Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Corporate Update (September 2022)
31 slides from Larimar Therapeutics's corporate update, Sep 14, 2022
Slide 1: Corporate & Clinical Update
Exhibit 99.2 Larimar Therapeutics Corporate & Clinical Update September 14, 2022 1
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: CTI-1601 Cleared for Return to Clinic
Investment Highlights: CTI-1601 Cleared for Return to Clinic Clinical-stage biotechnology company with a novel protein replacement therapy platform Focused on addressing unmet needs in Friedreich's ataxia (FA) and other complex rare diseases based on a platform technology backed by a strong intellec
Slide 4: Friedreich's Ataxia (FA): Rare and Progressive Disease
Friedreich’s Ataxia (FA) Rare and Progressive Disease Caused by genetic defect resulting in low levels of frataxin • Patients with FA only produce ~20-40% of normal frataxin levels depending on the 1 tissue, sampling technique, and assay considered • Affects ~20,000 patients globally, with ~5,000 pa
Slide 5: CTI-1601 is Designed to Deliver Additional Frataxin (FXN)
CTI-1601 is Designed to Deliver Additional Frataxin (FXN) CTI-1601 maintains the cleavage site between the MTS and mature human FXN STRUCTURE OF CTI-1601 STRUCTURE OF ENDOGENOUS FXN Mitochondrial Targeting Mature Mitochondrial Targeting Mature Sequence (MTS) Human FXN Sequence (MTS) Human FXN Cleava
Slide 6: Upcoming Phase 2, Four-week Dose Exploration Study
Upcoming 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 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 = Administration of CTI-1601 or placeb
Slide 7: Completed Multiple Ascending Dose Study Treatment Schedules
Completed Multiple Ascending Dose Study Treatment Schedules for Each Cohort Cohort 1 (25 mg; n = 8) Cohort 2 (50 mg; n = 9) Cohort 3 (100 mg n = 10) 13-day Treatment Period 13-day Treatment Period 13-day Treatment Period 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7
Slide 8: Dose Dependent Increases in FXN Levels Observed in Buccal Cells
Dose Dependent Increases in FXN Levels Observed in Buccal Cells FXN* Levels By Dose Group FXN* Change from Baseline By Dose Group (Buccal Cells) (Buccal Cells) Baseline Day 4/7 Day 13 Day 4/7 Day 13 th th *FXN levels measured via detection of peptide derived from mature FXN; Data represent median an
Slide 9: 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 Benchmarking Clinical Relevance (Buccal Cells) • FXN levels in buccal cells and blood have been shown to co
Slide 10: Clinical & Non-clinical Safety Data Support Phase 2 Initiation
Clinical & Non-clinical Safety Data Support Initiation of the 4-Week, Phase 2 Dose Exploration Study’s 25 mg Cohort 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
Slide 11: Upcoming CTI-1601 Trials
Upcoming CTI-1601 Trials Future Planned Trials Include: Phase 2, four-week dose Jive OLE trial for eligible patients MAD trial in patients 2 to 17 Global double-blind exploration study intended who participated in SAD, MAD, years of age. Participants placebo-controlled pivotal trial. to identify dos
Slide 12: Summary: CTI-1601 Advancing to Phase 2 Trial
Summary: CTI-1601 Advancing to Phase 2 Trial Designed to address the root cause of Friedreich’s ataxia by delivering CTI-1601 mature FXN to mitochondria. Daily dosing of 50 mg or 100 mg of CTI-1601 for at least 7 days resulted in buccal cell Clinical POC Data FXN levels that met or exceeded those ex
Slide 13: Thank You
Larimar Therapeutics Corporate & Clinical Update THANK YOU 13
Slide 14: Appendix
Larimar Therapeutics Appendix 14
Slide 15: Platform Technology is Supported by a Strong IP Portfolio
Platform Technology is Supported by a Strong IP Portfolio Pending CTI-1601 patent application, if issued, extends IP into 2040 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 Expiration TAT-MTS-FXN Composition of Matter (broad coverage of CTI-1601) October 2024 US 9,045,552 (Exclusive license from
Slide 16: Phase 1 Top-line Data Demonstrated POC for CTI-1601 in FA
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 Safety administered daily for 13 days Daily dosing of CTI-1601 resulted in dose-dependent increases in FXN levels from Pharmacodynamics baseline compared to placebo control
