On March 6, 2025 ALX Oncology Holdings Inc., ("ALX Oncology" or "the Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives, reported financial results for the fourth quarter and full year ended December 31, 2024, and provided a corporate update (Press release, ALX Oncology, MAR 6, 2025, View Source [SID1234650946]).

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"In 2024, we delivered strong progress and continued momentum for our clinical development program evaluating evorpacept as a potential first- and best-in-class CD47 blocker with the ability to deepen and enhance responses to a variety of important, available therapies across a wide range of cancer types," said Jason Lettmann, Chief Executive Officer of ALX Oncology. "With multiple important clinical trial readouts, significant momentum for our ongoing clinical studies and key additions to our leadership team, we have positioned ALX Oncology for near- and long-term success. Yesterday during our R&D Day webcast, we shared updates on how we are prioritizing operations and capital to support our new and ongoing clinical programs that are expected to extend our cash runway into the fourth quarter of 2026, including taking the difficult decision to streamline our organization aligned to these priorities."

Fourth Quarter 2024 Highlights and Recent Developments

At the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2025, reported updated results from the multi-center, international ASPEN-06 Phase 2 clinical trial (NCT05002127) evaluating evorpacept in combination with HERCEPTIN (trastuzumab), CYRAMZA (ramucirumab) and paclitaxel (Evo-TRP) against trastuzumab, CYRAMZA (ramucirumab) and paclitaxel (TRP) for the treatment of patients with HER2-positive gastric/gastroesophageal junction (GEJ) cancer, where all patients had received an anti-HER2 agent in prior lines of therapy.
Data highlighted evorpacept as the first CD47-blocker to show substantial tumor response and a well-tolerated safety profile in a prospective randomized trial.
Greatest benefit observed among patients with confirmed HER2-positive cancer, as demonstrated by either fresh biopsy or ctDNA HER2-expression, with a confirmed objective response rate (cORR) of 48.9% and median duration of response (mDOR) of 15.7 months vs. 24.5% ORR and mDOR of 9.1 months in the control group, and a progression-free survival Hazard Ratio of 0.64.
Evo-TRP was generally well tolerated, with the incidence of adverse events in the evorpacept population consistent with those in TRP control.
At the San Antonio Breast Cancer Symposium (SABCS) 2024, presented new data from the Phase 1b/2 clinical trial demonstrating evorpacept in combination with zanidatamab generates promising antitumor activity in metastatic breast cancer (mBC).
Patients who were HER2-positive by central assessment (n=9) showed the greatest anti-tumor activity with a cORR of 55.6% and a median progression-free survival (mPFS) of 7.4 months.
Combination therapy was well tolerated with a manageable safety profile consistent with prior experience with each investigational agent.
Announced strategic prioritization and resource optimization efforts, including approximately 30% workforce reduction primarily in preclinical research, expected to extend cash runway into Q4 2026.
Announced key additions to our leadership team and Board of Directors throughout 2024 and early 2025.
Allison Dillon, Ph.D., an experienced drug development, commercial strategy and business development leader, as Chief Business Officer.
Alan Sandler, M.D., a distinguished leader with more than 30 years of experience in oncology and drug development, as Chief Medical Officer.
Harish Shantharam, CFA, a proven biotech industry executive with over two decades of senior leadership experience in finance, commercial and corporate operations, as Chief Financial Officer.
Barbara Klencke, M.D., a seasoned clinical leader in oncology drug development with more than 20 years of industry experience, appointed to ALX Oncology’s Board of Directors.
Chris H. Takimoto, M.D., Ph.D., FACP, a distinguished researcher and drug developer with a proven track record in oncology with 17 years of industry experience, appointed to ALX Oncology’s Board of Directors.
Announced that Jaume Pons, Ph.D., Founder, President and Chief Scientific Officer, will be departing from his current position and transitioning to the role of Senior Scientific Advisor in Q2 2025.
Upcoming Clinical Milestones

