Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Investor Presentation (January 2025)
59 slides from Larimar Therapeutics's investor presentation, Jan 10, 2025
Slide 1: Larimar Therapeutics Corporate Deck
pro January 2025 Larimar Therapeutics Corporate Deck 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: 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 4: 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 5: Friedreich's Ataxia (FA): A rare and progressive disease
Friedreich’s Ataxia (FA): A rare and progressive disease 5 * 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 6: 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 7: 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 8: Completed Phase 2 Dose Exploration Study
Completed Ph 2 Dose Exploration Study (25 & 50 mg Cohorts) Goal: Further characterize PK/PD and assess safety to inform long-term dose and dose regimen 28-day Treatment Period - nomlabofusp (CTI-1601) or placebo 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 = Subcutaneou
Slide 9: 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 10: 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 11: 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 12: 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 13: Gene Expression and Lipid Data Presented at the International Congress for Ataxia Research
Gene Expression and Lipid Data Presented at the International Congress for Ataxia Research, November 2024
Slide 14: Increase Towards Normal Gene Expression in Adults with FA
Increase Towards Normal Gene Expression in Adults with FA* Observed After Nomlabofusp Treatment Select Baseline Gene Expression Patients with FA* vs. Healthy Volunteers (HV)** Post-treatment Changes in Gene Expression From Baseline Data presented at the International Congress for Ataxia Research, No
Slide 15: Decrease Towards Normal Lipid Profiles in Adults with FA
Decrease Towards Normal Lipid Profiles in Adults with FA* Observed After Nomlabofusp Treatment *Samples from Phase 2 dose exploration study evaluating nomlabofusp 25 mg (Cohort 1) and 50 mg (Cohort 2) or placebo via subcutaneous injection daily for 14 days followed by alternate day administration fo
Slide 16: Nomlabofusp Long-term Open Label Extension Study
Nomlabofusp Long-term Open Label Extension Study
Slide 17: Open-label Extension: 25 mg Completed, Increasing to 50 mg Daily
Open-label Extension: 25 mg Completed, Increasing to 50 mg Daily Key Eligibility Criteria Previous participation in Phase 1 or Phase 2 trials Key Study Objectives Safety and tolerability Long-term PK Tissue FXN concentrations Clinical efficacy measures compared to FACOMS* database once enrollment is
Slide 18: Positive Initial Data from Long-Term OLE Study in FA
Positive Initial Data from Long-Term OLE Study in FA FA: Friedreich’s ataxia; OLE: Open-label extension; HV: Healthy volunteers; FXN: Frataxin Daily 25 mg nomlabofusp administered in 14 participants for up to 260 days Generally well tolerated for over 8 months SAEs occurred in two study participants
Slide 19: Increased FXN Levels in Skin Cells Sustained Over Time
Increased FXN Levels in Skin Cells Sustained Over Time Skin Cells - Absolute FXN Levels Participants dosed daily with 25 mg nomlabofusp for up to 90 days Skin Cells - FXN Levels Change from Baseline FXN levels measured via detection of peptide derived from mature FXN; FXN concentrations are normaliz
Slide 20: Increased FXN Levels in Buccal Cells Sustained Over Time
Increased FXN Levels in Buccal Cells Sustained Over Time Participants dosed daily with 25 mg nomlabofusp for up to 90 days and reached steady state by 30 days Buccal Cells - Absolute FXN Levels Buccal Cells - FXN Levels Change from Baseline FXN levels measured via detection of peptide derived from m
Slide 21: Observed Increases in Tissue FXN Levels in OLE Comparable to Phase 2
Open Label Extension Buccal FXN levels (pg/μg) Skin FXN levels (pg/μg) n Median Mean n Median Mean Baseline 11 1.13 1.19 8 2.41 2.60 Day 30 11 2.08 3.62 8 5.34 7.45 Change from Baseline 11 0.58 2.43 8 2.42 4.85 Day 60 9 2.46 2.41 Change from Baseline 9 0.53 1.13 Day 90 6 1.89 2.48 5 7.65 11.73 Chang
Slide 22: Tissue FXN Levels are Higher as a % of Healthy Volunteers at Day 90
Tissue FXN Levels are Higher as a % of Healthy Volunteers at Day 90 30% at Day 90 (18.68 min, 53.18 max) 15% at baseline (5.30 min, 26.67 max) Mean % of healthy volunteers Buccal FXN Levels 72% at Day 90 (43.86 min, 160.61 max) 16% at baseline (9.33 min, 24.48 max) Skin FXN Levels Mean % of healthy
Slide 23: Observed Trends Towards Improvement in Clinical Outcomes at Day 90
Observed Trends Towards Improvement in Clinical Outcomes at Day 90 After Daily 25 mg Nomlabofusp Visit Statistic mFARS 93-Point Scale FARS-ADL 36-Point Scale Modified Fatigue Impact Scale 84-Point Scale 9 Hole Peg Test Dominant Hand Time (Seconds) N = 8 N = 8 N = 8 N = 8 Baseline Mean (SD) 55.81 (13
Slide 24: Nomlabofusp: Predictable Long-Term Pharmacokinetics
Nomlabofusp: Predictable Long-Term Pharmacokinetics Rapid absorption after subcutaneous administration 1 2 Nomlabofusp reached steady state in plasma by Day 30 with no further accumulation 3 Pharmacokinetic profile consistent with Phase 1 and Phase 2 studies
