On January 10, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported The New England Journal of Medicine (NEJM) has published data from the registrational Phase 1/2 TRIDENT-1 study evaluating repotrectinib (TPX-0005) in patients with ROS1 fusion-positive (ROS1+) non-small cell lung cancers (NSCLCs) (Press release, Zai Laboratory, JAN 10, 2024, View Source [SID1234639192]). Repotrectinib is a tyrosine kinase inhibitor (TKI) that has shown robust anti-tumor activity against ROS1+ cancers in preclinical models. In the TRIDENT-1 study, repotrectinib demonstrated high response rates and durable activity in patients with ROS1+ NSCLC, including patients with TKI-naïve and TKI-pretreated tumors, ROS1 G2032R resistance mutations and brain metastases. Treatment with repotrectinib was generally well tolerated with a manageable safety profile compatible with long-term administration.

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Turning Point Therapeutics, a wholly owned subsidiary of the Bristol-Myers Squibb Company, sponsored and designed the global, registrational TRIDENT-1 study. In August 2022, Bristol Myers Squibb acquired the company, including its asset repotrectinib. As part of its exclusive license agreement with Turning Point Therapeutics to develop and commercialize repotrectinib in Greater China (mainland China, Hong Kong, Taiwan, and Macau), Zai Lab participated and enrolled 81 patients for this trial.

Every year in China, more than 800,000 people are newly diagnosed with lung cancer, and NSCLC accounts for approximately 85% of the cases. ROS1 rearrangements occur in ≤2% of patients with NSCLC1. Brain metastases are common among patients with ROS1+ NSCLC and intracranial activity of approved ROS1 TKIs can be suboptimal.

"The results from the TRIDENT-1 study suggest repotrectinib results in high and durable response rates in patients with ROS1+ NSCLC, in the settings of both treatment naïve, treatment resistant, and intracranial disease, which may address the limitations of first-generation TKIs," said Rafael G. Amado, M.D., president, head of Global Oncology Research and Development, Zai Lab. "We look forward to advancing the development of repotrectinib in Greater China as a next generation treatment in this clinical setting."

TRIDENT-1 is a registrational, first-in-human Phase 1/2 study assessing the efficacy and safety of repotrectinib in patients with advanced solid tumors, including ROS1+ NSCLC. In the study, 519 patients received one or more doses of repotrectinib, with 103 treated in Phase 1 and 416 treated in Phase 2. Primary endpoints were maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and confirmed objective response rate (ORR), as assessed by blinded independent central review (BICR) using RECIST v1.1 (Phase 2). Secondary endpoints included duration of response (DOR), progression-free survival (PFS) and safety.

Based on the results of this trial, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) for repotrectinib submitted by Zai Lab for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC, after granting priority review in May 2023. In November 2023, the U.S. Food and Drug Administration approved repotrectinib for use in adult patients with locally advanced or metastatic ROS1+ NSCLC in the United States.

About Repotrectinib

Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) targeting the ROS1 and NTRK oncogenic drivers of advanced solid tumors, including non-small cell lung cancer (NSCLC). Patients with tumor harboring ROS1 and NTRK gene fusions treated with approved targeted therapies often develop resistance mutations, eventually leading to tumor progression. Repotrectinib is the first next-generation TKI for ROS1-positive metastatic NSCLC and tumors with NTRK fusions, uniquely designed to address key drivers of disease progression.

In China, repotrectinib has been granted four Breakthrough Therapy Designations from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in ROS1-positive metastatic NSCLC patients who have not been treated with a ROS1 TKI; ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and who have not received prior platinum-based chemotherapy; ROS1-positive metastatic NSCLC patients who have previously been treated with a ROS1 TKI and one prior line of platinum-based chemotherapy; and patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with prior TRK tyrosine kinase inhibitors (TKIs).

Zai Lab has an exclusive license agreement with Turning Point Therapeutics, a wholly owned subsidiary of the Bristol-Myers Squibb Company, to develop and commercialize repotrectinib in Greater China (mainland China, Hong Kong, Taiwan and Macau).

