On April 25, 2025 CatalYm reported the presentation of the first preclinical data demonstrating that the company’s clinical-stage antibody visugromab can improve the anti-tumor activity of antibody-drug conjugates (ADCs). The data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place in Chicago, IL, April 25-30, 2025 (Press release, Catalym, APR 25, 2025, View Source [SID1234652140]). The poster will highlight the potential of targeting Growth Differentiation Factor 15 (GDF-15) to enhance the activity and overcome resistance to ADC therapies, which are increasingly used as frontline treatments in several solid tumor indications. The full abstract is available on the AACR (Free AACR Whitepaper) Annual Meeting website.

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The study showed that several clinically validated ADCs, including topoisomerase I and microtubule inhibitor-based regimens, consistently triggered GDF-15 expression, suggesting a potential resistance mechanism to ADC therapy. Across in vitro and in vivo models of multiple solid tumor types, ADC treatment induced GDF-15 release from tumor cells, leading to elevated serum levels and reduced ADC efficacy. Combining ADC treatment with GDF-15 neutralization improved anti-tumor responses, resulting in reduced tumor growth and enhanced infiltration and activation of T cells and myeloid cells in the tumor microenvironment.

"We are building a broader understanding of GDF-15 as a key resistance mechanism activated by targeted approaches like ADCs as well as the leading immunotherapies like PD-1 inhibitors," said Christine Schuberth-Wagner, PhD, Chief Scientific Officer at CatalYm. "By blocking GDF-15, visugromab restores anti-tumor immune activity and enhances treatment efficacy, underscoring its potential as a versatile combination partner across a broad spectrum of cancer therapies beyond immunotherapies."

"ADCs continue to demonstrate potent and specific therapeutic impact, nevertheless resistance is a significant challenge for long-term patient benefit. In addition to our Phase 2 clinical development program, CatalYm will continue to investigate how our GDF-15 neutralizing antibody visugromab can create a novel path to address cancer resistance effectively," added Scott Clarke, Chief Executive Officer at CatalYm.

The preclinical findings build on clinical evidence from the GDFATHER-1/2a trial (GDF-15 Antibody-mediaTed Human Effector T Cell Relocation Phase 1/2a Trial; NCT04725474), that was recently published in Nature. The data show that visugromab induces deep and durable responses in patients with relapsed or refractory solid tumors who had progressed on prior anti-PD-1/PD-L1 therapies. In addition to restoring anti-tumor immune responses, visugromab also demonstrated the potential to mitigate cancer-associated cachexia. CatalYm is currently conducting a broad, global Phase 2b clinical development program for visugromab, evaluating its effectiveness in earlier treatment lines of non-squamous non-small-cell lung cancer and hepatocellular carcinoma, as well as neoadjuvant treatment in urothelial cancer in combination with standard of care.

Poster details

Session title: "PO.IM01.03 – Antibodies and Antibody-Drug Conjugates"

Abstract title: "GDF-15 neutralization enhances the therapeutic activity of antibody-drug conjugates"

Abstract number: 4777/13

Location: Section 36

Date and time: April 29, 2025, 9:00 AM – 12 PM CT/ 4:00 PM – 7:00 PM CEST

About Visugromab
Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and induction of interferon-γ.

On April 25, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncologic, autoimmune, cardiovascular and metabolic, ophthalmologic and other major diseases, reported that China’s National Medical Products Administration (NMPA) has approved the New Drug Application (NDA) for limertinib as the first-line treatment for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R mutations (Press release, Innovent Biologics, APR 25, 2025, View Source [SID1234652156]). Innovent and ASK Pharm entered into a commercial collaboration agreement for limertinib in Mainland China in 2024.

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The approval of this new indication is supported by positive results from a randomized, double-blind, positive-controlled Phase 3 clinical trial. A total of 337 treatment-naïve patients with EGFR-sensitive mutation-positive locally advanced or metastatic NSCLC were enrolled and randomized 1:1 to receive either limertinib or gefitinib. The primary endpoint was progression-free survival (PFS), as assed by an independent review committee (IRC).

The data showed that limertinib significantly prolonged median PFS compared to gefitinib (20.7 months vs. 9.7 months), representing a 56% risk reduction in disease progression or death (hazard ratio [HR] 0.44; 95% CI: 0.34–0.58; p < 0.0001). In patients with central nervous system (CNS) lesions at baseline, median CNS PFS was also significantly longer with limertinib (20.7 months vs. 7.1 months), corresponding to a 72% risk reduction for CNS progression or death (HR 0.28; 95% CI: 0.10–0.82; p = 0.0136), underscoring its robust intracranial activity and clinical utility in such population with high-unmet-needs.

