Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Investor Presentation (June 2023)
43 slides from Larimar Therapeutics's investor presentation, Jun 1, 2023
Slide 1: Larimar Therapeutics Corporate Presentation June 2023
June 2023 Larimar Therapeutics Corporate Presentation
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements that are based on the beliefs and assumptions of Larimar Therapeutics, Inc. ( “Company”) and on information currently available to management. All statements contained in this presentation other than statements of histo
Slide 3: Investment Highlights
Investment Highlights Double-blind, placebo-controlled Phase 1 proof-of-concept trials in individuals with FA complete Data show CTI-1601 was generally well tolerated when dosed daily for up to 13 days; Dose dependent increases were observed in frataxin (FXN) levels from baseline compared to placebo
Slide 4: Platform Technology is Supported by a Strong IP Portfolio
2015 2020 2030 2035 2040 2045 2050 2055 2010 2025 *Additional pending applications for platform disease targets Est. Expiration March 2041 CTI-1601 Composition of Matter and Methods of Treatment US 11,459,363 (Exclusive license from Indiana University) US continuation and foreign applications pendin
Slide 5: Friedreich's Ataxia: Disease Overview
Caused by genetic defect resulting in low levels of frataxin Patients with FA only produce ~20-40% of normal frataxin levels depending on the tissue, sampling technique, and assay considered1 Affects ~20,000 patients globally, with ~5,000 patients in the U.S. and majority of the remaining patients i
Slide 6: CTI-1601 is Designed to Deliver Additional Frataxin (FXN)
CTI-1601 is Designed to Deliver Additional Frataxin (FXN) The presence of the cleavage site allows the CPP and MTS to be removed by mitochondrial processing peptidase to produce mature human FXN in the mitochondria STRUCTURE OF ENDOGENOUS FXN STRUCTURE OF CTI-1601 Cleavage by mitochondrial processin
Slide 7: Completed Phase 1 Multiple Ascending Dose Study
Completed Phase 1 Multiple Ascending Dose Study Treatment Schedules for Each Cohort 13-day Treatment Period Cohort 2 (50 mg; n = 9) 2 3 4 5 1 6 7 8 9 10 11 12 13 14 = Administration of CTI-1601 or placebo = No Administration 13-day Treatment Period Cohort 1 (25 mg; n = 8) 2 3 4 5 1 6 7 8 9 10 11 12
Slide 8: Dose Dependent Increases in FXN Levels Observed in Skin and Buccal Cells in Phase 1
Dose Dependent Increases in FXN Levels Observed in Skin and Buccal Cells in Phase 1 *FXN levels measured via detection of peptide derived from mature FXN; FXN concentrations are normalized to total cellular protein content in each sample; Data represent median and 25th and 75th percentiles; FXN leve
Slide 9: Increases in FXN Correlated with Increasing CTI-1601 Dose in Phase 1 Trial
Increases in FXN Correlated with Increasing CTI-1601 Dose in Phase 1 Trial Skin Biopsies Day 13 FXN* Change from Baseline# Buccal Cells Day 4/7 FXN* Change from Baseline◊ *FXN levels measured via detection of peptide derived from mature FXN. FXN concentrations are normalized to total cellular protei
Slide 10: Phase 2, Four-week Dose Exploration Study
Phase 2, Four-week Dose Exploration Study Goal: Further characterize PK/PD and assess safety to inform long-term dose and dose regimen Treatment Schedule 28-day Treatment Period 16 17 18 19 15 20 21 22 23 24 25 26 27 28 2 3 4 5 1 6 7 8 9 10 11 12 13 14 = Administration of CTI-1601 or placebo = No Ad
Slide 11: Preliminary Top-line Data from 25 mg Cohort of Phase 2 Trial
