On January 8, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported a corporate update and highlighted key milestones anticipated in 2024 (Press release, Repare Therapeutics, JAN 8, 2024, View Source [SID1234639218]).

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"We significantly advanced our pipeline in 2023 and presented strong data from key programs, notably for lunresertib in combination with camonsertib, and for camonsertib in combination with PARP inhibitors. In addition, we presented compelling preclinical data sets for RP-3467, which we’re developing as a potential best-in-class Polq inhibitor, and for RP-1664, a potential first- and best-in-class PLK4 inhibitor," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "2024 will be a substantial year for Repare as we aim to expand our pipeline to four clinical-stage programs by the second half of 2024, and we expect to share data readouts from ongoing studies of lunresertib combinations."

Recent Accomplishments:

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Presented initial clinical data from the Phase 1/2 TRESR and ATTACC trials evaluating camonsertib (RP-3500/RG6526, now partnered globally with Roche) in combination with three poly (ADP-ribose) polymerase (PARP) inhibitors in a Clinical Trials Plenary Session at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Camonsertib, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase), showed 48% overall clinical benefit rate in patients with advanced solid tumors across tumor types regardless of choice of PARP inhibitor or platinum resistance, with a favorable safety and tolerability profile. Data from the TRESR trial were also published in Nature Medicine highlighting the clinical benefit of camonsertib in advanced solid tumors.

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Presented initial positive data from its ongoing Phase 1 MYTHIC trial evaluating lunresertib (RP-6306) alone and in combination with camonsertib in patients with advanced solid tumors harboring CCNE1 amplification or FBXW7 or PPP2R1A deleterious alterations at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). Initial combination data included an overall RECIST response rate of 50% in patients with heavily pre-treated gynecological tumors at the preliminary recommended Phase 2 dose.

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Disclosed polo-like kinase 4 (PLK4) as the target of its RP-1664 development program and reported comprehensive preclinical data for both RP-1664 and the Company’s Polq inhibitor, RP-3467, both of which we expect to enter clinical trials in 2024. RP-1664 demonstrated potent and selective inhibition of PLK4 and synthetic lethality in TRIM37-high tumor cells in preclinical studies. RP-3467 demonstrated complete, sustained regressions preclinically in combination with PARP inhibitors, and compelling anti-tumor activity in combination with radioligand therapy (RLT) and chemotherapy.

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Announced a partnership with Debiopharm to explore the potential clinical synergy of Debio 0123, a highly selective clinical WEE1 inhibitor, and lunresertib in a trial expected to start in H1 and for which the companies have developed substantial pre-clinical validation. Repare will sponsor the global study as a new arm in the ongoing MYTHIC study with costs being shared equally by Debiopharm and Repare.

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Enrollment of patients is ongoing in the camonsertib arm of Roche’s TAPISTRY trial ( NCT04589845), a Phase 2, global, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy in patients with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations. With multiple patients in advanced stages of screening, dosing of the first patient with camonsertib is expected in the near term, which would result in the achievement of a $40 million milestone payment from Roche to Repare. In October 2023, Roche also dosed the first patient in a camonsertib-based arm in its Phase 1b/2 clinical trial of multiple immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (Morpheus Lung; NCT03337698).

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Announced the appointment of Susan M. Molineaux, Ph.D., to its Board of Directors. Dr. Molineaux currently serves as President and Chief Executive Officer at Para Therapeutics and previously served as Chief Executive Officer of Calithera Biosciences and of Proteolix. Additionally, Repare expanded its senior leadership team with the appointment of Daniel Bélanger as EVP of Human Resources.

Anticipated Key Milestones in 2024:

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Initiation of a Phase 1 dose escalation study of RP-1664, a potential first-in-class, oral PLK4 inhibitor, in adult and adolescent patients with TRIM37-high solid tumors in the first half of 2024.