Slide 25: Nomlabofusp 25 mg Daily is Generally Well-Tolerated for Up to 260 Days
14 participants with FA were included in the safety data OLE Study: Nomlabofusp 25 mg Daily is Generally Well-Tolerated for Up to 260 Days One additional participant started dosing after the data cut and one additional participant is scheduled for dosing before year-end 2024 Two participants withdre
Slide 26: Totality of Data Supports Potential to Slow Disease Progression
Totality of Data to Date Supports that Nomlabofusp has the Potential to Slow Disease Progression FDA alignment that FXN deficiency appears to be the pathogenic mechanism of FA Dose dependent increases in FXN levels that were maintained over time Addresses underlying deficiency Displays functional ac
Slide 27: Nomlabofusp Clinical Development Program
Nomlabofusp Clinical Development Program Planned global double-blind placebo-controlled confirmatory/registration study on track to initiate mid- 2025* Pediatric PK run-in study initiated in adolescents (12-17 yrs), followed by children (2-11 yrs) in 1H 2025 Intend to pursue accelerated approval pat
Slide 28: Updates for Nomlabofusp Development Program
Updates for Nomlabofusp Development Program* *Approximately $204 Million in cash @ 9/30/24, providing projected cash runway into Q2 2026 FA: Friedreich’s ataxia; OLE: Open-label extension; BLA: Biologics License Application Six participants receiving 50 mg daily as of 12/16/24 Increasing dose in oth
Slide 29: 2025 Milestones
Q1 2025: Dose adolescents (ages 12-17 years old) in pediatric run-in study 1H 2025: Initiate PK run-in study in children (ages 2-11 years old) Mid 2025: Initiate global confirmatory/registration study Mid 2025: Data from 50 mg dose in OLE study 2H 2025: BLA submission; intend to pursue accelerated a
Slide 30: Appendix
Appendix Larimar Therapeutics
Slide 31: 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 32: Mitochondrial Localization and Preclinical Data
Mitochondrial Localization and Preclinical Data
Slide 33: 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 34: 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 35: 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 36: 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 37: 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 38: 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 39: Phase 1 Clinical Data
Phase 1 Clinical Data o \.
Slide 40: 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 41: 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 42: Dose Dependent Increases in FXN Levels Observed 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 43: 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 44: 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 45: 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 46: Additional Phase 2 Dose Exploration Data
Additional Phase 2 Dose Exploration Data
Slide 47: 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 48: 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 49: 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 50: Additional Phase 1 and 2 Data Presented at the International Congress for Ataxia Research
Additional Phase 1 and 2 Data Presented at the International Congress for Ataxia Research, November 2024
Slide 51: Clinical Studies Included a Broad, Representative Population of Adults with FA
Nomlabofusp Clinical Studies Included a Broad, Representative Population of Adults with FA N* Median Mean Min Max Age 61 28.0 31.9 19 69 Age of Onset 61 15.0 15.9 5 60 Age of Diagnosis 61 19.0 21.0 5 64 Shorter GAA (GAA1) 60 550.0 555.8 99 1000 Longer GAA (GAA2) 60 900.0 890.2 265 1300 Frataxin, % o
Slide 52: Pooled Data Confirms Disease and FXN Relationships Consistent with Literature
Pooled Data from Completed Phase 1 & 2 Studies Confirms Disease & FXN Relationships are Consistent with Literature Quartile FXN Concentration* (pg/mcg) Age at Symptom Onset** Age at Diagnosis** GAA1** GAA2** Q1 (N=14) < 1.31 10.5 14.5 616.5 899.5 Q2 (N=14) 1.31 - <1.95 13.5 23.0 486.0 866.0 Q3 (N=14
Slide 53: Modeling/Simulation Predicts 50mg Daily Can Achieve Skin FXN Levels
Modeling/Simulation Predicts* 50mg Daily Can Achieve Skin FXN Levels ≥50% of Healthy Controls in Most Patients Dashed red line – 50% the average skin FXN/protein ratio (8.17 pg/ug) in a non-interventional study in healthy controls (HC) Blue line – median of simulated values across trials Red lines –
Slide 54: Non-Interventional Study Data
Non-Interventional Study Data
Slide 55: 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
Slide 56: FDA START Pilot Program
FDA START Pilot Program o \.
Slide 57: Nomlabofusp Selected by FDA for START Pilot Program
Nomlabofusp Selected by FDA for START Pilot Program Highlights FDA commitment to augment formal meetings with more rapid, ad-hoc communications to accelerate program development of rare diseases START Pilot Program Support for Clinical Trials Advancing Rare Disease Therapeutics A new milestone-drive
Slide 58: FARA
FARA
Slide 59: Strong Relationship with FARA – TRACK-FA Neuroimaging Consortium
Strong Relationship with FARA – Joined FARA’s TRACK-FA Neuroimaging Consortium as an Industry Partner 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 recrui
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