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CStone Submits Clinical Trial Application in Australia for CS5001 (ROR1 ADC) in Combination with First-Line Standard-of-Care for DLBCL

On March 5, 2025 CStone Pharmaceuticals ("CStone", HKEX: 2616), a biopharmaceutical company dedicated to developing innovative cancer therapies, reported the submission of a Phase Ib clinical trial application in Australia for CS5001, its ROR1-targeting antibody-drug conjugate (ADC), in combination with first-line standard-of-care (SoC) for DLBCL (Press release, CStone Pharmaceauticals, MAR 5, 2025, View Source [SID1234650917]). CS5001 is also being evaluated as both a monotherapy and in combination with a PD-L1 inhibitor for advanced solid tumors in an ongoing global multi-center clinical trial.

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Building on promising data from CS5001 monotherapy in later-line aggressive and indolent lymphomas, this Phase Ib trial aims to expand the therapeutic potential of CS5001 across all DLBCL stages and solid tumors. The study will explore:

CS5001 + R-CHOP: First-line treatment for DLBCL patients who have not received prior systemic therapy.
CS5001 + SoC: For patients with relapsed or refractory DLBCL.
CS5001 Monotherapy: Targeting ROR1-expressing solid tumors.
CS5001 + Sugemalimab: Combination therapy for advanced solid tumors.
Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, stated: "We are thrilled to reach another key clinical milestone for CS5001. The existing data underscore its broad potential in both lymphomas and solid tumors. Notably, a ROR1 ADC combined with R-CHP has demonstrated an impressive complete response (CR) rate in a Phase II trial for first-line DLBCL. As we advance from late-line monotherapy to frontline combination therapy, we are optimistic that CS5001 will provide significant clinical benefits to DLBCL patients and establish itself as a first-line treatment option. Meanwhile, we continue to explore CS5001’s potential in solid tumors and eagerly anticipate further positive outcomes."

The global multi-center Phase Ib trial for CS5001 is actively enrolling patients across the United States, Australia, and China. Recruitment is ongoing for monotherapy cohorts targeting aggressive and indolent advanced lymphomas, which could potentially expand into a Phase II single-arm registrational study. Additional cohorts, including the first-line DLBCL combination therapy and solid tumor monotherapy and combination therapy arms, will be initiated soon.

About CS5001 (ROR1 ADC)

CS5001 is a clinical-stage antibody-drug conjugate ("ADC") targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1). CS5001 has been uniquely designed with proprietary tumor-cleavable linker and pyrrolobenzodiazepine ("PBD") prodrug. Only after reaching the tumor, the linker and prodrug are cleaved to release the PBD toxin, resulting in lethal DNA cross-links in cancer cells. The use of the linker plus PBD prodrug effectively helps address the toxicity associated with traditional PBD payloads, leading to a better safety profile. CS5001 has demonstrated complete tumor suppression in several preclinical cancer models and demonstrated favorable serum half-life and pharmacokinetic characteristics. CS5001 is a promising candidate drug with precision treatment potential in both hematologic tumors and malignant solid tumors. Additionally, CS5001 utilizes site-specific conjugation for a precise drug antibody ratio of which enables homogeneous production and large-scale manufacturing.

In October 2020, CStone signed a licensing agreement with LigaChem Biosciences, Inc. (LCB) for the development and commercialization of CS5001 which was originally generated by collaboration of LCB and ABL Bio, both South Korea-based leading biotech companies. Under the agreement, CStone obtains the exclusive global right to develop and commercialize CS5001 outside the Republic of Korea.

The first-in-human data for CS5001 in patients with advanced solid tumors and lymphomas was presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Additionally, the latest clinical data on CS5001 as a monotherapy in patients with advanced lymphomas has recently been presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

CS5001 has demonstrated encouraging safety and robust anti-tumor activity in the Phase 1a dose escalation trials across 10 dose levels.

At the tentative recommended Phase 2 dose (RP2D) of DL8 (125 μg/kg), CS5001 achieved objective response rates (ORRs) of 70% in advanced B-cell lymphoma and 100% in Hodgkin lymphoma.
Encouraging efficacy signals were also observed in advanced solid tumors, including non-small cell lung cancer and pancreatic cancer.
CS5001 was well tolerated in heavily pre-treated patients with advanced B-cell lymphomas and solid tumors.