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Initiation of a Phase 1/1b study of lunresertib and Debio 0123, a WEE1 inhibitor, in the first half of 2024.

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Report initial data from the Phase 1 MINOTAUR study evaluating lunresertib in combination with FOLFIRI for the treatment of advanced solid tumors in the first half of 2024.

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Report data from the dose expansion cohorts of the Phase 1 MYTHIC study evaluating lunresertib in combination with camonsertib in selectively advanced solid tumors in the second half of 2024.

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Repare has closed enrollment in the Phase 1 MAGNETIC study evaluating lunresertib in combination with gemcitabine for

the treatment of advanced solid tumors. The Company expects to report initial data from this study in the second half of 2024.

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Initiation of a Phase 1 dose finding study of RP-3467, a potential best-in-class Polq inhibitor, in the second half of 2024.

Cash Position and Financial Guidance

Repare ended 2023 with approximately $223 million in cash, cash equivalents and marketable securities, which is anticipated to fund planned operations into mid-2026.

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On January 8, 2024 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported its "OnTarget 2026" operating plan to guide efforts towards having its first potential approved product in 2026 (Press release, Nuvalent, JAN 8, 2024, View Source [SID1234639162]).

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"Over the last three years, Nuvalent has evolved from an emerging preclinical-stage start-up to an established biotech leader in advanced clinical development. In this period, we have disclosed three novel programs, demonstrated preliminary proof-of-concept for our two lead clinical programs, and launched our first registration-directed study," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "These accomplishments demonstrate a track record of successful execution and resolute focus on our founding goal: to translate our expertise in chemistry and structure-based drug design into potential best-in-class treatments for patients with cancer."

Dr. Porter continued, "2024 marks the beginning of the ‘next 3 years’ culminating in our first potential FDA approval expected in 2026, a critical milestone towards fulfilling our commitment to patients. Throughout this year, our priority is on execution of the global registrational strategies for our ROS1 and ALK programs that underpin our ultimate goal of moving up the treatment paradigm, including the potential launch of our first-line ALK strategy. We expect pivotal data from at least one of our parallel-lead programs in 2025 in support of potential New Drug Application submissions in 2026. By 2026, we also anticipate further advancing our HER2 program and our pipeline of discovery programs."

"‘OnTarget 2026’ outlines a clear set of mission-driven priorities that also deliver multiple transformative catalysts for our stakeholders over the short, intermediate, and long term," said Alexandra Balcom, Chief Financial Officer at Nuvalent. "Backed by strong product candidates, scientific rigor, and a bolstered balance sheet, we believe we are well positioned to continue achieving our goals as a growing team aligned around a firm commitment to patient impact."

OnTarget 2026: The Path to Patient Impact

OnTarget 2026 delineates Nuvalent’s 3-year operating plan towards bringing new, potential best-in-class medicines to patients with cancer. As part of this plan, Nuvalent expects to achieve the following anticipated milestones throughout 2024, leading to the company’s first potential pivotal data in 2025 and first potential approved product in 2026:

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2024: Execute on Global Registrational Strategies
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Progress the Phase 2 portion of its ARROS-1 trial of NVL-520 in patients with advanced ROS1-positive NSCLC with registrational intent;
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Initiate the Phase 2 portion of its ALKOVE-1 trial of NVL-655 in patients with advanced ALK-positive NSCLC with registrational intent;

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Launch the front-line development strategy for its ALK program;
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Initiate the Phase 1 trial for its HER2 program; and,
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Present interim data from its ongoing ARROS-1 and ALKOVE-1 clinical trials at medical meetings.
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2025: First Pivotal Data
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2026: First Approved Product

2023 Year-End Cash and Guidance

Nuvalent ended 2023 with approximately $719.9 million in cash, cash equivalents and marketable securities (unaudited), which, based on its current operating plans, is expected to fund its operations into 2027. This amount is a preliminary, unaudited estimate only as of today, could change following completion of year-end closing procedures, and does not present all information necessary for an understanding of our financial position as of December 31, 2023.

