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.

On March 6, 2025 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, reported 2024 financial results and provided a business update (Press release, CytomX Therapeutics, MAR 6, 2025, View Source [SID1234650950]).

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"Throughout 2024 we continued to advance and prioritize our multi-modality clinical pipeline with disciplined capital allocation. Entering 2025, our top strategic priority is the clinical development of our lead program, CX-2051, in advanced colorectal cancer. CX-2051 is a masked EpCAM-targeting ADC armed with a topoisomerase-1 payload, specifically designed to address profound unmet need in CRC. EpCAM is highly expressed in more than 90 percent of colorectal cancers and we believe our PROBODY platform offers a unique strategy to unlock the tremendous potential of this previously undruggable target," said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX.

Dr. McCarthy continued, "We are encouraged by our progress to date in the first in human evaluation of CX-2051, having successfully escalated to doses predicted to be in the biologically active range. We believe CX-2051 is behaving as designed, and we look forward to sharing preliminary clinical data and future plans for CX-2051 in the coming months. We are optimistic about the potential for CX-2051 in colorectal cancer, and also in many other solid tumor types that express EpCAM and where major unmet needs remain to be addressed."

Pipeline Program Updates:

CX-2051 (EpCAM PROBODY Topo-1 ADC)

CX-2051 has been prioritized as Company’s lead clinical program with an initial focus in advanced metastatic CRC. The Phase 1 study of CX-2051 was initiated in April of 2024 and is focused on advanced metastatic CRC, one of many tumor types where there is high expression of EpCAM. CX-2051 contains a next generation topoisomerase-1 payload (CAMP59) and a cleavable payload-antibody linker licensed from AbbVie (formerly Immunogen).
EpCAM (Epithelial Cell Adhesion Molecule) is a highly expressed tumor antigen that has been previously undruggable with systemically administered agents due to expression on normal tissues. CX-2051 is designed to open a therapeutic window for this high potential target and deliver meaningful anti-cancer activity in solid tumors, including CRC. CRC remains an area of high unmet medical need, especially in the late-line setting, where outcomes from currently approved standard of care remain extremely poor, with objective response rates in the low-single digit percentages and approximately two to four months of progression free survival1.
The CX-2051 study is currently enrolling patients with advanced CRC who have generally received three or more prior lines of systemic therapy in the metastatic setting. Enrolled patients are not being pre-selected for EpCAM expression or for disease characteristics such as KRAS mutational status or liver metastases.
In Phase 1 dose escalation to date, CX-2051 has demonstrated a favorable tolerability profile and doses predicted to be therapeutically active, based on preclinical modeling, have been attained.
The CX-2051 Phase 1 study is ongoing and is evaluating the seventh dose level.
Initial Phase 1a data in CRC are expected to be presented in the first half of 2025.
CX-801 (PROBODY Interferon-alpha 2b)

Phase 1 dose escalation continues with a focused early development strategy in metastatic melanoma and with the goal of initiating combination therapy with CX-801 and KEYTRUDA in 2025.
The Phase 1 study is currently in the fourth monotherapy dose escalation cohort where the dose of CX-801 exceeds the approved dose of the unmasked peginterferon alfa-2b (SYLATRON)2.
Initial Phase 1a translational and biomarker data in advanced melanoma is expected in the second half of 2025.
KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA

CX-904 (EGFR-CD3 PROBODY TCE)

Based on CX-904 clinical observations to-date as well as CytomX pipeline priorities, CytomX and Amgen have jointly decided to not further develop CX-904.
Corporate and Financial:

Organization: In January 2025, CytomX announced a reduction of organizational headcount by approximately 40 percent in order to direct capital resources primarily to CX-2051 and create additional flexibility in its cost structure. Headcount reductions primarily impact areas supporting non-partnered early research and general and administrative functions and are expected to be completed by the end of the first quarter of 2025.
Financial: Cost reductions realized from the January 2025 restructuring combined with focused clinical development priorities are expected to extend cash runway into the second quarter of 2026. CytomX ended 2024 with $100.6 million of cash, cash equivalents and investments.
Research collaborations:
New milestone achieved in Astellas T-cell engager collaboration: In February 2025, Astellas advanced the second program to GLP toxicology studies, triggering a $5 million milestone payment to CytomX.
Multiple drug discovery programs continue across our research collaborations with a focus on T-cell engagers. CytomX has research collaborations with Bristol Myers Squibb, Amgen, Astellas, Regeneron, and Moderna.

