Creating transformative gene-based medicines for serious diseases Corporate Overview Q2 2025 CRISPR THERAPEUTICS – CONFIDENTIAL © 2025 CRISPR Therapeutics | 11 Forward-Looking Statements Statements contained in this presentation and other related materials regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ material ...

Core Insights - CRISPR Therapeutics (CRSP) shares have increased by 14% over the past month, primarily due to positive results from its in vivo gene therapy candidates [1][10] Group 1: In Vivo Therapy Developments - CRSP reported promising initial results from its early-stage study on CTX310, a CRISPR-based gene therapy targeting ANGPTL3 for atherosclerotic heart disease, showing peak reductions of up to 82% in triglyceride levels and 81% in low-density lipoprotein levels [2][3] - The success of CTX310 has generated excitement for another in vivo candidate, CTX320, which targets lipoprotein(a) and is expected to release initial data by the end of the month [4] Group 2: Casgevy and Market Position - Casgevy, CRSP's approved ex vivo gene therapy for sickle cell disease and transfusion-dependent beta-thalassemia, has seen a steady uptake post-launch, with $14.2 million in product revenues recorded in Q1, up from $8 million in the previous quarter [6][8] - As of May 1, over 65 authorized treatment centers have been activated globally, with nearly 90 patients undergoing their first cell collection [8] Group 3: Future Pipeline and Competition - CRSP plans to expand its pipeline with two additional in vivo programs, CTX340 and CTX450, by the end of the year, while also advancing two next-generation CAR-T therapy candidates [12][13] - The company faces competition from other firms utilizing CRISPR technology, such as Beam Therapeutics and Intellia Therapeutics, which are developing their own therapies for similar indications [14][15] Group 4: Stock Performance and Valuation - CRSP shares have outperformed the industry and the S&P 500 Index, rising 9% year-to-date compared to a 1% decline in the industry [17] - The stock is currently trading at a price-to-book value (P/B) ratio of 2.03, which is lower than the industry average of 3.14, indicating a discount [20]

Core Viewpoint - CRISPR Therapeutics has faced financial struggles despite clinical advancements, with shares down 24% over the past three years, while the S&P 500 gained 41%. However, potential catalysts could double its stock price by 2030, indicating a compound annual growth rate of about 14.9% [1] Group 1: Clinical Progress and Products - CRISPR Therapeutics has developed Casgevy, a one-time treatment for sickle cell disease and transfusion-dependent beta-thalassemia, showcasing the potential of its gene-editing technology [2] - The complexity of ex vivo gene-editing treatments, which involve collecting, editing, and reinserting patient cells, presents manufacturing and administration challenges [3] - Although Casgevy was approved in late 2023, it has not yet significantly impacted financial results, but it is expected to exceed $1 billion in annual sales at its peak due to limited competition [5][6] Group 2: Market Potential - The addressable market for Casgevy is estimated at 58,000 patients in targeted regions, with a treatment cost of $2.2 million in the U.S., indicating substantial revenue potential [6] - The competitive landscape for CRISPR and Vertex Pharmaceuticals appears favorable, particularly in the Middle East where they have received product approvals [5] Group 3: Future Catalysts - CRISPR Therapeutics has several promising candidates in its pipeline, including CTX112 and CTX131 for cancer, with CTX112 receiving Regenerative Medicine Advanced Therapy designation from the FDA [10] - Data from an ongoing clinical trial for CTX320, aimed at lowering lipoprotein(a) levels, is also anticipated, along with other investigational treatments like a functional cure for type 1 diabetes [11] - A 50% success rate in bringing products to market could significantly benefit the company, and clinical wins may positively impact stock performance [12]

Core Insights - CRISPR Therapeutics reported a first-quarter 2025 loss of $1.58 per share, wider than the Zacks Consensus Estimate of a loss of $1.27 per share, and compared to a loss of $1.43 per share in the same period last year [1] - Total revenues for the quarter were $0.86 million, significantly missing the Zacks Consensus Estimate of $5 million, and up from $0.5 million in the year-ago period [1] - The company's shares fell nearly 12% following the weak quarterly performance, with a year-to-date decline of 15.8%, compared to the industry decline of 2.3% [2] Financial Performance - Research and development expenses decreased by approximately 5% year over year to $72.5 million, attributed to reduced employee-related costs [6] - General and administrative expenses increased by 7.2% year over year to $19.3 million [6] - Collaboration expenses rose to $57.5 million in the first quarter from $47.0 million in the previous year, driven by costs related to the Casgevy therapy [6] - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling $1.86 billion, down from $1.90 billion as of December 31, 2024 [7] Product Development and Pipeline - CRISPR Therapeutics and Vertex Pharmaceuticals' Casgevy therapy received approval for treating sickle cell disease and transfusion-dependent beta thalassemia in several countries [4] - Vertex reported Casgevy sales of $14.2 million in the first quarter, with over 65 authorized treatment centers activated and more than 90 patients initiating cell collection [5] - The company is evaluating two in-vivo candidates, CTX310 and CTX320, in separate phase I clinical studies targeting atherosclerotic heart disease [8] - Initial data from the CTX310 study showed dose-dependent decreases in LDL and TG levels, with peak reductions of up to 82% in TG and 81% in LDL [9] - CTX320 is targeting the LPA gene in patients with elevated Lp(a), with updates expected in the second quarter of 2025 [10] - CRISPR is also conducting phase I/II studies on next-generation allogeneic CAR T product candidates, CTX112 and CTX13, with updates anticipated in mid-2025 [10][11]

-Initial CTX310™ Phase 1 clinical data demonstrates dose-dependent decreases in triglycerides (TG) and low- density lipoprotein (LDL), with peak reduction of up to 82% in TG and up to 81% in LDL, with a well-tolerated safety profile; presentation anticipated at a medical meeting in the second half of 2025- -CASGEVY® continues to gain momentum; more than 65 authorized treatment centers (ATCs) activated globally for CASGEVY, and more than 90 patients have had cells collected across all regions; new patient in ...