Presentation at 42nd Annual J.P. Morgan Healthcare Conference

Dr. Porter will present at the 42nd Annual J.P. Morgan Healthcare Conference in San Francisco on Tuesday, January 9, 2024 at 7:30 a.m. PT in San Francisco. A live webcast will be available in the Investors section of Nuvalent’s website at www.nuvalent.com, and will be archived for 30 days following the conference.

About NVL-520

NVL-520 is a brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. NVL-520 is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, NVL-520 is designed for brain penetrance to potentially improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy. NVL-520 has received orphan drug designation for ROS1+ non-small cell lung cancer (NSCLC) and is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced NSCLC and other solid tumors.

About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim 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 both single or compound treatment-emergent ALK mutations such as those involving G1202R. In addition, NVL-655 is designed for CNS penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. NVL-655 has received orphan drug designation for ALK+ non-small cell lung cancer (NSCLC) and 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 NSCLC and other solid tumors.

About NVL-330

NVL-330 is a novel, brain-penetrant, and HER2-selective tyrosine kinase inhibitor designed to address the combined medical need of treating HER2-mutant tumors, including those with HER2 exon 20 insertion mutations, avoiding treatment related adverse events due to off-target inhibition of wild-type EGFR, and treating brain metastases.

On January 9, 2024 Cyclacel pharmaceuticals presented its corporate presenation (Presentation, Cyclacel, JAN 8, 2024, View Source [SID1234639153]).

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On January 8, 2024 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported data from its CLOVER WaM pivotal study, evaluating iopofosine I 131, a potential first-in-class, targeted radiotherapy candidate for the treatment of relapsed/refractory Waldenstrom’s macroglobulinemia (WM) patients that have received at least two prior lines of therapy, including Bruton tyrosine kinase inhibitors (BTKi) (Press release, Cellectar Biosciences, JAN 8, 2024, View Source [SID1234639149]). CLOVER WaM is the largest study to date in relapsed or refractory WM patients post-BTKi therapy and represents the most refractory population ever tested in clinical studies based upon a review of published literature.

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The CLOVER WaM study met its primary endpoint with a major response rate (MRR) of 61% (95% confidence interval [44.50%, 75.80%, two-sided p value < 0.0001]). The overall response rate (ORR) in evaluable patients was 75.6%, and 100% of patients experienced disease control. Responses were durable, with median duration of response not reached and 76% of patients remaining progression free at a median follow-up of eight months. These outcomes exceed real world data, which demonstrate a 4-12% MRR and a duration of response of approximately six months or less despite continuous treatment in a patient population that is less pretreated and less refractory to multiple classes of drugs. Notably, iopofosine monotherapy achieved an 8% stringent complete remission (sCR) in this highly refractory WM population.

"There is a critical need for new therapies with novel mechanisms of action to treat WM. There are no approved treatments for patients post BTKi therapy, where currently the expected response rate to salvage treatments is approximately 10%, and the expected duration of response in those patients is less than six months," said Sikander Ailawadhi, M.D., professor of medicine at Mayo Clinic, and lead investigator in the CLOVER WaM study. "The results from this pivotal study utilizing just four doses of iopofosine monotherapy in heavily pretreated patients are very compelling, demonstrating deep and durable remissions. The combination of the safety profile and deep durable responses with a high proportion of patients remaining treatment free is impressive."

CLOVER WaM is a single-arm registration study with a target enrollment of 50 patients. The study is fully enrolled and topline safety data is being reported on 45 patients meeting criteria for modified intent to treat (mITT) with a data cut-off date of January 3, 2024. Topline efficacy evaluable population (41) is defined as patients who have received a total administered dose of greater than 60 mCi and had follow up of at least 60 days post last dose. Among mITT patients, median age was 71 years, median IgM level prior to treatment with iopofosine was 2,185, 90% were refractory to either a BTKi (18/36 50%) or anti-CD20 therapy (18/41 40%), with 26.7% multiclass refractory, and 80% of patients were previously treated with a BTKi therapy.

