On March 6, 2025 Nuvation Bio Inc. (NYSE: NUVB), a global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported financial results for the fourth quarter and full year ended December 31, 2024, and provided a business update (Press release, Nuvation Bio, MAR 6, 2025, View Source [SID1234650993]).

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"Nuvation Bio had a transformative year in 2024, marked by significant milestones. We acquired AnHeart Therapeutics, reported positive pivotal data for taletrectinib, and submitted the NDA for taletrectinib, which was accepted by the U.S. FDA for Priority Review. This sets the stage for a potential U.S. commercial launch following our PDUFA goal date of June 23. We are also proud to now offer an Expanded Access Program in the U.S. for taletrectinib, addressing the urgent needs of patients with advanced ROS1-positive NSCLC," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "Beyond taletrectinib, we anticipate further updates in 2025 from our additional pipeline programs, including safusidenib and NUV-1511. With an exceptionally talented team and the closing of our recent non-dilutive financings of up to $250 million, we are well-positioned to continue toward our goal of improving the lives of people with cancer."

Recent Pipeline Updates:

Taletrectinib, ROS1 inhibitor: Advanced ROS1+ NSCLC

In December 2024, the U.S FDA accepted and granted Priority Review to the Company’s NDA for taletrectinib for advanced ROS1+ NSCLC (line agnostic, full approval). The PDUFA goal date of June 23, 2025, positions Nuvation Bio to commercialize taletrectinib in the U.S., if approved, in mid-2025.
In January 2025, China’s National Medical Products Administration (NMPA) approved taletrectinib for adult patients with locally advanced or metastatic ROS1+ NSCLC. As part of an exclusive license agreement, Innovent Biologics is commercializing taletrectinib in Greater China.
In February 2025, Nuvation Bio launched an EAP in the U.S., enabling eligible patients with advanced ROS1+ NSCLC to access taletrectinib outside of the ongoing pivotal TRUST-II study.
In March 2025, Nippon Kayaku completed submission of a MAA for taletrectinib for advanced ROS1+ NSCLC to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). As part of an exclusive license agreement, Nippon Kayaku will commercialize taletrectinib in Japan.
Safusidenib, mIDH1 inhibitor: Diffuse IDH1-mutant glioma

Safusidenib is a potentially best-in-class, novel, oral, brain penetrant inhibitor of mutant IDH1.
Phase 2 study in patients with diffuse IDH1-mutant glioma is ongoing.
NUV-1511, drug-drug conjugate (DDC): Advanced solid tumors

NUV-1511, the Company’s first clinical-stage DDC, fuses a targeting agent to a widely used chemotherapy agent.
Phase 1/2 dose escalation study in patients with advanced solid tumors is ongoing.
NUV-868, BD2-selective BET inhibitor: Advanced solid tumors

As previously announced, the Company is evaluating next steps for the NUV-868 program, including external partnership opportunities or further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients.
Corporate Update:

In March 2025, Nuvation Bio secured up to $250 million in non-dilutive financings from Sagard Healthcare Partners. The Company will receive $150 million in royalty interest financing and $50 million in debt upon U.S. FDA approval of taletrectinib by September 30, 2025, with access to an additional $50 million in debt at the Company’s option after first commercial sale. The royalty interest financing is expected to fully fund the U.S. commercial launch of taletrectinib. The Company’s pro forma cash balance is expected to fully fund development of the Company’s clinical-stage pipeline and create a path to potential profitability without a need for additional fundraising.
Fourth Quarter and Full Year 2024 Financial Results

As of December 31, 2024, Nuvation Bio had cash, cash equivalents, and marketable securities of $502.7 million.

For the three months ended December 31, 2024, research and development expenses were $29.3 million, compared to $15.4 million for the three months ended December 31, 2023. The increase was due to a $11.7 million increase in personnel-related costs driven by the acquisition of AnHeart Therapeutics, stock-based compensation and other benefits, a $2.1 million increase in third-party costs related to research services and drug manufacturing as a result of clinical trial expense for taletrectinib, and a $0.1 million increase in amortization of assembled workforce.

For the three months ended December 31, 2024, selling, general, and administrative expenses were $26.1 million, compared to $5.5 million for the three months ended December 31, 2023. The increase was due to a $9.5 million increase in personnel-related costs as a result of the acquisition of AnHeart Therapeutics, a $7.8 million increase in sales and marketing expenses, a $1.3 million increase in professional fees, a $1.2 million increase in other expenses as a result of the integration of AnHeart Therapeutics, a $0.7 million increase in foreign currency impact, and a $0.2 million increase in legal fees, offset by a $0.1 million decrease in insurance expense.

