CRISPR Therapeutics AG · NASDAQ:CRSP
CRISPR Therapeutics — Investor Presentation (2025)
38 slides from CRISPR Therapeutics's investor presentation, Nov 18, 2025
Slide 1: Creating transformative gene-based medicines for serious diseases
Creating transformative gene-based medicines for serious diseases Corporate Overview Q4 2025 CRISPR THERAPEUTICS – CONFIDENTIAL © 2025 CRISPR Therapeutics | 11
Slide 2: Forward-Looking Statements
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
Slide 3: Executing on Our Vision Across Four Therapeutic Franchises
Executing on Our Vision Across Four Therapeutic Franchises Heme CAR T In vivo T1D Best-in-class allogeneic cell Establishing a differentiated LNP- Partnered with Vertex on global therapies with novel potency edits mRNA platform, initially focused Utilizing gene editing to develop an launch of CASGEV
Slide 4: Broad and Diversified Pipeline
Broad and Diversified Pipeline Program Disease(s) Research IND-enabling Clinical Approved Partner Severe sickle cell disease (SCD) CASGEVY1 Heme Transfusion-dependent β-thalassemia (TDT) CD117 ADC / In vivo HSC editing2 SCD, TDT and others I/O & Autoimmune SLE, SSc, and IIM CTX112 Anti-CD19 allogene
Slide 5: Hemoglobinopathies
Hemoglobinopathies CRISPR THERAPEUTICS – CONFIDENTIAL 5
Slide 6: 2024: A Foundational Year for CASGEVY
2024: A Foundational Year for CASGEVY Addressable Market2 Unparalleled speed and execution to a landmark approval1 ~60,000 Severe patients in approved territories eligible for treatment Investments made to meet global demand for disease-modifying therapy 1 Approved by the U.S. FDA for treatment of p
Slide 7: 2025: Focused on Execution and Expansion of Opportunity
2025: Focused on Execution and Expansion of Opportunity Continued Progress in U.S. to Expanding into untapped Middle Manufacturing Expansion to Serve Significant Unmet Need East and ex-U.S. Markets Support Launch1 New CMMI model to improve access and First GCC patient reimbursed at ~$2M; Manufacturi
Slide 8: Serial Innovation in Enabling Technologies to Broaden Access
Serial Innovation in Enabling Technologies to Broaden Access Targeted conditioning In vivo editing of HSCs DELIVERY EDITING cKit (CD117) antibody-drug conjugate (ADC) for specific depletion of hematopoietic stem cells (HSCs) and no off-target/bystander toxicity Proprietary GMP monoclonal antibody wi
Slide 9: In Vivo
In Vivo CRISPR THERAPEUTICS – CONFIDENTIAL 9
Slide 10: Role of ANGPTL3 in Lipid Metabolism
Role of ANGPTL3 in Lipid Metabolism Uptake by liver and/or extra-hepatic tissues VLDL IDL LDL Lipoprotein lipase Lipoprotein lipase Endothelial lipase Endothelial lipase TG → FFA TG → FFA ANGPTL3 Lipoprotein lipase Endothelial lipase Chylomicron Chylomicron remnant CRISPR THERAPEUTICS – CONFIDENTIAL
Slide 11: CTX310: CRISPR-Cas9 Editing of ANGPTL3
CTX310: CRISPR-Cas9 Editing of ANGPTL3 Hepatocyte Cas9-sgRNA ribonucleoprotein The transportation of Endosome Cas9-sgRNA ribonucleoprotein Endocytosis complex into the nucleus of LNP Breakdown of LNP and Translation of Cas9 mRNA release of Cas9 mRNA and and complex formation ANGPTL3-specific sgRNA w
Slide 12: Phase I Study Evaluating the Safety and Efficacy of CTX310
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 dysli
Slide 13: Baseline Patient Characteristics
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 CRISPR THERAPEUTICS – CONFIDENTIAL © 2025 CRISPR Thera
Slide 14: Mean Percent Change from Baseline in ANGPTL3
Mean Percent Change from Baseline in ANGPTL3 9.6% 9.4% Percent change from baseline (%) -32.7% -73.2% -79.7% 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg 0.7 mg/kg 0.8 mg/kg (N=3) (N=3) (N=3) (N=2) (N=4) *Mean percent change from baseline are reported at 30 days for all subjects.CRISPR THERAPEUTICS – CONFIDENTIAL
