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CRISPR THERAPEUTICS – CONFIDENTIAL 1© 2025 CRISPR Therapeutics | 1 Creating transformative gene-based medicines for serious diseases Corporate Overview Q4 2025
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CRISPR THERAPEUTICS – CONFIDENTIAL 2© 2025 CRISPR Therapeutics | 2 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 materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding any or all of the following: (i) CRISPR Therapeutics’ preclinical studies, clinical trials and pipeline products and programs, including, without limitation, manufacturing capabilities, status of such studies and trials, potential expansion into new indications and expectations regarding data, safety and efficacy generally; (ii) data included in this presentation, as well as the ability to use data from ongoing and planned clinical trials for the design and initiation of further clinical trials; (iii) CRISPR Therapeutics’ strategy, goals, anticipated financial performance and the sufficiency of its cash resources; (iv) plans and expectations for the commercialization of, and anticipated benefits of, CASGEVY, including anticipated patient access to CASGEVY; (v) regulatory submissions and authorizations, including timelines for and expectations regarding additional regulatory agency decisions; (vi) expected benefits of CRISPR Therapeutics’ collaborations; and (vii) the therapeutic value, development, and commercial potential of gene editing technologies and therapies, including CRISPR/Cas9 and SyNTase, as well as other technologies, and as compared to other therapies. Risks that contribute to the uncertain nature of the forward-looking statements include, without limitation, the risks and uncertainties discussed under the heading “Risk Factors” in CRISPR Therapeutics’ most recent annual report on Form 10-K and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this presentation and any related materials, other than to the extent required by law. This presentation also contains estimates, projections, and/or other information regarding our industry, our business and the markets for certain of our product candidates, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions. Unless otherwise expressly stated, we obtained this industry, business, market and other data from reports, research surveys, clinical trials, studies and similar data prepared by market research firms and other third parties, from industry, medical and general publications, and from government data and similar sources. Information that is based on estimates, forecasts, projections, market research, or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. This presentation and related materials discuss investigational therapies and is not intended to convey conclusions about efficacy or safety as to those investigational therapies or uses of such investigational therapies. There is no guarantee that any investigational therapy will successfully complete clinical development or gain approval from applicable regulatory authorities. Caution should be exercised when interpreting results from separate trials involving separate product candidates. There are differences in the clinical trial design, patient populations, and the product candidates themselves, and the results from the clinical trials of autologous products may have no interpretative value on our existing or future results. CRISPR THERAPEUTICS® standard character mark and design logo, SyNTase , CTX112 , CTX211 , CTX213 , CTX310®, CTX320 , CTX340 , and CTX460 , are trademarks and registered trademarks of CRISPR Therapeutics AG. CASGEVY® and the CASGEVY logo are registered trademarks of Vertex Pharmaceuticals Incorporated, and Vertex Pharmaceuticals Incorporated is the manufacturer and exclusive license holder of CASGEVY. All other trademarks and registered trademarks are the property of their respective owners. Solely for convenience, trademarks, service marks and trade names referred to in this presentation or any related material may appear without the ® or symbols and any such omission is not intended to indicate waiver of any such rights.
