EX-99.2
Exhibit 99.2 Larimar Therapeutics Corporate Presentation November 2020
1Exhibit 99.2 Larimar Therapeutics Corporate Presentation November 2020 1
Forward Looking Statements This presentation contains forward-looking
statements that are based on the Company’s beliefs and assumptions 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 our business, Company’s ability to develop and commercialize CTI-1601 and other planned product candidates, Company’s planned
research and development efforts, and other matters regarding 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 success, cost and timing of the Company’s product development activities, studies and clinical trials; the ongoing impact of the COVID-19
pandemic on the Company’s clinical trial timelines, ability to raise additional capital and general economic conditions; the Company’s ability 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 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 Form 8-K/A filed on June 26, 2020, and the Company’s subsequent 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
Securities and Exchange Commission 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. 2Forward Looking Statements This presentation contains forward-looking statements that are based on the Company’s beliefs and assumptions 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 our business, Company’s ability to develop and commercialize
CTI-1601 and other planned product candidates, Company’s planned research and development efforts, and other matters regarding 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 success, cost and timing of the Company’s product development
activities, studies and clinical trials; the ongoing impact of the COVID-19 pandemic on the Company’s clinical trial timelines, ability to raise additional capital and general economic conditions; the Company’s ability 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 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 Form 8-K/A filed on June 26, 2020, and the Company’s subsequent 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 Securities and Exchange Commission 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 Novel protein replacement therapy platform
designed to address complex rare diseases Lead candidate CTI-1601 is a recombinant fusion protein being developed to CTI-1601 deliver human frataxin to the mitochondria for the treatment of Friedreich’s ataxia (FA) Placebo-controlled Phase 1
clinical trials in Friedreich’s ataxia patients ongoing Phase 1 clinical development with topline data expected 1H 2021 Orphan Drug (US & EU), Rare Pediatric Disease, and Fast Track designations; May Regulatory benefits be eligible for
priority review voucher and 12 years of market exclusivity upon approval, if received Strong balance sheet ~$102M in cash as of 9/30/20 with projected runway into first half of 2022 Includes investors such as Deerfield, Cowen, RA Capital, OrbiMed,
Acuta, High quality shareholder base Vivo, Logos, Altium, Janus and Atlas 3 3Investment Highlights Novel protein replacement therapy platform designed to address complex rare diseases Lead candidate CTI-1601 is a recombinant fusion protein being
developed to CTI-1601 deliver human frataxin to the mitochondria for the treatment of Friedreich’s ataxia (FA) Placebo-controlled Phase 1 clinical trials in Friedreich’s ataxia patients ongoing Phase 1 clinical development with topline
data expected 1H 2021 Orphan Drug (US & EU), Rare Pediatric Disease, and Fast Track designations; May Regulatory benefits be eligible for priority review voucher and 12 years of market exclusivity upon approval, if received Strong balance sheet
~$102M in cash as of 9/30/20 with projected runway into first half of 2022 Includes investors such as Deerfield, Cowen, RA Capital, OrbiMed, Acuta, High quality shareholder base Vivo, Logos, Altium, Janus and Atlas 3 3
Scientific Advisory Board Giovanni Manfredi, Marshall Summar, Marni J.
Falk, Russell Clayton, Mark Payne, MD MD, PhD DO (Chairman) MD MD Finbar and Marianne Kenny Co-founder of Chondrial Chief of the Division of Executive Director of the Former Chief Medical Officer Professor in Clinical and Therapeutics, which
Genetics and Metabolism, Mitochondrial Medicine Frontier at Alcresta Therapeutics, a Research Neurology at Weill became Larimar Director of the Rare Disease Program at The Children’s medical device company Cornell Medicine. Therapeutics, Inc.
