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 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 Agenus Inc. ("Agenus" or the "Company") (Nasdaq: AGEN), an immuno-oncology company advancing innovative cancer therapies, reported financial and operational results for Q4 and full-year 2024, highlighting strategic measures to substantially reduce operational costs while preserving and enhancing the potential of its leading BOT/BAL program (Press release, Agenus, MAR 11, 2025, View Source [SID1234651063]).

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"In line with our strategic objectives, we significantly reduced our annualized operational burn rate. We anticipate further reducing our annual burn to an annualized rate of approximately $50 million by mid-2025 through the externalization of development costs associated with BOT/BAL, monetization of our CMC assets, and other reductions in operating expenses," stated Garo Armen, Ph.D., Chairman and CEO of Agenus. "These steps reflect our commitment to prioritizing resources for BOT/BAL— our most promising clinical asset— while maintaining its development trajectory."

Key Operational Highlights:

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Achieved Q4 2024 operational cash burn of $28.7 million, substantially reducing annualized expenditures.
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Initiated further operational cost reductions expected to lower annual burn to approximately $50 million by mid-2025.
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Continued aggressive monetization of non-core assets, including manufacturing infrastructure in Emeryville, Berkeley, and Vacaville, CA, to bolster cash position and reduce operating expenses.
Clinical Progress and Strategic Validation:

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Botensilimab/balstilimab (BOT/BAL) program demonstrated groundbreaking clinical outcomes in resistant tumor types, strongly validated by external clinical trials and global oncology experts. Specifically, data presented at ASCO (Free ASCO Whitepaper)-GI 2025 demonstrate the potential of BOT/BAL to deliver meaningful, durable responses across neoadjuvant and later lines of CRC treatment—especially for patients whose tumors are unresponsive to existing checkpoint inhibitors.
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Presentations of preclinical and clinical data at major medical congresses during 2024 at ASCO (Free ASCO Whitepaper)-GI, AACR (Free AACR Whitepaper), ASCO (Free ASCO Whitepaper), ESMO (Free ESMO Whitepaper), ESMO (Free ESMO Whitepaper)-GI, and SITC (Free SITC Whitepaper).
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Continued BOT/BAL data generation via investigator-sponsored trials (ISTs), led by top global oncology centers, providing independent validation and substantial cost-efficiencies.

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Discussions ongoing for potential partnerships and external funding aimed at accelerating BOT/BAL clinical registration in key cancer indications, notably colorectal cancer.
These deliberate operational and strategic actions position Agenus to effectively sustain and advance its high-potential BOT/BAL program, ensuring the company continues delivering substantial value for both patients and shareholders.

Financial Highlights

Agenus ended the year 2024 with a consolidated cash balance of $40.4 million compared to $76.1 million on December 31, 2023. Cash used in operations for the year ended December 31, 2024 was $158.3 million, reduced from $224.2 million for the prior year.

For the year ended December 31, 2024, Agenus recognized revenue of $103.5 million and incurred a net loss of $232.3 million, or $10.59 per share. For the fourth quarter ended December 31, 2024, Agenus recognized revenue of $26.8 million and incurred a net loss of $46.8 million or $2.04 per share. Revenue primarily includes non-cash royalty revenue.

Conference Call

Date: Tuesday, March 11th, at 8:30 a.m. ET
To access dial-in numbers, please register here.
Conference ID: 73242

Webcast

A live webcast and replay of the conference call will be accessible on the company’s website at View Source

About Botensilimab (BOT)

Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

About Balstilimab (BAL)

Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in >900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types.

On March 10, 2025 Agilent Technologies Inc. (NYSE: A) reported its PD-L1 IHC 28-8 pharmDx kit has received two new companion diagnostic indications approvals under EU IVDR1, expanding the eligibility of treatment to early-stage non-small cell lung cancer (NSCLC) and previously untreated advanced melanoma patients (Press release, Agilent Technologies, MAR 10, 2025, View Source [SID1234651055]). These two new indications bring the total indications launched in Europe for PD-L1 IHC 28-8 pharmDx to nine. PD-L1 IHC 28-8 pharmDx is approved for exclusive use with the Agilent Autostainer Link 48 advanced staining solution.

