ARV-393 / Arvinas - LARVOL DELTA

Phase 1 study of ARV-393, a PROTAC BCL6 degrader, as monotherapy in patients with advanced non-Hodgkin lymphoma (NHL) or combined with glofitamab in patients with diffuse large B-cell lymphoma (DLBCL) (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Metastases • Monotherapy • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6

MYC-BCL6 state transition drives metabolomic cycling and leukemia-initiating capacity in B-ALL (AACR 2026) - "To experimentally induce transitions, we engineered PDX with MYC-dTAG knock-in alleles and employed the BCL6 PROTAC ARV-393... These findings reveal a MYC-BCL6 state-transition program in B-ALL that coordinates quiescence-proliferation cycling, anabolic-catabolic metabolism, and leukemia-initiating potential."

Hematological Malignancies • Leukemia • Oncology • ABL1 • BCL6 • BCR • MYC

Anticipated Upcoming Milestones and Expectations (GlobeNewswire) - "Continue enrollment in the Phase 1 trial of ARV-806 in patients with solid tumors harboring KRAS G12D mutations (ClinicalTrials.gov Identifier: NCT07023731); Share initial clinical data in patients with solid tumors harboring KRAS G12D mutations (2026)...Anticipate sharing updated clinical data from the ongoing Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin’s lymphoma (ClinicalTrials.gov Identifier: NCT06393738) at a medical congress (2H 2026); Initiate enrollment of a combination cohort with glofitamab in patients with DLBCL in the ongoing Phase 1 clinical trial (1H 2026)....Identify and select a partner with the capabilities and expertise to maximize the commercial potential of vepdegestrant; Advance towards Prescription Drug User Fee Act (PDUFA) action date on June 5, 2026."

Clinical data • Commercial • PDUFA • Trial status • Angioimmunoblastic T-cell Lymphoma • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Non-Hodgkin’s Lymphoma • Pancreatic Ductal Adenocarcinoma • Solid Tumor

ARV-393-101: A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=255 | Recruiting | Sponsor: Arvinas Inc. | N=112 ➔ 255 | Trial completion date: Dec 2025 ➔ Mar 2028 | Trial primary completion date: Dec 2025 ➔ Mar 2028

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Secondary Central Nervous System Lymphoma • T Cell Non-Hodgkin Lymphoma

Alternating cycles of quiescent and proliferative cell states determine stemness and leukemia-initiation capacity in acute lymphoblastic leukemia (ASH 2025) - "In addition to the MYC-dTAG degron system, we used the BCL6 PROTAC degrader ARV-393 for acute ablation of either MYC orBCL6, which was achieved within 90 minutes... This study uncovers previously unrecognized cell state transitions in B-ALL that arecontrolled by MYC- and BCL6-dependent transcriptional programs. Alternating cycles of quiescent andproliferative cell states balance anabolic and catabolic metabolism, promote drug resistance, andenhance leukemia-initiating potential."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Targeted Protein Degradation • ABL1 • BCL6 • BCR • MYC

ARV-393, a PROTAC BCL6 degrader, combined with the CD20×CD3 bispecific glofitamab in a preclinical model of high-grade B-cell lymphoma (HGBCL) (ASH 2025) - P1 | "ARV-393 demonstrated combinatorial antitumor activity with glofitamab as evidenced bydeeper TGI than single-agent ARV-393 or glofitamab and by an increase in tumor regressions with bothconcomitant and sequential dosing of the combination. These findings suggest mechanistic synergiesbetween BCL6 degradation with ARV-393 and T-cell engagement through a CD20-targeted bispecificantibody and support clinical investigation of this chemotherapy-free combination in patients withDLBCL."

Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Targeted Protein Degradation • BCL6 • CD20 • CD34

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 (GlobeNewswire) - "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)....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."

P1 data • Preclinical • Trial status • Diffuse Large B Cell Lymphoma • High-grade B-cell lymphoma • Non-Hodgkin’s Lymphoma

Phase 1 Study of ARV-393, a PROTAC BCL6 Degrader, in Advanced Non-Hodgkin Lymphoma (ASH 2024) - P1 | "Secondary objectives are to characterize the pharmacokinetic profile of ARV-393 and evaluate its preliminary antitumor activity. Enrollment is currently ongoing."

Metastases • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • High-grade B-cell lymphoma • Hypereosinophilic Syndrome • Immunology • Infectious Disease • Interstitial Lung Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Organ Transplantation • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • BCL6 • CRBN

ARV-393: Oral PROTAC BCL6 degrader (Arvinas Press Release) - "Share preclinical data in combination with glofitamab in models of aggressive high grade DLBCL at the American Society of Hematology Annual Meeting (Dec. 6-9, 2025); Share updated clinical data from the ongoing Phase 1 clinical trial in patients with NHL (ClinicalTrials.gov Identifier: NCT06393738) at a medical congress (2026); Initiate enrollment in Phase 1 clinical trial in combination with glofitamab in patients with DLBCL (2026)."

