– ARV-393 demonstrated significant single-agent activity in models of nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (also known as AITL) and transformed follicular lymphoma –
– In combination with small molecule inhibitors, ARV-393 demonstrated enhanced tumor growth inhibition, including tumor regressions, in models of aggressive diffuse large B-cell lymphoma (DLBCL) –
NEW HAVEN, CT, USA I June 13, 2025 I Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, today presented data from preclinical studies of ARV-393, the company’s investigational PROteolysis TArgeting Chimera (PROTAC) B-cell lymphoma 6 protein (BCL6) degrader. BCL6 is a transcriptional repressor protein and a known driver of B-cell lymphomas. 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). The results from these preclinical studies were shared at the European Hematology Association (EHA) 2025 Congress in Milan, Italy.
Key findings from the preclinical studies included:
- Single-agent ARV-393 significantly reduced tumor burden in peripheral blood, bone marrow and spleen in a systemic PDX model of nTFHL-AI derived from a patient who relapsed post chemotherapy. This is potentially the first preclinical evidence of anti-tumor activity with an efficacious BCL6-targeted small-molecule degrader in a human nTFHL-AI model.
- ARV-393 monotherapy treatment resulted in robust (≥95%) tumor growth inhibition (TGI) in two PDX models of tFL.
- ARV-393 in combination with 5 classes of SMIs targeting potentially cooperative oncogenic drivers (tazemetostat, palbociclib, everolimus, acalabrutinib, or venetoclax) demonstrated increased TGI in CDX models of HGBCL and aggressive DLBCL compared with the respective monotherapy treatments. Tumor regressions were observed when ARV-393 was combined with tazemetostat, palbociclib, acalabrutinib, or venetoclax.
- RNA sequencing studies carried out to further characterize downstream mechanism of action suggested that ARV-393 inhibits tumor cell cycle progression and promotes differentiation, driving antitumor activity and broad combinability in preclinical models.
“We are encouraged by the marked single-agent activity of ARV-393 in PDX models of AITL and transformed follicular lymphoma and by the enhanced antitumor activity of ARV-393 in combination with five classes of small molecule inhibitors in models of aggressive DLBCL,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “We believe these preclinical data potentially suggest the broad utility of ARV-393 across non-Hodgkin lymphoma subtypes with unmet need beyond DLBCL and provide a compelling rationale for considering combination strategies including chemotherapy-free approaches as we work to bring forward new therapeutic options for adult patients with lymphoma.”
A Phase 1 study of ARV-393 is enrolling adult patients with relapsed/refractory non-Hodgkin lymphoma, including DLBCL and nTFHL-Al (AITL) (NCT06393738).
Additional detail on the ARV-393 data presentation at the EHA 2025 Congress:
Poster Title: ARV-393, a PROteolysis TArgeting Chimera (PROTAC) BCL6 Degrader, is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma, Nodal T-Follicular Helper Cell Lymphoma, and Transformed Follicular Lymphoma
Abstract: PF1000
Session Title: Lymphoma biology & translational research
Date: Thursday, June 13, 2025
Time: 6:30-7:30 pm CEST
About ARV-393
ARV-393 is an investigational orally bioavailable PROteolysis TArgeting Chimera (PROTAC) designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma.
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 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 vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin lymphoma; ARV-102, targeting LRRK2 for neurodegenerative disorders; and ARV-806, targeting KRAS G12D for mutated cancers, including pancreatic and colorectal cancers. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X.
SOURCE: Arvinas
Post Views: 1,814
– ARV-393 demonstrated significant single-agent activity in models of nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (also known as AITL) and transformed follicular lymphoma –
– In combination with small molecule inhibitors, ARV-393 demonstrated enhanced tumor growth inhibition, including tumor regressions, in models of aggressive diffuse large B-cell lymphoma (DLBCL) –
NEW HAVEN, CT, USA I June 13, 2025 I Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, today presented data from preclinical studies of ARV-393, the company’s investigational PROteolysis TArgeting Chimera (PROTAC) B-cell lymphoma 6 protein (BCL6) degrader. BCL6 is a transcriptional repressor protein and a known driver of B-cell lymphomas. 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). The results from these preclinical studies were shared at the European Hematology Association (EHA) 2025 Congress in Milan, Italy.
Key findings from the preclinical studies included:
- Single-agent ARV-393 significantly reduced tumor burden in peripheral blood, bone marrow and spleen in a systemic PDX model of nTFHL-AI derived from a patient who relapsed post chemotherapy. This is potentially the first preclinical evidence of anti-tumor activity with an efficacious BCL6-targeted small-molecule degrader in a human nTFHL-AI model.
- ARV-393 monotherapy treatment resulted in robust (≥95%) tumor growth inhibition (TGI) in two PDX models of tFL.
- ARV-393 in combination with 5 classes of SMIs targeting potentially cooperative oncogenic drivers (tazemetostat, palbociclib, everolimus, acalabrutinib, or venetoclax) demonstrated increased TGI in CDX models of HGBCL and aggressive DLBCL compared with the respective monotherapy treatments. Tumor regressions were observed when ARV-393 was combined with tazemetostat, palbociclib, acalabrutinib, or venetoclax.
- RNA sequencing studies carried out to further characterize downstream mechanism of action suggested that ARV-393 inhibits tumor cell cycle progression and promotes differentiation, driving antitumor activity and broad combinability in preclinical models.
“We are encouraged by the marked single-agent activity of ARV-393 in PDX models of AITL and transformed follicular lymphoma and by the enhanced antitumor activity of ARV-393 in combination with five classes of small molecule inhibitors in models of aggressive DLBCL,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “We believe these preclinical data potentially suggest the broad utility of ARV-393 across non-Hodgkin lymphoma subtypes with unmet need beyond DLBCL and provide a compelling rationale for considering combination strategies including chemotherapy-free approaches as we work to bring forward new therapeutic options for adult patients with lymphoma.”
A Phase 1 study of ARV-393 is enrolling adult patients with relapsed/refractory non-Hodgkin lymphoma, including DLBCL and nTFHL-Al (AITL) (NCT06393738).
Additional detail on the ARV-393 data presentation at the EHA 2025 Congress:
Poster Title: ARV-393, a PROteolysis TArgeting Chimera (PROTAC) BCL6 Degrader, is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma, Nodal T-Follicular Helper Cell Lymphoma, and Transformed Follicular Lymphoma
Abstract: PF1000
Session Title: Lymphoma biology & translational research
Date: Thursday, June 13, 2025
Time: 6:30-7:30 pm CEST
About ARV-393
ARV-393 is an investigational orally bioavailable PROteolysis TArgeting Chimera (PROTAC) designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma.
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 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 vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin lymphoma; ARV-102, targeting LRRK2 for neurodegenerative disorders; and ARV-806, targeting KRAS G12D for mutated cancers, including pancreatic and colorectal cancers. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X.
SOURCE: Arvinas
Post Views: 1,814
