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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 resu

Key Takeaway: Company Presentation KOL Breakfast Event December 5, 2019 Exhibit 99.1 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, pro

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Company Presentation KOL Breakfast
Event December 5, 2019 Exhibit 99.1
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 and development programs, including management's assessment of such results; regulatory activities, including the Company's expectation that positive results from a single pivotal Phase 3
clinical trial of Tebipenem HBr and ancillary supportive studies to be conducted in parallel with the Phase 3 trial will support the approval of Tebipenem HBr; the timing of the availability of data from the Company's clinical trials; the
timing of the Company's filings with regulatory agencies; product candidate benefits; competitive position; business strategies; objectives of management; potential growth opportunities; potential market size; reimbursement matters;
possible or assumed future results of operations; projected costs; and the Company's cash forecast and the availability of additional non-dilutive funding from governmental agencies beyond any initially funded awards. In some cases,
forward-looking statements can be identified by terms such as "may," "will," "should," "expect," "plan," "aim," "anticipate," "could,"
"intent," "target," "project," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or the negative of these terms or
other similar expressions. All statements other than statements of historical facts contained in this presentation are forward-looking statements. The Company may not actually achieve the plans, intentions or expectations disclosed in
these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: whether results
obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials and whether preliminary data from the Company's clinical trials will be predictive of final results from such
trials; whether the Company's product candidates will advance through the preclinical development and clinical trial process on a timely basis, or at all, taking into account such factors as the effects of possible regulatory delays,
slower than anticipated patient enrollment, manufacturing challenges, clinical trial design, clinical data requirements and clinical outcomes; whether the results of such clinical trials will warrant submission for approval from the U.S. Food
and Drug Administration (FDA) or equivalent foreign regulatory agencies; decisions made by the FDA and equivalent foreign regulatory agencies with respect to the development and commercialization of the Company's product
candidates; the commercial potential of the Company's product candidates; the Company's ability to obtain adequate third-party reimbursement for its product candidates; the Company's ability to implement its strategic
plans; the Company's ability to obtain, maintain and enforce intellectual property and other proprietary rights for its product candidates; whether the Company's cash resources will be sufficient to fund its continuing operations
for the periods and/or trials anticipated; and other factors discussed in the "Risk Factors" section of the Company's periodic reports filed with the U.S. Securities and Exchange Commission (SEC), and risks described in other
filings the Company may make with the SEC in the future. The forward-looking statements included in this presentation represent the Company's views as of the date of this presentation. The Company anticipates that subsequent events and
developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not
be relied upon as representing the Company's views as of any date subsequent to the date of this presentation.
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 cleared to go home. His discharge was delayed because the resistant nature of the bacteria would require insurance approval of home IV antibiotics. " Profession: Pharmacy Resident Infection: ESBL E. coli Nearly
13 million annual episodes of Gram-negative infections in the hospital in developed markets Bad Bugs, No Drugs: A Public Health Crisis Brews
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 in bacterial infections: Over 2M cUTI patients annually need better therapies No approved competition and marketed outside hospital Fully funded through Phase 3 top line data for Tebipenem HBr BARDA/DTRA award of up to $57M
supports Tebipenem HBr activities SPR720: First potential oral therapy for NTM infections - Positive Preliminary Phase I data supports advancement to Phase 2 Single Phase 3 trial required for approval in cUTI ongoing; Interim PK evaluation
supports continuing trial at selected dose Phase 2 supports activity in cUTI; marketed since 2009 in Japan cUTI = complicated urinary tract infections; ancillary supportive studies also required for Tebipenem HBr in addition to single Phase 3 trial
NTM = non-tuberculous mycobacterial PK - Pharmacokinetic
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 Inhibitor for Non-tuberculous Mycobacterial (NTM) Disease SPR720 NTM Positive preliminary Phase 1 data; Phase 2 planned 2H20 IV Potentiator Platform for Gram Negative MDR Infections SPR206 and SPR741
MDR Infections Phase 1 ongoing - data in 4Q19 Multiple Near-term Catalysts Across the Rare and Infectious Disease Portfolio As of December 5, 2019
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 per indication, with exception of NTM at 270 days. Addressable DOT = Prevalence x resistance x LOT Sources: IMS/Quintiles market assessment 2017; Clarion Market Assessment 2017; Decision Resources Gram Negative 2015; AMR
Data 2015; CDEEP, AAFP; Postgrad Med., 2010;12(2):130-141. J Antimicrob Chemother 2013;68: 4-11; Antimicrobial Agents and Chemotherapy 2014;58 (4): 2469 - 2471 Branded Agents (approved or in late development) 2 2 6 3 2
First Oral Carbapenem: Tebipenem
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 Forum Infectious Diseases 4.1 (2017): ofw281. PMC. Web. 15 Mar. 2018.; (Simmering et al. 2011) Avoidable hospitalization estimates derived primarily from QuintilesIMS market assessment (August
2017); *Resistance estimates directly from market assessment cUTI= Complicated urinary tract infection Major Unnecessary Cost Growing Fluoroquinolone Resistance 2000-2004 2013-2014 Hospital Community 2000-2004 2013-2014 35%
