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.

On March 2, 2025, Akari Therapeutics, Plc (the "Company") reported to have entered into a securities purchase agreement (the "Purchase Agreement") with certain investors, including the Company’s Chairman, Dr. Hoyoung Huh, director, President and Chief Executive Officer, Dr. Samir R. Patel, and all other members of the Company’s board, pursuant to which the Company agreed to sell and issue in a private placement (the "Offering") an aggregate of 6,637,626 unregistered American Depository Shares ("ADSs"), each representing 2,000 of the Company’s ordinary shares (the "Shares"), or prefunded warrants in lieu thereof ("Pre-Funded Warrants"), and, in each case, Series A warrants to purchase ADS ("Series A Warrants") and Series B warrants to purchase ADS ("Series B Warrants", together with the Pre-Funded Warrants and Series A Warrants, the "Warrants," and together with the ADSs or Pre-Funded Warrants, the "Units")) (Filing, 8-K, Akari Therapeutics, MAR 2, 2025, View Source [SID1234650820]). The Units consist of (i) for investors committing less than $1.0 million in the Offering ("Tier 1 Investors") one ADS or Pre-Funded Warrant plus a Series A Warrant to purchase one ADS and a Series B Warrant to purchase one ADS, (ii) for investors committing at least $1.0 million but less than $3.0 million in the Offering ("Tier 2 Investors") one ADS or Pre-Funded Warrant plus a Series A Warrant to purchase 1.25 ADSs and a Series B Warrant to purchase one ADS, and (iii) for investors committing $3.0 million or more in the Offering ("Tier 3 Investors"), one ADS or Pre-Funded Warrant plus a Series A Warrant to purchase 1.5 ADSs and a Series B Warrant to purchase one ADS. The purchase price per Unit for investors purchasing ADSs is equal to $0.87 plus (a) $0.25 cents for Tier 1 Investors, (b) $0.28125 cents for Tier 2 Investors, or (c) $0.3125 for Tier 3 Investors (the "ADS Unit Purchase Price"). The purchase price per Pre-Funded Warrant and accompanying Series A Warrant and Series B Warrant is equal to $0.67 (which represents the ADS purchase price minus the $0.20 exercise price for such Pre-Funded Warrant) plus (a) $0.25 cents for Tier 1 Investors, (b) $0.28125 cents for Tier 2 Investors, or (c) $0.3125 for Tier 3 Investors (the "Pre-Funded Unit Purchase Price").

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In addition, Dr. Huh, the Company’s Chairman, agreed to purchase $1 million of Units, with the purchase price thereof to be satisfied through his agreement to terminate a $1 million convertible note previously issued to him by the Company (the "Note Termination").

The gross proceeds from the Offering, including the $1 million Note Termination, and excluding the proceeds to be received upon exercise of the Pre-Funded Warrants, are expected to be approximately $7.1 million before deducting approximately $401,000 representing the fees and expenses of the placement agent payable by the Company. The Company intends to use the net proceeds from the Offering for working capital and general corporate purposes.

The Series A and Series B Warrants will have an exercise price of $0.87 per ADS, which is equal to the Nasdaq official closing price of the Company’s ADSs on the Nasdaq Capital Market on February 28, 2025 and will be exercisable immediately following the date of issuance. The Series A Warrants and Series B Warrants will expire one year or five years, respectively, from the closing date of the Offering. The Pre-Funded Warrants will be exercisable immediately and may be exercised at any time until all of the Pre-Funded Warrants are exercised in full.

The Company paid Paulson Investment Company, LLC ("Paulson") (the "Placement Agent") (i) a cash fee equal to 7% (or 3.5% for any investor that is a director, insider or affiliate of the Company) of the aggregate purchase price for the Units sold in the Offering (and excluding the Units issued to Dr. Huh in respect to the Note Termination) and (ii) 3% of the total number of ADS issued in the Offering, including any of the ADSs issuable upon exercise of the Pre-Funded Warrants (and excluding the ADSs issued to Dr. Huh in respect to the Note Termination).

Pursuant to the Purchase Agreement, the Company has agreed to prepare and file a registration statement on Form S-3 with the Securities and Exchange Commission no later sixty days following the closing of the Offering to register the resale of the Shares (including ADSs issuable upon exercise of the Warrants) purchased pursuant to the Purchase Agreement. The Purchase Agreement also contains representations, warranties, indemnification and other provisions customary for transactions of this nature. The Offering is expected to close on March 5, 2025, subject to the satisfaction of customary closing conditions.

The securities to be issued to the purchasers under the Purchase Agreement were offered in reliance on an exemption from registration provided by Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act") and Rule 506 of Regulation D promulgated thereunder. The Company relied on this exemption from registration based in part on representations made by the purchasers, including that each purchaser is an "accredited investor", as defined in Rule 501(a) promulgated under the Securities Act.

The offer and sale of the securities pursuant to the Purchase Agreement have not been registered under the Securities Act or any state securities laws. The securities may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements. Neither this Current Report on Form 8-K, nor the exhibits attached hereto, is an offer to sell or the solicitation of an offer to buy the securities described herein or therein.

The foregoing summary of the terms of the Warrants and the Purchase Agreement is subject to, and qualified in its entirety by, the full text of such agreements, which are filed as Exhibits 4.1, 4.2, 4.3 and 10.1, respectively, to this Current Report on Form 8-K and are incorporated by reference herein.

