Precision BioSciences, Inc. · NASDAQ:DTIL
Precision BioSciences — Investor Presentation (May 2025)
55 slides from Precision BioSciences's investor presentation, May 2025
Slide 1: Corporate Deck
PRECISION BIOSCIENCES Corporate Deck May 2025 my
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements, as may any related presentations, within the meaning of the Private Securities Litigation Reform Act of 1995. The Company intends such forward-looking statements to be covered by the safe harbor provisions for forward-
Slide 3: Precision BioSciences Leadership Team Brings Strategic and Operational Experience
Precision BioSciences Leadership Team Brings Strategic and Operational Experience Michael Amoroso Jeff Smith, Ph.D. Cassie Gorsuch, Ph.D. Alex Kelly Cindy Atwell Since Oct 2021 Since March 2006 Since June 2016 Since Oct 2020 Since April 2019 President & Chief Research Officer, Chief Scientific Offic
Slide 4: Precision BioSciences is a Clinical Stage In Vivo Gene Editing Company
Precision BioSciences is a Clinical Stage In Vivo Gene Editing Company Expected First Clinical Multiple Programs in or Nearing Clinical Data Data Timing 〉 Investigational New Drug (IND) clearance and Fast Track designation PBGENE-HBV received in United States 2025 In Vivo Gene Editing 〉 Global phase
Slide 5: We Believe our Gene Editing Platform is Best Suited for the Indications We are Pursuing
We Believe our Gene Editing Platform is Best Suited for the Indications We are Pursuing
Slide 6: ARCUS is Our Proprietary Gene Editing Platform
ARCUS is Our Proprietary Gene Editing Platform: Naturally Evolved to Drive High Efficiency Editing • ARCUS wholly owned by Precision BioSciences • Evolved to safely edit by inserting in genome, adding function ― CRISPR-based editing tools engineered from enzymes evolved ARCUS to knockout DNA only •
Slide 7: The ARCUS Cut is Uniquely Designed to Drive Defined Outcomes
The ARCUS Cut is Uniquely Designed to Drive Defined Outcomes ARCUS cut leads to HDR or “Perfect” Re-ligation Cas9 C C G TAT G C A AT TA G C TA G G T C G Blunt cut G G C ATA C G T TA AT C G AT C C A G C induces NHEJ The ARCUS Cut TALEN/ZFN Generates a DNA replication direction C C G TAT G C A AT TA G
Slide 8: Size Matters for Where You Can Deliver
Size Matters for Where You Can Deliver ARCUS can use different delivery vehicles to target diverse tissue types ARCUS LNP AAV Liver Eye Muscle CNS Other 7
Slide 9: Size Matters for What You Can Deliver
ARCUS 1500 bp SaCas9 4200 bp AAV Genome Capacity ~4700 bp Size Matters for ARCUS Cas12a 4900 bp What You Can Deliver: Small ARCUS Size Allows SpCas9 Two Nucleases in One AAV 5100 bp ARCUS for Gene Excision as in our PBGENE-DMD program Base Editor (ABEmax) 5800 bp – 6500 bp Prime Editor (PEmax) 7200
Slide 10: Simplicity: ARCUS is the Only Single Protein Component Editor
Simplicity: ARCUS is the Only Single Protein Component Editor ARCUS Single protein with a DNA recognition motif and catalytic 1 activity all in one; no guide RNA required Editing outcome not dependent on simultaneous delivery of multiple components leading to higher efficiency Single component requi
Slide 11: ARCUS for the More Sophisticated Gene Edit
ARCUS for the More Sophisticated Gene Edit Designed by nature for a multitude of applications versus other gene editing modalities Replace Remove defective and insert functional gene Insertion Insert gene to add function Degree of Difficulty ARCUS Remove portion of genome, high Capability To Perform
Slide 12: Ornithine Transcarbamylase (OTC) Deficiency Program
