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 and submission to

Corporate Presentation September 16,

2020 Cantor Healthcare Conference 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 and submission to the U.S. Food and Drug Administration (FDA) of a New Drug

Application (NDA) for tebipenem HBr and the potential approval of tebipenem HBr by the FDA; future commercialization, the potential number of patients who could be treated by tebipenem HBr and market demand for tebipenem HBr generally; expected

broad access across payer channels for tebipenem HBr; the expected pricing of tebipenem HBr and the anticipated shift from intravenous to oral administration; 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; 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: the Company's ability to timely complete related Phase 1

trials for NDA submission, taking into account the possible effects of the COVID-19 pandemic; the Company's need for additional funding; the lengthy, expensive, and uncertain process of clinical drug development; the Company's reliance

on third parties to manufacture, develop, and commercialize its product candidates, if approved; the ability to develop and commercialize the Company's product candidates, if approved; the potential impact of the COVID-19 pandemic; the

Company's ability to retain key personnel and to manage its growth; 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 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; whether

the FDA will accept a rolling NDA submission with respect to tebipenem HBr; whether the Company will satisfy all of the pre-conditions to receipt of the development milestone payment under its agreement with Everest Medicines; whether BARDA elects

to exercise its second option under the Company's agreement with BARDA; 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; the risks and uncertainties related to market conditions; 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. 102931629v.1 102931629v.1

Tebipenem HBr (previously SPR994):

First oral carbapenem ADAPT-PO Phase 3 met its primary endpoint in landmark trial - Oral tebipenem HBr demonstrated noninferiority to IV ertapenem in cUTI and AP; well-tolerated with comparable safety profile to intravenous ertapenem NDA

submission planned for 2Q21 Pipeline of assets supported by positive Phase 1 data SPR720: First potential oral therapy for NTM infections; granted orphan designation; Phase 2 planned for 2H20 SPR206: Novel therapy for MDR Gram-negative infections;

Phase 1 BAL study planned for 1H21 Multi-billion dollar opportunity for cUTI and NTM Largest unmet needs in infectious disease No approved branded or generic oral competition Marketed outside the hospital Spero: Robust Rare and Infectious Disease

Portfolio led by Oral Tebipenem HBr 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; MDR =

multidrug resistant infections; Tebipenem HBr = tebipenem pivoxil hydrobromide (formerly SPR994)

Cristina Larkin I Chief Operating

Officer Prior Vice President, Infection, Forest Laboratories 25+ years of commercial expertise with multiple antibiotic launches including Teflaro, Dalvance, Avycaz, Levaquin Launched seven products across variety of therapeutic categories in retail

and hospital Leadership Team Ankit Mahadevia, MD I Chief Executive Officer 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 David Melnick, MD I Chief Medical Officer Prior Vice President Clinical Development for anti-infectives; Allergan, AstraZeneca 18 years in anti-infective drug development including 16 Phase 3 trials Seven successful anti-infective

drug approvals Timothy Keutzer I Chief Development Officer Prior VP Program and Portfolio Management, Cubist Extensive antibiotic development experience from pre-clinical to approval Over 20 years in the pharmaceutical industry Tom Parr, PhD I Chief

Scientific Officer Prior CSO at Fedora Pharma and Targanta; Microcide, Head of Antibacterials, Eli Lilly Worked on a broad range of antibiotic classes and marketed antibiotics (oritavancin, vancomycin, ceftazidime, daptomycin, cephalexin, cefaclor,

loracarbef, anidulafungin) Over 26 years in drug discovery Stephen J. DiPalma I Chief Financial Officer (Interim) Managing Director of Danforth Advisors, LLC Worked as interim Chief Financial Officer to several public and emerging companies Previous

Chief Financial Officer at Forum Pharmaceuticals

Multiple Catalysts Across the Pipeline

Program Indication Preclinical Phase 1 Phase 2 Phase 3 Upcoming Milestone Partnerships/Alliances Partnerships/Alliances Oral Carbapenem for Gram Negative Multidrug Resistant (MDR) Infections Tebipenem HBr Complicated UTI (cUTI) NDA submission

for the treatment of cUTI planned for 2Q21 Oral DNA Replication Inhibitor for Non-tuberculous Mycobacterial (NTM) Disease SPR720 NTM Phase 2 study planned for 2H20 Direct Acting IV Potentiator for Gram Negative MDR Infections