On January 9, 2024 MimiVax, Inc., a biotechnology company focused on the development of SurVaxM, a survivin-targeted vaccine therapy for glioblastoma and other cancers, reported new investments from the venture philanthropy arms of leading brain tumor patient organizations, VC, private and existing investors (Press release, MimiVax, JAN 9, 2024, View Source;utm_medium=rss&utm_campaign=new-investments-in-mimivax [SID1234639159]).

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The investments from the Brain Tumor Investment Fund (BTIF), an affiliate of the National Brain Tumor Society (NBTS), the Sontag Innovation Fund, LLC, a subsidiary of the Sontag Foundation, MEDA Angels, LLC, Varia Ventures and private investors will support the ongoing phase 2b clinical study, subsequent registration-related work and prepare the company for commercialization of SurVaxM for ndGBM. Glioblastoma is a rare but deadly cancer with median overall survival of only about 16 months. SurVaxM was developed to bring a paradigm shift to a field that has seen little advancement in decades.

MimiVax is rapidly enrolling subjects in its SURVIVE trial [NCT05163080], a randomized, blinded, placebo-controlled Phase 2b clinical trial of SurVaxM among patients with ndGBM at 11 cancer centers across the USA. This follows the successful Phase 2a study published in the Journal of Clinical Oncology which met its primary endpoint, achieving a median overall survival (mOS) of 25.9 months – and found that 41% of the patients receiving SurVaxM survived at least 3 years, with several long term progression-free survivors.

Investment funding is designed to help MimiVax achieve its goal of revolutionizing the landscape of brain tumor treatment. "We are honored to receive significant investments from the Brain Tumor Investment Fund, the Sontag Innovation Fund, MEDA Angels, Varia Ventures and our private investors. "Their confidence in our mission further propels our efforts to make a meaningful impact in the lives of those affected by brain tumors," said Michael Ciesielski, CEO, MimiVax, Inc.

The Brain Tumor Investment Fund, known for its dedication to funding pioneering solutions in neuro-oncology, expressed enthusiasm about the partnership. "Brain tumor patients and caregivers desperately need better outcomes. The results seen in previous trials of SurVaxM make us optimistic for the SURVIVE Phase 2b trial and the potential for a new treatment on the horizon" said John Higgins, Managing Director of BTIF.

MEDA Angels, (part of the Tech Coast Angels (TCA) network) are a health-care focused investor group founded by physician, payers and scientist-angel investors, supported by a team of regulatory, reimbursement, legal and financial advisors. "We knew the grave unmet need for game-changing therapy for glioblastoma, a devasting brain cancer with median overall survival of just 16 months. After review of MimiVax’ approach, novel survivin targeting and strong data through their Phase 2a, we became confident they were well worth backing." -MEDA Angels

The Sontag Innovation Fund, building on the reputation of the Sontag Foundation as one of the largest private funders of brain tumor research in North America, is proud to have MimiVax as a portfolio company. "There is an extraordinary unmet need for new treatments that make a major impact in the brain tumor space. We are excited to play a role in the development of promising therapies like SurVaxM" said Scott Davis, Managing Director of the Sontag Innovation Fund.

MimiVax extends its gratitude to the Brain Tumor Investment Fund, the Sontag Innovation Fund, MEDA Angels, Varia Ventures and our private investors for their support and confidence in the company’s vision. This investment fortifies MimiVax’s position as a key player in the quest for innovative solutions in the fight against brain tumors.

On January 9, 2024 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, and NEC Corporation (NEC; TSE: 6701), a leader in IT, network and AI technologies, reported the signing of a further development collaboration agreement to continue the clinical evaluation of the individualized neoantigen cancer vaccine TG4050 (Press release, NEC, JAN 9, 2024, View Source [SID1234639160]).

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TG4050 is currently being evaluated in a randomized multicenter Phase I trial as a single agent in the adjuvant treatment of HPV-negative head and neck cancers. Based on promising data obtained in this Phase I* trial (new windowNCT04183166), Transgene and NEC are preparing a randomized Phase I/II extension of this trial slated to start in 2024. This new trial builds on compelling first signs of efficacy and induction of specific T-cell responses with the aim of generating a comprehensive set of immunological and clinical data to further demonstrate the potential of TG4050.

