On October 24, 2025 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported preclinical data for ARV-806, a PROTAC KRAS G12D degrader, at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, Massachusetts. The ARV-806 data presented show a differentiated profile based on degradation potency, antiproliferative activity, and induction of cancer cell death. ARV-806 is designed to target both the ON and OFF forms of KRAS G12D, which is the most common mutation of the KRAS protein. ARV-806 has the potential to address high unmet need in solid tumors, such as pancreatic, colorectal and non-small cell lung cancer.

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"These data suggest the potential of targeted protein degradation to overcome historical limitations in addressing undruggable KRAS mutations," said Angela Cacace, Ph.D., Chief Scientific Officer of Arvinas. "ARV-806’s ability to eliminate both ON and OFF forms of KRAS G12D, combined with its potency and durability shown in preclinical models, supports our confidence in its clinical potential to deliver meaningful benefit for patients with KRAS G12D-mutated cancers."

Key highlights from the presentation include:

In vitro, ARV-806 degraded KRAS G12D with picomolar potency across pancreatic, colorectal, and lung cancer cell lines but did not induce degradation of wild-type and other mutant RAS isoforms.
ARV-806 is differentiated from other KRAS G12D targeting agents in development and has potential to be a best-in-class therapy for KRAS G12D mutated cancers due to:
Catalytic activity, which allows it to overcome upregulation, a common mechanism of resistance to inhibitor treatment
Compared with clinical-stage KRAS G12D ON and OFF inhibitors and another clinical-stage G12D degrader, ARV-806 demonstrated:
>25-fold greater potency in reducing cancer cell proliferation,
>40-fold higher potency in degrading KRAS G12D protein (versus the comparable clinical-stage G12D degrader), and
>10-fold lower concentrations required to induce pro-apoptotic BIM expression.
Following a single intravenous dose in a colorectal tumor xenograft model, ARV-806 degraded >90% of KRAS G12D for seven days, with parallel suppression of c-MYC (a key driver of cancer cell proliferation) and induction of BIM (Bcl-2-interacting mediator of cell death, a pro-apoptotic factor) for ≥5 days.
ARV-806 demonstrated robust efficacy responses at low doses in tumor models including: ≥30% tumor volume reductions in pancreatic and colorectal cell line-derived xenograft (CDX) models and a patient-derived xenograft (PDX) model of lung cancer.

These data demonstrate sustained pharmacodynamic activity consistent with long-lasting target degradation, which we believe supports intermittent clinical dosing. Arvinas is currently evaluating ARV-806 in a Phase 1 clinical trial in patients with KRAS G12D–mutated advanced solid tumors (NCT07023731).

Also shown in the poster, orally bioavailable pan-KRAS degraders have been identified that potently degrade multiple variants of KRAS and spare other RAS isoforms. A tool pan-KRAS PROTAC demonstrated robust single-agent activity and superior combination efficacy with immune checkpoint blockade compared with a pan-RAS ON inhibitor (7 complete responses compared with 2 complete responses).

About ARV-806
ARV‑806 is a novel, investigational PROTAC degrader designed to selectively target and degrade mutant Kirsten rat sarcoma (KRAS) G12D which is the most common mutation of the KRAS protein. Therefore, ARV-806 has the potential to address high unmet need in solid tumors, such as pancreatic, colorectal and lung cancer. ARV‑806 is currently being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors harboring KRAS G12D mutations.

(Press release, Arvinas, OCT 24, 2025, View Source [SID1234656974])

On October 24, 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 an update on the ongoing Phase 1 ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) study. The latest results show that, at the 100 mg APR-1051 dose level, 3 out of 4 patients achieved stable disease, as measured using RECIST v1.1 criteria.

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A poster titled Early safety and efficacy of APR-1051, a novel WEE1 inhibitor, in patients with cancer-associated gene alterations: Updated data from ACESOT-1051 Phase 1 trial will be presented today at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). The poster, to be presented by Drs. Timothy Yap MBBS, PhD, FRCP, University of Texas MD Anderson Cancer Center and lead investigator of the study, and Philippe Pultar, MD, Senior Medical Advisor at Aprea, summarizes preliminary results from the trial with a cutoff date of September 17, 2025. A copy of the poster will be available on Investors page of the Aprea corporate website under "Investor Presentations & Resources."

"We continue to be encouraged by these early clinical findings, which demonstrate signals of anti-tumor activity with APR-1051 in a heavily pre-treated patient population," said Dr. Pultar. "We believe the observation of disease control in tumors harboring FBXW7, CCNE1, and KRAS mutations align with our mechanistic understanding of WEE1 inhibition and reinforces the scientific rationale for APR-1051 development. We believe these promising data provide an important foundation as we continue with dose escalation in the ongoing study and we look forward to providing further updates as we advance to higher dose level in the ongoing study."

ACESOT-1051 Clinical Update (data cutoff October 19, 2025)

The primary objective of the trial is to characterize the safety profile, dose-limiting toxicity, maximum tolerated dose or maximum administered dose, and recommended Phase 2 dose of APR-1051. Secondary objectives are to 1) to characterize the pharmacokinetics of APR-1051 and the major metabolites and active metabolites of APR-1051, and 2) to assess preliminary efficacy of APR-1051
Results from Dose Level 6 (100 mg), show 3 out of 4 patients achieved stable disease, per RECIST v1.1 in heavily pretreated gastrointestinal and gynecologic malignancies
Disease stabilization was observed in patients with FBXW7, CCNE1, and KRASG12V + TP53 alterations
Favorable tolerability: No dose limiting toxicities (DLTs) or unexpected safety issues reported to date.
Following successful clearance of the 100 mg cohort, dose escalation has progressed to Dose Level 7 (150 mg)
For more information on ACESOT-1051, refer to ClinicalTrials.gov NCT06260514.

Individual Patient Results

86-year-old female with rectal cancer: Treated at a 100 mg dose after five prior lines, the patient achieved stable disease (-13% reduction). Tumor harbored FBXW7 mutation which is a mechanistically relevant biomarker for WEE1 inhibition. 145 days on treatment and ongoing
55-year-old male with rectal cancer: Treated at a 100 mg dose after four prior lines, the patient achieved stable disease (+1%). Tumor harbored KRASG12V + TP53-mutant patient supports mechanistic activity in this genotype. 63 days on treatment and ongoing
73-year-old female with endometrial cancer: Treated at a 100mg after five prior lines, patient achieved stable disease by RECIST v1.1 criteria (+15%) at the first evaluation before voluntarily withdrawing consent after approximately two months of treatment. Tumor harbored CCNE1 and TP53 mutations supports mechanistic activity in this genotype.
50-year-old female with colon cancer: Treated at 100mg after two prior lines. This patient had disease progression at first assessment (8 weeks).

(Press release, Aprea, OCT 24, 2025, View Source [SID1234656973])

On October 23, 2025 CDR-Life, Inc., a biotechnology company developing highly selective T cell engagers (TCEs) to treat cancer and autoimmune diseases, reported the first clinical data showing that CDR404, the company’s lead M-gager TCE, achieved all four canonical pharmacodynamic (PD) hallmarks of TCE activity in patients with MAGE-A4+ solid tumors. The data, presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), in Boston, Massachusetts, highlights CDR404’s robust immune activation and early signals of clinical activity, including tumor stabilization and biomarker improvements in patients with ovarian cancers and synovial sarcomas.

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CDR404 is an antibody-based TCE designed to target intracellular tumor antigens presented on HLA molecules. It engages MAGE-A4 peptides displayed by HLA-A*02:01 on cancer cells and redirects CD3+ T cells for targeted tumor cell killing. The ongoing Phase 1 CDR404 trial (NCT06402201) is being conducted at leading cancer centers across the United States and Europe. Unlike conventional approaches utilizing T cell receptors, the proprietary M-gager platform leverages antibody-derived binding domains that combine exceptional specificity with strong potency, excellent developability and ease of manufacturing.

At initial dose levels of 100–200 μg, CDR404 triggered the full cascade of immune activation associated with effective TCE therapy, including CD8+ T cell activation and expansion, reprogramming to a memory phenotype and recruitment of lymphocytes into tumors. Notably, repeated dosing did not induce PD-1–mediated T cell exhaustion, suggesting sustained biological activity. In one patient, a transient tumor flare followed by stabilization was observed, which is consistent with tumor infiltration by cytotoxic T cells.

