On March 6, 2025 The board (the "Board") of directors ("Directors", and each a "Director") of the Company reported that the Group has received approval from the National Medical Products Administration of the People’s Republic of China (the "NMPA") for a clinical trial of IMM01 (Timdarpacept) in combination with IMM2510 (palverafusp α) and with or without chemotherapy, for the treatment of advanced malignant tumors (Press release, ImmuneOnco Biopharma, MAR 6, 2025, View Source [SID1234655708]). This significant progress marks another key step in the Company’s rapid advancement of clinical research of IMM01 (Timdarpacept) and IMM2510 (palverafusp α).

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ABOUT IMM01 (TIMDARPACEPT)
IMM01 (Timdarpacept), the Group’s core product, is an innovative molecule targeting CD47. It is the first SIRPα-Fc fusion protein to enter into clinical stage in China. IMM01 (Timdarpacept) designed with immunoglobulin G1 (IgG1) Fc can fully activate macrophages via a dual mechanism — simultaneously blocking the "don’t eat me" signal by disrupting CD47/SIRPα interaction and delivering the "eat me" signal through the engagement of activating Fc-gamma (Fcγ) receptors on macrophages. Furthermore, the CD47-binding domain of IMM01 (Timdarpacept) was specifically engineered to avoid human red blood cell (RBC) binding. With the differentiated molecule design, IMM01 (Timdarpacept) has achieved a favorable safety profile and demonstrated its ability to activate macrophages. IMM01 (Timdarpacept) in combination with azacitidine was granted orphan-drug designation by the Food and Drug Administration of the United States (FDA) for the first-line treatment of CMML in November 2023. The Group owns the global intellectual property rights and commercial rights of IMM01 (Timdarpacept). As of the date of this announcement, in relation to IMM01 (Timdarpacept), the Group owned one patent family, which includes issued patents in China, the United States, Japan and the European Union.

ABOUT IMM2510 (PALVERAFUSP α)
IMM2510 (palverafusp α), independently developed by the Group, is a bispecific molecule with a mAb-Trap structure targeting vascular endothelial growth factor (VEGF) and programmed cell death ligand 1 (PD-L1). IMM2510 (palverafusp α) can inhibit angiogenesis, leading to tumor shrinkage, and sensitize tumor cells to immune responses, while activating T cells, NK cells, and macrophages via the blockade of PD-L1/programmed cell death protein 1 (PD-1) interaction and the induction of Fc-mediated antibody-dependent cellular cytotoxicity (ADCC)/antibody-dependent cellular phagocytosis (ADCP) activity. The Company and Axion Bio, Inc. (formerly known as SynBioTx Inc.), a wholly-owned subsidiary of Instil Bio, Inc. (NASDAQ: TIL), have entered into a license and collaboration agreement, pursuant to which the Company owns the commercial rights of IMM2510 (palverafusp α) in the Greater China region, including mainland China, Hong Kong Special Administrative Region of China, Macau Special Administrative Region of China and Taiwan (the "Greater China Region") and agreed to grant Axion Bio, Inc. an exclusive license to research, develop and commercialize IMM2510 (palverafusp α), outside the Greater China region.

On March 6, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported that it has completed enrollment of its a Phase II trial of fanregratinib (HMPL-453) for intrahepatic cholangiocarcinoma ("IHCC") patients with fibroblast growth factor receptor ("FGFR")2 fusion/rearrangement (Press release, Hutchison China MediTech, MAR 6, 2025, View Source [SID1234650967]).

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The study is a single-arm, multi-center, open-label, Phase II registration study to evaluate the efficacy, safety and pharmacokinetic of fanregratinib in treating advanced IHCC patients with FGFR2 fusion/rearrangement. Primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), disease control rate (DCR), duration of response (DoR) and overall survival (OS). A total of 87 patients were enrolled into the registration phase of the study. Additional details may be found at clinicaltrials.gov using identifier NCT04353375.

The first patient received the first dose in March 2023 and HUTCHMED expects to announce topline results from the study around the end of 2025. If favorable, the results could enable a New Drug Application submission to China’s National Medical Products Administration (NMPA).

About Fanregratinib

Fanregratinib (HMPL-453) is a novel, highly selective and potent inhibitor targeting FGFR 1, 2 and 3. Aberrant FGFR signaling has been found to be a driving force in tumor growth, promotion of angiogenesis and resistance to anti-tumor therapies. Abnormal FGFR gene alterations are believed to be the drivers of tumor cell proliferation in several solid tumor settings.

HUTCHMED currently retain all rights to fanregratinib worldwide.

About IHCC with FGFR2 Fusion/Rearrangement

IHCC is one of the subtypes of primary bile duct cancer. In China, an estimated 61,900 newly diagnosed IHCC occurred in 2015 and the overall IHCC incidence increased by 9.2% per year between 2006 and 2015.1 FGFR2 fusion has been reported to have a prevalence of 10-15% in IHCC patients.