For the three months ended December 31, 2024, Nuvation Bio reported a net loss of $49.4 million, or $(0.15) per share. This compares to a net loss of $13.8 million, or $(0.06) per share, for the comparable period in 2023.

About Taletrectinib

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

Based on pooled results of the TRUST-I and TRUST-II clinical studies, the U.S. FDA has accepted and granted Priority Review to Nuvation Bio’s NDA for taletrectinib for advanced ROS1+ NSCLC (line agnostic, full approval) and assigned a PDUFA goal date of June 23, 2025. The U.S. FDA previously granted taletrectinib Breakthrough Therapy Designation for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC who either have or have not previously been treated with ROS1 TKIs, and Orphan Drug Designation for the treatment of patients with ROS1+ NSCLC and other NSCLC indications. In January 2025, China’s NMPA approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC.

On March 6, 2025 Everest Medicines (HKEX 1952.HK, "Everest", or the "Company"), a biopharmaceutical company focused on the discovery, clinical development, manufacturing, and commercialization of innovative therapeutics, reported that the first patient has been dosed with the Company’s internally developed personalized mRNA cancer vaccine EVM16 at Peking University Cancer Hospital in the investigator-initiated clinical trial (IIT) EVM16CX01 (Press release, Everest Medicines, MAR 6, 2025, View Source [SID1234650992]). EVM16CX01 is the first-in-human (FIH) trial for EVM16, conducted jointly at Peking University Cancer Hospital and Fudan University Shanghai Cancer center, to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EVM16 as a monotherapy and in combination with a PD-1 antibody in patients with advanced or recurrent solid tumors.

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EVM16 is a novel personalized therapeutic mRNA cancer vaccine internally developed by Everest. It contains neoantigens with high immunogenicity potential, predicted based on the unique tumor mutations of each patient using Everest’s proprietary AI-based neoantigen prediction algorithm, EVER-NEO-1. The vaccine is designed to encode dozens of tumor neoantigens. The vaccine uses a lipid nanoparticle (LNP) delivery system to efficiently deliver neoantigen-encoded mRNA in vivo, activating neoantigen-specific tumor-killing T cells and inhibiting tumor growth.

In preclinical studies, vaccination with EVM16 stimulated a strong neoantigen-specific T cell response in different mouse models and showed significant tumor growth inhibition in the syngeneic B16F10 mouse melanoma model. EVER-NEO-1, the AI-based neoantigen prediction algorithm developed in-house by Everest, can identify the majority of reported tumor neoantigens, as well as several previously unreported neoantigens. Furthermore, the neoantigen prediction capability of EVER-NEO-1 was shown to be either comparable to or superior to leading industry algorithms in multiple independent validation studies.

Preclinical data also demonstrated that the combination of EVM16 and a PD-1 antibody has synergistic effects, which supports the combination of EVM16 with checkpoint inhibitors in clinical settings. In preclinical toxicity studies, repeated dosing with EVM16 was well tolerated and safe. Taken together, the preclinical studies show that EVM16 is safe and efficacious and has potential to bring benefits to cancer patients.

"The first patient dosed with the personalized mRNA cancer vaccine EVM16 represents a notable milestone in its clinical development. EVM16 is a customized vaccine based on each patient’s tumor-specific mutations, and using the cutting-edge mRNA technology, to activate the patient’s tumor-specific immune response to recognize and attack tumor cells." said Professor Shen Lin, Director of the Gastrointestinal Oncology Department at Beijing Cancer Hospital and Chair of the Gastric Cancer Expert Committee of the Chinese Society of Clinical Oncology. " In preclinical studies, we are excited to discover that EVM16, when combined with PD-1 antibodies, demonstrated synergistic anti-tumor effects, further highlighting its broader potential for clinical application. We are confident in achieving positive outcomes in the upcoming clinical trials, bringing hope to cancer patients."