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CRISPR THERAPEUTICS – CONFIDENTIAL 3© 2025 CRISPR Therapeutics | 3 Executing on Our Vision Across Four Therapeutic Franchises Heme Partnered with Vertex on global launch of CASGEVY, best-in-class, commercial ex vivo CRISPR-Cas9 therapy for sickle cell disease and beta-thalassemia Continued focus on innovation to expand potential market for CASGEVY Advancing in vivo approaches leveraging LNP delivery CAR T Best-in-class allogeneic cell therapies with novel potency edits CTX112 clinical trials ongoing in SLE / SSc / IIM; competitive profile in autoimmune indications CTX112 demonstrated promising efficacy/safety profile in oncology In Vivo CAR T efforts in research for both transient and permanent integrated CAR Ts T1D Utilizing gene editing to develop an allogeneic beta-cell replacement therapy for diabetes Goal to achieve insulin independence without chronic immunosuppressive Advancing dual delivery strategies: device-based (CTX211) and deviceless (CTX213) approaches In vivo Establishing a differentiated LNP- mRNA platform, initially focused on the liver Two Phase I programs (CTX310 and CTX320) in cardiovascular disease to de-risk platform CTX310 targeting ANGPTL3 has potential to benefit >40M patients in the U.S. Next-gen SyNTase editing enables gene correction approaches Multi-target siRNA deal with Sirius Therapeutics including lead asset SRSD107, a potential biannual siRNA targeting Factor XI, currently in Phase 2 clinical development SLE: Systemic Lupus Erythematosus; SSC: Systemic Sclerosis; IIM: Idiopathic Inflammatory Myopathies
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CRISPR THERAPEUTICS – CONFIDENTIAL 4© 2025 CRISPR Therapeutics | 4 Program Disease(s) Research IND-enabling Clinical Approved Partner Heme CASGEVY1 Severe sickle cell disease (SCD) Transfusion-dependent β-thalassemia (TDT) CD117 ADC / In vivo HSC editing2 SCD, TDT and others CAR T I/O & Autoimmune CTX112 Anti-CD19 allogeneic CAR T SLE, SSc, and IIM B cell malignancies In Vivo CAR T Autoimmune and Oncology indications In Vivo Cardiovascular & Rare Disease CTX310: ANGPTL3 HeFH, HoFH, Mixed dyslipidemias, and sHTG CTX320: LPA ASCVD with elevated Lp(a) CTX340: AGT Refractory hypertension CTX460: SERPINA1 Alpha-1 Antitrypsin Disorder T1D CTX211 Type I diabetes mellitus CTX213 Type I diabetes mellitus Other disclosed partnered SRSD107 Thromboembolic conditions Duchenne's muscular dystrophy (DMD), myotonic dystrophy type I (DM1), cystic fibrosis (CF) HeFH: Heterozygous familial hypercholesterolemia; HoFH: Homozygous familial hypercholesterolemia; sHTG Severe hypertriglyceridem ia SLE: Systemic Lupus Erythematosus; SSC: Systemic Sclerosis; IIM: Idiopathic Inflammatory Myopathies 1 Currently approved in some countries for certain eligible patients with SCD or TDT; 2 Collaboration with Vertex for applications in TDT and SCD Broad and Diversified Pipeline
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CRISPR THERAPEUTICS – CONFIDENTIAL 5 Hemoglobinopathies
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CRISPR THERAPEUTICS – CONFIDENTIAL 6© 2025 CRISPR Therapeutics | 6 Unparalleled speed and execution to a landmark approval1 Investments made to meet global demand for disease-modifying therapy Addressable Market2 ~60,000 Severe patients in approved territories eligible for treatment 2024: A Foundational Year for CASGEVY 1 Approved by the U.S. FDA for treatment of patients aged 12 years and older with sickle cell disease (SCD) with recurrent vaso occlusive crises (VOCs) and transfusion-dependent ß-thalassemia (TDT) Granted conditional marketing authorization by the UK MHRA and Bahrain NHRA f or patients 12 years of age and older with SCD with recurrent VOCs or TDT for whom hematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related hematopoietic stem cell donor is not available. CASGEVY has also been approved in other countr ies for certain eligible patients with SCD or TDT 2 Including U.S., U.K., E.U., Kingdom of Saudi Arabia (KSA), Bahrain, Qatar, Canada, Switzerland, and United Arab Emirates (UAE )