On March 6, 2025 CStone Pharmaceuticals (stock code: 2616.HK), an innovation-driven biopharmaceutical company focused on developing oncology drugs, reported the successful submission of a Phase Ib clinical trial application in Australia for CS5001 (ROR1 ADC), a key product in its 2.0 pipeline, in combination with standard-of-care therapy, in first-line diffuse large B-cell lymphoma (DLBCL) (Press release, CStone Pharmaceauticals, MAR 6, 2025, View Source [SID1234656220]). Additionally, a global, multi-center clinical trial evaluating CS5001 alone and in combination with a PD-L1 monoclonal antibody for the treatment of advanced solid tumors is also underway.

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This Phase Ib clinical trial further expands upon the previous studies of CS5001 monotherapy in patients with advanced, aggressive, and indolent lymphomas. It aims to further explore the clinical application value of CS5001 across the full spectrum of DLBCL disease and continue to expand its scope in solid tumor treatment. The trial expansion includes:

• In combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for the treatment of patients with DLBCL who have not received prior systemic therapy;

• Combination with standard therapy for patients with relapsed or refractory DLBCL;

• Monotherapy for patients with ROR1-positive advanced solid tumors;

• Combined with sugemalimab for the treatment of patients with advanced solid tumors.

Dr. Jianxin Yang, CEO, President of R&D, and Executive Director of CStone Pharmaceuticals, said, "We are very pleased to see this important progress in the clinical development of CS5001 (ROR1 ADC). Existing data have demonstrated that CS5001 exhibits broad potential in both solid tumors and lymphomas. In a Phase II clinical study, the ROR1 ADC combined with R-CHP achieved impressive complete response (CR) rates in first-line DLBCL. With the expansion of our Phase Ib clinical trial from late-line monotherapy to combination therapy in the frontline setting, CS5001 has the potential to bring groundbreaking therapeutic benefits to patients with DLBCL and reshape the standard of care for this disease. Furthermore, as the first ROR1 ADC with demonstrated clinical anti-tumor activity in both solid tumors and lymphomas, we are actively advancing the development of CS5001 in solid tumors and look forward to its subsequent clinical success."

Currently, a global, multicenter Phase Ib clinical trial of CS5001 is progressing simultaneously in the United States, Australia, and China. Enrollment is underway in the monotherapy cohort for both aggressive and indolent advanced lymphomas, with the goal of subsequently expanding into a Phase II, single-arm, registrational study. Enrollment is also expected to commence in combination with CS5001 for first-line or relapsed/refractory DLBCL, as well as in the monotherapy and combination treatment of advanced solid tumors.

About the CS5001 (ROR1 ADC)

CS5001 is an antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). This drug utilizes a unique design, combining a tumor-specifically activated pyrrolobenzodiazepine (PBD) protoxin payload and a linker. CS5001 is internalized by tumor cells only after reaching them. Within lysosomes, the linker is cleaved by a specific enzyme highly expressed in tumor cells, releasing the PBD protoxin. The PBD protoxin is then activated within the tumor cells, leading to precise cell killing. This "dual-control" mechanism of linker plus protoxin effectively mitigates the toxicity issues associated with traditional PBD payloads and significantly extends the safety window. CS5001 has demonstrated complete tumor suppression in multiple preclinical cancer models, along with favorable serum half-life and pharmacokinetic properties, demonstrating its significant clinical development potential and broad application prospects in the treatment of various solid and hematological tumors. In addition, CS5001 uses directed coupling technology to achieve a precise drug-antibody ratio (DAR), providing strong guarantees for homogeneous production and large-scale production.

In October 2020, CStone Pharmaceuticals and LigaChem Biosciences, Inc. (LCB) entered into a licensing agreement for the development and commercialization of CS5001. CS5001 was originally co-synthesized by LCB and ABL bio, two leading Korean biotech companies. Under the terms of the agreement, CStone Pharmaceuticals obtained exclusive development and commercialization rights for CS5001 worldwide, excluding Korea.

At the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, first-in-human data from a CS5001 study in patients with advanced solid tumors and lymphomas were presented as a poster. Subsequently, at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, updated clinical data on CS5001 as a monotherapy for advanced lymphomas were also presented.

CS5001 demonstrated a favorable safety profile and significant anti-tumor activity across 10 dose cohorts in a Phase 1a dose-escalation trial:

• At the initially selected Phase II recommended dose (RP2D) level (125 μg/kg), CS5001 achieved an objective response rate (ORR) of 70% and 100% for advanced B-cell non-Hodgkin lymphoma and Hodgkin lymphoma, respectively;

• Significant efficacy signals for CS5001 were observed in advanced solid tumors such as pancreatic cancer, ovarian cancer, non-small cell lung cancer, and triple-negative breast cancer;

• CS5001 showed good tolerability in patients with multi-line-treated advanced B-cell lymphoma and solid tumors.

