On December 22, 2024 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, reported the submission of clinical trial application in Australia for CS2009 (PD-1/VEGF/CTLA-4 trispecific antibody), a leading asset from the Company’s Pipeline 2.0 to address various solid tumors (Press release, CStone Pharmaceauticals, DEC 22, 2024, View Source [SID1234649250]). This first-in-human study has also been registered and published on Clinicaltrials.gov (NCT number: NCT06741644).

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CS2009 features an innovative molecular design that targets PD-1, VEGFA, and CTLA-4 simultaneously, maintaining balanced affinity for PD-1 and CTLA-4. This design enables preferential targeting of double-positive tumor-infiltrating T lymphocytes (TILs), effectively blocking both PD-1 and CTLA-4 while sparing CTLA-4 on single-positive cells. This approach could potentially reduce systemic toxicity without compromising efficacy. Additionally, CS2009 induces high and rapid internalization, leading to the down-regulation of PD-1 and CTLA-4 expression on the TIL cell membrane. Notably, CS2009 retains full VEGF inhibitory function, and preclinical data indicate that its anti-VEGF activity exhibits significant synergistic effects with its immune checkpoint inhibitory functions—crosslinking with VEGFA markedly enhances both anti-PD-1 and anti-CTLA-4 activities.

At the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC Annual Meeting) in 2024, CStone presented compelling preclinical data for CS2009, demonstrating superior anti-tumor activity compared to potential competitors. The data underscored the potential of CS2009 to address a wide range of tumor types, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer. CS2009 is positioned as a potential first-in-class or best-in-class next-generation immuno-oncology backbone.

Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, stated: "We are excited to announce the timely submission of the Phase I clinical trial application for CS2009, marking another significant milestone in CStone’s Pipeline 2.0 strategy. Designed and developed in-house since 2022, CS2009 has evolved into a tri-specific antibody with a novel molecular design and robust preclinical data, holding the potential to replace current anti-PD-(L)1 therapies. Thanks to close collaboration across departments, we have rapidly advanced CS2009 to the clinical stage. The first-in-human study will soon commence in Australia, and we look forward to exploring the potential benefits CS2009 could bring to cancer patients, particularly those with low or negative PD-L1 expression who respond poorly to existing PD-(L)1 treatments."

CStone plans to initiate a multi-regional, first-in-human clinical trial for CS2009 in Australia in early 2025, followed by expansion into China and the United States.

About CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody)

CS2009 is a trispecific antibody targeting PD-1, VEGFA, and CTLA-4, with the potential to be first- or best-in-class for major tumor types. Its differentiated molecular design combines three clinically validated targets, preferentially invigorating exhausted TILs while demonstrating VEGF neutralization comparable to existing anti-VEGF antibodies. CS2009 covers a wide range of cancers, including non-small cell lung cancer, ovarian cancer, renal cell carcinoma, cervical cancer, hepatocellular carcinoma, and gastric cancer.

In November 2024, CStone presented preclinical data for CS2009 at the 39th SITC (Free SITC Whitepaper) Annual Meeting. These results show that CS2009 exhibits superior anti-tumor activity compared to potential competitors, including PD-1/CTLA-4 bispecific antibodies, PD-1/VEGF bispecific antibodies, and PD-1/CTLA-4 combination therapies.

On December 20, 2024 Foresight Diagnostics, Inc. ("Foresight") a leading diagnostics company specializing in the development of ultra-sensitive minimal residual disease (MRD) detection, reported that CEO, Jake Chabon, will present at the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15, 2025, at 7:30am Pacific Time (Press release, Foresight Diagnostics, DEC 20, 2024, View Source [SID1234649248]).

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Foresight Diagnostics will be hosting meetings at the LifeSci Corporate Access Event from January 13-15, 2025, and will also be available for additional meetings on January 16. To schedule a meeting with the Company, please contact [email protected].

On December 20, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) reported that its executives will be speaking at the following investor conference (Press release, Gilead Sciences, DEC 20, 2024, View Source [SID1234649247]):

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J.P. Morgan Healthcare Conference on Monday, January 13, 2025 beginning at 11:15 a.m. Pacific Time
The live webcast can be accessed at investors.gilead.com and the replay will be available for at least 30 days following the presentation.

On December 20, 2024 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision T cell activation, reported the dosing of the first patient in the Phase 2 portion of its STARt-001 trial. The clinical study builds on the Phase 1/2 trial evaluating invikafusp alfa as a monotherapy in biomarker-enriched patients with advanced anti-PD-1 resistant solid tumors (Press release, Marengo Therapeutics, DEC 20, 2024, View Source [SID1234649246]).

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The results of the Phase 1 portion of the STARt-001 trial were recently presented during a plenary late-breaking oral session at the SITC (Free SITC Whitepaper) Annual Meeting and an oral presentation at the 2024 ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress. The data collectively validate Marengo’s STAR platform design and demonstrate early single agent anti-tumor activity of invikafusp alfa (STAR0602), including clinical benefit in heavily pre-treated, anti-PD-1 resistant cancer patients. Invikafusp alfa exhibited a manageable safety profile consistent with its novel mechanism of action, reinforcing its potential as a treatment option across high tumor mutation burden (TMB-H) cancers or virally associated malignancies.

The Phase 2 clinical trial will treat patients with the RP2D (0.08mg/kg) and is now enrolling patients in Europe at leading oncology centers, with initial activation of sites in France and Spain.