"In recent years, AI has become a major force in drug development, especially in the area of mRNA vaccines. AI is increasingly seen as a crucial tool for boosting research efficiency and accuracy, attracting substantial attention from both the biopharmaceutical industry and governments worldwide. Everest has demonstrated the clinical validation capabilities of its mRNA platform since 2021, with an emphasis on employing AI to identify tumor neoantigens. By continually optimizing its algorithms, the company has enhanced the precision of neoantigen recognition and validation, giving it a strong foundation and a competitive edge in developing mRNA-based cancer vaccines." said Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines. "EVM16 is the first personalized mRNA cancer vaccine internally developed by Everest. The first patient dosing marks a significant milestone in its clinical development of EVM16, indicating our proprietary tumor neoantigen AI-based algorithm system and mRNA technology platform have advanced to human trials. As a cancer vaccine candidate developed using our proprietary mRNA platform, we look forward to demonstrating EVM16’s therapeutic potential in upcoming clinical trials, with the goal of offering innovative treatment options to cancer patients worldwide and expand choices for those facing life-threatening diseases."

According to the Globocan’s data in 2022, there were 19.976 million new cancer cases globally, with 9.744 million cancer-related deaths1. Immunotherapy including checkpoint inhibitors has become an important part of treating some cancer types. However, they are only effective for some patients, and there is an urgent need to develop new generations of immunotherapies, such as personalized mRNA cancer vaccines, that have demonstrated early promise in clinical setting.

Everest Medicines is currently developing a range of mRNA cancer therapeutics, including personalized cancer vaccines (PCVs), tumor-associated antigen (TAA) vaccines, immunomodulatory cancer vaccines, etc. Additionally, the company is working on next-generation lipid nanoparticle (LNP) delivery systems to enhance cell-mediated immune responses. Everest Medicines will submit an investigational new drug application for its TAA vaccines in China and the United States in 2025.

About EVM16

EVM16 is a novel personalized mRNA cancer vaccine independently developed by Everest Medicines. EVM16 contains neoantigens with high immunogenicity potential and predicted by Everest-proprietary algorithm EVER-NEO-1 and uses an LNP delivery system to efficiently deliver neoantigen-expressing mRNAs into the human body. After vaccination with EVM16, neoantigens-encoding mRNAs are delivered into human body to produce neoantigen peptides, which activate neoantigen-specific T cell immune responses to kill tumor cells, thereby inhibiting tumor growth.

About EVM16CX01 study

The study is a FIH, dose escalation and expansion study to evaluate the safety, tolerability, immunogenicity, and initial efficacy of EVM16 injection as a single and in combination with PD-1 antibody in subjects with advanced or recurrent solid tumors. The primary objectives are to evaluate the safety and tolerability of EVM16 monotherapy and EVM16 in combination with PD-1 antibody in subjects with advanced or recurrent solid tumors, and to determine the recommended phase 2 dose (RP2D) of EVM16. The secondary objectives are to evaluate the immunogenicity of EVM16, and the initial efficacy of EVM16 in combination with PD-1 antibody in subjects with advanced or recurrent solid tumors.

On March 6, 2025 Bantam Pharmaceutical, a drug discovery and development company targeting selective modulation of mitochondrial dynamics in cancer, reported it is proceeding with a Phase 1 clinical trial evaluating BTM-3566 in relapsed/refractory mature B-cell lymphomas, based on a recent Clinical Trial Application (CTA) cleared by Health Canada (Press release, Bantam Pharmaceutical, MAR 6, 2025, View Source [SID1234650990]). This regulatory milestone enables Bantam to expand its ongoing clinical program and to activate multiple clinical trial sites in Canada early in the second quarter of 2025.

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This clearance follows the recent activation of Bantam’s first U.S. clinical trial site at The University of Texas MD Anderson Cancer Center for its BTM-3566 Phase 1 study. BTM-3566 is a first-in-class, small molecule cancer therapeutic which targets mitochondrial homeostasis via the ATF4-Integrated Stress Response (ISR) pathway to treat aggressive tumors.

"Activating clinical sites in Canada alongside our U.S. study sites is a key step in building a high-quality, efficient, and thoughtful clinical program," said Michael Stocum, President & CEO of Bantam Pharmaceutical. "This complementary approach accelerates the identification of clinically active doses for lymphoma patients while maintaining the scientific rigor needed to ensure a meaningful impact for those in need. We anticipate this expansion to enable us to achieve our clinical objectives sooner than originally projected."

The Phase 1 trial is designed to evaluate the safety, tolerability, and preliminary efficacy of BTM-3566 in patients with relapsed/refractory mature B-cell lymphomas. The Canadian trial will follow a similar overall design to the ongoing U.S. Phase 1 trial, a multicenter, open-label, and dose-escalation study assessing the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of BTM-3566. The dual country strategy was implemented to accelerate the development of BTM-3566 and will support future harmonization between the studies to generate a robust dataset and inform future development. Initial clinical data from the trial are expected in the second half of 2025.

