Forward-looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, development plans, regulatory activities,

Company Presentation November 13, 2018

Forward-looking Statements This

presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, development plans, regulatory activities, anticipated milestones, product candidate benefits,

competitive position, business strategies, objectives of management, potential growth opportunities, potential market size, possible or assumed future results of operations, projected costs and use of proceeds. 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: uncertainties inherent in the initiation and completion

of preclinical studies and clinical trials and clinical development of the Company's product candidates, including adverse results in our clinical development processes; whether results from one clinical trial will be predictive of the results

of future trials and whether preliminary data from our clinical trials will be predictive of final results from such trials; decisions made by the U.S. Food and Drug Administration and other regulatory authorities with respect to the development and

commercialization of our products; availability of funding sufficient for the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements; our ability to obtain, maintain and enforce intellectual property

and other proprietary rights for our product candidates; our ability to implement our strategic plans; and other factors discussed in the "Risk Factors" section of the Company's periodic reports filed with the Securities and

Exchange Commission, and risks described in other filings the Company may make with the Securities and Exchange Commission 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.

Building the Next Great ID Company

Clinical Assets with Multiple Near Term Catalysts Significant Commercial Opportunity with SPR994 SPR994 has Supportive Safety and Efficacy Data Strong Management Team & Capital Base A multi-billion dollar U.S. market opportunity Focus on

community setting and early discharge from hospital Phase 3 trial designed to demonstrate "IV in a pill" value proposition Advancement into Phase 3 supported by positive Phase 1 study Phase 2 studies in Japan; 9 years of

clinical/post-marketing experience in Japan Proven management team with 14 approved drugs and 6 antibiotic launches Fully funded through Phase 3 SPR994 data readout, including up to $65M in non-dilutive support SPR994 - Oral Carbapenem - Phase

3 Initiation around YE18 SPR720 - Oral agent for NTM-Phase 1 Initiation early 2019 Potentiator platform: IV agents for Gram-negative infections - Phase 1 Initiation around YE18

Development Activities through 2019

Three Clinical-Stage Programs Phase 1 SPR994* SPR741 Phase 1b GRAM-NEGATIVE PROGRAM POTENTIATOR PLATFORM SPR720 Preclinical NTM PROGRAM 2018 SPR206 Preclinical Phase 3 Initiation in cUTI: Around YE18 As of November 13, 2018 Ongoing Development

Activity Planned Future Development Activity Our ability to progress SPR994 to a pivotal Phase 3 cUTI clinical trial is subject to a pre-Phase 3 meeting with the FDA to confirm no additional clinical trials or preclinical studies are required prior

to initiating a Phase 3 clinical trial. Following our discussions with the FDA, we expect to initiate a pivotal Phase 3 clinical trial of SPR994 for the treatment of cUTI around year-end 2018 in support of a new drug applications (NDA). Phase 3 Oral

Carbapenem IV Potentiator Oral Rare Orphan Disease Evaluation Ongoing Phase 1 Initiation: Early 2019 2019 Phase 1 Phase 1 Phase 1 Initiation: Around YE18

Blockbuster Anti-infectives Share

Common Attributes Estimated Peak Year Worldwide Sales High unmet need, limited generic competition Community Focus* Community focus < $200 M Sales* Dalvance;

Orbactive; Sivextro $200 - 500 M Sales* Avycaz; Vabomere; Tygacil $1 B+ Sales* Zyvox; Cubicin; Levaquin

Spero's Vision: High Value,

Sustainable Products Do not compete with generics Focus outside hospital DRG payment system Phase 3 data drives clinical and economic decisions Pipeline products that leverage sales force

First Oral Carbapenem:

SPR994: Fills Major Unmet Need for New

Oral Therapies for Resistant Infections 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. FQ= Fluoroquinolone; uUTI: Uncomplicated urinary tract infection Hospitalizations due to UTI are growing and cost

healthcare system $2.8 B a year Fluoroquinolone Resistance to E. coli in United States 2000-2004 2013-2014 Hospital Community 2000-2004 2013-2014 76% Increase in hospitalizations 1999-2011 Oral fluoroquinolones are the most widely used agents for

UTI Fluoroquinolone resistance and safety concerns are increasing Resistant patients are hospitalized due to lack of oral options

SPR994 Activity Comparable to IV

Carbapenems JMI Laboratories, 2017 Data on file; N=66 FQR: Fluoroquinolone resistant SPR994 against FQR Isolates of E. coli Result (mg/mL) SPR994 (tebipenem) Ertapenem (ETP) MIC90 0.06 0.25 MIC50 0.03 0.03 Range 0.015-0.25 0.015-0.5

