Eloxx Pharmaceuticals, Inc. · NASDAQ:ELOX
Eloxx Pharmaceuticals — Investor Presentation (April 2021)
38 slides from Eloxx Pharmaceuticals's investor presentation, Apr 20, 2021
Slide 1: RARE Thinking for RARE Solutions
RARE Thinking for RARE Solutions Creating a World Leader in Ribosome Targeted Genetic Therapies April 2021
Slide 2: Forward-looking statements
/ 2 Forward - looking statements This presentation contains forward - looking statements, which are generally statements that are not historical facts . Forward - looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook
Slide 3: Eloxx + Zikani: Positioned to be the world leader in ribosome RNA-targeted genetic therapies
/ 3 * RDEB and JEB : Recessive Dystrophic and Junctional Epidermolysis Bullosa; APC : Adenomatous Polyposis Coli Eloxx + Zikani: Positioned to be the world leader in ribosome RNA - targeted genetic therapies Strengthened leadership Complementary platforms targeting the human ribosome Rare disease an
Slide 4: Meet the new Eloxx Leadership Team
/ 4 Meet the new Eloxx Leadership Team Sumit Aggarwal President and CEO • 20+ years investing and transforming healthcare companies • Raised >$150M • Biotech Investor Vijay Modur Head of Research & Development • 20+ years in translation and drug development • Led Venglustat rare disease program at S
Slide 5: Transaction overview
/ 5 Transaction overview • Eloxx issued ~ 7.6 million shares • Zikani stockholders have pro forma ownership ~ 16% of Eloxx • Silvia Noiman, Ph.D., and Martijn Kleijwegt stepped down from Eloxx Board • Alan Walts, Ph.D., and Raj Parekh, Ph.D., current Zikani directors, appointed to fill vacancies and
Slide 6: Strong advisors and collaborators supporting programs
/ 6 Strong advisors and collaborators supporting programs Prof. Eitan Kerem Cystic Fibrosis Former Head of Pediatrics Hadassah Hospital Former SAB member Vertex Keith Flaherty Oncology, Chairman SAB Loxo Oncology co - founder Pedro Huertas Clinical Translation ex - CMO Eloxx, Shire Dr. David Sidrans
Slide 7: Complementary human ribosome targeting technologies
/ 7 RMA: Ribosome Modulating Agent; ERSG: Eukaryotic Ribosome Selective Glycoside Complementary human ribosome targeting technologies that address defects in protein translation Ribosome = “protein factory”: Correcting mRNA and ribosomal mutations Ribosome large subunit Ribosome small subunit mRNA A
Slide 8: Ribosome: correcting nonsense mutations
/ 8 RMA: Ribosome Modulating Agent; ERSG: Eukaryotic Ribosome Selective Glycoside Complementary human ribosome targeting technologies that address defects in protein translation Ribosome = “protein factory”: Correcting mRNA and ribosomal mutations Truncated peptide chain = Loss of Function Premature
Slide 9: Ribosome: ribosomal mutations
/ 9 RMA: Ribosome Modulating Agent; ERSG: Eukaryotic Ribosome Selective Glycoside Complementary human ribosome targeting technologies that address defects in protein translation Ribosome = “protein factory”: Correcting mRNA and ribosomal mutations Ribosomal mutations Dysregulated Onco - and Mitoribo
Slide 10: ERSG and RMA restore proteins and inhibit translation
/ 10 RMA: Ribosome Modulating Agent; ERSG: Eukaryotic Ribosome Selective Glycoside Complementary human ribosome targeting technologies that address defects in protein translation Ribosome = “protein factory”: Correcting mRNA and ribosomal mutations Ribosome large subunit Ribosome small subunit ERSG
Slide 11: Clinically relevant readthrough reported in different rare diseases
/ 11 Clinically relevant readthrough reported in over 36 different rare diseases Diseases Evidence Readthrough Agent(s) Tested Macrolides Aminoglycosides Familial Adenomatous Polyposis (FAP) Clinical 1 Ery, Tyl Gen Cystic Fibrosis Class 1 Clinical 2 Tyl Gen, G418 Duchenne Muscular Dystrophy Clinical
Slide 12: Large and broad applications for human ribosome targeted genetic therapies
/ 12 Large and broad applications for human ribosome targeted genetic therapies Readthrough = “Functional Gene Therapy” RMA ERSG Protein Translation Inhibition RMA Stop codon readthrough in rare diseases and cancer • 10 – 12% of patients across >1800 rare diseases • 6 – 10% of cancer patients have n