For more information about the ongoing clinical trial, visit ClinicalTrials.gov and search NCT number NCT06792734.

About BTM-3566

BTM-3566 is a novel, orally available small molecule designed to target a wide range of cancers, including both hematologic and solid tumors. Its initial clinical focus is on mature B-cell lymphomas, such as mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). In preclinical studies, BTM-3566 demonstrated potent anti-cancer activity, driving significant tumor regression – and in many cases, complete tumor elimination – in models resistant to standard treatments, including CAR-T cell therapy. BTM-3566 works by disrupting the mitochondrial function in tumor cells, triggering their natural cell death process (apoptosis). With its unique mechanism of action and strong preclinical data, Bantam also plans to expand clinical development into solid tumors, broadening its potential impact for patients with limited treatment options.

On March 6, 2025 ImmunoGenesis, a clinical-stage biotech company developing innovative, science-driven immunotherapies, reported the first patient has been dosed in the company’s Phase 1/2 clinical trial of its hypoxia reversal agent IMGS-101 (evofosfamide) in combination with Balstilimab (anti-PD-1) and Zalifrelimab (anti-CTLA-4) at The University of Texas MD Anderson Cancer Center in Houston, Texas (Press release, ImmunoGenesis, MAR 6, 2025, View Source;head–neck-t-302393719.html [SID1234650989]). Tumor hypoxia (low oxygen levels) is an immunosuppressive factor in solid tumors. By reversing hypoxia, IMGS-101 may improve the efficacy of immunotherapies in cancer types that are otherwise resistant to immune-based treatments.

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The Phase 1/2, open-label, multicenter study (NCT06782555) consists of a dose escalation and expansion portion to evaluate the safety, pharmacokinetics, and anti-tumor activity of IMGS-101 in combination with Balstilimab and Zalifrelimab in adult patients with locally advanced or metastatic castration-resistant prostate cancer (CRPC), pancreatic cancer, and human papillomavirus-(HPV) negative squamous cell carcinoma of the head and neck (SCCHN). The study is being conducted in collaboration with Agenus, a clinical-stage immuno-oncology company developing the checkpoint inhibitors Balstilimab and Zalifrelimab.

"Launching this trial represents a significant milestone in our mission to target key mechanisms of immune resistance," said ImmunoGenesis President and CEO James Barlow. "By targeting and reversing hypoxia, we aim to unlock the immune system’s full potential and redefine the therapeutic landscape for these cancers with high unmet medical needs."

"This trial marks an exciting step forward in addressing one of the key challenges in cancer immunotherapy," said Dr. Charles Schweizer, Senior Vice President of Clinical Development at ImmunoGenesis. "Hypoxia limits T-cell infiltration and suppresses immune responses, especially in prostate, pancreatic, and head and neck cancers. By reversing hypoxia, IMGS-101 may restore T-cell access to tumors, enhancing the effectiveness of checkpoint inhibitors and potentially transforming outcomes in these hard-to-treat cancers."

On March 6, 2025 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (NASDAQ: ALLR), a Phase 2 clinical-stage pharmaceutical company dedicated to developing stenoparib—a differentiated dual PARP/Wnt pathway inhibitor—reported plans for a Phase 2 trial evaluating the combination of stenoparib with temozolomide, a DNA-alkylating chemotherapy agent, for the treatment of recurrent Small Cell Lung Cancer (SCLC) (Press release, Allarity Therapeutics, MAR 6, 2025, View Source [SID1234650985]). The trial is fully funded by the U.S. Veterans Administration (VA) through the Special Emphasis Panel on Precision Oncology and is being led by the VA and Academic Medical Oncologists at Indianapolis and Pittsburgh VA Medical Centers.

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This phase 2 trial builds on the compelling mechanistic synergy of temozolomide with a PARP inhibitor and selection of patients most likely to respond to this combination. Prior clinical studies had shown that PARP inhibitors combined with temozolomide provide clinical benefit as evidenced by ~40% response rates in recurrent SCLC patients but that these prior clinical studies showed dose-limiting hematologic toxicity.

