Larimar Therapeutics, Inc DEFA14A, filed Feb 5, 2020
Larimar Therapeutics, Inc. (LRMR)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
SCHEDULE 14A INFORMATION
Proxy Statement Pursuant to Section 14(a) of
the Securities Exchange Act of 1934
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ZAFGEN, INC.
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This Schedule 14A consists of an investor presentation. Members of Zafgen, Inc. management will be participating in upcoming meetings with investors. The following presentation will be used in connection with the meetings with investors.
The presentation was first used or made available on February 5, 2020.
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Zafgen and Chondrial Therapeutics Planned Definitive Merger February 2020
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Forward Looking Statements Additional Information about the Proposed Merger and Where to Find It This may communication be deemed to be relates solicitation to the material proposed in merger respect transaction of the proposed involving merger Zafgen, involving Inc. (“Zafgen”) Zafgen and and Chondrial. Chondrial In Therapeutics, connection with Inc. the (“Chondrial”) proposed merger, and Zafgen intends to file relevant materials with the Securities and Exchange Commission (the “SEC”), including a proxy statement relating to the approval of contain the merger important agreement. information Investors about and Zafgen, security Chondrial holders and of Zafgen the proposed are urged merger. to read The these proxy materials statement when and they other become relevant available materials because (when they they will become addition, available), investors and and security any other holders documents may obtain filed by free Zafgen copies with of the the SEC, documents may be filed obtained with the free SEC of charge by Zafgen at the by directing SEC web site a written at www. request sec.gov. to: In Zafgen, Inc. statement , 3 Center and Plaza, other Suite relevant 610, materials Boston, Massachusetts when they become 02108, available Attention: before Secretary. making Investors any voting and or security investment holders decision are urged with respect to read to the the proxy proposed merger. This there communication be any sale of securities shall not constitute in any jurisdiction an offer in to which sell or such the solicitation offer, solicitation of an offer or sale to would sell or the be unlawful solicitation prior of to an registration offer to buy or any qualification securities, nor under shall the securities laws of any such jurisdiction. Participants in the Solicitation Zafgen and its directors and executive officers and Chondrial and its directors and executive officers may be deemed to be participants in the solicitation directors and of executive proxies from officers the stockholders in the proposed of Zafgen merger in will connection be included with in the the proposed proxy statement merger. referred Information to above. regarding Additional the special information interests regarding of these the directors and executive officers of Zafgen is also included in Zafgen’s definitive proxy statement in connection with its 2019 Annual Meeting of Stockholders Secretary of Zafgen filed with at the the address SEC on above. April 26, 2019. These documents are available free of charge at the SEC web site (www.sec.gov) and from the 2
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Forward Looking Statements Zafgen Forward-Looking Information is Subject to Risks and Uncertainty This involve communication risks and uncertainties, contains forward-looking and include, but statements are not limited based to, upon statements Zafgen’s about and Chondrial’s the structure, current timing expectations. and completion Forward-looking of the proposed statements merger; the combined company’s listing on Nasdaq after the closing of the proposed merger; expectations regarding the ownership structure of the combined company; the nature, the strategy combined and focus company’s of the expected combined cash company; position the at development the closing of and the proposed commercial merger; potential the and future potential operations benefits of the of combined any product company; candidates of headquarters; the combined and company; other statements the executive that and are not board historical structure fact. of Actual the combined results and company; the timing the location of events of may the differ combined materially company’s from those corporate indicated by the these proposed forward-looking merger are statements not satisfied, as a result including of various the failure important to timely factors, obtain including, stockholder without approval limitation: for the (i) proposed the risk that merger, the conditions if at all; (ii) to uncertainties the closing of as to the timing of the consummation of the proposed merger and the ability of each of Zafgen and Chondrial to consummate the proposed merger; (iii) risks related related to the to failure Zafgen’s or delay ability in to obtaining manage its required operating approvals expenses from and any its governmental expenses associated or quasi-governmental with the proposed entity merger necessary pending to consummate closing; (iv) risks the proposed less of the merger; combined (v) company the risk that than as is a currently result of adjustments anticipated; (vi) to the risks exchange related to ratio, the Zafgen market stockholders price of Zafgen’s and Chondrial common stock stockholders relative to could the own exchange more or business ratio; (vii) relationships unexpected costs, resulting charges, from the expenditures announcement or expenses or completion resulting of from the proposed the proposed merger; merger; (ix) Zafgen’s (viii) potential ability adverse to retainreactions personnel or as changes a result to of the the announcement proposed merger, or including completion with of