Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Investor Presentation (March 2024)
47 slides from Larimar Therapeutics's investor presentation, Mar 11, 2024
Slide 1: Larimar Therapeutics Corporate Deck
March 2024 Larimar Therapeutics Corporate Deck
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: Positive Topline Phase 2 Data for Nomlabofusp (CTI-1601)
Positive Topline Phase 2 Data for Nomlabofusp (CTI-1601) Dose-dependent increases in tissue frataxin (FXN) levels in skin and buccal cells Participants treated with 50 mg daily for 14 days and then every other day for an additional 14 days until day 28 Nomlabofusp was generally well-tolerated follow
Slide 4: Clinical-Stage Novel Protein Replacement Therapy Platform
Clinical-Stage Novel Protein Replacement Therapy Platform Lead candidate nomlabofusp (CTI-1601) is a recombinant fusion protein designed to directly address frataxin deficiency in patients with Friedreich's ataxia (FA) by delivering the protein to mitochondria. Granted Orphan Drug (US & EU), Rare Pe
Slide 5: Larimar Technology is Supported by a Strong IP Portfolio
2015 2020 2030 2035 2040 2045 2050 2055 2010 2025 Nomlabofusp 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 Technology is Supported by
Slide 6: Friedreich's Ataxia (FA): A rare and progressive disease
Friedreich’s Ataxia (FA): A rare and progressive disease 6 * E.C. Deutsch et al. Molecular Genetics and Metabolism 101 (2010) 238–245. Most patients with FA only produce ~20-40% of normal frataxin levels depending on the tissue, sampling technique, and assay considered* Genetic defect on both allele
Slide 7: Nomlabofusp is Designed to Deliver Additional Frataxin
Nomlabofusp is Designed to Deliver Additional Frataxin 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 NOMLABOFUSP Cleavage by mitochondrial processin
Slide 8: FXN Levels Predict Disease Progression in FA
FXN Levels Predict 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 (Y
Slide 9: Phase 2 Dose Exploration Study for 25 and 50 mg Cohorts
Phase 2 Dose Exploration Study for 25 and 50 mg Cohorts Goal: Further characterize PK/PD and assess safety to inform long-term dose and dose regimen Treatment Schedule - nomlabofusp (CTI-1601) or placebo 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
Slide 10: Dose-Dependent Increase in FXN Levels in Skin Cells
Dose-Dependent Increase in FXN Levels in Skin Cells Skin Cells FXN Levels* Change from Baseline** FXN Levels* in Skin Cells Change from Baseline at Day 14 Participants dosed daily for 14 days, then every other day until day 28 *FXN levels measured via detection of peptide derived from mature FXN; FX
Slide 11: Dose-Dependent Increase in FXN Levels in Buccal Cells
Dose-Dependent Increase in FXN Levels in Buccal Cells Buccal Cells FXN Levels* Change from Baseline** FXN Levels* in Buccal Cells Change from Baseline at Day 14 Participants dosed daily for 14 days, then every other day until day 28 *FXN levels measured via detection of peptide derived from mature F
Slide 12: Absolute Increases in Skin FXN Levels
Absolute Increases in Skin FXN Levels Day 14 Skin FXN Levels Dose Visit Absolute Values (pg/µg) Median Mean 25 mg Baseline 3.70 3.38 Day 14 5.53 6.40 Change from Baseline 2.81 3.02 50 mg Baseline 2.12 2.08 Day 14 7.40 7.32 Change from Baseline 5.57 5.24 Dose response in tissue FXN concentrations and
Slide 13: Absolute Increases in Buccal FXN Levels
Absolute Increases in Buccal FXN Levels Day 14 Buccal FXN Levels Dose Visit Absolute Values (pg/µg) Median Mean 25 mg Baseline 1.78 1.80 Day 14 2.24 2.22 Change from Baseline 0.56 0.42 50 mg Baseline 1.61 1.69 Day 14 2.44 2.38 Change from Baseline 0.72 0.69 Dose response in tissue FXN concentrations
Slide 14: Skin Cell FXN Levels Achieve Higher % of Healthy Volunteers
Skin Cell FXN Levels Achieve Higher % of Healthy Volunteers* Following 14 days of Daily Nomlabofusp Only participants with quantifiable levels at baseline and day 14 are included in the figures. *% of healthy volunteer FXN level is calculated by dividing each participant's FXN level by the average F
