UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 10, 2020
Larimar Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
| Delaware | 001-36510 | 20-3857670 | ||
| (State or other jurisdiction of incorporation or organization) |
(Commission File Number) |
(I.R.S. Employer Identification No.) | ||
| Three Bala Plaza East. Suite 506 Bala Cynwyd, Pennsylvania |
19004 | |||
| (Address of principal executive offices) | (Zip Code) | |||
Registrant’s telephone number, including area code: (844) 511-9056
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
| Common Stock, par value $0.001 per share | LRMR | Nasdaq Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 2.02 | Results of Operations and Financial Condition |
On November 10, 2020, Larimar Therapeutics, Inc. (the “Company”) announced its financial results and operational highlights for the third quarter ended September 30, 2020. A copy of the press release is being furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
The information in this Current Report on Form 8-K and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 7.01 | Regulation FD Disclosure |
On November 10, 2020, the Company posted on its website an updated slide presentation, which is being furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference. Representatives of the Company will use the presentation in various meetings with investors, analysts and other parties from time to time.
The information in this Item 7.01 (including Exhibit 99.2) is being furnished solely to satisfy the requirements of Regulation FD and shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, nor shall it be deemed to be incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits |
(d) Exhibits
Below is a list of exhibits included with this Current Report on Form 8-K.
| Exhibit |
Document | |
| 99.1 | Press Release issued by Larimar Therapeutics, Inc. on November 10, 2020* | |
| 99.2 | Larimar Therapeutics, Inc. Corporate Presentation, dated November 10, 2020* | |
| * | Furnished herewith |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Larimar Therapeutics, Inc. | ||
| By: | /s/ Carole S. Ben-Maimon, M.D. | |
| Name: | Carole S. Ben-Maimon, M.D. | |
| Title: | President and Chief Executive Officer | |
Date: November 10, 2020
Exhibit 99.1
Larimar Therapeutics Reports Third Quarter 2020 Operating and Financial Results
Phase 1 trials evaluating CTI-1601 as a treatment for Friedreich’s ataxia on track for topline data in 1H 2021
Received orphan drug designation for CTI-1601 from the European Commission
Cash, cash equivalents, and marketable securities of $102.3 million as of September 30, 2020
Bala Cynwyd, PA – November 10, 2020 – Larimar Therapeutics, Inc. (Nasdaq:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today reported its third quarter 2020 operating and financial results.
“I am very pleased with the progress Larimar has made over the past few months, as we achieved key clinical, regulatory, and corporate milestones that have left us well positioned for continued growth,” said Carole Ben-Maimon, MD, President and Chief Executive Officer of Larimar Therapeutics. “In the third quarter, we continued to advance our lead program in development for Friedreich’s ataxia (FA), resuming our Phase 1 trials evaluating CTI-1601 in patients with FA. Though the trials were delayed due to the impact of the COVID-19 pandemic, they are now on track for topline results in the first half of 2021.”
Dr. Ben-Maimon continued, “Alongside this clinical achievement, we also complemented previous regulatory designations from the U.S. Food and Drug Administration (FDA) with an orphan drug designation from the European Commission and strengthened Larimar’s leadership team with the formation of a Scientific Advisory Board (SAB). Members of the SAB are key opinion leaders in the fields of rare disease, pediatrics, and mitochondrial disease who will provide strategic scientific guidance as we build our pipeline.”
Third Quarter and Subsequent Highlights
| • | In July 2020, Larimar resumed its Phase 1 clinical trials to evaluate the safety and tolerability of CTI-1601 for the treatment of FA with the dosing of its third cohort. The trials were previously delayed due to the impact of the COVID-19 pandemic. Topline data from the trials are expected in the first half of 2021. |
| • | In August 2020, the European Commission granted an orphan drug designation for CTI-1601 for the treatment of FA. This designation complements previously received Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the FDA. |
| • | In October 2020, Larimar announced the formation of its SAB. The SAB will provide strategic scientific guidance to company management and is comprised of key opinion leaders in the fields of rare disease, pediatrics, and mitochondrial disease. Members of the SAB include: Russell (Rusty) Clayton, DO; Marni J. Falk, MD; Giovanni Manfredi, MD, PhD; Mark Payne, MD; and Marshall Summar, MD. |
Third Quarter 2020 Financial Results
As of September 30, 2020, the Company had cash, cash equivalents, and marketable debt securities totaling $102.3 million.