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CRISPR THERAPEUTICS – CONFIDENTIAL 7© 2025 CRISPR Therapeutics | 7 As of September 30th 2025, CASGEVY is approved in 10 jurisdictions, >75 authorized treatment centers (ATCs) have been activated globally and ~165 patients have initiated cell collection Continued Progress in U.S. to Serve Significant Unmet Need New CMMI model to improve access and health outcomes, as well as reduce expenditures ($3B annual U.S. SCD cost) Expanding into untapped Middle East and ex-U.S. Markets First GCC patient reimbursed at ~$2M; NHS reimbursement achieved for beta-thal. Manufacturing Expansion to Support Launch1 Manufacturing agreement for global commercial supply with Lonza 2025: Focused on Execution and Expansion of Opportunity CMMI: Center for Medicare and Medicaid Innovation; GCC: Gulf Cooperation Council 1 Vertex leads development, regulatory filings, manufacturing and commercialization
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CRISPR THERAPEUTICS – CONFIDENTIAL 8© 2025 CRISPR Therapeutics | 8 Targeted conditioning In vivo editing of HSCs Studies in non-human primates (NHP) ongoing ss TOXINTOXIN Validated GMP toxin with HSC activity and reduced hydrophobicity to limit non-target cell toxicity Proprietary GMP monoclonal antibody with short half-life to enable rapid infusion of edited cells cKit (CD117) antibody-drug conjugate (ADC) for specific depletion of hematopoietic stem cells (HSCs) and no off-target/bystander toxicity DELIVERY EDITING Creating optimized system for in vivo HSC editing with ideal characteristics, including: Core research focus in 2025 – NHP studies ongoing • Tolerable doses with no off-target toxicities • Editing of LT-HSCs for durable effects vs. HSPCs only • Potential for redosability to enhance editing 150k+ addressable patients worldwide 400k+ addressable patients worldwide Serial Innovation in Enabling Technologies toBroaden Access
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CRISPR THERAPEUTICS – CONFIDENTIAL 9 In Vivo
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CRISPR THERAPEUTICS – CONFIDENTIAL 10© 2025 CRISPR Therapeutics | 10 Role of ANGPTL3 in Lipid Metabolism Uptake by liver and/or extra-hepatic tissues VLDL IDL LDL Lipoprotein lipase Endothelial lipase Lipoprotein lipase Endothelial lipase ANGPTL3 Chylomicron Chylomicron remnant Lipoprotein lipase Endothelial lipase TG → FFATG → FFA
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CRISPR THERAPEUTICS – CONFIDENTIAL 11© 2025 CRISPR Therapeutics | 11 CTX310: CRISPR-Cas9 Editing of ANGPTL3 Translation of Cas9 mRNA and complex formation with sgRNA The transportation of Cas9-sgRNA ribonucleoprotein complex into the nucleus Breakdown of LNP and release of Cas9 mRNA and ANGPTL3-specific sgRNA into cytoplasm Endocytosis of LNP Endosome Cas9-sgRNA ribonucleoprotein Hepatocyte Cytoplasm
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CRISPR THERAPEUTICS – CONFIDENTIAL 12© 2025 CRISPR Therapeutics | 12 Phase Ia: Single ascending dose escalation to identify optimal biological dose Phase Ib Patients with refractory hypercholesterolemia and or hypertriglyceridemia Phase Ib dose informed by Phase Ia DL4 – 0.8mg/kg DL3 – 0.6mg/kg DL2 – 0.3mg/kg DL1 – 0.1mg/kg Day 30 Acute toxicity monitoring Day 1 12-month total follow-up CTX310 infusion Screening Long-term follow-up Key eligibility criteria Age ≥18-75 years TG (>300 mg/dL) and/or LDL-C (>100 mg/dL); >70 mg/dL for subjects with ASCVD No significant comorbidities Key Objectives/Endpoints Safety and Tolerability Preliminary efficacy including changes in ANGPTL3, LDL, TG and ApoB compared to baseline Pharmacokinetics Phase I Study Evaluating the Safety and Efficacy of CTX310 Open-label, multicenter, Phase Ia/Ib study evaluating the safety and efficacy of CTX310 in homozygous familial hypercholesterolemia (HoFH), heterozygous familial hypercholesterolemia (HeFH), severe hypertriglyceridemia (sHTG), or mixed dyslipidemias Dose Level (DL); Estimated lean body weight -based doses
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CRISPR THERAPEUTICS – CONFIDENTIAL 13© 2025 CRISPR Therapeutics | 13 Baseline Patient Characteristics All participants (n=15) Median Age 53 years Male 87% Clinical ASCVD 40% Familial hypercholesterolemia 40% Severe hypertriglyceridemia 13% Mixed dyslipidemia 40% Mean LDL-C 155 mg/dL Median triglycerides 192 mg/dL
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CRISPR THERAPEUTICS – CONFIDENTIAL 14© 2025 CRISPR Therapeutics | 14 Mean Percent Change from Baseline in ANGPTL3 9.6% 9.4% -32.7% -79.7% -73.2% Percent change from baseline (%) 0.1 mg/kg (N=3) 0.3 mg/kg (N=3) 0.6 mg/kg (N=3) 0.7 mg/kg (N=2) 0.8 mg/kg (N=4) *Mean percent change from baseline are reported at 30 days for all subjects.
