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

Corporate Presentation June 4, 2020

Jefferies 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, 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; the intention, completion and timing related to the Company's rights offering and the intended use of proceeds from the rights offering; 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; the risks and uncertainties related to market conditions and the satisfaction of customary closing conditions related to the company's rights offering; 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 and the prospectus relating to the Company's rights

offering 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.

Spero Company Overview Spero

Therapeutics, Inc. is a multi-asset, clinical-stage company focused on developing and commercializing novel treatments for multidrug-resistant bacterial infections and rare diseases 1) as of 6/2/2020 2) as of 3/31/20 NASDAQ GS SPRO Market

Capitalization $254M1 Cash & equivalents $88.8M2 HQ Cambridge MA Founded 2013

Tebipenem HBr (previously SPR994):

First oral carbapenem Single Phase 3 trial required for approval in cUTI ongoing; Interim PK evaluation supports continuing trial at selected dose; Enrollment complete with topline data expected 3Q20 Phase 2 supports activity in cUTI; marketed since

2009 in Japan 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 2H20 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 Fully funded through potential NDA filing for tebipenem

HBr BARDA/DTRA award of up to $57M supports tebipenem HBr activities; additional non-dilutive funding supports pipeline Well capitalized through major inflection points 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 Led the commercial hospital antibiotic franchise team at Actavis/Forest; launched Teflaro, Dalvance, Avycaz Over 22 years of experience in commercial strategy 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) 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 Status Partnerships/Alliances Partnerships/Alliances Oral Carbapenem for Gram Negative Multidrug Resistant (MDR) Infections Tebipenem HBr Complicated UTI (cUTI) Phase 3 (ADAPT - PO)

enrollment complete; topline data in 3Q20 Oral DNA Replication Inhibitor for Non-tuberculous Mycobacterial (NTM) Disease SPR720 NTM Positive Phase 1 data; Phase 2 study planned for 2H20 Direct Acting IV Potentiator for Gram

Negative MDR Infections SPR206 MDR Infections Positive preliminary Phase 1 data; Phase 1 BAL study planned for 2H20 Tebipenem HBr Enrollment Complete and Phase 3 Data Expected in 3Q20 As of May 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 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 Tebipenem HBr Phase 3 Data Expected in 3Q20 Sources: NYT Aug 20, 2019; IDSA Faces of Antimicrobial

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 2013-2014 2000-2004 2013-2014 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).Avoidable hospitalization estimates derived primarily from QuintilesIMS market assessment (August 2017); *Resistance estimates directly from market assessment . cUTI= Complicated urinary

2 Pivotal Phase 3 Trial Evaluates Oral

Tebipenem HBr Efficacy Equivalence to IV Ertapenem Randomization All Oral Tebipenem HBr ~685 patients All IV Ertapenem ~685 patients Primary Endpoint Head-to-Head Comparison: Oral vs. IV Oral Only Tebipenem HBr (600mg TID) 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 and IV Regimen for cUTI and Acute Pyelonephritis Showing active treatment arm only; study is

placebo-controlled double-blind, double-dummy 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)* Screening Overall Response rate at TOC in micro-ITT population (17-21 days after first dose of study drug) vs. Abbreviations: 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

Safety, Efficacy and Pharmacokinetic

Data Support Ongoing Tebipenem HBr Phase 3 Trial Approximately 60% oral bioavailability High drug levels at infection site Interim Phase 3 data on plasma PK levels in patients confirms treatment dose Phase 2 cUTI studies demonstrate comparability to

the efficacy of approved IV agents Marketed in Japan for over 10 years; 3,540 patient safety database

Tebipenem Pivoxil Phase 2 Data are

Supportive of Activity in cUTI Tebipenem pivoxil hydrobromide = Spero's API, orally available prodrug salt; listed doses refer to dose of active tebipenem. Tebipenem pivoxil = Meiji's API, orally available prodrug; Phase 2 conducted by

Meiji Note: No head-to-head studies have been conducted and as such the data cannot be directly compared Sources:: 1) Tebipenem-PI Studies - L-084 04 CSR; ME-1211-1 CSR; cUTI subset of Phase 2 data; 2) Wagenlehner et al, Clin Inf Dis 63:754, 2016;

