CRISPR Therapeutics (NASDAQ:CRSP) used a fireside chat at TD Cowen’s 46th Annual Healthcare Conference to outline how the company is trying to broaden its identity beyond its first commercial product, Casgevy, and build franchises in cardiovascular disease and autoimmune conditions.
Chief Executive Officer and Chairman Samarth Kulkarni said 2025 was “quite the pivotal year” as the company moved “to go beyond Casgevy.” He described the business through two lenses: value distribution across the portfolio and a strategic shift from being “technology-forward” to “disease-backed.”
Portfolio framing: beyond Casgevy
- Casgevy representing about a third of value,
- Phase 1 assets with promising data representing another third—specifically CTX310, CTX320, and CTX611,
- Pipeline depth beyond early programs making up the remaining portion.
Looking ahead, he said that by mid-2027 the company expects to have data from “six programs beyond Casgevy across more than six indications.”
From a disease-area standpoint, he highlighted two franchises the company is building capabilities around:
- Cardiovascular, including CTX310 (ANGPTL3), CTX611 (Factor XI siRNA via its partnership), Lp(a) efforts (CTX320/CTX321), and CTX340 for refractory hypertension (angiotensinogen).
- Autoimmune, including CTX320 (described as a cell therapy approach that could function like an FcRn-type platform across indications) and an additional siRNA target in autoimmune that the company expects to announce.
Casgevy: launch funnel expansion and timing dynamics
Discussing Casgevy with partner Vertex, Kulkarni said 2024 and 2025 were “foundational” years, noting “well over $100 million” in full-year 2025 sales. He did not provide specific 2026 sales guidance in the discussion, but said both companies are “quite excited about 2026,” pointing to a growing “top of the funnel.”
He said patient initiations increased from about 100 in 2024 to “300+” in 2025, and he expects that number to be “much larger” in 2026. He also said cell collections are beginning to “inflect,” and that revenue should follow as more sites become productive, citing a “geometric growth” pattern as the funnel expands. Kulkarni added that, based on experience so far, the dropout rate is “very low” once patients are initiated and cells are collected.
On timing from referral to treatment and reimbursement, he said thalassemia patients can progress “quite fast,” potentially around six months, while sickle cell patients can take “as long as a year,” with real-world timelines landing somewhere in between.
On profitability, Kulkarni reiterated that CRISPR Therapeutics expects 2025 to be the peak year of spend for the Casgevy franchise from its perspective, but said the company cannot yet specify when the franchise reaches profitability and indicated that Vertex would guide on that. He also emphasized ongoing investments in a “gentler conditioning agent” and in vivo hematopoietic stem cell (HSC) delivery, and said pediatric expansion could further expand the market. He referenced data presented at the J.P. Morgan conference showing durable editing of HSCs in non-human primates, while noting more work remains.
CTX310: early in vivo data and regulatory path questions
Kulkarni highlighted CTX310, an in vivo program targeting ANGPTL3, and said the company’s American Heart Association presentation served as a “coming out party” for its in vivo platform. He said that at the highest dose levels CRISPR Therapeutics has seen “completely saturate” editing in hepatocytes for ANGPTL3, producing about an 80% reduction in ANGPTL3 levels. Because some ANGPTL3 is produced outside the liver, that portion is not affected by the approach, he said.
He said the observed biomarker effects included nearly a 50% reduction in LDL cholesterol and nearly a 60% reduction in triglycerides. Kulkarni discussed multiple potential subpopulations for development, including severe hypertriglyceridemia (he referenced triglycerides above 800), mixed dyslipidemia, and familial hypercholesterolemia, including homozygous FH patients who may be refractory to PCSK9 therapies. He said the company is working to define responses in each group and is focused on meeting with regulators to clarify the “path forward for registrational trials,” which he framed as a key de-risking and spending “ungating” event.
Asked about the bar for LDL reduction and whether the program could advance across multiple populations, Kulkarni said it could. He also described synergy with PCSK9 therapies, noting that two patients on PCSK9 therapy saw 50%–60% LDL reductions on top of that background treatment, attributing this to ANGPTL3’s distinct mechanism compared with PCSK9.
Lp(a), hypertension, and platform expansion: CTX320/CTX321, CTX340, SyNTase, and siRNA
On lipoprotein(a), Kulkarni said the category “hinges” heavily on the upcoming HORIZON outcomes data from Novartis’ antisense oligonucleotide program, describing it as an important readout for the field. He said CRISPR Therapeutics has completed dose escalation with CTX320 and previously disclosed a peak ~73% reduction in Lp(a). However, he said the company will not “click go” on a large Phase II study until HORIZON reads out.
