On March 11, 2025 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company developing innovative treatments that exploit specific cancer cell vulnerabilities while minimizing damage to healthy cells, reported that it has entered into a Material Transfer Agreement (MTA) with MD Anderson Cancer Center (Press release, Aprea, MAR 11, 2025, View Source [SID1234651064]). Under the agreement, Aprea will supply its proprietary WEE1 kinase inhibitor, APR-1051, to support preclinical research aimed at exploring its potential in treating HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC) expressing genomic markers of replication stress.

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The agreement will enable the research group at MD Anderson to conduct a series of pre-clinical experiments designed to generate preliminary efficacy and mechanistic data to support future clinical trials and treatment regimens. The goal of this research is to further characterize the therapeutic potential of APR-1051 in HNSCC and generate insights that could support future clinical development strategies. The studies will include combining APR-1051 with immune checkpoint inhibitors (ICIs) to treat both HPV+ and HPV- HNSCC tumors harboring genomic markers of replication stress. The project is being overseen by Professors Jeffrey N. Myers, M.D., Ph.D., F.A.C.S., and Abdullah A. Osman, Ph.D., both from the Department of Head and Neck Surgery, MD Anderson Cancer Center. Prof. Myers is the leading expert on head and neck cancers.

"This agreement with MD Anderson Cancer Center underscores our commitment to leveraging strong academic partnerships to advance our pipeline of DDR inhibitors" said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "HNSCC represents a major global health burden, and prior work conducted at MD Anderson, and published by Professors Myers, Osman and their colleagues, suggests that WEE1 kinase may present a promising therapeutic target. We look forward to the insights that will emerge from this important research."

Head and neck cancers, particularly those associated with HPV infection, present significant clinical challenges. WEE1 kinase inhibition represents a novel therapeutic strategy by targeting the effectiveness of DNA damage response, potentially enhancing the sensitivity of cancer cells to existing treatments.

A high proportion of HNSCC cases are attributable to HPV. An estimated 70% of the 20,000 cases of OPSCC (HNSCC that occurs in the oropharynx) seen annually in the US are attributable to HPV. Although these HPV+ tumors generally have a better prognosis than their HPV- counterparts, standard of care chemotherapy and radiation is very toxic and surviving patients often face a lifetime of difficulties. The group at MD Anderson was the first to observe that HPV+ HNSCC tumor lines are very sensitive to WEE1 kinase inhibition both in vitro and in vivo. Their findings were published in a paper in Clinical Cancer Research in 2015. The researchers also showed in their previous experiments that a subset of HPV- HNSCC tumors may also be susceptible to this mechanism.

Under the terms of the agreement, Aprea will retain all rights, title, and interest in APR-1051.

APR-1051 is a potent and selective small molecule that has been designed to potentially solve tolerability challenges of the WEE1 class and may achieve greater clinical activity than other programs currently in development. The candidate is currently being tested in the ongoing ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) clinical trial. This Phase 1 clinical trial is evaluating single-agent APR-1051 in patients advanced solid tumors harboring cancer-associated gene alterations.

On March 11, 2025 Caris Life Sciences (Caris), a leading next-generation AI TechBio company and precision medicine pioneer, reported that the company and collaborators within the Caris Precision Oncology Alliance (Caris POA) will collectively present five studies across multiple gynecological tumor types at the Society of Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer, March 14-17, 2025, in Seattle, Washington (Press release, Caris Life Sciences, MAR 11, 2025, View Source [SID1234651083]). The findings demonstrate the power of Caris’ comprehensive clinico-genomic database to enable novel insights into cancer that could have profound effects on a patient’s diagnosis, prognosis, care plan and response to treatment.

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"Caris and our POA collaborators are proud to present five studies at this year’s SGO Annual Meeting highlighting the critical role of molecular profiling and biomarkers in personalizing treatment for gynecological cancers," said Caris EVP and Chief Medical Officer George W. Sledge, Jr., MD. "By utilizing our comprehensive clinico-genomic database, we have improved the understanding of tumor biology and shown how specific molecular characteristics affect prognosis and treatment efficacy. This work exemplifies our dedication to advancing precision medicine and optimizing oncology treatment strategies."

Oral Presentations

Improved Real World Outcomes in Patients with Low-Grade Serous Ovarian Carcinoma and MAPK Pathway Mutations Treated with Trametinib
Focused Forum IV Finding IMPACT: The Needle in the Haystack
March 15: 4:52-4:58 PM PST

Impact of CCNE1 Amplification on Molecular Signatures and Patient Outcomes in High Grade Serous Ovarian and Endometrial Cancer
Focused Forum X Future IMPACT
March 16: 3:32-3:40 PM PST
Oral Featured Poster

Genomic and Immunohistochemical Characterization of NSMP Endometrial Cancer: A Novel Approach to Estrogen Receptor Positivity
Oral Featured Poster Session II: Multiple Ways to Make an IMPACT
March 15: 4:23-4:26 PM PST
Posters

GPR171, a Prognostic Marker of Improved Survival in Cervix Cancer – A Deep South Consortium in Oncology (DSCO) Project
Poster Session | March 16, 2:00 – 3:30 PM PST

Comparison of Breast and Gastric HER2 Immunohistochemistry (IHC) Scoring Criteria in the Assessment of Endometrial Carcinoma
Poster Session | March 16, 2:00 – 3:30 PM PST
Poster and abstract summaries highlighting this research will be available onsite at Caris’ booth #416. The full abstracts will be available on the Caris website following the presentation.

