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Forward Looking Statements This presentation contains forward-looking
statements that are based on the beliefs and assumptions of Larimar Therapeutics, Inc. (the "Company") and on information currently available to management. All statements contained in this presentation other than statements of
historical fact are forward-looking statements, including but not limited to statements regarding the expectations and assumptions regarding the future of the Company's business, including its ability to resolve the clinical hold by the FDA
related to CTI-1601and the timing of such resolution, the Company's ability to develop and commercialize CTI-1601 and other planned product candidates, the Company's planned research and development efforts, and other matters regarding
the Company's business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. In some cases, you can identify forward-looking statements by the words "may,"
"will," "could," "would," "should," "expect," "intend," "plan," "anticipate," "believe," "estimate," "predict,"
"project," "potential," "continue," "ongoing" or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve
risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. These risks, uncertainties and other factors
include, among others, the Company's ability to successfully engage with the FDA and satisfactorily respond to the current request, and future requests, if any, from the FDA for further information and data regarding CTI-1601, the timing and
outcomes of Larimar's interactions with the FDA, including with respect to the clinical hold on CTI-1601, the success, cost and timing of the Company's product development activities, non-clinical studies and clinical trials, including
CTI-1601 clinical milestones; that clinical trial results may differ from final clinical trial results, that earlier non-clinical and clinical data and testing of CTI-1601 may not be predictive of the results or success of clinical trials, and that
clinical trial data are subject to differing interpretations and assessments; the ongoing impact of the COVID-19 pandemic on the Company's clinical trials, manufacturing, regulatory and nonclinical study timelines, the ongoing impact of the
COVID-19 pandemic and the potential impact of the Russian invasion of Ukraine on the Company's ability to raise additional capital and general economic conditions; the Company's ability and the ability of third-party manufactures the
Company engages to optimize and scale CTI-1601's manufacturing process; the Company's ability to obtain regulatory approval for CTI-1601 and future product candidates; the Company's ability to develop sales and marketing
capabilities, whether alone or with potential future collaborators, and to successfully commercialize any approved product candidates; the Company's ability to raise the necessary capital to conduct its product development activities; and
other risks described in the filings made by the Company with the Securities and Exchange Commission (SEC), including but not limited to the Company's periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q
and current reports on Form 8-K, filed with or furnished to the SEC and available at www.sec.gov. These forward- looking statements are based on a combination of facts and factors currently known by the Company and its projections of the future,
about which it cannot be certain. As a result, the forward-looking statements may not prove to be accurate. These forward-looking statements are based on information currently available to us, and we assume no obligation to update any
forward-looking statements, except as required by law. 2
Investment Highlights 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 intellectual property portfolio Lead candidate: CTI-1601, a
recombinant fusion protein designed to deliver frataxin to mitochondria Orphan Drug (US & EU), Rare Pediatric Disease (US), Fast Track (US), & PRIME (EU) designations for FA Double-blind, placebo-controlled Phase 1 proof-of-concept trials in
FA patients complete Data show dose dependent increases in FXN levels from baseline compared to placebo in all evaluated tissues with daily dosing and that CTI-1601 was generally well tolerated when dosed for up to 13 days -Currently on clinical
hold; responding to FDA data request to allow initiation of additional clinical studies Deerfield funded company; went public through a reverse merger/PIPE in May 2020 Shareholder base includes high-quality institutional investors; estimated $70
million in cash at 12/31/21*; Projected runway at least into 2023, with ability to extend, if needed FXN: Frataxin *This estimate is preliminary and actual results may differ due to the completion of our closing procedures with respect to the fiscal
year ended December 31, 2021, 3 final adjustments and other developments that may arise between now and the time the financial results for the 2021 fiscal year are finalized. As such, these estimates should not be viewed as a substitute for our full
audited financial statements prepared in accordance with U.S. generally accepted accounting principles.