respect the proposed to future merger; financial and and (x) risks operating associated results. with Actual the possible results and failure the to timing realize of certain events anticipated may differ materially benefits of from those anticipated in such forward-looking statements as a result of these risks and uncertainties. These and other risks and uncertainties are more on Form fully 10-Q described for the in quarter periodic ended filings September with the SEC, 30, 2019 including filed the with factors the SEC, described and in other in the filings section that entitled Zafgen “Risk makes Factors” and will in make Zafgen’s with Quarterly the SEC Report in connection Where to Find with It. ” the You proposed should not merger, place including undue reliance the proxy on these statement forward-looking described above statements, under “Additional which apply Information only as of the about date the of Proposed this communication. Merger and Zafgen herein to expressly reflect any disclaims change any in obligation its expectations or undertaking with regard to thereto release publicly or any change any updates in events, or revisions conditions to any or circumstances forward-looking on statements which any such contained statements are based. 3
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Definitive merger agreement announced December 2019 Criteria included: üNear-term milestones within 6 – 9 months post-transaction üWell funded beyond value inflection milestone üEither early stage (IND or Phase 1) or late (pivotal trial) üInnovative scientific approach in an attractive field – both market opportunity and patient need – especially if focus is on rare disease üPlatform opportunity for multiple assets or multiple value streams Thorough evaluation of strategic alternatives Unanimous decision by Zafgen Board of Directors and leadership team 4
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About the proposed merger Post-transaction ownership ~60% Chondrial / ~40% Zafgen stockholders Anticipated 1H 2020 closing New company will operate under new name, Larimar Therapeutics Blended Board of Directors (four from Chondrial / three from Zafgen) President and Chief Executive Officer will be Dr. Carole Ben-Maimon 5
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Compelling value-creation opportunity Publicly traded, clinical-stage biopharmaceutical company focused on rare disease Strong scientific approach and platform opportunity Targeting significant market opportunities Upcoming near-term value creating events expected Experienced leadership team Potential to have impact on significant and devastating diseases 6
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Chondrial Therapeutics Overview 7
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Introduction to Chondrial Therapeutics Clinical-stage biotech with a novel protein replacement therapy platform to address untreated, serious and complex rare diseases Lead candidate, CTI-1601, in Phase 1 clinical development for potential treatment of Friedreich’s ataxia (FA) Only frataxin (FXN) protein replacement therapy in clinical development to our knowledge Nonclinical studies have shown promising results in several models of FA, including heart, brain and muscle function, and overall survival Topline Phase 1 data expected end of 2020 Experienced leadership team Strong IP with 12 years market exclusivity expected if approved and patents pending around efficacy biomarkers 8
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Proprietary protein replacement platform Peptide technology with proven ability to design molecules using cell-penetrating peptides (CPPs) that enable intracellular delivery of bioactive cargos Highly relevant and applicable to a range of cargos and rare disease indications 9
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Friedreich’s ataxia (FA): significant medical need Rare disease caused by a genetic defect resulting in abnormally low levels of frataxin (FXN), affects ~5,000 patients in U.S. and ~10,000 patients in EU-5 Progressive, irreversible, systemic disease that affects multiple body systems, particularly the brain and heart Onset: Age of onset correlated with severity and speed of progression (earlier onset correlated with more drastic progression) Significant asymptomatic period; >70% of patients present before age 14 Initial symptoms (age 10 – 15) may include unsteady posture, frequent falling and progressive difficulty in walking due to impaired ability to coordinate voluntary movements (ataxia) By the time symptoms occur, heart damage has already occurred Progression of disease: Symptoms worsen and may include development of advanced limb ataxia often requiring patient confinement to wheelchair, hypertrophic cardiomyopathy, scoliosis, fatigue, diabetes and hearing loss Life expectancy: 30 – 50 years, early death usually caused by heart disease due to advanced cardiomyopathy Treatment limited to symptom management; no approved therapies 10
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CTI-1601 – Delivering frataxin to the mitochondria CTI-1601: recombinant fusion protein intended to deliver human frataxin, the protein deficient in FA NH3 CPP MTS Human FXN Mature Human FXN COOH Site of MPP cleavage STEP 1: CTI-1601 crosses cell membrane into cytoplasm and then crosses mitochondrial membrane STEP 2: Mitochondrial Processing Peptidase (MPP) cleaves CTI-1601 STEP 3: Mitochondrial Targeting Sequence (MTS) and CPP complex leave and cell mitochondria STEP 4: Mature human frataxin remains trapped within the mitochondria to function 11
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CTI-1601: Proof of concept achieved through multiple nonclinical studies Nonclinical efficacy and PD data provides proof of concept in support of continued development to potentially replace FXN in patients with FA Extended survival in a well-characterized nonclinical model of FA Prevents ataxic gait in another nonclinical model of FA Demonstrated capability of delivering sufficient amounts of FXN to mitochondria Safe and well tolerated in multiple species 12
