On January 9, 2025 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported a significant milestone for its proprietary Nectin-4 targeted ADC (9MW2821). On January 8, 2025, 9MW2821 was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China (Press release, Mabwell Biotech, JAN 9, 2025, View Source [SID1234649555]). 9MW2821 is given in combination with toripalimab, an anti-PD-1 monoclonal antibody, for treatment-naïve, unresectable, locally advanced or metastatic urothelial carcinoma(la/mUC). Up to now, 40 treatment-naïve patients with la/mUC were enrolled and received the combination therapy. ORR was 87.5% (comfirmed ORR was 80%) and DCR was 92.5%. Median PFS and DoR were not reached.

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A pivotal Phase III study of 9MW2821 in combination with PD-1 is ongoing. Compared with similar ADC and PD-1 combos, 9MW2821 has shown significant increase in ORR. Previously, 9MW2821 had been granted BTD by the CDE as monotherapy for the treatment of locally advanced or metastatic urothelial carcinoma that has failed to platinum-based chemotherapy and PD-(L)1 inhibitor therapy.

The BTD is a recognition aimed at expediting the development of new medicines for serious diseases. It is awarded to therapies that have shown significant efficacy or safety advantages over existing treatments in early-stage clinical trials. For drugs included in the BTD list, the CDE prioritizes resource allocation to facilitate communication and provide guidance, thereby accelerating both clinical development progress and speeding up market review and approval processes.

On January 9, 2025 CatalYm reported the appointment of Scott Clarke as Chief Executive Officer. Mr. Clarke brings over two decades of executive leadership experience in driving company growth, developing products, and shaping and executing transactions in the biopharmaceutical industry (Press release, Catalym, JAN 9, 2025, View Source [SID1234649538]). He takes the helm as CatalYm enters a new stage of corporate and clinical development, including the initiation of a broad Phase 2b program for its lead candidate, visugromab, in non-squamous non-small-cell lung cancer and additional tumor indications. Based in the US, he will oversee both EU and US operations.

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"Scott Clarke is a fantastic addition to CatalYm’s leadership team. The company is in a strong position following its oversubscribed $150 million Series D financing and its recent publication in Nature of positive visugromab data. These events provide significant momentum for Scott’s start as CEO," said Jon Edwards, Interim Chair of CatalYm’s Board of Directors. "We are confident that his experience in oncology and partnering will be a substantial asset as we initiate CatalYm’s broad Phase 2b program with visugromab in hard-to-treat, metastatic solid tumor indications."

"I am impressed by CatalYm’s compelling clinical data demonstrating that visugromab is uniquely positioned as a novel cancer treatment capable of reversing key resistance mechanisms and reinstating an efficient anti-tumor response," said Scott Clarke, Chief Executive Officer at CatalYm. "I am very excited to join the CatalYm team at such a pivotal stage. I am committed to realizing visugromab’s potential to deliver unprecedented cancer remission depth and durability for patients with very limited therapeutic options."

Scott Clarke joins CatalYm from Ambagon Therapeutics, where he oversaw the company’s $85 million Series A financing and the evolution of its discovery pipeline of molecular glues. Previously, he served as CEO at Tizona Therapeutics, overseeing significant transactions and the development of its first-in-class anti-CD39 antibody for advanced cancers. Earlier in his career, he led oncology partnering at Roche, and was responsible for product development at BioMarin, contributing to multiple approved medicines. Mr. Clarke earned a Bachelor of Science in Chemical Engineering at the University of California, Berkeley, a Master of Science in Biotechnology at Northwestern University, and an MBA at London Business School.

On January 9, 2025 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported a new strategic collaboration and worldwide license agreement with MediLink Therapeutics (Suzhou) Co., Ltd. ("MediLink") to use MediLink’s TMALIN antibody-drug conjugate (ADC) platform for the development of a novel LRRC15 ADC, ZL-6201, consisting of an antibody discovered by Zai Lab (Press release, Zai Laboratory, JAN 9, 2025, View Source [SID1234649556]).

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Through this collaboration, Zai Lab further expands its global oncology pipeline with another potential first-in-class ADC targeting multiple solid tumors and addressing significant unmet medical needs. ZL-6201 has demonstrated encouraging preclinical data with an IND expected to be filed in 2025.

"MediLink has built a differentiated proprietary ADC technology platform, and we are excited to broaden our global partnership," said Rafael G. Amado, M.D., President, Head of Global Research and Development at Zai Lab. "Building on the promising findings from our ongoing clinical trials for ZL-1310, this new collaboration demonstrates our continued focus on developing cancer therapies with ADC drugs and enriches our global oncology pipeline to address unmet medical needs. We look forward to working with MediLink to advance this compound into the clinic soon."

"Zai Lab’s strong commitment to innovation and proven track record of global development impressed us through our existing collaboration," said Tony Xue, PhD, CEO at MediLink. "This new partnership further validates our technology and enhances our strategic partnership. We believe our collaboration with Zai Lab will bring this innovative therapy to patients worldwide."