Slide 15: Buccal Cell FXN Levels Achieve Higher % of Healthy Volunteers
Buccal Cell FXN Levels Achieve Higher % of Healthy Volunteers* Following 14 days of Daily Nomlabofusp Only participants with quantifiable levels at baseline and day 14 are included in the figures. *% of healthy volunteer FXN level is calculated by dividing each participant's FXN level by the average
Slide 16: Increasing FXN Levels May Slow Disease Progression
Increasing FXN Levels May Slow Disease Progression *FARS: Friedreich’s ataxia rating scale, measures disease progression with a higher score indicating a greater level of disability. **FXN levels measured in peripheral blood mononuclear cells (PBMCs). FXN levels as measured by % of normal demonstrat
Slide 17: Encouraging Therapeutic Potential for Nomlabofusp
Encouraging Therapeutic Potential for Nomlabofusp Continue nomlabofusp clinical development Dose-dependent increases in frataxin levels with nomlabofusp in several studies Frataxin deficiency is the root cause of the disease Lower levels of frataxin correlate with disease burden Animal models show t
Slide 18: Nomlabofusp: Predictable Pharmacokinetics
Nomlabofusp: Predictable Pharmacokinetics Quick absorption after subcutaneous administration 1 2 3 Dose-proportional increases in exposure observed cc Pharmacokinetic profile consistent with Phase 1 studies
Slide 19: Ph1 & Ph2 Data: Nomlabofusp is Generally Well Tolerated
Ph1 & Ph2 Data: Nomlabofusp is Generally Well Tolerated 44 of 46 clinical trial participants dosed with nomlabofusp completed their respective study One Phase 2 participant in the 25 mg cohort withdrew due to allergic reaction that resolved with standard treatment One Phase 1 participant in the 50 m
Slide 20: Open-label Extension Study
Open-label Extension Study: Dosed first patient in Q1 2024 Preliminary interim data expected in Q4 2024 Key Eligibility Criteria Previous participation in Phase 1 or Phase 2 trials Key Study Objectives Safety and tolerability Long-term PK Tissue FXN concentrations and potential use as surrogate endp
Slide 21: Nomlabofusp Clinical Development Plan
Nomlabofusp Clinical Development Plan Planned global double-blind placebo-controlled registration/confirmatory study** Plan to include pediatric patients 2 to 17 years of age in clinical development* Intend to pursue accelerated approval pathway with potential BLA submission targeted for 2H 2025 *Co
Slide 22: Nomlabofusp is a Competitively Differentiated Treatment Approach
Nomlabofusp is a Competitively Differentiated Treatment Approach* *Competitive landscape focuses on clinical-stage, industry-sponsored programs from public companies Acquisition supports the robust market potential for FA treatments Nomlabofusp is a potential first-and-only protein replacement thera
Slide 23: Regulatory Updates
Regulatory Updates Q1 2024: Dosed first patient in OLE study Q4 2024: Initial data from OLE study 2H 2024: Final Phase 2 data planned to be presented at a conference 2H 2025: BLA submission 2024/2025 Milestones Consistent Ph 1 and Ph 2 Findings Initiated discussions with FDA regarding use of FXN as
Slide 24: Clinical-Stage Novel Protein Replacement Therapy Platform
Clinical-Stage Novel Protein Replacement Therapy Platform Lead candidate nomlabofusp (CTI-1601) is a recombinant fusion protein designed to directly address frataxin deficiency in patients with Friedreich's ataxia (FA) by delivering the protein to mitochondria. Granted Orphan Drug (US & EU), Rare Pe
Slide 25: Thank You
THANK YOU Larimar Therapeutics March 2024 Corporate Deck
Slide 26: Appendix
Appendix Larimar Therapeutics
Slide 27: 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 28: 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 29: Mitochondrial Localization and Preclinical Data
