ContraFect. Differentiated, first-in-class anti-infectives for life-threatening, drug-resistant infections. September 2018

Transcription

1 ContraFect Differentiated, first-in-class anti-infectives for life-threatening, drug-resistant infections September 2018

2 Forward Looking Statements This presentation contains, and our officers and representatives may from time to time make, forward-looking statements within the meaning of the U.S. federal securities laws. Forward-looking statements can be identified by words such as projects, may, will, could, would, should, believe, expect, target, anticipate, estimate, intend, plan, proposed, potential or similar references to future periods. Examples of forward-looking statements in this presentation include statements made regarding ContraFect Corporation s ( ContraFect ) therapeutic product candidates, including their ability to treat life-threatening, drug resistant infections, CF-301 properties and activity including but not limited to the ability of CF-301 used in addition to SOC antibiotics to significantly improve clinical success rates compared to SOC antibiotics alone, synergy with conventional antibiotics and clearance of biofilms, CF-301 s value proposition and product attributes, expectations regarding clinical outcomes and efficacy of CF-301, in vitro and in vivo study results, anticipated timing of topline study results, timing of the completion of clinical trials, ability to achieve Phase 2 study endpoints, CF-404 s ability to treat influenza, ContraFect s CF-296, Gram-positive and Gram-negative lysins and other discovery programs and patent protection. Forward-looking statements are statements that are not historical facts, nor assurances of future performance. Instead, they are based on ContraFect s current beliefs, expectations and assumptions regarding the future of its business, future plans, proposals, strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent risks, uncertainties and changes in circumstances that are difficult to predict and many of which are beyond ContraFect s control, including those detailed in ContraFect's most recent Quarterly Report on Form 10-Q and its Annual Report on Form 10-K for the year ended December 31, 2017 and other filings with the Securities and Exchange Commission. Actual results may differ from those set forth in the forwardlooking statements. Important factors that could cause actual results to differ include, among others, the occurrence of any adverse events related to the discovery, development and commercialization of ContraFect s product candidates such as unfavorable clinical trial results, insufficient supplies of drug products, the lack of regulatory approval, or the unsuccessful attainment or maintenance of patent protection. Any forward-looking statement made by ContraFect in this presentation is based only on information currently available and speaks only as of the date on which it is made. No representation or warranty is made as to the completeness or accuracy of the information provided in this presentation. Except as required by applicable law, ContraFect expressly disclaims any obligations to publicly update any forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Audiences are cautioned that forwardlooking statements or similar information are not guarantees of future performance and, accordingly, are expressly cautioned not to put undue reliance on forward-looking statements or similar information due to the inherent uncertainty therein. 2

3 Clinical-stage biotech leading the development of differentiated, first-in-class biologics for the treatment of life-threatening and drug-resistant infections

4 Resistant Infections are Expensive and Cost Lives Estimated global mortality 700,000 in 2016 Increasing to 10 million in 2050 Estimated deaths (per 100,000 cases) Estimated annual costs Up to $20 billion (direct costs in the U.S.) Up to 1.5 billion in the EU (additional hospital days alone) Sources: Review on Antimicrobial Resistance, O Neill, 2016, Clinical and Economic Consequences of MDR Pseudomonas, Nathwani, 2014 Staphylococcus aureus Bloodstream Infection, Kaasch, 2014, CDC, 2013, ECDC,

5 Favorable Environment for New Anti-Infective Modalities United States Potential for streamlined development June 2018 draft FDA guidance, Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) August 2017 FDA Guidance for Industry for Antibacterial Therapies for Patients With Unmet Medical Need for the Treatment of Serious Bacterial Diseases Global LEGISLATIVE May 2018 EMA concept paper to revise guideline on products for treatment of bacterial infections WHO Global Priority List of Antibiotic- Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics, February st Century Cures Act GAIN ACT Global Antibiotic Research & Development Partnership (GARDP), May

