On September 15, 2025 Akeso Inc. (9926.HK) reported that its proprietary next-generation humanized IgG4 monoclonal antibody targeting CD47, ligufalimab (AK117), has been granted Orphan Drug Designation (ODD) by the U.S. FDA for the treatment of acute myeloid leukemia (AML) (Press release, Akeso Biopharma, SEP 15, 2025, View Source [SID1234655979]).

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The Orphan Drug Designation is a program established by the FDA to incentivize the development of therapies for rare diseases. Drugs with this designation benefit from comprehensive FDA guidance during development, tax incentives, and up to seven years of market exclusivity upon approval.

Akeso is actively advancing the international clinical development for ligufalimab, which is being evaluated in both hematologic malignancies and solid tumors. In addition to its application in AML, patient enrollment has been completed in a randomized, double-blind, multicenter Phase II study assessing ligufalimab combined with azacitidine in higher-risk myelodysplastic syndromes (HR-MDS).

Ligufalimab is also the first CD47 monoclonal antibody to enter registrational Phase III trials in solid tumors. Two Phase III studies are currently ongoing: one evaluating the combination of ligufalimab and ivonescimab as first-line treatment for PD-L1-positive head and neck squamous cell carcinoma (HNSCC), and another study assessing this combination as first-line therapy for pancreatic cancer.

Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal proliferation of myeloid blasts in the bone marrow, peripheral blood, and extramedullary tissues. It is the most common type of acute leukemia in adults. Treatment strategies for AML, as outlined in the NCCN Guidelines, are primarily based on whether patients are eligible for intensive induction chemotherapy. For those ineligible for such chemotherapy, treatment options remain limited.

The FDA has currently approved venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine for newly diagnosed AML patients aged 75 years or older, or for those with comorbidities that preclude intensive chemotherapy. However, more than half of these patients relapse within 6–9 months, with a median overall survival of approximately one year, highlighting a significant unmet clinical need.

Ligufalimab is a humanized IgG4 monoclonal antibody that binds specifically to CD47 expressed on tumor cells, blocking its interaction with the SIRPα receptor. This disrupts the "don’t eat me" signal, thereby enhancing macrophage-mediated phagocytosis of tumor cells and inhibiting tumor growth. Ligufalimab’s unique design prevents red blood cell agglutination and demonstrates significantly improved safety and efficacy compared to other CD47-targeting agents.

Preclinical studies have shown that ligufalimab, when combined with azacitidine or venetoclax, synergistically enhances the expression of "eat me" signals (such as calreticulin), leading to more efficient activation of phagocytic immune responses. This combination may thus offer a promising treatment option for AML patients ineligible for standard induction chemotherapy.

Clinical trials have demonstrated that ligufalimab combined with azacitidine shows a favorable safety profile and promising efficacy in first-line AML treatment. Even at high doses (up to 45 mg/kg, administered biweekly), ligufalimab was well tolerated, with no significant safety differences observed across patient groups. The complete remission (CR) rate at the target dose reached 50%, and the composite complete remission (cCR) rate was 55%.

Building on these encouraging results, Akeso has launched a Phase II study to further investigate the safety and efficacy of ligufalimab in combination with venetoclax and azacitidine for first-line AML patients ineligible for intensive chemotherapy.

On September 15, 2025 Biostar Pharma, Inc., the US subsidiary of Beijing Biostar Pharmaceuticals Co., Ltd. ("Biostar", Stock Code: 2563.HK) which is a synthetic biology driven biopharma company focusing on the discovery, development and commercialization of innovative oncology drugs, reported that the first patients have been dosed for two phase II/III multiregional clinical trials (MRCT) of "Utidelone Capsule (UTD2) first-line treatment for locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma" (NCT06841679) and "UTD2 treatment for platinum-resistant advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer" (NCT07044349) on September 11, 2025 and September 12, 2025, respectively (Press release, Biostar, SEP 15, 2025, View Source [SID1234655978]).