fluoroquinolone resistance to E. coli in the hospital, 12% in the community Median Cost Median Reimbursement Admitted cUTI patients cost US hospitals almost $11K; only $7K is reimbursed $10,741 $7,083 Oral Tebipenem HBr could offer cUTI patients the
chance to Go Home Sooner or Stay Home Resistance + No Viable Oral cUTI Option = 2.3M Avoidable Hospitalizations
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 competition Existing market with current prevalence in millions
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 infection site: Key to Go Home / Stay Home value proposition Clinical Data Support Efficacy Potential Interim Phase 3 data on plasma PK levels in patients comparable to plasma levels in Phase 1 trial of healthy
volunteers; confirms treatment dose Phase 2 cUTI studies demonstrate comparability to approved IV agents Significant Safety Database and Post Market Experience 9 years of post market experience with tebipenem pivoxil in Japan; 3,540 patient safety
database Phase I and preclinical studies correlate with safety database
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-Head Comparison: Oral vs. IV Oral Only Tebipenem HBr (600 mg TID) IV Only Ertapenem (1 g q24h) Duration of therapy 7-10 days Adult patients 18 years Abbreviations: AP, acute pyelonephritis; cUTI, complicated urinary
tract infection; ITT, intent-to-treat; IV, intravenous; LFU, long-term follow-up; q24h, every 24 hours; TID, three times daily; TOC, test-of-cure. Masked individual and composite PK data reviewed by an independent review committee after enrolling
the first 70 patients to confirm dose; trial remains blinded Innovative Placebo-Controlled, Double-Blind, Double-Dummy Trial Design Compares an Oral-Only Regimen Directly Against IV Showing active treatment arm only Combined Clinical
Cure and Microbiological Eradication (non-inferiority margin of 10%). Additional evaluation at LFU (23-27 days after first dose of study drug) PK lead-in data from 33 patients support continuing without dose modification (Oct 2019)*
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 volunteers, where coverage was similar to that of IV ertapenem Plasma concentrations confirm Phase 3 dose Data support advancing ADAPT-PO trial as per protocol at the current dose with topline data expected in 3Q20 Dataset Conclusion
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 concentrations in patients are comparable to Phase 1 plasma concentrations in healthy subjects Pharmacokinetic Model Utilizing Tebipenem HBr Phase 1 Data
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 evaluate Tebipenem HBr's ability to treat serious infection without IV lead-in, going beyond the limitation of current oral options by offering a powerful and effective IV replacement. IV to Oral = IV Objective of Tebipenem
HBr Oral = IV Significant Momentum Behind Oral Therapy for Serious Infections Source: Iversen et al. N Engl J Med 2019; 380:415-424; Pranita D. Tamma et al. JAMA Intern Med. 2019;179(3):316-323; Ho-Kwang li et al. N Engl J Med 2019;
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 Unnecessary hospitalization; prolonged LOS Emphasis on Treating Patients in Lowest Acuity Setting Feasible IV carbapenem use is 60% OPAT1 UTI Patients are Forced to Higher Acuity Settings Specialist / Ambulatory Center Increased use of UC
vs. ED Acute care in sub-acute settings Sources: 1. IQVIA 2018; 2. IBM 2019
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 months and had to get a medical withdrawal," she said. Timothy, a medical student, was hospitalized with E. coli that was highly resistant to a wide variety of antibiotics. His discharge was
delayed because the resistant nature of the bacteria would require insurance approval of home IV antibiotics. " The RRF Patient: Recurring and Resistant UTIs that Failed prior treatment Sources: NYT Aug 20, 2019; IDSA Faces of
Antimicrobial Resistance
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 cost (25% complication rate) Tebipenem HBr Stay Home Opportunity Hospital Avoidance while Reducing Overall Cost of Care Source: Allison GM, Muldoon EG, Kent DM, et al. Prediction model for 30-day hospital readmissions among patients
discharged receiving outpatient parenteral antibiotic therapy. Clin Infect Dis. 2014;58(6):812-819. doi: 10.1093/cid/cit920 https://www.the-hospitalist.org/hospitalist/article/128764/transitions-care/ready-post-acute-care FQ = Fluoroquinolone;
CPH = Cephalosporin ; OPAT - Outpatient Parenteral Antimicrobial Therapy Home Urologist OPAT Hospital 99% of patients are eligible for oral therapy
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 Hospital per patient & ~$9,000 Post Acute Care Costs per patient Tebipenem HBr Go Home Opportunity Early Hospital Discharge while Reducing Cost of Care Source: Allison GM, Muldoon EG, Kent DM, et al. Prediction model for 30-day
hospital readmissions among patients discharged receiving outpatient parenteral antibiotic therapy. Clin Infect Dis. 2014;58(6):812-819. doi: 10.1093/cid/cit920
https://www.the-hospitalist.org/hospitalist/article/128764/transitions-care/ready-post-acute-care FQ = Fluoroquinolone; CPH = Cephalosporin ; OPAT - Outpatient Parenteral Antimicrobial Therapy Home OPAT Hospital Post Acute Care Ctr 35% (1 M) are
resistant to oral therapies and require continued IV therapy
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 preferred oral option for ESBL switch therapy "Wow, wow, wow! We don't have any oral carbapenems now to send them home. This would shorten length of stay markedly and it covers ESBLs for hospital and community!"
Hospitalist "This would be good! I love it! It's an oral, well tolerated, it gives us another alternative." Urologist Sources: IQVIA research 2016 & 2019; based on provider interviews to inquire about agents in development
Provider call point is diversified beyond Infectious Disease for Tebipenem HBr
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 2021 Assumes pricing per day at of $350 Oral Resistant* 13% 35% Total Patients 9.2M 3.3M US Market Opportunity Overview X X Target Population 1.2M 1M = = UTI Infection Prevalence (In millions) Addressable DOT (In millions) Price Value
(in billions) 12.5 16 $350 $5.4 x = Branded Agents (approved or in late development) 2 99% 85% Eligible for oral
Last updated: Dec 5, 2019