6 ContraFect Portfolio Overview Lysin platform Novel class of anti-infectives Preclinical data supports multiple advantages as therapeutics CF-301 first-in-class lysin candidate for Staph aureus bacteremia Currently in Phase 2 superiority clinical trial Enrollment completed Top-line data expected by end of 2018 Fast Track status granted by FDA Broad pipeline Novel lysins directed at drug resistant gram-negative (GN) pathogens o Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Enterobacter spp., E. coli Novel phage derived peptides with broad spectrum activity against GN pathogens CF-296 engineered CF-301 variant potential line extension in pre-clinical evaluation CF-404 inhaled triple antibody cocktail to treat influenza in pre-clinical evaluation 6

7 ContraFect Pipeline Program Target Pathogen Discovery Preclinical Phase 1 Phase 2 CF-301 Staphylococcus aureus Complicated bacteremia, including endocarditis CF-296 Staphylococcus aureus GN lysins Pseudomonas aeruginosa GP lysins CF-404 Klebsiella pneumoniae Escherichia coli Enterobacter cloacae Acinetobacter baumannii Streptococcus pneumoniae Enterococcus faecalis Group B streptococcus Bacillus anthracis Influenza GN Gram-negative GP Gram-positive 7

8 Lysin Platform: A Novel Class of Antimicrobials Lysins are enzymes that rupturing the bacterial cell wall leading to the disintegration of the bacterial cell Bacteriophage infects bacterial cells, replicated inside the cell and produces lysins to break the cell wall We have produced lysins as purified recombinant therapeutic proteins, enabling the hydrolysis of peptidoglycan bonds of bacterial cell walls Lysins are introduced externally to the pathogen leading to cell death Lysin = 8

9 Lysins: Hallmark Features of a New Class Rapid, potent and targeted bactericidal activity Eradicates biofilms Synergy with conventional antibiotics Low propensity for resistance 9

10 Lysins Exhibit Rapid and Potent Bactericidal Activity Please click the picture below to view a video (on YouTube ) of lysin activity against Gram-positive bacteria. Video repeats at higher magnification. 10

11 CF-301 (exebacase) Innovative Anti-Infective for Complicated Staph aureus Infections Based on Novel Lysin Technology 11

12 CF-301: First-in-Class Lysin Candidate Key attributes 26 kda modular bacterial cell wall hydrolase enzyme Highly potent against all Staph aureus species Rapid eradication of Staph biofilms Potent synergy with broad range of antistaphylococcal antibiotics Clinical-stage program Ongoing Phase 2 superiority study for potential to improve clinical response rates for Staph aureus bacteremia and endocarditis, used in addition to standard of care (SOC) antistaphylococcal antibiotics Well tolerated with predictable PK in Phase 1 Robust IP position Exclusive license granted by The Rockefeller University Patent for composition of matter in effect until

13 CF-301: Eradicates Biofilms Biofilm: A major medical problem Biofilms harbor and protect bacteria from immune defenses Conventional antibiotics cannot clear or penetrate biofilms Biofilms can increase antibiotic resistance 1,000-fold Mature MRSA biofilms are highly susceptible to CF-301 in vitro and resistant to Daptomycin (DAP) CF-301 MBEC 90 * = 0.25 ug/ml DAP MBEC 90 * >1,024 ug/ml CF-301 clears in vitro biofilm in 15 min on a MRSA-infected catheter Before exposure to CF-301 After 15 min exposure to CF-301 Expanded IP position Patent issued for prevention, control, disruption and treatment of biofilms using lysin technology in effect until 2033 Source: Schuch, et al, AAC, *minimum biofilm-eradicating concentration 13

14 Mean Log10 CFU/Gram CF-301: Eradicates Human Staphylococcal Biofilms Demonstrated susceptibility of MRSA biofilms to CF-301 and resistance to DAP Infected hemodialysis catheter removed from a patient as part of clinical care Biofilm from MRSA and other staphylococcal species found inside catheter CF-301 cleared biofilm and reduced staph CFUs inside the catheter Daptomycin was ineffective against biofilms Correlates to in vitro findings 4 Reduction of Staph species on explanted human catheter *LOD = Limit of detection 0 Pretreatment Buffer DAP 1 ug/ml CF ug/ml CF-301+ DAP 1 ug/ml 14