Institute, and Margaret Hospital of Philadelphia (CHOP) O'Malley Chair of Genetic Former Senior Vice Professor of Neuroscience at Professor of Pediatrics Medicine at Children’s Professor in the Division of President of Research and Weill
Cornell Medicine. at Indiana University School National Hospital Human Genetics, Department of Development at Discovery of Medicine Pediatrics at University of Labs, a pharmaceutical and Pennsylvania Perelman School medical device company of
Medicine 4Scientific Advisory Board Giovanni Manfredi, Marshall Summar, Marni J. Falk, Russell Clayton, Mark Payne, MD MD, PhD DO (Chairman) MD MD Finbar and Marianne Kenny Co-founder of Chondrial Chief of the Division of Executive Director of the
Former Chief Medical Officer Professor in Clinical and Therapeutics, which Genetics and Metabolism, Mitochondrial Medicine Frontier at Alcresta Therapeutics, a Research Neurology at Weill became Larimar Director of the Rare Disease Program at The
Children’s medical device company Cornell Medicine. Therapeutics, Inc. Institute, and Margaret Hospital of Philadelphia (CHOP) O'Malley Chair of Genetic Former Senior Vice Professor of Neuroscience at Professor of Pediatrics Medicine at
Children’s Professor in the Division of President of Research and Weill Cornell Medicine. at Indiana University School National Hospital Human Genetics, Department of Development at Discovery of Medicine Pediatrics at University of Labs, a
pharmaceutical and Pennsylvania Perelman School medical device company of Medicine 4
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 1 depending on the tissue considered >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 has already occurred • Progressive disease: Symptoms worsen and patients are eventually confined to 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 5 5 1. E.C. Deutsch et al. Molecular Genetics and Metabolism 101 (2010) 238–245Friedreich’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 1 depending on the tissue considered >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 has already occurred • Progressive disease: Symptoms worsen and patients are eventually confined to 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 5 5 1. E.C. Deutsch et al. Molecular Genetics and
Metabolism 101 (2010) 238–245
Market Opportunity Regulatory Prevalence Dosing Benefits Replacement
therapy may be 5,000 patients in US and Well known by FDA; “Voice of needed throughout life to 20,000 patients in EU the Patient” report for FA was Dosing Dosing Dosing maintain frataxin (FXN) levels released in 2017 Additional affected
populations Upon Biologics License Disease is progressive and in Australia and Brazil Application (BLA) approval, irreversible; initiating therapy Highly sophisticated and active CTI-1601, if approved, may be early and continuing advocacy group
(FARA) driving eligible for: replacement therapy quest for treatments • 12 years market exclusivity throughout life may be a • Rare pediatric disease necessity priority review voucher 6Market Opportunity Regulatory Prevalence Dosing
Benefits Replacement therapy may be 5,000 patients in US and Well known by FDA; “Voice of needed throughout life to 20,000 patients in EU the Patient” report for FA was Dosing Dosing Dosing maintain frataxin (FXN) levels released in 2017
Additional affected populations Upon Biologics License Disease is progressive and in Australia and Brazil Application (BLA) approval, irreversible; initiating therapy Highly sophisticated and active CTI-1601, if approved, may be early and continuing
advocacy group (FARA) driving eligible for: replacement therapy quest for treatments • 12 years market exclusivity throughout life may be a • Rare pediatric disease necessity priority review voucher 6
CTI-1601 is Being Developed to Deliver 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 CPP allows CTI-1601 to
traverse the cell and mitochondrial membranes where the CPP and MTS are removed by mitochondrial processing peptidase to produce mature human FXN 7CTI-1601 is Being Developed to Deliver 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 CPP allows CTI-1601 to traverse the cell and
mitochondrial membranes where the CPP and MTS are removed by mitochondrial processing peptidase to produce mature human FXN 7
CTI-1601 – Delivering Frataxin to the Mitochondria CPP allows
CTI-1601 to traverse the 01 cell membrane into the cytoplasm CPP allows CTI-1601 to traverse 02 the mitochondrial membrane MPP cleaves CTI-1601. MTS and CPP 03 leave cell mitochondria Mature human frataxin remains within 04 the mitochondria to
function 8CTI-1601 – Delivering Frataxin to the Mitochondria CPP allows CTI-1601 to traverse the 01 cell membrane into the cytoplasm CPP allows CTI-1601 to traverse 02 the mitochondrial membrane MPP cleaves CTI-1601. MTS and CPP 03 leave cell
mitochondria Mature human frataxin remains within 04 the mitochondria to function 8
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” 9Strong 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” 9
CTI-1601: Phase 1 Clinical Program in FA Phase 1 Development Plan
• Two Double-blind, Placebo Controlled Dosing Studies • Patient dosing began December 2019 • Safety Review Committee assesses all blinded data between each cohort to ensure patient safety • Topline results expected in 1H 2021
Number of subjects: 32-34 Dose levels: 25mg, 50mg, 75mg and 100mg (subcutaneous administration) Single Ascending Dose Treatment Duration: 1 day rd Status: After dosing 2 cohorts, paused in March due to COVID-19. Restarted in July with 3 cohort (SAD)
1º Endpoint: Safety and tolerability Patients from SAD 2º Endpoints: PK; PD; hFXN levels (gene expression in buccal swab and blood); multiple exploratory trial are eligible to enroll in MAD trial Number of Subjects: Currently planning for
3 cohorts, 24-30 subjects Dose Range: To be determined based on SAD data and adjusted continuously based on PK/PD data Multiple Ascending Dose Treatment Regimen: Multiple increasing doses administered subcutaneously over 14 days (MAD) 1º
Endpoint: Safety and tolerability 2º Endpoints: PK; PD; hFXN levels (gene expression in buccal swab and blood); multiple exploratory 10CTI-1601: Phase 1 Clinical Program in FA Phase 1 Development Plan • Two Double-blind, Placebo
Controlled Dosing Studies • Patient dosing began December 2019 • Safety Review Committee assesses all blinded data between each cohort to ensure patient safety • Topline results expected in 1H 2021 Number of subjects: 32-34 Dose
levels: 25mg, 50mg, 75mg and 100mg (subcutaneous administration) Single Ascending Dose Treatment Duration: 1 day rd Status: After dosing 2 cohorts, paused in March due to COVID-19. Restarted in July with 3 cohort (SAD) 1º Endpoint: Safety and
tolerability Patients from SAD 2º Endpoints: PK; PD; hFXN levels (gene expression in buccal swab and blood); multiple exploratory trial are eligible to enroll in MAD trial Number of Subjects: Currently planning for 3 cohorts, 24-30 subjects
Dose Range: To be determined based on SAD data and adjusted continuously based on PK/PD data Multiple Ascending Dose Treatment Regimen: Multiple increasing doses administered subcutaneously over 14 days (MAD) 1º Endpoint: Safety and
tolerability 2º Endpoints: PK; PD; hFXN levels (gene expression in buccal swab and blood); multiple exploratory 10
Upcoming Clinical Milestones 1H 2021 Topline Phase 1 Data Future
Planned Studies Include: Open-label extension (OLE) study Pediatric MAD Study Phase 2/3 Double-Blind for patients who participated in (followed by an OLE) Placebo-Controlled Study SAD or MAD studies 11Upcoming Clinical Milestones 1H 2021 Topline
Phase 1 Data Future Planned Studies Include: Open-label extension (OLE) study Pediatric MAD Study Phase 2/3 Double-Blind for patients who participated in (followed by an OLE) Placebo-Controlled Study SAD or MAD studies 11
CTI-1601 Open Label Extension Trial Patients from SAD and MAD trials
are eligible to enter an open label extension (OLE) Multicenter Open Label Extension Trial Dose Level: To be determined based on PK/PD from SAD and MAD trials SAD Trial Patients Patients eligible to enroll Treatment Duration: Planned for 24 months
with any from Phase 1/Pediatric necessary extensions Number of Subjects: Up to 50 Dose Regimen: To be determined based on PK/PD from SAD and MAD trials MAD Trial Patients Comparator Arm: Derived from Critical Path Institute Data (includes FACOMS and
placebo arms from two FA studies) 1º Endpoint: Safety and tolerability Key 2º Endpoints: Long-term PD; efficacy assessments 12CTI-1601 Open Label Extension Trial Patients from SAD and MAD trials are eligible to enter an open label
extension (OLE) Multicenter Open Label Extension Trial Dose Level: To be determined based on PK/PD from SAD and MAD trials SAD Trial Patients Patients eligible to enroll Treatment Duration: Planned for 24 months with any from Phase 1/Pediatric
necessary extensions Number of Subjects: Up to 50 Dose Regimen: To be determined based on PK/PD from SAD and MAD trials MAD Trial Patients Comparator Arm: Derived from Critical Path Institute Data (includes FACOMS and placebo arms from two FA
studies) 1º Endpoint: Safety and tolerability Key 2º Endpoints: Long-term PD; efficacy assessments 12
CTI-1601: Positive Non-Clinical Data Support Development Studies
demonstrate the ability of CTI-1601 to deliver Proof-of-Concept Achieved Through Multiple sufficient amounts of FXN to mitochondria in rodent Non-Clinical Studies: and non-human primate non-clinical models CTI-1601 extended survival in a
well-characterized non- CTI-1601 prevented left ventricle dilation and maintained clinical mouse model of FA function in non-clinical mouse models CTI-1601 prevented ataxic gait in another non-clinical CTI-1601 is safe and well tolerated in rats and
non-human mouse model of FA primates 13CTI-1601: Positive Non-Clinical Data Support Development Studies demonstrate the ability of CTI-1601 to deliver Proof-of-Concept Achieved Through Multiple sufficient amounts of FXN to mitochondria in rodent
Non-Clinical Studies: and non-human primate non-clinical models CTI-1601 extended survival in a well-characterized non- CTI-1601 prevented left ventricle dilation and maintained clinical mouse model of FA function in non-clinical mouse models
