Korro Bio, Inc. · NASDAQ:KRRO
Korro Bio — Merger or Acquisition (July 2023)
30 slides from Korro Bio's merger presentation, July 2023
Slide 1: Edit the Message, Rewrite the Future
Edit the Message, Rewrite the Future July 2023 1 Copyright (c) 2023 Korro Bio, Inc.
Slide 2: Disclaimers
Disclaimers Forward Looking Statements Certain statements in this Presentation may constitute “forward-looking statements”. Forward-looking statements include, but are not limited to, statements regarding expectations, hopes, beliefs, intentions or strategies of Korro Bio, Inc. (Korro) and/or Freque
Slide 3: Risk factors
Risk factors Both Frequency and Korro are subject to various risks associated with their businesses and their industries. In addition, the Proposed Transaction, including the possibility that the Proposed Transaction may not be completed, poses a number of risks to each company and its respective se
Slide 4: Experienced management team with proven track record
Experienced management team with proven track record Ram Aiyar, PhD Steve Colletti, PhD Vineet Agarwal Todd Chappell Venkat Krishnamurthy, PhD Stephanie Engels Shelby Walker President and Chief Scientific Officer Chief Financial Officer SVP, Strategy and SVP, Head of Platform SVP, HR, People SVP, Ge
Slide 5: Merger of Korro Bio and Frequency Therapeutics
Merger of Korro Bio and Frequency Therapeutics • Korro Bio, a privately-held leading company in RNA editing, intends to merge with Frequency Therapeutics (NASDAQ: FREQ) Transaction • Upon close, Frequency Therapeutics is expected to be renamed “Korro Bio, Inc.” summary • Supported by the Board of Di
Slide 6: Uniquely positioned to expand the frontier of genetic medicines through RNA editing
Uniquely positioned to expand the frontier of genetic medicines through RNA editing Experienced management team: Proven track record supported by an expert BoD and SAB with experience building genetic medicines companies OPERA, a transient and potentially safer base editing approach: Single edit (A-
Slide 7: Using an oligonucleotide to affect an A-to-I edit on a target RNA sequence
Using an oligonucleotide to affect an A-to-I edit on a target RNA sequence Harnessing an endogenous editing 1 Non-viral intracellular delivery of enzyme, ADAR, that is ubiquitously Korro oligo designed to edit a specific expressed in all human cells adenosine on the target mRNA 2 Oligo-RNA duplex re
Slide 8: Discovery of missense mutations for common diseases increases the therapeutic opportunity
Discovery of missense mutations for common diseases increases the therapeutic opportunity for genetic medicines Nature volume 577, pages 179–189 (2020) 8 Copyright (c) 2023 Korro Bio, Inc.
Slide 9: RNA editing with synthetic oligonucleotide expands the promise of base editing
RNA editing with synthetic oligonucleotide expands the promise of base editing to large common diseases Oligo-based RNA Editing DNA Editing Specificity ✓ High sequence specificity Risk of indels and chromosomal integration Delivery ✓ Precedented (efficient and targeted) Inefficient in vivo ✓ Lon
Slide 10: OPERA: Our differentiated approach for RNA editing
OPERA: Our differentiated approach for RNA editing Deep understanding of ADAR Expertise in oligonucleotide biology chemistry Machine learning optimization Fit-for-purpose delivery of oligonucleotides Broad IP estate of 29 patent families that cover our platform technology and target-specific editing
Slide 11: Broad and versatile applications for our RNA editing approach
Broad and versatile applications for our RNA editing approach Development candidate Current focus Unlocking other target classes expected in 2H’23 PoC achieved Disrupting protein-protein interactions Repairing pathogenic variants (e.g., AATD, SERPINA1) Preventing protein aggregation Selectively modu
Slide 12: Deep pipeline with multiple high-value targets
Deep pipeline with multiple high-value targets Preclinical Phase 1 Phase 2 Phase 3 Wholly Concept Indication Target Discovery development owned? Repairing a Alpha-1 anti- Regulatory filing expected SERPINA1 in 2H’241 pathogenic variant trypsin deficiency Repairing a Parkinson disease LRRK2 pathogeni
Slide 13: Alpha-1 antitrypsin deficiency (AATD)
Alpha-1 antitrypsin deficiency (AATD) 13 Copyright (c) 2023 Korro Bio, Inc.