"These early data demonstrate that our M-gager platform can extend the precision and power of antibody-based T cell engagers to intracellular antigens, an area long thought to be accessible only to TCR-based modalities," said Christian Leisner, PhD, Chief Executive Officer of CDR-Life. "Seeing all four pharmacodynamic hallmarks of activity in patients even at low doses underscores the potential of this approach to redefine how we target solid tumors."

The study’s first-in-human dose was guided by quantitative systems pharmacology modeling, enabling detection of pharmacodynamic effects more quickly than traditional approaches. Based on these encouraging signals, the trial will begin to focus on patients with MAGE-A4–positive ovarian cancers, a population with high unmet need.

Additional analyses, including integrated pharmacokinetic-pharmacodynamic and circulating tumor DNA (ctDNA) data, are ongoing.

Presentation Details:

Title: Hallmarks of pharmacodynamic activity of CDR404, a new antibody-
derived T cell engager (TCE) targeted against MAGE-A4+ solid tumors in
HLA-A02:01+ patients
Presenter: Melissa Vrohlings, Head of Translational Science, CDR-Life
Date and Time: October 23, 2025 | 12:30 – 4 pm ET
Location: Poster Session A
Level 2, Exhibit Hall D

In addition to the poster presentation on CDR404, CDR-Life is also presenting a poster on CDR609, the company’s newest T cell engager clinical candidate that targets LGR5, a highly cancer-specific cell surface antigen widely expressed on common solid tumors.

Presentation Details:

Title: CDR609: A First-in-Class LGR5-targeted T Cell Engager for treatment of
Colorectal Cancer and other solid tumors
Presenter: Sophie Barsin, Project Leader, CDR-Life
Date and Time: October 23, 2025 | 12:30 – 4 pm ET
Location: Poster Session A
Level 2, Exhibit Hall D

(Press release, CDR-Life, OCT 23, 2025, View Source [SID1234666504])

On October 23, 2025 Biomed Valley Discoveries reported the first time Joey Carlsen Martinez came to Memorial Sloan Kettering Cancer Center (MSK), he was in terrible shape. He had a rare blood cancer called Erdheim-Chester disease, and his symptoms included crushing fatigue, severe joint pain, and memory loss. He needed a wheelchair to get around.

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Three years later, thanks to an experimental targeted therapy drug treatment for Erdheim-Chester disease that he is receiving at MSK, his life is much improved.

"Today, I have a mostly normal life," says Joey, 34, a stay-at-home dad who homeschools his two young daughters. "I still get tired easily, but I go grocery shopping, I cook dinner, and I take care of my family. And because I know how bad things can get, I feel so grateful for everything that I have."

Ulixertinib for Erdheim-Chester Disease and Other Forms of Histiocytosis
Joey’s extraordinary turnaround is the result of a novel targeted drug called ulixertinib. His doctor, neuro-oncologist and early drug development specialist Eli Diamond, MD, is first author of a paper published October 23, in Cancer Cell that reports outcomes for Joey and four other patients — the first patients to receive ulixertinib for a family of diseases called histiocytosis. Erdheim-Chester disease is a type of histiocytosis.

The MSK study found four out of five patients with histiocytosis benefited from ulixertinib. Based on that work, ulixertinib is being tested in a bigger phase 2 clinical trial now open at MSK and two other hospitals.

How MSK Has Led the Development of Histiocytosis Treatments
Dr. Diamond is an internationally recognized leader in treating histiocytosis and led the development of the only two drugs approved by the U.S. Food and Drug Administration (FDA) for treating histiocytosis — vemurafenib (Zelboraf) and cobimetinib (Cotellic).

"The patients in this study were treated on what is called a single-patient investigational new drug (IND) application," Dr. Diamond explains. "We essentially write an individual clinical trial for each participant. For rare diseases like histiocytosis, this approach is a good way to evaluate potential new treatments on a small number of patients."

What Is Histiocytosis and What Symptoms Does It Cause?
Histiocytosis is a collection of rare diseases diagnosed in only a few hundred people in the United States every year and can affect patients of any age, including children.

Histiocytosis starts when the body makes too many histiocytes, a type of white blood cell, which can build up and form tumors in any part of the body and cause a broad range of symptoms, including:

Bone and joint pain
General symptoms such as fatigue and malaise
Rashes and other skin problems
Blurred vision and tumors in or around the eyes and sinuses
Problems with the brain including balance issues, memory loss, and hormone imbalances
Joey experienced all of these symptoms on and off for nearly a decade before he was diagnosed with Erdheim-Chester at age 29.

