On March 3, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy in oncology and autoimmune diseases, reported that Ipsen (Euronext: IPN; ADR: IPSEY) has nominated a second drug candidate (DC) under its multi-year strategic oncology collaboration with Marengo (Press release, Marengo Therapeutics, MAR 3, 2025, View Source [SID1234650853]).

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This nomination marks the successful advancement of the second STAR bispecific T cell activator program included in the partnership between Ipsen and Marengo since it began in August 2022. The first DC nomination under the collaboration was announced in April 2024.

"This second DC nomination is a testament to our strong collaboration with Ipsen and once again underscores the dedication and ingenuity of Marengo’s research team in advancing innovative immunotherapy candidates to clinical trials," said Andrew Bayliffe Ph.D., Chief Scientific Officer of Marengo. "Our novel, first in class TCRVβ-targeted dual T cell agonists drive the revitalization of anti-tumor T cell responses in immunotherapy refractory tumor models, and we look forward to working with Ipsen as we translate this potential into people living with cancer."

Under the terms of the agreement, Marengo will receive a milestone payment for this pre-defined pre-clinical milestone. Per the agreement, Marengo has led research and preclinical development efforts in partnership with Ipsen. Ipsen will assume responsibilities for IND filing, regulatory submissions, clinical development and commercialization.

On March 3, 2025 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported a business update and reported financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Mersana Therapeutics, MAR 3, 2025, View Source [SID1234650836]).

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"We made significant progress advancing the clinical development of Emi-Le in 2024," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "These efforts enabled us to begin 2025 by announcing positive initial Phase 1 clinical data, the initiation of expansion and a Fast Track designation for HER2-negative breast cancer patients who have previously been treated with at least one topo-1 ADC. With promising monotherapy activity reported in patients across multiple tumors, including those with heavily pretreated triple-negative breast cancer, as well as a differentiated tolerability profile that may enable combination approaches, we believe Emi-Le offers us unique development opportunities that are unavailable to other B7-H4 ADCs."

Emiltatug Ledadotin (Emi-Le; XMT-1660)
In January 2025, Mersana announced positive initial Phase 1 clinical data for Emi-Le, the company’s lead Dolasynthen ADC candidate targeting B7-H4, from 130 patients who were enrolled in dose escalation and backfill cohorts as of a December 13, 2024 data cutoff. The company also announced that Emi-Le had received a second Fast Track designation from the U.S. Food and Drug Administration (FDA).

The expansion portion of the company’s Phase 1 clinical trial continues at a dose of 67.4 mg/m² administered every four weeks in patients with TNBC who had received one to four prior lines of therapy, including at least one topo-1 ADC. In parallel, the company continues to explore higher doses in dose escalation and backfill cohorts to identify a second dose for expansion.

In 2025, Mersana plans to initiate expansion enrollment at a second dose in patients with TNBC who have received one to four prior lines of treatment, including at least one prior topo-1 ADC. The company also plans to present additional Phase 1 clinical data from dose escalation and backfill cohorts in 2025.

XMT-2056
Mersana has continued to advance the dose escalation portion of its Phase 1 clinical trial of XMT-2056, the company’s lead Immunosynthen ADC candidate targeting a novel HER2 epitope. GSK plc has an exclusive global license option to co-develop and commercialize XMT-2056. Mersana plans to continue enrolling patients in dose escalation and expects to present initial clinical pharmacodynamic STING activation data for XMT-2056 in 2025.

Collaborations
Mersana continues to advance its collaborations with both Johnson & Johnson (Dolasynthen research collaboration) and Merck KGaA, Darmstadt, Germany (Immunosynthen research collaboration).