On March 2, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology, and other major diseases, reported that the first patient has been dosed in its registrational study evaluating IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, as monotherapy versus pembrolizumab (Keytruda) in patients with unresectable locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy (Press release, Innovent Biologics, MAR 2, 2025, View Source [SID1234650787]). This is IBI363’s first pivotal study and a significant milestone for China’s innovative immuno-oncology (IO) therapy in addressing the global challenge of treating "cold tumors."

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This is a randomized, multicenter, pivotal study designed to evaluate the efficacy and safety of IBI363 monotherapy versus pembrolizumab monotherapy in patients with unresectable, locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy. The primary endpoint is progression-free survival (PFS), as assessed by an Independent Radiology Review Committee (IRRC) based on RECIST v1.1 criteria.

IBI363 has demonstrated outstanding efficacy signals in immunotherapy (IO)-naïve melanoma patients across two earlier clinical trials (Phase 1a/1b study NCT05460767 and Phase 2 study NCT06081920), which enrolled a total of 26 patients with advanced acral or mucosal melanoma:

The overall objective response rate (ORR) was 61.5%, and the disease control rate (DCR) was 84.6%—significantly higher than current domestic immunotherapy standards.
Prolonged follow-up revealed sustained tumor responses and long-term benefits, suggesting the potential superiority of IBI363 over existing standard therapies.
These preliminary data were presented at SITC (Free SITC Whitepaper) 2024[1], and updated follow-up results will be shared at international conferences in 2025.

IBI363 has also demonstrated a manageable safety profile. To date, IBI363 monotherapy or combination therapy has been administered to hundreds of patients with advanced solid tumors globally. The overall safety profile remains consistent with known toxicities of PD-1/PD-L1 and IL-2 therapies, with common treatment-related adverse events (TRAEs) including arthralgia, anemia, thyroid dysfunction, and rash—all of which are manageable with routine clinical care.

Professor Jun Guo, Principal Investigator of the Study and Director of Peking University Cancer Hospital, stated: "Melanoma has a high mortality rate in China, and its incidence is rising annually. IO-naïve melanoma patients currently have a median PFS of only around three months, reflecting a significant unmet clinical need. Moreover, non-cutaneous subtypes like mucosal melanoma—which are more prevalent in China—are particularly resistant to immunotherapy with limited clinical benefits. IBI363 has shown the potential to convert ‘cold tumors’ into ‘hot tumors’ by the dual activation of PD-1 and IL-2 pathways. Encouraging efficacy observed in Phase 1a/1b and 2 studies suggest its potential as a next-generation IO therapy for melanoma. Along with my fellow investigators, I hope this trial will lead to more effective treatment options for patients with acral and mucosal melanoma."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "As Innovent’s first-in-class next-generation IO therapy, IBI363 simultaneously and selectively inhibits the PD-1/PD-L1 pathway and activates the IL-2 pathway. In previous studies, IBI363 has demonstrated outstanding efficacy and safety in melanoma and multiple cancer types. This pivotal trial, through a head-to-head comparison with pembrolizumab, aims to validate IBI363’s potential as a superior treatment option for melanoma patients over the current standard-of-care. We are also accelerating the global development of IBI363 across multiple tumor types, with the goal of extending the benefits of China’s innovation to patients worldwide."

About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein))

IBI363 is a first-in-class drug candidate independently developed by Innovent Biologics. It is a PD-1/IL-2 bispecific antibody fusion protein designed to enhance efficiency while minimizing toxicity. The IL-2 arm of IBI363 has been engineered to optimize therapeutic effects with reduced side effects, while the PD-1 binding arm enables PD-1 blockade and selective IL-2 delivery. By simultaneously inhibiting the PD-1/PD-L1 pathway and activating the IL-2 pathway, IBI363 facilitates more precise and efficient targeting and activation of tumor specific T cells. Preclinical studies have shown that IBI363 exhibits strong anti-tumor activity across multiple tumor-bearing pharmacological models, including those resistant to PD-1 inhibitors and metastatic models. Additionally, it has demonstrated a favorable safety profile in preclinical models.

Clinical trials of IBI363 are currently underway in China, the United States, and Australia to evaluate its safety, tolerability and preliminary efficacy in subjects with advanced malignancies. The first pivotal study of IBI363 has been initiated, for the treatment of IO-naive mucosal or acral melanoma. Furthermore, IBI363 has received two fast track designations (FTD) from the U.S. FDA, for the treatment of squamous non-small cell lung cancer and melanoma, respectively.

On March 2, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) to satricabtagene autoleucel ("satri-cel", CT041) for the treatment of Claudin18.2-positive advanced gastric/gastroesophageal junction cancer (G/GEJ) in patients who have failed at least two prior lines of therapy (Press release, Carsgen Therapeutics, MAR 2, 2025, View Source [SID1234650789]).

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The company plans to submit a New Drug Application (NDA) for satri-cel to the NMPA in the first half of 2025.

"We are fully committed to advancing the preparation work for the NDA submission of satri-cel. We are delighted that satri-cel has received Breakthrough Therapy Designation, which is expected to expedite its approval process and bring this therapy to patients as soon as possible," said Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics.

About Satri-cel

Satri-cel is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be the first-in-class globally. Satri-cel targets the treatment of Claudin18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). Ongoing trials include investigator-initiated trials (CT041-CG4006, NCT03874897), a confirmatory Phase II clinical trial for advanced gastric/gastroesophageal junction cancer in China (CT041-ST-01, NCT04581473), a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). Satri-cel was granted Regenerative Medicine Advanced Therapy (RMAT) designation by U.S. FDA for the treatment of advanced GC/GEJ with Claudin18.2-positive tumors in January 2022. Satri-cel received Orphan Drug designation from the U.S. FDA in September 2020 for the treatment of GC/GEJ.