"I finally found out what was wrong with me two months after my wife found out she was pregnant with our first child," Joey says. "It was a crazy time, especially because nobody had ever heard of this disease."

Joey, who lives in Washington state, was fortunate to find a doctor in Seattle who was familiar with treating histiocytosis. He tried three different therapies, and while they helped with some of his symptoms, they caused severe side effects, especially nausea and vomiting. Joey was running out of options. That’s when he heard about Dr. Diamond and decided to make the trip to New York to visit MSK.

How New Discoveries About the ERK Gene and MEK Protein Led to a New Drug for Histiocytosis
Laboratory mouse models and other studies have revealed how histiocytosis is driven by mutations in a cell-signaling pathway driven by the protein MEK. The mutations lead to uncontrolled cell growth and, ultimately, cancer. MEK is implicated not only in histiocytosis but several other cancer types, especially melanoma.

The two previous drugs approved for histiocytosis act on genes within the MEK pathway to block histiocyte growth. The new drug, ulixertinib, also acts on this pathway, but on a different gene, called ERK.

"MSK has a very active program in histiocytosis, both in the lab and in the clinic," says MSK physician-scientist Omar Abdel-Wahab, MD, Chair of the Molecular Pharmacology Program in the Sloan Kettering Institute. Dr. Abdel-Wahab is co-senior author of the new paper, along with Benjamin Durham, MD, a former trainee and member of his lab who is now at the Rutgers Cancer Institute.

"Drugs that block ERK have been studied for a number of different cancers, but some patients have notable side effects at high doses," Dr. Diamond explains. "But with histiocytosis, ulixertinib works at very low doses, allowing patients to avoid most of these side effects."

Side Effects and Benefits of Ulixertinib for Erdheim-Chester Disease
For Joey, the only major side effect of ulixertinib has been an acne-like rash. He continues to take the drug daily. Early in his treatment, he had to make frequent trips to MSK, but now Dr. Diamond is able to coordinate with doctors in Seattle so that Joey can have scans and blood tests closer to home. He travels to MSK periodically, and Dr. Diamond partners with his Seattle oncologist to make adjustments to the dosage that Joey is taking, based on his levels of disease and the treatment’s side effects.

Joey and his wife recently celebrated their sixth wedding anniversary. He is still unable to work full-time but is thankful to be home with his daughters. "I can’t think of another situation in which I’d get to spend so much time with my girls every single day," he says. "That’s been the biggest blessing out of all of this."

Joey has joined support groups for patients with Erdheim-Chester and enjoys helping others with the disease, especially those who are newly diagnosed. "The whole Erdheim-Chester disease community is so amazing," he says. "I’m so grateful for them, and grateful for Dr. Diamond and the whole team at MSK."

MSK’s History of Leadership in Treating Rare Blood Cancers Like Histiocytosis
MSK’s leadership in developing treatments for histiocytosis is the result of a dedication to fundamental lab research. Fifteen years ago, Dr. Abdel-Wahab developed the first-ever mouse models for studying histiocytosis. These models have allowed researchers to learn much more about the genes and proteins that drive the disease, as well as to test experimental therapies that block them.

Patient samples sent to MSK by histiocytosis specialists from all over the world also have helped to build a better understanding of these rare diseases. Several of those specialists are co-authors on the Cancer Cell paper.

"Our work in histiocytosis and the ways this work has ultimately benefited patients all over the world is a great example of the importance of continuing to fund basic and translational lab research," Dr. Abdel-Wahab says.

Key Takeaways
Memorial Sloan Kettering Cancer Center is a leader in lab and clinical research on different forms of histiocytosis, including Erdheim-Chester disease.
Scientists at MSK, led by physician-scientist Omar Abdel-Wahab, MD, have collected histiocytosis patient samples from all over the world and developed mouse models to study this family of rare blood cancers.
Based on a single-patient investigational new drug application study from neuro-oncologist and early drug development specialist Eli Diamond, MD, ulixertinib for histiocytosis was found to be beneficial in four out of five people (80%) and is now being studied in a phase 2 clinical trial.
Ulixertinib for histiocytosis works by controlling histiocyte cell growth caused by a mutation in the MEK signaling pathway via the ERK gene.
Histiocytosis happens when the body makes too many histiocytes, a type of white blood cell, which can build up and form tumors in any part of the body and cause a broad range of symptoms like fatigue, bone pain, trouble with speech and balance, skin rashes, and more.
Dr. Abdel-Wahab holds the Evnin Family Chair in Molecular Pharmacology at MSK.
Additional Authors, Funding, and Disclosures
Biomed Valley Discoveries, the company that makes ulixertinib, provided the drug through an extended access program for the single-patient studies reported in the article. The company is providing funding support for the current clinical trial.

