Can CRISPR Build on Casgevy's Success With Its In Vivo Pipeline?

CRISPR Therapeutics (CRSP) is shifting focus to in vivo gene therapies after the success of its ex vivo therapy, Casgevy, with early trials of CTX310 showing dose-dependent reductions of up to 82% in triglycerides and 81% in LDL in patients with atherosclerotic heart disease; the company plans to add two more in vivo programs by year-end. While CRSP is behind Intellia Therapeutics in clinical-stage in vivo programs, the company is trading at a discount to the industry based on its price-to-book value, though estimates for 2025 and 2026 losses per share have recently widened.

Analysis

CRISPR Therapeutics (CRSP) is strategically pivoting towards in vivo gene therapies following the landmark approval of Casgevy, its ex vivo treatment developed with Vertex Pharmaceuticals. Early data from its in vivo candidate CTX310 targeting atherosclerotic heart disease is promising, with a single dose demonstrating dose-dependent reductions in low-density lipoprotein (LDL) and triglyceride (TG) levels, achieving peak reductions of up to 81% and 82% respectively in the first 10 patients. The company intends to broaden this focus by advancing two additional in vivo programs into clinical trials by the end of the year, signaling a significant expansion of its pipeline. However, CRSP faces notable competition, particularly from Intellia Therapeutics (NTLA), which has multiple in vivo gene editing programs in late-stage development, including a candidate for hereditary angioedema (HAE) expected for FDA submission next year. Beam Therapeutics (BEAM) is also advancing early-stage in vivo candidates using a differentiated base-editing approach. Financially, CRSP's shares have underperformed the industry year-to-date. From a valuation perspective, CRSP trades at a price-to-book (P/B) ratio of 1.80, which is below the industry average of 3.10 and its own five-year mean of 2.41, suggesting a current discount. Despite this, analyst estimates for CRSP's loss per share have widened in the past 60 days, with 2025 estimates increasing from $4.96 to $5.54 and 2026 estimates rising from $3.65 to $4.11, indicating heightened near-term financial headwinds.

Key Decisions for Investors

• Investors should weigh the long-term potential of CRISPR Therapeutics' expanding in vivo pipeline, underscored by encouraging early CTX310 data, against the heightened competitive landscape and recent widening of loss per share estimates for 2025 and 2026.
• Consider the current valuation discount, with the P/B ratio below industry and historical averages, as a potential entry point, but acknowledge the stock's recent underperformance and the financial risks associated with pre-profitability biotech firms.
• Monitor key upcoming catalysts, particularly the CTX320 clinical trial readout expected in the second quarter of 2025 and progress reports on the two new in vivo programs slated to enter the clinic by year-end, as these could significantly impact the company's trajectory.