The Company reported a net loss for the third quarter of 2020 of $10.3 million, or $0.64 per share, compared to a net loss of $8.6 million, or $1.42 per share, for the third quarter of 2019.
Research and development expenses for the third quarter of 2020 were $6.9 million compared to $8.0 million for the third quarter of 2019. The decrease in research and development expenses compared to the prior year period was primarily driven by lower clinical supply manufacturing costs and toxicology studies partially offset by an increase in external clinical trial expenditures, an increase in personnel related costs due to headcount additions in our research and development functions and an increase in stock-based compensation expense associated with stock option grants made in July 2020.
General and administrative expenses for the third quarter of 2020 were $3.4 million, compared to $0.6 million for the third quarter of 2019. The increase in general and administrative expenses as compared to the prior year period was primarily driven by an increase in professional fees and insurance costs that are primarily due to the costs of operating as a public company, an increase in personnel related costs due to increased headcount, an increase in stock-based compensation associated with stock option grants made in July 2020 and an increase in facilities costs.
About CTI-1601
CTI-1601 is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with Friedreich’s ataxia (FA) who are unable to produce enough of this essential protein. Currently in Phase 1 clinical trials in the U.S., CTI-1601 has been granted Rare Pediatric Disease designation, Fast Track designation and Orphan Drug designation by the U.S. Food and Drug Administration (FDA) and orphan drug designation by the European Commission. Topline results from the Phase 1 clinical program are planned for the first half of 2021.
About Friedreich’s ataxia
Friedreich’s ataxia (FA) is a rare, progressive, multi-symptom genetic disease that typically presents in mid-childhood and affects the functioning of multiple organs and systems. The most common inherited ataxia, FA is a debilitating neurodegenerative disease resulting in multiple symptoms including progressive neurologic and cardiac dysfunction – poor coordination of legs and arms, progressive loss of the ability to walk, generalized weakness, loss of sensation, scoliosis, diabetes, and cardiomyopathy as well as impaired vision, hearing, and speech. FA affects an estimated 4,000-5,000 individuals living in the United States and approximately 20,000 in the European Economic Area and United Kingdom. FA results from a deficiency of the mitochondrial protein, frataxin (FXN), which is found in cells throughout the body. To date, there are no medical treatment options approved for patients with FA.
About Larimar Therapeutics
Larimar Therapeutics, Inc. (Nasdaq:LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. The company’s lead compound, CTI-1601, is currently being evaluated in a Phase 1 clinical program in the U.S. as a potential treatment for Friedreich’s ataxia (FA). Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com.
Forward-Looking Statements
This press release contains forward-looking statements that are based on Larimar’s management’s beliefs and assumptions and on information currently available to management. All statements contained in this release other than statements of historical fact are forward-looking statements, including but not limited to statements regarding Larimar’s ability to develop and commercialize CTI-1601 and other planned product candidates, Larimar’s planned research and development efforts, and other matters regarding Larimar’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 Larimar’s product development activities, studies and clinical trials; the ongoing impact of the COVID-19 pandemic on Larimar’s clinical trial timelines, ability to raise additional capital and general economic conditions; Larimar’s ability to optimize and scale CTI-1601’s manufacturing process; Larimar’s ability to obtain regulatory approval for CTI-1601 and future product candidates;; Larimar’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators, and successfully commercialize any approved product candidates; Larimar’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 Larimar’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 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 Larimar 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. The forward-looking statements in this press release represent views as of the date hereof. Larimar undertakes no obligation to update any forward-looking statements for any reason, except as required by law.