SPR994: Clinical Data Supportive of

"IV Therapy in a Pill" Unique Molecule: Only carbapenem with >50% Oral Bioavailability High drug serum levels and urine concentrations at site of infection Phase 1 SAD/MAD final data supports 600 mg PO TID dose for Phase 3; comparable

to IV Ertapenem Enables powerful Phase 3 study design in cUTI: IV vs. Oral in patients with resistant infections Commercial and clinical experience in Japan add to strength of data package 3,500 patient post-marketing study supports safety and

tolerability Phase 2 cUTI studies support 600 mg PO TID dose Over 8 years on the market in Japan Phase 1 details: N=124 subjects dosed with Spero formulation or placebo (3:1 randomization), including 16 multiple dose exposures (x14 days) Source:

Phase 1 SAD/MAD Data: High Urine and

Plasma Exposures Relative to MIC90 600 mg 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 Free Plasma Concentrations of SPR994

Urine Concentration of SPR994 after a Single Dose 50% of TID dosing interval

Ertapenem IV + placebo oral SPR994

600 mg TID + placebo IV Planned Phase 3 Study to Demonstrate Oral-IV Equivalency Primary Endpoint: Microbiological response and Clinical Response at TOC (micro-ITT). Resolution of symptoms of cUTI present at screening and no new symptoms of cUTI,

and reduction of baseline bacterial pathogens to fewer than 103 CFU/mL on urine culture. Secondary Endpoints: 1. PK parameters (Vd, Cmax, AUC, T>MIC) in SPR994 recipients compared to PK parameters reported from Phase 1 studies in normal healthy

volunteers; 2) Population PK in SPR994 based on sparse sampling; 3) Clinical response at EOT, TOC, and LTFU visits (micro-ITT, CE, and ME); 4) Microbiological response at TOC and LTFU (micro-ITT and ME) by Overall, Baseline pathogen, Stratified

infection category, Country/Region; 5) Time to resolution of cUTI and AP; 6) Time to clinical cure (resolution of symptoms of cUTI present at randomization); 7) Time to microbiological success (reduction of the baseline bacterial pathogen(s) to

fewer than 104 CFU/mL on urine culture obtained daily during the treatment period; 8) Time to defervescence; 9) Time to urine sterility; 10) Rate of relapse, recurrence and superinfection at LTFU; 11) Rates of AE incidence Screening Follow-Up Phase

3 with lead-in PK 1:1 Randomization Double-blind, double-dummy N=1,100 Stratified by type of infection (pyelonephritis vs. complicated lower tract UTI) Up to 10 days total therapy 17 2 days from 1st dose of study drug 25 4 days from

1st dose of study drug TOC: Test-of-Cure Visit LTFU: Long-term Follow-up Visit * Masked individual and composite PK data will be reviewed by an IDMC after enrolling the first 70 patients to confirm the SPR994 dose. Efficacy and safety will remain

blinded. Patients 18 years with cUTI / AP Critical value proposition of SPR994 is that oral medication can achieve same outcomes as IV Only trial design in field to definitively address this question Lead-in PK to confirm dose TOC LTFU

SPR994 Has Differentiated Profile vs

Current and Future Oral Agents for cUTI ESBL Coverage Class A & Amp C High Bioavailability Safety & Tolerability Oral Only Trial for cUTI SPR994 Quinolones Sulopenem Etzadroxil/ Probenecid Omadacycline Source: Sulopenem scientific posters;

Paratek investor slides

Hospital UTI FQ-Resistant SPR994:

Multi-Billion Dollar Market Opportunity Market Segment LOT DAYS 7 DAYS 5.5 Community UTI FQ-Resistant Source: Estimates derived primarily from QuintilesIMS market assessment (August 2017); *Resistance estimates directly from market assessment FQ:

Fluoroquinolone Assumes pricing per day at peak of $348 DAYS 7 Hospital "Other" FQ-Resistant (BSI, HAP, cIAI) FQ-R* 12% 35% 35% Total Patients 10.2M 2.2M 1.1M $1.9 Billion Market Opportunity $900 Million US Market Opportunity Overview

SPR994 Commercial Benefits Hospitalized patients to shorten length of hospital stay Community patients to avoid hospitalization $2.3 Billion