Ornithine Transcarbamylase (OTC) Deficiency Program: Partnered Program First ARCUS in vivo Gene Editing Program Validated In Clinical Study Employing ARCUS Nuclease Initial Clinical Validation for ARCUS in vivo Gene Insertion First Infant Achieves Complete Clinical Response in Our Partner iECURE’s P
Slide 13: PBGENE-HBV is First Wholly Owned In Vivo Gene Editing Application of ARCUS
PBGENE-HBV is First Wholly Owned In Vivo Gene Editing Application of ARCUS
Slide 14: PBGENE-HBV Positioned to Potentially Impact More Patients than Other Gene Editing Programs
PBGENE-HBV Positioned to Potentially Impact More Patients than Other Gene Editing Programs Gene Editing Company - Lead Programs SCD and Transfusion- Dependent Beta Size based on worldwide prevalence Thalassemia 25M WW Prevalence 300 Million HeFH Patients 8M PiZ-AATD US Prevalence (Lung and Liver) Up
Slide 15: Chronic Hepatitis B Multi-Billion Dollar Market Opportunity
Chronic Hepatitis B Multi-Billion Dollar Market Opportunity: Large patient population currently on non-curative treatment options Ch > 300 Million U.S. Market Opportunity of ~$10 Billion1 cHBV infections globally Driven by the drug treated patient population today with total global aggregate revenue
Slide 16: Risk of Liver Cancer, Complications, and Mortality Remain on Current SoC
Risk of Liver Cancer, Complications, and Mortality Remain on Current SoC: cHBV Patients Have Up to a 30% Risk of Liver Cancer Over 10 years on Nucleos(t)ide Analogs Up to 40% of patients with chronic HBV infections may develop life-threatening complications including cirrhosis and/or HCC1 cHBV Resul
Slide 17: PBGENE-HBV Dual Mechanism: Targeting Root Cause of Disease
PBGENE-HBV Dual Mechanism: Designed to Drive Potential Cures By Targeting Root Cause of Disease & Eliminate Eliminate Inactivate cccDNA cccDNA IntegratedHBV Integrated HBVDNA DNA PBGENE- HBV + viral replication
Slide 18: ARCUS is Only Clinical Stage Gene Editor Designed to Eliminate cccDNA
ARCUS is Only Clinical Stage Gene Editor Designed to Eliminate cccDNA ARCUS Gene Editing Single-component ARCUS protein interacts with cccDNA directly, not through use of a guide RNA Small size Enables delivery efficiency Designed to ELIMINATE cccDNA and and accessibility to cccDNA INACTIVATE integr
Slide 19: Majority of Modalities in Development Target HBV Downstream
Majority of Modalities in Development Target HBV Downstream to Disrupt the Viral Lifecycle but Leave the Root Cause of Disease Intact No therapies today target the root cause of disease by eliminating the cccDNA and inactivating the integrated HBV DNA ANTISENSE NUCLEOS(T)IDE ANALOGS OLIGONUCLEOTIDES
Slide 20: PBGENE-HBV Directly Targets Root Cause of Disease
However, PBGENE-HBV Directly Targets Root Cause of Disease Targeting the origin of viral genesis ANTISENSE NUCLEOS(T)IDE ANALOGS PBGENE OLIGONUCLEOTIDES CAPSID ASSEMBLY HBV SMALL INTERFERING RNA MODULATORS HBV DNA HBV RNA Hepatocyte NUCLEIC ACID POLYMER HBsAg cccDNA Eliminates cccDNA HBV transcripts
Slide 21: Very Few Patients Get To Functional Cure Today
Very Few Patients Get To Functional Cure Today: PBGENE-HBV has opportunity to be clinically meaningful by increasing functional cures Current Approved Drug Modalities or in Late-stage Development Clinically Meaningful show single-digit functional cure rates Average Functional Cure Rates (%) 30% 20%
Slide 22: ELIMINATE-B Trial: 5 Countries, Up to 45 Patients
5 Countries HBeAg-negative patients controlled on nucleos(t)ide analogs Up to 45 Patients ClinicalTrials.gov identifier NCT06680232. 21
Slide 23: ELIMINATE-B Principal Investigators
United Kingdom Moldova Hong Kong Kosh Agarwal, MD Alina Jucov, MD, PhD Hepatologist and Transplant Principal Investigator, ARENSIA Physician Institute of Liver Studies, Research Clinic, Chisinau, Moldova King’s College Hospital NHS Assistant Professor, Department of Foundation Trust Gastroenterology