Transgene and NEC expect to present additional immunological and clinical data from the Phase I trial at a scientific conference in the first half of 2024.

TG4050 is based on Transgene’s viral vector based myvac platform and powered by NEC’s cutting-edge AI capabilities for the identification and prediction of the most immunogenic neoantigens.

Alessandro Riva, Chairman and CEO of Transgene, commented: "We are pleased to announce the extension of our agreement with NEC, which marks a significant milestone in our collaboration. We are looking forward to continuing to treat patients with our individualized cancer vaccine TG4050. The compelling initial Phase I data presented with NEC at ASCO (Free ASCO Whitepaper) 2023 showed that all evaluable patients treated with TG4050 monotherapy developed a specific immune response and remained disease-free.

"Our joint clinical development plan builds on these promising data in a setting where there is no approved treatment to prevent patient relapse after adjuvant chemoradiotherapy. We believe that TG4050, by combining a powerful and immunogenic viral vector with an extremely sophisticated neoantigen selection tool, has the potential to address major medical needs in the adjuvant treatment of solid tumors."

Masamitsu Kitase, Corporate SVP, Head of Healthcare and Life Sciences Division, NEC Corporation, commented: "Transgene has been our trusted partner in developing our joint neoantigen asset TG4050. I am excited that the positive results from the Phase I study have encouraged us to further collaborate on this very promising asset for treating head and neck cancers. We are happy that our state-of-the-art artificial intelligence (AI)/ machine learning (ML) models help in predicting clinically meaningful neoantigens which impact patient outcomes. NEC’s Healthcare and Life Sciences Division is committed to bringing novel AI-based treatments to patients across the globe and achieving meaningful advances in the pharmaceutical industry."

About myvac
myvac is a viral vector (MVA – Modified Vaccinia Ankara) based, individualized immunotherapy platform that has been developed by Transgene to target solid tumors. myvac-derived products are designed to stimulate the patient’s immune system to recognize and destroy tumors using their own cancer specific genetic mutations. Transgene has set up an innovative network that combines bioengineering, digital transformation, established vectorization know-how and unique manufacturing capabilities. Transgene has been awarded "Investment for the Future" funding from Bpifrance for the development of its platform myvac. TG4050 is the first myvac-derived product being evaluated in clinical trials.
Click new windowhere to watch a short video on myvac.

About TG4050
TG4050 is an individualized immunotherapy being developed for solid tumors that is based on Transgene’s myvac technology and powered by NEC’s longstanding artificial intelligence (AI) and machine learning (ML) expertise. This virus-based therapeutic vaccine encodes neoantigens (patient-specific mutations) identified and selected by NEC’s Neoantigen Prediction System. The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary data allowing it to accurately prioritize and select the most immunogenic sequences.
TG4050 is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to recognize and destroy tumor cells based on their own neoantigens. This individualized immunotherapy is developed and produced for each patient.

About the clinical trial
TG4050 is being evaluated in a Phase I clinical trial for patients with HPV-negative head and neck cancers (new windowNCT04183166). An individualized treatment is created for each patient after they complete surgery and while they receive adjuvant therapy. Half of the participants received their vaccine immediately after completing adjuvant treatment. The other half were given TG4050 as an additional treatment at the time of recurrence of the disease as an additional treatment to standard of care (SoC). This randomized study is evaluating the treatment benefits of TG4050 in patients who are at risk of relapse. Thirty-two patients have been included in this trial under way in France, the UK, and the USA. The principal investigator of the trial is Prof. Christian Ottensmeier, MD, PhD, Consultant Medical Oncologist at the Clatterbridge Cancer Centre and Professor of Immuno-Oncology at the University of Liverpool. In France, the clinical trial is conducted at Institut Curie by Prof. Christophe Le Tourneau, MD, PhD, Head of the Department of Drug Development and Innovation (D3i), and at the IUCT-Oncopole, Toulouse by Prof. Jean-Pierre Delord, MD, PhD. In the USA, the trial is being led by Yujie Zhao, MD, PhD, at the Mayo Clinic. Endpoints of the trial include safety, feasibility, and biological activity of the therapeutic vaccine. Initial immunological and clinical data presented at AACR (Free AACR Whitepaper) 2023 and ASCO (Free ASCO Whitepaper) 2023 are very encouraging.