Zyvox $1.4 B Peak Year Analogue for

Launch Success of SPR994 Zyvox MRSA Gram-positive Market SPR994 FQ-R Gram-negative Market Mkt size (pts) community 1 M 1.2 M IV/Oral switch 700 K 1.1 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 Peak year sales $1.4 B $1 B+** Zyvox Launch Curve-Time to Peak 5 Years to Peak *Estimated for SPR994 column based on 5.5% growth rate ** Estimated for SPR994 column based on

assumptions presented and $348 peak price Market Size for Zyvox is based on 14 M community cSSSI visits @ 5% resistance & 3.3 M hospital visits @ 29% IMS 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. Retail reaches peak share by Q20 Quarters Since Launch

SPR994: Differentiated Antibiotic

for a Large, Unmet Need Innovative oral carbapenem Safety and tolerably backed by a dataset of over 4,000 subjects and patients High drug serum levels and urine concentrations at the site of infection support utility in cUTI Rapid development plan

with single pivotal Phase 3 trial initiation in cUTI planned around year-end 2018 Multi-billion dollar U.S. market opportunity

First Novel Oral NTM Treatment:

NTM is a Rare Chronic Infectious

Disease A Growing Market 50,000-100,000 patients in U.S. suffer from NTM 8% annual increase in prevalence predicted YOY in the U.S. Unsatisfied Market No currently approved oral agents for NTM SOC has limited efficacy, high toxicity 5-yr mortality

rate of 35% Promising Regulatory Incentives Orphan designation Breakthrough status QIDP 1. Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir

Crit Care Med. 2012;185(8):881-886. 2. Strollo SE, Adjemian J, Adjemian MK, Prevots DR. The burden of pulmonary nontuberculous mycobacterial disease in the United States. Ann Am Thorac Soc. 2015;12(10):1458-1464. 3. NTMfacts.com

Current NTM Treatment Options Have

Limitations Approved Inhaled Therapy Generic Standard of Care FDA Approved Yes No Sputum Clearance: Refractory Patients 29% 9% Patient Outcomes: Refractory Patients No Improvement No Improvement Activity in Na ve Patients No No Broad Spectrum

No No No Black Box Warnings No No Oral Therapy No Yes Source: Briefing Information for the August 7, 2018 Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC)

SPR720: First Novel Oral Candidate

to Treat NTM Infections Clinical Stage Small Molecule Phase 1 SAD/MAD trial initiation in early 1Q19 - double-blind, placebo-controlled in healthy volunteers Oral Therapy Potentially first approved oral regimen for NTM Potent, Broad Spectrum of

Activity Potent activity against most common NTM species ( M. avium, M. abscessus, M. kansasii ) Multiple in vivo M. abscessus studies demonstrated efficacy No Significant Safety Findings Safety demonstrated in 7 day non-GLP; 28 day GLP NHP and 31

day GLP rat toxicity studies

Dose Responsive Efficacy Against

Difficult to Treat NTM Pathogens 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 n=6 n=6 n=6 n=6 n=6 n=6

Potentiator Platform: SPR741 &

Potentiators Allow Entry of

Antibiotics Into Gram-Negative Bacteria TREAT WITH POTENTIATOR Ab Ab Ab Ab Inner membrane Outer membrane Lipopolysaccharide Ab Ab Ab Peptidoglycan layer Ab Ab Ab Inner membrane Outer membrane Peptidoglycan layer Ab Ab Ab Ab Ab Lipopolysaccharide Ab

Ab Ab Ab Ab Zgurskaya, ACS Infectious Disease Potentiators Interact with lipopolysaccharide, disrupting the outer cell membrane and allow antibiotics to pass into the cell

Potentiator Platform Addresses IV

MDR Gram-Negative Hospital Market SPR741+partner SPR206 single agent WHO Priority Pathogens Potency against ESBLs Potency against CRE Potency against P. aeruginosa Potency against A. baumannii MOA Expands coverage of partner agents Single agent

SPR206 as Single Stand Alone Agent

Demonstrates Potency Against MDR & XDR Gram-Negative Pathogens SPR206 Meropenem Amikacin % isolates inhibited (n=20) MIC ( g/mL) MIC ( g/mL) MIC ( g/mL) IND Enabling Studies: Demonstrated wide therapeutic margins for the treatment

of serious Gram-negative infections Data supports advancement into clinical development

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 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 Cristina Larkin Chief

Operating Officer Prior Chief Financial Officer at Forward Pharma; three successful IPOs 17 years as a senior equity research analyst covering biotechnology, including at Lazard and Stifel 25 years of experience in the life sciences sector Joel

Sendek Chief Financial 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 David Melnick,

MD Chief Medical 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 Tom Parr,

PhD Chief Scientific Officer