The safety profile of limertinib was consistent with that of known EGFR-targeted therapies. Adverse events were predominantly mild to moderate and well-tolerated, with no new safety signals identified during the clinical trial. Full data and analysis from this pivotal Phase 3 study will be published in academic journals.

"Limertinib has demonstrated exceptional efficacy and safety as first-line therapy in patients with EGFR-muted locally advanced or metastatic NSCLC, including notable efficacy in those with brain metastases. The approval of this first-line indication introduces a new treatment option for Chinese patients, addressing a critical clinical need in this population." said Professor Shi Yuankai, MD, Department of Medical Oncology at Chinese Academy of Medical Sciences and Principal Investigator of the Phase 3 Clinical Study.

Dr. Hui Zhou, Senior Vice President of Innovent, stated："We are delighted that both the first-line and second-line indications for limertinib have been successively approved. As a next-generation EGFR TKI, limertinib is poised to significantly improve survival outcomes for mutation-positive patients. Innovent has built a rich portfolio of precision therapies for lung cancer—including limertinib, Retsevmo(selpercatinib), Dupert(fulzerasib) and DOVBLERON (taletrectinib)—with ongoing efforts to enhance their synergistic value. We will continue to work closely with Ask Pharm to ensure that limertinib brings a new hope to the broad population of patients with EGFR-mutated NSCLC."

Mr. Jingfei Ma, CEO of ASK Pharm, stated: "Within a few months, limertinib has obtained approvals for both second-line and first-line indications. The approval of the first-line indication further expands its clinical applicability. Meanwhile, ASK Pharm is advancing a clinical trial of limertinib in combination with the cMET inhibitor ASKC202 for patients with NSCLC resistant to third-generation EGFR-TKIs. We look forward to working with our partner Innovent to accelerate the accessibility of limertinib for more patients in need."

About EGFR mutation-positive non-small-cell lung cancer (NSCLC)

Lung cancer remains one of the deadliest and most common cancers globally[1], with NSCLC accounting for approximately 85% of cases. Around 70% of NSCLC patients are diagnosed at locally advanced or metastatic stages that are not amenable to surgical resection. EGFR mutations are particularly prevalent among Asian NSCLC patients, affecting 30% to 50% of cases. EGFR-TKIs are the recommended standard of care in the first-line setting, with third-generation EGFR-TKIs offering the broadest treatment applicability.

About Limertinib

Limertinib is an orally-administrated, third-generation EGFR TKI with proprietary rights. It has been approved by the China’s NMPA for: 1) the treatment of adult patients with locally advanced or metastatic EGFR T790M-mutated non-small cell lung cancer (NSCLC), who have previously experienced disease progression during or after treatment with EGFR TKI; and 2) the first-line treatment of adult patients with locally advanced or metastatic NSCLC carrying EGFR exon 19 deletions or exon 21 L858R mutations.

In October 2024, Innovent and ASK Pharm entered into a strategic collaboration and license agreement for limertinib in Mainland China.

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 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported preclinical data from four pipeline programs during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting taking place in Chicago (Press release, Cogent Biosciences, APR 25, 2025, View Source [SID1234652141]).

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"We welcome the opportunity to present updated results from these programs that represent our exciting pipeline of potential best-in-class targeted therapies," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "These data demonstrate Cogent’s ability to discover and advance novel therapies for rare disease populations with high unmet medical need, and we look forward to continuing to advance these candidates."

Poster Details

Title: Identification of a potent KRAS (ON) inhibitor with selectivity for mutant KRAS over HRAS and NRAS
Session Category: Chemistry
Session Title: Lead Identification and Optimization
Session Date and Time: April 30, 2025 – 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)
Location: Poster Section 25
Poster Board Number: 3
Published Abstract Number: 6974

Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The poster presented today describes Cogent’s internally-developed pan KRAS(ON) inhibitor program with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations. In response to our 30mg/kg oral dose we observed robust PD including 90% tumor growth inhibition in a mouse TGI model. Lead optimization of this series is ongoing.

Title: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitor
Session Category: Experimental and Molecular Therapeutics
Session Title: Kinase and Phosphatase Inhibitors 2
Session Date and Time: April 28, 2025 – 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)
Location: Poster Section 20
Poster Board Number: 5
Published Abstract Number: 3004

Cogent is developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage for the both the H1047R mutation as well as E542K and E545K helical mutants. The phosphoinositide 3-kinase (PI3K) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα.

In the poster being presented today, Cogent’s preclinical candidate CGT6297 demonstrates broad cellular panel profiling across multiple resistant and mutated cell lines, including, for the first time, efficacy against PI3K helical mutations. The poster also showcases the activity of CGT6297 in both ST1056 (H1047R mutant) and MCF-7 (E545K mutant) breast cancer TGI models.