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CRISPR THERAPEUTICS – CONFIDENTIAL 15© 2025 CRISPR Therapeutics | 15 Mean Percent Change from Baseline in LDL-C and Triglycerides 4.2% 15.4% -39.2% -21.0% -48.9% 46.7% 38.8% -62.0% -19.2% -55.2% Percent change from baseline (%) Percent change from baseline (%) 0.1 mg/kg (N=3) 0.3 mg/kg (N=2) 0.6 mg/kg (N=3) 0.7 mg/kg (N=2) 0.8 mg/kg (N=4) 0.1 mg/kg (N=3) 0.3 mg/kg (N=3) 0.6 mg/kg (N=3) 0.7 mg/kg (N=2) 0.8 mg/kg (N=4) LDL Cholesterol Triglycerides Mean percent change from baseline are reported at 90 days following 0.1, 0.3, 0.6 mg/kg CTX310 doses and at 60 days following 0.7 and 0.8 mg/kg CTX310 doses.
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CRISPR THERAPEUTICS – CONFIDENTIAL 16© 2025 CRISPR Therapeutics | 16 Mean Percent Change in ApoB and Non-HDL-C Apolipoprotein B Non-HDL Cholesterol 9.7% 14.3% -38.0% -23.7% -33.4% 13.3% 15.7% -44.6% -22.9% -49.8% Percent change from baseline (%) Percent change from baseline (%) 0.1 mg/kg (N=3) 0.3 mg/kg (N=2) 0.6 mg/kg (N=3) 0.7 mg/kg (N=2) 0.8 mg/kg (N=4) 0.1 mg/kg (N=3) 0.3 mg/kg (N=3) 0.6 mg/kg (N=3) 0.7 mg/kg (N=2) 0.8 mg/kg (N=4) Mean percent change from baseline are reported at 90 days following 0.1, 0.3, 0.6 mg/kg CTX310 doses and at 60 days following 0.7 and 0.8 mg/kg CTX310 doses.
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CRISPR THERAPEUTICS – CONFIDENTIAL 17© 2025 CRISPR Therapeutics | 17 Mean Percent Change in Remnant Cholesterol and Apo CIII Apolipoprotein CIII Remnant Cholesterol -3.0% -52.5% -43.8% -61.7% 55.9% -33.3% -58.3% -27.3% -42.2% 31.7% 0.1 mg/kg (N=3) 0.3 mg/kg (N=2) 0.6 mg/kg (N=3) 0.7 mg/kg (N=2) 0.8 mg/kg (N=4) 0.1 mg/kg (N=3) 0.3 mg/kg (N=2) 0.6 mg/kg (N=3) 0.7 mg/kg (N=2) 0.8 mg/kg (N=4) Percent change from baseline (%) Percent change from baseline (%) Mean percent change from baseline are reported at 90 days following 0.1, 0.3, 0.6 mg/kg CTX310 doses and at 60 days following 0.7 and 0.8 mg/kg CTX310 doses.
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CRISPR THERAPEUTICS – CONFIDENTIAL 18© 2025 CRISPR Therapeutics | 18 Adverse Events and Laboratory-Related Safety Findings N (%) Any serious adverse events 2 (13) Serious adverse events related to CTX310 0 (0) Participants with any investigator-reported adverse event 14 (93) Adverse event deemed related to CTX310 7 (47) Adverse event of special interest 4 (27) Allergic or localized reaction 1 (7) Infusion-related reaction 3 (20) Elevation in AST or ALT 1 (7) Death1 1 (7) 1Occurred in a participant 179 days after treatment with the 0.1 mg/kg dose, deemed unrelated to CTX310
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CRISPR THERAPEUTICS – CONFIDENTIAL 19© 2025 CRISPR Therapeutics | 19 Change in Liver Enzymes Over Time 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 Alanine Aminotransferase Relative Days from Infusion Times Upper Limit of Normal 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg 0.7 mg/kg 14 214 7 30 90 0.8 mg/kg 0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 Aspartate Aminotransferase Relative Days from Infusion Times Upper Limit of Normal 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg 0.7 mg/kg 0.8 mg/kg 0 4 7 14 21 30 90 *1 participant with elevated baseline aminotransferases experienced a transient aminotransferase elevation without concurrent bilirubin elevation between 3 and 5 times their baseline peaking on day 4 and returning to baseline by day 14 * *
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CRISPR THERAPEUTICS – CONFIDENTIAL 20© 2025 CRISPR Therapeutics | 20 Changes Alkaline Phosphatase and Total Bilirubin over Time 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 Alkaline Phosphatase Relative Days from Infusion Times Upper Limit of Normal 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg 0.7 mg/kg 14 214 7 30 90 0.8 mg/kg 0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Total Bilirubin Relative Days from Infusion Times Upper Limit of Normal 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg 0.7 mg/kg 0.8 mg/kg 0 4 7 14 21 30 90