Akeso Announces Completion of Patient Enrollment in The Phase III Clinical Trial of Cadonilimab for Adjuvant Treatment of High-Risk Recurrent Hepatocellular Carcinoma

On March 5, 2025 Akeso, Inc. (9926. HK) ("Akeso" or the "Company") reported the completion of patient enrollment for its Phase III registrational clinical trial (COMPASSION-22/AK104-306) evaluating cadonilimab, the world’s first PD-1/CTLA-4 bispecific antibody independently developed by the company, as an adjuvant treatment for hepatocellular carcinoma (HCC) with high recurrence risk following curative resection or ablation (Press release, Akeso Biopharma, MAR 5, 2025, View Source [SID1234650916]).

The completion of patient enrollment in the COMPASSION-22/AK104-306 trial marks a significant milestone in the clinical development of cadonilimab for HCC. In addition to this Phase III study, another Phase III trial investigating cadonilimab in combination with lenvatinib and transarterial chemoembolization (TACE) for the treatment of unresectable intermediate to advanced HCC is currently progressing on schedule. The extensive exploration of combination therapies involving cadonilimab for HCC is expected to offer more effective treatment options for both early-stage and advanced HCC patients.

HCC is one of the most common malignant tumors globally. According to 2024 data, there are about 865,000 new cases of liver cancer worldwide, with 370,000 occurring in China. The recurrence rate after surgery is high, especially in patients with high-risk factors, with a five-year recurrence rate exceeding 70%. Currently, no standard adjuvant treatment exists for HCC in clinical practice. Identifying effective adjuvant therapies to reduce recurrence risk and extend survival is a critical unmet need in HCC treatment.

Cadonilimab is the world’s first approved bispecific immunotherapy for cancer. Previous studies have shown its significant efficacy and favorable safety profile in treating HCC. Research presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Annual Meeting demonstrated that cadonilimab combined with FOLFOX-HAIC as neoadjuvant therapy for resectable multinodular HCC achieved a 100% disease control rate (DCR) with manageable safety. Furthermore, data from the 2023 ESMO (Free ESMO Whitepaper) Congress highlighted that cadonilimab combined with lenvatinib as a first-line treatment for advanced HCC showed superior antitumor activity compared to approved therapies, effectively controlling tumor progression and offering long-term survival benefits over current treatment options.

Akeso will continue to advance cadonilimab clinical development for multiple malignant tumors, with the aim to provide more therapeutic options for patients worldwide. Currently, cadonilimab is currently involved in over 23 clinical studies across 16 indications, including gastric cancer, lung cancer, liver cancer, cervical cancer, and pancreatic cancer. It has already received approval for the treatment of recurrent/metastatic cervical cancer and first-line gastric cancer. The sNDA for cadonilimab for the treatment of first-line cervical cancer is currently under review. Additionally, five Phase III trials for HCC, non-small cell lung cancer (NSCLC), and gastric cancer are underway. Studies across multiple indications, including cervical cancer, gastric cancer, and NSCLC, have shown that cadonilimab offers meaningful efficacy benefits in all patient populations, regardless of PD-L1 expression levels (high, low, or negative). These patient data indicates that cadonilimab can also significantly broadens the eligible patient population that can benefit from cancer immunotherapies.

Puma Biotechnology to Present at Barclays Annual Global Healthcare Conference

On March 05, 2025 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that Alan H. Auerbach, Chairman, Chief Executive Officer, President and Founder, will provide an overview of Puma at 2:00 p.m. ET on Tuesday, March 11, at Barclays 27th Annual Global Healthcare Conference (Press release, Puma Biotechnology, MAR 5, 2025, View Source [SID1234650915]). The conference will be held at the Loews Miami Beach.

A live webcast of the presentation will be available on the Puma Biotechnology website at View Source The presentation will be archived on the website and available for replay for 30 days.

Nuvectis Pharma’s NXP900 Demonstrates Superior Efficacy in NSCLC When Combined with Tagrisso in Cleveland Clinic Study, Following New Buy Recommendation

On March 05, 2025 Nuvectis Pharma (NASDAQ: NVCT)* reported that new independent research conducted at the Lerner Research Institute, Cleveland Clinic (at Case Western Reserve University) has demonstrated the superior efficacy of NXP900 when combined with osimertinib (Tagrisso) in EGFR-mutated non-small cell lung cancer (NSCLC) models (Press release, Nuvectis Pharma, MAR 5, 2025, View Source [SID1234650914]). The peer-reviewed study, published in Molecular Cancer Research, demonstrated that the combination therapy led to decreased cancer cell proliferation and increased apoptosis compared to osimertinib alone.