CTI-1601 prevented ataxic gait in another non-clinical CTI-1601 is safe and well tolerated in rats and non-human mouse model of FA primates 13
Human Frataxin Distributed Into All Tissues Tested Tissues Examined
Study Vehicle Human Frataxin Distribution Rats Brain, Heart, Liver Neuro KO Mice Brain, Dorsal Root Ganglia, Spinal Cord Cardiac KO Mice Mitochondria of Skeletal Muscle and Cardiomyocytes Cynomolgus Monkey Cerebrospinal fluid, Skin, Buccal Cells,
Platelets 14Human Frataxin Distributed Into All Tissues Tested Tissues Examined Study Vehicle Human Frataxin Distribution Rats Brain, Heart, Liver Neuro KO Mice Brain, Dorsal Root Ganglia, Spinal Cord Cardiac KO Mice Mitochondria of Skeletal Muscle
and Cardiomyocytes Cynomolgus Monkey Cerebrospinal fluid, Skin, Buccal Cells, Platelets 14
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 vehicle
mean (107.5 days) • 87.5% (CTI-1601) vs. 33% (Vehicle) • Demonstrates that CTI-1601 is capable of delivering Days sufficient amounts of FXN to mitochondria CTI-1601 rescues a severe disease phenotype in a well characterized cardiac mouse
model of FA 15 Percent SurvivalCTI-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 vehicle mean (107.5 days) • 87.5% (CTI-1601) vs. 33% (Vehicle) • Demonstrates that CTI-1601 is capable of delivering Days sufficient amounts
of FXN to mitochondria CTI-1601 rescues a severe disease phenotype in a well characterized cardiac mouse model of FA 15 Percent Survival
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 mice Human
frataxin present in brain, dorsal root ganglia and spinal cord demonstrating central nervous system penetration In-Vivo Efficacy Data in Neurologic KO Mouse Model 16CTI-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 mice Human frataxin present in
brain, dorsal root ganglia and spinal cord demonstrating central nervous system penetration In-Vivo Efficacy Data in Neurologic KO Mouse Model 16
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, increases in a dose-dependent manner after administration of CTI-1601; activity plateaus at 30 mg/kg and is equivalent to activity in wild type animals • Demonstrated normalization of gene expression in cardiac tissue N o r m a l i z
e d M i t o c h o n d r i a l h F X N Normalized SDH activity Normalized SDH Activity (Muscle) Normalized Mitochondrial FXN (Heart) ( H e a r t ) (Muscle) 80 *** *** 2 0 0 *** K O V e h i c l e *** 60 ** K O 2 M P K 1 5 0 K O 1 0 M P K 40 K O 3 0 M
P K 1 0 0 K O 6 0 M P K 20 K O 1 0 0 M P K 5 0 W i l d T y p e V e h i c l e 0 0 MPK = mg/kg MPK = mg/kg 17 F e m a l e s M a l e s KO Vehicle KO 2MPK KO 10MPK KO 30MPK KO 60MPK KO 100MPK Wild Type Vehicle N o r m a l i z e d h F X N ( p g / m g p r
o t e i n ) SDH Activity mU/mg proteinCTI-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, increases in a dose-dependent manner after administration of CTI-1601; activity plateaus at 30 mg/kg and is equivalent to
activity in wild type animals • Demonstrated normalization of gene expression in cardiac tissue N o r m a l i z e d M i t o c h o n d r i a l h F X N Normalized SDH activity Normalized SDH Activity (Muscle) Normalized Mitochondrial FXN (Heart)
( H e a r t ) (Muscle) 80 *** *** 2 0 0 *** K O V e h i c l e *** 60 ** K O 2 M P K 1 5 0 K O 1 0 M P K 40 K O 3 0 M P K 1 0 0 K O 6 0 M P K 20 K O 1 0 0 M P K 5 0 W i l d T y p e V e h i c l e 0 0 MPK = mg/kg MPK = mg/kg 17 F e m a l e s M a l e s
KO Vehicle KO 2MPK KO 10MPK KO 30MPK KO 60MPK KO 100MPK Wild Type Vehicle N o r m a l i z e d h F X N ( p g / m g p r o t e i n ) SDH Activity mU/mg protein
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
volume as healthy controls; echocardiogram shows significant differences between vehicle and CTI-1601 treated (10 mg/kg every other day) KO mice Left Ventricle Internal Diameter (Systole) Left Ventricle Volume (Systole) Age in Weeks Age in Weeks KO:
CTI-1601 KO: Vehicle Wildtype: Vehicle 18 Diameter (mm) Volume (μL)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 volume as healthy controls; echocardiogram shows significant differences between vehicle and CTI-1601
treated (10 mg/kg every other day) KO mice Left Ventricle Internal Diameter (Systole) Left Ventricle Volume (Systole) Age in Weeks Age in Weeks KO: CTI-1601 KO: Vehicle Wildtype: Vehicle 18 Diameter (mm) Volume (μL)
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
treated KO mice Left Ventricle Ejection Function Left Ventricle Fractional Shortening Age in Weeks Age in Weeks KO: CTI-1601 KO: Vehicle Wildtype: Vehicle 19 Percent Change Percent ChangeCTI-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 treated KO mice Left Ventricle Ejection Function Left Ventricle Fractional Shortening Age in Weeks Age in Weeks KO: CTI-1601 KO: Vehicle Wildtype: Vehicle 19 Percent Change Percent Change
Favorable PK/PD Profile in Healthy Cynomolgus Monkeys Study Design