15 CF-301: Synergy with SOC in Rat Endocarditis Model DAP alone at human therapeutic equivalent dose daily x 4 days 3 log reduction in CFUs Single dose of CF-301 plus DAP daily dose x 4 days 6 log reduction in CFUs p vs. DAP alone 4/9 rats tested culture-negative tissues with CF-301/DAP combo Vegetations, Kidney, Spleen 9/9 Dap Monotherapy Culture- Positive Source: Oral Presentation at ICAAC,

16 L o g 1 0 C F U /g tis s u e CF-301: Synergy Confirmed in Rabbit Endocarditis Model Single dose of CF-301 plus DAP daily dose x 4 days ~6-log reduction in CFUs at all CF-301 doses vs. vehicle (p 0.001) > 3 log reduction in CFUs at all CF- 301 doses tested vs. DAP alone (p 0.002) Efficacy maintained at the lowest CF- 301 dose tested (0.09 mg/kg) (p 0.001) R a b b it H e a r t V e g e ta tio n B u rd e n Human Equivalent Dose approximates Phase 2 dose Similar efficacy demonstrated with a wide-range of timing of CF-301 dose relative to initial dose of SOC 1 0 V e h ic le D a p to m y c in (4 m g /k g ) C F m g /k g C F m g /k g C F m g /k g C F m g /k g D a p to m y c in (4 m g /k g, Q D x 4 ) C F m g /k g Source: Schuch et.al. Oral Presentation, CDMRP/MIDRP Meeting, April

17 CF-301: Low Propensity For Drug Resistance After serial passage for 26 days, CF-301 minimal inhibitory concentration remained stable (MIC increased <2 fold) Combination with CF-301 suppresses resistance to DAP. Similar results seen with vancomycin or oxacillin No cross-resistance with other antibacterial classes Able to re-sensitize MRSA to methicillin and derivative antibiotics in vitro In vitro Drug Resistance Studies - MRSA Source: Schuch et al JID 2014:209 17

18 CF-301: Phase 1 Demonstrated Safety and Tolerability Single escalating IV dose, double-blind, placebo-controlled 20 healthy volunteer; 4 dosing cohorts (0.04, 0.12, 0.25, 0.40 mg/kg) Well tolerated; no clinical adverse safety signals No serious adverse events (AEs) No CF-301-related hypersensitivity AEs 5 non-serious AEs were mild, transient and resolved by end of study o o CF headache, contact dermatitis, allergic rhinitis Placebo - viral upper respiratory tract infection, viral infection 9 of 13 CF-301 subjects developed anti-drug antibodies Complete or near complete resolution by Day 180 Not correlated with markers of allergic immune response Well behaved pharmacokinetic (PK) profile Estimated effective exposures at 0.25 mg/kg dose 18

19 CF-301: Ongoing Phase 2 Superiority Study Study population Adult patients with complicated Staph aureus bacteremia, including endocarditis, caused by MRSA or MSSA, receiving standard of care (SOC) antibiotic therapy Incidence ~200,000 hospitalizations/year in the US Current Therapy Clinical cure rates <50% with SOC therapy Mortality Mortality rates exceed 20% Resource Utilization Average length of hospital stay up to 21 days and cost up to $114,000 Source: AMR 2015 Data; 2012 GlobalData Market Research Report; Editor BWJ Mahy; Vol 6. Antimicrobial Resistance: Beyond the Breakpoint; Editor J. Todd Weber (US CDC) Klevens JAMA. 2007;298(15): ; Issues in Infectious Diseases; Fowler VG Jr, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med Aug 17;355(7):

20 CF-301: Ongoing Phase 2 Superiority Study Study design International, multi-center, randomized, double-blind, placebo-controlled clinical trial Superiority design compares CF SOC vs. Placebo + SOC 115 patients randomized 3:2 to receive single 2-hour IV infusion CF-301 or placebo Endpoints Primary endpoint: early clinical response (Day 14) Safety, tolerability and pharmacokinetics Additional clinical, microbiological and health resource utilization measures Key milestones First patient randomized in May 2017 Enrollment completed September 2018 Topline data expected in 4Q18 20

