CAMBRIDGE, MA, USA I August 22, 2022 I Verve Therapeutics, Inc., a clinical-stage biotechnology company pioneering a new approach to the care of cardiovascular disease with single-course gene editing medicines, today announced new preclinical data supporting the nomination of the company’s second product candidate, VERVE-201. VERVE-201 is designed to permanently turn off the ANGPTL3 gene in the liver, a key regulator of cholesterol and triglyceride metabolism, with a precise A-to-G base pair DNA change. Verve is initially developing VERVE-201 for the treatment of homozygous familial hypercholesterolemia (HoFH), a rare genetic subtype of atherosclerotic cardiovascular disease (ASCVD) characterized by extremely high blood low-density lipoprotein cholesterol (LDL-C), as well as for patients with ASCVD who have not achieved goal LDL-C with oral therapy and a PCSK9 inhibitor. The preclinical data will be highlighted on August 29, 2022 in a poster session during the European Society of Cardiology 2022 Congress in Barcelona.
“ANGPTL3 is a well-validated target for lowering LDL-C. Through turning off this gene in the liver, we believe we have a significant opportunity to help patients with HoFH or ASCVD reach LDL-C goals and improve clinical outcomes,” said Andrew Bellinger, M.D., Ph.D., chief scientific and medical officer of Verve. “Our research and development team has now generated two cardiovascular gene editing clinical candidates, as well as novel delivery technology, which is a testament to the ingenuity and dedication of an incredible team. Today we share some of this extensive research to identify a product candidate that we believe can provide potent and durable inactivation of ANGPTL3 with limited to no off-target editing. The selection of VERVE-201 is an exciting step forward, and we look forward to initiating studies this year to enable an investigational new drug application and potentially bring VERVE-201 into the clinic in 2024.”
Prior to nominating VERVE-201, Verve used a rigorous process to optimize preclinical safety and efficacy. Verve screened more than 200 engineered and chemically modified adenine base editor (ABE) and guide RNA (gRNA) configurations targeting ANGPTL3 to assess their potency and on-target/off-target profiles. An optimized configuration was selected and evaluated in primary human liver cells, which showed potent, on-target editing of the ANGPTL3 gene with no detectable off-target and no detectable structural variants as assessed using high-coverage whole genome optical mapping. Verve also conducted a non-human primate (NHP) study (n=9), which showed that the optimized configuration, an NHP surrogate version of VERVE-201, demonstrated potent liver ANGPTL3 editing ranging from 54-57% and reductions in blood ANGPTL3 protein ranging from 95-98% across three dose levels. To enable efficient delivery of VERVE-201 in HoFH patients with the highest unmet need, VERVE-201 is using Verve’s proprietary GalNAc-lipid nanoparticle (GalNAc-LNP) delivery technology.
In addition to the VERVE-201 work, Verve shared an update on previously reported data with an ANGPTL3 precursor formulation targeting the same base editing outcome in NHPs. These data demonstrated durable editing in the liver of treated NHPs (n=4) of 61% at over two years following dosing, which was identical to editing levels measured via liver biopsy on day 15.
Presentation Details
- Title: An in vivo CRISPR base editing therapy to inactivate the ANGPTL3 gene: nomination of a development candidate for VERVE-201
- Session: RNA and gene therapy of vascular diseases
- Date & Time: August 29, 2022, between 3:15 – 4:00 p.m. CEST
About Verve Therapeutics
Verve Therapeutics, Inc. (Nasdaq: VERV) is a clinical-stage genetic medicines company pioneering a new approach to the care of cardiovascular disease, potentially transforming treatment from chronic management to single-course gene editing medicines. The company’s initial two programs – VERVE-101 and VERVE-201 – target genes that have been extensively validated as targets for lowering low-density lipoprotein cholesterol (LDL-C), a root cause of cardiovascular disease, in order to durably reduce blood LDL-C levels. VERVE-101 is designed to permanently turn off the PCSK9 gene in the liver and is initially being developed for heterozygous familial hypercholesterolemia. VERVE-201 is designed to permanently turn off the ANGPTL3 gene in the liver and is initially being developed for homozygous familial hypercholesterolemia and those with atherosclerotic cardiovascular disease who have not achieved goal LDL-C with oral therapy and a PCSK9 inhibitor. For more information, please visit www.VerveTx.com.