Slide 24: Eliminate-B Trial is Starting in Largest Real World Patient Segment
Eliminate-B Trial is Starting in Largest Real World Patient Segment More than 80% of HBV Patients are E-Negative 81% of Diagnosed 84% of Patients Treated on Patients are E-Negative Nucleos(t)ide Analogs are E-Negative 16% 19% Still only 1-3% achieve functional cure and up to 30% 10-year cumulative i
Slide 25: Phase 1/2a Study Design
Phase 1/2a Study Design Potential for rapid evaluation of safety and efficacy of PBGENE-HBV in 2025 Part 1: Multiple Ascending Dose Escalation Part 2 : Dose Expansion N= 3-6 Patients at Each Dose Level Finite Treatment: Patient Receives up to 3 dose administrations Dose Level 3 | High Dose Safety &
Slide 26: Phase 1/2a Study Goals to Demonstrate Both Safety and Efficacy
Phase 1/2a Study Goals to Demonstrate Both Safety and Efficacy Key Endpoints Safety determined by: Efficacy determined by: Frequency and severity of dose-limiting Antiviral activity through fixed duration toxicities (DLTs) PBGENE-HBV treatment Monitoring Biomarkers Reduction/Negativity in HBsAg: Sus
Slide 27: Chronic Hepatitis B Program: Second ARCUS Program Validated In Clinical Study
Chronic Hepatitis B Program: Second ARCUS in vivo Gene Editing Program Validated In Clinical Study Initial Data Demonstrates Safety in the ELIMINATE-B Clinical Trial After Multiple Doses1 and Antiviral Activity After Single Administration2 • Investigational New Drug Application cleared in the U.S. a
Slide 28: PBGENE-DMD
PBGENE-DMD Excision of a section of the Dystrophin Gene responsible for ~60% of the defects in Duchenne’s Muscular Dystrophy (DMD)
Slide 29: PBGENE-DMD Opportunity
PBGENE-DMD Opportunity: Potential to provide a first-in-class and best-in-class therapeutic for patients High Unmet Need Clear Regulatory Growing Opportunity for Guidance Innovative Treatments 28
Slide 30: DMD is a Genetic Disorder Resulting in Progressive Muscle Degeneration and Early Death
DMD is a Genetic Disorder Resulting in Progressive Muscle Degeneration and Early Death Brain 〉Learning disability or serious cognitive disability in a subset of patients Heart 〉Cardiomyopathy and arrythmias 〉Eventual cardiac failure leading to premature death in late teens or 20s Diaphragm & Interco
Slide 31: Today, Patients with DMD are in Dire Need with Limited Therapeutic Options
Today, Patients with DMD are in Dire Need with Limited Therapeutic Options Ideal therapy Microdystrophin Exon Skipping PBGENE-DMD would have: Gene Therapies Therapies Target Product Profile Improved muscle function over time Long-term durable benefit Broadly applicable to patients Corrects human dys
Slide 32: Global DMD Market Poised for Innovative Breakthroughs Like PBGENE-DMD
Global DMD Market Poised for Innovative Breakthroughs Like PBGENE-DMD Prevalence & Incidence1 Global Market Size Projection2 ~300-400k ~15k ~20% growth $8B DMD Patients globally DMD Patients in US rate >20k births ~550 births per year globally per year in US 2025 2030 1. Prevalence and Incidence bas
Slide 33: PBGENE-DMD is Designed to Provide Durable Functional Muscle Improvement
Novel Mechanism Corrects Human Dystrophin Gene Resulting in a Functional Dystrophin Protein PBGENE-DMD is Designed to Provide Durable Functional Muscle Improvement for the Majority of Patients with DMD Designed For Safety Through Lower Dose AAV 32
Slide 34: PBGENE-DMD Designed to Provide Durable Functional Improvement