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CRISPR THERAPEUTICS – CONFIDENTIAL 21© 2025 CRISPR Therapeutics | 21 CTX310 Phase 1 Conclusions CTX310, an in vivo CRISPR-Cas9 gene editing product targeting ANGPTL3, can be safely administered to patients to reduce ANGPTL3 levels Although the study was small, reduction in LDL-C was approximately 50% and triglyceride lowering about 55% Lifelong reductions in atherogenic lipoproteins can potentially overcome the issue of waning adherence to current therapies Assessment of efficacy in specific populations will be feasible in further trials
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CRISPR THERAPEUTICS – CONFIDENTIAL 22© 2025 CRISPR Therapeutics | 22 Full Manuscript
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CRISPR THERAPEUTICS – CONFIDENTIAL 23© 2025 CRISPR Therapeutics | 23 1Cegla et al. 2019; 2: 2Gurdasani et al. 2012; 3Laschkolnig et al. 2014; 4Nordestgaard et al. 2010 Comparison of atherogenicity of Lp(a) and LDL Lp(a) is 6x more atherogenic than LDL on a per-particle basis4, highlighting Lp(a) as a key target for drug-based intervention Lp(a): lipoprotein(a); 1 Enas et al. 2019; 2 Gurdasani et al. 2012; 3 Laschkolnig et al. 2014; 4 Björnson et al. 2024 Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) • Lp(a) is an LDL-like lipoprotein synthesized and secreted by hepatocytes • Epidemiologic, Mendelian randomization, and genome- wide association studies have shown that elevated Lp(a) levels increase ASCVD risk 1,2,3 • The genetic risk associated with elevated Lp(a) is cumulative over a person's lifetime and cannot be adequately reduced by lifestyle changes or currently approved therapies Lp(a): An Emerging Key Target to Potentially Reduce CV Events
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CRISPR THERAPEUTICS – CONFIDENTIAL 24© 2025 CRISPR Therapeutics | 24 Single dose of CTX320 (2 mg/kg) administered to NHPs (N=4) on Day 1; Editing data presented at the American Heart Association Scientific Sessions. 11 Nov 2023; Editing rate reflects whole liver editing 1 LPA gene encodes apolipoprotein(a), a key component of lipoprotein(a) ~95% reduction in plasma Lp(a) sustained at 2 years~70% editing of LPA1 at 1 year 0 8 16 24 32 40 48 56 64 72 80 88 96 104 -100 -80 -60 -40 -20 0 Study Week Change from Baseline (%) 1 0 20 40 60 80 Liver Editing (%) 2 mg/kg Updated NHP data demonstrate continued durability of CTX320 out to 2 years Single CTX320 Dose Resulted in Durable Lp(a) Reduction (NHP)
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CRISPR THERAPEUTICS – CONFIDENTIAL 25© 2025 CRISPR Therapeutics | 25 Phase I: Single ascending dose escalation to identify optimal biological dose Phase II Patients with elevated levels of Lp(a) Phase II dose informed by Phase I Dose level 4 Dose level 3 Dose level 2 Dose level 1 Day 30 Acute toxicity monitoring Day 1 12-month total follow-up CTX320 infusion Screening Long-term follow-up Key eligibility criteria Age ≥18-65 years Elevated levels of Lp(a) (>200nmol/l) and CVD Adequate renal, liver, cardiac, and pulmonary organ function No significant comorbidities Objectives/Endpoints Safety and Tolerability Change in Lp(a) compared to baseline Pharmacokinetics CTX320 update in 1H 2026 Phase I Study Evaluating the Safety and Efficacy of CTX320