New P1 trial • P1 data • Preclinical • Diffuse Large B Cell Lymphoma • High-grade B-cell lymphoma

Arvinas, Inc…announced that preclinical data for PROTAC BCL6 degrader ARV-393, in combination with glofitamab, a CD20xCD3 bispecific antibody, will be presented in a poster presentation at the 2025 American Society of Hematology (ASH) Annual Meeting, being held December 6–9, 2025, in Orlando, Florida. (GlobeNewswire)

Preclinical • Hematological Malignancies

ARV-393, a PROTAC BCL6 Degrader, in Preclinical Models of Diffuse Large B-cell Lymphoma (DLBCL), Nodal T-Follicular Helper Cell Lymphoma (nTFHL), and Transformed Follicular Lymphoma (tFL) (SOHO 2025) - P1 | " We assessed oral ARV-393 in a systemic PDX model from a patient with nTFHL-AI who relapsed post-cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and in 2 tFL PDX models. ARV-393 plus SMIs of EZH2 (tazemetostat), BCL2 (venetoclax), BTK (acalabrutinib), and CDK4/ 6 (palbociclib) was evaluated in preclinical DLBCL CDX models...ARV-393 performed similarly to romidepsin, a histone deacetylase inhibitor used for nTFHL-AI... ARV-393 demonstrated pronounced single-agent activity in a CHOP-refractory nTFHL-AI PDX model, which, to our knowledge, is the first preclinical evidence of an efficacious BCL6-targeted small-molecule degrader in human nTFHL-AI, an indication with high unmet need. ARV-393 also induced robust TGI in two tFL PDX models. These data support clinical evaluation of ARV-393 in patients with nTFHLAI and tFL."

Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CDK4

ARV-393, a PROTAC BCL6 Degrader, Combined With Biologics or Small-Molecule Inhibitors (SMIs) Induces Tumor Regressions in Diffuse Large B-Cell Lymphoma (DLBCL) Models (SOHO 2025) - P1 | "ARV-393 was also combined with investigational SMIs of lymphoma-associated oncoproteins EZH2 (tazemetostat), BCL2 (venetoclax), and BTK (acalabrutinib) in HGBCL or aggressive CDX models SU-DHL-6 (EZH2mut), OCILy1 (BCL2+), and activated B-cell-like OCI-Ly10 (MYD88 mut), respectively. ARV-393 plus SOC biologics increased tumor growth inhibition (TGI) vs monotherapy, with complete tumor regressions in 9/9 mice when combined with rituximab, 10/10 with tafasitamab (vs 55% TGI tafasitamab + lenalidomide), and 4/10 with polatuzumab vedotin... ARV-393 demonstrates synergistic antitumor activity, including complete regressions, in combination with SOC biologics and select SMIs in high-grade and aggressive DLBCL models, supporting future clinical investigation of ARV-393 combinations for DLBCL. Adapted from A Van Acker, et al. Cancer Res 15 April 2025; 85 (8_Supplement_1): 1655."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CREBBP • EP300 • MYC • MYD88

Arvinas Reports Second Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Added a combination cohort of vepdegestrant plus Pfizer’s KAT6 inhibitor (PF-07248144) to Pfizer’s ongoing Phase 1 clinical trial (ClinicalTrials.gov Identifier: NCT04606446)....ARV-393: Oral PROTAC BCL6 degrader: Continued recruiting patients in the first-in-human Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) (ClinicalTrials.gov Identifier: NCT06393738)....ARV-806: Novel PROTAC KRAS G12D degrader: Initiated enrollment in the Phase 1 clinical trial evaluating ARV-806 in patients with solid tumors harboring KRAS G12D mutations (ClinicalTrials.gov Identifier: NCT07023731)."

Trial status • Castration-Resistant Prostate Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Solid Tumor

Arvinas Reports Second Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "ARV-393: Oral PROTAC BCL6 degrader - Share preclinical data in combination with glofitamab in models of aggressive high grade DLBCL (2H 2025). Share preliminary clinical data from the ongoing Phase 1 clinical trial in patients with NHL (ClinicalTrials.gov Identifier: NCT06393738) (2H 2025). ARV-806: Novel PROTAC KRAS G12D degrader - Share preclinical data from the clinical stage ARV-806 program (2H 2025)."

P1 data • Preclinical • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma

Phase 1 Study of ARV-393, a PROTAC BCL6 Degrader, in Advanced Non-Hodgkin Lymphoma (NHL) (SOHO 2025) - P1 | "Blood. 2024; 144 (suppl 1):6505."

