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 design, initiation, timing and submis

Corporate Presentation Evercore ISI

HealthCONx Conference December 3, 2020 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 design, 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 direct and indirect impact of the pandemic caused by an outbreak of a new strain of coronavirus on the Company's

business and operations; 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 its planned NDA submission for tebipenem HBr, 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 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): 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; safety results similar to intravenous ertapenem NDA submission planned for 2H21

Pipeline of assets supported by positive Phase 1 data SPR720: First potential oral therapy for NTM infections; granted orphan designation; initiation of patient dosing in Phase 2 study planned by YE20 SPR206: Novel therapy for MDR Gram-negative

infections; Phase 1 BAL study planned for 1H21 Multi-billion dollar opportunity for cUTI and NTM Large unmet needs in infectious disease No approved branded or generic oral competition within carbapenem class Marketed primarily outside the hospital

Spero: Robust Infectious Disease and Rare 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) Stephen J. DiPalma I Chief Financial Officer (Interim) Managing Director of Danforth Advisors, LLC; Previous CFO at Forum Pharmaceuticals Worked as interim Chief Financial Officer to several public and emerging companies

*Trademarks are properties of their respective owners Tamara Joseph I Chief Legal Officer Over 20 years of leadership and legal experience in the biotech sector Prior General Counsel at several biotechnology companies including Millendo

Therapeutics, Enzyvant Therapeutics, InVivo Therapeutics, and Cubist

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 2H21 Oral DNA Replication Inhibitor for Non-tuberculous Mycobacterial (NTM) Disease SPR720 NTM Initiation of patient dosing in Phase 2 study planned by YE20 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 2H21 As of December 3, 2020

Spero Pipeline 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 *Trademarks are properties of their respective owners

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 2H21 One well-controlled

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

for treatment of complicated urinary tract infections (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 safety results similar to ertapenem Tebipenem HBr, if approved 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 to 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 Demonstrated 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 TBP-PI-HBr, tebipenem HBr; ERT, ertapenem

ADAPT-PO Key Secondary Endpoints

Evaluating Patient Outcomes Clinical cure rates at test-of cure (TOC) 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 Durable clinical response observed with high clinical cure rates at TOC sustained through late follow-up visit Clinical cure rate is a key determinant in routine clinical management

ADAPT-PO Safety and Tolerability

Results Safety and tolerability profiles similar across the oral tebipenem HBr and IV ertapenem arms TEAE rates generally 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 regulatory submission of tebipenem HBr for the treatment of cUTI/AP Landmark trial demonstrating value of all oral regimen Safety results similar to IV

ertapenem Met primary endpoint of combined clinical cure and microbiological response at TOC No drug related SAEs for tebipenem HBr; comparable GI TEAE rates First all oral regimen for cUTI in 26 years, if approved Non-inferior efficacy to IV

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 Potentially Avoidable Hospitalizations Major

Unnecessary Cost Growing Fluoroquinolone Resistance 2000-2004 If approved, 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 if Approved No branded or generic oral substitutes in the carbapenem class Existing, large, and growing unmet need Primary reimbursement outside of the hospital Current practice and financial incentives support

usage Prescriber base beyond infectious disease specialists

Tebipenem HBr Developed to Address 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. Stay Home: Hospital Avoidance "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." Go Home: Get Home Sooner From Hospital Sources: NYT Aug 20, 2019; IDSA Faces of Antimicrobial Resistance OPAT: Outpatient parenteral antimicrobial

therapy Treatment currently includes: Evaluation for systemic involvement requiring hospitalization Referral to urologist to evaluate structure abnormalities Cycling through available oral antibiotics to avoid hospital admittance Treatment currently

includes: Full course of IV antibiotics within the hospital OR Transition from hospital to outpatient IV antibiotic therapy and monitor for complications

Source: IQVIA NDS Database, Accessed

11/06/2018; AMR data on use by indication; 2017 UTI data projected Source: IQVIA NDS Database, accessed 11/06/2018 Ertapenem is the most used carbapenem to treat UTI Outpatient calculated as volume in "Clinics" and "Home Health and

Long Term Care" channels *Analysis excludes Meropenem - price, dosing regimen and stability data do not make it a widely used outpatient option 12% 115% *9M DOT x $350/day = $3 billion Carbapenem use in UTI and in outpatient setting has

increased significantly Carbapenem Market Estimated at $3B in United States Alone*

Large Market Opportunity for

Patients Able to Be Treated at Home Source: IQVIA 2019; Komodo 2020 data; Becton Dickinson Market Research, 2020 Pip/tazo = Piperacillin and tazobactam Targeted patients often cycle through multiple therapies Spero Focus 2.7M UTI

prescriptions 2nd line+ Oral or IV therapy Lack of effective oral treatment options has resulted in increased Outpatient visits Emergency department visits Unwarranted outpatient IV use Unnecessary hospitalizations Hospital days Home Health