Arvinas Presents Preclinical Data Supporting Mechanistic Synergies and Enhanced Antitumor Activity with the Combination of ARV-393 and Glofitamab at the 2025 American Society of Hematology Annual Meeting and Exposition

Rhea-AI Summary

Arvinas (NASDAQ: ARVN) presented preclinical data showing enhanced antitumor activity when its PROTAC BCL6 degrader ARV-393 is combined with glofitamab (CD20×CD3) at ASH 2025.

Key findings: concomitant ARV-393 (3 mg/kg) + glofitamab (0.15 mg/kg) produced 81% tumor growth inhibition (TGI) and sequential dosing produced 91% TGI vs 38% and 36% for each agent alone; higher-dose ARV-393 (6 mg/kg) combinations yielded markedly higher tumor regressions (10/10 and 7/8 mice vs 5/11 and 0/11 for single agents). RNA sequencing showed CD20 upregulation and increased interferon/antigen-presentation gene expression. Arvinas plans to initiate a Phase 1 combination cohort in DLBCL in 2026.

Positive

• Planned Phase 1 combo cohort initiation in DLBCL in 2026
• 91% TGI with sequential ARV-393 (3 mg/kg) then glofitamab (0.15 mg/kg)
• 81% TGI with concomitant ARV-393 (3 mg/kg) + glofitamab (0.15 mg/kg)
• 10/10 tumor regressions observed with higher-dose ARV-393 (6 mg/kg) plus glofitamab (concomitant)
• CD20 upregulation and increased interferon/antigen-presentation gene expression after ARV-393

Negative

• None.

Key Figures

TGI concomitant combo 81% TGI ARV-393 3 mg/kg + glofitamab 0.15 mg/kg, concomitant dosing in HGBCL CDX model

TGI sequential combo 91% TGI ARV-393 3 mg/kg then glofitamab 0.15 mg/kg, sequential dosing in HGBCL CDX model

ARV-393 monotherapy TGI 38% TGI Single-agent ARV-393 in HGBCL CDX model

Glofitamab monotherapy TGI 36% TGI Single-agent glofitamab in HGBCL CDX model

Low-dose ARV-393 3 mg/kg Dose of ARV-393 used in combination with glofitamab

High-dose ARV-393 6 mg/kg Higher ARV-393 dose used in combination with glofitamab

Tumor regressions concomitant 10/10 mice High-dose ARV-393 + glofitamab, concomitant dosing tumor regressions

Tumor regressions sequential 7/8 mice High-dose ARV-393 + glofitamab, sequential dosing tumor regressions

Market Reality Check

$12.79 Last Close

Volume Volume 945,264 is 0.37x the 20-day average of 2,539,255, indicating muted pre-news interest. low

Technical Shares at $12.79 trade above the $8.83 200-day MA but remain 52.24% below the $26.78 52-week high and 116.78% above the $5.90 52-week low.

Peers on Argus

ARVN gained 1.39% while close peers were mostly down (e.g., XNCR -5.98%, VSTM -2.36%, OLMA -2.33%, SAGE -0.69%, NRIX +0.50%). This points to a stock-specific reaction rather than a broad biotech move.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 26	Conference appearance	Neutral	+2.5%	Announcement of fireside chat at a major healthcare conference.
Nov 24	Clinical data previews	Positive	+2.2%	Multiple vepdegestrant data presentations accepted for SABCS.
Nov 05	Earnings and pipeline	Positive	+0.3%	Q3 results with NDA acceptance and strong cash balance update.
Nov 03	ASH data preview	Neutral	-1.9%	Notice of upcoming ARV-393 plus glofitamab preclinical poster at ASH.
Nov 03	Investor conferences	Neutral	-4.1%	Participation in multiple November investor conferences with webcasts.

Pattern Detected

Recent news flow shows modest single-day reactions, with small positive moves for conferences and clinical updates and mild negatives around some investor events, suggesting generally contained volatility around announcements.

Recent Company History

Over the last few months, Arvinas has reported a mix of clinical, financial, and conference-related updates. Q3 2025 results highlighted cash of $787.6M and an accepted NDA for vepdegestrant with a June 5, 2026 PDUFA date. Conference and presentation notices, including those for ARV-393 at ASH and multiple investor events, produced small positive and negative moves, all within a few percentage points. Today’s ASH preclinical combination data for ARV-393 fits into this pattern of steady R&D progress across oncology and neurology programs.

Market Pulse Summary

This announcement details preclinical synergy between ARV-393 and glofitamab, with combo TGI up to 91% and high tumor regression rates in lymphoma models, supporting a Phase 1 combination cohort planned for 2026. In context, Arvinas recently reported Q3 results with cash of $787.6M and an accepted NDA for vepdegestrant, providing multiple future catalysts. Investors following this story may watch for 2026 clinical data readouts and how these early findings translate into patient outcomes.