The Caris POA includes 96 cancer centers, academic institutions, research consortia and healthcare systems, including 47 NCI-designated cancer centers, collaborating to advance precision oncology and biomarker-driven research. Caris and POA members work together to establish and optimize standards of care for molecular testing through innovative research to improve clinical outcomes for cancer patients.

On March 11, 2025 GenScript reported its annual results for the year 2024 (Presentation, GenScript, MAR 11, 2025, https://www.genscript.com/gsfiles/IPO/2024_GenScript_Annual_Results_EN.pdf?=2?1720353431 [SID1234652211]).

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On March 11, 2025 Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) reported positive topline results from the Phase 3 VERITAC-2 clinical trial (NCT05654623) evaluating vepdegestrant monotherapy versus fulvestrant in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer whose disease progressed following prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy (Press release, Arvinas, MAR 11, 2025, View Source [SID1234651065]). These are the first pivotal data for vepdegestrant, a potential first-in-class investigational oral PROteolysis TArgeting Chimera (PROTAC) ER degrader.

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The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to fulvestrant. The results exceeded the pre-specified target hazard ratio of 0.60 in the ESR1m population. The trial did not reach statistical significance in improvement in PFS in the intent-to-treat (ITT) population.

"The first Phase 3 data readout for a PROTAC degrader represents a significant achievement and these data show that vepdegestrant has the potential to provide clinically meaningful outcomes for thousands of patients with metastatic breast cancer whose tumors harbor estrogen receptor 1 mutations," said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. "We want to thank the patients and investigators who participated in this trial, and we look forward to sharing these data with health authorities as well as at a medical conference in 2025."

Overall survival was not mature at the time of the analysis, with less than a quarter of the required number of events having occurred. The trial will continue to assess overall survival as a key secondary endpoint. In the trial, vepdegestrant was generally well tolerated and its safety profile was consistent with what has been observed in previous studies. Detailed results from VERITAC-2 will be submitted for presentation at a medical meeting later this year, and these data will be shared with global regulatory authorities to potentially support regulatory filings.

"Patients with advanced ER+/HER2- metastatic breast cancer face significant clinical challenges, with limited treatment options following disease progression and the development of resistance to available endocrine therapies," said Megan O’Meara, M.D., Interim Chief Development Officer, Pfizer Oncology. "These data from VERITAC-2 support the potential of vepdegestrant to give patients whose tumors harbor ESR1 mutations additional time without disease progression, compared to fulvestrant."

Vepdegestrant is an investigational oral PROTAC ER degrader for ER+/HER2- breast cancer being jointly developed by Arvinas and Pfizer and is designed to harness the body’s natural protein disposal system to specifically target and degrade the ER. In February 2024, the companies announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the investigation of vepdegestrant for monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.

About Metastatic Breast Cancer
About 2.3 million new breast cancer diagnoses were reported globally in 2022,1 and it is estimated there will be nearly 320,000 people diagnosed with breast cancer in the U.S. in 2025.2 Estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer accounts for approximately 70% of all cases.3

Nearly 30% of women initially diagnosed with early-stage breast cancer will ultimately develop metastatic breast cancer (MBC),4 the most advanced stage in which the disease has spread beyond the breast to other parts of the body. Treatment advances have helped those with MBC better manage symptoms, slow tumor growth, and may allow them to live longer, but most patients ultimately develop resistance to current standard-of-care treatments in the first-line setting and experience disease progression. ESR1 mutations are a common cause of acquired resistance and are found in approximately 40% of patients in the second-line setting.5 6 7

About the VERITAC-2 Clinical Trial
The Phase 3 VERITAC-2 clinical trial (NCT05654623) is a global randomized study evaluating the efficacy and safety of vepdegestrant (ARV-471) as a monotherapy compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer. The trial enrolled 624 patients at sites in 26 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy.

Patients were randomized to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. The primary endpoint was progression-free survival (PFS) in the intent-to-treat and ESR1m populations as determined by blinded independent central review. Overall survival is a key secondary endpoint.

About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC (PROteolysis TArgeting Chimera) protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER-positive (ER+)/human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.

On March 11, 2025 Luminary Therapeutics reported that it has been awarded up to $5.8 million in funding from the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services, to develop a mesothelin chimeric antigen receptor T cells ("CAR T") targeting non-small cell lung cancer and colorectal cancer (Press release, Luminary Therapeutics, MAR 11, 2025, View Source [SID1234651084]).

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"While CAR T therapies have been effective for blood cancers, solid tumors like lung and colorectal cancers have proven to be resistant to current CAR T therapies", said Jeff Liter, CEO and President of Luminary Therapeutics. "This project combines an allogeneic CAR T for direct killing of tumor cells with the ability to utilize the patient’s immune system to target tumor cells by also leveraging the gamma delta cell’s ability to work as professional antigen-presenting cells (APCs) and presenting tumor-specific neo antigens. Combining neo antigen-presenting functions with CAR directed killing in a single cellular chassis will increase the effectiveness of cellular therapies by recruiting a patient’s immune system to increase the response and durability of tumor clearance."

Since its founding in 2019, Luminary Therapeutics has developed a proprietary gamma delta expansion platform that is unique in the industry and allows Luminary to manufacture cell therapies with a significantly lower cost and reduced time to clinic. Leveraging this platform, the Company has developed two groundbreaking therapeutic programs designed to overcome current challenges of CAR T therapies for solid tumors and autoimmune disorders. The award from ARPA-H represents not only a significant step forward in scaling Luminary’s therapeutic pipeline, while expanding the capabilities of its gamma delta expansion platform, but also aligns with ARPA-H’s mission to improve health outcomes for everyone.