Dr. Diamond is supported by the Frame Family Fund, the Joy Family West Foundation, and Applebaum Foundation. Dr. Diamond and Dr. Abdel-Wahab are together supported by National Institutes of Health (NIH) grant R37CA259260, Cycle for Survival, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology. Dr. Abdel-Wahab is also supported by NIH grants R01 CA251138, R01 CA283364, R01 HL128239, R01 CA242020, and P50 CA254838-01, as well as the Edward P. Evans Foundation and Blood Cancer United. Dr. Durham has been and is supported by NIH grant K08 CA218901 and the American Society of Hematology (ASH) (Free ASH Whitepaper) Fellow Scholar Award in Basic/Translational Research and a Junior Faculty Scholar Award in Basic/Translational Research.

(Press release, BioMed Valley Discoveries, OCT 23, 2025, View Source [SID1234666000])

On October 23, 2025 Tango Therapeutics, Inc. (NASDAQ: TNGX), a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, reported positive data from its ongoing Phase 1/2 study of vopimetostat (TNG462) in patients with MTAP-deleted cancers.

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"Today, we are presenting a substantive dataset on our lead PRMT5 inhibitor vopimetostat, which has the potential to be a turning point for treatment of multiple difficult-to-treat MTAP-del cancers, beginning with pancreatic cancer," said Barbara Weber, M.D., President and CEO of Tango Therapeutics. "Across the 16 cancer types enrolled in the trial, the ORR is 27% in patients with a median follow-up of 9.4 months, which supports the potential for vopimetostat as the best-in-class PRMT5 inhibitor. In 2L MTAP-deleted pancreatic cancer, the median PFS is 7.2 months and the ORR is 25%, more than double that observed in historical control studies, supporting our decision to initiate a pivotal trial in this patient population in 2026. With FDA alignment on the go-forward dose of 250 mg QD, we anticipate that this study will enroll rapidly, underscoring the potential for vopimetostat to be the first MTAP-selective PRMT5 inhibitor to market."

Dr. Weber continued, "Our ongoing study of vopimetostat in combination with two Revolution Medicines (RVMD) RAS(ON) inhibitors is enrolling rapidly and we anticipate sharing safety and efficacy data from that study in 2026. Today, we also announced data from the histology-agnostic cohort of the vopimetostat phase 1/2 trial, where we observed a 49% ORR and mPFS of 9.1 months (excluding sarcoma). These data from the histology agnostic cohort demonstrate the potential of vopimetostat in multiple cancers in addition to pancreatic and lung cancer and provide further optionality for clinical development in a large patient population with high unmet need. In summary, the efficacy data we have provided, supported by a favorable tolerability profile to date, reinforce the potential for vopimetostat to be the first- and best-in-class PRMT5 inhibitor for patients with a wide range of MTAP-deleted cancer types."

"Current standard of care for patients with advanced pancreatic cancer is multi-agent chemotherapy that confers modest benefit along with side effects that can adversely affect patient quality of life," said Brian Wolpin, M.D., M.P.H., Director, Gastrointestinal Cancer Center and Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute. "These initial data support the potential of vopimetostat to meaningfully change the treatment of patients with advanced pancreatic cancer by providing more durable benefit, along with a better safety and tolerability profile, and the convenience of a once-daily pill as opposed to intravenous chemotherapy."