Investor Contact:
Joyce Allaire
LifeSci Advisors
(212) 915-2569
jallaire@lifesciadvisors.com
Media Contact:
Gina Cestari
6 Degrees
(917) 797-7904
gcestari@6degreespr.com
LARIMAR THERAPEUTICS, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(Unaudited)
| September 30, | December 31, | |||||||
| 2020 | 2019 | |||||||
| Assets |
||||||||
| Current assets: |
||||||||
| Cash and cash equivalents |
$ | 101,308 | $ | 1,009 | ||||
| Marketable debt securities |
1,001 | — | ||||||
| Prepaid expenses and other current assets |
5,507 | 3,741 | ||||||
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|
|
|
|||||
| Total current assets |
107,816 | 4,750 | ||||||
| Property and equipment, net |
630 | 274 | ||||||
| Operating lease right-of-use assets |
4,094 | 87 | ||||||
| Restricted cash |
1,339 | — | ||||||
| Other assets |
78 | 90 | ||||||
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| Total assets |
$ | 113,957 | $ | 5,201 | ||||
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| Liabilities and Stockholders’ Equity (Deficit) |
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| Current liabilities: |
||||||||
| Accounts payable |
$ | 1,269 | $ | 3,539 | ||||
| Accrued expenses |
3,384 | 2,259 | ||||||
| Operating lease liabilities, current |
525 | 97 | ||||||
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| Total current liabilities |
5,178 | 5,895 | ||||||
| Operating lease liabilities |
6,138 | — | ||||||
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| Total liabilities |
11,316 | 5,895 | ||||||
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| Commitments and contingencies (See Note 9) |
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| Stockholders’ equity: |
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| Preferred stock; $0.001 par value per share; 5,000,000 shares authorized as of September 30, 2020 and December 31, 2019; no shares issued and outstanding as of September 30, 2020 and December 31, 2019 |
— | — | ||||||
| Common stock, $0.001 par value per share; 115,000,000 shares authorized as of September 30, 2020 and December 31, 2019; 15,356,206 and 6,091,250 shares issued and outstanding as of September 30, 2020 and December 31, 2019, respectively |
15 | 6 | ||||||
| Additional paid-in capital |
154,038 | 22,432 | ||||||
| Accumulated deficit |
(51,410 | ) | (23,132 | ) | ||||
| Accumulated other comprehensive loss |
(2 | ) | — | |||||
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| Total stockholders’ equity (deficit) |
102,641 | (694 | ) | |||||
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| Total liabilities and stockholders’ equity (deficit) |
$ | 113,957 | $ | 5,201 | ||||
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LARIMAR THERAPEUTICS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(In thousands, except share and per share data)
(Unaudited)
| Three Months Ended September 30, |
Nine Months Ended September 30, |
|||||||||||||||
| 2020 | 2019 | 2020 | 2019 | |||||||||||||
| Operating expenses: |
||||||||||||||||
| Research and development |
$ | 6,919 | $ | 8,034 | $ | 20,833 | $ | 15,384 | ||||||||
| General and administrative |
3,416 | 594 | 7,575 | 1,672 | ||||||||||||
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| Total operating expenses |
10,335 | 8,628 | 28,408 | 17,056 | ||||||||||||
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| Loss from operations |
(10,335 | ) | (8,628 | ) | (28,408 | ) | (17,056 | ) | ||||||||
| Other income, net |
61 | — | 130 | — | ||||||||||||
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| Net loss |
$ | (10,274 | ) | $ | (8,628 | ) | $ | (28,278 | ) | $ | (17,056 | ) | ||||
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| Net loss per share, basic and diluted |
$ | (0.64 | ) | $ | (1.42 | ) | $ | (2.69 | ) | $ | (2.80 | ) | ||||
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| Weighted average common shares outstanding, basic and diluted |
15,984,609 | 6,091,250 | 10,505,826 | 6,091,250 | ||||||||||||
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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