Slide 14: AATD: Correcting a pathogenic missense mutation in the liver
AATD: Correcting a pathogenic missense mutation in the liver Potential to target both manifestations Clinically-validated lipid nanoparticles (LNP) Resolving both liver pathology and alleviating from Genevant lung effects Increased levels of oligo concentration in liver Provides natural regulation o
Slide 15: Severe AATD caused by a single missense mutation in SERPINA1 gene
Severe AATD caused by a single missense mutation in SERPINA1 gene leading to lung and/or liver disease(s) MM Genotype (normal liver and lung) Opportunity: Unmet need WT A1AT • Only FDA-approved therapy is protein replacement augmentation therapy • Plasma derived A1AT from pooled Normal levels of Inh
Slide 16: Getting AATD patients between MM and MZ phenotypes has potential to modify disease progression
Getting AATD patients between MM and MZ phenotypes has potential to modify disease progression Ranges of serum A1AT levels for different genotypes Median A1AT for genotype 50 μM serum AAT Levels 40 100% editing Korro goal for median 30 editing has potential to reduce lung and liver risk 50% editing
Slide 17: Korro's approach potentially provides superior patient benefit over other modalities in AATD
Korro’s approach potentially provides superior patient benefit over other modalities in AATD DNA EDITING siRNA FUSION PROTEIN Simple drug product ✓ ✓ ✓ Lung ✓ ✓ ✓ alleviation Liver alleviation ✓ ✓ ✓ Target genotype to Between MM and MZ <MZ ZZ ZZ be achieved Potential to Potential ✓ Reversibl
Slide 18: Key milestones achieved to obtain >50% editing in humans
Key milestones achieved to obtain >50% editing in humans Korro’s AATD candidates are antisense oligonucleotides delivered to liver cells encapsulated in a lipid nanoparticle vehicle Key Attribute Criteria Status In vitro activity • >50% editing1 in human cells with Z mutation ✓ In vivo activity • >5
Slide 19: >50% editing achieved in the right system – human gene with human ADAR
>50% editing achieved in the right system – human gene with human ADAR In vitro Editing in hepatocyte like cells (HLCs) Editing in MZ Primary Human Hepatocytes (PHH) Editing measured as number of transcripts 100 100 1 nM 1 nM 10 nM 10 nM 100nM 81 80 100nM 80 64 80 Editing at E342K (%) Editing at E34
Slide 20: Demonstrated >50% editing in PiZ mice model of AATD with a single dose
Demonstrated >50% editing in PiZ mice model of AATD with a single dose achieving high levels of corrected protein In vivo – PiZ mice Editing in PiZ mice (single-dose) M-A1AT protein in PiZ mice (single-dose) Oligo A; 3mg/kg (single-dose) Oligo A; 3mg/kg (single-dose) 100 18μM Day 1 20 M-A1AT concent
Slide 21: Potential to provide liver benefit by clearing aggregation and preventing lung damage
Potential to provide liver benefit by clearing aggregation and preventing further lung damage due to level of M-A1AT in secretion In vivo – PiZ mice Editing in PiZ mice at Ctrough Total A1AT (1 day post last dose) Reduction in Z-A1AT at Day 28 Oligo A; 2mg/kg (multi-dose) 50 Vehicle A1AT concentrati
Slide 22: Upcoming milestones
Upcoming milestones Milestone Timing Expected close of reverse merger and concurrent $117M private financing 4Q 2023 Nominate a development candidate for AATD program 2H 2023 Submit regulatory filing 2H 2024 Potential interim clinical data readout for AATD 2H 2025 22 Copyright (c) 2023 Korro Bio, In
Slide 23: Editing in NHPs
Editing in NHPs (Gene = SERPINA1) 23 Copyright (c) 2023 Korro Bio, Inc.
Slide 24: Editing of SERPINA1 coding region in NHPs and PiZ model showed correlation
Editing of SERPINA1 coding region in NHPs and PiZ model showed correlation In vivo – mice and NHP Editing in PiZ mice (%) Editing in NHPs (%) Early-gen oligo1 Early-gen oligo1 3mg/kg (single dose) For reference: 2mg/kg (single and multi-dose) 100 ~63% 40 Day 4 (post-single dose) 80 40 % editing 60 4
Slide 25: Editing with Korro Oligo in Genevant LNP
Editing with Korro Oligo in Genevant LNP 25 Copyright (c) 2023 Korro Bio, Inc.
Slide 26: Korro's Oligo A in Genevant LNP has demonstrated potential for increased editing efficiency
Korro’s Oligo A in Genevant LNP has demonstrated potential for increased editing efficiency and normal A1AT in PiZ mice Editing in PiZ mice (%) Normal A1AT in circulation (%) Oligo A; 2mg/kg (Single dose): 4-days post dose Oligo A; 2mg/kg (Single dose): 4-days post dose For reference: 100 ~63% 100 1
Slide 27: Editing in NHPs with Korro's oligo in a Genevant LNP shows enhanced therapeutic index
Editing of SERPINA1 coding region in NHPs with Korro’s oligo in a Genevant LNP has demonstrated potential for enhanced therapeutic index Editing in NHP (%) ALT levels in NHP (U/L) Early-gen oligo1 Early-gen oligo1 2mg/kg (Single dose): 4-days post dose 2mg/kg (Single dose) HISTORICAL 1200 HISTORICAL
Slide 28: Opportunity to bring ground-breaking therapeutic option based on single-nucleotide-variants
Opportunity to bring ground-breaking therapeutic option for patients based on single-nucleotide-variants Examples ✓ PoC achieved ✓ Activating Kinases Modulating kinase activity with a single missense variant Disrupting Protein-Protein ✓ Activating transcription factor expression by disrupting bindin
Slide 29: Uniquely positioned to expand the frontier of genetic medicines through RNA editing
Uniquely positioned to expand the frontier of genetic medicines through RNA editing Experienced management team: Proven track record supported by an expert BoD and SAB with experience building genetic medicines companies OPERA, a transient and potentially safer base editing approach: Single edit (A-
Slide 30: Copyright (c) 2023 Korro Bio, Inc.
30 Copyright (c) 2023 Korro Bio, Inc.