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Lung cancer and malignant melanoma are major healthcare concerns worldwide, with lung cancer accounting for over two million new cases in 2020 and an estimated 1.77 million deaths each year, and malignant melanoma accounting for over 324,000 new cases in 2020 and over 57,000 deaths each year2. PD-L1 is a critical biomarker for potential response to anti-PD-1 therapies, which are revolutionizing the treatment of cancer. Pathology labs play an important role in informing treatment decisions.

When used in conjunction with the PD-L1 IHC 28-8 pharmDx as a companion test, in the European Union: (a) resectable NSCLC patients with PD-L1 expression ≥1% and at high risk of recurrence may be eligible for treatment with Bristol Myers Squibb’s OPDIVO (nivolumab) in combination with platinum based chemotherapy; and (b) patients 12 years of age and older with tumor cell PD-L1 expression < 1% that have previously untreated advanced (metastatic or unresectable) melanoma may be eligible for treatment with Bristol Myers Squibb’s Opdualag (nivolumab and relatlimab).

PD-L1 IHC 28-8 pharmDx is the only clinically validated test for identifying patients for these treatments; these two new indications will aid pathologists, in conjunction with oncologists, in selecting appropriate treatment options, offering hope for patients diagnosed with these cancers. IVDR compliance certification further enhances the confidence of patients, consumers, and healthcare professionals in the EU by demonstrating that these medical devices can be safely relied upon as part of the diagnostic workflow.

Simon May, senior vice president of Agilent’s Life Sciences and Diagnostics Markets Group, remarked: "The two added indications of PD-L1 IHC 28-8 pharmDx will give physicians in Europe critical information to inform treatment decisions for patients with these common and potentially deadly cancers. This endorsement underscores Agilent’s leadership in the development of companion diagnostics for groundbreaking therapies containing anti-PD-1 antibodies."

An innovative industry leader with more than 50 years of experience, Agilent launched the first FDA-approved companion diagnostic and continues to deliver world-class CDx products in close collaboration with pharma partners.

OPDIVO is a registered trademark of Bristol-Myers Squibb Company; Opdualag is a trademark of Bristol-Myers Squibb Company.

In Vitro Diagnostic Medical Devices Regulation (europa.eu)
Sung. H., Ferlay. J., et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA. Cancer J. Clin. 2021, 71, 209–249

On March 10, 2025 enGene Holdings Inc. (Nasdaq: ENGN, or "enGene" or the "Company"), a clinical-stage, non-viral genetic medicines company, reported its financial results for the first quarter ended January 31, 2025, and provided a business update (Press release, enGene, MAR 10, 2025, View Source [SID1234651054]).

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"With the expansion of LEGEND study sites into Europe and Asia, enrollment in our pivotal cohort continues to track in-line with our plan to file a BLA for detalimogene in mid-2026," said Ron Cooper, Chief Executive Officer of enGene. "We look forward to the remainder of 2025, during which we expect to announce enrollment completion of LEGEND’s pivotal cohort and provide additional updates on other LEGEND study cohorts. We continue to believe in detalimogene’s opportunity to transform the treatment landscape of NMIBC through a unique and differentiated overall profile that is highly attractive to both patients and physicians due to its potential for tolerability, ease-of-use, and efficacy."

Recent Corporate Updates

LEGEND study trial site expansion: Over the course of the first quarter of 2025, the Company expanded its clinical footprint for the LEGEND study with the addition of trial sites in Europe and Asia. In addition, all four of LEGEND’s cohorts are now open for enrollment, including the pivotal cohort evaluating detalimogene voraplasmid (also known as detalimogene, and previously EG-70) in high-risk, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with CIS as well as Cohort 2a and 2b (i.e., NMIBC patients with CIS who are naïve to treatment with BCG and NMIBC patients with CIS who have been exposed to BCG, but have not received adequate BCG treatment), and Cohort 3 (BCG-unresponsive high-risk NMIBC patients with papillary-only disease). Global enrollment is taking place under an amended protocol that is designed to align with the American Urological Association’s current treatment guidelines and real-world practices.

