CRISPR Therapeutics AG

(a) On May 6, 2025, we announced initial top-line data from our ongoing clinical trial of CTX310.

CTX310 targets ANGPTL3, a gene that encodes for key protein involved in the regulation of low-density lipoprotein, or LDL, and triglyceride, or TG, levels – both well-established risk factors for atherosclerotic heart disease, or ASCVD. Loss-of-function mutations in ANGPTL3 are associated with significantly reduced levels of LDL and TGs, as well as reduced risk of ASCVD, without adverse effects on overall health. In the United States alone, more than 40 million patients are affected by elevated LDL, severely elevated TGs or both – representing a large addressable patient population. CTX310 is initially focused on a high-risk subset of this group with the greatest unmet medical need and limited effective treatment options.

CTX310 is in an ongoing Phase 1 first-in-human dose escalation clinical trial targeting ANGPTL3 in four patient groups with elevated LDL, TG or both, including homozygous familial hypercholesterolemia , or HoFH, severe hypertriglyceridemia, or sHTG, heterozygous familial hypercholesterolemia, or HeFH, or mixed dyslipidemias, or MDL, with levels of TG (>300 mg/dL) and/or LDL-C (>100 mg/dL); >70 mg/dL for subjects with ASCVD. TG and LDL, both of which are validated as surrogate endpoints for clinical benefit and accepted by regulatory agencies, were assessed at various timepoints.

The top-line data are from the first 10 patients across the first four cohorts (lean body weight-based doses of dose level 1 [0.1 mg/kg], dose level 2 [0.3 mg/kg], dose level 3 [0.6 mg/kg] and dose level 4 [0.8 mg/kg] with at least 30 days of follow-up for each participant as of a data cutoff date of April 16, 2025.

A single dose of CTX310 demonstrated dose-dependent decreases in ANGPTL3, TGs, and LDL. Based upon ANGPTL3 knockdown, dose level 1 and dose level 2 were minimally active doses, whereas treatment at dose level 3 and dose level 4 resulted in reductions of up to 75% of baseline levels in ANGPTL3. CTX310 has been well-tolerated, with no treatment-related severe adverse events and no grade ≥3 adverse events reported. No clinically significant changes in alanine aminotransferase, aspartate aminotransferase, bilirubin or platelets were observed at any dose level. There were no dose-dependent trends in any of these laboratory measurements.

Individual patient responses highlight the therapeutic potential of CTX310: a dose level 4 patient with sHTG had an 82% reduction in triglycerides from a baseline of 1073 mg/dL at day 30, and a dose level 3 patient with HeFH had an 81% reduction in LDL-C from a baseline of 256 mg/dL at day 90 – supporting the potential for targeted efficacy in high-risk populations.

(b) Not applicable.

(c) From time to time, our officers (as defined in Rule 16a–1(f)) and directors may enter into Rule 10b5-1 or non-Rule 10b5-1 trading arrangements (as each such term is defined in Item 408 of Regulation S-K). During the three months ended March 31, 2025, none of our officers and directors adopted, modified orterminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement.