Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Zafgen — Merger or Acquisition (February 2020)
22 slides from Larimar Therapeutics's merger presentation, Feb 5, 2020
Slide 1: Zafgen and Chondrial Therapeutics Planned Definitive Merger
Exhibit 99.1 Zafgen and Chondrial Therapeutics Planned Definitive Merger February 2020Exhibit 99.1 Zafgen and Chondrial Therapeutics Planned Definitive Merger February 2020
Slide 2: Forward Looking Statements: Additional Information about the Proposed Merger
Forward Looking Statements Additional Information about the Proposed Merger and Where to Find It This communication relates to the proposed merger transaction involving Zafgen, Inc. (“Zafgen”) and Chondrial Therapeutics, Inc. (“Chondrial”) and may be deemed to be solicitation material in respect of
Slide 3: Forward Looking Statements
Forward Looking Statements Zafgen Forward-Looking Information is Subject to Risks and Uncertainty This communication contains forward-looking statements based upon Zafgen’s and Chondrial’s current expectations. Forward-looking statements involve risks and uncertainties, and include, but are not limi
Slide 4: Definitive merger agreement announced December 2019
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
Slide 5: About the proposed merger
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 Office
Slide 6: Compelling value-creation opportunity
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 te
Slide 7: Chondrial Therapeutics Overview
Chondrial Therapeutics Overview 7Chondrial Therapeutics Overview 7
Slide 8: Introduction to Chondrial Therapeutics
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 (F
Slide 9: Proprietary protein replacement platform
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 9Proprietary protein
Slide 10: Friedreich's ataxia (FA): significant medical need
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, particular
Slide 11: CTI-1601 – Delivering frataxin to the mitochondria
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 mitochondria
Slide 12: CTI-1601: Proof of concept achieved through multiple nonclinical studies
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 atax
Slide 13: CTI-1601 extends survival in FXN-deficient KO Mice
CTI-1601 extends survival in FXN-deficient KO Mice Initial Proof of Concept for FXN Replacement Therapy in FA Dramatic Survival in Cardiac üCTI-1601 extended survival in a well characterized KO Mouse Model cardiac mouse model of FRDA üConfirms that CTI-1601 is capable of delivering sufficient amount
Slide 14: CTI-1601 prevents neurological phenotype and ataxic gait in FXN-KO mice
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
Slide 15: CTI-1601 effectively traffics to mitochondria; delivers hFXN
CTI-1601 effectively traffics to mitochondria; delivers hFXN ü 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 o
Slide 16: CTI-1601 prevents left ventricle (LV) dilation
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
Slide 17: CTI-1601 preserves left ventricle (LV) function
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 Fr
Slide 18: PK/PD study in healthy cynomolgus monkey
PK/PD study in healthy cynomolgus monkey (study PK-1601-08) CTI-1601 Human Human/Monkey 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
Slide 19: Human frataxin distributed into all tissues tested following CTI-1601 dosing
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 Spinal Cord ü Skin ü Heart ü Cardiac Mitochondria ü Buccal Cells ü Liver ü CSF (Cerebrospinal Fluid) ü Platelets ü Dorsal Root Ganglia ü Skeletal
Slide 20: CTI-1601: Safe and well tolerated in multiple animal models
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 Sprague Dawley Rat Injection Site Observations Injection Site Observations • Some injection sites raised and firm; • Some injection sites
Slide 21: CTI-1601: Initiated Phase 1 clinical program in FA patients
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
Slide 22: - @eeChondrial
- @eeChondrial Zafgen Therapeutics, Inc.