• CTI-1601 is bioavailable when given subcutaneously 6 healthy cynomolgus monkeys (3M / 3F) • Sustained levels of hFXN are found in blood cells (platelets) and peripheral Pre-dosed for 2 days with Vehicle tissues (buccal cells, skin) as
early as Pre-dose collection of platelets, cerebrospinal fluid, buccal swab, skin punch th the 7 day and still present after 14 Dosing starts 15 mg/kg SC BID days Day 10 (7 days dosing) • Sustained levels of hFXN are found after 14 days in the
Collection of platelets, buccal swab, skin punch cerebrospinal fluid of monkeys, suggesting CNS penetration th Day 16 (following 14 day of dosing) • Preliminary results from 90 Day GLP toxicology study support these findings Collection of
cerebrospinal fluid platelets, buccal swab, skin punch 20Favorable PK/PD Profile in Healthy Cynomolgus Monkeys Study Design • CTI-1601 is bioavailable when given subcutaneously 6 healthy cynomolgus monkeys (3M / 3F) • Sustained levels of
hFXN are found in blood cells (platelets) and peripheral Pre-dosed for 2 days with Vehicle tissues (buccal cells, skin) as early as Pre-dose collection of platelets, cerebrospinal fluid, buccal swab, skin punch th the 7 day and still present after
14 Dosing starts 15 mg/kg SC BID days Day 10 (7 days dosing) • Sustained levels of hFXN are found after 14 days in the Collection of platelets, buccal swab, skin punch cerebrospinal fluid of monkeys, suggesting CNS penetration th Day 16
(following 14 day of dosing) • Preliminary results from 90 Day GLP toxicology study support these findings Collection of cerebrospinal fluid platelets, buccal swab, skin punch 20
Biodistribution in Healthy Cynomolgus Monkey Buccal Swabs Skin Biopsies
Platelets (Pre-treatment) (Pre-treatment) (Pre-treatment) CTI-1601 Human FXN Human + Monkey FXN • Treatment of monkeys with CTI-1601 results in sustained levels of hFXN in peripheral tissues that are accessible in the clinic • FXN levels
increase ~4X or more following CTI-1601 administration 1 • For comparison, FA patients show FXN levels that range from ~20-40% of normal FXN levels depending on the tissue considered 1 - Heterozygous carriers show no phenotype and display
levels of FXN representing ~2-3X higher than most FA patients 21 1. E.C. Deutsch et al. Molecular Genetics and Metabolism 101 (2010) 238–245Biodistribution in Healthy Cynomolgus Monkey Buccal Swabs Skin Biopsies Platelets (Pre-treatment)
(Pre-treatment) (Pre-treatment) CTI-1601 Human FXN Human + Monkey FXN • Treatment of monkeys with CTI-1601 results in sustained levels of hFXN in peripheral tissues that are accessible in the clinic • FXN levels increase ~4X or more
following CTI-1601 administration 1 • For comparison, FA patients show FXN levels that range from ~20-40% of normal FXN levels depending on the tissue considered 1 - Heterozygous carriers show no phenotype and display levels of FXN
representing ~2-3X higher than most FA patients 21 1. E.C. Deutsch et al. Molecular Genetics and Metabolism 101 (2010) 238–245
CTI-1601: Safe and Well Tolerated in Early Tox Studies Cynomolgus
Monkey Sprague Dawley Rat Injection Site Observations Injection Site Observations • Some injection sites raised and firm; • Some injection sites showed irritation, increased injection site pathology at higher firmness, inflammation at
higher doses doses most likely due to local irritation Systemic Toxicity Analysis Systemic Toxicity Analysis • No other clinical observations or treatment- • No significant clinical observations or related changes in food consumption,
body clinical pathology results weight or organ weight • No systemic histopathological findings • No systemic histopathological findings No systemic clinical or pathological observations related to CTI-1601 in 28-day GLP IND-enabling
studies 22CTI-1601: Safe and Well Tolerated in Early Tox Studies Cynomolgus Monkey Sprague Dawley Rat Injection Site Observations Injection Site Observations • Some injection sites raised and firm; • Some injection sites showed
irritation, increased injection site pathology at higher firmness, inflammation at higher doses doses most likely due to local irritation Systemic Toxicity Analysis Systemic Toxicity Analysis • No other clinical observations or treatment-
• No significant clinical observations or related changes in food consumption, body clinical pathology results weight or organ weight • No systemic histopathological findings • No systemic histopathological findings No systemic
clinical or pathological observations related to CTI-1601 in 28-day GLP IND-enabling studies 22
CTI-1601 is Protected by a Strong IP Portfolio Pending CTI-1601 patent
application extends into 2040 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 Expiration TAT-MTS-FXN Composition of Matter (broad coverage of CTI-1601) US 9,045,552 (Exclusive license from Wake Forest) October, 2024 Methods of treating FA using
TAT-MTS-FXN and delivering TAT-MTS- Expiration FXN to mitochondria (broad coverage of CTI-1601) December 2025 US 8,735,341 (Exclusive license from Wake Forest) (including Patent Term Adjustment) CTI-1601 Composition of Matter and Methods of
Treatment Est. Expiration (specific coverage of CTI-1601) July, 2040 US/PCT applications pending (Exclusive license from Indiana University) Will be filed in foreign jurisdictions accordingly Granted Pending Additional intellectual property (IP)
protection • Additional pending applications cover key biomarkers, analytical tools, quantification methods and platform technology • CTI-1601 is eligible for 12 years of market exclusivity upon approval in the US (independent of
patents) • CTI-1601 is eligible for at least 10 years of market exclusivity upon approval in Europe (independent of patents) 23CTI-1601 is Protected by a Strong IP Portfolio Pending CTI-1601 patent application extends into 2040 2000 2005 2010
2015 2020 2025 2030 2035 2040 2045 Expiration TAT-MTS-FXN Composition of Matter (broad coverage of CTI-1601) US 9,045,552 (Exclusive license from Wake Forest) October, 2024 Methods of treating FA using TAT-MTS-FXN and delivering TAT-MTS- Expiration
FXN to mitochondria (broad coverage of CTI-1601) December 2025 US 8,735,341 (Exclusive license from Wake Forest) (including Patent Term Adjustment) CTI-1601 Composition of Matter and Methods of Treatment Est. Expiration (specific coverage of
CTI-1601) July, 2040 US/PCT applications pending (Exclusive license from Indiana University) Will be filed in foreign jurisdictions accordingly Granted Pending Additional intellectual property (IP) protection • Additional pending applications
cover key biomarkers, analytical tools, quantification methods and platform technology • CTI-1601 is eligible for 12 years of market exclusivity upon approval in the US (independent of patents) • CTI-1601 is eligible for at least 10
years of market exclusivity upon approval in Europe (independent of patents) 23
Investment Highlights Novel protein replacement therapy platform
designed to address complex rare diseases Lead candidate CTI-1601 is a recombinant fusion protein being developed to CTI-1601 deliver human frataxin to the mitochondria for the treatment of Friedreich’s ataxia (FA) Placebo-controlled Phase 1
clinical trials in Friedreich’s ataxia patients ongoing Phase 1 clinical development with topline data expected 1H 2021 Orphan Drug (US & EU), Rare Pediatric Disease, and Fast Track designations; May Regulatory benefits be eligible for
priority review voucher and 12 years of market exclusivity upon approval, if received Strong balance sheet ~$102M in cash as of 9/30/20 with projected runway into first half of 2022 Includes investors such as Deerfield, Cowen, RA Capital, OrbiMed,
Acuta, High quality shareholder base Vivo, Logos, Altium, Janus and Atlas 24 24Investment Highlights Novel protein replacement therapy platform designed to address complex rare diseases Lead candidate CTI-1601 is a recombinant fusion protein being
developed to CTI-1601 deliver human frataxin to the mitochondria for the treatment of Friedreich’s ataxia (FA) Placebo-controlled Phase 1 clinical trials in Friedreich’s ataxia patients ongoing Phase 1 clinical development with topline
data expected 1H 2021 Orphan Drug (US & EU), Rare Pediatric Disease, and Fast Track designations; May Regulatory benefits be eligible for priority review voucher and 12 years of market exclusivity upon approval, if received Strong balance sheet
~$102M in cash as of 9/30/20 with projected runway into first half of 2022 Includes investors such as Deerfield, Cowen, RA Capital, OrbiMed, Acuta, High quality shareholder base Vivo, Logos, Altium, Janus and Atlas 24 24
Larimar Therapeutics Corporate Presentation THANK YOU 25Larimar
Therapeutics Corporate Presentation THANK YOU 25
Leadership Team Michael Celano Carole Ben-Maimon, MD Jennifer
Johansson, JD Chief Financial Officer Chief Executive Officer VP Regulatory Affairs & Counsel David Bettoun, PhD Nancy M. Ruiz, MD, FACP, FIDSA Keith E. Lynch, Jr. VP Discovery & Non-clinical R&D VP, Manufacturing and Supply Chain Chief
Medical Officer Francis Michael Conway Noreen Scherer John Berman, CPA Vice President Controller VP, Clinical Operations VP Finance & Operations 26Leadership Team Michael Celano Carole Ben-Maimon, MD Jennifer Johansson, JD Chief Financial
Officer Chief Executive Officer VP Regulatory Affairs & Counsel David Bettoun, PhD Nancy M. Ruiz, MD, FACP, FIDSA Keith E. Lynch, Jr. VP Discovery & Non-clinical R&D VP, Manufacturing and Supply Chain Chief Medical Officer Francis
Michael Conway Noreen Scherer John Berman, CPA Vice President Controller VP, Clinical Operations VP Finance & Operations 26
Scientific Advisory Board Russell (Rusty) Clayton, DO, Scientific
Advisory Board Chair • Nearly two decades of executive experience in pharmaceutical, biologics and medical device development and commercialization as a consultant in clinical development, medical affairs and regulatory affairs. • Prior
to consulting, he was chief medical officer at Alcresta Therapeutics, a medical device company; senior vice president of research and development at Discovery Labs, a pharmaceutical and medical device company, where he led the scientific and
regulatory efforts leading to the marketing authorization of Discovery’s first product. • Dr. Clayton is a board-certified pediatric pulmonologist who practiced at St. Christopher’s Hospital for Children and the Children’s