21 CF-301: Potential Advantages for Patient Care Our differentiated, first-in-class biologic should be compelling to key stakeholders Patients Rapid onset and more effective, well tolerated Providers Highly targeted activity, synergy when used in addition to standard of care and supportive of antibiotic stewardship Payors Decrease length of stay, reduce overall costs Regulators Novel approach, defined mechanisms of action, potentiates standard of care antibiotic therapies Aspirational Profile Assumes Clinical Results Replicate Expectations From Animal Models and Ultimate Regulatory Approval 21

22 GN Lysins Combating Multi-Drug Resistant Gram-Negative Infections Based on Novel Lysin Platform 22

23 Lysins Against GN Pathogens: Next IND Candidates Based on novel lysin platform Cloned a panel of over 500 native GN lysins and engineered them to bypass the outer membrane of GN bacteria and for high level activity in human blood Potential therapeutics to improve clinical cure rates for resistant Pseudomonas aeruginosa and other gram-negative infections Discovery-stage program Encouraging in vitro data of our GN lysins demonstrates the hallmark features of the lysin class Rapid, potent and targeted bactericidal activity Eradicates biofilms Synergy with SOC antibiotics Ability to re-sensitize resistant strains to antibiotics in vitro Low propensity for drug resistance Superior in vivo activity to be confirmed in future studies Robust IP position Patents filed for GN lysin candidates Source: Sauve et al., ASM Late Breaker Abstract (Sunday-HMB LB14),

24 GN Lysin Discovery Program Primary target 500+ lysins cloned 15 leads with potent in vitro activity against MDR P. aeruginosa Optimization ongoing Pseudomonas aeruginosa Escherichia coli 10 lysin candidates cloned In vitro characterization under way 2 lysin candidates cloned Ongoing identification of additional candidates Enterobacter cloacea Klebsiella pneumoniae 10 lysin candidates cloned In vitro characterization under way 24

25 MIC (CAA/HuS, µg/ml) GN Lysins: Engineered for Greater Potency Reduction in median MICs against MDR P. aeruginosa from 16 down to Native vs. Engineered Lysin Potency GN4 Family GN37 Family Median Native Median Engineered MICs (µg/ml) against a carbapenem-resistant clinical P. aeruginosa isolate were determined CAA (cationic adjusted media) plus human serum Source: Sauve et al., ASM Late Breaker Abstract (Sunday-HMB LB14),

26 MBEC (µg/ml) GN Lysins: Highly Potent Anti-Biofilm Activity MBECs of <1 against P. aeruginosa biofilms 0.7 Native and Engineered Lysin Anti-Biofilm Activity GN4 Family GN37 Family Median Native Median Engineered Eradication of biofilms formed by P. aeruginosa strain ATCC was examined in the Minimal Biofilm Eradicating Concentration (MBEC) assay. Source: Sauve et al., ASM Late Breaker Abstract (Sunday-HMB LB14),

27 FIC GN Lysins: Synergy with Antibiotics Synergistic across a broad range of antibiotics tested* Re-sensitized carbapenem-resistant P. aeruginosa (WC-453) to imipenem 5 Native and Engineered Lysin Synergy with Antibiotics Antagonistic Additive Strongly Additive Synergy Median Native Median Engineered *Fractional inhibitory concentrations (FICs) are the sum of MICs for two drugs used in combination to inhibit growth and are determined by a standard methodology; values of 0.5 are represent a synergistic interaction. Source: Sauve et al., ASM Late Breaker Abstract (Sunday-HMB LB14),

28 Therapeutic Potential of GN Lysins Against P. aeruginosa Attributes Rapid bacterial killing Biofilm eradication Synergy with SOC antibiotics Potential to re-sensitize antibiotic resistant strains Unmet needs Hospital acquired pneumonia/ventilator associated pneumonia Potential therapeutic uses In addition to conventional antibiotics to improve clinical cure rates compared to antibiotics alone To treat infections caused by XDR (extreme drugresistant) and PDR (pan drug resistant) P. aeruginosa Cystic fibrosis exacerbations Bacteremia Burns 28