Full Year 2024 Financial Results:

Cash, cash equivalents and investments totaled $100.6 million as of December 31, 2024, compared to $174.5 million as of December 31, 2023.

Total revenue was $138.1 million for the year ended December 31, 2024, compared to $101.2 million in 2023. The increase in revenue was driven primarily by a higher percentage of completion for research programs in the Bristol Myers Squibb collaboration as well as the collaborations with Moderna, Astellas, and Regeneron.

In 2024, CytomX remained focused on controlling costs and efficiently progressing its pipeline programs. Total operating expense in 2024 was $113.1 million compared to $107.7 million in 2023, an increase of $5.4 million. The increase in operating expenses was primarily due to a $5.0 million milestone payment to AbbVie (formerly ImmunoGen) as a result of dosing the first patient for CX-2051 in Phase 1 based upon the ImmunoGen 2019 License Agreement.

Research and development expenses increased by $5.7 million during the year ended December 31, 2024, to $83.4 million compared to $77.7 million in 2023. The $5.0 million milestone payment to AbbVie for dosing of the first patient in the CX-2051 Phase 1 study was recorded in 2024 as a research and development expense and was the primary driver of increased research and development spend in 2024 compared to 2023.

General and administrative expenses were essentially flat in 2024 compared to 2023, decreasing by $0.3 million to $29.7 million for the year ended December 31, 2024.

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, Bio-Path Holdings, Inc. (the "Company") reported to have entered into a securities purchase agreement (the "Purchase Agreement") with 1800 Diagonal Lending LLC, a Virginia limited liability company (the "Lender"), an accredited investor, for the issuance and sale of a promissory note in the aggregate principal amount of $161,000 (the "Note") for a purchase price of $140,000 after deducting the original issue discount of $21,000 (Filing, Bio-Path Holdings, MAR 6, 2025, View Source [SID1234651019]). The Note bears a one-time interest charge of twelve percent that is applied on the date of issuance, March 6, 2025. The Note shall be paid in five payments with the first payment of $90,160 due on August 30, 2025 and each subsequent payment shall be equal to $22,540 which are due on September 30, 2025, October 30, 2025, November 30, 2025 and December 30, 2025.

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Upon the occurrence and during any continuation of any Event of Default (as defined in the Note), the Note shall become immediately due and payable and the Company shall pay to the Lender, in full satisfaction, an amount equal to 150% times the sum of (i) the then outstanding principal amount of the Note plus (ii) accrued and unpaid interest on the unpaid principal amount of the Note to the date of payment plus (iii) default interest, if any, at a rate of 22% per annum on the amounts referred to in clauses (i) and/or (ii) plus (iv) any amounts owed to the Lender pursuant to the Conversion Right (as defined below). In addition, only upon an Event of Default and during any continuation thereof, the Lender may elect to convert all or any part of the outstanding principal and interest on the Note in fully paid and non-assessable shares of the Company’s common stock, par value $0.001 per share ("Common Stock") at a conversion price per share equal to 65% of the lowest closing bid price of the Common Stock for the ten trading days prior to the date of conversion (the "Conversion Right"). The Lender, together with its affiliates, may not convert any portion of such Note to the extent that the Lender would own more than 4.99% of the Company’s outstanding Common Stock immediately after the conversion

The issuance of the Note and the issuance of the shares of Common Stock issuable upon any Event of Default will not be registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state securities laws. The Note and the shares of Common Stock, if issued, will be issued in reliance on the exemptions from registration provided by Section 4(a)(2) under the Securities Act and/or Regulation D promulgated thereunder.

The Note and the Purchase Agreement contain standard and customary representations and warranties, agreements and obligations, and events of default. The foregoing descriptions of terms and conditions of the Purchase Agreement and the Note do not purport to be complete and are qualified in their entirety by the full text of the form of the Purchase Agreement and the Note, which are attached hereto as Exhibits 10.1 and 4.1, respectively.

This Current Report on Form 8-K does not constitute an offer to sell the securities or a solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.