Stenoparib, a novel dual PARP and tankyrase inhibitor, may offer a more favorable tolerability profile while providing additional therapeutic advantages. Its inhibition of PARP prevents DNA repair, possibly increasing temozolomide-induced cancer cell death, while its tankyrase inhibition uniquely impacts the Wnt pathway, which is known to be implicated in SCLC progression and treatment resistance. Given these properties, stenoparib could provide a next-generation approach to overcoming temozolomide resistance while potentially avoiding the severe toxicity observed with other PARP inhibitors when combined with temozolomide.

This phase 2 study aims to evaluate the safety and efficacy of stenoparib in combination with temozolomide to determine whether this approach could offer improved therapeutic options for SCLC patients who have relapsed following frontline therapy, a population with a dire need for additional treatment options. Moreover, many patients with metastatic SCLC present with brain metastases. Importantly, stenoparib can cross the blood brain barrier, making it a promising option for treating both systemic tumors and brain metastases.

Thomas Jensen, CEO of Allarity Therapeutics, stated, "We are excited to see stenoparib being investigated in additional cancer indications, especially this trial for recurrent SCLC, a patient population with a significant unmet medical need. This trial fits perfectly with our long-term strategy for stenoparib- to leverage the unique clinical benefit we have seen from stenoparib in advanced ovarian cancer for additional cancer indications and our deeper appreciation of its differentiated mechanism of therapeutic action. Given the safety profile of stenoparib we have seen thus far, this study—the first to explore a stenoparib-based combination treatment—may help to establish stenoparib as the PARP inhibitor of choice for therapeutic combinations. This study will further allow Allarity to build out the stenoparib franchise and to drive enterprise value for the whole of Allarity Therapeutics. Importantly, our recently completed drug product campaign more than covers the amount of stenoparib needed for our clinical plans in ovarian cancer, in this combination trial and in others."

Clinical Study Design
The trial is expected to enroll approximately 65 extensive-stage SCLC patients on the drug combination treatment across 11 VA medical centers. It will assess progression-free survival, as well as determine the recommended Phase 2 dose for the combination in an initial safety lead-in phase.

Clinical Study Rationale
Stenoparib is a dual PARP/tankyrase inhibitor that blocks DNA repair, making tumor cells more susceptible to DNA-damaging agents like temozolomide. Its tankyrase inhibition also affects the Wnt signaling pathway, which is linked to SCLC progression and treatment resistance, setting stenoparib apart from first-generation PARP inhibitors.

Temozolomide is an oral chemotherapy drug that damages tumor DNA, leading to cell death. However, resistance can develop through the MGMT enzyme, which repairs DNA damage, and mismatch repair (MMR) deficiency, which allows tumors to tolerate the drug. This study will assess whether stenoparib’s dual mechanism can help overcome resistance by disrupting key DNA repair pathways and targeting Wnt signaling.

Regulatory Status and Next Steps
Investigators are in the process of obtaining final regulatory approvals for this stenoparib-temozolomide combination trial from the U.S. Food and Drug Administration (FDA), the VA, and the Institutional Review Board (IRB) before patient enrollment can be initiated..

Funding and Financial Considerations
As previously disclosed on November 14, 2024, Allarity’s cash position supports operations into 2026. Since this Phase 2 trial of stenoparib in combination with temozolomide for recurrent SCLC is fully funded by the VA, it will not impact Allarity’s financial outlook, its Phase 2 program in advanced ovarian cancer, or its share repurchase plan.

About Stenoparib
Stenoparib is an orally available, small-molecule dual-targeted inhibitor of PARP1/2 and tankyrase 1/2. At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in regulating the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of numerous cancers. By inhibiting PARP and blocking Wnt pathway activation, stenoparib’s unique therapeutic action shows potential as a promising therapeutic for many cancer types, including ovarian cancer. Allarity has secured exclusive global rights for the development and commercialization of stenoparib, which was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121.

About Temozolomide
Temozolomide is an orally available, small-molecule alkylating agent used as the standard-of-care chemotherapy for glioblastoma multiforme and other high-grade brain tumors. As a DNA-methylating agent, temozolomide exerts its cytotoxic effect by inducing DNA damage, primarily through the formation of O6-methylguanine adducts, which trigger cell death in tumor cells lacking functional O6-methylguanine-DNA methyltransferase (MGMT) repair activity. Due to its ability to cross the blood-brain barrier, temozolomide remains one of the few effective systemic therapies for central nervous system malignancies. Originally developed by researchers at Aston University, temozolomide was later licensed by Schering-Plough (now part of Merck & Co.) and has been commercially available since 1999 under the brand name Temodar (Temodal outside the U.S.).