Hospital of Philadelphia prior to beginning his career in the pharmaceutical, biologics, and medical device industry. He received his DO from the Philadelphia College of Osteopathic Medicine. Marni J. Falk, MD • Dr. Falk is Executive Director
of the Mitochondrial Medicine Frontier Program at The Children’s Hospital of Philadelphia (CHOP) and Professor in the Division of Human Genetics, Department of Pediatrics at University of Pennsylvania Perelman School of Medicine. • She
also serves as a principal investigator of a National Institutes of Health, pharma and philanthropic-funded translational laboratory group at CHOP that investigates the causes and global metabolic consequences of mitochondrial disease and directs
multiple clinical treatment trials in mitochondrial disease patients. • Dr. Falk received her BS in biology and MD from the George Washington University School of Medicine. In addition, she completed dual specialty training in the Pediatrics
and Clinical Genetics residency program at Case Western Reserve University. Giovanni Manfredi, MD, PhD • Dr. Manfredi is the Finbar and Marianne Kenny Professor in Clinical and Research Neurology at Weill Cornell Medicine. He is also a
Professor of Neuroscience and directs the graduate program in Neuroscience at Weill Cornell Medicine. Dr. Manfredi’s lab studies alterations of mitochondrial metabolism in neurodegenerative diseases, particularly amyotrophic lateral sclerosis
and primary inherited mitochondrial encephalomyopathies. • Dr. Manfredi has authored more than 100 publications focused in areas including neurodegenerative and mitochondrial diseases. • Dr. Manfredi received his MD and PhD in anatomy
and cell biology from Catholic University of the Sacred Heart in Rome, where he also completed a residency in neurology. Mark Payne, MD • Dr. Payne is a renowned scientist and practicing cardiovascular physician who brings a long-standing
scientific focus on protein targeting to mitochondria and a dedication to treating cardiomyopathies of childhood, including Friedreich’s ataxia. He is the inventor of the original therapy for frataxin protein replacement in Friedreich’s
ataxia and co-founded Chondrial Therapeutics, which became Larimar Therapeutics, Inc. • He holds multiple patents on mitochondrial biology and repair. He is a tenured professor of pediatrics at Indiana University School of Medicine where he
directs multiple NIH-funded training, clinical, and research programs as a principal investigator. • Dr. Payne received his BS in natural sciences from Washington & Lee University, and his MD from the University of Texas at Houston. He
performed his postdoctoral clinical and research training at Washington University in St. Louis. He is a Fellow of the American College of Cardiology and the American Academy of Pediatrics. Marshall Summar, MD • Dr. Summar serves as Chief of
the Division of Genetics and Metabolism, Director of the Rare Disease Institute and is the Margaret O'Malley Chair of Genetic Medicine at Children’s National Hospital. • In addition to guiding clinical research and treatment, he
developed and launched the world’s first Rare Disease Institute (RDI) at Children’s. The RDI is the first Clinical Center of Excellence designated by the National Organization for Rare Diseases (NORD) and focuses on building best
clinical practices and diagnostic pathways for patients. With NORD and the FDA, Dr. Summar has worked to develop a patient- driven natural history platform employed by over 35 rare disease advocacy organizations. • He received his BS in
molecular biology from Vanderbilt University and his MD from University of Tennessee Center for Health Sciences. 27Scientific Advisory Board Russell (Rusty) Clayton, DO, Scientific Advisory Board Chair • Nearly two decades of executive
experience in pharmaceutical, biologics and medical device development and commercialization as a consultant in clinical development, medical affairs and regulatory affairs. • Prior to consulting, he was chief medical officer at Alcresta
Therapeutics, a medical device company; senior vice president of research and development at Discovery Labs, a pharmaceutical and medical device company, where he led the scientific and regulatory efforts leading to the marketing authorization of
Discovery’s first product. • Dr. Clayton is a board-certified pediatric pulmonologist who practiced at St. Christopher’s Hospital for Children and the Children’s Hospital of Philadelphia prior to beginning his career in the
pharmaceutical, biologics, and medical device industry. He received his DO from the Philadelphia College of Osteopathic Medicine. Marni J. Falk, MD • Dr. Falk is Executive Director of the Mitochondrial Medicine Frontier Program at The
Children’s Hospital of Philadelphia (CHOP) and Professor in the Division of Human Genetics, Department of Pediatrics at University of Pennsylvania Perelman School of Medicine. • She also serves as a principal investigator of a National