Key Terms

PROTAC medical

"a PROTAC BCL6 degrader, in combination with glofitamab, a CD20×CD3"

A PROTAC (proteolysis targeting chimera) is a small engineered molecule that tags a specific protein inside cells and brings it to the cell’s disposal machinery so the protein is destroyed rather than just blocked. Think of it as a targeted cleanup crew that removes a problematic part instead of temporarily turning it off. Investors care because PROTACs can tackle disease targets that traditional drugs cannot, creating potential for breakthrough therapies, larger markets, and binary clinical readouts that can sharply affect company value.

bispecific antibody medical

"glofitamab, a CD20×CD3 bispecific antibody, presented in a poster"

A bispecific antibody is a specially designed protein that can attach to two different targets at the same time. Think of it as a custom-made connector that brings two things together—such as a disease cell and an immune system component—helping the body fight illnesses more effectively. For investors, understanding bispecific antibodies is important because they represent innovative therapies that could lead to new treatments and potentially lucrative market opportunities.

xenograft medical

"high-grade B-cell lymphoma (HGBCL) cell line–derived xenograft (CDX) model"

A xenograft is biological tissue or cells taken from one species and placed into another, most commonly human tumor cells implanted into laboratory animals to study disease or test drugs. Investors watch xenograft results because they serve like a controlled dress rehearsal for a therapy: positive responses in these models can de‑risk programs, attract funding or partnerships, and influence the likelihood and timing of clinical trials and regulatory milestones.

RNA sequencing medical

"RNA sequencing and biomarker analyses revealed that ARV-393 upregulated"

RNA sequencing is a laboratory method that reads the active genetic messages inside cells, like scanning the recipe cards a cell is using at a given moment to make proteins. For investors, it matters because the results can reveal how diseases operate, identify targets for new drugs or diagnostics, and help companies show whether a treatment is working—information that can change a biotech firm's value much like a new product test result can affect a tech stock.

biomarker medical

"RNA sequencing and biomarker analyses revealed that ARV-393"

A biomarker is a measurable indicator found in the body, such as in blood or tissues, that provides information about health, disease, or how the body responds to treatment. For investors, biomarkers can signal the potential success or risk of medical products or therapies, influencing the value of related companies and industry trends. They act like signals or clues that help assess the progress of medical advancements and their market impact.

Phase 1 regulatory

"ongoing Phase 1 clinical trial to evaluate ARV-393 plus glofitamab"

Phase 1 is the first stage of testing a new drug or medical treatment in people, focused primarily on safety, how the body handles the product, and finding a tolerated dose. Think of it as a short, tightly controlled experiment with a small group to check for dangerous side effects before wider testing; for investors it is an early milestone that reduces some uncertainty but still carries high risk and potential for both big value changes and setbacks.

non-Hodgkin lymphoma medical

"Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma"

A group of cancers that start in the lymphatic system, which is part of the body’s defense network of nodes and vessels; malignant cells multiply in lymph nodes, spleen or blood and can impair immune function. It matters to investors because diagnosis rates, available treatments, and regulatory approvals drive demand for drugs, influence clinical trial outcomes, and can shift revenue, development risk and valuation for companies in biotech, diagnostics and healthcare.

AI-generated analysis. Not financial advice.

– Data support initiation of a combination cohort in the ongoing Phase 1 clinical trial to evaluate ARV-393 plus glofitamab as a chemotherapy-free combination approach in diffuse large B-cell lymphoma (DLBCL); initiation expected in 2026 –

NEW HAVEN, Conn., Dec. 06, 2025 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, today announced preclinical data for ARV-393, a PROTAC BCL6 degrader, in combination with glofitamab, a CD20×CD3 bispecific antibody, presented in a poster at the 67th American Society of Hematology (ASH^®) Annual Meeting and Exposition, held December 6–9, 2025, in Orlando, Florida. In a humanized high-grade B-cell lymphoma (HGBCL) cell line–derived xenograft (CDX) model, the combination of ARV-393 and glofitamab resulted in significantly enhanced tumor growth inhibition (TGI) and increased rates of tumor regression compared with either agent alone. These preclinical data suggest mechanistic synergies between BCL6 degradation with ARV-393 and T-cell engagement.

“Despite advances in treatment options, many patients with diffuse large B-cell lymphoma continue to face limited options once standard therapies fail. By pursuing a chemotherapy-free combination approach, we aim to address this significant unmet need and potentially offer patients a more targeted, better-tolerated therapeutic alternative,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer, Arvinas. “The initiation of our Phase 1 combination clinical trial, planned for 2026, represents an important step toward defining the potential of ARV-393 in the treatment of this aggressive form of lymphoma.”

Key highlights from the poster presentation include:

• In a humanized HGBCL CDX model ARV-393 (3 mg/kg) combined with glofitamab (0.15 mg/kg) achieved 81% TGI with concomitant dosing and 91% TGI with sequential dosing (ARV-393 followed by glofitamab), versus 38% for single-agent ARV-393 and 36% for glofitamab alone.
• At a higher ARV-393 dose (6 mg/kg) combined with glofitamab (0.15 mg/kg), an increase in tumor regressions was observed with concomitant (10/10 mice) and sequential dosing (7/8 mice) vs single-agent ARV-393 (5/11 mice) or glofitamab (0/11 mice).
• RNA sequencing and biomarker analyses revealed that ARV-393 upregulated CD20 expression and genes that promote interferon signaling and antigen presentation, while downregulating proliferation-associated gene sets. These collective effects likely contributed to the observed synergistic antitumor activity.
  