Slide 17: CTI-1601: Phase 1 Clinical Program in Patients with FA
CTI-1601: Phase 1 Clinical Program in Patients with FA Program consisted of double-blind, placebo controlled single- and multiple-ascending dose trials Phase 1 Development Plan • Two double-blind, placebo-controlled dosing trials in patients with FA • Patient dosing began December 2019 • Safety Revi
Slide 18: MAD Trial Patient Demographics
MAD Trial Patient Demographics 25 mg 50 mg 100 mg All All placebo Overall Parameter Statistic CTI-1601 CTI-1601 CTI-1601 CTI-1601 (n=7) (n=27) (n=6) (n=7) (n=7) (n=20) Sex 4 ( 57.1) 3 ( 42.9) 10 ( 50.0) 15 (55.6) Male n (%) 5 (71.4) 3 ( 50.0) Female n (%) 2 (28.6) 3 ( 50.0) 3 ( 42.9) 4 ( 57.1) 10 (
Slide 19: MAD Trial Patient Disease Characteristics
MAD Trial Patient Disease Characteristics 25 mg 50 mg 100 mg All All placebo Overall Parameter Statistic CTI-1601 CTI-1601 CTI-1601 CTI-1601 (n=7) (n=27) (n=6) (n=7) (n=7) (n=20) Age at Symptom Onset 14.1 24.0 19.3 11.9 18.1 17.1 Mean SD 5.34 14.48 6.21 6.72 10.37 9.39 15.0 18.0 19.0 10.0 18.0 16.0
Slide 20: Dose Dependent Increases in FXN Levels Observed in Skin
Dose Dependent Increases in FXN Levels Observed in Skin Daily SC injections of 100 mg CTI-1601 resulted in an ~3 fold increase in FXN levels from baseline FXN* Levels By Dose Group FXN* Change from Baseline By Dose Group (Skin Biopsies) (Skin Biopsies) Baseline Day 13 Day 13 th th *FXN levels measur
Slide 21: Dose Dependent Increases in FXN Levels Observed in Platelets
Dose Dependent Increases in FXN Levels Observed in Platelets with Daily Dosing Daily SC injections of 100mg CTI-1601 resulted in increases in FXN levels from baseline compared to placebo FXN* Levels By Dose Group FXN* Change from Baseline By Dose Group (Platelets) (Platelets) Baseline Day 4/7 Day 13
Slide 22: Summary of PK Analyses
Summary of PK Analyses PK analyses CTI-1601 was quickly absorbed after subcutaneous administration support evaluating Dose-proportional increases in exposure observed with increasing doses of CTI-1601 a once-daily Mean half life of CTI-1601 in plasma was approximately 11 hours dosing regimen for CTI
Slide 23: Leadership Team
Leadership Team Carole Ben-Maimon, MD Michael Celano Nancy Ruiz, MD, FACP, FIDSA Jennifer Johansson, JD Mohamed Hamdani Chief Executive Officer Chief Financial Officer Chief Medical Officer VP, Regulatory Affairs & Counsel VP, Biometrics David Bettoun, PhD Keith E. Lynch, Jr. John Berman, CPA Noreen
Slide 24: Strong Relationship with FARA
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
Slide 25: Scientific Advisory Board
Scientific Advisory Board Giovanni Manfredi, Marni J. Falk, Jill Ostrem, Russell Clayton, Mark Payne, MD DO (Chairman) MD, PhD MD MD Finbar and Marianne Kenny Co-founder of Chondrial Executive Director of the Medical director and division Former Chief Medical Officer Professor in Clinical and Therap
Slide 26: CTI-1601: Positive Mouse Model Data Support Development
CTI-1601: Positive Mouse Model Data Support Development Proof-of-Concept Demonstrated In Mouse Models of FA Cardiac Knock Out Mouse Model Studies Neurologic Knock Out Mouse Model Study (MCK-Cre FXN KO Mouse) (Pvalb-CRE FXN KO Mouse) Extended survival Prevented development of ataxic gait Demonstrated
Slide 27: CTI-1601 Extends Survival in FXN-deficient KO Mice
CTI-1601 Extends Survival in FXN-deficient KO Mice Initial Proof-of-Concept for FXN Replacement Therapy in Cardiac Mouse Model of FA 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 P=0.0001 Survival beyond veh
Slide 28: CTI-1601 Prevents Ataxic Gait in Pvalb-Cre FXN-KO Mouse
CTI-1601 Pvalb-Cre FXN-KO mouse Prevents The Single dose level: 10 mg/kg CTI-1601 or vehicle given intraperitoneally three times per week Development of hFXN replacement with CTI-1601 prevents the development of ataxic gait Ataxic Gait in CTI-1601-treated mice survive longer than untreated mice KO m
Slide 29: 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 functi
Slide 30: 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
Slide 31: 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-16
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