PBGENE-DMD Designed to Provide Durable Functional Improvement for Majority Patients with DMD PBGENE-DMD: A single AAV encodes two ARCUS proteins designed to permanently edit a patient’s own DNA sequence, resulting in naturally-expressed, functional dystrophin ARCUS 1 ARCUS 2 ARCUS 1 Dystrophin gene
Slide 35: ARCUS is Uniquely Positioned for DMD Gene Editing
ARCUS is Uniquely Positioned for DMD Gene Editing Why Other Gene Editors Cannot Follow Unique Smallest Single Cut gene editor component editor Promotes safety Enables delivery Increases efficiency DMD: Safety and Efficacy DMD: Safety and Efficacy DMD: Efficacy Predictable repair enhances Both nuclea
Slide 36: PBGENE-DMD Showed Durable Functional Improvement Over Time
PBGENE-DMD Showed Durable Functional Improvement Over Time
Slide 37: PBGENE-DMD Significantly Improved Muscle Function and Demonstrated Long-Term Durability
New Data PBGENE-DMD Significantly Improved Muscle Function and Demonstrated Long-Term Durability Untreated Untreated PBGENE-DMD PBGENE-DMD Diseased Healthy (1x1014 vg/kg) (3x1013 vg/kg) 200% Normalized Force/BW 150% to Untreated Disease 100% 50% 0% 〉Improved muscle function observed from 3 to 6 mont
Slide 38: Long-term Functional Improvement Driven by Stable Levels of Dystrophin Protein
New Data Long-term Functional Improvement Driven by Increasing and Stable Levels of Dystrophin Protein Expression Heart Calf Quadricep 20 30 25 25 20 Dystrophin Restoration (%) Dystrophin Restoration (%) Dystrophin Restoration (%) 15 20 15 10 15 10 10 5 5 5 0 0 0 Treated disease mice Treated disease
Slide 39: Editing Satellite Cells is Essential for Durable Effect
Editing Satellite Cells is Essential for Durable Effect Satellite cells are the resident stem cells in skeletal muscle and Myocytes Myofiber essential for muscle regeneration In DMD where myofiber degeneration is continuous, editing satellite cells is essential for long-term therapeutic effect 38
Slide 40: PBGENE-DMD Edited Muscle Satellite Stem Cells
PBGENE-DMD Edited Muscle Satellite Stem Cells, Providing Potential for Durable Functional Improvement Edited PAX7+ cell PBGENE-DMD has demonstrated permanent editing of satellite cells, beyond transient transduction Observed edited dystrophin mRNA in PAX7+ cells, a marker for muscle satellite stem c
Slide 41: Novel Mechanism and Proven Dystrophin Protein
Novel Mechanism and Proven Dystrophin Protein
Slide 42: PBGENE-DMD's Novel Mechanism Enables Durable Improvements Independent of AAV Persistence
PBGENE-DMD’s Novel Mechanism Potentially Enables Durable Improvements in Muscle Function Independent of the Persistence of AAV PBGENE-DMD: The dystrophin protein is expressed by the human genome, preventing the need for AAV persistence Microdystrophin Gene Therapies: Microdystrophin protein is expre
Slide 43: PBGENE-DMD Designed to Produce a Near Full-Length Dystrophin Protein
PBGENE-DMD Designed to Produce a Near Full-Length Dystrophin Protein, Proven to be Functional in Humans H1 H2 H3 H4 Full-length ABD R1 R2 R3 R4 R5 R6 R7 R8 R9 R10 R11 R12 R13 R14 R15 R16 R17 R18 R19 R20 R21 R22 R23 R24 CR CT Dystrophin Full-length Dystrophin “ H1 H2 H4 ABD R1 R2 R3 R24 CR Truncated
Slide 44: PBGENE-DMD Designed to Produce a Near Full-Length Dystrophin Protein
PBGENE-DMD Designed to Produce a Near Full-Length Dystrophin Protein, Proven to be Functional in Humans H1 H2 H3 H4 Full-length ABD R1 R2 R3 R4 R5 R6 R7 R8 R9 R10 R11 R12 R13 R14 R15 R16 R17 R18 R19 R20 R21 R22 R23 R24 CR CT Dystrophin Full-length Dystrophin H1 H2 H4 Functional ABD R1 R2 R3 R4 R5 R6
Slide 45: Near Full-Length Dystrophin Protein Has Proven Function in Del45-55 Genotype
