On December 7, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines in oncology and autoimmune disease, reported new clinical data from the Company’s ongoing Phase 1a/1b NX-5948-301 study of bexobrutideg (NX-5948) in patients with relapsed or refractory B-cell malignancies. These data will be presented in an oral session at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, FL, on December 6, 2025, at 9:45 a.m. ET, by Zulfa Omer, M.D., Assistant Professor of Internal Medicine at the University of Cincinnati and a principal investigator in the study.

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"The clinical activity and durability observed with bexobrutideg in this study are highly encouraging for patients with relapsed or refractory CLL/SLL, many of whom have limited treatment options," said Dr. Omer. "The responses we are seeing across heavily pretreated patients, including those with prior exposure to both covalent and non-covalent BTK inhibitors and BCL-2 inhibitors, support continued evaluation of bexobrutideg as a therapeutic approach for patients with relapsed or refractory CLL/SLL and ultimately earlier line patients."

The new and updated data from the Phase 1a/1b study (NX-5948-301) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) include safety findings across all patients, safety findings for patients treated at the RP2D of 600 mg once daily, updated Phase 1a results with extended follow-up, and emerging efficacy results from the randomized Phase 1b cohort 1 comparing 200 mg and 600 mg once-daily dosing. Collectively, these results provide a maturing clinical picture of bexobrutideg’s efficacy, durability, and tolerability, which form the foundation for Nurix’s advancing pivotal clinical program.

"We are excited to share this important data update for bexobrutideg, which continues to demonstrate compelling efficacy and durability for patients with relapsed or refractory CLL/SLL" said Paula O’Connor, M.D., chief medical officer of Nurix. "Advancing the 600 mg dose into our pivotal DAYBreak program reflects our conviction that this regimen offers patients the greatest opportunity for sustained clinical benefit, supported by a favorable safety profile."

Data presented at the 2025 ASH (Free ASH Whitepaper) Annual Meeting include baseline demographics and safety findings for all patients with CLL/SLL in the ongoing Phase 1a/1b study (n=126) and safety findings for patients treated at the RP2D of 600 mg (n=70). Efficacy results are presented for patients treated with bexobrutideg at doses ranging from 50 mg to 600 mg in the Phase 1a study (n=48) and for patients in the Phase 1b cohort 1, who were randomized and treated with either a 200 mg or 600 mg dose (n=42) in accordance with FDA’s Project Optimus.

Phase 1a/1b demographics and safety findings
Overall, the heavily pretreated Phase 1a/1b population had received a median of three prior lines of therapy (range = 1–17) including prior BTK inhibitors (85.7%), prior BCL-2 inhibitors (61.9%), and prior non-covalent BTK inhibitors (27.0%). The Phase 1a population was more heavily pretreated with a median of four prior lines of therapy (range = 2-12) including prior BTK inhibitors (97.9%), prior BCL-2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (27.1%). At baseline, many patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (39.6% overall, 38.3% in the Phase 1a population) and PLCG2 (8.1% overall, 14.9% in the Phase 1a population). Poor prognostic features were common, including TP53 mutations (39.6% overall, 44.7% in the Phase 1a population). Of the five patients (4.0%) in the trial who had central nervous system (CNS) involvement, all five were in the Phase 1a population.

Bexobrutideg was well tolerated across all dose levels evaluated, consistent with prior disclosures. The treatment emergent adverse event (TEAE) profile was similar between the RP2D of 600 mg and the overall study population with the most common treatment emergent adverse events being purpura/contusion, neutropenia, and petechiae. There were no dose-limiting toxicities, no systemic fungal infections or Grade 4 infections of any kind, and a single event of new onset atrial fibrillation was consistent with the rate in the age-matched general population.