"We are thrilled to advance invikafusp alfa into Phase 2 with the addition of premier European oncology centers," said Ke Liu, M.D., Ph.D., Chief Development Officer of Marengo Therapeutics. "The single-agent anti-tumor activity observed in Phase 1, particularly in PD-1-resistant ‘cold’ tumors like colorectal cancer, gives us confidence in our approach and fuels our hope to reach as many patients as possible. The addition of renowned European institutions expands our geographical footprint and enhances our ability to enroll more PD-1 resistant patient populations. Through our Phase 2 study, we aim to deepen our understanding of invikafusp alfa’s mechanism of action across diverse tumor types."

On December 20, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that China’s National Medical Products Administration (NMPA) has approved a New Drug Application (NDA) of DOVBLERON (taletrectinib adipate capsule), a next-generation ROS1 tyrosine kinase inhibitor (TKI), for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have been previously treated with ROS1 TKIs. DOVBLERON marks the 13th addition to Innovent’s commercial portfolio, representing an innovative precision therapy expected to benefit more lung cancer patients alongside our strong TKI franchise (Press release, Innovent Biologics, DEC 20, 2024, View Source [SID1234649245]).

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Lung cancer continues to have one of the highest global incidences and mortality rates, with NSCLC accounting for about 85% of all cases. In China, it is estimated that approximately 2.6% of patients living with NSCLC are ROS1-positive[i]. Furthermore, brain metastases are a common challenge, affecting up to 35% of patients newly diagnosed with metastatic ROS1-positive NSCLC, and increasing to as much as 55% of patients whose cancer has progressed following initial treatment. In addition, patients treated with approved ROS1 TKIs often develop resistance mutations to these therapies, representing a major limitation for patients in terms of duration of response. The approval of DOVBLERON provides a new and effective treatment option for patients who are no longer responding to previously approved therapies.

The approval is based on positive results from the pivotal Phase 2 TRUST-I trial (NCT04395677), a multicenter, open-label, single-arm trial that evaluated taletrectinib in Chinese patients with advanced ROS1-positive NSCLC. The findings, presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and published in the Journal of Clinical Oncology (JCO), demonstrated the potential of DOVBLERON to address unmet needs, particularly in patients with limited therapeutic options after treatment with prior ROS1-targeted therapies. [Link]

In addition, a second NDA for DOVBLERON was accepted and granted Priority Review Designation by China’s NMPA in March 2024 for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who have not previously been treated with ROS1 TKIs.

Caicun Zhou, M.D., Ph.D., Director of the Department of Oncology at Shanghai East Hospital, Tongji University, commented: "The treatment landscape for advanced ROS1-positive NSCLC remains challenging, especially for patients with brain metastases, who account for more than half of patients who have progressed following initial treatment with a ROS1 TKI, as well as those patients who develop resistance mutations. DOVBLERON demonstrated significant therapeutic effects on brain lesions, as well as efficacy in crizotinib-resistant patients. Moreover, DOVBLERON has a favorable safety profile and tolerability with low rates of dose reduction and treatment discontinuation due to adverse events. The efficacy and safety profile of DOVBLERON offers a new hope for patients and I look forward to its benefit in the ROS1-positive NSCLC patients in China ."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "The approval of DOVBLERON is a reflection of its potential best-in-class efficacy and safety profile, as demonstrated in the TRUST-I trial. We are delighted about the approval of DOVBLERON and will bring this precision therapy to NSCLC patients who need novel treatment options. Innovent’s robust TKI product pipeline—including RETSEMOV, PEMAZYRE, DUPERT and DOVBLERON—showcases our leadership and synergistic strengths in precision oncology. We endeavor to advance more innovative medicines to enhance patients’ quality of life."

About ROS1-positive Non-small Cell Lung Cancer

Lung cancer continues to have one of the highest global incidences and mortality rates, with NSCLC accounting for about 85% of all cases. In China, it is estimated that approximately 2.6% of patients living with NSCLC are ROS1-positive Up to 35% of patients newly diagnosed with metastatic ROS1-positive NSCLC have tumors that spread to their brain, increasing to as much as 55% for those whose cancer has progressed following initial treatment. Despite recent progress for patients with ROS1-positive NSCLC, there remains a need for more effective and tolerable treatment options.

About DOVBLERON (Taletrectinib Adipate Capsule)

DOVBLERON is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with advanced ROS1-positive NSCLC. Taletrectinib, the active ingredient in DOVBLERON is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II(NCT04919811), a global study.

In December 2024, DOVBLERON was approved by China’s National Medical Products Administration (NMPA) for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who have previously been treated with ROS1 TKIs. In addition, a second NDA for taletrectinib was accepted and granted Priority Review Designation by China’s NMPA for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who have not previously been treated with ROS1 TKIs.

Taletrectinib has been granted Orphan Drug Designation by the U.S. FDA for the treatment of patients with ROS1-positive NSCLC and other NSCLC indications, and Breakthrough Therapy Designations by both the U.S. FDA and China’s NMPA for the treatment of patients with locally advanced or metastatic ROS1-positive NSCLC. Based on pooled results of the TRUST-I and TRUST-II clinical studies, Nuvation Bio Inc. (NYSE: NUVB) submitted an NDA for taletrectinib to the U.S. FDA for the treatment of patients with advanced ROS1-positive NSCLC (line agnostic, full approval).

In June 2021, Innovent and AnHeart Therapeutics (Hangzhou) Co. Ltd., a Nuvation Bio Inc. company, entered into an exclusive license agreement for the co-development and commercialization of taletrectinib in Greater China, including mainland China, Hong Kong, Macau and Taiwan.