Slide 15: Mean Percent Change from Baseline in LDL-C and Triglycerides
Mean Percent Change from Baseline in LDL-C and Triglycerides LDL Cholesterol Triglycerides 46.7% 15.4% 38.8% Percent change from baseline (%) Percent change from baseline (%) 4.2% -21.0% -19.2% -39.2% -48.9% -55.2% -62.0% 0.1 0.3 0.6 0.7 0.8 0.1 0.3 0.6 0.7 0.8 mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg
Slide 16: Mean Percent Change in ApoB and Non-HDL-C
Mean Percent Change in ApoB and Non-HDL-C Apolipoprotein B Non-HDL Cholesterol 14.3% 9.7% Percent change from baseline (%) Percent change from baseline (%) 13.3% 15.7% -23.7% -22.9% -33.4% -38.0% -44.6% -49.8% 0.1 0.3 0.6 0.7 0.8 0.1 0.3 0.6 0.7 0.8 mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg
Slide 17: Mean Percent Change in Remnant Cholesterol and Apo CIII
Mean Percent Change in Remnant Cholesterol and Apo CIII Apolipoprotein CIII Remnant Cholesterol 31.7% 55.9% Percent change from baseline (%) Percent change from baseline (%) -3.0% -27.3% -33.3% -43.8% -42.2% -52.5% -58.3% -61.7% 0.1 0.3 0.6 0.7 0.8 0.1 0.3 0.6 0.7 0.8 mg/kg mg/kg mg/kg mg/kg mg/kg m
Slide 18: Adverse Events and Laboratory-Related Safety Findings
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) Alle
Slide 19: Change in Liver Enzymes Over Time
Change in Liver Enzymes Over Time Alanine Aminotransferase Aspartate Aminotransferase 5.5 0.1 mg/kg 5.5 0.1 mg/kg * Times Upper Limit of Normal Times Upper Limit of Normal 5.0 0.3 mg/kg 5.0 0.3 mg/kg 4.5 4.5 * 0.6 mg/kg 0.6 mg/kg 4.0 4.0 0.7 mg/kg 0.7 mg/kg 3.5 3.5 0.8 mg/kg 0.8 mg/kg 3.0 3.0 2.5 2.
Slide 20: Changes Alkaline Phosphatase and Total Bilirubin over Time
Changes Alkaline Phosphatase and Total Bilirubin over Time Alkaline Phosphatase Total Bilirubin 5.5 0.1 mg/kg 3.5 0.1 mg/kg Times Upper Limit of Normal Times Upper Limit of Normal 5.0 0.3 mg/kg 0.3 mg/kg 3.0 4.5 0.6 mg/kg 0.6 mg/kg 4.0 2.5 0.7 mg/kg 0.7 mg/kg 3.5 0.8 mg/kg 2.0 0.8 mg/kg 3.0 2.5 1.5
Slide 21: CTX310 Phase 1 Conclusions
CTX310 Phase 1 Conclusions CTX310, an in vivo Although the study was Lifelong reductions in Assessment of efficacy CRISPR-Cas9 gene small, reduction in atherogenic in specific populations editing product LDL-C was lipoproteins can will be feasible in targeting ANGPTL3, can approximately 50% and pote
Slide 22: Full Manuscript
Full Manuscript CRISPR THERAPEUTICS – CONFIDENTIAL © 2025 CRISPR Therapeutics | 22 22
Slide 23: Lp(a): An Emerging Key Target to Potentially Reduce CV Events
Lp(a): An Emerging Key Target to Potentially Reduce CV Events Lp(a) is an independent risk factor for atherosclerotic Comparison of atherogenicity of Lp(a) and LDL cardiovascular disease (ASCVD) • Lp(a) is an LDL-like lipoprotein synthesized and secreted by hepatocytes • Epidemiologic, Mendelian ran
Slide 24: Single CTX320 Dose Resulted in Durable Lp(a) Reduction (NHP)
Single CTX320 Dose Resulted in Durable Lp(a) Reduction (NHP) ~70% editing of LPA1 at 1 year ~95% reduction in plasma Lp(a) sustained at 2 years 80 0 Change from Baseline (%) -20 60 Liver Editing (%) -40 40 -60 20 -80 0 -100 1 2 mg/kg 0 8 16 24 32 40 48 56 64 72 80 88 96 104 Study Week Updated NHP da
Slide 25: Phase I Study Evaluating the Safety and Efficacy of CTX320
Phase I Study Evaluating the Safety and Efficacy of CTX320 CTX320 infusion Acute toxicity monitoring 12-month total follow-up Long-term Screening follow-up Day 1 Day 30 Phase I: Single ascending dose escalation to identify optimal biological dose Phase II Key eligibility criteria Dose level 4 Age
Slide 26: CTX320 Has Potential to Address Population with Elevated Lp(a)