Phase 1a efficacy update (n=48)
The updated Phase 1a dataset includes patients treated at starting dose levels ranging from 50 mg to 600 mg once daily with a median follow-up of 19.0 months (range = 13.5 – 32.3). Among the 47 efficacy evaluable patients, the objective response rate (ORR) was 83.0% including two patients (4.3%) with a complete response, an improvement from earlier disclosures due to additional follow-up and deepening of response. Overall, the disease control rate (DCR) was 95.7%. Importantly, the median progression-free survival was 22.1 months, and the median duration of response (DOR) was 20.1 months. Responses were observed across clinically challenging subgroups including patients who had progressed on prior BTK inhibitors, patients who were double-exposed to both BTK inhibitors and BCL-2 inhibitors, patients who had received prior non-covalent BTK inhibitors, patients with baselines mutations associated with BTK inhibitor resistance including non-C481 BTK mutations, and patients with high-risk molecular features such as TP53 mutations. Meaningful reductions in lymph node burden were also observed independent of baseline mutations associated with BTK inhibitor resistance and poor prognosis.

Phase 1b Cohort 1: Randomized evaluation of 200 mg vs 600 mg once daily (n=42)
In the randomized Phase 1b cohort, 42 patients were assigned to receive either 200 mg (n = 22) or 600 mg (n = 20) once daily. Among the 37 efficacy evaluable patients, preliminary data showed the 600 mg dose with an ORR of 83.3% compared to 73.7% for the 200 mg dose. With a median follow up of 9.8 months, the preliminary PFS curves suggest longer progression free survival for the 600 mg group compared to the 200 mg group.

Across Phase 1a and Phase 1b, the totality of clinical data supports 600 mg once daily as the optimal dose for further development. At this dose level, bexobrutideg demonstrated the strongest clinical activity observed to date, including higher response rates and a favorable trend toward longer progression-free survival in the randomized Phase 1b cohort. Importantly, the 600 mg dose maintained a tolerable safety profile comparable to the overall study population, with no dose-limiting toxicities, no systemic fungal infections, and no Grade 4 infections reported. Taken together, in accordance with FDA’s Project Optimus, these results provide a robust foundation for advancing 600 mg as the recommended Phase 2 dose and for the ongoing pivotal DAYBreak development program.

"These exciting, positive results reinforce the potential for bexobrutideg to be best-in-class and form a strong foundation to support our pivotal development program," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer, Nurix. "Nurix has entered this next phase of clinical development with momentum and a commitment to deliver a transformative new medicine for patients with B-cell malignancies."

Webcast Details
Date and time: Monday, December 8, 2025, 8:15 p.m. ET
Access Details: The live webcast and subsequent archived replay will be available in the Investors section of the Nurix website under Events.

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, highly selective small molecule degrader of BTK currently being evaluated in the DAYBreak CLL-201 clinical trial (NCT07221500), a pivotal single-arm Phase 2 study of bexobrutideg in patients with relapsed or refractory chronic lymphocytic leukemia. Nurix also continues enrollment in the NX-5948-301 Phase 1a/1b clinical trial (NCT05131022) of bexobrutideg in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trials can be accessed at clinicaltrials.gov.

(Press release, Nurix Therapeutics, DEC 7, 2025, View Source [SID1234661204])

On December 7, 2025 Orna Therapeutics (Orna), a biotechnology company dedicated to engineering immune cells in vivo to treat autoimmune and oncology diseases, reported new preclinical data supporting the Company’s in vivo CAR programs to target and treat a broad range of B cell-mediated autoimmune diseases and plasma cell or BCMA-related diseases at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place in Orlando, Florida from December 6-9, 2025.

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"The preclinical data presented at this year’s ASH (Free ASH Whitepaper) Annual Meeting further highlights our potent, non-viral, transient, tunable, and scalable approach to in vivo CAR therapies in both autoimmune diseases and oncology," said Joseph Bolen, Ph.D., Chief Executive Officer of Orna. "Our panCAR platform has demonstrated robust activity in B cell autoimmunity and BCMA-related diseases without the need for preconditioning lymphodepletion. Additionally, the non-human primate (NHP) data presented across both programs demonstrated specific and targeted depletion of B cells or plasma cells. As we look ahead, we anticipate submitting our first Clinical Trial Application for ORN-252, our anti-CD19 panCAR program this year and entering the clinic in early 2026."

Oral Presentation details:

In Vivo panCAR Therapy Utilizing Circular RNA for Treatment of Autoimmune Diseases

In this presentation, Orna highlighted preclinical data demonstrating the potential of its proprietary circular (oRNA) technology paired with its best-in-class lipid nanoparticle (LNP) delivery platform to enable the next generation of in vivo therapies and treat a variety of B cell-mediated autoimmune diseases.