  

“We believe these results underscore the potential for ARV-393 and provide a strong mechanistic rationale for exploring ARV-393 in combination with glofitamab as a chemotherapy-free treatment strategy for patients with diffuse large B-cell lymphoma,” said Angela Cacace, Ph.D., Chief Scientific Officer, Arvinas. “These preclinical results support our belief in the clinical potential and combinability of ARV-393 and the possibility to provide real benefit to patients in need.”

ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma and Arvinas plans to share clinical data from this trial at a medical congress in 2026. Additionally, Arvinas plans to add a glofitamab combination cohort in patients with DLBCL in the ongoing Phase 1 clinical trial of ARV-393 in 2026.

About ARV-393

ARV-393 is an investigational, orally bioavailable PROTAC designed to specifically target and degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. During B-cell development, tightly controlled BCL6 protein expression regulates >600 genes to facilitate rapid B-cell proliferation and tolerance of somatic hypermutation and gene recombination for antibody generation. Deregulated BCL6 expression is common in B-cell lymphoma and promotes cancer cell survival, proliferation, and genomic instability. PROTAC-mediated degradation has the potential to address the historically undruggable nature of BCL6.

About Arvinas

Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC (PROteolysis TArgeting Chimera) protein degrader platform, Arvinas is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including ARV-102, targeting LRRK2 for neurodegenerative disorders; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; ARV-806, targeting KRAS G12D for mutated cancers, including pancreatic and colorectal cancers; and vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding: Arvinas’ beliefs regarding the clinical potential and combinability of ARV-393 and possibility to benefit patients; Arvinas’ plans to add a glofitamab combination cohort in patients with diffuse large B-cell lymphoma (“DLBCL”) to Arvinas’ ongoing Phase 1 clinical trial of ARV-393, and the timing thereof; Arvinas’ plans to share clinical data from the Phase 1 clinical trial of ARV-393 in patients with relapsed/refractory non-Hodgkin lymphoma, and the timing thereof; whether a chemotherapy-free combination approach will address significant unmet need for patients with DLBCL and potentially offer patients a more targeted, better-tolerated therapeutic alternative; and the ARV-393 preclinical data showing the potential for ARV-393, and providing a strong mechanistic rationale for exploring ARV-393 in combination with glofitamab as a chemotherapy-free treatment strategy for patients with DLBCL. All statements, other than statements of historical fact, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “target,” “goal,” “potential,” “will,” “would,” “could,” “should,” “look forward,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: whether Arvinas will be able to successfully conduct and complete development for its product candidates, including ARV-393; other risks associated with drug development, including unexpected costs or delays; that positive data from preclinical or early clinical studies of Arvinas’ product candidates, including ARV-393, are not necessarily predictive of the results of later clinical studies and any future clinical trials of Arvinas’ product candidates; Arvinas’ ability to protect its intellectual property portfolio; Arvinas’ reliance on third parties; whether Arvinas will be able to raise capital when needed; whether Arvinas’ cash and cash equivalents will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2024 and subsequent other reports on file with the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release.

Contacts

Investors:
Jeff Boyle
+1 (347) 247-5089
Jeff.Boyle@arvinas.com

Media:
Kirsten Owens
+1 (203) 584-0307
Kirsten.owens@arvinas.com

FAQ

What preclinical results did Arvinas (ARVN) report at ASH 2025 for ARV-393 plus glofitamab?

Arvinas reported combination results showing 81% TGI (concomitant) and 91% TGI (sequential) at ARV-393 3 mg/kg plus glofitamab 0.15 mg/kg and increased tumor regressions at ARV-393 6 mg/kg.

When does Arvinas plan to start the ARV-393 plus glofitamab combination cohort in DLBCL?

Arvinas plans to initiate the combination cohort in its ongoing Phase 1 trial in patients with DLBCL in 2026.

How did ARV-393 affect tumor biology in the preclinical study presented by Arvinas (ARVN)?

RNA sequencing showed ARV-393 upregulated CD20 and genes linked to interferon signaling and antigen presentation while downregulating proliferation-associated genes.

What dosing produced the highest tumor regression rates in the ARV-393 plus glofitamab study?

Higher-dose ARV-393 (6 mg/kg) combined with glofitamab 0.15 mg/kg produced the highest regressions: 10/10 mice with concomitant dosing and 7/8 with sequential dosing.

Is ARV-393 already in clinical testing and will clinical data be shared soon?

Yes; ARV-393 is being evaluated in a Phase 1 trial in relapsed/refractory non-Hodgkin lymphoma and Arvinas plans to share clinical data at a medical congress in 2026.