Fourth Quarter 2024 Financial Results

Cash, cash equivalents and marketable securities as of December 31, 2024 were $134.6 million. Mersana continues to expect that its capital resources will be sufficient to support its current operating plan commitments into 2026.
Net cash used in operating activities for the fourth quarter of 2024 was $19.3 million.
Collaboration revenue for the fourth quarter of 2024 was $16.4 million, compared to $10.7 million for the same period in 2023. The year-over-year change was primarily related to increased collaboration revenue recognized under Mersana’s collaboration and license agreements with Johnson & Johnson, Merck KGaA, Darmstadt, Germany and GSK.
Research and development (R&D) expenses for the fourth quarter of 2024 were $22.3 million, compared to $21.5 million for the same period in 2023. Included in the fourth quarter of 2024 R&D expenses were $1.7 million in non-cash stock-based compensation expenses. The year-over-year increase in R&D expenses was primarily related to increased costs associated with manufacturing and clinical development activities for Emi-Le and XMT-2056, primarily offset by reduced costs related to clinical development activities for UpRi, a discontinued ADC candidate.
General and administrative (G&A) expenses for the fourth quarter of 2024 were $8.9 million, compared to $10.1 million during the same period in 2023. Included in the fourth quarter of 2024 G&A expenses were $1.7 million in non-cash stock-based compensation expenses. The year-over-year decline in G&A expenses was primarily related to reduced employee compensation expense following the company’s 2023 restructuring and reduced consulting and professional services fees.
Net loss for the fourth quarter of 2024 was $14.1 million, or $0.11 per share, compared to a net loss of $19.5 million, or $0.16 per share, for the same period in 2023.
Full Year 2024 Financial Results

Net cash used in operating activities for full year 2024 was $82.3 million.
Collaboration revenue for full year 2024 was $40.5 million, compared to $36.9 million for 2023. The year-over-year increase was primarily related to incremental milestone payments associated with the company’s Johnson and Johnson collaboration and license agreement.

R&D expenses for full year 2024 were $73.0 million, compared to $148.3 million for the full year 2023. Included in 2024 R&D expenses were $8.9 million in non-cash stock-based compensation expenses. The decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical development activities for UpRi, reduced employee compensation expenses following the company’s restructuring in 2023, and reduced consulting and professional services fees, partially offset by increased costs for clinical development activities for Emi-Le.
G&A expenses for full year 2024 were $40.8 million, compared to $59.5 million for the full year 2023. Included in 2024 G&A expenses were $7.6 million in non-cash stock-based compensation expenses. The year-over-year decline in G&A expenses was primarily related to reduced consulting and professional services fees and reduced employee compensation expense following the aforementioned restructuring.
Net loss for full year 2024 was $69.2 million, or $0.56 per share, compared to a net loss of $171.7 million, or $1.48 per share, for the full year 2023.

Conference Call Reminder

Mersana will host a conference call today at 8:00 a.m. ET to discuss business updates and its financial results for the fourth quarter and full year of 2024. To access the call, please dial 833-255-2826 (domestic) or 412-317-0689 (international). A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com, and a replay of the webcast will be available in the same location following the conference call for approximately 90 days.

On March 3, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a research collaboration with ATTMOS as part of its efforts to build a physics-based computational small molecule discovery platform that rapidly unlocks what are currently perceived as undruggable oncology targets (Press release, Ideaya Biosciences, MAR 3, 2025, View Source [SID1234650854]).

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The collaboration will integrate IDEAYA’s differentiated and proven capabilities in structural biology and pharmaceutical drug discovery across multiple first-in-class oncology targets with ATTMOS’s capabilities in computational chemistry method development, high performance computing, and software development. The focus of the partnership will be to engineer and optimize a workflow solution for high-throughput absolute binding free energy perturbation predictions (ABFEP) of first-in-class drug candidate molecules. This approach enables application of gold-standard physics-based statistical mechanics calculations of protein-ligand affinities at the scale required for virtual screens and represents what could become the industry’s go-to standard for high-speed and high probability-of-success drug hit-finding against structurally-enabled novel biological targets.

"Current AI/ML-enabled drug discovery approaches have been largely applied to either already drugged targets or well-understood biological target classes and often fail when applied to first-in-class target opportunities. IDEAYA continues to enhance its computational drug discovery capabilities to pursue first-in-class oncology targets that are perceived as undruggable," said Michael White, Ph.D., Chief Scientific Officer, IDEAYA Biosciences. "Our partnership with ATTMOS will enable us to apply the principles of engineering to the field of drug discovery, at scale, for efficient prosecution of unprecedented oncology targets," said Paul Barsanti, Ph.D., Chief Technology Officer, IDEAYA Biosciences.