Key findings in the study include:

ORN-252, Orna’s anti-CD19 panCAR mediated robust B cell depletion in humanized mice in vivo at doses as low as 0.03 mg/kg.
In a humanized mouse lupus model, ORN-252 showed robust B cell depletion with concurrent reduction in dsDNA titers in contrast to rituximab.
Treatment with ORN-252 led to complete peripheral and splenic B cell depletion in NHP at doses as low as 0.1 mg/kg.
CAR+ T cells upregulated cytotoxicity markers after the first dose when the majority of cell killing occurs.
ORN-252 demonstrated durable B cell depletion with a reduction in switched memory and an increase in naïve B cell phenotype upon repopulation.
ORN-252 showed superior binding affinity, expression, and killing of CD19 cells in human vs. NHP cells, potentially providing increased potency upon translation to humans.
Orna anticipates filing a Clinical Trial Application for this program by the end of 2025 and expects to initiate a first-in-human study in early 2026.

Poster Presentation details:

In Vivo panCARTM Therapy Utilizing Circular RNA for Treatment of Multiple Myeloma

In today’s poster presentation, Orna will showcase preclinical data demonstrating the potential of its in vivo panCARTM therapy to treat a range of plasma cell or BCMA-related diseases including multiple myeloma.

Key findings in the study include:

High surface expression of anti-BCMA panCAR was observed in a dose-dependent manner on human and cynomolgus immune cells and was maintained at least 72 hours in vitro.
In a humanized mouse model engrafted with BCMA-expressing tumor cells, anti-BCMA panCAR demonstrated superior tumor control, eliminating tumors for at least 30 days, functionally outperforming a clinically validated anti-BCMA binder.
In NHPs, treatment with BCMA panCAR resulted in specific and targeted plasma cell depletion.
Anti-BCMA panCAR is highly selective, demonstrating no significant impact on the overall B cell repertoire in NHPs.

(Press release, Orna Therapeutics, DEC 7, 2025, View Source [SID1234661206])

On December 7, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on developing innovative CAR T-cell therapies, reported that clinical data from its allogeneic BCMA-targeted CAR T-cell product candidate, CT0596, for the treatment of relapsed/refractory multiple myeloma (R/R MM) was presented in a poster at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The poster was titled "A First-in-Human Study of CT0596, an Allogeneic CAR T-Cell Therapy Targeting BCMA, in Patients with Relapsed/Refractory Multiple Myeloma." The publication number was 2296.

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This clinical trial (NCT06718270) enrolled 8 patients with R/R MM in the dose-escalation phase who received CT0596 infusion. The median number of prior lines of therapy was 4.5 (range: 3-9). Enrollment was not restricted by NKG2A expression levels. Regarding lymphodepletion, 6 patients received full-dose lymphodepletion with fludarabine (30 mg/m²/day) and cyclophosphamide (500 mg/m²/day) for 3 consecutive days, while 2 patients received reduced-dose lymphodepletion. CT0596 was administered at dose levels of 1.5×10⁸ (n=1), 3×10⁸ (n=5), and 4.5×10⁸ CAR-T cells (n=2), with one patient receiving two infusions.

As of August 31, 2025, all 8 infused patients were evaluable for efficacy, with a median follow-up of 4.14 months (range: 0.9-7.9 months). Six patients achieved a partial response (PR) or better: 3 achieved complete response/stringent complete response (CR/sCR) (all in the full-dose lymphodepletion group), 1 achieved very good partial response (VGPR), and 2 achieved PR. Among the 6 patients who received full-dose lymphodepletion, 5 achieved PR or better. Six patients in the full-dose lymphodepletion group achieved minimal residual disease (MRD)-negativity at Week 4. Patient 01 maintained ongoing sCR and MRD-negativity as of Month 8. Patient 04 achieved PR with resolution of extramedullary disease following the second infusion. CAR-T cell expansion was observed in all 8 patients. Among the two patients who received the 4.5×10⁸ dose, one achieved sCR, and the other exhibited deepening response to VGPR.