Near Full-Length Dystrophin Protein Has Proven Function in Individuals with Dystrophin Del45-55 Genotype Lifespan: Lifespan: • Early death in late teens or 20s • Can live into 60-70s1-3 Clinical Presentation: Clinical Presentation: • Progressive muscle weakness • Asymptomatic or mild leading to loss
Slide 46: PBGENE-DMD Program is Quickly Moving Towards Clinical Stage
PBGENE-DMD Program is Quickly Moving Towards Clinical Stage Identified Clinical Candidate Received Positive Pre-IND Feedback From FDA Initiated GLP Toxicology Studies Manufacture Clinical Trial Material Target Filing Of CTA and/or IND in 2025 Initiate First-in-Human Clinical Study 45
Slide 47: PBGENE-DMD: Highly Desirable Target Product Profile
PBGENE-DMD: Highly Desirable Target Product Profile Ideal therapy PBGENE-DMD Potential to Provide Best-In-Class Therapeutic Profile would have: Improvements in muscle Nonclinical evidence of muscle function improvement over time function Long-term durable benefit Data demonstrating improvement is du
Slide 48: PBGENE-3243 Program Development Paused
PBGENE-3243 Program Development Paused —Exploring Opportunities for Advancement Precision BioSciences remains We are encouraged by the We are grateful to the committed to our goal of preclinical data supporting mitochondrial community continuing to advance ARCUS- the potential for PBGENE-3243 to inc
Slide 49: Precision BioSciences Offering Meaningful Catalysts in Next 6-18 Months
Precision BioSciences Offering Meaningful Catalysts in Next 6-18 Months Ample cash runway to fund multiple potential regulatory submissions and clinical data readouts CASH RUNWAY INTO 2H 2026 ~$100M Potential to Advance 3 Programs to Phase I Clinical Data Cash and cash equivelents1 As of 3/31/25 Exp
Slide 50: Appendix: PBGENE-HBV Preclinical Data
Appendix: PBGENE-HBV Preclinical Data
Slide 51: NHP Study Demonstrated Up to 99% Viral Engagement
Efficacy: NHP Study Demonstrated Up to 99% Viral Engagement, Suggestive of Strong Potential Efficacy Profile of PBGENE-HBV Optimized Nuclease 99% 100 95% 93% Viral Engagement (%) 2nd dose administration 1st dose administration HBV LNP 0% 0 Control 2mg/kg LNP 1mg/kg LNP 0.5mg/kg LNP Increased editing
Slide 52: PBGENE-HBV Showed Minor and Transient Elevations in Liver Transaminases
Safety: PBGENE-HBV Showed Minor and Transient Elevations in Liver Transaminases NHP data supports safety of multi-dosing to achieve functional cure 1.5 1000 1000 1.5 mg/kg PBGENE-HBV Control 800 800 1.0 AST (U/L) ALT (U/L) TBIL (mg/dL) 600 600 400 400 0.5 200 200 PBGENE-HBV 0 20 40 0 20 40 0 20 40 T
Slide 53: PBGENE-HBV Significantly and Sustainably Reduced HBV DNA in Mouse Model
Efficacy: PBGENE-HBV Significantly and Sustainably Reduced HBV DNA as a Monotherapy in Transgenic Mouse Model HBV DNA 1st 2nd ARCUS ARCUS Saline Dose Dose NUC Log [HBV DNA (copy/µl)] 5 PBGENE-HBV + NUC 4 No Viral Rebound 3 start NUC stop LLoQ=2.08 2 -4 0 3 7 10 14 1721 2428 3135 38 42 Days Even afte
Slide 54: PBGENE-HBV Eliminates cccDNA in Primary Human Hepatocytes
Efficacy: PBGENE-HBV Eliminates cccDNA and Inhibits Viral Markers in HBV-Infected Primary Human Hepatocytes (PHH) NEW DATA 100 ARCUS mRNA (µg) 90 Medium 0.001 80 0.003 0.01 0.03 HBV DNA NUC % Inhibition 70 0.1 0.3 HBsAg 60 HBeAg 50 HBV RNA 40 30 cccDNA 20 10 0 *siRNA also do 0.001 0.003 0.01 0.03 0.
Slide 55: PBGENE-HBV Demonstrates Up to 95% Durable HBsAg Reduction
Efficacy: PBGENE-HBV Demonstrates Up to 95% Durable HBsAg Reduction Across Dose Levels in Episomal Mouse Study NEW DATA Final Clinical Candidate 200 PBS Prior Nuclease ARCUS LNP ARCUS LNP 0.3 mg/kg 95% administration HBsAg Inhibition (% of baseline) ARCUS LNP 0.1 mg/kg 90% ARCUS LNP 0.03 mg/kg viral
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