Head and Neck Squamous Cell Carcinoma: Topline results from Phase 2 ASPEN-03 randomized clinical trial of evorpacept with KEYTRUDA (pembrolizumab) anticipated in Q2 2025
Head and Neck Squamous Cell Carcinoma: Topline results from Phase 2 ASPEN-04 randomized clinical trial of evorpacept with KEYTRUDA and chemotherapy anticipated in Q2 2025
Urothelial Cancer: Updated results from Phase 1 ASPEN-07 clinical trial of evorpacept in combination with PADCEV (enfortumab vedotin) anticipated in Q2 2025
Gastric/GEJ Cancer: Regulatory guidance on the gastric cancer registrational path to be provided in Q2 2025
Breast Cancer: Topline results from Phase 1b I-SPY clinical trial of evorpacept with ENHERTU (fam-trastuzumab deruxtecan-nxki) anticipated in 2H 2025
Breast Cancer: Patient dosing anticipated to initiate for ASPEN-BREAST Phase 2 clinical trial in mid-year 2025
Colorectal Cancer (CRC): Patient dosing anticipated to initiate for ASPEN-CRC Phase 1b clinical trial in mid-year 2025
New ADC Clinical Candidate: Novel EGFR-directed ADC, ALX2004, planned IND submission in March 2025
2024 Full Year and Fourth Quarter Financial Results:

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments as of December 31, 2024, were $131.3 million. The Company believes its cash, cash equivalents and investments are sufficient to fund planned operations into Q4 of 2026. Potential impact of near-term catalysts related to ASPEN-03/04 HNSCC read out and FDA interaction on ASPEN-06 (for e.g., gastric cancer accelerated approval and/or Phase 3 initiation) are excluded from cash runway guidance.
Research and Development ("R&D") Expenses: R&D expenses consist primarily of preclinical, clinical and development costs related to the development of the Company’s current lead product candidate, evorpacept, and R&D personnel-related expenses including stock-based compensation. R&D expenses for the three months ended December 31, 2024 were $23.5 million compared to $41.8 million for the prior-year period or a decrease of $18.3 million. This decrease was primarily attributable to a decrease of $17.3 million in clinical and development costs primarily due to less manufacturing of clinical trial materials to support active clinical trials for our lead product candidate, evorpacept, and a decrease in stock-based compensation expense slightly offset by increased preclinical costs for development of new targets and increased personnel and related costs. R&D expenses for the year ended December 31, 2024 were $116.4 million, compared to $141.8 million for the prior-year period.
General and Administrative ("G&A") Expenses: G&A expenses consist primarily of administrative personnel-related expenses, including stock-based compensation and other costs such as legal and other professional fees, patent filing and maintenance fees, and insurance. G&A expenses for the three months ended December 31, 2024 were $7.1 million compared to $6.2 million for the prior year period or an increase of $0.8 million. This increase was primarily attributable to an increase in personnel and related costs. G&A expenses for the year ended December 31, 2024 were $26.1 million compared to $28.5 million for the prior-year period.
Net loss: GAAP net loss was ($29.2) million for the three months ended December 31, 2024, or ($0.55) per basic and diluted share, as compared to a GAAP net loss of ($45.5) million for the three months ended December 31, 2023, or ($0.93) per basic and diluted share. The lower net loss is primarily attributed to lower R&D expenses. GAAP net loss was ($134.9) million for the year ended December 31, 2024, or ($2.58) per basic and diluted share, as compared to a GAAP net loss of ($160.8) million for the year ended December 31, 2023, or ($3.74) per basic and diluted share. Non-GAAP net loss was ($23.2) million for the three months ended December 31, 2024, as compared to a non-GAAP net loss of ($38.7) million for the three months ended December 31, 2023. Non-GAAP net loss was ($107.5) million for the year ended December 31, 2024, as compared to a non-GAAP net loss of ($134.3) million for the year ended December 31, 2023. A reconciliation of GAAP to non-GAAP financial results can be found at the end of this news release.

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 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported financial results for the fourth quarter and full year ended December 31, 2024, and provided a corporate update (Press release, Black Diamond Therapeutics, MAR 6, 2025, View Source [SID1234650947]).

