Spero Therapeutics, Inc. · NASDAQ:SPRO
Spero Therapeutics — Investor Presentation (December 2019)
42 slides from Spero Therapeutics's investor presentation, Dec 5, 2019
Slide 1: Company Presentation KOL Breakfast Event
Company Presentation KOL Breakfast Event December 5, 2019 Exhibit 99.1
Slide 2: Forward-looking Statements
Forward-looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, the initiation, timing, progress and results of the Company’s preclinical studies and clinical trials and its research an
Slide 3: Bad Bugs, No Drugs: A Public Health Crisis Brews
Lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by Gram-negative pathogens “This particular strain of E. coli is highly resistant to a wide variety of antibiotics, making these infections especially difficult to treat. After many weeks, he was finally
Slide 4: Spero: Addressing Unmet Needs with Differentiated Assets led by Oral Tebipenem HBr
Spero: Addressing Unmet Needs with Differentiated Assets led by Oral Tebipenem HBr Tebipenem HBr (previously SPR994): First oral carbapenem Multibillion dollar opportunity for cUTI Well capitalized through major inflection points Differentiated pipeline with 2019 inflection points Largest unmet need
Slide 5: Multiple Near-term Catalysts Across the Rare and Infectious Disease Portfolio
Program Indication Preclinical Phase 1 Phase 2 Phase 3 Status Partnerships/ Alliances Partnerships/ Alliances Oral Carbapenem for Gram Negative Multidrug Resistant (MDR) Infections Tebipenem HBr Complicated UTI (cUTI) Phase 3 (ADAPT – PO) ongoing with topline data in 3Q20 Oral DNA Replication Inhibi
Slide 6: Spero's Pipeline Products are in $4B+ Markets
Spero’s Pipeline Products are in $4B+ Markets UTI Infection Prevalence (In millions) Addressable DOT (In millions) Price Value (in billions) ABSSSI CABP NTM CRE 12.5 16 $350 $5.4 17.3 7.6 0.1 0.2 1.7 .8 16 .7 $350 $350 $250 $1,000 $0.5 $0.2 $4.0 $0.7 x = Notes: Days of treatment range from 7 – 10 pe
Slide 7: First Oral Carbapenem: Tebipenem HBr
First Oral Carbapenem: Tebipenem HBr
Slide 8: Lack of Oral Options for cUTI is Widespread, Costly, and Addressable
Lack of Oral Options for cUTI is Widespread, Costly, and Addressable QuintilesIMS NDTI and MIDAS Database; Quintiles/IMS Market Assessment 2017, Simmering, Jacob E. et al. “The Increase in Hospitalizations for Urinary Tract Infections and the Associated Costs in the United States, 1998–2011.” Open F
Slide 9: Oral Tebipenem HBr has the Potential to be a Highly Differentiated Therapy
Oral Tebipenem HBr has the Potential to be a Highly Differentiated Therapy ✓ Primary reimbursement outside of the hospital Physician call point is diversified beyond infectious disease Usage consistent with current treatment paradigm and financial incentives No approved branded or generic competitio
Slide 10: Tebipenem HBr: Power of an IV in a Pill
Tebipenem HBr: Power of an IV in a Pill Tebipenem HBr = Spero’s API, orally available prodrug salt; Tebipenem pivoxil hydrobromide Tebipenem pivoxil = Meiji’s API, orally available prodrug High Oral Bioavailability Only Carbapenem with approximately 60% Oral Bioavailability High drug levels at infec
Slide 11: ADAPT-PO: Phase 3 cUTI / AP Trial to Evaluate Oral Tebipenem HBr Equivalence to IV Ertapenem
ADAPT-PO: Phase 3 cUTI / AP Trial to Evaluate Oral Tebipenem HBr Equivalence to IV Ertapenem Randomization All Oral Tebipenem HBr ~600 patients All IV Ertapenem ~600 patients Primary Endpoint Overall Response‡ rate at TOC in micro-ITT population (17-21 days after first dose of study drug) Head-to-He
Slide 12: Tebipenem HBr Phase 3 Interim Data Supports Continuing Trial to Topline Data
Tebipenem HBr Phase 3 Interim Data Supports Continuing Trial to Topline Data Following enrollment of first 70 patients, independent review committee evaluated blinded data from 33 patients on Tebipenem HBr Plasma PK levels in patients comparable to plasma levels seen in Phase I trial of healthy volu
Slide 13: Phase 3 Interim Data Confirms Dosing Rationale of Tebipenem HBr versus Ertapenem