SPR206 MDR Infections Phase 1 BAL study planned for 1H21 Positive Tebipenem HBr ADAPT-PO Phase 3 Topline Data Supports Expected NDA Submission in 2Q21 As of September 8, 2020

Spero Assets Share Common Attributes

With Other Successful ID Drugs Non-DRG reimbursement High unmet need with strong economic benefit $1 B+ Sales* *Estimated Peak Year Worldwide Sales

First Oral Carbapenem Tebipenem

Tebipenem HBr: Positive ADAPT-PO Phase

3 Trial Results Robust Results Support NDA Submission and Potential Treatment Shift from IV to Oral in cUTI Landmark ADAPT-PO Trial Met Primary Endpoint Positive ADAPT-PO Trial Results Support an NDA Submission in 2Q21 One well-controlled

pivotal trial to form the basis for an NDA submission as per FDA interactions Continue to expect to complete a new drug application (NDA) submission to the FDA in the second quarter of 2021 If approved, tebipenem HBr would be the only oral

carbapenem approved for complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) Potential to Transform how cUTI Patients are Treated Positive results in landmark study unprecedented for the field Overall combined response

rate: Oral tebipenem HBr response rate of 58.8% versus 61.6% for IV ertapenem (-3.3%; -9.7, 3.2; -12.5% NI margin)* Tebipenem HBr demonstrates favorable safety profile similar to ertapenem Tebipenem HBr, as the first oral carbapenem,

could allow appropriate patients the opportunity to receive treatment in the community setting Provides an important value proposition that could benefit patients, hospitals and payers NI, non-inferiority; NDA, new drug application * The trial at

95% confidence interval (CI) achieved success (a -9.7 NI margin) within the original -10% NI margin

Pivotal Phase 3 Trial Design:

Evaluation of Oral Tebipenem HBr compared IV Ertapenem Randomization All Oral Tebipenem HBr 685 patients All IV Ertapenem 687 patients Primary Endpoint Head-to-Head Comparison: Oral vs. IV Oral Only Tebipenem HBr (600mg q8h) IV Only Ertapenem

(1g q24h) Duration of therapy 7-10 days Adult patients 18 years Innovative Trial Design Compares an Oral-Only Regimen Directly Against an IV Regimen for cUTI and Acute Pyelonephritis (AP) Showing active treatment arms only; study is

placebo-controlled double-blind, double-dummy Combined Clinical Cure and Microbiological Eradication Additional evaluation at LFU (23-27 days after first dose of study drug) Non-inferiority margin of -12.5% Masked individual and composite PK

data reviewed by an independent review committee after enrolling the first 70 patients to confirm dose Screening Overall Response rate at TOC in micro-ITT population (17-21 days after first dose of study drug) vs. 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

ADAPT-PO Safety Population

Demographics: Representative of Anticipated cUTI Population Parameters balanced across treatment arms Mean age: 57 years; 43.6% age 65 years of age or older 55% female, 45% male population Baseline diagnosis of cUTI (52%) vs. AP

(48%) within range anticipated based on historical trials ~8% bacteremia at baseline; 19% met modified SIRS criteria; 39% infected with FQ non-susceptible pathogens SIRS, systemic inflammatory response syndrome FQ-non-susceptible = Levofloxacin MIC

ADAPT-PO Met Its Primary Efficacy

Endpoint ADAPT-PO primary endpoint: Clinical cure + microbiological eradication at test-of-cure in micro-ITT population Tebipenem HBr Demonstrates Statistical Non-inferiority Compared to Ertapenem Demonstrated non-inferiority at margin

of -12.5%* Results were similar between treatment arms across all subgroups of patients * The trial at 95% confidence interval (CI) achieved success (a -9.7 NI margin) within the original -10% NI margin

