ARV-393 / Arvinas - LARVOL DELTA

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

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

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

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) - No abstract available

Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • 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) - No abstract available

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6

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

Arvinas…Highlights Upcoming Milestones, and Provides Corporate Update (GlobeNewswire) - "ARV-393: Oral PROTAC BCL6 degrader - Present initial data from the ongoing Phase 1 clinical trial in patients with B-cell lymphomas (NCT06393738). Novel PROTAC KRAS G12D degrader: File an Investigational New Drug (IND) application."

IND • P1 data • Non-Hodgkin’s Lymphoma • Oncology

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 • Bone Marrow Transplantation • 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

Arvinas Reports Third Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "ARV-393: Oral PROTAC BCL6 degrader - Continue recruiting patients in the first-in-human Phase 1 clinical trial evaluating ARV-393 in patients with B-cell lymphomas. Novel PROTAC KRAS G12D degrader: File an Investigational New Drug (IND) application in 2025."

IND • Trial status • Non-Hodgkin’s Lymphoma

ARV-393-101: A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Arvinas Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

ARV-393-101: A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=112 | Not yet recruiting | Sponsor: Arvinas Inc. | Initiation date: Apr 2024 ➔ Aug 2024

Metastases • Trial initiation date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Arvinas Announces Presentations for Two of its PROTAC Investigational Programs Targeting BCL6 and LRRK2 (GlobeNewswire) - "Data presented at EHA showed anti-tumor activity for the company’s investigational PROTAC BCL6 degrader, ARV-393, in preclinical models of B-cell lymphoma. In these preclinical models, ARV-393 potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines. ARV-393 showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma."

Preclinical • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ORAL ARV-393 IS A BCL6 DEGRADING PROTAC EFFICACIOUS AS MONOTHERAPY IN B-CELL LYMPHOMA PRECLINICAL CDX AND PDX MODELS (EHA 2024) - "ARV-393 is an oral PROTAC BCL6 degrader that demonstrated potent anti-tumormonotherapy activity in numerous preclinical models of NHL, indicating this molecule may provide a significanttherapeutic benefit to NHL patients."

IO biomarker • Monotherapy • Preclinical • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Targeted Protein Degradation • BCL2 • BCL6 • CRBN

TRIAL IN PROGRESS: PHASE 1 STUDY OF ARV-393, A PROTAC BCL6 DEGRADER, IN ADVANCED NON-HODGKIN LYMPHOMA (EHA 2024) - "This will be the first clinical study of ARV-393, a potent, selective, oral PROTAC BCL6degrader, in patients with advanced relapsed/refractory NHL."

Metastases • P1 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Organ Transplantation • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • Transplantation • BCL6 • CRBN

Arvinas Reports First Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate discussion with regulatory authorities on a second-line Phase 3 trial of vepdegestrant in combination with palbociclib and potentially other CDK4/6 inhibitors, and a new first-line Phase 3 trial of vepdegestrant plus atirmociclib, Pfizer’s novel CDK4 inhibitor....Initiate dosing in first-in-human Phase 1 clinical trial in B-cell lymphomas with PROTAC BCL6 degrader ARV-393 (2Q 2024)....The decrease in research and development expenses of $11.0 million for the quarter was primarily due to a decrease in expenses related to our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $8.2 million, our ER program (which includes the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement) of $2.3 million and our platform and exploratory programs of $0.5 million."

Commercial • Regulatory • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of ARV-393 in Relapsed/Refractory Non-Hodgkin Lymphoma. (clinicaltrials.gov) - P1 | N=112 | Recruiting | Sponsor: Arvinas Inc.

Metastases • New P1 trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

The discovery of ARV-393, a potent, orally bioavailable BCL6 targeting PROTAC® for the treatment of Non-Hodgkin's Lymphoma (AACR 2024) - "Despite the success of R-CHOP treatment, approximately 40% of patients are refractory or relapse. This agent demonstrates deep BCL6 degradation in vitro and in vivo, resulting in excellent TGI in several tumor xenograft models supporting a first-in-human trial in 1H 2024. We will present the chemical structure of ARV-393 and selected pre-clinical data."

Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6 • CRBN

Arvinas Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Initiate first-in-human Phase 1 clinical trial in B-cell lymphomas with BCL6 targeting PROTAC ARV-393 (1H 2024)....The increase in research and development expenses of $64.7 million for the year was primarily due to an increase in expenses associated with our platform and exploratory programs of $1.1 million, our AR program (which includes ARV-766 and bavdegalutamide (ARV-110)) of $22.0 million and our ER program of $41.6 million, which includes the cost sharing of vepdegestrant (ARV-471) under the Vepdegestrant (ARV-471) Collaboration Agreement."

Commercial • New P1 trial • Hematological Malignancies • Lymphoma • Oncology

Arvinas Reports Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Submit two investigational new drug (IND)/clinical trial authorization (CTA) applications for the Company’s BCL6 (oncology)...Progress at least two additional PROTAC protein degrader programs into IND- or CTA-enabling studies by year-end 2023....The increase in research and development expenses of $8.4 million for the quarter was primarily due to increases our AR program of $5.2 million, which includes ARV-766 and bavdegalutamide, and our ER program of $6.2 million, which is net of the cost sharing of vepdegestrant under the Vepdegestrant (ARV-471) Collaboration Agreement, offset by a decrease in our platform and exploratory programs of $3.0 million."

Commercial • IND • Oncology