 1 PARG inhibitor, IDE161," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

Details of the oral presentation are as follows:

Title: A first-in-human Phase 1 study of SHR-4849 (IDE849), a DLL3-directed antibody drug conjugate (ADC) in relapsed SCLC

Date and time: Sunday, September 7th, 4:45-6:00 PM (CET)

Session: OA6 – Novel ADCs in SCLC

Details of the poster presentation are as follows:

Control #: 2165

Title: Dual PARG-TOP1 Inhibition Exacerbates DNA-Protein Crosslinks and Replication Stress: A Promising Strategy for Enhancing TOP1i-ADC Efficacy

Presenter: Reeja Maskey, Ph.D.

Date and time: Monday September 8th, 10:30 AM – 12:00 PM (CET)

Session: P2.10 – Metastatic Non-small Cell Lung Cancer – Antibody-Drug Conjugate and Cytotoxic Therapy

The oral presentation and poster will be available online at View Source following the presentation.

On July 22, 2025 Caris Life Sciences (NASDAQ: CAI), a leading, patient-centric, next-generation AI TechBio company and precision medicine pioneer, reported original data in the New England Journal of Medicine independently validating recent findings on tumor-infiltrating clonal hematopoiesis (TI-CH), and further reinforcing its leadership in precision oncology (Press release, Caris Life Sciences, JUL 22, 2025, View Source [SID1234654473]).

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As a champion of scientific collaboration, Caris appreciated the opportunity to validate a recent study published in the New England Journal of Medicine, which brought attention to the clinical challenge of TI-CH—blood-derived mutations that infiltrate tumor tissue and are often misinterpreted as tumor-specific mutations. These misinterpretations can lead to inappropriate treatment decisions and poorer patient outcomes.

"The ability to validate important studies shows how collaboration between Caris scientists and a Caris Precision Oncology Alliance member can quickly respond to and confirm new discoveries, enhancing clinically meaningful insights for oncologists and their patients," said David Spetzler, MS, PhD, MBA, President of Caris. "This precision ensures that treatment decisions are based on true tumor biology, ultimately leading to better outcomes for patients."

Caris built on the findings from the study and analyzed 3,255 matched tumor–blood NGS samples from its extensive real-world clinico-genomic database of over 500,000 samples. The study focused on patients with late-stage cancer and confirmed TI-CH is prevalent across solid tumors, with the highest incidence in non-small cell lung cancer (NSCLC) – approximately 1 in every 4 patients (23%). Patients with TI-CH have worse outcomes, with a 30% higher risk of death compared to patients without TI-CH.

"Clonal hematopoietic mutations play a critical role in the precision oncology puzzle," said George W. Sledge, Jr., MD, Caris EVP and Chief Medical Officer. "Understanding their role in treatment response will lead to improved patient outcomes."

On July 21, 2025 Orion’s collaboration partner Bayer reported that the European Commission has granted marketing authorization in the European Union (EU) for darolutamide, an oral androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) (Press release, Orion, JUL 21, 2025, View Source [SID1234654457]). The approval is based on positive results from the pivotal Phase III ARANOTE trial, which showed that darolutamide plus ADT significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR 0.54; 95% CI 0.41–0.71; P<0.0001) in patients with mHSPC.

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Darolutamide, under the brand name Nubeqa, is already approved in over 85 countries for use with ADT and docetaxel in mHSPC, and with ADT alone in non-metastatic castration-resistant prostate cancer (nmCRPC) in patients who are at high risk of developing metastatic disease. Darolutamide is developed jointly by Orion and Bayer.

Prostate cancer is the second most common cancer and the fifth most common cause of cancer death in men worldwide. In 2022, an estimated 1.5 million men were diagnosed with prostate cancer, and about 397,000 died from the disease worldwide.1 In Europe, there were almost 474,000 estimated new cases of prostate cancer in 2022 with approximately 115,000 deaths. 2 Prostate cancer diagnoses are projected to increase to 2.9 million by 2040.3

About the ARANOTE trial

The ARANOTE trial is a randomized, double-blind, placebo-controlled Phase III study designed to assess the efficacy and safety of darolutamide plus ADT in patients with mHSPC. 669 patients were randomized 2:1 to receive 600mg of darolutamide twice daily or matching placebo in addition to ADT.

The primary endpoint of this study is radiological progression free survival (rPFS), measured as time from randomization to date of first documented radiological progressive disease or death due to any cause, whichever occurs first. Secondary endpoints include overall survival (time to death from any cause), time to first castration resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety assessments.

Results from the Phase III ARANOTE trial presented at ESMO (Free ESMO Whitepaper) 2024 and published in The Journal of Clinical Oncology showed that darolutamide plus ADT significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR 0.54; 95% CI 0.41–0.71; P<0.0001), in patients with mHSPC. Consistent benefits in rPFS were observed across prespecified subgroups, including patients with high-volume (HR 0.60, 95% CI: 0.44-0.80) and low-volume (HR 0.30, 95% CI: 0.15-0.60) mHSPC. The incidence of adverse events in the treatment group with darolutamide plus ADT in the ARANOTE study was comparable to placebo plus ADT. Darolutamide plus ADT was generally well tolerated and showed lower discontinuation rates due to adverse events compared to placebo plus ADT.