He also discussed CTX321, initially considered a backup, which he said has shown nearly 2x greater editing in animal models. Kulkarni said the company plans to use the HORIZON data to determine the required level of Lp(a) reduction and then decide how to prioritize between CTX320 and CTX321, balancing potency and timing differences.
On safety for in vivo gene editing, he said the company has been transparent with liver function test (LFT) data for CTX310 and described its lipid nanoparticle platform as “very safe,” with any minor LFT increases self-resolving. He also said regulators are “very, very supportive of gene editing,” and referenced that Intellia had come off clinical hold “today,” which he characterized as a positive development for the field.
For CTX340 in refractory hypertension, Kulkarni said the program targets angiotensinogen and was informed by Alnylam’s KARDIA trials with an siRNA against the same target. He summarized those results as nearly 90% angiotensinogen reduction and double-digit systolic blood pressure reductions, with low side effects, no hyperkalemia, and “no risk of hypotension” noted as a concern that did not appear to manifest in that data set. He said CRISPR Therapeutics will enter the clinic “soon” but did not commit to a specific timing for dose-escalation data, while stating there is a possibility of double-digit systolic reductions and that outcomes may differ based on background therapies.
Kulkarni also discussed the company’s SyNTase technology, which he said enables precise editing at high efficiencies and has shown near-saturating edits in hepatocytes in animal models at 0.1 mg/kg—“about 6x better” than CTX310 from a potency standpoint. He said alpha-1 antitrypsin deficiency (A1AT) was chosen as the first indication and compared results from animal models to what he described as base editing data in the clinic showing ~2.2x improvement over background. He said CRISPR Therapeutics saw a 5x AAT elevation in similar models and suggested this could plausibly translate to higher micromolar levels in patients. He said the company expects to be in the clinic “mid this year.”
Finally, he outlined the company’s siRNA partnership with Sirius, describing Sirius’ approach as combining learnings and chemical modifications drawn from across the sector to create potent, durable siRNAs lasting 6 to 12 months. Kulkarni said the deal provides CRISPR Therapeutics with 50% of a Factor XI siRNA program that already has Phase I data, plus two additional siRNA assets whose targets will be revealed this year and are expected to move quickly toward the clinic.
On Factor XI, he argued against permanent gene editing of the clotting cascade and said a twice-yearly dosing approach could fit the biology and clinical need. He referenced the OCEANIC trial of asundexian, describing it as a large study showing a significant reduction in secondary stroke risk, and said CRISPR Therapeutics expects Phase II proof-of-concept data in the second half, including readouts from a thrombosis model study (the “TK study”) and multiple ascending dose data to guide dose and indication selection.
Cell therapy and in vivo CAR-T: zugo-cel and platform interest
In cell therapy, Kulkarni called zugo-cel the “most underappreciated asset” in the portfolio and said the company will provide lymphoma follow-up in the second half of the year, alongside updates in autoimmune. He said he believes CRISPR Therapeutics is positioned “to win the autoimmune race with zugo-cel,” and added that in oncology the company is exploring a development strategy that includes pembrolizumab.
On in vivo CAR-T, he said CRISPR Therapeutics has shown mRNA engineering that yields persistent CAR-T cells out to day 14 in models, contrasting with other approaches he said peak around day four and are gone by day seven. He said non-human primate B-cell depletion data should come in the “not-too-distant future,” and noted increased inbound interest from pharmaceutical companies. He also said the company is working on in vivo permanent CARs that do utilize editing, with mouse data described as encouraging, though not yet in non-human primates.
About CRISPR Therapeutics (NASDAQ:CRSP)
CRISPR Therapeutics AG is a biopharmaceutical company specializing in the development of gene-editing therapies based on the CRISPR/Cas9 platform. The company applies its proprietary technology to modify genes in human cells, aiming to create durable treatments for a range of serious diseases. Its research and development efforts focus on both ex vivo and in vivo applications, enabling targeted correction or disruption of disease-causing genes.
Among its lead programs is CTX001, an ex vivo edited cell therapy designed to treat sickle cell disease and transfusion-dependent ?-thalassemia in collaboration with Vertex Pharmaceuticals.