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CRISPR THERAPEUTICS – CONFIDENTIAL 26© 2025 CRISPR Therapeutics | 26 10 Elevated Lp(a) is considered the most common genetically inherited risk factor for cardiovascular disease (CVD)1 A one-time durable reduction in Lp(a) has the potential to transform the current treatment paradigm in cardiovascular disease (compliance with small molecules and mAbs remains key issue) siRNA cardiovascular outcomes trials in 2025/2026 have the potential to significantly de-risk Lp(a) as a therapeutic target CTX320 has potential to benefit >60M U.S. patients with elevated Lp(a) Approximately one-fifth of the global population have elevated Lp(a) levels ~3x greater lifetime risk for most elevated Lp(a) population Distribution of Lp(a) levels in general population2 Population Lp(a) level based on male distribution; similar distribution seen across women 1 Madsen et al. 2020; 2 Nordestgaard et al. 2010; 3 Kronenberg et al. 2022 350 nmol/L 230 nmol/L 175 nmol/L 115 nmol/L 70 nmol/L 16 nmol/L Lifetime risk of major cardiovascular events with increasing Lp(a) levels3 (Population median) mg/dL 0 50 100 150 200 nmol/L 0 115 230 350 460 Age (years) 40 50 60 70 80 0 10 20 30 40 Fraction of population CTX320 Has Potential to Address Population with Elevated Lp(a)
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CRISPR THERAPEUTICS – CONFIDENTIAL 27© 2025 CRISPR Therapeutics | 27 CTX460 Targeting SERPINA1 for AATD CTX340 Targeting AGT For Refractory Hypertension CTX340 durably reduced MAP by Day 7, sustained through the study (~8.5 months) Editing rates reflect whole liver editing; MAP: mean arterial pressure; SHR: spontaneous hypertensive rat 1 Zhou et al. 2021; 2 Danaei et al. 2009 • Hypertension is the leading cause of cardiovascular morbidity and mortality worldwide1,2 • By going upstream of typical therapeutic approaches by targeting AGT, we can significantly impact hypertension and reduce dependence on other antihypertensives • Alpha-1 antitrypsin (AAT) is a serine protease inhibitor which is encoded by SERPINA1. Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency (AATD). • CTX460, comprising novel SyNTase editing payload enables highly efficient, durable and specific SERPINA1-E342K gene correction, without bystander edits. Additional Programs Advancing Toward Clinic CTX340 Administration Leads to Persistent Pharmacological Benefit in SHR Model Precise and efficient correction of SERPINA1-E342K (day 7 post-injection) Durable, high proportion corrected serum M-AAT (LC-MS; DRC: day 7, durability: 0.5 mg/kg)
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CRISPR THERAPEUTICS – CONFIDENTIAL 28© 2025 CRISPR Therapeutics | 28 CAR T
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CRISPR THERAPEUTICS – CONFIDENTIAL 29© 2025 CRISPR Therapeutics | 29 Other CTX112 Competitive Advantages Ability to multiplex gene edits precisely and efficiently Comprehensive and FDA-validated genomic analysis Scalability and low COGS to enable global expansion In-house manufacturing enables direct control over process and timelines Multiple scientific, manufacturing and regulatory advantages for CTX112 CTX112 Novel Potency Edits (TGFBR2, Regnase-1) Regnase-1 and TGFBR2 edits synergistically increase CAR T potency Anti-CD19 CAR TCR disruptionMHC I disruption TGFBR2 disruption TGFBR2 Regnase-1 𝛽𝛽2M TRAC CTX112: An Allogeneic CAR T Optimized for Potency
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CRISPR THERAPEUTICS – CONFIDENTIAL 30© 2025 CRISPR Therapeutics | 30 CTX112 Phase I Autoimmune Basket Trial Ongoing D28 assessment and follow-up Open-label, Phase 1 study evaluating the safety and efficacy of CTX112 in adult subjects with refractory autoimmune disease Primary endpoint Incidence of Adverse Events, defined as Dose-limiting toxicities Secondary endpoints Pharmacodynamic (PD) response to CTX112 (e.g. disease specific autoantibodies, B cell levels) CTX112 Pharmacokinetics (PK) Preliminary efficacy based on disease-specific criteria and assessments Key eligibility criteria: Age ≥18 years and ≤70 years Patient population: Adult subjects with active SLE (with or without renal involvement), systemic