Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Investor Presentation (August 2023)
44 slides from Larimar Therapeutics's investor presentation, Aug 14, 2023
Slide 1: Larimar Therapeutics Corporate Presentation
August 2023 Larimar Therapeutics Corporate Presentation Exhibit 99.1
Slide 2: 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 historical fact are forward-look
Slide 3: Investment Highlights
Investment Highlights Clinical-stage biotechnology company focused on addressing unmet needs in Friedreich's ataxia (FA) and potentially other complex rare diseases based on a platform technology backed by a strong intellectual property portfolio Lead candidate CTI-1601 is a recombinant fusion prote
Slide 4: Recent Progress Advances Long-Term Dosing OLE and Phase 2 Dose Escalation
Recent Progress Advances Long-Term Dosing Open Label Extension, and Phase 2 Dose Escalation of CTI-1601 for FA Second cohort evaluating 50 mg in Phase 2 trial Assesses long-term safety, PK, frataxin levels, efficacy outcomes and self-administration Enables the comparison of clinical function with a
Slide 5: Larimar Technology is Supported by a Strong IP Portfolio
2015 2020 2030 2035 2040 2045 2050 2055 2010 2025 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 pending Expiration July 2040 Composition of Matter Patent Larimar Te
Slide 6: Friedreich's Ataxia: Caused by low frataxin levels
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 7: FXN Levels Determine Disease Progression in FA
FXN Levels Determine Disease Progression in FA Lower FXN levels are associated with earlier onset of disease, faster rate of disease progression, and shorter time to loss of ambulation Adapted from H.L.Plasterer et al. PLoS ONE 2013 8(5):e63958 Age of Onset (Years) Median Time to Loss of Ambulation
Slide 8: 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 9: Completed Phase 1 Multiple Ascending Dose Study Treatment Schedules
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 10: Dose Dependent Increases in FXN Levels 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 11: Phase 2 Dose Exploration Study Advancing to 50 mg Cohort
Phase 2 Dose Exploration Study Advancing to 50 mg Cohort 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
Slide 12: Increases in FXN Levels in Phase 2 Trial's 25 mg Cohort
Increases in FXN Levels in Phase 2 Trial’s 25 mg Cohort Skin Cells FXN* Change from Baseline** Median placebo-adjusted increase from baseline of 3.5 pg/µg with 14 days daily dosing *FXN levels measured via detection of peptide derived from mature FXN; FXN concentrations are normalized to total cellu
Slide 13: CLIN-1601-002: Top-line Non-interventional Study Results
CLIN-1601-002: Top-line Non-interventional Study Results Recently completed non-interventional study measured FXN in homozygous healthy volunteers FXN concentrations were measured in skin and buccal cells from 60 homozygous healthy volunteers utilizing the same sampling technique and assay as clinic
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: Open-label Extension Trial: Initiation Expected in Q1 2024
Open-label Extension Trial: Initiation Expected in Q1 2024 Preliminary interim data expected in Q4 2024 Screening Period ≤ 42 days Key Eligibility Criteria Previous participation in Phase 1 or Phase 2 trials Subcutaneous Injections of 25 mg CTI-1601 Treatment Period: Planned for ≥ 1 year with any ne
Slide 16: CTI-1601 Clinical Development Plan
CTI-1601 Clinical Development Plan Ongoing and Planned Trials* Include: Global double-blind placebo-controlled pivotal trial*** Open-label extension trial with 25 mg daily dosing for eligible patients who participated in SAD, MAD, and/or four-week dose exploration studies. Initiation expected Q1 202
Slide 17: CTI-1601 is a Competitively Differentiated FA Treatment Approach
CTI-1601 is a Competitively Differentiated FA Treatment Approach* *Competitive landscape focuses on clinical-stage, industry-sponsored programs Pending acquisition supports the robust market potential for FA treatments CTI-1601 is a potential first-and-only protein replacement therapy designed to ad
Slide 18: Regulatory Updates and Expected Milestones
Regulatory Updates Q3 2023: Initiation of 50 mg cohort in Phase 2 dose exploration trial Q1 2024: Initiation of open-label extension trial 1H 2024: Top-line data from Phase 2 trial’s 50 mg cohort Q4 2024: Interim data from open-label extension trial Expected Milestones CTI-1601 Phase 2 dose explorat
Slide 19: Investment Highlights
Investment Highlights Clinical-stage biotechnology company focused on addressing unmet needs in Friedreich's ataxia (FA) and potentially other complex rare diseases based on a platform technology backed by a strong intellectual property portfolio Lead candidate CTI-1601 is a recombinant fusion prote
Slide 20: Thank You
THANK YOU Larimar Therapeutics August 2023 Corporate Update
Slide 21: Appendix
Appendix Larimar Therapeutics
Slide 22: Scientific Advisory Board
Scientific Advisory Board Co-founder of Chondrial Therapeutics, which became Larimar Therapeutics, Inc. Professor of Pediatrics at Indiana University School of Medicine Mark Payne, MD Executive Director of the Mitochondrial Medicine Frontier Program at The Children’s Hospital of Philadelphia (CHOP)
Slide 23: 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 24: Additional Phase 1 Data
Additional Phase 1 Data O\.
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: Completed Phase 1 Multiple Ascending Dose Study Treatment Schedules
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 27: Dose Dependent Increases in FXN Levels 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 28: 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 29: 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 30: Repeated subcutaneous injections of CTI-1601 were generally well tolerated in Phase 1 MAD
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 31: 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 32: Additional Phase 2 Cohort Data
Additional Phase 2 Cohort 1 Data
Slide 33: Phase 2 Dose Exploration Study Advancing to 50 mg Cohort
Phase 2 Dose Exploration Study Advancing to 50 mg Cohort 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
Slide 34: Increases in FXN Levels Observed in Skin Cells
Increases in FXN Levels Observed in Skin Cells 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; Data
Slide 35: 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 36: 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 37: 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 38: 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 39: Preclinical Data
Preclinical Data
Slide 40: 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 41: 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 42: 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 43: 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 44: 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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