29 CF-404 Inhaled Combination of mabs for Influenza 29

30 CF-404: Overview Based on a combination of three novel recombinant, fully-human mabs CF-401 Influenza A, Group 1 CF-402 Influenza A, Group 2 CF-403 Influenza B of both Yamagata and Victoria linages Preclinical-stage program Novel inhaled delivery facilitates direct viral neutralization in the upper and lower airway viral reservoirs thereby halting replication Encouraging in vivo data Rapid, potent and targeted activity Extends treatment window Robust IP Position Patent exclusivity until 2034 covering intranasal and inhaled administration 30

31 % Body Weight CF-404: Aerosolized Formulation Potent At Low Doses Aerosolized CF-404 in a mouse model of H1N1 influenza (3xLD 50 ), dose response study 110 Mice Infected with H1N1 Results: Mice treated with 0.8mg/kg were protected from morbidity and mortality Mice treated with lower doses (down to 0.04mg/kg) exhibited a delay in transient weight loss and were protected from lethal challenge Untreated mice succumbed to lethal infection Inhaled administration at lower doses more effective than higher systemic dose Days Post-Infection CF-404 (0.82mg/kg) CF-404 Alt. Formulation IP (5 mg/kg) 5mg/kg CF-404 (0.13mg/kg) CF-404 (0.04mg/kg) No Treatment No Virus 31

32 % Survival CF-404: Extends Treatment Window Mice with H1N1 Influenza (Survival at 14 Days) CF-404 (Single Dose) Tamiflu (Twice Daily x 5) Time to Initiate Therapy Source: ContraFect Data (Unpublished) 32

33 Corporate Information 33

34 ContraFect Leadership Proven Track Record of Creating Long-Term Shareholder Value Executive Management Steven C. Gilman, PhD CEO EVP, R&D and CSO, Cubist Pharmaceuticals, Chairman and CEO of ActivBiotics; Pfizer, Wyeth Natalie Bogdanos General Counsel & Corporate Secretary Assoc General Counsel Memorial Sloan-Kettering; General Counsel Enzo Biochem Cara Cassino, MD FCCP EVP, Research & Development & CMO SVP Global Clinical Development at Forest; VP Pfizer; Boehringer-Ingelheim Pharmaceuticals Michael Messinger SVP, Finance Director of Finance at Lexicon Pharmaceuticals Board of Directors Steven C. Gilman, PhD Chairman Sol Barer, PhD Lead Independent Director Former Chairman and CEO of Celgene Roger Pomerantz, MD Vice Chairman President, CEO and Chmn Seres Therapeutics; Former Global Head of Inf. Disease, Merck; J&J Isaac Blech Founder of Leading Biotech Companies: Celgene and ICOS David Low Investment Banker: MTS, Lazard, JP Morgan, Lehman Brothers Michael Otto, PhD Former Chief Scientific Officer, Pharmasset Cary Sucoff President, Equity Source Partners LLC 34

35 Key Financial Information Key Metrics As of June 30, 2018 Cash and Investments Total Debt Basic Shares Outstanding $33.3 million* $0.0 million 73.7 million* *on August 13, 2018, ContraFect issued 5.8 million shares with net proceeds of $10.4 million Analyst Coverage Chardan Janney Ladenburg Piper Jaffray William Blair Zacks Keay Nakae Esther Hong Kevin DeGeeter Edward Tenthoff Katherine Xu David Bautz Institutional investors Insiders Retail/Other 35

36 ContraFect Overview Lysin platform Novel class of anti-infectives Preclinical data supports multiple advantages as therapeutics CF-301 first-in-class lysin candidate for Staph aureus bacteremia Currently in Phase 2 superiority clinical trial, Enrollment completed Top-line data expected by end of 2018 Fast Track status granted by FDA Broad pipeline Novel lysins directed at drug resistant gram-negative (GN) pathogens o Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Enterobacter spp., E. coli Novel phage derived peptides with broad spectrum activity against GN pathogens CF-296 engineered CF-301 variant potential line extension in pre-clinical evaluation CF-404 inhaled triple antibody cocktail to treat influenza in pre-clinical evaluation 36

37 ContraFect Corporation First in class anti-infectives for life-threatening, drug-resistant infections Nasdaq: CFRX 37