sclerosis (SSc), or idiopathic inflammatory myopathy (IIM) despite use of standard therapies No prior anti-CD19 therapy or any gene therapy or genetically modified cell therapy No prior solid organ or hematopoietic cell transplant Adequate organ function Fludarabine 30 mg/m2 + Cyclophosphamide 500 mg/m2 for 3 days CTX112 infusion Screening Standard Lymphodepletion Trial Design: Benefits of Allogeneic CAR T: Concomitant therapy stays until shortly before LD chemo On-site availability of CAR T cell product Site specific CAR insertion No apheresis Dose Level (DL), CAR+ T cells; DL1 = 100M; DL2 = 300M; DL3 = 600M cells
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CRISPR THERAPEUTICS – CONFIDENTIAL 31© 2025 CRISPR Therapeutics | 31 CTX112 vs. Autologous CAR T • Safety benefits are critical in context of larger patient populations and in community hospital settings • Improved patient experience with no apheresis; enables rapid enrollment to dosing without the need to pause immunosuppressants • Significantly lower COGS and scalability are critical for expanding the addressable population CTX112 vs. TCE • Initial clinical results with CAR Ts show deep B-cell depletion in tissues, likely critical for immune reset • Long-term data in oncology supports more durable clinical responses with CAR T therapy vs. TCEs • Initial CTX112 data shows promising efficacy in post-TCE patients (e.g., 100% OR rate) CTX112 vs. Other Allogeneic CAR T / NK • Case studies from other allogeneic CAR T therapies in AID provide derisking for CTX112 • CTX112 may be superior, with potency edits leading to significantly higher CAR T cell expansion and functional persistence Broad CTX112 update across Oncology and Autoimmune disease expected by year end CTX112 is Positively Differentiated From Other CD19 Therapies
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CRISPR THERAPEUTICS – CONFIDENTIAL 32© 2025 CRISPR Therapeutics | 32 D28 assessment and follow-up Open-label, multicenter, Phase I/II study evaluating the safety and efficacy of CTX112 in relapsed or refractory B-cell malignancies Primary endpoint Incidence of AEs, defined as DLTs ORR (per Lugano 2014 criteria or iwCLL 2018 guidelines for CLL/SLL) Secondary endpoints CR rate Duration of response (DOR) Key eligibility criteria: Age ≥18 years Patient population: R/R FL grade 1-3a, MZL, MCL, DLBCL NOS, DLBCL/high- grade lymphoma with MYC and BCL-2 rearrangement, grade 3b FL, DLBCL arising from FL or MZL or LBCL with prior CAR T No prior allogeneic SCT and no history of CNS lymphoma involvement Adequate organ function Fludarabine 30 mg/m2 + Cyclophosphamide 500 mg/m2 for 3 days CTX112 infusion Screening Standard Lymphodepletion Dose Level (DL), CAR+ T cells; DL1 = 30M; DL2 = 100M; DL3 = 300M cells; DL4 = 600M cells (NCT05643742); AE, adverse event; BCL-2, B-cell lymphoma 2; CNS, central nervous system; DLT, dose-limiting toxicity; iwCLL, International Workshop on CLL; ORR, overall response rate; R/R, relapsed or refractory; SCT, stem cell therapy. Trial Design: Patients could receive an additional infusion of CTX112 with LD chemotherapy if they achieved a partial response Progression-free survival (PFS) Overall survival Benefits of Allogeneic CAR T: No bridging chemotherapy On-site availability of CAR T cell product Short screening timeframe No apheresis CTX112 Phase I Immuno-Oncology Clinical Trial Design