Preliminary Top-line Data from 25 mg Cohort of Ph 2 Trial Frataxin (FXN) Levels A meeting between Larimar and FDA is scheduled to discuss the information needed to gain clearance to initiate a 50 mg cohort in the Phase 2 trial Update on CTI-1601 program expected in Q3 2023 Next Steps Participants do
Slide 12: Increases in FXN Levels Observed in Skin Biopsies
Increases in FXN Levels Observed in Skin Biopsies Median placebo-adjusted increase from baseline of 3.5 pg/µg in skin with 14 days daily dosing *FXN levels measured via detection of peptide derived from mature FXN; FXN concentrations are normalized to total cellular protein content in each sample; D
Slide 13: Increases in FXN Levels Observed in Buccal Cells
Increases in FXN Levels Observed in Buccal Cells Median placebo-adjusted increase from baseline of 0.9 pg/µg in buccal cells with 14 days daily dosing *FXN levels measured via detection of peptide derived from mature FXN; FXN concentrations are normalized to total cellular protein content in each sa
Slide 14: Clinical Data Indicate CTI-1601 is Generally Well Tolerated
Clinical Data Indicate CTI-1601 is Generally Well Tolerated CTI-1601 administered to 37 different adults with FA in multiple studies 35 of 37 clinical trial participants dosed with CTI-1601 completed their respective study One Phase 2 participant withdrew due to an allergic reaction that resolved wi
Slide 15: CTI-1601 Clinical Development Plan
CTI-1601 Clinical Development Plan Planned Trials Include: Global double-blind placebo-controlled pivotal trial. Jive open-label extension trial for eligible patients who participated in SAD, MAD, and/or four-week dose exploration studies MAD trial in patients 2 to 17 years of age. Participants elig
Slide 16: CTI-1601: In Development as the First Therapeutic Intended to Increase FXN
Phase 2 (25 mg cohort) A meeting between Larimar and FDA is scheduled to discuss the information needed to gain clearance to initiate a 50 mg cohort in the Phase 2 trial Update on CTI-1601 program expected in Q3 2023 Regulatory Generally well tolerated Dose-dependent increases in FXN levels in all e
Slide 17: Investment Highlights
Investment Highlights Double-blind, placebo-controlled Phase 1 proof-of-concept trials in individuals with FA complete Data show CTI-1601 was generally well tolerated when dosed daily for up to 13 days; Dose dependent increases were observed in frataxin (FXN) levels from baseline compared to placebo
Slide 18: Thank You
THANK YOU Larimar Therapeutics June 2023 Corporate Update
Slide 19: Appendix
Appendix Larimar Therapeutics
Slide 20: Leadership Team
Leadership Team Gopi Shankar, PhD, MBA, FAAPS Chief Development Officer John Berman, CPA VP, Finance & Operations Mohamed Hamdani VP, Biometrics Noreen Scherer VP, Clinical Operations Michael Celano Chief Financial Officer Keith E. Lynch, Jr. VP, Technical Operations Francis Michael Conway VP, Contr
Slide 21: Scientific Advisory Board
Scientific Advisory Board Giovanni Manfredi, MD, PhD Finbar and Marianne Kenny Professor in Clinical and Research Neurology at Weill Cornell Medicine. Professor of Neuroscience at Weill Cornell Medicine. Russell Clayton, DO (Chairman) Former Chief Medical Officer at Alcresta Therapeutics, a medical
Slide 22: Strong Relationship with FARA
Company has strong relationship with Friedreich’s Ataxia Research Alliance (FARA) National, non-profit organization dedicated to the pursuit of scientific research leading to treatments and a cure for FA FARA provides industry with several key items Assistance with patient recruitment and education
Slide 23: Additional Phase 1 Data
Additional Phase 1 Data O\.