Title: The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitors
Session Category: Clinical Research
Session Title: Targeted Therapies and Combinations 2
Session Date and Time: April 29, 2025 – 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)
Location: Poster Section 34
Poster Board Number: 27
Published Abstract Number: 4729

FGFR inhibitors are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. The poster presented today describes Cogent’s internally-developed FGFR2/3 inhibitor which maintains potency on FGFR2 mutations and is selective against the entire kinome and a broad panel of channels and receptors. Exploratory pharmacokinetics (PK) studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in an AN3 CA model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at >2.5 mg/kg QD or BID and was well-tolerated.

Cogent is currently enrolling patients in an ongoing Phase 1 trial with CGT4859 in patients with confirmed FGFR2 or FGFR3 mutations, including patients with advanced cholangiocarcinoma. The trial is designed to explore the safety, tolerability and clinical activity of escalating doses with the goal of selecting an active and well tolerated dose for further clinical investigation.

Title: Identification of CGT4255 an EGFR-sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetration
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 3
Session Date and Time: April 29, 2025 – 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)
Location: Poster Section 21
Poster Board Number: 1
Published Abstract Number: 5623

Cogent’s potential best-in-class EGFR-sparing, brain-penetrant ErbB2 inhibitor includes potent coverage of key mutations (YVMA, S310F, V842I, L755S) inadequately addressed by currently approved therapies. Activating mutations in the ErbB2 gene have been identified in multiple cancers and demonstrate a tumorigenic role similar to that of ErbB2 amplification. New data presented on this compound describes CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species. In addition, CGT4255 is expected to have equivalent brain to plasma exposure suggesting potential best-in class properties.

All posters will be available on the ‘Posters and Publications’ page of Cogent’s website.

New Leadership Appointments
Cogent also announced today that Ray Frost has joined Cogent as Senior Vice President, Market Access and Adam Boyd, Ph.D. has joined Cogent as Senior Vice President, Corporate Strategy.

Mr. Frost joins Cogent with over 20 years of industry experience. Previously he served as Vice President Market Access at Ono Pharma USA and Zealand Pharma (Zealand). While at Zealand he played an integral part in building the commercial infrastructure to support the launch of their first product. Prior to Zealand he held roles of increasing responsibility in Market Access and Health Policy at Melinta Therapeutics, The Medicines Company, Bayer Healthcare, Eisai and MGI PHARMA. Mr. Frost is a graduate of Hofstra University.

Dr. Boyd joins Cogent with nearly 25 years of industry experience building and leading global teams across Development functions including Biostatistics, Clinical Pharmacology, Clinical Operations, and Data Management. In these roles, he was instrumental in bringing several products to market, including Mektovi (binimetinib), Braftovi (encorafenib), Jakafi (ruxolitinib), and Folotyn (pralatrexate). Prior to joining Cogent, Dr. Boyd was Vice President, Biometrics at Intellia Therapeutics, and prior to that, held various roles of increasing responsibility at Pfizer, Array BioPharma, Novartis, and Allos Therapeutics. Dr. Boyd earned his Ph.D. in Biostatistics from the University of Colorado, where he is currently a member of the Colorado School of Public Health’s Dean’s Advisory Board.

Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)
Cogent also announced today that, on April 14, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of "inducement" equity awards to five new employees, including Mr. Frost and Dr. Boyd, under the company’s 2020 Inducement Plan with a grant date of April 21, 2025. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 446,000 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date.

On April 25, 2025 BillionToOne, a molecular diagnostics company with a mission to create powerful and accurate tests accessible to all, reported several abstract presentations that will be showcased at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 25–30, 2025, in Chicago, IL (Press release, BillionToOne, APR 25, 2025, View Source [SID1234652157]).

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Each abstract highlights BillionToOne’s relentless focus in advancing the field of liquid biopsy technology:

Title: "Tumor fraction estimation and tissue copy number inference using copy number signal from a liquid biopsy assay"
Session Time: 4/29/25 at 9:00 AM – 12:00 PM
Location: Poster Section 20

Title: "Detection of a novel GNA11 processed pseudogene from cfDNA and implications for liquid biopsy"
Session Time: 4/29/25 at 2:00 – 5:00 PM
Location: Poster Section 31

Title: "Circulating cell-free methylated tumor DNA measurements correlate with plasma VAF-based tumor fraction estimates"
Session Time: 4/29/25 at 2:00 – 5:00 PM
Location: Poster Section 32

"These data presented at AACR (Free AACR Whitepaper) represent our dedication in advancing liquid biopsy testing with our proprietary single molecule precision technology and setting new standards in what can be achieved with plasma-based tests," said Dr. Gary Palmer, Chief Medical Officer, Oncology at BillionToOne. "Together, these innovations enhance the accuracy and robustness of ctDNA-based cancer profiling and monitoring, which will ultimately enable more precise treatment decisions for patients."