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.).

On March 6, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company" or "Plus Therapeutics"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system cancers, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Rhenium (186Re) Obisbemeda for the treatment of leptomeningeal metastases (LM) in patients with lung cancer (Press release, Plus Therapeutics, MAR 6, 2025, View Source [SID1234650984]).

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"Receiving Orphan Drug Designation for Rhenium (186Re) Obisbemeda marks a significant milestone in our efforts to develop a much-needed therapy for lung cancer patients with leptomeningeal metastases," said Mike Rosol, Ph.D., Plus Therapeutics Chief Development Officer. "These patients currently have limited treatment options, and the growing incidence of LM in lung cancer underscores the urgency for new therapies. This designation, in combination with our previously granted Fast Track designation, strengthens our pathway toward delivering an innovative, targeted radiotherapeutic solution for this highly underserved patient population."

The FDA grants ODD status to an investigational drug or biologic intended to prevent, diagnose, or treat a rare disease or condition affecting fewer than 200,000 people in the United States. ODD provides certain benefits to drug developers, including seven potential years of market exclusivity, tax credits for qualified clinical trials, and exemptions from significant regulatory fees, including the Prescription Drug User Fee Act (PDUFA) charge of $4.3 million in 2025 and the Pediatric Research Equity Act (PREA) requirements.

This milestone follows the recent completion of the ReSPECT-LM Phase 1 single-dose trial, which established the recommended Phase 2 dose (RP2D). The Company is now advancing a Phase 2 single-dose expansion trial and a Phase 1 multiple-dose trial while actively engaging the FDA to define the optimal pivotal trial strategy.

Additional details on the ReSPECT-LM trial can be found here.

About Leptomeningeal Metastases (LM)

LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells, yet there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

About Rhenium (186Re) obisbemeda
Rhenium (186Re) obisbemeda is a novel injectable radiotherapy specifically formulated to deliver highly targeted high dose radiation in CNS tumors in a safe, effective and convenient manner to optimize patient outcomes. Rhenium (186Re) obisbemeda has the potential to reduce risks and improve outcomes for CNS cancer patients, versus currently approved therapies, with a more targeted and potent radiation dose. Rhenium-186 is an ideal radioisotope for CNS therapeutic applications due to its short half-life, beta energy for destroying cancerous tissue and gamma energy for live imaging. Rhenium (186Re) obisbemeda is being evaluated for the treatment of recurrent glioblastoma and leptomeningeal metastases in the ReSPECT-GBM and ReSPECT-LM clinical trials. ReSPECT-GBM is supported by an award from the National Cancer Institute (NCI), part of the U.S. National Institutes of Health (NIH), and ReSPECT-LM is funded by a three-year $17.6M grant by the Cancer Prevention & Research Institute of Texas (CPRIT).

On March 6, 2025 Cidara Therapeutics, Inc. (Nasdaq: CDTX) (the Company), a biotechnology company using its proprietary Cloudbreak platform to develop drug-Fc conjugate (DFC) immunotherapies, reported financial results for the fourth quarter and full year ended December 31, 2024 and provided recent business updates (Press release, Cidara Therapeutics, MAR 6, 2025, View Source [SID1234650980]).

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"2024 was a transformational year for Cidara as we reacquired rights to the CD388 program, our long-acting, universal influenza drug, and raised $240.0 million in April to conduct the 5,000 subject Phase 2b NAVIGATE trial evaluating CD388 for the single-dose prevention of seasonal influenza. We raised an additional $105.0 million with new and existing investors in November to support our continued development efforts," said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara. "Based on these collective achievements and the promising CD388 clinical data generated to date, we believe we are well-positioned to continue advancing CD388 as a potential long-acting, universal influenza preventative. We look forward to continuing this momentum in 2025 and sharing additional important milestones and inflection points on our clinical programs throughout the year."

Recent Corporate Highlights

Completed enrollment of Phase 2b NAVIGATE trial evaluating CD388 for prevention of seasonal influenza. In December 2024, Cidara announced that it had reached full planned enrollment of at least 5,000 subjects in the Phase 2b NAVIGATE trial across clinical sites in the U.S. and UK. The randomized, double-blind, controlled Phase 2b trial is designed to evaluate the efficacy and safety of CD388, the Company’s DFC for the pre-exposure prophylaxis of seasonal influenza. Three CD388 dose groups and one placebo group were randomized in a 1:1:1:1 ratio and administered CD388 at the beginning of the 2024-25 influenza season. Subjects will be followed for the remainder of the 2024-25 influenza season to monitor for breakthrough cases. Rates of laboratory and clinically confirmed influenza will be compared between subjects receiving the various single doses of CD388 or placebo.