Slide 24: Phase 1 Top-line Data Demonstrated POC for CTI-1601 in FA
CTI-1601 appears to be generally well tolerated at doses up to 100 mg administered daily for 13 days Safety Pharmacodynamics Pharmacokinetics Conclusion Daily dosing of CTI-1601 resulted in dose-dependent increases in FXN levels from baseline compared to placebo controls in all evaluated tissues Pha
Slide 25: CTI-1601: Phase 1 Clinical Program in Patients with FA
CTI-1601: Phase 1 Clinical Program in Patients with FA Phase 1 Development Plan Two double-blind, placebo-controlled dosing trials in patients with FA Patient dosing began December 2019 Safety Review Committee assessed all blinded data between each cohort to ensure patient safety Number of subjects:
Slide 26: MAD Trial Patient Demographics
MAD Trial Patient Demographics Parameter Statistic All placebo (n=7) 25 mg CTI-1601 (n=6) 50 mg CTI-1601 (n=7) 100 mg CTI-1601 (n=7) All CTI-1601 (n=20) Overall (n=27) Sex Male n (%) 5 (71.4) 3 ( 50.0) 4 ( 57.1) 3 ( 42.9) 10 ( 50.0) 15 (55.6) Female n (%) 2 (28.6) 3 ( 50.0) 3 ( 42.9) 4 ( 57.1) 10 (
Slide 27: MAD Trial Patient Disease Characteristics
MAD Trial Patient Disease Characteristics Parameter Statistic All placebo (n=7) 25 mg CTI-1601 (n=6) 50 mg CTI-1601 (n=7) 100 mg CTI-1601 (n=7) All CTI-1601 (n=20) Overall (n=27) Age at Symptom Onset Mean 14.1 24.0 19.3 11.9 18.1 17.1 SD 5.34 14.48 6.21 6.72 10.37 9.39 Median 15.0 18.0 19.0 10.0 18.
Slide 28: Data Compare Favorably to FXN Levels Expected in Heterozygous Carriers
Data Compare Favorably to FXN Levels Expected in Heterozygous Carriers Achieved median FXN levels that were >60% of the median FXN levels observed in healthy controls FXN* Levels By Dose Group (Buccal Cells) Baseline Day 4/7 Day 13 *FXN levels measured via detection of peptide derived from mature FX
Slide 29: Repeated Subcutaneous Injections of CTI-1601 Generally Well Tolerated in Phase 1 MAD Trial
Repeated subcutaneous injections of CTI-1601 were generally well tolerated in Phase 1 MAD trial Summary of MAD trial safety data: Repeated doses (25 mg, 50 mg, and 100 mg) of CTI-1601 or placebo were administered subcutaneously. No serious adverse events (SAEs), important medical events, or treatmen
Slide 30: Summary of MAD Trial PK Analyses
Summary of MAD Trial PK Analyses CTI-1601 was quickly absorbed after subcutaneous administration Dose-proportional increases in exposure observed with increasing doses of CTI-1601 Mean half life of CTI-1601 in plasma was approximately 11 hours CTI-1601 appeared to be at or close to steady state expo
Slide 31: FDA Cleared Phase 2 Study Initiation Following Review of Data
FDA cleared Phase 2 study’s initiation following review of clinical and non-clinical data SUMMARY OF MULTIPLE-ASCENDING DOSE (MAD) TRIAL SAFETY DATA Repeated SC injections of CTI-1601 appear to be generally well tolerated at doses up to 100 mg administered daily for 13 days. No serious adverse event
Slide 32: Additional Phase 2 Cohort Data
Additional Phase 2 Cohort 1 Data
Slide 33: Demographics of Phase 2 (Cohort 1)
Demographics of Phase 2 (Cohort 1) Demographics similar between Phase 1 and Phase 2 trials of CTI-1601 Parameter, n (%) Placebo (N=4) CTI-1601 25 mg (N=9) Overall (N=13) Mean Age (SD) (Years) 34.0 (9.20) 37.8 (14.93) 36.6 (13.16) Male 2 (50.0%) 5 (55.6%) 7 (53.8%) White 4 (100.0%) 8 (88.9%) 12 (92.3