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"We continue to focus on advancing BDTX-1535 for the treatment of patients with EGFRm NSCLC and providing a clinical update on our Phase 2 trial for newly diagnosed patients in the second quarter of 2025," said Mark Velleca, M.D., Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "We also look forward to the expansion in the first quarter of 2025 of the investigator sponsored window of opportunity trial of BDTX-1535 into newly diagnosed glioblastoma patients with EGFR aberrations, an area of high unmet medical need."
Recent Developments & Upcoming Milestones:

BDTX-1535:

Black Diamond anticipates the following upcoming key milestones for BDTX-1535:

•Initial Phase 2 clinical data in newly diagnosed patients with non-classical epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC) in the second quarter of 2025 (NCT05256290).
•Updated Phase 2 clinical data in patients with recurrent EGFRm NSCLC with a broad spectrum of classical, non-classical, and C797S resistance mutations in the second half of 2025.
•Planning to solicit U.S. Food and Drug Administration (FDA) feedback on a potential pivotal registrational path for BDTX-1535 in newly diagnosed EGFRm NSCLC patients in the second half of 2025.
•Expansion of the investigator sponsored "window of opportunity" trial (also known as a Phase 0/1 "Trigger" trial) into a Phase 0/2 trial in newly diagnosed glioblastoma (GBM) patients with epidermal growth factor receptor (EGFR) aberrations in the first quarter of 2025. The trial is sponsored by the Ivy Brain Tumor Center in Phoenix, Arizona (NCT06072586).
Financial Highlights
•Cash Position: Black Diamond ended 2024 with approximately $98.6 million in cash, cash equivalents, and investments compared to $131.4 million as of December 31, 2023. Net cash used in operations was $62.3 million for the year ended December 31, 2024 compared to $66.7 million for the year ended December 31, 2023.

•Research and Development Expenses: Research and development (R&D) expenses were $12.3 million for the fourth quarter of 2024, compared to $15.3 million for the same period in 2023. Research and development expenses were $51.3 million for the year ended December 31, 2024, compared to $59.4 million for the year ended December 31, 2023. The decrease in R&D expenses was primarily due to workforce efficiencies and increased focus on advancing and optimizing development plans for BDTX-1535.
•General and Administrative Expenses: General and administrative (G&A) expenses were $6.0 million for the fourth quarter of 2024, compared to $5.6 million for the same period in 2023, and $27.5 million for the year ended December 31, 2024, compared to $27.1 million for the year ended December 31, 2023. The increase in G&A expenses was primarily related to one-time restructuring costs.
•Net Loss: Net loss for the fourth quarter of 2024 was $16.0 million, as compared to $19.4 million for the same period in 2023. Net loss for the year ended December 31, 2024 was $69.7 million compared to $82.4 million for the year ended December 31, 2023.
Financial Guidance
•Black Diamond ended 2024 with approximately $98.6 million in cash, cash equivalents and investments which the Company believes is sufficient to fund its anticipated operating expenses and capital expenditure requirements into the fourth quarter of 2026.

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 Merck, a leading science and technology company, reported profitable growth in 2024 and delivered on its guidance for the year (Press release, Merck KGaA, MAR 6, 2025, View Source [SID1234654166]). A strong performance of Healthcare, a rebound in Life Science and profitable growth in Electronics contributed to this. During the year, Merck also strategically sharpened its portfolio’s focus on future growth areas. After a strong fourth quarter 2024, the company is looking toward 2025 with confidence and expects continued profitable growth.

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"Merck is back on a growth path with all three businesses. The challenges of recent years have been taken as an opportunity to strengthen our supply chains and invest in Europe, the United States and Asia. In 2025, we will continue to deliver profitable growth across our company. With our innovation-driven portfolio, we are ideally positioned to benefit from global macro trends such as complex biologics, novel modalities, and semiconductors for the AI era," said Belén Garijo, Chair of the Executive Board and CEO of Merck.