On March 6, 2025 Integral Molecular, a leader in antibody discovery against membrane proteins, reported that its out-licensed anti-Claudin 6 (CLDN6) bispecific antibody, CTIM-76, has been dosed in the first patient in a Phase 1 clinical trial by its licensing partner, Context Therapeutics Inc (Press release, Integral Molecular, MAR 6, 2025, View Source [SID1234650968]). This milestone is part of a Phase 1 dose escalation and expansion trial enrolling patients with advanced or metastatic ovarian, endometrial, and testicular cancers.

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CLDN6 is a structurally complex protein that is expressed in multiple cancers but absent from healthy tissue, making it an attractive drug target. However, targeting CLDN6 is challenging because numerous related proteins are present in healthy tissues.

Using their MPS Antibody Discovery platform, Integral Molecular isolated a lead molecule targeting a unique CLDN6 epitope to deliver potential best-in-class specificity compared with other molecules undergoing clinical development. Under a licensing agreement, Context Therapeutics Inc. is leading clinical development of CTIM-76, following the successful completion of IND-enabling studies.

CTIM-76 was generated using Integral Molecular’s proprietary technologies for discovering therapeutics against challenging targets:

MPS Antibody Discovery platform tailored to produce robust immune responses even against the most complex proteins and rare epitopes
Bispecific antibody engineering strategies that assess numerous bispecific antibody stoichiometries and formats in vitro and in vivo
Selection for exquisite specificity using Integral Molecular’s Membrane Proteome Array that screens biologics for reactivity against 6,000 native membrane proteins
"Our antibody discovery platform continues to advance untapped targets across oncology, autoimmune diseases, and other therapeutic areas to discover breakthrough treatments for patients," said Joseph Rucker, PhD, Vice President of R&D at Integral Molecular. "We are proud to work with partners like Context Therapeutics who are bringing novel therapeutics to the clinic."

On March 6, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported it has received a Notice of Intent to Grant for the European patent application titled, "Method of Reconstituting Liposomal Annamycin" (Press release, Moleculin, MAR 6, 2025, View Source [SID1234650970]). The grant is subject to payment of fees and completion of final amendments and formalities. Such grant will enhance the global exclusivity of Annamycin with the potential to be a next generation, non-cardiotoxic treatment for certain cancers.

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When issued, the patent claims will cover methods of making liposomal Annamycin suspension as well as the resulting compositions for use in the treatment of cancers, with a base patent term currently extending until June 2040, subject to extension to account for time required to fulfill requirements for regulatory approval. Moleculin’s novel drug candidate is being positioned to become the first ever non-cardiotoxic anthracycline to be approved and is currently being developed for the treatment of acute myeloid leukemia (AML) and soft tissue sarcoma lung metastases (STS lung mets). Additional preclinical studies performed at a world-renowned cancer center indicate Annamycin may be a potential treatment for many more other types of cancers. The new chemical entity uses a unique lipid-based delivery technology and has shown the potential to be used in a wide range of cancers. In addition to the expected European patent and previously issued U.S. patents, Moleculin has additional patent applications related to Annamycin pending in the U.S., Europe and in major jurisdictions worldwide.

Wally Klemp, Chairman and CEO of Moleculin, said "Acknowledgment by the European Patent Office of the innovation underlying Annamycin is an important milestone for Moleculin, underscoring the importance and proprietary nature of the innovation that makes this next generation anthracycline possible. We expect Europe to be an important market for Annamycin and look forward to making an important new treatment available to patients in this region. This enhancing of our exclusivity for Annamycin is exciting when coupled with our continued expectation for an initial data readout for the MIRACLE trial in the second half of 2025."

The Company is initiating the MIRACLE (Moleculin R/R AML AnnAraC Clinical Evaluation) Trial (MB-108), a pivotal, adaptive design Phase 3 trial evaluating Annamycin in combination with cytarabine, together referred to as AnnAraC, for the treatment of relapsed or refractory acute myeloid leukemia. Following a successful Phase 1B/2 study (MB-106), with input from the FDA, the Company believes it has substantially de-risked the development pathway towards a potential approval for Annamycin for the treatment of AML. This study is subject to appropriate future filings with potential additional feedback from the FDA and their foreign equivalents.

Additionally, the Company is developing WP1066, an Immune/Transcription Modulator capable of inhibiting p-STAT3 and other oncogenic transcription factors while also stimulating a natural immune response, targeting brain tumors, pancreatic and other cancers. Moleculin is also engaged in the development of a portfolio of antimetabolites, including WP1122 for the potential treatment of pathogenic viruses, as well as certain cancer indications.