Metastases • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6

ARV-393, A PROTAC BCL6 DEGRADER, COMBINED WITH BIOLOGICS OR SMALL-MOLECULE INHIBITORS INDUCES TUMOR REGRESSIONS IN DIFFUSE LARGE B-CELL LYMPHOMA MODELS (ICML 2025) - P1 | "ARV-393 was also combined with investigational SMIs of EZH2 (tazemetostat), BCL2 (venetoclax), and BTK (acalabrutinib), in HGBCL or aggressive CDX models SU-DHL-6 (EZH2mut), OCI-Ly1 (BCL2+) and activated B-cell (ABC)-like OCI-Ly10 (MYD88 mut), respectively. ARV-393 combined with SOC biologics resulted in superior tumor growth inhibition (TGI) compared with monotherapy, with complete tumor regressions in 9/9 mice when combined with rituximab, 4/10 with polatuzumab vedotin, and 10/10 with tafasitamab (vs 55% TGI tafasitamab + lenalidomide)... ARV-393 demonstrates synergistic antitumor activity, including complete regressions, in combination with SOC agents and select SMIs in high grade and aggressive DLBCL models. These findings support future clinical investigation of ARV-393 in combination with other therapies for DLBCL."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CREBBP • EP300 • MYC • MYD88

ARV-393, A PROTAC BCL6 DEGRADER, IN PRECLINICAL MODELS OF DIFFUSE LARGE B-CELL LYMPHOMA, NODAL T-FOLLICULAR HELPER CELL LYMPHOMA, AND TRANSFORMED FOLLICULAR LYMPHOMA (ICML 2025) - P1 | " We assessed orally dosed ARV-393 antitumor activity in a systemic PDX model developed from the tumor of a patient with nTFHL-AI who relapsed post-cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy and in 2 different tFL PDX models...ARV-393 performed similarly to romidepsin, a histone deacetylase inhibitor commonly used to treat patients with nTFHL-AI...ARV-393 demonstrated complete tumor regressions with tazemetostat in the high-grade B-cell lymphoma (HGBCL) SU-DHL-6 CDX model and with venetoclax in the OCI-LY1 CDX model, and marked tumor regressions (TGI ≥ 100%) with acalabrutinib in the OCI-LY10 CDX model and with palbociclib in the SU-DHL-6 CDX model... ARV-393 demonstrated pronounced single-agent activity in a CHOP-refractory nTFHL-AI PDX model, which, to our knowledge, is the first preclinical evidence of an efficacious BCL6-targeted small-molecule degrader in human nTFHL-AI, an indication with high unmet need. ARV-393 also induced..."

Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CDK4

ARV-393, A PROTAC BCL6 DEGRADER, IS EFFICACIOUS IN PRECLINICAL MODELS OF DIFFUSE LARGE B CELL LYMPHOMA (DLBCL), NODAL T-FOLLICULAR HELPER CELL LYMPHOMA (NTFHL), AND TRANSFORMED FOLLICULAR LYMPHOMA (TFL) (EHA 2025) - P1 | "We assessed orally dosed ARV-393 antitumor activity in a systemic PDX model developed from the tumor of a patient with nTFHL-AI who relapsed post-cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy...Lastly, we tested the activity of ARV-393 in combination with SMIs of EZH2 (tazemetostat), BCL2 (venetoclax), BTK (acalabrutinib), and CDK4/6 (palbociclib) in preclinical CDX models of DLBCL.In the nTFHL-AI PDX model, ARV-393 demonstrated significant single-agent activity, reducing the tumor burden in the peripheral blood (8-fold decrease, p<0.01), bone marrow (5-fold decrease, p<0.0001), and spleen (3-fold decrease in weight, p<0.001). ARV-393 performed similarly to romidepsin, a histone deacetylase inhibitor commonly used to treat patients with nTFHL-AI... ARV-393 demonstrated pronounced single-agent activity in a CHOP-refractory PDX model of nTFHL-AI, which, to our knowledge, is the first preclinical evidence of an efficacious..."

Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • BCL2 • BCL6 • CDK4

Arvinas Presents Preclinical Data for PROTAC BCL6 Degrader, ARV-393, at the European Hematology Association 2025 Congress (GlobeNewswire) - "ARV-393 demonstrated significant single-agent activity in a patient derived xenograft (PDX) model of nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI also known as AITL) and PDX models of transformed follicular lymphoma (tFL). In combination with oral small molecule inhibitors (SMIs), ARV-393 demonstrated enhanced antitumor activity, including tumor regressions, in cell line-derived xenograft (CDX) models of high-grade B-cell lymphoma (HGBCL) and aggressive diffuse large B-cell lymphoma (DLBCL)."