CTX320 Has Potential to Address Population with Elevated Lp(a) Elevated Lp(a) is considered the most common genetically inherited risk factor for cardiovascular disease (CVD)1 Distribution of Lp(a) levels in Lifetime risk of major cardiovascular events general population2 with increasing Lp(a) level
Slide 27: Additional Programs Advancing Toward Clinic
Additional Programs Advancing Toward Clinic CTX340 Targeting AGT For Refractory Hypertension CTX460 Targeting SERPINA1 for AATD • Hypertension is the leading cause of cardiovascular morbidity • Alpha-1 antitrypsin (AAT) is a serine protease inhibitor which is and mortality worldwide1,2 encoded by SE
Slide 28: CAR T
CAR T CRISPR THERAPEUTICS – CONFIDENTIAL © 2025 CRISPR Therapeutics | 28 28
Slide 29: CTX112: An Allogeneic CAR T Optimized for Potency
CTX112: An Allogeneic CAR T Optimized for Potency CTX112 Novel Potency Edits (TGFBR2, Regnase-1) Other CTX112 Competitive Advantages TGFBR2 Anti-CD19 disruption CAR Ability to multiplex gene edits precisely TCR and efficiently disruption MHC I disruption Comprehensive and FDA-validated genomic analy
Slide 30: CTX112 Phase I Autoimmune Basket Trial Ongoing
CTX112 Phase I Autoimmune Basket Trial Ongoing Open-label, Phase 1 study evaluating the safety and efficacy of CTX112 in adult subjects with refractory autoimmune disease CTX112 infusion Trial Design: Screening Standard Lymphodepletion D28 assessment and follow-up Fludarabine 30 mg/m2 + Dose Level (
Slide 31: CTX112 is Positively Differentiated From Other CD19 Therapies
CTX112 is Positively Differentiated From Other CD19 Therapies • Safety benefits are critical in context of larger patient populations and in community hospital settings CTX112 vs. • Improved patient experience with no apheresis; enables rapid enrollment to dosing without the need Autologous CAR T to
Slide 32: CTX112 Phase I Immuno-Oncology Clinical Trial Design
CTX112 Phase I Immuno-Oncology Clinical Trial Design Open-label, multicenter, Phase I/II study evaluating the safety and efficacy of CTX112 in relapsed or refractory B-cell malignancies Patients could receive an additional infusion of CTX112 CTX112 infusion with LD chemotherapy if they achieved a pa
Slide 33: Initial Efficacy Data On Par with Auto CAR T
Initial Efficacy Data On Par with Auto CAR T 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 Patient-level data Aggregated data
Slide 34: Updated CTX112 Data Shows PK in Line with Auto CAR T
Updated CTX112 Data Shows PK in Line with Auto CAR T Analysis from subsequent data cut on Dec 20, 2024 (N=25) CTX112 Cell Expansion Data CAR T Cell Expansion Comparison 100,000 DL1/2 DL3/4 10,000 [CAR] (Copies/μg) Other 1,000 CTX112 Autologous Allogeneic (DL3/4) CAR T CAR T 100 Mean Cmax 45,000- Apx
Slide 35: Updated CTX112 Data Shows Efficacy in post-TCE Subset
Updated CTX112 Data Shows Efficacy in post-TCE Subset Analysis from subsequent data cut on Dec 20, 2024 # TCE CTX112 Histology Prior Prior Bispecific T Cell Engager (TCE) Best Overall Response Best Overall Response Lines FL 7 5L: Mosunetuzumab PR PR Dose level 3 LBCL 2 2L: R-ICE & Epcoritamab PD PR
Slide 36: Optimizing Key Levers to Create Best-in-Class In Vivo CAR T
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 chemistr
Slide 37: Three Parallel Efforts in Type 1 Diabetes (T1D)
Three Parallel Efforts in Type 1 Diabetes (T1D) Gene editing is key to achieving the goal of developing a beta-cell replacement product to treat diabetes without requiring long-term immunosuppression 1 2 3 CTX211 CTX213 Non-exclusive license with Vertex First-in-class edited beta-cell Deviceless, iP
Slide 38: CRISPR Therapeutics
CRISPR Therapeutics www.crisprtx.com CRISPR THERAPEUTICS – CONFIDENTIAL © 2025 CRISPR Therapeutics | 38 38