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."

On January 8, 2024 HighField Biopharmaceuticals, a clinical stage immuno-oncology company using lipid-based therapeutics to treat cancer, reported that it has completed its Phase 1a study of HF1K16 (Press release, HighField Biopharmaceuticals, JAN 8, 2024, View Source [SID1234639137]). Treating patients having multiple tumor types, the data demonstrated that the drug, administered as a single agent, is well-tolerated with only one dose-limiting toxicity (DLT) at the highest dose level. HF1K16 is a drug encapsulated immune modulating liposome containing all-trans retinoic acid.

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"We were especially encouraged by the outcome being correlated to the treatment duration, with the drug being tolerated for extended periods," said Dr. Yuhong Xu, CEO of HighField. "One glioma patient experienced complete remission after 10 months of treatment, remained on the treatment for two years and is cancer free. Another patient, with grade IV duodenal cancer, maintained stable disease for more than 5 months."

A total of 14 patients, suffering from a variety of refractory metastatic solid tumors such as gliomas and stomach, colorectal, liver, lung and ovarian cancers, were treated in China with HF1K16 at escalating doses beginning in 2022.

Overall, the disease control rate for the patients is about 35% with a median overall survival of 8.5 months. The maximum survival period has exceeded 24 months and five patients have survived more than 10 months.

"Given the disease state of the patients in the study, a monotherapy outcome of 35% disease control rate is impressive," said Dr. Xu. "Moreover, we found significant changes in the patients’ myeloid cell and T cell profiling after treatment. Because it shows a new mechanism and excellent safety profile, our next step is to explore HF1K16 in combination with chemotherapy and other immuno-oncology therapies."

HF1K16 is a unique liposome construct of ATRA, a small molecule metabolite of vitamin A. It is administered by infusion, travels through the blood stream and infiltrates the tumor microenvironment. ATRA is released and initiates the maturation of myeloid-derived suppressor cells (MDSCs).

MDSCs are immature myeloid cells which have not differentiated. ATRA promotes the maturation and differentiation of MDSCs into functional cells, such as dendritic cells, which then summon T cells to attack the cancer.

For more information on the Phase 1a open label trial see NCT05388487 at clinicaltrials.gov.