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Utidelone has demonstrated excellent clinical data in gastric cancer: in a completed Phase II study of Utidelone Injection (UTD1) combined with PD-1 inhibitor and oxaliplatin for the first-line treatment of unresectable locally advanced or recurrent/metastatic HER2-negative gastric cancer, 23 patients had completed efficacy evaluation. Among them, 15 achieved partial response (PR) and 8 achieved stable disease (SD), resulting in a 65.2% objective response rate (ORR) and 100% clinical benefit rate (CBR). The median progression-free survival (mPFS) was 6.1 months. The combination regimen was generally well-tolerated. Most treatment-related adverse events (TRAEs) were Grade 1-2, reversible, and manageable. The longest treatment duration received by a patient was 22 cycles [1]. Consequently, Utidelone was granted an Orphan Drug Designation by the U.S. FDA for the treatment of advanced gastric cancer.

Besides gastric cancer, Utidelone has also shown considerable potential for treating ovarian cancer in previous clinical studies. A US Phase I clinical study of UTD2 as a monotherapy for advanced solid tumors had 12 evaluable patients, including one ovarian cancer patient with a complete response (CR) and another with PR, who had previously undergone 7 and 9 lines of therapy, respectively [2]. A Phase II clinical study of UTD1 as monotherapy for the treatment of advanced solid tumors had 10 evaluable patients in advanced ovarian cancer cohort, among them there were 1 PR and 3 SD.

Compared to taxanes, which are difficult for oral formulation development, Utidelone is not susceptible to P-glycoprotein thus cannot be pumped out of the cancer cell by P-glycoprotein and has the advantage for higher oral bioavailability and lower risk of developing cross-resistance. By utilizing its technology platform, Biostar developed Utidelone Capsule, and its efficacy and safety have been confirmed in both US and China’s studies. Utidelone Capsule will significantly improve the convenience of administration, compliance of patients, decrease in treatment cost and ease of combination therapy with other oral anti-cancer drugs, and more suitable for adjuvant or maintenance therapy. Beyond gastric and ovarian cancers, Biostar is actively planning and advancing multiple clinical studies to expand UTD2’s indications, including breast cancer adjuvant intensification therapy, pancreatic cancer, esophageal cancer, colorectal cancer, and so on.

About NCT06841679 Study

This study is a multi-national, open-label, randomized phase II/III clinical study of UTD2 combined with standard of care to evaluate the efficacy and safety in first-line patients with locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, untreated with systemic treatment in the advanced setting. For the Phase II part, 78 subjects are planned to be enrolled in China, US, Europe and Japan. Its primary objectives are to evaluate the safety, efficacy, and pharmacokinetic profile of UTD2 in combination therapy. The Phase III part plans to enroll 700 subjects across multiple countries/regions. The primary endpoint is overall survival (OS), with secondary endpoints including PFS, ORR, and safety.

About NCT07044349 Study

This study is a multi-national, open-label, randomized Phase II/III clinical trial of UTD2 for the treatment of patients with platinum-resistant advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. The Phase II part plans to enroll approximately 84 subjects. Its primary objective is to evaluate the safety, efficacy, and pharmacokinetic (PK) characteristics of UTD2 under different dosing regimens in the target patient population and to recommend a dose for Phase III. The Phase III part plans to enroll 480 subjects and is planned to be conducted in multiple countries and regions worldwide. Its primary objective is to evaluate the efficacy and safety of UTD2 compared to the investigator’s choice of standard treatment in the target patient population. The primary endpoint is PFS, with secondary endpoints including OS, ORR, and others.

About Utidelone

Utidelone is a new-generation genetically engineered microtubule inhibitor, and has similar mechanism of action with that of taxanes while demonstrating multiple advantages, including better anti-tumor activity, broader anti-tumor spectrum, better safety profile with very low hematologic toxicity, effective against multidrug-resistant tumors, less prone to developing drug resistance, capability of crossing the blood-brain barrier to prevent and treat brain tumors, and high oral bioavailability. Biostar has developed two formulations of Utidelone: injection (UTD1) and capsule (UTD2). UTD1 has been launched in China in 2021 for the treatment of metastatic breast cancer (MBC), who have progressed after at least one anthracycline- or taxane-containing chemotherapy regimen. The phase III study data showed that UTD1 plus capecitabine achieved both PFS and OS benefits versus capecitabine for heavily pretreated MBC patients, and the results were orally presented twice at ASCO (Free ASCO Whitepaper) annual meetings and published in prestigious journals.

On September 15, 2025 Merck reported that raludotatug deruxtecan (R-DXd) has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab (Press release, Merck & Co, SEP 15, 2025, View Source [SID1234655977]).

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Raludotatug deruxtecan is a specifically engineered, potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.

