Zoliflodacin (ETX0914) for Uncomplicated Gonorrhoea Global Antibiotic Research and Development Partnership, Pasteur Institute, 29 February, 2016
Entasis Therapeutics - Introduction Entasis Therapeutics is developing a portfolio of innovative cures for serious drug-resistant bacterial infections Located in Waltham, MA, USA; established May 2015 Strong financial position with $40 MM Series A financing First-in-class Phase 2 drug candidate to cure uncomplicated gonorrhoea Proprietary discovery platform with the potential to deliver additional novel drug candidates Innovative chemistry, unique biological and mechanistic insights Highly experienced team with an impressive scientific and managerial track record 1
Entasis has a Highly Experienced Leadership Team Manos Perros, PhD, President and Chief Executive Officer Head of Infection imed and Site Head, AZ Boston Director, Novartis Institute for Tropical Diseases CSO, Antivirals, Pfizer; co-inventor of maraviroc, PhRMA Discovers Award 2010 & Prix Galien 2008 Michael Fitzgerald, Chief Financial Officer SVP & CFO, Link Medicine Corp. CFO, Hypnion Inc. Robin Isaacs, MD, Chief Medical Officer VP and Therapeutic Area Head, Vaccines/Infectious Diseases Clinical Development, Merck Oversight of development and approval of numerous anti-infective, antiviral and vaccine products John Mueller, PhD, Vice President Program Management & Early Development Senior Project Director, AstraZeneca Infection imed Senior Director & Biology Head, Antibacterial Research, Pfizer Alexion Pharmaceuticals Ruben Tommasi, PhD, Chief Scientific Officer Executive Director, Infectious Disease Chemistry, AstraZeneca Executive Director Infection Chemistry; Head, Hit to Lead Optimization & Chemogenetics, Novartis Co-inventor tipranavir Chris White, Chief Business Officer CBO, AMAG Pharmaceuticals Partner at management consulting firms A.T. Kearney and Accenture Antibiotic product manager, Merck 2
Zoliflodacin (ETX0914) Overview 3
Gonorrhea is an Area of Significant Unmet Need N. gonorrhoeae is an immediate public health threat Highly contagious with low rates of resistance sufficient to drive new treatment recommendations Resistance to cefixime (oral cephalosporin) >1% 1 ; not recommended for use by CDC since 2012 Resistance to ceftriaxone (injectable cephalosporin, current standard-ofcare) is growing A 2012 report from the WHO reported worldwide estimates of over 106MM new cases of gonorrhea in 2008, up from ~90MM new cases in 2005 If untreated/poorly treated, gonorrhea can lead to pelvic inflammatory disease, infertility, and epididymitis % of N. gonorrhoeae Isolates with Reduced Susceptibility to Extended-spectrum Cephalosporins 3, * 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% China Japan Europe US 2010 2011 2012 1. CDC 2013 STD surveillance, susceptibility rates in the United States 2. CDC Antibiotic Resistance Threats in the United States, 2013 3. Cole MJ, et al. Euro surveill 2014;19(45) Cole MJ, et al. BMC Infect Dis 2015 4. Zheng H, et al. Japan J Infect Dis 2014;67:288-91 Hamasuna R, et al Japan J Infect Dis 203;19:571-8 Gu et al. BMC Infect Dis 2014 14:731 Hamasuna R, et al. J Infect Chemother 2015;21:1-6 CDC. STD Surveillance 2013.Atlanta, US Department of HHS 2014 http://www.cdc.gov/std/gisp2013/default.htm * Includes oral cefixime and ceftriaxone 4
Magnitude of Global Gonorrhoea Threat WHO Region Incidence (per 1,000) Male Female Incidence (Millions of cases) African 60.3 49.7 21.1 Americas 27.6 18.5 11.0 South-East Asia 37.0 16.2 25.4 European 7.0 8.3 3.4 Eastern Mediterranean 11.6 8.1 3.1 Western Pacific 49.9 34.9 42.0 Derived from WHO 2012 5
Resistance to extended-spectrum cephalosphorins is of great concern Territory % of N. gonorrhoeae Isolates with Reduced Susceptibility to Extended- Spectrum Cephalosporins *, 1 USA 0.9% Europe 4.5% China 21% * Includes cefixime and ceftriaxone 1 CDC 2013 STD surveillance, susceptibility rates in the US; CDC Antibiotic Resistance Threats in the US, 2013; Cole MJ, et al. Euro Surveill 2014 19(45); Zheng H et al. Japan J Infect Dis 2014 67:288-91; Hamasuna R et al Japan J Infect Dis 203 19:571-8; Hamasuna R et al J Infect Chemo 2015 21:1-6 6
Zoliflodacin for Uncomplicated Gonorrhea Drug Profile First of a novel class of topoisomerase inhibitors against Neisseria gonorrhoeae Population CDC estimates 820,000 cases of gonorrhea per year Concerns of growing resistance in available therapies Zoliflodacin s unique resistance profile, excellent tolerability and oral dosing will differentiate it from other therapies Label / Indications One time oral therapy for eradication of infection Data to Date Status Next Steps Phase 1: Linear PK and well tolerated up to 4 grams Achieved exposures in excess of those required for efficacy Phase 2 conducted in partnership with NIAID; enrollment complete FDA and MHRA endorsed Phase 2 and 3 endpoints Phase 3 formulation development on track Initiate thorough QT study/relative bioequivalence of Phase 3 formulation 7
Zoliflodacin is a First-in-class Antibiotic for the Treatment of Uncomplicated Gonorrhoea Current standard of care faces emerging resistance Threat of resistance rated as Urgent by CDC Zoliflodacin is from a novel class, no pre-existing resistance 1 Zoliflodacin is orally bioavailable Oral treatment could expedite partner therapy, increasing commercial potential Zoliflodacin is generally well-tolerated up to 4g Designated QIDP* and granted Fast Track status by the US FDA 1. Responding to the challenge of untreatable gonorrhea: Zoliflodacin, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases. Basarab, G. et al. Nature Scientific Reports; September, 2015 * Qualified Infectious Disease Product 8
Zoliflodacin has the Best Microbiological Profile Against Contemporary Clinical Isolates of N. gonorrhoeae Lack of Cross Resistance to Other Antibiotic Classes Mechanism Distinct from Fluoroquinolones Cumulative % at Each MIC (µg/ml)* Compound 0.008 0.015 0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 >32 Zoliflodacin 4.4 4.4 7.6 30 87.6 100 Ciprofloxacin 19.6 28.4 29.2 29.2 30.8 34.8 35.2 36.8 39.2 48 57.2 63.2 88.8 100 Azithromycin 0.4 3.6 8 16.4 32.4 54.8 83.2 88.8 92 94.8 97.2 98.4 100 Cefixime 29.6 60.4 71.2 80.4 89.2 95.6 98.4 98.8 98.8 99.6 100 Ceftriaxone 44 56 72.4 87.6 97.6 98.8 98.8 98.8 99.6 100 Susceptible Intermediate Resistant * The strains comprised 29 international gonococcal reference strains, including the 2008 WHO reference strains, 100 consecutive clinical Swedish gonococcal isolates obtained in 2013, and 121 isolates selected for their resistance phenotype. The collection included all of the currently described XDR gonococcal strains, additional isolates with in vitro and clinical ESC resistance, different types of ciprofloxacin resistance, and other high-level clinical resistance and multidrug resistance (MDR) to other antimicrobials previously used for treatment. (Jacobsson S. et al. Antimicrob. Agents Chemother. 2014. 58:9:5585-8) 9
Development Plan for Zoliflodacin 2015 2016 2017 2018 2019 Phase 2 Safety & Efficacy Phase 2 Read-out Phase 3 Prep (TQT, Rel. Bio) Phase 3 Efficacy Phase 3 Read-out NDA Prep, Submission & Review Approval & Launch Phase 3 Trial Design Multi-center, randomized, open-label Approximately 600 patients (2:1) Non-inferiority vs. ceftriaxone 500mg I.M. Primary endpoint: Microbiologic eradication Partnering strategy being evaluated 10
Zoliflodacin offers a medical breakthrough in the management of uncomplicated gonorrhea Product s Characteristics Oral Therapy for Gonorrhea Eradication Benefits Avoids painful intramuscular injections No need for crash cart or patient monitoring following treatment Opportunity to treat both the patient & their partner Novel Mechanism of Action Lack of pre-existing clinical resistance limits concerns about treatment failure One Time Treatment Single visit for treatment 11
Entasis Therapeutics is seeking a partner to support the Phase 3 clinical development program of zoliflodacin Phase 2 study has completed enrollment Licensure in the US and in the EU will require a single Phase 3 study Approximately 600 patients Approximately 18-24 months from first patient enrolled to final clinical study report (approximately 13-months to enrol) Preliminary assessment does not predict significant ethnic sensitivity Results from clinical program in developed world should be directly relevant to low/middle-income areas 12
Questions? 13