Phase 3 Interim Data Confirms Dosing Rationale of Tebipenem HBr versus Ertapenem Das et al, ECCMID, 2019 PK - PD modeling from Phase 1 trial supports that the antimicrobial effect of oral Tebipenem HBr is comparable to IV ertapenem Phase 3 interim data suggests that Tebipenem HBr plasma concentratio
Slide 14: Bar has been raised to demonstrate oral equivalency to IV for serious infections
Bar has been raised to demonstrate oral equivalency to IV for serious infections Recent studies of other agents show that with oral potency equal to IV, transition to oral therapy is appropriate for serious infections such as endocarditis, osteomyelitis and bacteremia. ADAPT-PO has been designed to
Slide 15: Tebipenem HBr Designed to shift Treatment Momentum for Our Target UTI Patients
Tebipenem HBr Designed to shift Treatment Momentum for Our Target UTI Patients in the Right Direction Hospital ED / Urgent Care PCP Home Multiple rounds of failed oral antibiotics 1-2 ED visits per episode2 Focus on home health Limited specialist visits Hospital avoidance; early discharge Unnecessar
Slide 16: Tebipenem HBr Intended to Treat a Large and Existing UTI Population
Get Home Sooner From Hospital Hospital Avoidance Tebipenem HBr Intended to Treat a Large and Existing UTI Population Katrina, college student at the University of Kansas, experienced “a U.T.I. that did not respond to three different rounds of antibiotics.” “It got so bad that I was out of school for
Slide 17: Tebipenem HBr Stay Home Opportunity
9.2 M UTI patients will visit urgent care, ED, Urology and PCPs and receive Rx or oral medication 86% (8 M) will improve and get back to life 13% (1.2 M) fail or are resistant to oral therapies and require IV therapy Tebipenem HBr Potentially Avoids: ~$10,700 Hospitalization cost OR ~$5,000 OPAT cos
Slide 18: Tebipenem HBr Go Home Opportunity
65% (1.8 M) will transition to oral therapy and go home 3.3 M UTI patients either require hospitalization or acquire UTI during hospitalization 3-4 Day 85% of patients are stable and ready to be discharged at day 3-4 Tebipenem HBr Potentially Avoids: +2 Days Longer in Hospital & ~$2K/day loss to Hos
Slide 19: High Demand for Oral Carbapenems by Providers
High Demand for Oral Carbapenems by Providers Specialists: Urology ID 2nd line high volume MDs: LTC/PCP/IM Urgent Care Specialists: Urology ID Generalists: Hospitalists ED Community Prescribers cUTI 60-80% of MDs would prescribe Tebipenem HBr Hospital Prescribers cUTI Tebipenem HBr would be preferre
Slide 20: Tebipenem HBr: Multi-Billion Dollar Market Opportunity
Hospital UTI Shorten LOS Tebipenem HBr: Multi-Billion Dollar Market Opportunity Community UTI Hospital Avoidance Source: Estimates derived primarily from QuintilesIMS market assessment (August 2017); *Resistance estimates directly from market assessment FQ: Fluoroquinolone *Estimated resistance in 2
Slide 21: Tebipenem HBr Has Differentiated Profile
Tebipenem HBr Has Differentiated Profile Source: Sulopenem scientific posters; Phase 1 Tebipenem HBr trial, in vitro studies and post marketing data for Tebipenem Pivoxil; FQ warnings - Levaquin product label, September 2008; TMP/SMX - Sentry surveillance 1/2019; Nitrofurantoin - Camargo et al., Tre
Slide 22: Zyvox "Go-Home/Stay Home" Analogue for Tebipenem HBr Launch
Zyvox $1.4 B Peak Year “Go-Home/Stay Home” Analogue for Tebipenem HBr Launch Zyvox MRSA Gram-positive Market Tebipenem HBr FQ-R Gram-negative Market Mkt size (pts) 1.8 M 1.9 M Resistance to oral options at launch 29% 36% Resistance to oral options at peak 64% 66%* Reimbursement landscape Restricted
Slide 23: Rare Disease Pipeline: SPR720
Rare Disease Pipeline: SPR720
Slide 24: NTM is a rare infectious disease eligible for orphan designation and breakthrough status
NTM is a rare infectious disease where drugs are eligible for orphan designation and breakthrough status SPR720 could be the first and only oral treatment for NTM Severe cough: “It [coughing] could go on for a good 90 minutes, and I'm just down on the floor, on my knees, grabbing my ribs, hacking.”
