On January 9, 2025 TriSalus Life Sciences, Inc. ("TriSalus" or the "Company") (Nasdaq: TLSI), TriSalus Life Sciences seeks to transform outcomes for patients with solid tumors by integrating our innovative delivery technology with standard-of-care therapies and our investigational immunotherapy, reported the publication of research titled, "Pressure Enabled Drug Delivery (PEDD) Significantly Increases Intraarterial Delivery of Embolic Microspheres to Liver Tumors in a Porcine Model," in the peer-reviewed Journal of Vascular and Interventional Radiology (Press release, TriSalus Life Sciences, JAN 9, 2025, View Source [SID1234649559]). The study, conducted in a transgenic tumor model, highlights the superior performance of the TriNav Infusion System in delivering Embospheres into liver tumors when compared to delivery with a traditional microcatheter.

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Key Findings:

Improved Tumor Penetration: PEDD achieved a 227 % increase (p=0.029) in the concentration of fluorescently labeled Embospheres within tumor tissue compared to a traditional microcatheter.
Improved Tumor Selectivity: The tumor-to-normal (T:N) ratio rose from 2.7 for a traditional microcatheter to 4.2 when delivered by PEDD, indicating more precise tumor targeting and reduced off-target delivery.
Increased Peritumoral Delivery: Delivery to peritumoral regions increased by 209% (p=0.045), demonstrating PEDD’s ability to overcome challenging tumor associated microenvironments.
"This study further validates the potential of TriNav using the PEDD approach to transform the treatment of liver tumors," said Bryan F. Cox, Ph.D., Chief of Research for TriSalus. "By significantly enhancing therapeutic delivery and sparing healthy tissue, PEDD offers a promising advancement for patients whose outcomes may be limited by conventional delivery methods."

The study was conducted using a transgenic porcine (Oncopig) liver tumor model, employing fluorescent imaging and advanced deep-learning algorithms to quantify therapeutic delivery with millimeter-scale resolution. Results showed the TriNav Infusion System using the PEDD approach markedly outperforms traditional microcatheters in delivering embolic microspheres into liver tumors.

These findings add to the growing body of clinical and real-world evidence supporting PEDD’s ability to improve the delivery of therapeutic agents for patients with primary and metastatic liver cancers.

On January 9, 2025 TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics ("BBOT" or the "Company"), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BBO-8520, an investigational oral therapy for the treatment of adult patients with previously treated, KRASG12C-mutated metastatic non-small cell lung cancer (NSCLC) (Press release, BridgeBio, JAN 9, 2025, View Source [SID1234649558]).

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BBO-8520 is designed to inhibit the "ON and OFF" state to provide optimal target coverage and to address KRASG12C amplification and receptor tyrosine kinase activation – the two key mechanisms of adaptive resistance to current "OFF" state inhibitors. It drives substantial tumor growth inhibition in multiple preclinical models, even after emergence of resistance to sotorasib, an FDA approved "OFF" state inhibitor of KRASG12C.i The discovery of BBO-8520 was the result of a collaboration between the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research, Lawrence Livermore National Laboratory, and BBOT.

"Receiving Fast Track designation for BBO-8520 is a significant milestone in our efforts to overcome the limitations of existing therapies for KRASG12C-mutant cancers," said Yong Ben, MD, Chief Medical and Development Officer of BBOT. "BBO-8520 represents a first-in-class approach with potential to address high unmet medical needs and shift the paradigm for cancer treatment. We will continue to work closely with the FDA to expedite the development of BBO-8520, which is currently being evaluated in a Phase 1 study (NCT06343402) of KRASG12C NSCLC patients pre-treated with first generation KRASG12C "OFF" inhibitors or with no prior KRASG12C targeted therapy experience."

Fast Track designation is intended to help rapidly advance the development and review process for promising therapeutic candidates for serious conditions that may fill an unmet medical need.

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.

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 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.