About LRRC15

Leucine-rich repeat-containing protein 15 (LRRC15) is a type I transmembrane protein involved in cell-cell and cell-extracellular matrix (ECM) interactions. It is overexpressed in various mesenchymal tumors such as sarcoma, glioblastoma and melanoma, where it promotes tumor metastasis. Additionally, LRRC15 is upregulated in cancer-associated fibroblasts (CAFs) across various cancer types, contributing to immune-excluded and immune-suppressive tumor microenvironment (TME). This makes LRRC15 an appealing target for cancer therapy.

On January 9, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported it has been notified by the U.S. Food and Drug Administration (FDA) that the supplemental New Drug Application (sNDA) for cabozantinib (CABOMETYX) for the treatment of adults with previously treated advanced pancreatic neuroendocrine tumors (pNET) and advanced extra-pancreatic (epNET) will no longer be the subject of discussion at an Oncologic Drugs Advisory Committee meeting (Press release, Exelixis, JAN 9, 2025, View Source [SID1234649539]). The sNDA remains under consideration by FDA with a Prescription Drug User Fee Act action date of April 3, 2025.

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On January 9, 2025 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported a re-alignment of resources and a re-prioritization of its clinical portfolio to focus on the continued advancement of its Phase 1 clinical programs, RP-1664 (PLK4 inhibitor) and RP-3467 (Polθ ATPase inhibitor) (Press release, Repare Therapeutics, JAN 9, 2025, View Source [SID1234649557]). Repare also announced its intention to seek partnering opportunities across its portfolio, including for lunresertib and camonsertib ("Lunre+Camo") prior to any start of pivotal development. The consequent savings of late-stage clinical funding combined with planned cost and headcount reductions are expected to extend Repare’s cash runway into mid-2027.

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"While Lunre+Camo demonstrated positive results from our Phase 1 clinical trial, after careful consideration we have decided to progress this program into pivotal trials contingent on securing a strategic partner to fund further development. We are focused on achieving near-term inflection points for our Phase 1 clinical assets, RP-1664 and RP-3467, both of which have the potential to address significant unmet patient needs and deliver important catalysts in 2025," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "Combined with other initiatives, these changes, which we will implement later this quarter, provide the foundation for meaningful value creation."

Recent Pipeline Progress & Upcoming Milestones of Prioritized Clinical Programs:

RP-1664: First-in-class, highly selective, oral inhibitor of PLK4

Repare is evaluating RP-1664 as a monotherapy in the Phase 1 LIONS clinical trial in adult and adolescent patients with TRIM37-high solid tumors.

Upcoming Expected Milestones:

Q3 2025: Initiation of a Phase 1/2 expansion trial in pediatric neuroblastoma
Q4 2025: Initial topline safety, tolerability and early efficacy data from the LIONS trial
Mid-2026: Trial completion, final trial readout for proof-of-concept from the LIONS trial
RP-3467: Potential best-in-class Polθ ATPase inhibitor

Repare is dosing patients in the Phase 1 POLAR clinical trial evaluating RP-3467 alone and in combination with the poly-ADP ribose polymerase (PARP) inhibitor, olaparib. This trial is enrolling patients with locally advanced or metastatic epithelial ovarian cancer, metastatic breast cancer, metastatic castration-resistant prostate cancer, or pancreatic adenocarcinoma.

Upcoming Expected Milestones:

Q3 2025: Topline safety, tolerability and early efficacy data from the POLAR trial in monotherapy and in combination with olaparib.
Lunresertib and Camonsertib

Repare recently reported positive efficacy and safety data from the Phase 1 MYTHIC gynecologic expansion clinical trial evaluating the combination of lunresertib and camonsertib (Lunre+Camo) at the recommended Phase 2 dose (RP2D) in patients with endometrial cancer (EC) and platinum-resistant ovarian cancer (PROC). Nearly half of patients with gynecologic cancers maintained progression-free survival (PFS) at 24 weeks, comparing favorably to PFS for current standard of care. Repare intends to seek partnering opportunities for this program as a condition to advancing the program into planned and regulatory-supported pivotal development.

Repare is currently evaluating lunresertib in combination with Debio 0123, a highly selective, brain-penetrant, clinical WEE1 inhibitor, in patients with advanced solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A deleterious alterations as part of an ongoing 50/50 cost sharing collaboration with Debiopharm.

The Company will not continue to develop lunresertib or camonsertib in other studies, including the ongoing camonsertib non-small cell lung cancer expansion study, absent securing a partnership with a development partner.

Upcoming Expected Milestone:

Q2 2025: Enrollment completion of MYTHIC trial evaluating lunresertib in combination with Debio 0123 (WEE1 inhibitor)
Cash Position and Financial Guidance:

Repare ended 2024 with approximately $153 million in cash, cash equivalents and marketable securities, which is anticipated with the implementation of the cost-saving measures announced above to fund the Company’s streamlined operations into mid-2027.