Efficacy Results Across Study Indications:

As of September 1, 2025, 179 patients were enrolled across all histologies, with 154 at active doses (200 mg and above). Ninety-four tumor evaluable patients were enrolled more than 6 months prior to the efficacy analysis and included regardless of outcome. Across cancer types:
ORR: 27%
DCR: 78%
mPFS: 6.4 months
37/94 patients remained on treatment as of September 1, 2025.
Efficacy Results in Pancreatic Cancer Patients

As of September 1, 2025, 64 patients with pancreatic cancer were enrolled. 39 of these patients received active doses and were enrolled more than 6 months prior to the analysis; in these patients:
ORR in 2L pancreatic cancer patients: 25%
ORR for all pancreatic cancer patients: 15%
DCR for all pancreatic cancer patients: 71%
mPFS in 2L patients: 7.2 months
mPFS in 3L+ patients: 4.1 months
Median follow up: 7.8 months
Development Strategy in Pancreatic Cancer

Following consultation with the FDA on the trial design scheduled later this quarter, the company plans to start a global, randomized, pivotal study in patients with MTAP-del pancreatic cancer who have received one prior line of therapy, comparing patients treated with 250 mg QD vopimetostat to patients treated with one of four standard chemotherapy regimens. The company anticipates this study will enroll approximately 300 patients and is intended to begin enrollment in 2026.
The phase 1/2 combination study of vopimetostat with RAS(ON) multi-selective inhibitor daraxonrasib, and RAS(ON) G12D-selective inhibitor zoldonrasib (both from Revolution Medicines, RVMD), is ongoing with robust enrollment in previously treated MTAP-del/RAS mut pancreatic and lung cancer. The first dose escalation cohort of this study has been fully enrolled (n=7) and backfill is ongoing. Vopimetostat in combination with both daraxonrasib and zoldonrasib have been well-tolerated to date with exposures in the active range for each compound. The second cohort was initiated in early October. A cohort of 1L patients is expected to begin enrolling after go-forward doses have been selected. The data from this study have the potential to support a pivotal study in 1L MTAP-del/RAS mut pancreatic cancer. Initial data from the Phase 1/2 study are anticipated in 2026.
Enrollment in Lung Cancer

As of September 1, 2025, 41 patients with 2L+ lung cancer were enrolled, 12 of whom had received active doses and were enrolled more than 6 months prior to the analysis.
Emerging data are consistent with expectations, and the company anticipates providing a safety and efficacy update in 2026.
Efficacy Results in the Histology Agnostic Cohort:

As of September 1, 2025, 41 patients with 13 different cancers were enrolled at active doses and had received a first dose more than 6 months prior to the analysis. This cohort excludes pancreatic and lung cancers (being evaluated in histology-specific cohorts) and sarcomas (where no activity was observed, n=0/9 responses). In this histology agnostic cohort:
ORR: 49%
DCR: 89%
mPFS: 9.1 months
Safety and Tolerability
Consistent with previously reported data, vopimetostat is generally well tolerated at 250 mg QD, the go-forward dose agreed with the FDA, with a potentially best-in-class safety profile. The most common treatment-related adverse events (TRAEs), predominantly grade 1, were nausea (26%), anemia (20%), fatigue (19%), dysgeusia (19%) and thrombocytopenia (13%). No treatment-related Grade 4 or 5 events occurred. Grade 3 events were rare, with the exception of anemia which was observed in 13% of patients. No drug related dose discontinuations have occurred as of September 1, 2025, and only 8% of patients treated at 250 mg QD required dose reduction to 200 mg QD.

Study Design
The Phase 1/2 study (NCT05732831) is a multicenter, open-label, first in human study in solid tumor patients whose tumor has a confirmed homozygous MTAP deletion. The first part of the study was an open-label, dose escalation and the second part is an open label dose expansion/optimization in specific MTAP-deleted tumor types.

Investor Webcast and Conference Call Information
The company will host a conference call to discuss these data at 8:30 a.m. ET today, October 23, 2025. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.tangotx.com. The webcast will be available for replay for at least 30 days on the company website. Analysts who wish to join the teleconference and participate in Q&A should register here.

About Vopimetostat
Vopimetostat is a potentially best-in-class oral, once-daily, MTA-cooperative PRMT5 inhibitor that works selectively in cancer cells with MTAP (methylthioadenosine phosphorylase) deletion. MTAP deletions occur in 10-15% of all human cancers, including approximately 35% of pancreatic cancer and 15% of lung cancer. Vopimetostat is being evaluated as a monotherapy and in combination clinical studies. In ongoing clinical studies, vopimetostat has demonstrated a favorable safety and tolerability profile to date and shown durable activity in multiple tumor types.

(Press release, Tango Therapeutics, OCT 23, 2025, View Source [SID1234662278])