Potential early analysis of efficacy data in the first half of 2025. Given the severity of the 2024-25 flu season, we may consider a potential early analysis of efficacy data from the ongoing CD388 Phase 2b NAVIGATE study in the first half of 2025. This would potentially enable the initiation of a Phase 3 study during the 2025-26 Northern Hemisphere influenza season.

Closed $105.0 million private placement. In November 2024, Cidara entered into a securities purchase agreement with certain investors and raised $105.0 million in gross proceeds. The private placement was led by new investor, Venrock Healthcare Capital Partners, with significant participation by new and existing life sciences-focused investors, including RA Capital Management, TCGX, BVF Partners LP, Vivo Capital, Spruce Street Capital, Adage Capital Partners LP, and Checkpoint Capital.

Significantly expanded Equity Research Coverage. Guggenheim (Seamus Fernandez), Cantor (Eric Schmidt) and RBC (Gregory Renza) initiated coverage between November 2024 and January 2025 with Buy, Overweight and Outperform ratings, respectively.
Appointed Frank Karbe as Chief Financial Officer. In February 2025, Cidara announced the appointment of Frank Karbe as Chief Financial Officer. Mr. Karbe brings more than 25 years of leadership experience in the biopharma industry transitioning companies from research and development (R&D) to commercialization.

Fourth Quarter and Full Year 2024 Financial Results

Cash, cash equivalents and restricted cash totaled $196.2 million as of December 31, 2024, compared with $35.8 million as of December 31, 2023.

Collaboration revenue totaled zero and $1.3 million for the three months and full year ended December 31, 2024, respectively, compared to $2.8 million and $23.3 million for the same periods in 2023.

Collaboration revenue for the years ended December 31, 2024 and 2023 related to the achievement of milestones and ongoing R&D and clinical supply services provided to J&J Innovative Medicine, previously Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), under our license and collaboration agreement with Janssen (the Janssen Collaboration Agreement). The Janssen Collaboration Agreement was terminated upon the effectiveness of our license and technology transfer agreement with Janssen (the Janssen License Agreement) on April 24, 2024, pursuant to which we re-acquired the rights to CD388.
Acquired in-process research and development expenses were $84.9 million for year ended December 31, 2024 and related to an upfront payment of $85.0 million paid to Janssen under the Janssen License Agreement, on April 24, 2024, plus $0.4 million in direct transaction costs, offset by a settlement gain of $0.5 million to settle the preexisting Janssen Collaboration Agreement relationship.

R&D expenses were $46.9 million and $71.9 million for the three months and full year ended December 31, 2024, respectively, compared to $8.0 million and $36.8 million for the same periods in 2023. The increase in R&D expenses is primarily due to higher expenses associated with our CD388 Phase 2b NAVIGATE study and higher personnel costs, including $1.2 million for severance payments and employee benefits incurred related to a reduction in force, offset by lower nonclinical expenses associated with our Cloudbreak platform.

General and administrative (G&A) expenses were $7.3 million and $20.6 million for the three months and full year ended December 31, 2024, respectively, compared to $3.4 million and $13.6 million for the same periods in 2023. The increase in G&A expenses is primarily due to higher audit fees and legal costs associated with our corporate transactions during 2024, as well as higher personnel costs.

On April 24, 2024, we entered into an asset purchase agreement with Napp Pharmaceutical Group Limited (Napp), an affiliate of Mundipharma Medical Company, pursuant to which we sold to Napp all of our rezafungin assets and related contracts. We completed all conditions of the sale on April 24, 2024 and classified the sale of rezafungin as discontinued operations. Accordingly, we have separately reported the financial results of rezafungin as discontinued operations in the consolidated statements of operations and comprehensive loss for all periods presented. Income from discontinued operations was $0.1 million and $0.5 million for the three months and full year ended December 31, 2024, respectively, compared to $5.0 million and $2.1 million for the same periods in 2023.
Net loss was $52.3 million and $169.8 million for the three months and full year ended December 31, 2024, respectively, compared to $3.2 million and $22.9 million for the same periods in 2023.