About darolutamide

Darolutamide is an oral ARi with a unique chemical structure that binds with high affinity to the androgen receptor and exhibits a strong antagonistic effect against the androgen receptor inhibiting the receptor function and the growth of prostate cancer cells. Additionally, preclinical models and neuroimaging data in healthy humans, support darolutamide’s low potential for blood-brain barrier penetration.

Darolutamide (plus ADT or plus ADT and docetaxel) demonstrated a side effect profile, in both mHSPC registrational studies where the incidences of adverse events were roughly similar to the respective comparator arm. Darolutamide is a treatment option for doctors and patients, considering its tolerability and low risk of drug interaction.

A robust clinical development program is underway investigating darolutamide across various stages of prostate cancer. The program includes the Phase III ARASTEP trial evaluating darolutamide plus ADT compared to ADT alone in hormone-sensitive high-risk biochemical recurrence (BCR) prostate cancer, who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline. Furthermore, darolutamide is also being investigated by Bayer in the collaborative Phase III DASL-HiCaP (ANZUP1801) trial led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). The study evaluates darolutamide as a treatment for localized prostate cancer in combination with radiotherapy.

About metastatic hormone-sensitive prostate cancer

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. mHSPC is a stage in the disease where the cancer has spread outside of the prostate to other parts of the body. Up to 10% of men will present with mHSPC when first diagnosed.4,5,6 For patients with mHSPC, ADT is the cornerstone of treatment, in combination with chemotherapy docetaxel and/or an androgen receptor inhibitor (ARi).

Despite treatment, most men with mHSPC will eventually progress to castration-resistant prostate cancer (CRPC), a condition with limited survival.

On July 21, 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 European Commission (EC) has granted marketing authorization for AUCATZYL (obecabtagene autoleucel or "obe-cel") for the treatment of adult patients, 26+, with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-ALL) (Press release, Autolus, JUL 21, 2025, View Source [SID1234654458]).

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The EC approval 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 were published in the New England Journal of Medicine in November 20241. 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%).

"We believe AUCATZYL represents an important new treatment option for physicians treating adult r/r B-ALL patients. With the EU marketing authorization, we are now evaluating market entry opportunities in EU countries," said Dr. Christian Itin, Chief Executive Officer of Autolus.

Obe-cel 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.

ALL is an aggressive type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. In Europe, there are approximately 6,0002 new cases of ALL diagnosed every year. In frontline treatment for adult B-ALL, up to 50% of patients will ultimately relapse3. Survival rates remain very poor in adult patients with r/r ALL, with median overall survival of eight months with conventional treatments4, and the standard-of-care treatment can trigger severe toxicities5.

The EC approval applies to all 27 European Union Member States, Iceland, Norway and Liechtenstein. AUCATZYL is currently approved by the U.S. Food and Drug Administration (FDA) and authorized by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA).

On July 21, 2025 ImCheck Therapeutics reported that the European Medicines Agency (EMA) has granted Orphan Drug Designation (ODD) to its lead program, ICT01, a humanized anti-butyrophilin 3A (BTN3A) monoclonal antibody designed to selectively activate γ9δ2 T cells, for the treatment of acute myeloid leukemia (AML) (Press release, ImCheck Therapeutics, JUL 21, 2025, View Source [SID1234654459]). The designation in the EU follows the recently granted U.S. FDA ODD and provides additional validation of the therapeutic potential of ICT01 in AML, a disease with high unmet medical need and limited treatment options for older or unfit patients who are not eligible for intensive chemotherapy.

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"Securing orphan drug designation from both the EMA and the FDA in close succession is a major regulatory milestone for ImCheck,"said Pierre d’Epenoux, Chief Executive Officer of ImCheck Therapeutics."It reflects growing international recognition of ICT01’s potential and supports our objective to accelerate clinical development in both the U.S. and Europe. The EMA ODD’s broad market exclusivity for ICT01 once approved provides additional value as we consider our development strategy."

"The EMA’s rapid decision reinforces the highly encouraging clinical data supporting ICT01 and its differentiated mechanism of action," added Stephan Braun, MD, PhD, Chief Medical Officer of ImCheck Therapeutics. "By selectively activating γ9δ2 T cells, a powerful component of the immune system, ICT01 offers a novel therapeutic pathway in AML. This momentum brings us closer to our goal of delivering new therapeutic options to AML patients who currently have limited treatment options."

The EMA’s orphan drug designation is granted to medicines intended for the treatment of life-threatening or chronically debilitating rare conditions affecting fewer than 5 in 10,000 people in the EU. Benefits of the designation include protocol assistance, reduced regulatory fees, and ten years of market exclusivity in Europe following approval.