The collaboration will leverage the Amber molecular dynamics suite as the GPU-accelerated back-end free energy simulation engine. IDEAYA will train and evaluate ABFEP-based active learning cycles based on extensive ground-truth data sets derived from its successful wet-lab drug discovery campaigns against novel targets. These models will be used to screen enormous libraries of synthetically tractable chemical space for accurate and efficient de novo discovery of small molecule ligands for new targets. The work aims to overcome the limitations of current virtual screening approaches and accelerate the discovery of novel small molecule oncology therapeutics that address unmet clinical need.

On March 3, 2025 Pliant Therapeutics, Inc. (Nasdaq: PLRX), a clinical-stage biotechnology company and leader in the discovery and development of novel therapeutics for the treatment of fibrotic diseases, reported a corporate update and reported fourth quarter 2024 financial results (Press release, Pliant Therapeutics, MAR 3, 2025, View Source [SID1234650837]).

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Fourth Quarter and Recent Highlights
Bexotegrast Highlights
•BEACON-IPF discontinued following recommendation from expanded data safety monitoring board (DSMB). Following a prespecified data review and recommendation by the trial’s independent DSMB, as well as a secondary review and recommendation by an outside expert panel, Pliant has discontinued the BEACON-IPF Phase 2b trial. While an imbalance in unadjudicated IPF-related adverse events between the treatment and placebo groups led to the discontinuation of the trial, early evidence of efficacy on the forced vital capacity (FVC) endpoint was also observed. The Company plans to analyze the complete data from the BEACON-IPF trial and evaluate next steps for bexotegrast’s development. BEACON-IPF is a 52-week, multinational, randomized, dose-ranging, double-blind, placebo-controlled trial evaluating bexotegrast at once-daily doses of 160 mg or 320 mg in patients with idiopathic pulmonary fibrosis (IPF).

Oncology Program
•Phase 1 trial of PLN-101095 in solid tumors continues to enroll, with interim data expected in the first quarter 2025. This is a Phase 1 open label trial of PLN-101095, an oral, small molecule, dual selective inhibitor of αvβ8 and αvβ1 integrins designed to block TGF-β activation in the tumor microenvironment. The trial is currently dosing the fourth of five planned dose cohorts in a Phase 1 open label dose-escalation trial of PLN-101095 as monotherapy and in combination with pembrolizumab in patients with solid tumors that are resistant to immune checkpoint inhibitors. Interim data from the first three cohorts is expected in the first quarter of 2025.

Neuromuscular Program
•PLN-101325 for treatment of muscular dystrophies. PLN-101325 is a monoclonal antibody that acts as an allosteric agonist of integrin α7β1, currently in development for treatment of muscular dystrophies. PLN-101325 is Phase 1 ready with clinical trial approval (CTA) open in Australia.

Corporate Highlights
•Appointment of Delphine Imbert, Ph.D. as Chief Technical Officer. Dr. Imbert brings 25 years of product development, process optimization and manufacturing experience across multiple drug modalities. Most recently, Dr. Imbert served as Senior Vice President of CMC and Technical Operations at Chinook Therapeutics.

Fourth Quarter 2024 Financial Results
•Research and development expenses were $38.8 million, as compared to $33.2 million for the prior-year quarter. The increase was primarily due to costs associated with the BEACON-IPF Phase 2b/3 clinical trial.
•General and administrative expenses were $14.5 million, as compared to $13.9 million for the prior-year quarter. The increase was primarily due to employee-related expenses driven by increased headcount over prior year.

•Net loss was $49.7 million as compared to $41.1 million for the prior-year quarter. The increase was due to higher operating expenses primarily attributable to costs associated with the BEACON-IPF Phase 2b/3 clinical trial and reduced interest income on short-term investments.
•As of December 31, 2024, the Company had cash, cash equivalents, restricted cash and short-term investments of $357.2 million which the Company expects to be sufficient to fund operations for the next 12 months and beyond.