On January 9, 2024 Nerviano Medical Sciences S.r.l. (NMS), a part of NMS Group S.p.A. (NMS Group) and Nerviano Medical Sciences, Inc. (NMS-US), a wholly owned subsidiary of NMS Group, focused on the discovery and development of oncology drugs and the largest oncological R&D company in Italy, reported that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for its next-generation FLT3 inhibitor NMS-03592088 for the treatment of Acute Myeloid Leukemia (AML) (Press release, Nerviano Medical Sciences, JAN 9, 2024, View Source [SID1234639161]).

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NMS-03592088 is a potent inhibitor of FLT3, KIT and CSF1R that is being assessed as new therapeutic option for AML patients who are relapsed or refractory after treatment with prior standard of care drugs including prior FLT3 inhibitors. Preclinical characterization demonstrated that NMS-03592088 has superior features with respect to approved FLT3 inhibitor drugs supporting its positioning as next generation FLT3 inhibitor. Notably, in addition to the higher biochemical and cellular potency and superior in vivo efficacy, NMS-03592088 showed potent activity in the presence of the gatekeeper resistance mutation F691L, reported as cause of relapse after treatment with first generation FLT3 inhibitors opening the potential for treatment of patients who failed prior FLT3 inhibitor treatment.

The clinical efficacy of NMS-03592088 is being evaluated as monotherapy in a Phase I/II study in Europe and the US. Preliminary evidence of activity was observed during Phase I dose escalation with efficacy demonstrated in patients who had failed prior standard of care including patients who failed prior FLT3 treatments (LINK: AACR (Free AACR Whitepaper)2023). The trial is currently enrolling patients in Phase II with different FLT3 positive AML settings explored (NCT03922100).

"The orphan drug designation for NMS-03592088 is a significant achievement for NMS. It underscores the potential of NMS-03592088 and our dedication to making a difference in the lives of patients with FLT3 AML. We are proud to be at the forefront of innovation and remain steadfast in our mission to address unmet medical needs" said Lisa Mahnke, MD, PhD, CMO of NMS | CEO and Managing Director of NMS-US.

"Receiving orphan drug designation for NMS-03592088 is a critical milestone in our development journey. This recognition not only highlights the scientific merit of our approach but also reinforces our commitment to bringing novel therapies to those who need them most. We look forward to advancing NMS-03592088 through further clinical development and regulatory milestones" said Elena Ardini, MSc, Asset Leader of NMS.

The FDA’s Office of Orphan Products Development grants ODD status to drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. ODD provides benefits to drug developers designed to support the development of drugs and biologics for small patient populations with unmet medical needs. These benefits include potential for market exclusivity for seven years upon FDA approval eligibility for tax credits for qualified clinical trials, and waiver of Prescription Drug User Fee Act Application fee.

On January 9, 2024 Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported that Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board, will present recent clinical progress and 2024 corporate milestones at the 42nd Annual J.P. Morgan Healthcare Conference on Tuesday, January 9, 2024 from 8:15 am – 8:55 am PST (Press release, Biomea Fusion, JAN 9, 2024, View Source [SID1234639146]).

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A live webcast of the presentation will be available on the Investors & Media page of Biomea’s website at: View Source

"2023 was a truly remarkable year for Biomea as we had several positive data readouts in both type 2 diabetes and AML. Meanwhile, we initiated the expansion portion of the type 2 diabetes trial and received IND and CTA clearance for type 1 diabetes and have just now dosed our first patient in that study. Our second pipeline asset BMF-500 was also advanced into the clinic and is enrolling steadily," stated Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board. "We believe BMF-219 has the potential to address the root cause of diabetes and modify its progression in patients. Our goal is to develop a short-term treatment that will reconstitute insulin producing beta cells and thereby allow a patient with diabetes to normalize blood sugar levels in a natural way. Over the past months, we have built out our team and the necessary study sites to fully explore the potential utility of BMF-219 across the different subtypes of diabetes patients. In 2024, we are planning to complete the dosing and follow-up of over 200 expansion cohort patients. This data is expected to provide the foundation for registrational studies in type 2 diabetes, which we plan to start in 2025. We are also set up to explore BMF-219’s potential in type 1 diabetes with our Phase 2 study, COVALENT-112, and will share data from the 40 patient open label portion within this year. And finally, we will continue the patient enrollment in our liquid and solid tumor studies and anticipate completing the dose escalation steps in each of the cohorts within this year. 2024 will be an exciting year for Biomea and we are looking forward to providing you continued updates throughout as we further define a registrational path forward for each of our diabetes and oncology assets."

