CRISPR Therapeutics AG

(a) On November 8, 2025, we announced positive Phase 1 data from our ongoing clinical trial evaluating CTX310, an investigational, in vivo CRISPR/Cas9 gene-editing therapy targeting ANGPTL3. A single-course treatment with CTX310 produced dose-dependent, durable reductions in circulating ANGPTL3 with a mean reduction from baseline of -73% (maximum -89%), a mean reduction in triglycerides, or TG, of -55% (maximum -84%) and a mean reduction of low-density lipoprotein, or LDL, of -49% (maximum -87%) at the highest dose. These data were presented during a late-breaking session at the American Heart Association Scientific Sessions and published simultaneously in The New England Journal of Medicinein a peer-reviewed article entitled “Phase 1 Trial of CRISPR-Cas9 Gene Editing Targeting ANGPTL3.”

The Phase 1, open label, dose-escalation trial evaluated single-course intravenous doses of CTX310 ranging from 0.1 to 0.8 mg/kg (lean body weight) targeting ANGPTL3 in four patient groups: homozygous familial hypercholesterolemia, severe hypertriglyceridemia, or sHTG, heterozygous familial hypercholesterolemia, or mixed dyslipidemias (elevated TG and LDL). Eligible participants had uncontrolled TG levels >150 mg/dL and/or LDL cholesterol >100 mg/dL (or >70 mg/dL for those with established atherosclerotic cardiovascular disease) despite background standard of care per local guidelines. The majority of participants were receiving statins and/or ezetimibe, while 40% were taking PCSK9 inhibitors. The trial was designed to evaluate safety and tolerability as primary endpoints, with changes in circulating ANGPTL3 protein, TG, and LDL as secondary endpoints.

Single-course ascending doses of CTX310 were administered to 15 participants across sequential cohorts, and all participants completed at least 28 days of follow-up as of the data cutoff. CTX310 was generally well tolerated, and no dose-limiting toxicities or serious adverse events related to treatment.

Adverse events were generally mild to moderate. One participant experienced an allergic reaction that resolved the following day with supportive care. Infusion-related reactions occurred in three participants (two at 0.6 mg/kg and one at 0.8 mg/kg dose), all Grade 2. All events resolved, and all participants completed their infusions. One participant with elevated transaminases level at baseline had a Grade 2 elevation of transaminases that peaked by Day 4 and resolved completely by Day 14 without any rise in bilirubin.

Overall, CTX310 demonstrated a well-tolerated safety and tolerability profile that supports continued advancement of the program.

These new results build upon previously disclosed top-line data from 12 participants across the first four sequential cohorts, corresponding to lean body weight-based doses of dose level, or DL, 1 [0.1 mg/kg], DL2 [0.3 mg/kg], DL3 [0.6 mg/kg] and DL4 [0.8 mg/kg]. All participants had at least 30 days of follow-up.

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Dose-dependent reductions in circulating ANGPTL3 protein: Mean (range) among participants treated with 0.1, 0.3, 0.6, 0.7, and 0.8 mg/kg doses were 10% (-22 to 71), 9% (-25 to 64), -33% (-51 to -19), -80% (-87 to -73), and -73% (-89 to -67), respectively, at Day 30 following CTX310 infusion.

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Among participants treated at 0.8 mg/kg, TG reductions of up to 84% were observed, with a mean reduction of 55% at Day 60 following CTX310 infusion.

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In participants with elevated TG (>150 mg/dL) at baseline, mean reductions of 60% were observed at the therapeutic dose levels at Day 60 following CTX310 infusion.

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Among participants treated at 0.8 mg/kg, LDL reductions of up to 87% were observed, with a mean reduction of 49% at Day 60 following CTX310 infusion.

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Two participants on background PCSK9 inhibitors achieved >80% reduction in LDL from baseline.

We are advancing CTX310 into Phase 1b clinical trials, prioritizing development in sHTG and mixed dyslipidemia.

(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 September 30, 2025, our officers and directors took the following actions with respect to 10b5-1 trading arrangements:

In addition, on August 27, 2025, Samarth Kulkarni, Ph.D., our Chief Executive Officer, terminated a Rule 10b5-1 trading arrangement he had previously adopted with respect to the sale of up to an aggregate of 75,000 common shares of the Company pursuant to the terms of such trading plan. Dr. Kulkarni’s Rule 10b5-1 trading arrangement was adopted on June 10, 2025 and was active through March 31, 2026. As of the date of termination of such rule 10b5-1 trading arrangement, Dr. Kulkarni had not sold any common shares under the terms of such trading plan.