Slide 25: SPR720: First Novel Oral Candidate Designed to Treat NTM Infections
SPR720: First Novel Oral Candidate Designed to Treat NTM Infections Broad spectrum, well-tolerated oral candidate: applicable to both non-refractory and refractory patients More than 75% of NTM patients are non-refractory; lack any approved options Planned once daily dose supported by clinical and n
Slide 26: Limitations of Current Therapy for NTM
Limitations of Current Therapy for NTM Approved Inhaled Therapy Generic Standard of Care Tolerability Poor Poor Proven Activity in Naïve and Newly Treated Patients No Limited Oral Therapy No Yes Source: Briefing Information for the August 7, 2018 Meeting of the Antimicrobial Drugs Advisory Committee
Slide 27: SPR720: Potential to Serve Multiple Unmet Needs in NTM
Source: Clarion market assessment, 2016; 2019 estimates assume 10% annual increase in diagnosed patients; U.S. Prevalence of 82K SPR720: Potential to Serve Multiple Unmet Needs in NTM Untreated: 29K Treated Front-line: 32K Treated Refractory: 21K Current US NTM Market = ~82K Prevalence Avg duration
Slide 28: SPR720 Patient Focus
Colonization Inflammatory disease (tissue burden drives inflammatory response) Anatomical disease (fixed lung injury) Treatment Naive Treatment Inexperienced Refractory Treatment benefits limited by: Declining lung function Additional co-morbidities Delay treatment due to: Intolerability Inconvenien
Slide 29: SPR720: Differentiated from Current Treatment
GyrB/ParE ATP DNA Gyrase is primarily responsible for introducing negative supercoils into conformationally constrained DNA during DNA replication SPR720: Differentiated from Current Treatment Novel chemical class: aminobenzimidazole Mechanism-of-Action: Gyrase inhibitor, not a fluoroquinolone High
Slide 30: SPR720 Support for Advancement to Phase 2
SPR720 Support for Advancement to Phase 2 In vivo and in vitro studies: Activity, tissue penetration PD modeling: Identify predicted therapeutic exposure Safety pharmacology, preclinical toxicology: Safety and tolerability at dose range SAD/MAD Phase 1: Assess dosing in healthy volunteers to determi
Slide 31: SPR720 Phase 1 SAD/MAD to Assess Safety, Tolerability and Pharmacokinetics
SPR720 Phase 1 SAD/MAD to Assess Safety, Tolerability and Pharmacokinetics N = 56 Subjects Dose Range: 100mg – 2000mg among 6 cohorts (including fed cohort at 1000mg) Additional Cohorts: Elderly at 500mg Randomization: 3:1, SPR720: placebo SAD Cohorts MAD Cohorts N = 40 Subjects Dose Range: 500mg –
Slide 32: Preliminary Phase 1 SAD/MAD Data Supports Advancing to Phase 2 Trial
Preliminary Phase 1 SAD/MAD Data Supports Advancing to Phase 2 Trial Preliminary, blinded data indicates therapeutic exposure can be attained with a well-tolerated dose (500 – 1000mg once daily) Single Ascending Dose Cohorts: Well Tolerated No SAEs reported; Mild GI symptoms at >1500mg Multiple Asce
Slide 33: Proposed Once Daily Phase 2 Treatment Dose Supported by Several Models
Proposed Once Daily Phase 2 Treatment Dose Supported by Several Models SPR720 500mg – 1000mg QD dose range supported by: In vitro models Inhibitory concentrations (MIC 90 ) <4 m g/mL for clinically relevant NTM strains. Favorable to amikacin In vivo models Activity comparable to amikacin in murine N