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CTI-1601 extends survival in FXN-deficient KO Mice Initial Proof of Concept for FXN Replacement Therapy in FA üCTI-1601 extended survival in a well characterized cardiac mouse model of FRDA üConfirms that CTI-1601 is capable of delivering sufficient amounts of FXN to mitochondria, rescuing a severe disease phenotype TAT-FXN was administered 10 mg/kg SC every other day Median Survival of MCK-Cre FXN-KO Mice 166 days (CTI-1601) vs 98.0 days (Vehicle) Survival beyond Vehicle mean (107.5 days) 87.5% (CTI-1601) vs. 33% (Vehicle) Dramatic Survival in Cardiac KO Mouse Model Survival Percent P=0.0001 Days MCK = Muscle creatine kinase 13
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CTI-1601 prevents neurological phenotype in neuro KO mouse model and ataxic gait in FXN-KO mice (brain and DRG KO) In- Vivo Efficacy Data in Neurologic KO Mouse Model Pvalb-Cre FXN-KO mouse CTI-1601 given intraperitoneally (IP) three times per week Single dose level: 10 mg/kg CTI-1601 or Vehicle Dosing Groups: Wild Type, Pvalb-CRE (Vehicle), Pvalb-Cre (CTI-1601) Outcome Measures Prevents behavioral phenotype in mice that lack endogenous FXN in the brain/DRG Gait analysis over time in adult mice Computerized assessment (DigiGait) Stance width Stance phase (swing) Stance length variability Survival analysis Gait parameters remain similar to wild type in CTI-1601-treated mice hFXN replacement via IP treatment with CTI-1601 prevents development of ataxic gait phenotype Treated mice survive longer than untreated mice 14
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hFXN concentration within mitochondria increases in a dose-dependent manner ü Given subcutaneously CTI-1601 functionally replaces hFXN in mitochondria of KO mice ü SDH* activity increases in a dose-dependent manner after administration of CTI-1601; activity plateaus at 30 mg/kg and is equivalent to activity in wildtype animals ü Demonstrated normalization of gene expression in cardiac tissue CTI-1601 effectively traffics to mitochondria; delivers hFXN 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 ( H e a r t ) Normalized SDH activity (Muscle) *Succinate dehydrogenase
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CTI-1601 prevents left ventricle (LV) dilation ü Left ventricular 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 ü CTI-1601-treated mice similar to controls; echocardiogram shows significant differences between KO: Vehicle and KO: CTI-1601 treated mice LV Internal Diameter, Systole LV Volume, Systole KO: CTI-1601 KO: Vehicle Wildtype: Vehicle 16
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CTI-1601 preserves left ventricle (LV) function ü Left Ventricular function drops significantly in untreated mice by week 8 ü CTI-1601-treated mice are similar to controls; echocardiogram again shows significant differences between KO: Vehicle and KO: CTI-1601 treated mice LV Ejection Fraction LV Fractional Shortening KO: CTI-1601 KO: Vehicle Wildtype: Vehicle
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PK/PD study in healthy cynomolgus monkey (study PK-1601-08) ü Treatment of monkeys with CTI-1601 results in sustained levels of hFXN in peripheral tissues that are accessible in the clinic ü FXN levels increase 4x or more following CTI-1601 administration For comparison, FRDA patients have 10-20% of levels of “healthies” Parents who are heterozygous carriers and show no phenotype have ~50% of “healthies” levels (2-3x higher than FRDA patients CSF was collected pre- and post-dose; measured levels of processed hFXN in the CSF that was not present before dosing was initiated 18
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Human frataxin found to be distributed into all tissues tested following CTI-1601 dosing Observed hFXN across all tissue and cell types tested: ü Brain ü Heart ü Liver ü Dorsal Root Ganglia ü Spinal Cord ü Cardiac Mitochondria ü CSF (Cerebrospinal Fluid) ü Skeletal Muscle ü Skin ü Buccal Cells ü Platelets Tissues Examined, By Study Study Study Vehicle Human Frataxin Distribution TOX-1601-01RatsBrain, Heart, Liver PHARM-1601-02Neuro KO MiceBrain, Dorsal Root Ganglia, Spinal Cord PHARM-1601-03Cardiac KO MiceMitochondria of Skeletal Muscle and Cardiomyocytes PK-1601-08Cynomolgus Monkey CSF, Skin, Buccal Cells, Platelets 19
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CTI-1601: Safe and well tolerated in multiple animal models No systemic clinical or pathological observations related to CTI-1601 in GLP studies Cynomolgus Monkey Injection Site Observations Some injection sites raised and firm; increased injection site pathology at higher doses most likely due to local irritation Systemic Toxicity Analysis No other clinical observations or treatment-related changes in food consumption, body weight or organ weight No systemic histopathological findings Sprague Dawley Rat Injection Site Observations Some injection sites showed irritation, firmness, inflammation at higher doses Systemic Toxicity Analysis No significant clinical observations or clinical pathology results No systemic histopathological findings 20
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CTI-1601: Initiated Phase 1 clinical program evaluating safety and efficacy in FA patients Double, placebo-controlled SAD/MAD clinical trials Assessing safety, tolerability, PK/PD of subcutaneous CTI-1601 vs. placebo in adult patients with Friedreich’s ataxia Changes from baseline in frataxin levels and gene expression will also be evaluated Patient dosing began December 2019 Sufficient drug supply for clinical program (5 GMP batches) Topline results from this Phase 1 clinical program expected by the end of 2020 Orphan Drug Designation Rare Pediatric Disease (RPD) Designation (Voucher) Fast Track Designation 21
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