Slide 34: Disease Characteristics (Phase 2 Cohort 1)
Disease Characteristics (Phase 2 Cohort 1) Parameter Statistic Placebo (N=4) CTI-1601 (n=9) Overall (n=13) Age at Symptom Onset (years) n 4 8 12 Mean (SD) 14.5 (4.93) 13.0 (10.47) 13.5 (8.77) Median 14.5 10.0 11.0 Q1, Q3 11, 19 8, 13 9, 15 Min, Max 9, 20 5, 38 5, 38 Age at Diagnosis (years) n 4 9 13
Slide 35: Summary of Phase 2 Trial Safety Data (25 mg Cohort)
Summary of Phase 2 trial safety data (25 mg cohort): 25 mg CTI-1601 or placebo were administered subcutaneously daily for 14 days and then every other day until day 28. 13 participants were dosed in the trial (9 active, 4 placebo). Of the 9 CTI-1601-treated participants, 8 completed the trial with 1
Slide 36: Top-line Results from Non-interventional Study
Top-line Results from Non-interventional Study Recently completed non-interventional study (CLIN-1601-002) measured FXN in homozygous HVs FXN concentrations were measured1 in skin and buccal cells from 60 homozygous healthy volunteers: Median FXN in Skin = 16 pg/µg Median FXN in Buccal cells = 8 pg/
Slide 37: Preclinical Data
Preclinical Data
Slide 38: CTI-1601: Positive Mouse Model Data Support Development
CTI-1601: Positive Mouse Model Data Support Development Cardiac Knock Out Mouse Model Studies (MCK-Cre FXN KO Mouse) Proof-of-Concept Demonstrated In Mouse Models of FA Neurologic Knock Out Mouse Model Study (Pvalb-CRE FXN KO Mouse) Extended survival Prevented development of ataxic gait Demonstrated
Slide 39: CTI-1601 Extends Survival in FXN-deficient KO Mice
CTI-1601 Extends Survival in FXN-deficient KO Mice Median Survival of MCK-Cre FXN-KO Mice 166 days (CTI-1601) vs. 98 days (Vehicle) CTI-1601 was administered 10 mg/kg SC every other day Survival beyond vehicle mean (107.5 days) 87.5% (CTI-1601) vs. 33% (Vehicle) Demonstrates that CTI-1601 is capable
Slide 40: In-Vivo Efficacy Data in Neurologic KO Mouse Model
Pvalb-Cre FXN-KO mouse Single dose level: 10 mg/kg CTI-1601 or vehicle given intraperitoneally three times per week hFXN replacement with CTI-1601 prevents the development of ataxic gait CTI-1601-treated mice survive longer than untreated mice Human frataxin present in brain, dorsal root ganglia and
Slide 41: CTI-1601 Delivers hFXN to Mitochondria in KO Mice
CTI-1601 Delivers hFXN to Mitochondria in KO Mice hFXN concentration within mitochondria increases in a dose-dependent manner Given subcutaneously, CTI-1601 functionally replaces hFXN in mitochondria of KO mice Succinate dehydrogenase (SDH) activity, which is indicative of mitochondrial function, in
Slide 42: CTI-1601 Prevents Left Ventricle Dilation in KO Mice
CTI-1601 Prevents Left Ventricle Dilation in KO Mice Left ventricular (LV) volume increases in systole in untreated mice by 8 weeks (after 4 weeks of dosing with vehicle), but remains similar to wildtype when treated with CTI-1601 (10 mg/kg every other day) CTI-1601-treated mice have similar LV volu
Slide 43: CTI-1601 Preserves Left Ventricle Function in KO Mice
CTI-1601 Preserves Left Ventricle Function in KO Mice Left ventricular (LV) function drops significantly in vehicle treated mice by week 8 CTI-1601-treated (10 mg/kg every other day) mice have similar LV as healthy controls; echocardiogram shows significant differences between vehicle and CTI-1601 t
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