CT0596 demonstrated a manageable safety profile. Four patients experienced Grade 1 cytokine release syndrome (CRS); no Grade 2 or higher CRS was observed. No immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD) was reported. No dose-limiting toxicities, treatment discontinuations, or deaths were observed.

The study is still in the dose-exploration phase. The lymphodepletion regimen has been determined, and higher cell doses are being explored to further define the recommended dose (RD). The company plans to initiate a Phase 1b registrational study for CT0596 in 2026.

About CT0596

CT0596 is an allogeneic BCMA-targeted CAR-T therapy developed using CARsgen’s proprietary THANK-u Plus platform. It is currently being evaluated in investigator-initiated trials for relapsed/refractory multiple myeloma (R/R MM) or plasma cell leukemia (PCL). CT0596 demonstrated preliminary favorable tolerability and encouraging efficacy signals. Further investigation is planned in additional plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells. The company anticipates submitting an Investigational New Drug (IND) application in the second half of 2025.

(Press release, Carsgen Therapeutics, DEC 7, 2025, View Source [SID1234661222])

On December 6, 2025 Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company, reported new data from a post hoc analysis of the Phase 2 eNRGy trial (NCT02912949) evaluating zenocutuzumab in patients with treatment-naïve non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion. Results were presented in a late-breaking oral session at the IASLC-ASCO North America Conference on Lung Cancer (NACLC), in Chicago, Illinois.

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The new analysis evaluated the efficacy and safety of zenocutuzumab-zbco in treatment-naïve and previously treated NRG1+ NSCLC. Among 20 treatment-naïve and 121 previously treated patients, zenocutuzumab demonstrated an overall response rate (ORR) of 35% and 31%, respectively. The clinical benefit rate, defined as partial/complete response or stable disease for ≥24 weeks, was 65% in treatment-naïve and 58% in previously treated patients. Median duration of response was 17.1 months in treatment naïve patients, notably longer than in previously treated patients, 7.4 months. All treatment-related adverse events were grade 1 or 2. Zenocutuzumab safety profile was favorable and consistent with prior data.

"These data underscore the potential of zenocutuzumab as a first-line option for patients with NRG1-positive NSCLC, a patient population that typically responds poorly to standard first-line therapy," said Stephen Liu, MD, of Georgetown University. "Early and durable responses, coupled with a favorable safety profile are encouraging and highlight the importance of targeted therapy in this rare molecular subset."

"Consistent with other therapies targeting key oncogenic drivers, early intervention can lead to better outcomes — and we see the same with zenocutuzumab," said Pritesh J. Gandhi, Chief Development Officer at Partner Therapeutics. "These findings strengthen our conviction that early targeted inhibition of the NRG1 pathway with zenocutuzumab has the potential to meaningfully improve outcomes for patients with NRG1+ NSCLC."

"For patients and families facing NRG1+ lung cancer, these results mark meaningful progress," said Danielle Hicks, Chief Patient Officer of GO2 for Lung Cancer. "The durable responses and manageable safety profile of zenocutuzumab offer renewed hope and reinforce the need for continued innovation in biomarker-driven lung cancer care."

The abstract will be available on the Partner Therapeutics website under the research tab following the conference. Additional meeting information can be found on the IASLC-ASCO NACLC website.

In December 2024, zenocutuzumab-zbco (BIZENGRI) received U.S. Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The indications were approved under accelerated approval based on ORR and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.

About NRG1 Gene Fusions

NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably tissue-based RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1.

About BIZENGRI (zenocutuzumab-zbco)

INDICATIONS

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

BOXED WARNING: EMBRYO-FETAL TOXICITY

Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.

WARNINGS AND PRECUATIONS

Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions

BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.

Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.

Interstitial Lung Disease/Pneumonitis

BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated.

Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed.

Left Ventricular Dysfunction

BIZENGRI can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.

Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI.

Embryo-Fetal Toxicity

Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.

ADVERSE REACTIONS

NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC

Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).

In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).

NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI.

There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).

Please see full Prescribing Information, including Boxed Warning

(Press release, Partner Therapeutics, DEC 6, 2025, View Source [SID1234661223])

On December 6, 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-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) (Free ASH Whitepaper) 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.

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"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.

(Press release, Arvinas, DEC 6, 2025, View Source [SID1234661193])