Mitochondrial Localization and Preclinical Data
Slide 30: Nomlabofusp Transduction of Cells In Vitro Leads to hFXN Located in Mitochondria
Nomlabofusp Transduction of Cells In Vitro Leads to hFXN Located in Mitochondria FXN DAPI TOMM20 DAPI FXN TOMM20 DAPI FXN co-localizes with TOMM20 FXN staining TOMM20 (mitochondria) staining Rat cardiomyocytes (H9C2) were transduced with nomlabofusp Cells were fixed and analyzed by immunofluorescenc
Slide 31: Nomlabofusp Extends Survival in FXN-deficient KO Mice
Nomlabofusp Extends Survival in FXN-deficient KO Mice Median survival of MCK-Cre FXN-KO mice 166 days (nomlabofusp) vs. 98 days (Vehicle) Nomlabofusp administered 10 mg/kg SC every other day Survival beyond vehicle mean (107.5 days) 87.5% (nomlabofusp) vs. 33% (Vehicle) Demonstrates that nomlabofusp
Slide 32: Nomlabofusp Prevents Development of Ataxic Gait in Neurologic KO Mouse Model
Nomlabofusp Prevents Development of Ataxic Gait in Neurologic KO Mouse Model hFXN replacement with nomlabofusp prevents development of ataxic gait Nomlabofusp-treated mice survive longer than untreated mice Human frataxin present in brain, dorsal root ganglia and spinal cord demonstrating central ne
Slide 33: Nomlabofusp Delivers hFXN to Mitochondria and Restores SDH Activity
Nomlabofusp Delivers hFXN to Mitochondria and Restores SDH Activity in KO Mice Mitochondria hFXN concentration increases dose-dependently Given subcutaneously, nomlabofusp functionally replaces hFXN in mitochondria of KO mice MPK = mg/kg MPK = mg/kg Mitochondrial FXN (Heart) SDH Activity (Muscle) Su
Slide 34: Nomlabofusp Prevents Left Ventricle Dilation in KO Mice
Nomlabofusp 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 nomlabofusp (10 mg/kg every other day) Diameter (mm) Age in Weeks Age in We
Slide 35: Nomlabofusp Preserves Left Ventricle Function in KO Mice
Nomlabofusp Preserves Left Ventricle Function in KO Mice Percent Change Age in Weeks Left Ventricle Ejection Function Left Ventricle Fractional Shortening Percent Change Age in Weeks KO: CTI-1601 Wild-type: Vehicle KO: Vehicle Study Design – Cardiac and skeletal muscle FXN knockout mice (MCK-CRE) we
Slide 36: Phase 1 Clinical Data
Phase 1 Clinical Data O\.
Slide 37: 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 38: Completed Phase 1 Multiple Ascending Dose Study
Completed Phase 1 Multiple Ascending Dose Study Treatment Schedules for Each Cohort- nomlabofusp (CTI-1601) or placebo 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 nomlabofusp or placebo = No Administration 13-day Treatment Period Cohort 1 (25
Slide 39: 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 40: 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 41: 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 42: 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 43: Phase 2 Demographic/Disease Characteristics Data
Phase 2 Demographic/ Disease Characteristics Data
Slide 44: Demographics – Phase 2 Trial
Demographics – Phase 2 Trial 25 mg Cohort 50 mg Cohort Placebo N = 4 Nomlabofusp N = 9 Overall N = 13 Placebo N = 5 Nomlabofusp N = 10 Overall N = 15 Age at Screening (Years) Mean (SD) 34.0 (9.20) 37.8 (14.93) 36.6 (13.16) 28.6 (4.67) 28.1 (11.00) 28.3 (9.17) Median 33 31 31 27 24 26 Q1, Q3 27, 42 2
Slide 45: Disease Characteristics – Phase 2 Study
Disease Characteristics – Phase 2 Study 25 mg Cohort 50 mg Cohort Placebo N = 4 Nomlabofusp N = 9 Overall N = 13 Placebo N = 5 Nomlabofusp N = 10 Overall N = 15 Age at Symptom Onset (Years) Mean (SD) 14.5 (4.93) 13.0 (10.47) 13.5 (8.77) 15.2 (7.26) 13.7 (8.37) 14.2 (7.78) Median 14.5 10 11 14 12.5 1
Slide 46: Non-Interventional Study Data
Non-Interventional Study Data
Slide 47: CLIN-1601-002: Top-line Non-interventional Study Results
CLIN-1601-002: Top-line Non-interventional Study Results 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 clinical trials of nomlab
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