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 Wake Forest)
Methods of treating FA using TAT-MTS-FXN and delivering TAT-MTS-FXN Expiration CTI-1601 to mitochondria (broad coverage of CTI-1601) December 2025 US 8,735,341 (Exclusive license from Wake Forest) (including Patent Term Adjustment) Patents /
Applications CTI-1601 Composition of Matter and Methods of Treatment Est. Expiration (specific coverage of CTI-1601) July 2040 US/foreign applications pending (Exclusive license from Indiana University) Platform Technology*: Molecules for Protein
Delivery Est. Expiration Platform US/PCT applications pending March 2041 Applications Will be filed in foreign jurisdictions accordingly *Additional pending applications for platform disease targets Additional CTI-1601 IP protection CTI-1601
pending applications cover key biomarkers, analytical tools and quantification methods CTI-1601 is eligible for 12 years of market exclusivity upon approval in the US (independent of patents) and at least 10 years of market exclusivity upon
approval in EU (independent of patents) Granted Pending 4
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 Cleavage by
mitochondrial processing Cell Cleavage by mitochondrial processing peptidase (MPP) at this site produces Penetrating peptidase (MPP) at this site produces mature human FXN in mitochondria Peptide (CPP) mature human FXN in mitochondria The
maintenance of the cleavage site allows the CPP and MTS to be removed by mitochondrial processing peptidase to produce mature human FXN in the mitochondria 5
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 1 on the tissue, sampling technique, and assay considered Affects ~5,000 patients in the U.S. & ~20,000
patients in the EU >70% of patients present before age 14 Initial symptoms may include unsteady posture, frequent falling and progressive difficulty in walking By the time symptoms occur, heart damage may have already occurred
Progressive disease: Symptoms worsen and patients are eventually confined to a wheelchair with speech becoming hesitant and jerky (often referred to as "scanning of speech") Life expectancy of 30-50 years Early death
usually caused by heart disease No approved therapies available Current treatment options are limited to symptom management 6 1 1. E.C. Deutsch et al. Molecular Genetics and Metabolism 101 (2010) 238-245
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 Access to Global Patient Registry with demographic and clinical information on more than 1,000 FA patients Sponsored a Patient-Focused Drug Development Meeting in 2017 resulting in a publication
titled "The Voice of the Patient" 7
Executive Summary of Phase 1 POC Data 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 controls in all evaluated tissues
Pharmacokinetics Pharmacokinetic analyses support evaluating a once-daily dosing regimen for CTI-1601 Daily subcutaneous (SC) administration of 50mg and 100mg doses of CTI-1601 resulted in FXN levels in buccal cells that are at, or in excess of,
those we would Conclusion expect to see in phenotypically normal heterozygous carriers (who have FXN levels of ~50% of unaffected persons) 8 8 POC: Proof-of-concept
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 Review
Committee assessed all blinded data between each cohort to ensure patient safety Number of subjects: 28 Dose levels: 25 mg, 50 mg, 75 mg and 100 mg (subcutaneous administration) Single Ascending Dose Treatment Duration: 1 day 1 Endpoint:
Safety and tolerability (SAD) 2 Endpoints: PK; PD; FXN levels; multiple exploratory Eligible patients Status: Complete with analysis ongoing from SAD trial could enroll in MAD trial Number of Subjects: 27 Dose Range: 25 mg, 50 mg, 100 mg
(subcutaneous administration) Treatment Regimen: Multiple increasing doses administered subcutaneously over 13 days Multiple Ascending Dose 1 Endpoint: Safety and tolerability (MAD) 2 Endpoints: PK; PD; FXN levels (buccal cells,
platelets, optional skin biopsies); multiple exploratory Status: Complete with analysis ongoing 9
MAD Trial Patient Enrollment 16 out of 28 patients who participated in
the SAD trial enrolled in the MAD trial MAD Trial Patient Enrollment (n=27) Parameter Statistic Overall Participated in SAD trial? Yes n (%) 16 (59%) No n (%) 11 (41%) Cohort 1 (25 mg) Active vs. Placebo Active n (%) 6 (75%) Placebo n (%) 2 (25%)
Cohort 2 (50 mg) Active vs. Placebo Active n (%) 7 (78%) Placebo n (%) 2 (22%) Cohort 3 (100 mg) Active vs. Placebo Active n (%) 7 (70%) Placebo n (%) 3 (30%) 10
Multiple Ascending Dose Study Design 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 8 9 10 11 12 13
14 = Administration of CTI-1601 or placebo = Administration of CTI-1601 or placebo = Administration of CTI-1601 or placebo = No Administration = No Administration = No Administration FXN Level Sampling Days Presented for Each Cohort Cohort 1
Sampling Days Cohort 2 Sampling Days Cohort 3 Sampling Days Buccal Buccal Buccal Baseline, Day 4, Day 13 Baseline, Day 7, Day 13 Baseline, Day 7, Day 13 Cells Cells Cells Skin Skin Baseline, Day 13 Baseline, Day 13 Skin Baseline, Day 13 Platelets
