今天（2021年9月23日），Verve还正式宣布了其开发的 GalNAc-LNP 来进行对 LDLR 表达缺失人群的递送。因为在一部分患者人群中，比如HoFH，其肝脏细胞没有LDLR。
Verve 准备用这种新型的 GalNAc-LNP 来递送 Base Editor 来 KO ANGPTL3，用于治疗 HoFH and in heterozygous familial hypercholesterolemia 患者。公司准备在2022年开始IND-enabling studies。
这样一来，估计Verve明后两年都会各有一个项目进入临床阶段。
In some patient populations, such as HoFH, using LNPs for delivery of base editors is not possible, requiring the need for an alternative delivery approach to treat these patients. To address this, we have designed and developed a proprietary GalNAc-LNP to enable efficient and potent liver editing regardless of LDLR expression. We are very excited to share findings leveraging this delivery approach, which may allow us to reach patients who lack LDLR and may be applicable in other populations where liver-targeted delivery is advantageous.
High efficiency liver delivery of an adenine base editor targeting ANGPTL3 in both LDLR heterozygous and homozygous deficient mouse models;
Low GalNAc-lipid content with 0.05 mol% leading to maximal liver editing in an LDLR knockout model;
A scalable process of incorporating the GalNAc ligand into the LNP with near-homogenous distribution of GalNAc ligand; and
Potent editing in vivo regardless of the LDLR status of the mouse.
Verve is advancing a gene editing program that targets ANGPTL3, a gene known to regulate blood LDL-C and triglycerides. Such a program would have potential indications in both HoFH and in heterozygous familial hypercholesterolemia. Verve is designing this program to utilize a GalNAc-modified LNP encapsulating an mRNA encoding a base editor and a gRNA targeting the ANGPTL3 gene. The company’s program is currently in the lead optimization stage, and the company expects to name its development candidate and initiate IND-enabling studies in 2022.