Dive Brief:

潜水简介：

Verve Therapeutics has treated the first participant in a recently begun clinical trial of the company’s backup gene editing therapy for heart disease, about one month after a safety setback derailed what had been its lead candidate.

Verve Therapeutics治疗了该公司最近开始的心脏病备用基因编辑疗法临床试验的第一位参与者，大约一个月前，安全挫折使其主要候选人脱轨。

The Phase 1b study, dubbed Heart-2, is testing Verve’s therapy in people with a hereditary form of high cholesterol known as HeFH for short, or who have premature coronary artery disease. The company is currently cleared to enroll patients in the U.K. and Canada, although it eventually plans to expand the study to the U.S..

这项被称为Heart-2的1b期研究正在测试Verve对遗传性高胆固醇（简称HeFH）或早发冠心病患者的治疗效果。该公司目前已获准在英国和加拿大招募患者，尽管它最终计划将研究扩展到美国。。

Verve’s therapy uses a technique called base editing to change a single nucleotide, or base, in a liver gene called PCSK9. The effect is inactivation of the gene and, in theory, permanent lowering in LDL cholesterol, high levels of which are closely linked to heart disease.

Verve的疗法使用一种称为碱基编辑的技术来改变称为PCSK9的肝脏基因中的单个核苷酸或碱基。这种效应是基因失活，理论上是LDL胆固醇的永久降低，高水平的LDL胆固醇与心脏病密切相关。

Dive Insight:

潜水洞察：

Verve had been steadily progressing its lead base editing therapy Verve-101, enrolling patients with HeFH across three countries and, last November, revealing data that offered “proof of principle” for its treatment approach.

Verve一直在稳步推进其领先的基础编辑疗法Verve-101，在三个国家招募了HeFH患者，并于去年11月公布了为其治疗方法提供“原则证明”的数据。

But early last month, the company disclosed concerning laboratory test results for one participant, which showed elevated liver enzyme counts and lower levels of a clot-forming blood cell. The participant was observed in a hospital and released after the abnormalities resolved.

但上个月初，该公司披露了一名参与者的实验室检测结果，结果显示肝酶计数升高，血块形成血细胞水平降低。该参与者在医院接受了观察，并在异常解决后获释。

Since the irregularities occurred shortly after treatment with Verve-101, however, investigators judged the side effect as likely to be treatment induced. High counts in certain liver enzymes can be a warning sign of organ damage.

然而，由于这些不规则现象是在用Verve-101治疗后不久发生的，因此研究人员判断副作用可能是由治疗引起的。某些肝酶的高计数可能是器官损伤的警告信号。

In response, Verve paused study enrollment while it investigates the side effect and pivoted its efforts to Verve-102 instead.

作为回应，Verve在调查副作用时暂停了研究注册，并将精力转向Verve-102。

The two treatments are designed to shut off the PCSK9 gene in the same way, but Verve-102 uses a different lipid nanoparticle “shell” to deliver the gene editing components into the body and to the right cells. The company says the lipid nanoparticle used in Verve-101 may be the cause of the side effect it observed..

这两种治疗方法旨在以相同的方式关闭PCSK9基因，但Verve-102使用不同的脂质纳米颗粒“壳”将基因编辑成分传递到体内和正确的细胞。该公司表示，Verve-101中使用的脂质纳米颗粒可能是其观察到的副作用的原因。。

The shell for Verve-102 also enables the therapy to enter cells by two different receptors, potentially allowing Verve to test lower doses and avoid other side effects.

Verve-102的外壳还使该疗法能够通过两种不同的受体进入细胞，从而有可能使Verve测试较低剂量并避免其他副作用。

According to Verve, the Heart-2 trial will study Verve-102’s safety as well as its effects on blood PCSK9 protein and LDL cholesterol levels. The study will involve four dose cohorts, each enrolling three to nine patients with HeFH, heterozygous familial hypercholesterolemia, or premature coronary artery disease..

据Verve称，Heart-2试验将研究Verve-102的安全性及其对血液PCSK9蛋白和低密度脂蛋白胆固醇水平的影响。该研究将涉及四个剂量组，每个组招募三到九名HeFH，杂合性家族性高胆固醇血症或早发性冠状动脉疾病患者。。

Verve expects to report results from the trial in 2025.

Verve预计在2025年报告试验结果。