SOURCE: Verve Therapeutics
Post Views: 73
CAMBRIDGE, MA, USA I August 22, 2022 I Verve Therapeutics, Inc., a clinical-stage biotechnology company pioneering a new approach to the care of cardiovascular disease with single-course gene editing medicines, today announced new preclinical data supporting the nomination of the company’s second product candidate, VERVE-201. VERVE-201 is designed to permanently turn off the ANGPTL3 gene in the liver, a key regulator of cholesterol and triglyceride metabolism, with a precise A-to-G base pair DNA change. Verve is initially developing VERVE-201 for the treatment of homozygous familial hypercholesterolemia (HoFH), a rare genetic subtype of atherosclerotic cardiovascular disease (ASCVD) characterized by extremely high blood low-density lipoprotein cholesterol (LDL-C), as well as for patients with ASCVD who have not achieved goal LDL-C with oral therapy and a PCSK9 inhibitor. The preclinical data will be highlighted on August 29, 2022 in a poster session during the European Society of Cardiology 2022 Congress in Barcelona.
“ANGPTL3 is a well-validated target for lowering LDL-C. Through turning off this gene in the liver, we believe we have a significant opportunity to help patients with HoFH or ASCVD reach LDL-C goals and improve clinical outcomes,” said Andrew Bellinger, M.D., Ph.D., chief scientific and medical officer of Verve. “Our research and development team has now generated two cardiovascular gene editing clinical candidates, as well as novel delivery technology, which is a testament to the ingenuity and dedication of an incredible team. Today we share some of this extensive research to identify a product candidate that we believe can provide potent and durable inactivation of ANGPTL3 with limited to no off-target editing. The selection of VERVE-201 is an exciting step forward, and we look forward to initiating studies this year to enable an investigational new drug application and potentially bring VERVE-201 into the clinic in 2024.”
Prior to nominating VERVE-201, Verve used a rigorous process to optimize preclinical safety and efficacy. Verve screened more than 200 engineered and chemically modified adenine base editor (ABE) and guide RNA (gRNA) configurations targeting ANGPTL3 to assess their potency and on-target/off-target profiles. An optimized configuration was selected and evaluated in primary human liver cells, which showed potent, on-target editing of the ANGPTL3 gene with no detectable off-target and no detectable structural variants as assessed using high-coverage whole genome optical mapping. Verve also conducted a non-human primate (NHP) study (n=9), which showed that the optimized configuration, an NHP surrogate version of VERVE-201, demonstrated potent liver ANGPTL3 editing ranging from 54-57% and reductions in blood ANGPTL3 protein ranging from 95-98% across three dose levels. To enable efficient delivery of VERVE-201 in HoFH patients with the highest unmet need, VERVE-201 is using Verve’s proprietary GalNAc-lipid nanoparticle (GalNAc-LNP) delivery technology.
In addition to the VERVE-201 work, Verve shared an update on previously reported data with an ANGPTL3 precursor formulation targeting the same base editing outcome in NHPs. These data demonstrated durable editing in the liver of treated NHPs (n=4) of 61% at over two years following dosing, which was identical to editing levels measured via liver biopsy on day 15.
Presentation Details
- Title: An in vivo CRISPR base editing therapy to inactivate the ANGPTL3 gene: nomination of a development candidate for VERVE-201
- Session: RNA and gene therapy of vascular diseases
- Date & Time: August 29, 2022, between 3:15 – 4:00 p.m. CEST
About Verve Therapeutics
Verve Therapeutics, Inc. (Nasdaq: VERV) is a clinical-stage genetic medicines company pioneering a new approach to the care of cardiovascular disease, potentially transforming treatment from chronic management to single-course gene editing medicines. The company’s initial two programs – VERVE-101 and VERVE-201 – target genes that have been extensively validated as targets for lowering low-density lipoprotein cholesterol (LDL-C), a root cause of cardiovascular disease, in order to durably reduce blood LDL-C levels. VERVE-101 is designed to permanently turn off the PCSK9 gene in the liver and is initially being developed for heterozygous familial hypercholesterolemia. VERVE-201 is designed to permanently turn off the ANGPTL3 gene in the liver and is initially being developed for homozygous familial hypercholesterolemia and those with atherosclerotic cardiovascular disease who have not achieved goal LDL-C with oral therapy and a PCSK9 inhibitor. For more information, please visit www.VerveTx.com.
SOURCE: Verve Therapeutics
Post Views: 73