ADAPT-PO Key Secondary Endpoints

Support Robust Patient Outcomes Clinical cure rates at test-of cure for micro-ITT groups comparable between the oral tebipenem HBr and IV ertapenem treatment arms Comparable Clinical Cure Rates at TOC Median duration of therapy was similar for both

treatment groups Micro ITT = Microbiological Intent-to-treat

ADAPT-PO Safety and Tolerability

Results Safety and tolerability well balanced across the oral tebipenem HBr and IV ertapenem arms TEAE profile consistent with that of the carbapenem/beta-lactam class Diarrhea and headache were the most commonly reported TEAEs in both

treatment groups No C. difficile infections in tebipenem HBr arm No deaths reported SAE, serious adverse event; TEAE, treatment emergent adverse events; C.difficile, Clostridiodes difficile; ALT, alanine aminotransferase; AST, aspartate

aminotransferase Oral Tebipenem HBr IV Ertapenem Patients with at least one TEAE 25.7% 25.6% Diarrhea 5.7% 4.4% Headache 3.8% 3.8% ALT increase 1.0% 1.0% AST increase 1.0% 0.7% Serious TEAEs 1.3% 1.7% Drug-related SAEs 0.0% 0.3%

ADAPT-PO: Landmark Trial with

Potential to Change Clinical Practice Head-to-head results support potential effectiveness of tebipenem HBr with a favorable safety and tolerability profile in the treatment of cUTI/AP Landmark trial demonstrating value of

all oral regimen First all oral regimen for cUTI in 26 years, if approved Equivalent efficacy to IV ertapenem Meets primary endpoint in ADAPT-PO trial Safety profile comparable to IV ertapenem No drug related SAEs for tebipenem HBr; favorable GI

Lack of Oral Options for cUTI

is Widespread, Costly, and Addressable 2000-2004 Hospital Community $10,741 $7,083 76% Increase in hospitalizations +2 Days Longer Stays in Hospital Resistance + No Viable Oral cUTI Option = 2.3M Avoidable Hospitalizations Major Unnecessary

Cost Growing Fluoroquinolone Resistance 2000-2004 Tebipenem HBr could help shift care back to outpatient setting: Helping patients to Go Home or Stay Home 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). STEWARD 2019 Hospital resistance Data on file; BD 2019 community resistance data on file. Avoidable hospitalization estimates derived primarily from QuintilesIMS market assessment (August 2017); *Resistance

estimates directly from market assessment. cUTI= Complicated urinary tract infection 2019 2019

Tebipenem HBr has the Potential to

be a Highly Differentiated Therapy No branded or generic oral substitutes Existing, large, and growing unmet need Primary reimbursement outside of the hospital Current practice and financial incentives support usage Prescriber base beyond infectious

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. Hospital Avoidance Stay Home 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." Get Home Sooner From Hospital Go Home Sources: NYT Aug 20, 2019; IDSA Faces of Antimicrobial Resistance

Large Market Opportunity for Go Home

& Stay Home Patients Source: IQVIA 2019; Komodo 2020 data; Becton Dickinson Market Research, 2020 Targeted patients often cycle through multiple therapies 7.9 M UTI Patients in the US Spero Focus 2.7M UTI prescriptions 2nd line+ Oral or IV

therapy Lack of oral treatments has caused increased Outpatient visits Emergency department visits Unwarranted outpatient IV use Unnecessary hospitalization Hospital days Home Health and LTC stays post-hospitalization 5.2 M 1 st line Oral 1.6

M 2 nd line Oral (Resistant/Failed) 1.1 M IV Therapy/3rd+ line Oral (Resistant/Failed)

Targeted Launch Based on

Concentrated Prescribers and Focus on Urology Source:: IQVIA 2019; 1.35 = 50% of volume (deciles 6-10) from IQVIA 2019; Komodo 2020 data; Becton Dickinson Market Research, 2020 Initial sales team focused on high volume retail practices and hospitals

7.9 M UTI Patients in the US Spero Focus 50% patients in high-decile accounts Highly concentrated opportunity in both retail (4,000 accounts) and hospital (1,000 accounts) Spero will do staged ~100-125 FTE field force by further segmenting for:

Resistance (zip code level data) Favorable payer mix Adoption readiness, e.g. use of carbapenems Urologists: Largest treaters for 2nd line UTI patients across retail and hospital outlets2 5.2 M 1 st line Oral 1.6 M 2 nd line Oral (Resistant/Failed)

1.1 M IV Therapy/3rd+ line Oral (Resistant/Failed)

Unmet Need Identified by Healthcare

Providers; Expect Broad Access Across Payer Channels HCP identify carbapenems as the agent of choice for our target patients HCPs and Payers see value of tebipenem HBr Interactions with 100+ Health Care Professionals and 150M Payer Lives There is