On March 3, 2025 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, reported that the first patient has been successfully dosed in the global multicenter Phase I clinical trial of its novel PD-1/VEGF/CTLA-4 trispecific antibody, CS2009, with no infusion reactions or other adverse events observed (Press release, CStone Pharmaceauticals, MAR 3, 2025, View Source [SID1234650855]).

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This trial aims to evaluate the clinical potential of CS2009 in a wide range of advanced solid tumors including, but not limited to, non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer, in efforts to advance the development of innovative tumor immunotherapies.

CS2009, an innovative trispecific antibody designed and developed by CStone, combines three clinically validated targets—PD-1, VEGFA, and CTLA-4—and exerts multidimensional anti-tumor effects through synergistic actions. Specifically, anti-PD-1 activity that reverses T cell exhaustion, anti-CTLA-4 activity that promotes T cell activation and proliferation, while anti-VEGFA activity blocks tumor angiogenesis and improves the tumor micro-environment (TME). In the TME, anti-PD-1 and anti-CTLA-4 activities are significantly enhanced by crosslinking with VEGFA. Meanwhile, CS2009 preferentially blocks PD-1 and CTLA-4 on double-positive tumor-infiltrating T cells while minimizing interference with CTLA-4 regulation in peripheral T cells, thus potentially offering enhanced efficacy with lower systemic toxicity.

In preclinical studies, CS2009 demonstrated superior anti-tumor activity compared to potential competitors. By combining CTLA-4 inhibition with PD-1 and VEGFA blockade, CS2009 may further enhance benefits for patients with low or negative PD-L1 expression, who respond poorly to PD-(L)1 therapies. This well positions CS2009 as a next-generation, first- or best-in-class immunotherapy backbone, with the potential to replace current anti-PD-(L)1-based therapies.

Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, stated, "The initiation of the first-in-human study for CS2009 marks a breakthrough in our clinical development. Our robust preclinical data have confirmed CS2009’s potential across a wide range of solid tumor indications. In in vitro studies, CS2009 demonstrated its ability to effectively and specifically activate tumor-infiltrating T cells, as well as robust synergistic effect with anti-VEGF activity; in immunocompetent mouse models, CS2009 showed stronger anti-tumor effects than both PD-1/CTLA-4 and PD-1/VEGF bispecific antibodies; and in toxicology studies, CS2009 exhibited a safety margin which was greater than the PD-1/CTLA-4 bispecific antibody and comparable to the PD-1/VEGF bispecific antibody. These results give us confidence in CS2009’s clinical potential. We look forward to sharing additional clinical data that will further validate its safety and anti-tumor activity, paving the way for a new era in cancer immunotherapy."

Dr. Qingmei Shi, Chief Medical Officer of CStone, added, "We are pleased to achieve the first-patient-dosed milestone for CS2009, an innovative trispecific antibody that can potentially offer balanced efficacy and safety while addressing the unmet medical needs in patients with low or negative PD-L1 expression. We expect to see rapid and encouraging progress in this study and are committed to bringing improved treatment options to patients with solid tumors worldwide. We appreciate the exceptional efforts of our clinical team, who managed through the entire process—from submitting the clinical trial application in Australia to dosing the first patient—in two months that overlapped with major holidays in China and Australia. This is another testament to CStone’s outstanding clinical development efficiency and unwavering commitment to serving patients."

Currently, the multicenter Phase I clinical trial of CS2009 is being conducted in Australia, with plans to expand into China and the United States in the near future.

About CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody)

CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4, with the potential to be first- or best-in-class for major tumor types. Its differentiated molecular design combines three clinically validated targets, preferentially invigorating exhausted tumor infiltrating lymphocytes (TILs) while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including but not limited to non-small cell lung cancer, hepatocellular carcinoma, gastric adenocarcinoma, endometrial cancer, ovarian cancer, renal cell carcinoma, and cervical cancer.

In November 2024, CStone presented preclinical data for CS2009 at the 39th SITC (Free SITC Whitepaper) Annual Meeting. These results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-1/CTLA-4 bispecific antibodies, PD-1/VEGF bispecific antibodies, and PD-1/CTLA-4 combination therapies.