Institutes of Health, pharma and philanthropic-funded translational laboratory group at CHOP that investigates the causes and global metabolic consequences of mitochondrial disease and directs multiple clinical treatment trials in mitochondrial
disease patients. • Dr. Falk received her BS in biology and MD from the George Washington University School of Medicine. In addition, she completed dual specialty training in the Pediatrics and Clinical Genetics residency program at Case
Western Reserve University. Giovanni Manfredi, MD, PhD • Dr. Manfredi is the Finbar and Marianne Kenny Professor in Clinical and Research Neurology at Weill Cornell Medicine. He is also a Professor of Neuroscience and directs the graduate
program in Neuroscience at Weill Cornell Medicine. Dr. Manfredi’s lab studies alterations of mitochondrial metabolism in neurodegenerative diseases, particularly amyotrophic lateral sclerosis and primary inherited mitochondrial
encephalomyopathies. • Dr. Manfredi has authored more than 100 publications focused in areas including neurodegenerative and mitochondrial diseases. • Dr. Manfredi received his MD and PhD in anatomy and cell biology from Catholic
University of the Sacred Heart in Rome, where he also completed a residency in neurology. Mark Payne, MD • Dr. Payne is a renowned scientist and practicing cardiovascular physician who brings a long-standing scientific focus on protein
targeting to mitochondria and a dedication to treating cardiomyopathies of childhood, including Friedreich’s ataxia. He is the inventor of the original therapy for frataxin protein replacement in Friedreich’s ataxia and co-founded
Chondrial Therapeutics, which became Larimar Therapeutics, Inc. • He holds multiple patents on mitochondrial biology and repair. He is a tenured professor of pediatrics at Indiana University School of Medicine where he directs multiple
NIH-funded training, clinical, and research programs as a principal investigator. • Dr. Payne received his BS in natural sciences from Washington & Lee University, and his MD from the University of Texas at Houston. He performed his
postdoctoral clinical and research training at Washington University in St. Louis. He is a Fellow of the American College of Cardiology and the American Academy of Pediatrics. Marshall Summar, MD • Dr. Summar serves as Chief of the Division of
Genetics and Metabolism, Director of the Rare Disease Institute and is the Margaret O'Malley Chair of Genetic Medicine at Children’s National Hospital. • In addition to guiding clinical research and treatment, he developed and launched
the world’s first Rare Disease Institute (RDI) at Children’s. The RDI is the first Clinical Center of Excellence designated by the National Organization for Rare Diseases (NORD) and focuses on building best clinical practices and
diagnostic pathways for patients. With NORD and the FDA, Dr. Summar has worked to develop a patient- driven natural history platform employed by over 35 rare disease advocacy organizations. • He received his BS in molecular biology from
Vanderbilt University and his MD from University of Tennessee Center for Health Sciences. 27
Friedreich’s Ataxia (FA) Symptoms & Natural History 70% of
patients present before age 14 Age 10 – 30 years: Progression of disease Symptoms continue to worsen and may include Significant asymptomatic period of disease development of advanced limb ataxia often requiring patient 01 03 Age of onset
correlated with severity and speed of confinement to wheelchair, hypertrophic cardiomyopathy, progression (earlier onset correlated with more drastic scoliosis, fatigue, diabetes and hearing loss progression) Age 10 – 15 years: Initial onset
of disease Age 30 – 50 years: Life expectancy of typical FA Symptoms begin to appear and may include unsteady patient posture, frequent falling and progressive difficulty in walking Early death usually caused by heart disease due to advanced
02 04 due to impaired ability to coordinate voluntary movements cardiomyopathy: Most common type is hypertrophic By the time symptoms occur, heart damage has occurred cardiomyopathy, a thickening of the heart muscle 28Friedreich’s Ataxia (FA)
Symptoms & Natural History 70% of patients present before age 14 Age 10 – 30 years: Progression of disease Symptoms continue to worsen and may include Significant asymptomatic period of disease development of advanced limb ataxia often
requiring patient 01 03 Age of onset correlated with severity and speed of confinement to wheelchair, hypertrophic cardiomyopathy, progression (earlier onset correlated with more drastic scoliosis, fatigue, diabetes and hearing loss progression) Age
10 – 15 years: Initial onset of disease Age 30 – 50 years: Life expectancy of typical FA Symptoms begin to appear and may include unsteady patient posture, frequent falling and progressive difficulty in walking Early death usually caused
by heart disease due to advanced 02 04 due to impaired ability to coordinate voluntary movements cardiomyopathy: Most common type is hypertrophic By the time symptoms occur, heart damage has occurred cardiomyopathy, a thickening of the heart muscle
28