The FDA BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The medicine is required to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over currently available medicines.

The FDA granted this BTD based on data from a phase 1 trial and the ongoing REJOICE-Ovarian01 phase 2/3 trial. A subgroup analysis of the phase 1 trial was presented at the 2023 European Society for Medical Oncology meeting (#ESMO23). Subsequent subgroup analyses of the phase 1 trial were presented at the 2024 Society for Gynecologic Oncology Annual Meeting on Women’s Cancer and the 2025 European Society for Medical Oncology Gynaecological Cancers Congress. This is the first BTD for raludotatug deruxtecan and represents the second BTD since the start of the Daiichi Sankyo and Merck collaboration.

"Patients have limited treatment options once ovarian cancer becomes resistant to platinum-based chemotherapy, highlighting the urgent need for new medicines that can improve patient outcomes," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "The receipt of Breakthrough Therapy Designation represents an important step forward in our efforts to advance raludotatug deruxtecan as a novel medicine for patients with CDH6 expressing platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers previously treated with bevacizumab."

"The FDA’s Breakthrough Designation is a reflection of our commitment to advancing research for patients impacted by women’s cancers," said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. "Raludotatug deruxtecan has the potential to one day become an important option for the treatment of patients with CDH6-expressing platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers previously treated with bevacizumab, and we are excited to share data from REJOICE-Ovarian01 with the scientific community at an upcoming medical meeting and to continue working closely with the FDA."

About the Phase 1 Trial

The two-part, multicenter, open-label, first-in-human phase 1 trial is evaluating the safety and efficacy of investigational raludotatug deruxtecan in adult patients with advanced ovarian cancer previously treated with platinum-based chemotherapy and a taxane. Patients with renal cell carcinoma resistant or refractory to standard of care therapy were originally included, but that component of the study was discontinued.

The primary objective of the first part of the study (dose escalation) was to assess the safety and tolerability of increasing doses of raludotatug deruxtecan to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). The primary objective of the second part of the study (dose expansion) is to further evaluate the safety and efficacy of raludotatug deruxtecan in patients with advanced ovarian cancer and in patients with advanced renal cell carcinoma.

The study will evaluate safety endpoints, including dose-limiting toxicities and adverse events and efficacy endpoints, including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), clinical benefit rate, time to response and progression free survival (PFS). Pharmacokinetic and exploratory biomarker endpoints also will be assessed.

The phase 1 trial enrolled 179 patients in Asia and North America. For more information, please visit ClinicalTrials.gov.

About REJOICE-Ovarian01

REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan in patients with platinum-resistant, high-grade ovarian primary peritoneal or fallopian tube cancer, with disease progression following at least one but no more than three prior systemic lines of therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. Maintenance therapy (e.g., bevacizumab, poly ADP-ribose polymerase [PARP] inhibitors) is considered part of the preceding line of therapy.

The phase 2 part of REJOICE-Ovarian01 is assessing the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is ORR as assessed by blinded independent central review (BICR). Secondary endpoints include ORR as assessed by investigator, DoR, PFS and DCR – all assessed by both BICR and investigator – and overall survival (OS).

The phase 3 part of REJOICE-Ovarian01 is assessing the efficacy and safety of raludotatug deruxtecan at the selected dose (5.6 mg/kg) compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial.

REJOICE-Ovarian01 is expected to enroll approximately 710 patients across Asia, Europe, North America, and Oceania. For more information, please visit ClinicalTrials.gov.

About Ovarian Cancer

More than 324,000 women were diagnosed with ovarian cancer worldwide in 20221. The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.2,3

The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines4. Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens5. For patients who develop platinum-resistant ovarian cancer, defined as disease progression less than six months after completion of last platinum-based chemotherapy, prognosis is particularly poor and treatment options are limited.6,7

About CDH6

CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.8 An estimated 65% of patients with ovarian cancer have tumors that express CDH6. In addition, CDH6 expression is observed more frequently in high-grade serous carcinomas.8,9 There is currently no CDH6 directed medicine approved for treatment of any cancer.

About Raludotatug Deruxtecan

Raludotatug deruxtecan is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

On September 15, 2025 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported an agreement to collaborate with Novartis to develop novel degraders for immune- mediated diseases (Press release, Monte Rosa Therapeutics, SEP 15, 2025, View Source [SID1234655976]). The agreement is the Company’s second with Novartis, in addition to the global exclusive license agreement for Monte Rosa’s VAV1 degraders including MRT-6160, announced in October 2024.