Preclinical • Angioimmunoblastic T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • High-grade B-cell lymphoma

Arvinas to Present Preclinical Data for PROTAC BCL6 Degrader, ARV-393, at the 2025 European Hematology Association (EHA) Annual Meeting (The Manila Times) - "Company to showcase preclinical studies of ARV-393, an investigational oral PROTAC BCL6 degrader, as a single agent in models of nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL) and transformed follicular lymphoma, and in combination with small molecule inhibitors in models of diffuse large B-cell lymphoma."

Preclinical • Diffuse Large B Cell Lymphoma

ARV-393, a PROTAC B-cell lymphoma 6 (BCL6) degrader, combined with biologics or small molecule inhibitors (SMIs) induces tumor regressions in diffuse large B-cell lymphoma (DLBCL) models (AACR 2025) - P1 | "For example, CREBBP/EP300 and BCL6 have opposing transcriptional activities and BCL6 degradation may prevent CD20 downregulation by restoring CREBBP/EP300 chromatin access, supporting combination with anti-CD20 biologics; cooperation of EZH2 with the BCL6 repressor complex supports combining with tazemetostat (taz). Thus, we assessed the activity of ARV-393 in combination with biologics or SMIs based on potential complementary mechanistic roles.ARV-393 was administered in combination with clinically relevant doses of the standard of care (SOC) biologics rituximab, tafasitamab (tafa) and polatuzumab to mice bearing SU-DHL-4 CDX, representing a high-grade B-cell lymphoma (HGBCL, with MYC, BCL2 and BCL6 rearrangements). ARV-393 was also combined with investigational SMIs of EZH2 (taz), BCL2 (venetoclax) and BTK (acalabrutinib), in HGBCL or aggressive CDX models SU-DHL-6 (EZH2mut), OCI-Ly1 (BCL2+) and activated B-cell (ABC)-like OCI-Ly10 (MYD88 mut),..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Oncology • BCL2 • BCL6 • CREBBP • EP300 • MYC • MYD88

Anticipated Upcoming Milestones and Expectations (GlobeNewswire) - "Present new preclinical data demonstrating single agent activity of ARV-393 in patient derived xenograft models of transformed Follicular Lymphoma and a patient-derived xenograft model of nTFHL-AI (angioimmunoblastic type of nodal T-follicular helper cell lymphoma), a rare and aggressive non-Hodgkin lymphoma with high unmet need and limited treatment options, at the European Hematology Association 2025 conference in Milan, Italy (June 12-15, 2025); Share preclinical data in combination with an emerging SOC option in 2L DLBCL (2H 2025); Share preliminary clinical data from the ongoing Phase 1 clinical trial in patients with NHL (NCT06393738) (2H 2025)."

P1 data • Preclinical • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Non-Hodgkin’s Lymphoma

Arvinas Shares New Preclinical Combination Data for the PROTAC BCL6 Degrader, ARV-393, at the 2025 American Association for Cancer Research Annual Meeting (GlobeNewswire) - "Arvinas, Inc...presented data from preclinical combination studies of ARV-393, the company’s investigational PROteolysis TArgeting Chimera (PROTAC) B-cell lymphoma 6 protein (BCL6) degrader....ARV-393 in combination with SOC chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), induced significantly greater tumor growth inhibition compared with rituximab, CHOP, R-CHOP, or ARV-393 alone, with complete tumor regressions in all mice treated with the ARV-393 and R-CHOP combination. ARV-393 in combination with SOC biologics targeting CD20 (rituximab), CD19 (tafasitamab), or CD79b (polatuzumab vedotin) resulted in tumor regressions and demonstrated significantly stronger tumor growth inhibition compared with each agent alone."

Preclinical • Diffuse Large B Cell Lymphoma

Arvinas to Present Preclinical Data for PROTAC BCL6 Degrader, ARV-393, at 2025 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Arvinas, Inc...today announced that new preclinical combination data for ARV-393 will be presented at the American Association for Cancer Research (AACR) Annual meeting, April 25-30, 2025 in Chicago, Illinois. The poster highlights the potential for ARV-393 to be combined with various standard of care lymphoma treatments."

Preclinical • Diffuse Large B Cell Lymphoma

Arvinas Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "ARV-393: Oral PROTAC BCL6 degrader: Present preclinical data of ARV-393 in combination with standard of care biologic agents and small molecule inhibitors in high grade and aggressive diffuse large B-cell lymphoma in vivo models at the American Association for Cancer Research Annual Meeting (April 25-30, 2025). Disclose preliminary data from the ongoing Phase 1 clinical trial in patients with NHL (ClinicalTrials.gov Identifier: NCT06393738) in 2025....Novel PROTAC KRAS G12D degrader: File an Investigational New Drug (IND) application in 2025."

IND • P1 data • Preclinical • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Solid Tumor