Newton Guerin, International Waldenstrom’s Macroglobulinemia Foundation (IWMF) president and CEO, said, "These inspiring topline data represent important and exciting news for the entirety of the WM community battling this challenging disease. WM patients need new, clinically meaningful treatment modalities and currently, there are limited options for patients who have received prior BTKi therapy. Iopofosine’s product profile is notable because of its novel mechanism of action, fixed four-dose course of treatment completed within 75 days and the promise of an enhanced quality of life for patients, including a prolonged treatment-free interval."

Iopofosine I 131 was well tolerated and its toxicity profile was consistent with the Company’s previously reported safety data. There were no treatment-related adverse events (TRAEs) leading to discontinuation. The rates of Grade 3 or greater TRAEs observed in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%), and anemia (26%). All patients recovered from cytopenias with no reported aplastic sequalae. Importantly, there were no clinically significant bleeding events, and the rate of febrile neutropenia was 2%. There were no treatment related deaths in the study.

"We are most grateful to the patients and their families, participating study sites, their staff and our dedicated employees for the successful completion of this study. Their respective contributions may provide a meaningful new treatment option for patients where there currently are no approved therapies," said James Caruso, president and CEO of Cellectar. "Iopofosine’s high major response rate and achievement of the study’s primary endpoint in highly refractory, Waldenstrom’s macroglobulinemia patients exhibits its potentially practice-changing clinical profile. We believe the currently impressive response rates and the duration of responses will continue to improve as the data matures. We plan to include these outcomes in our NDA submission and will be requesting an accelerated approval based upon our WM Fast Track Designation."

Conference Call & Webcast Details

Cellectar management will host a conference call for investors today, January 8, 2024, beginning at 8:00 am ET / 5:00 am PT. Dial-in: 1-888-886-7786. Webcast Link: Click HERE

On January 8, 2023 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315), a global biotechnology company focused on the development of novel antibody therapeutics, reported that it has entered into an exclusive option and license agreement with Radiance Biopharma Inc. ("Radiance"), a biotechnology company that specializes in the development of next-generation antibody-drug conjugates (Press release, Biocytogen, JAN 8, 2024, View Source [SID1234639130]).

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The agreement grants Radiance an option to license from Biocytogen a first-in-class, fully human anti-HER2/TROP2 bispecific antibody drug conjugate (BsADC) for the development, manufacture and commercialization of therapeutic products for all human indications worldwide. HER2 and TROP2 are two tumor-associated antigens (TAAs) that are commonly expressed and co-expressed by various tumor types, including breast, gastric, colorectal, bladder, pancreatic, and non-small cell lung cancers.

Under the terms of the agreement, upon exercise of the option, Biocytogen will be entitled to an option fee, a royalty, development and commercialization milestone payments, and single-digit royalties on net sales. In addition, Biocytogen has the right to collect any sublicensing fee between Radiance and a third party.

Dr. Yuelei Shen, President and CEO of Biocytogen, said , " We are pleased to collaborate with Radiance, a strong team with extensive drug development experience, to develop a leading proprietary, fully human bispecific antibody-drug conjugate. We are optimistic that the combination of our strength in BsADC discovery and the extensive experience of the Radiance team will help accelerate the commercialization of this dual BsADC."

Marc Lippman, MD, Chairman of the Board of Radiance, said , " We are pleased to enter into this exclusive option and license agreement with Biocytogen for a novel human bispecific antibody-drug conjugate targeting HER2 and Trop2. Preclinical data from in vitro and in vivo testing with this BsADC show promising high potency of anti-tumor activities in leading tumor indications. We look forward to working with Biocytogen to bring the product into practice for the benefit of patients."