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The agreement announced today was uniquely structured by the companies to collaborate on accelerating development of degraders for important immune-mediated diseases driven by highly credentialed and difficult-to-drug targets. Under the agreement, Monte Rosa’s scientists will apply their proprietary AI/ML-enabled QuEEN product engine for the discovery and development of degraders to be further developed and commercialized by Novartis.

"We are extremely excited to extend our relationship with Novartis beyond our previously announced VAV1 agreement given the strong progress made to advance MRT-6160 toward initiation of multiple Phase 2 studies in immune-mediated diseases," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "We believe this new agreement further strengthens our relationship with Novartis, a recognized global leader in immune-mediated diseases, and reflects the expansive opportunity in the space for our highly selective and potent MGDs. Our AI/ML-enabled QuEEN product engine continues to generate new insights and opportunities, delivering an expanding pipeline of programs directed against a breadth of historically undruggable immunology targets. This new collaboration allows us to expedite the development of certain of those programs with Novartis, leveraging their recognized development and commercialization capabilities. The agreement further strengthens our financial position, which allows us to progress our wholly owned programs, including multiple undisclosed targets in Th1, Th2, and Th17-driven autoimmune conditions, and provides runway beyond multiple anticipated Phase 2 readouts for MRT-8102, MRT-6160, and MRT-2359."

"We are pleased to expand our collaboration with Monte Rosa Therapeutics, building on the strong foundation and progress established through the VAV1 program," said Fiona Marshall, Ph.D., President of Biomedical Research at Novartis. "This new agreement underscores our commitment to advancing targeted protein degradation as a promising approach to address immune-mediated diseases with high unmet need. We believe Monte Rosa’s QuEEN platform has the potential to uncover new insights in this field. We look forward to working together to translate these insights into transformative therapies for patients."

Agreement Details and Financial Terms

Under the terms of the agreement, Monte Rosa will receive an upfront payment of $120 million. Monte Rosa will also receive payments to maintain the options. In total deal value, Monte Rosa is eligible to receive up to $5.7 billion, including upfront, option maintenance, preclinical milestone, option exercise, and development, regulatory, and sales milestone payments across programs, as well as tiered royalties on global net sales in the high single to low double-digit range.

Monte Rosa’s publicly disclosed pipeline programs are outside the scope of this agreement.

Monte Rosa plans to provide further information regarding its updated cash position and runway in its third quarter 2025 earnings update.

Lazard served as the exclusive financial advisor to Monte Rosa for this agreement.

On September 15, 2025 Limula, a Swiss life sciences tools company advancing automated solutions for cell and gene therapy (CGT) manufacturing reported the collaboration with the Institut Paoli-Calmettes (IPC) to characterise the cell processing capabilities of LimONE for haematopoietic stem cell (HSC) transplantation applications (Press release, Limula, SEP 15, 2025, View Source [SID1234655975]).

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IPC is internationally recognised as a leading treatment centre for cell therapies in haematological cancers and runs one of the most established autologous and allogeneic stem cell transplantation programmes in Europe. Performing more than 150 transplants each year, IPC is committed to advancing clinical innovation and broadening patient access to cutting-edge treatments.

The collaboration will leverage Limula’s automated and closed LimONE platform for autologous HSC transplantation, a procedure impacting nearly 50,000 patients annually in Europe. After promising preliminary results using an early prototype of Limula’s technology in 2022, and with strong confirmatory results earlier in 2025, IPC will further document the performance of LimONE. The goal of the collaboration is to advance automated cell product processing, with a focus on the removing of cryoprotectants and cell debris from thawed apheresis products. A fast and efficient wash is critical for maintaining the quality and consistency of the cell product and also significantly improves the patient experience.

"We are impressed with the improvements we saw during the development of LimONE and are eager to adopt the platform into our facility," said Boris Calmels, Head of the Cellular Manufacturing Unit at IPC. "I see strong potential for Limula’s technology to play a key role in improving both our cell processes and the patient’s experience during stem cell transplantation."

Luc Henry, CEO of Limula added: "This collaboration is a powerful demonstration of the versatility of our platform. We are proud to support IPC in their mission to deliver high-quality transplantation products to their patients."