Slide 13: Deep pipeline of synergistic potential first-in-class therapies
/ 13 *Class 1 CF: Cystic fibrosis patients with class1 mutations; ADPKD: Autosomal dominant polycystic kidney disease; FAP: Familial adenomatous polyposis; CRC: Colorectal cancer Deep pipeline of synergistic potential first - in - class therapies Target Indication Discovery Early research Lead optim
Slide 14: ELX-02 (Clinical) and ERSG Preclinical programs
/ 14 ELX - 02 (Clinical) and ERSG Preclinical programs
Slide 15: ERSGs like ELX-02 designed to expand human ribosome selectivity
/ 15 Data adapted from: Kandasamy. Increased Selectivity toward Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficie ncy of Synthetic Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutations. J. Med. Chem . (2012) ERSGs like ELX
Slide 16: Class 1 CF opportunity and clinical rationale
/ 16 Class 1 CF opportunity and clinical rationale 1 Allelic frequency based on CFTR2 database (July 2020); CF population data based on 2019 Patient Registry Report. 2 Sermet - Gaudelus, I. BMC Med . 2007, 5, 5; Clinical validation for gentamicin supports ELX - 02 use in treating Class 1 Cystic Fibr
Slide 17: High ELX-02 efficacy in organoid swelling and Ussing chamber experiments
/ 17 Swelling response in G542X CF patient organoids 1 Ussing chamber results heterozygous G542X/Fdel508 HBE cells 1 Ordinary one - way ANOVA with Tukey’s multiple comparison testing was used; **** p<0.0001 versus vehicle control, ## p<0.01 versus next lower concentration, #### p<0.0001 versus next
Slide 18: Swelling response in CF organoids with ELX-02 vs. Symdeko
/ 18 Swelling response in Class 1 and Class 2 CF patient organoids when treated with ELX - 02 vs. Symdeko ClinicalTrials.gov Identifier: US Trial NCT04135495, EU/IL Trial NCT04126473 * From baseline to Day 7 of treatment periods 1 - 3, and Days 7 and 14 of treatment period 4 ** Lancet Respir Med. 20
Slide 19: Swelling response in CF patient organoids
/ 19 Swelling response in CF patient organoids ELX - 02 efficacy seen across CFTR nonsense mutations W1282X response example R553X response example R1162X response example
Slide 20: ELX-02 shows synergy with Kalydeco
/ 20 Ussing Chamber experiment: Treatment of Het G542X HBE cells ELX - 02 shows synergy with Kalydeco (VX770 - a potentiator) 0 5 10 15 20 (mg/mL) l s c ( m A / c m 2 ) ELX-02 ELX-02 & VX-770 (10µM) 0 25 50 75 100125250 **** ** *** * G542X/F508del
Slide 21: ELX-02 well tolerated in Phase 1 and 2 clinical studies
/ 21 Phase I trial records: NCT03776539, NCT03309605, NCT03292302, Phase II trial record: NCT04069260 ELX - 02 well tolerated in Phase 1 and 2 clinical studies • Single and Multiple ascending doses studied from 0.3 to 7.5 mg/kg. Generally well tolerated • No dose limiting toxicities, SAEs or off tar
Slide 22: ELX-02 Phase 2 cystic fibrosis trial design
/ 22 ClinicalTrials.gov Identifier: US Trial NCT04135495, EU/IL Trial NCT04126473 * From baseline to Day 7 of treatment periods 1 - 3, and Days 7 and 14 of treatment period 4 ELX - 02 Phase 2 cystic fibrosis trial designed to evaluate safety and short term sweat chloride reduction Up to 3 mg/kg SC Q
Slide 23: Orkambi Phase 3 showed FEV change leading to approval
/ 23 Larger and longer ORKAMBI Ph3 trial showed +2.6% FEV 1 change leading to its approval FEV 1 improvement is not significant for any dose group in small short trial -18 -16 -14 -12 -10 -8 -6 -4 -2 0 Day 7 Day 14 Day 21 Mean change (mmol/L Placebo Lumacaftor 200 mg once per day + ivacaftor 150 mg
Slide 24: Expect to complete enrollment by midyear and report data in 2H 2021
/ 24 Expect to complete enrollment in Phase 2 clinical trials by midyear and report data in 2H 2021 ELX - 02: Potential for transformative efficacy in Class 1 CF patients Demonstrated efficacy in clinically relevant pre - clinical models • Swelling response in Class 1 CF patient organoids • Induces
Slide 25: Readthrough in preclinical models of rare kidney and ocular diseases