3) Kaye et al, JAMA 319:788, 2018 - Removable = removable cystitis, no N provided Dose ranging studies with tebipenem pivoxil completed in 72 patients from 300mg to 900mg daily dose in cUTI caused by lower UTI Infections Response rates at TOC

in the tebipenem pivoxil studies align well with response rates at TOC for intravenously administered approved drugs in this patient subset2,3 Microbiological Eradication at TOC

Urine Concentration of Tebipenem HBr

after a Single Dose Free Plasma Concentrations of Tebipenem HBr 50% of TID dosing interval 600mg dose provides >50% fT>MIC for E. coli and K. pneumoniae, the most prevalent cUTI pathogens High urine concentration affords additional margin of

exposure in cUTI High Urine and Plasma Exposures in Clinical Trials Support Tebipenem HBr Phase 3 Dose Data from Phase 1 SAD/MAD trial

Tebipenem HBr Stay Home Opportunity

1.2M (13%) patients have Resistant/ Recurrent infections or Fail oral therapies and have to receive IV antibiotics* ~$10,700 Hospitalization cost OR ~$5,000 OPAT cost + 25% complication rate *99% of patients are eligible for oral therapy 9.2M UTI

patients will receive an RX for oral antibiotics in the community 8M (86%) patients improve on orals Tebipenem HBr restores the ability to treat RRF UTI patients with oral therapy Effective oral therapy is preferred & achievable for most

patients 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

Tebipenem HBr Go Home Opportunity 1M

(35%) are resistant to oral therapies and must remain on IV antibiotics +2 Days longer in Hospital & ~$2K/day Loss to Hospital per patient & ~$9,000 Post Acute Care costs per patient 3.3M UTI patients either require hospitalization or

acquire UTI during hospitalization 1.8M (65%) will transition to oral therapy and go home (85% of patients will be ready to transition by day 3-4) Tebipenem HBr should enable transition to oral for more patients Effective oral options are critical

for transitions 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

Total Patients Oral Resistant*

Eligible for oral Target Population Community UTI Hospital Avoidance 9.2M 13% 99% 1.2M Hospital UTI Shorten LOS 3.3M 35% 85% 1M Infection Prevalence (In millions) Addressable DOT (In millions) Price Value (in billions) Branded Agents (approved or in

late development) UTI 12.5 16 $350 $5.4 2 Tebipenem HBr is a Multi-Billion Dollar Market Opportunity US Market Opportunity Overview x = = X X = Source: Estimates derived primarily from QuintilesIMS market assessment (August 2017); *Resistance

estimates directly from market assessment FQ: Fluoroquinolone *Estimated resistance in 2021. Assumes pricing estimate per day at of $350

Zyvox MRSA Gram-positive Market

Tebipenem HBr FQ-R Gram-negative Market Mkt size (pts) 1.8 M 2.2 M Resistance to oral options at launch 29% 36% Resistance to oral options at peak 64% 66%* Reimbursement landscape Restricted Restricted Pricing model Premium Premium Zyvox Launch

Curve-Time to Peak 5 Years to Peak Retail reaches peak share by Q20 Quarters Since Launch Zyvox $1.4 B Peak Year "Go-Home/Stay Home" Analogue for Tebipenem HBr Launch *Estimated for tebipenem HBr column based on 5.5% growth rate Market

Size for Zyvox is based on 14 M community cSSSI visits @ 5% resistance & 3.3 M hospital visits @ 29%. MS extended units and sales for linezolid; Resistance trends, Moran, New England Journal Med 355:7;2006; Monique R. Bidell et al. Antimicrob.

Agents Chemother. 2016;60:3170-3173; OFID Simmering et al; 2017 Winter.

Rare Disease Pipeline

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." Fatigue "I've been in the grocery store with the shopping cart, but I didn't have the energy to wait in line to check out."

Dyspnea Limits the types of activities that people are able to do, including walking, shopping, or traveling. Non-tuberculous mycobacterial disease (NTM) causes chronic and serious lung disease with debilitating symptoms that leads to a decline in

lung function. It can have a significant physical and emotional impact on patients. SPR720 has orphan drug designation and could be the first and only oral treatment for NTM NTM: An Absence of Effective and Well-tolerated Drugs Leaves Patients