CRISPR Therapeutics has reported encouraging initial results from its investigational in vivo gene therapy CTX310, marking a significant milestone in the company's expansion beyond its approved ex vivo treatments. The early-stage study data showed that a single dose of CTX310 led to dose-dependent decreases in both low-density lipoprotein (LDL) and triglyceride (TG) levels, with peak reduction of up to 82% in TG and up to 81% in LDL.
Breakthrough in Direct Gene Delivery
CTX310 represents CRISPR Therapeutics' first major advancement in in vivo CRISPR-based gene therapy, designed to target ANGPTL3 for the treatment of atherosclerotic heart disease. Unlike ex vivo therapies like the company's approved Casgevy, where cells are removed, modified and then reinserted into the body, in vivo therapies involve infusing new genes directly into the body. Currently, there are no approved in vivo therapies based on CRISPR technology.
The positive results provide significant momentum for CRISPR Therapeutics, which had not offered any major pipeline updates last year beyond the approval of Casgevy, recognized as the world's first gene therapy based on CRISPR technology.
Pipeline Expansion and Upcoming Catalysts
The CTX310 results have generated excitement around CRISPR Therapeutics' other in vivo candidate, CTX320, which is being developed in a phase I study for targeting lipoprotein(a), also associated with heart disease. Initial data from this study is expected by the end of this month, which could serve as a significant catalyst if the results mirror CTX310's performance.
CRISPR Therapeutics is preparing for multiple pipeline readouts throughout 2025. The company is advancing two next-generation CAR-T therapy candidates: CTX112 targeting CD19-positive B-cell malignancies and CTX131 targeting relapsed or refractory solid tumors in separate phase I/II studies. Additionally, CTX131 is being evaluated in hematological malignancies including T-cell lymphomas, while CTX112 is being studied in autoimmune disorders such as systemic lupus erythematosus, systemic sclerosis and inflammatory myositis.
The company intends to further expand its in vivo pipeline with two more programs before year's end: CTX340 for refractory hypertension and CTX450 for acute hepatic porphyria.
Commercial Progress with Casgevy
CRISPR Therapeutics' partnership with Vertex Pharmaceuticals continues to show progress with their approved therapy Casgevy. The one-shot gene therapy was approved in late 2023/early 2024 for sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT) in the United States and Europe. As of May 1, more than 65 authorized treatment centers had been activated globally, and nearly 90 patients have had their first cell collection.
During its first-quarter earnings release, Vertex Pharmaceuticals recorded $14.2 million in product revenues from Casgevy sales compared with $8 million in the previous quarter, indicating steady commercial uptake despite the complex treatment process that requires stem cell collection, ex vivo gene editing, and reinfusion.
Competitive Landscape
The gene editing space remains highly competitive, with several companies pursuing CRISPR-based therapies. Beam Therapeutics is developing an investigational ex vivo therapy for SCD in a phase I/II study, while also evaluating in vivo therapies for alpha-1 antitrypsin deficiency and glycogen storage disease 1a. Intellia Therapeutics is advancing two late-stage in vivo candidates: NTLA-2002 for hereditary angioedema and nex-z (NTLA-2001) for transthyretin amyloidosis, with plans to submit a regulatory filing for the HAE therapy next year.
Casgevy faces competition from already-approved therapies including bluebird bio's Zyntelgo and Lyfgenia, Bristol Myers' Reblozyl, and Novartis' Adakveo for the same indications.
Financial Position and Market Performance
CRISPR Therapeutics maintains a strong cash balance of approximately $1.9 billion as of March 2025, providing financial stability for ongoing operations and potential late-stage studies. The company's shares have risen 14% over the past month and 9% year to date, outperforming the industry's 1% decline and trading above their 50-day moving average.
From a valuation perspective, the company's shares currently trade at a price-to-book ratio of 2.03, below the industry average of 3.14 and the company's five-year mean of 2.41. However, loss per share estimates have widened, with 2025 estimates increasing from $4.96 to $5.54 and 2026 estimates expanding from $3.65 to $4.30 over the past 60 days.