Platelets Baseline, Day 7, Day 13 Platelets Baseline, Day 4, Day 13 Baseline, Day 7, Day 13 11
Dose Dependent Increases in FXN Levels Observed in Buccal Cells Daily
SC injections of 100 mg CTI-1601 resulted in an ~2.5 fold increase in FXN levels from baseline 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 and 25 and 75 percentiles; FXN levels from baseline, Day 4, & 12 Day 13 measurements are shown for data derived from the 25 mg cohort; FXN levels from baseline, Day
7 & Day 13 measurements are shown for data derived from the 50 & 100 mg cohorts; Sample collection days varied in each cohort per the trial protocol FXN Concentration (pg/ g total protein) Additional FXN (Change from Baseline)
(pg/ g total protein)
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 measured via
detection of peptide derived from mature FXN; Data represent median and 25 and 75 percentiles 13 FXN Concentration (pg/ g total protein) Additional FXN (Change from Baseline) (pg/ g total protein)
Dose Dependent Increases in FXN Levels Observed in Platelets with Daily
Dosing Daily SC injections of 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 Day 4/7 Day 13 th th *FXN
levels measured via detection of peptide derived from mature FXN; Data represent median and 25 and 75 percentiles; FXN levels from baseline, Day 4, & 14 Day 13 measurements are shown for data derived from the 25 mg cohort; FXN levels from
baseline, Day 7 & Day 13 measurements are shown for data derived from the 50 & 100 mg cohorts; Sample collection days varied in each cohort per the trial protocol FXN Concentration (pg/ g total protein) Additional FXN (Change from
Baseline) (pg/ g total protein)
Increases in FXN Correlated with Increasing CTI-1601 Dose Individual
patient data further supports the dose-dependent effects of CTI-1601 in all tissues studied # Buccal Cells Day 13 FXN* Skin Biopsies Day 13 FXN* Platelets Day 13 FXN* Change from Baseline Change from Baseline Change from Baseline Subjects Subjects
Subjects 15 # *FXN levels measured via detection of peptide derived from mature FXN; Two patients in the 100 mg cohort declined skin biopsies Day 13 observation excluded from one subject in 25 mg group that did not get a Day 13 dose. Day 13 FXN CBL
(pg/ g total protein) Day 13 FXN CBL (pg/ g total protein) Day 13 FXN CBL (pg/ g total protein)
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 correlate
with 1 neurological function in FA patients Patients with FA only produce ~20-40% of normal frataxin levels 2 depending on the tissue considered 60% of median healthy # Heterozygous carriers who show no signs of disease have FXN
levels of control FXN levels (n=8) 2 ~50% of unaffected healthy persons Comparison to Healthy Controls FXN levels were measured in buccal cells from 8 healthy controls using the same assay and sampling technique employed in the Phase 1 MAD
trial With daily administration, patients in Cohorts 2 & 3 of the Phase 1 MAD trial achieved median buccal cell FXN levels that were >60% of the median FXN levels observed in healthy controls Baseline Day 4/7 Day 13 Data from
additional healthy control buccal cells, skin, and platelets will be collected in a separate non-interventional study # th th *FXN levels measured via detection of peptide derived from mature FXN; Data on file; Data represent median and 25 and 75
percentiles ; FXN levels from baseline, Day 4, & Day 13 measurements are shown for data derived from the 25 mg cohort; FXN levels from baseline, Day 7 & Day 13 measurements are shown for 16 data derived from the 50 & 100 mg cohorts;
Sample collection days varied in each cohort per the trial protocol. 1. Lazaropoulos et al. Ann Clin Transl Neurol. 2015 Aug; 2(8): 831-842; 2. E.C. Deutsch et al. Molecular Genetics and Metabolism 101 (2010) 238-245. FXN Level
(pg/ g total protein)
Summary of MAD trial safety data: Repeated SC Repeated doses (25 mg, 50
mg, and 100 mg) of CTI-1601 or placebo were injections of administered subcutaneously. 27 patients were dosed in the trial. 26 patients completed the trial. 1 patient receiving CTI-1601 in Cohort 2 (50 mg) withdrew CTI-1601 appear to after
experiencing mild/moderate symptoms (nausea and vomiting). be generally well No serious adverse events (SAEs), important medical events, or tolerated at doses treatment-related severe adverse events up to 100 mg The most common adverse events were
mild and moderate injection site administered daily reactions (at least one injection site reaction was seen in 43% of placebo patients and in 100% of CTI-1601 patients) for 13 days The number and severity of adverse events did not increase with
increasing exposure to CTI-1601 17
PK analyses Summary of 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-1601 appears to be
at or close to steady state exposure after 13 days of dosing 100 mg CTI-1601 once daily 18
Phase 1 Topline Data Demonstrated POC for CTI-1601 in FA 1 FXN levels