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Nuvalent to Present Preliminary Data from ALKOVE-1 Phase 1/2 Clinical Trial of NVL-655 at 35th AACR-NCI-EORTC Symposium

On September 18, 2023 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported it will present preliminary dose-escalation data from its ongoing ALKOVE-1 Phase 1/2 clinical trial of NVL-655 at the 35th AACR (Free AACR Whitepaper)-NCI-EORTC (ANE) Symposium taking place October 11-15, 2023, in Boston, Massachusetts (Press release, Nuvalent, SEP 18, 2023, View Source [SID1234635219]).

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The presentation marks the first disclosure of data characterizing the safety and clinical activity of NVL-655 from the Phase 1 dose-escalation portion of the ongoing ALKOVE-1 Phase 1/2 clinical trial evaluating NVL-655 in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors. NVL-655 has been designed with the aim to address challenges that limit clinical use of existing ALK tyrosine kinase inhibitors (TKIs), including treatment emergent resistance mutations, lack of brain penetrance, and off-target CNS adverse events. The ALKOVE-1 clinical trial is continuing to enroll patients in the Phase 1 portion of the trial.

Nuvalent plans to host a conference call and webcast on October 13, 2023. Details for the conference call will be provided at a future date and available on the Nuvalent website at www.nuvalent.com.

Details for the presentation are as follows:

Title: Safety and preliminary activity of the selective ALK inhibitor NVL-655 in patients with ALK fusion-positive solid tumors
Abstract Number: 35177
Poster Number: B154
Session: Poster Session B
Session Date and Time: Friday, October 13, 12:30 pm-4:00 pm
Presenting Author: Jessica J Lin, Massachusetts General Hospital (MGH), Boston, MA

About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

Medigene AG Announces Lead Selection for MDG2011 Representing the First TCR-T Therapy of its KRAS Library

On September 18, 2023 Medigene AG (Medigene, the "Company", FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported that it has selected its lead candidate for MDG2011, a T cell receptor engineered T cell (TCR-T) therapy targeting KRAS (Kirsten rat sarcoma viral oncogene homologue) G12V with HLA-A*11 and being developed in combination with the Company’s PD1-41BB costimulatory switch protein (CSP) technology (Press release, MediGene, SEP 18, 2023, View Source [SID1234635218]).

Medigene’s end-to-end (E2E) platform, has successfully generated not one but three KRAS G12V-HLA-A*11 TCRs, each with distinct, multiple HLA-A*11 subtype recognition patterns that exceed the Company’s selection criteria for highly specific, sensitive and potentially safer (3S) TCRs. After deploying Medigene’s proprietary algorithms for evaluation of the unique characteristics of each of the 3S TCRs, including peptide specificity, tumor cell recognition and off-target toxicity, the Company has prioritized one of the 3S TCRs as the lead to move forward to the pre-clinical stage for Medigene’s MDG2011 program.

"The unique approach of our E2E platform to generate and optimize 3S TCRs, has continued to deliver above expectations and we are delighted to have been presented with the positive challenge of having to select a lead from three strong candidates for our MDG2011 program targeting KRAS G12V-A11," said Dr. Selwyn Ho, Chief Executive Officer at Medigene.

"The selection of this first mKRAS (mutant KRAS) lead TCR further validates our capabilities to generate 3S TCRs across both neoantigens and cancer-testis antigens. By combining all our TCRs with our PD1-41BB or CD40L-CD28 costimulatory switch proteins, we remain convinced that our approach will consistently deliver best-in-class TCR-T therapies leading to improved outcomes for patients suffering from difficult-to-treat solid tumors. We look forward to presenting the first pre-clinical data on MDG2011 at upcoming scientific conferences in the last quarter of 2023."

The Company’s E2E platform continues to generate 3S TCRs with unique attributes that add additional dimensions to the potential of Medigene’s TCR-T therapies as well as to confirm the Company’s discovery research efforts. One such attribute is the identification of a TCR candidate demonstrating bi-specific recognition for both the KRAS G12V and G12C mutations. Directed TCR discovery efforts in the future will enable identification of an optimal KRAS G12C-specific TCR lead. The two remaining KRAS G12V-A11 TCRs not selected for the MDG2011 program will be added to Medigene’s KRAS TCR library for potential future programs that align the product vision with the profile of each TCR. Patents have been filed for each of the three TCRs.

MDG2011 is the first program of Medigene’s pipeline expansion into a library of neoantigens (also known as oncogenic driver mutations) that comprise multiple KRAS mutations and HLAs (human leukocyte antigens) including, but not limited to:

KRAS G12V-HLA-A*11 (MDG2011)
KRAS G12V-HLA-A*03 (MDG2012)
KRAS G12D-HLA-A*11 (MDG2021)

These TCRs will be combined with the PD1-41BB and/or the CD40L-CD28 costimulatory switch proteins to enhance penetration, proliferation, persistence and enhanced cytotoxic function of Medigene’s TCR-T cells while mitigating the immunosuppressive effects of the tumor microenvironment.

Neoantigens are tumor-specific antigens, which play a critical role in the growth and maintenance of tumors. These mutations are found in many solid tumors and their prevalence varies depending on the cancer type. Importantly, if present, these mutations are found in each tumor cell. KRAS mutations are widely recognized as the most common oncogene mutations in difficult to treat solid tumors existing in ~30% of solid tumors, such as pancreatic, colorectal, endometrial and non-small-cell lung cancer. Global incidence of solid tumors expressing KRAS mutations is estimated to be in excess of 300,000 patients.