LEGEND study now includes maintenance dosing: The amended LEGEND protocol allows patients from all cohorts who are in complete response at 12 months to continue receiving detalimogene on a dose-reduced maintenance schedule throughout their second year of treatment. At the end of year two, patients may elect to remain on maintenance therapy for another year, for a total of three years of therapy. Maintenance treatment consists of two instillations of detalimogene per three-month cycle, administered at week one and at week two of each cycle. The maintenance regimen is intended to evaluate the potential of longer-term detalimogene treatment to improve or maintain durability of response with the lower patient burden associated with a less frequent dosing regimen.

First Quarter 2025 Financial Results

As of January 31, 2025, cash, cash equivalents and marketable securities were $272.8 million. The Company expects that its existing cash, cash equivalents and marketable securities will fund operating expenses, debt obligations and capital expenditures into 2027.

Three Months ended January 31, 2025

Total operating expenses were $26.6 million for the three months ended January 31, 2025, compared to $10.8 million for the three months ended January 31, 2024. Research and development expenses increased by $14.3 million, mainly due to increasing manufacturing and clinical costs related to our pivotal LEGEND study and headcount costs. General and administrative expenses increased by $1.5 million, primarily driven by increased headcount intended to support the Company’s operation as a publicly traded company.

For the three months ended January 31, 2025, net loss attributable to common shareholders was approximately $24.6 million, or $0.48 per share, compared to approximately $10.7 million, or $0.46 per share, for the same period for the three months ended January 31, 2024. The increase in net loss is mainly attributed to the increase in operating expenses, partially offset by net interest income earned during the period.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Non-muscle invasive bladder cancer (NMIBC) is a disease with a significant patient burden, high clinical needs, and massive economic impact on our healthcare system. NMIBC occurs when cancer cells grow in the tissues that line the interior of the bladder, but the cancer has not yet penetrated deeper into the muscle of the bladder wall. About 75-80% of new bladder cancer diagnoses are NMIBC. Patients suffering from high-risk NMIBC who are unresponsive to the standard of care, Bacillus Calmette-Guérin (BCG), face high rates of disease recurrence (50-70%) and are subject to full removal of the bladder (cystectomy) as a curative but life-altering next step.

About Detalimogene

Detalimogene is a novel, investigational, non-viral genetic medicine for patients with high-risk, non-muscle invasive bladder cancer (NMIBC), including Bacillus Calmette-Guérin (BCG)-unresponsive disease. It is designed to be instilled in the bladder and elicit a powerful yet localized anti-tumor immune response.

Detalimogene was developed using the Company’s Dually Derivatized Oligochitosan (DDX) platform, a technology designed to transform how gene therapies are accessed by patients and utilized by clinicians. Medicines developed with the DDX platform can potentially overcome the limitations of viral-based gene therapies, simplify safe handling and cold storage complexities, and streamline both manufacturing processes and administration paradigms.

Detalimogene has received Fast Track designation from the U.S. Food and Drug Administration (FDA) based on its potential to address the high unmet medical need for patients with BCG-unresponsive carcinoma in situ (CIS) NMIBC with or without resected papillary tumors who are unable to undergo cystectomy. Fast Track designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

About the Pivotal LEGEND Trial

Detalimogene is being evaluated in the ongoing, open-label, multi-cohort, Phase 2 LEGEND trial to establish its safety and efficacy in high-risk, non-muscle invasive bladder cancer (NMIBC). LEGEND’s pivotal cohort (Cohort 1) consists of approximately 100 patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC with carcinoma in situ (CIS) (with or without papillary disease) and is designed to serve as the basis of the Company’s planned Biologics License Application (BLA) filing. In addition to this pivotal cohort, three additional cohorts are actively enrolling patients, including NMIBC patients with CIS who are naïve to treatment with BCG (Cohort 2a); NMIBC patients with CIS who have been exposed to BCG but have not received adequate BCG treatment (Cohort 2b); and BCG-unresponsive high-risk NMIBC patients with papillary-only disease (Cohort 3). The LEGEND trial is actively enrolling patients with sites participating in the USA, Canada, Europe, and the Asia-Pacific region