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CRISPR THERAPEUTICS – CONFIDENTIAL 33© 2025 CRISPR Therapeutics | 33 Patient-level data Cell dose (CAR+ T cells) DL1 30M N=3 DL2 100M N=3 DL3 300M N=3 DL4 600M N=3 Total N=12 ORR n (%) 2 (67) 2 (67) 2 (67) 2 (67) 8 (67) CR n (%) 1 (33) 2 (67) 1 (33) 2 (67) 6 (50) PR n (%) 1 (33) 0 1 (33) 0 2 (17) CTX112 Initial Efficacy Data (N=12) High risk patient population (58% primary refractory; 67% >3 prior therapies; 50% with tumor SPD > 4000 mm2) CTX112 demonstrated tolerability with no CRS, ICANS or infections Grade ≥3 ORR/CR rate in line with approved autologous CAR T1 Ongoing Responses in Patients with Poor Prognostic Factors Aggregated data per dose level Data published at 2024 American Society of Hematology Annual Meeting 1 For example, Yescarta ORR/CRR 70- 90%/50-60% across indications. Response rates based on modified intent to treat analyses of infused patients in the Zuma -1 and Zuma-5 trials Initial Efficacy Data On Par with Auto CAR T
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CRISPR THERAPEUTICS – CONFIDENTIAL 34© 2025 CRISPR Therapeutics | 34 Cell expansion comparable to autologous CAR T2 CAR T Cell Expansion Comparison CTX112 Cell Expansion Data Dose Dependent Increases in AUC and Cmax Analysis from subsequent data cut on Dec 20, 2024 (N=25) CTX112 (DL3/4) Autologous CAR T Other Allogeneic CAR T Mean Cmax (copies/μg) 45,000- 70,0001 Apx. 6,000- 30,0002 Apx. 500- 5,0003 1 Mean +/- the SEM; 2 Per Kymriah and Breyanzi USPI; 3 Lekakis et al. ASH 2021, Hu et al. ASCO 2024 0 7 14 21 28 1 10 100 1,000 10,000 100,000 Timepoint (Day) [CAR] (Copies/μg) LLOQ LOD DL3/4 DL1/2 Updated CTX112 Data Shows PK in Line with Auto CAR T
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CRISPR THERAPEUTICS – CONFIDENTIAL 35© 2025 CRISPR Therapeutics | 35 Histology # Prior Lines Prior Bispecific T Cell Engager (TCE) TCE Best Overall Response CTX112 Best Overall Response Dose level 3 FL 7 5L: Mosunetuzumab PR PR LBCL 2 2L: R-ICE & Epcoritamab PD PR LBCL 10 5L: Mosunetuzumab UNK PR 6L: Tafasitamab & Rituximab & Lenalidomide PD Dose Level 4 LBCL 4 4L: Epcoritamab & GemOx CR CR FL 8 7L: Imvotamab (IGM-2323) PD CR FL 5 3L: Glofitamab & RG6333 (CD19/CD28) PR CR 100% overall response rate (ORR)for 6 patients receiving CTX112 post-TCE therapy 100% ORR for 3 LBCL patients at higher dose levels Updated CTX112 Data Shows Efficacy in post-TCE Subset Analysis from subsequent data cut on Dec 20, 2024 TCE: T-cell engager; FL: follicular lymphoma; LBCL: Large B -cell lymphoma
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CRISPR THERAPEUTICS – CONFIDENTIAL 36© 2025 CRISPR Therapeutics | 36 Optimizing Key Levers to Create Best-in-Class In Vivo CAR T 1 Ionizable lipids | Screening ionizable lipids for optimized T cell transfection 2 LNP Composition | Identifying proprietary LNP compositions to detarget liver 3 Targeting moieties | Screening binders and applying deep conjugation chemistry 4 Payload engineering | Access to multiple RNA technologies with improved properties CAR selection | Library of clinically validated binders, with ability to create bispecifics5
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CRISPR THERAPEUTICS – CONFIDENTIAL 37© 2025 CRISPR Therapeutics | 37 Gene editing is key to achieving the goal of developing a beta-cell replacement product to treat diabetes without requiring long-term immunosuppression CTX211 First-in-class edited beta-cell replacement therapy Encapsulated pancreatic progenitor cells derived from pluripotent stem cells with gene-edits for immune evasion and cell survival Phase I clinical trial 1 CTX213 Deviceless, iPS-derived, edited beta- cell replacement therapy Pancreatic progenitor cells derived from edited pluripotent stem cells directly infused vs. delivered via device Advancing into IND-enabling phase 2 Non-exclusive license with Vertex Covers Vertex’s gene-edited hypoimmune programs for T1D Up to $160M in additional research and development milestones, plus royalties on future products 3 $170M in upfront and milestone payments to CRISPR in 2023 T1D update in 2025 Three Parallel Efforts in Type 1 Diabetes (T1D)
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CRISPR THERAPEUTICS – CONFIDENTIAL 38© 2025 CRISPR Therapeutics | 38 CRISPR Therapeutics www.crisprtx.com