Slide 34: In vitro Activity Against a Range of NTM Species
In vitro Activity Against a Range of NTM Species Abbreviation: AMK: Amikacin Source: Brown-Elliott, B.A., et. al. Antimicrob Agents Chemother. 2018; 62 (11): e01503-18. *SPR719 is the active parent of SPR720 and is used for in vitro testing NTM Species N SPR719 MIC50 SPR719 MIC90 AMK MIC90 M. absces
Slide 35: SPR720 Demonstrated Clinical Dose Response
SPR720 Demonstrated Clinical Dose Response Multidrug resistant M. abscessus strain infection set for 27 days, dosing in SCID mice days 27 to 61. AMK=Amikacin SQ dosed every 24h. SPR720 dosed every 48h at the doses listed above Lung Infections in Multidrug Resistant M. abscessus Strains in Murine Mod
Slide 36: Macrophage Data Supports Intracellular and Extracellular Activity of SPR720
Macrophage Data Supports Intracellular and Extracellular Activity of SPR720 NTM is an intracellular pathogen residing in pulmonary macrophages SPR719 is concentrated intracellularly, where antimicrobial activity is needed >300:1 ratio of intracellular to extracellular concentration of SPR719 Underst
Slide 37: Bronchoalveolar Lavage Study in Non-Human Primates Supports Lung Exposure
Bronchoalveolar Lavage Study in Non-Human Primates Supports Lung Exposure The penetration of SPR719 into lung fluid (BAL, epithelial lining fluid) has previously been studied in non-human primates Drug concentrations in lung fluid in excess of the MIC90 of the targeted NTM strains were attained base
Slide 38: Proposed Phase 2a: Early and Robust Clinical Proof of Concept
Proposed Phase 2a: Early and Robust Clinical Proof of Concept Phase 2a Trial in NTM Treatment Population Objectives Safety, Tolerability, Plasma PK Lung PK, Macrophage analysis Number of patients with partial or complete microbiological response as assessed by a change in sputum bacterial burden ove
Slide 39: Initial Rate of Bacterial Response Predicts Long-term Response to Pulmonary MAC Treatment
Initial Rate of Bacterial Response Predicts Long-term Response to Pulmonary MAC Treatment Source: Semiquantitative Culture Analysis during Therapy for Mycobacterium avium Complex Lung Disease. David E. Griffith, Jennifer Adjemian et al. American Journal of Respiratory and Critical Care Medicine Volum
Slide 40: Financial Overview
Financial Overview Fully funded through Tebipenem HBr Phase 3 topline data expected in 3Q20 BARDA/DTRA non-dilutive funding support for up to $56.7M Recent awards and alliances provide additional funding for pipeline - Novo REPAIR Fund investment; Gates MRI collaboration; DoD award $ in 000’s Income
Slide 41: Leadership Team
Leadership Team Prior Venture Partner at Atlas Venture; Arcion Therapeutics, Genentech, McKinsey Formed eight companies in the life sciences sector; three as Acting CEO Background in healthcare policy Ankit Mahadevia, MD Chief Executive Officer Prior Chief Scientific Officer at Fedora Pharma and Tar
Slide 42: Experienced management team Multiple drugs in clinical development Large opportunity in complementary markets Signifi…
Experienced management team Multiple drugs in clinical development Large opportunity in complementary markets Significant near-term catalysts Accelerated path to market Novel approaches to development
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