According to the company, this research from Prof. Ruth Keri’s laboratory at Cleveland Clinic provides critical independent validation of previous findings from AstraZeneca researchers, confirming that NXP900 can effectively combat resistance mechanisms that limit the effectiveness of EGFR inhibitors like Tagrisso, which generates over $5 billion in annual sales.

NXP900, an oral SRC/YES1 kinase inhibitor with a unique mechanism that inhibits both catalytic and scaffolding functions, shows promise in addressing resistance to current standard-of-care treatments. The company is also advancing NXP800, a GCN2 activator in Phase 1b trials for platinum-resistant, ARID1a-mutated ovarian cancer, with encouraging interim data showing partial response and stable disease in several patients.

Industry analysts seem to have taken notice of Nuvectis’s potential. In February 2025, Lucid Capital Markets reportedly initiated coverage with a BUY rating and an $18 price target, projecting peak sales of over $900 million for NXP900 across multiple cancer indications. This represents significant potential upside potential from current levels. With multiple catalysts expected in 2025, including completion of the NXP900 Phase 1a study, initiation of Phase 1b trials, and updated NXP800 clinical data in Q2, Nuvectis seems to be a fascinating company to watch in 2025.

Anova Announces First Patient Enrolled to Phase 1/2a Study of DB107 for the Treatment of High-Grade Gliomas

On March 05, 2025 Anova Enterprises, Inc. (Anova), a technology-enabled CRO dedicated to accelerating promising treatments, reported enrollment of the first two patients in the highly anticipated study of DB107 for the treatment of brain tumors (Press release, Denovo Biopharma, MAR 5, 2025, View Source [SID1234650913]). The Phase 1/2a clinical trial is a multicenter, open-label study designed to confirm whether treatment DB107, when added to standard-of-care (SOC), provides clinical benefit to patients with newly diagnosed high-grade gliomas (HGG) when compared to historical performance.

The study is funded with a California Institute for Regenerative Medicine (CIRM) grant to advance the development of DB107 in patients with newly diagnosed high-grade glioma. Led by Noriyuki Kasahara, MD, PhD, Principal Investigator, Brain Tumor Research Center (BTRC) at University of California, San Francisco (UCSF), the study is also enrolling at the University of Southern California (USC) and the University of California at San Diego UCSD, and will enroll 70 participants over the coming months.

"Enrolling our first patients is an important milestone in our mission to advance treatment options for patients with high- grade glioma," said Nicholas Butowski, MD, Neuro-Oncologist and Lead Investigator at UCSF. "We are optimistic this trial will provide valuable insights into how we can better treat patients and improve survival in newly diagnosed patients."

High- grade gliomas remain one of the most challenging cancers to treat, with limited treatment options and a high degree of complexity. Treatment for the disease has not changed in 20 years. DB107 is an investigational gene therapy being developed by Denovo Biopharma for the treatment of HGG, including glioblastoma multiforme (GBM). It comprises two components: DB107-RRV (vocimagene amiretrorepvec), a retroviral replicating vector designed to selectively infect and change cancer cells, and DB107-FC, an extended-release oral formulation of 5-fluorocytosine (5-FC), which is converted into a chemotherapeutic agent within the tumor. This combination aims to eradicate tumor cells while stimulating a robust and durable anti-cancer immune response with minimal toxicity.

Chris Beardmore said, "This is revolutionary science where the treatment infects cancer cells and genetically changes them to make chemotherapy inside of the infected cells. This is known to reduce systemic toxicity commonly seen with systemic treatments. It also has a chance to infect cells that cannot be removed by surgery and other interventions to improve outcomes in newly diagnosed brain tumor patients."

The clinical trial is currently recruiting eligible patients who meet the study criteria at UCSF, USC and UCSD. Individuals interested in participating or learning more about the trial can contact the study team at [email protected].

To find out more, contact [email protected].

About Denovo’s RRV Platform and DB107

DB107 is an innovative approach utilizing a proprietary gene therapy platform, recombinant retroviral vector (RRV) bearing cytosine deaminase, combined with a prodrug of 5-FU (5-FC), to selectively infect and kill cancer cells while stimulating a robust and durable anti-cancer immune response against a tumor with minimal toxicity. DB107 has been tested clinically in solid tumors including recurrent high-grade GBM and colorectal cancer, most recently in a randomized 403-patient Phase 3 trial. DB107 received Orphan Drug Designation in GBM from the FDA and EMA, and Fast Track Designation from the FDA.