RECENT UPDATES & ANTICIPATED 2024 MILESTONES

DIABETES

COVALENT-111 (BMF-219 for Type 2 Diabetes)

Presented proof-of-concept clinical data in a Phase II study with only 4 weeks of dosing:
Compared to baseline, 84% of all type 2 diabetes patients dosed for four weeks with BMF-219 showed a reduction in HbA1c at Week 4 and 74% at Week 12 (n=32), two months after the final dose of BMF-219. 60% of type 2 diabetes patients dosed with 100 mg achieved a controlled HbA1c of 7% or below at the end of Week 12, two months after the last dose of BMF-219, and 36% of type 2 diabetes patients in the 200 mg cohorts showed a durable HbA1c reduction of 1% or more at Week 26, five months after the last dose of BMF-219.
FDA and Health Canada cleared the initiation of the expansion portion of the Phase II study, which will evaluate BMF-219 administered at 100 mg and 200 mg, with dosing durations up to 12 weeks in a minimum of 216 type 2 diabetes patients.
Anticipated 2024 Milestones:

On track to complete escalation portion of COVALENT-111 and present 26-week data, five months after last dose of BMF-219, from cohorts (50 mg, 100 mg, and 200 mg) that were dosed with BMF-219 for 28 days, at the Advanced Technologies and Treatments for Diabetes Meeting in March 2024.
On track to finish enrolling three expansion cohorts of COVALENT-111 and provide initial data in 2024
COVALENT-112 (BMF-219 for Type 1 Diabetes)

FDA and Health Canada cleared the IND / CTA for Phase II study COVALENT-112 of BMF-219 in type 1 diabetes. The study is designed to enroll 150 adults with type 1 diabetes and examine the safety and efficacy of BMF-219 at two oral dose levels, 100 mg and 200 mg, for 12 weeks of treatment followed by a 40 week off-treatment period. The trial will also include an open label portion (n=40), enrolling participants with type 1 diabetes up to 15 years since diagnosis.
Dosed the first type 1 diabetes patient in COVALENT-112.
Anticipated 2024 Milestones:

Complete enrollment of the open label portion (n=40).
On track to establish the initial proof of concept based on clinical data in type 1 diabetes patients treated in COVALENT-112 with BMF-219.
ONCOLOGY

COVALENT-101 (BMF-219 for Liquid Tumors)

Presented initial Phase I topline data in AML with first complete responder achieving Minimal Residual Disease negativity.
Continued patient enrollment exploring BMF-219’s utility in liquid tumors (AML/ALL, MM, CLL, DLBCL).
Anticipated 2024 Milestones:

On track to complete dose escalation portion of COVALENT-101 in liquid tumors and establish recommended Phase II dose.
COVALENT-102 (BMF-219 for KRAS-Mutant Solid Tumors)

Continued patient enrollment exploring BMF-219’s utility in KRAS driven solid tumors (PDAC, NSCLC, CRC).
Anticipated 2024 Milestones:

On track to complete dose escalation portion of COVALENT-102 in solid tumors and establish recommended Phase II dose.
COVALENT-103 (BMF-500 for Acute Leukemias)

Announced FDA clearance of IND for BMF-500 and started enrollment of leukemia patients with FLT3 mutations.
Anticipated 2024 Milestones:

On track to complete dose escalation portion of COVALENT-103 and establish recommended Phase II dose.
FUSION SYSTEM DISCOVERY PLATFORM

Built out and opened new lab facilities to validate and progress in-house research efforts.
Continued the development of the Biomea FUSION Platform technology.
Anticipated 2024 Milestones:

On track to announce a third development candidate from the Biomea FUSION Platform technology.