POINT Biopharma and Athebio Announce Partnership to Develop Designed Ankyrin Repeat Protein Targeted Radioligands

On September 18, 2023 POINT Biopharma Global Inc. (NASDAQ: PNT) (the "Company" or "POINT"), a company accelerating the discovery, development, and global access to life-changing radiopharmaceuticals, and Athebio AG ("Athebio"), an innovation leader in the discovery and design of designed ankyrin repeat proteins (DARPins), reported a collaboration and license agreement to develop and commercialize DARPin-targeted radioligands ("Radio-DARPins") (Press release, Point Biopharma, SEP 18, 2023, View Source [SID1234635217]).

DARPins are an attractive ligand class for cell-surface targets that could enable access to cell "surfaceome" targets beyond catalytic and ligand binding sites typically accessible to small molecules and peptides. DARPins combine the small molecule feature of rapid tumor penetration and clearance from the body, with the antibody-like ability of binding to a wider range of proteins and other cell surface targets. Their well-behaved and customizable formatting options, including stability at high concentrations and temperatures, are expected to facilitate rapid discovery, validation, and commercial scale manufacturing applicable to fast (212Pb) and slower (177Lu, 225Ac) decaying isotopes.

The collaboration gives POINT exclusive access to Athebio’s intellectual property and capabilities in DARPin development in the radioligand therapy field. Together, the parties will collaborate in discovery, candidate selection and preclinical development of Athebody DARPins for use as Radio-DARPin drug entities. POINT will be solely responsible for the clinical development and commercialization of Radio-DARPins translated from the discovery collaboration.

"The holy grail of radioligand development is the ability to engineer ligands that can precisely deliver radiation and also have physical properties that are resistant to radiolytic damage, enabling them to be manufactured at scale," said Joe McCann, Ph.D., Chief Executive Officer of POINT Biopharma. "DARPins represent a potential goldilocks opportunity in this regard, and could unlock new cell surface targets creating a new horizon for the development of novel targeted radioligand therapies. I am excited by this collaboration with Athebio, experts in DARPin technology, as it further expands our library of tools to engineer next-generation radioligands."

"We are very excited to join forces with POINT. POINT is uniquely positioned in the radiotherapy field and just as committed as we are to unlock the full potential of Athebody DARPins to develop radiopharmaceuticals for patients in need," said Patrik Forrer, one of the inventors of the DARPin technology and CEO and Chairman of Athebio. "The exceptional properties of our Athebody DARPins make them ideally suited for targeting radioisotopes. In particular their high stability should allow for simple conjugation to radioisotopes and their small size and high affinity binding with precise specificity should allow for superior targeting of tumors. The convergence of these attributes holds immense promise for pushing the boundaries of radiotherapy."

Terms were not disclosed.

Shifting the balance in cytokine therapeutics

On September 18, 2023 Werewolf therapeutics presented its corporate presentation (Presentation, Werewolf Therapeutics, SEP 18, 2023, View Source [SID1234635214]).

TRACON Pharmaceuticals Announces ENVASARC Phase 2 Pivotal Trial Exceeded Futility Threshold at Final Interim Analysis and Will Continue as Planned

On September 18, 2023 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported that the ENVASARC Phase 2 pivotal trial more than satisfied the futility threshold of 3 responses out of 46 based on the results of the second and final mandated independent data monitoring committee (IDMC) efficacy review, and the trial will continue as planned (Press release, Tracon Pharmaceuticals, SEP 18, 2023, View Source [SID1234635213]).

The IDMC reviewed interim safety and efficacy data from 46 patients enrolled into cohort C of treatment with single agent envafolimab who completed two on-treatment scans (a minimum of 12 weeks of efficacy evaluations). The objective response rate (ORR) in the initial 46 patients treated with single agent envafolimab was 13% by investigator review and 8.7% by blinded independent central review (BICR). The ORR assessed by BICR, all of which were confirmed responses, more than satisfied the prespecified futility rule and envafolimab monotherapy was generally well tolerated. Median duration of response by BICR was greater than six months. The primary endpoint of the study is achievement of an ORR in nine of 80 patients (11.25%) treated with envafolimab by BICR and median duration of response of greater than six months is a key secondary endpoint.

"Envafolimab continues to demonstrate durable single agent activity and has been generally well tolerated," said James Freddo, M.D., TRACON’s Chief Medical Officer. "Our goal is the demonstration of nine objective responses by BICR in the 80 patient cohort of single agent envafolimab treatment."

"We continue to believe that these data position envafolimab to become a potentially compelling treatment option for patients with the refractory sarcoma subtypes of UPS and MFS based on the ORR and tolerability data to date," said Charles Theuer, M.D., Ph.D., TRACON’s Chief Executive Officer.

The trial has enrolled more than 60 of the planned 80 patients and full accrual of the ENVASARC pivotal trial is expected in the fourth quarter of this year with final data anticipated in mid-2024.

About Envafolimab

Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology and licensed by TRACON, is the first approved subcutaneously injected PD-(L)1 inhibitor. Envafolimab was approved by the Chinese NMPA in November 2021 in adult patients with MSI-H/dMMR advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options. In December 2019, Alphamab Oncology, 3D Medicines and TRACON entered into a collaboration whereby TRACON has the right to develop and commercialize envafolimab in soft tissue sarcoma in North America. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the United States sponsored by TRACON and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines. TRACON has received orphan drug designation from the U.S. Food and Drug Administration for envafolimab for patients with soft tissue sarcoma and fast track designation from the U.S. Food and Drug Administration for envafolimab (KN035) for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at 30 top cancer centers in the United States and the United Kingdom that began dosing in December 2020. ENVASARC is enrolling patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor. A total of 80 patients will receive treatment with single agent envafolimab at 600 mg every three weeks. The primary endpoint is objective response rate by central review with duration of response a key secondary endpoint.