/ 25 Readthrough shown in preclinical models with other ERSG’s in rare kidney and ocular diseases -4.5 -4.0 -3.5 -3.0 -2.5 -2.0 0 5 10 15 20 25 PKD1 Dual luciferase % Read-through, ELX-10 Log [ELX-10] (M) % r e a d - t h r o u g h Q4042X R4228X R2430X PKD1 • Mutations in PKD1 or PKD2 lead to cyst gr
Slide 26: TURBO-ZM
TURBO-ZM" aes
Slide 27: TURBO-ZM: Applying macrolide SAR to RMA design
/ 27 TURBO - ZM Œ : Applying macrolide SAR to RMA design TURBO - ZM Œ ( TU ning the R i BO some with Z ikani M olecules) platform fully unlocks the potential of macrolides Optimize for: • Readthrough • Protein translation inhibition Interact with the peptide sequence Modulate: • PK • Safety: cardiac
Slide 28: Nascent peptide exit tunnel in E. coli vs. human ribosomes
/ 28 Nascent peptide exit tunnel in E. coli vs. human ribosomes 1 1 Nucleic Acids Res . 2019;47(8):4198 - 4210 Strong rationale for macrolides to bind to the human ribosome Macrolide binding site in prokaryotic (bacterial) ribosome 75% of binding site conserved in the human (eukaryotic) ribosome 1 F
Slide 29: Zikani RMA Library (2000+)
/ 29 Zikani RMA Library (2000+) Growing library of RMAs with drug - like properties
Slide 30: RMAs show superior readthrough to alternatives
/ 30 Readthrough Emax of selected RMA hits relative luciferase units compared to DMSO in W134X Nanoluc reporter assay RMAs show superior readthrough to alternatives 3,005 5,613 1,791 18,188 7,420 14,811 10,157 8,597 24,330 12,614 ZKN - 3 ZKN - 1 ZKN - 5 ZKN - 2 ZKN - 4 ZKN - 6 +710% +333% ZKN - 7 G4
Slide 31: RMA Preclinical programs: RDEB/JEB, CF and FAP
/ 31 RMA Preclinical programs: RDEB/JEB, CF and FAP
Slide 32: RDEB/JEB: Clinically validated path for RMAs in rare skin disease
/ 32 RDEB and JEB : Recessive Dystrophic and Junctional Epidermolysis Bullosa 1 Woodley, DT. J Clin Investig 2017, 127, 3028 - 3038; 2 Hammersen, Johanna et al. Dermatology May 2019 RDEB/JEB: Clinically validated path for RMAs in rare skin disease targeting patients with nonsense mutations • Mutatio
Slide 33: RMAs restore functional collagen protein in RDEB patient cells
/ 33 COL7 with 48 hr. exposure in RDEB patient derived primary fibroblasts* * Fibroblasts isolated from patients two and five in gentamicin clinical trial. J Clin Invest 2017, 127, 3028 - 3038 ** 48 hours treatment with media and compounds replaced and refreshed at 24 hours. Study repeated twice wit
Slide 34: Class 1 CF: RMA lead showed highest ever readthrough
/ 34 Summary of Class 1 CF data * Forskolin 10 µM/1µM VX - 770 - both chambers ** VX 809 and RMA data averaged from 2 separate Ussing chamber results Class 1 CF: RMA lead showed highest ever readthrough preclinical Ussing chamber assay Data generated at Chantest VX - 809 (3uM) DMSO RMA (15 uM) RMA (
Slide 35: APC readthrough: supported by prior clinical success of Erythromycin in FAP
/ 35 1 Kariv, R. Int J Cancer . 2019 doi: 10.1002/ijc.32557 APC readthrough: Supported by positive prior clinical success of Erythromycin in FAP Erythromycin treatment (250 mg/day po for 4 months) Change in polyp burden at 12 months 1 45.7 34.9 - 42.2 - 55.1 Change in polyp number Change in polyp cu
Slide 36: Efficacy of ZKN013 in colorectal cancer patient derived tumor grafts
/ 36 Efficacy of ZN013 in colorectal cancer patient derived tumor grafts ex - vivo Clear path treating FAP supported by efficacy in APC mutant cancer patient tumor grafts • Ex - vivo sensitivity assessment in tumor grafts • Potent tumor growth inhibition – GI50<15uM • Cancer xenograft studies planne
Slide 37: Positioned to be the world leader in ribosome targeted genetic therapies
/ 37 Positioned to be the world leader in ribosome targeted genetic therapies Proprietary ribosome targeted small molecule platforms targeting rare diseases and oncology Deep pipeline led by clinical stage program to treat class 1 nonsense mutations in Cystic Fibrosis Expect to file first IND for fi
Slide 38: Eloxx Pharmaceuticals
a Eloxx PHARMACEUTICALS TURBO-ZM" Eloxx
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