Tebipenem HBr (SPR994) - Oral Carbapenem - Tebipenem HBr's ADAPT-PO Phase 3 trial met its primary endpoint, demonstrating non-inferiority to IV ertapenem in complicated urinary tract infections (cUTI) and acute pyelonephritis (AP), with similar safety results [5] - The overall combined response rate in the ADAPT-PO trial was 58.8% for oral tebipenem HBr versus 61.6% for IV ertapenem, a difference of -3.3% [21] - The company plans to submit an NDA for Tebipenem HBr in 2Q21 for the treatment of cUTI [5, 11] - If approved, Tebipenem HBr could address a multi-billion dollar opportunity in cUTI and NTM markets, with no approved branded or generic oral competition in the carbapenem class [6] - The carbapenem market is estimated at $3 billion in the United States alone [51] SPR720 - Oral Therapy for NTM Infections - SPR720 is a potential first oral therapy for non-tuberculous mycobacterial (NTM) infections, with orphan drug designation, and initiation of patient dosing in a Phase 2 study planned by YE20 [5] - More than 75% of NTM patients are non-refractory and lack any approved options to treat NTM [95] SPR206 - Novel Therapy for MDR Gram-Negative Infections - SPR206 is a novel therapy for multidrug-resistant (MDR) Gram-negative infections, with a Phase 1 BAL study planned for 1H21 [5] Financial Status - As of September 30, 2020, the company had $127.244 million in cash, cash equivalents, and marketable securities, funding operations into the first quarter of 2022 [118]

Spero Therapeutics, Inc. (NASDAQ:SPRO) Q3 2020 Earnings Conference Call November 5, 2020 4:30 PM ET Company Participants Sharon Klahre – Vice President of Investor Relations and Strategic Finance Ankit Mahadevia – Chief Executive Officer David Melnick – Chief Medical Officer Cristina Larkin – Chief Operating Officer Steve DiPalma – Interim Chief Financial Officer Conference Call Participants Carvey Leung – Cantor Vishal Sethi – Cowen Ellen Sands – Stifel Operator Operator Good day, and welcome to the Spero ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2020 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38266 SPERO THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) ( State or other jurisdiction of inco ...

Financial Data and Key Metrics Changes - Total revenue for Q2 2020 was $1.7 million, a decrease from $2.2 million in Q2 2019 [34] - R&D expenses increased to $15.7 million in Q2 2020 from $12 million in the same period of 2019, primarily due to higher spending on the tebipenem HBr program [36] - Net loss for Q2 2020 was $17.5 million, or $0.85 per share, compared to a net loss of $13.2 million, or $0.74 per share, in Q2 2019 [39] - Cash and cash equivalents as of June 30, 2020, were $71.4 million, expected to fund operations into Q1 2021 [40] Business Line Data and Key Metrics Changes - The ADAPT-PO trial for tebipenem HBr completed enrollment of 1,372 patients, with follow-up now complete [18] - The Phase I bronchoalveolar lavage clinical trial for SPR206 has been delayed to the first half of 2021 due to COVID-19-related issues [26] Market Data and Key Metrics Changes - There is a rising resistance to fluoroquinolone antibiotics, with over 20% resistance to E. coli in the community setting, which is a significant concern for treating complicated urinary tract infections (cUTI) [29] - The company estimates that over two million patients annually could benefit from a new oral therapy for cUTI [30] Company Strategy and Development Direction - The company aims to file a rolling NDA submission for tebipenem HBr in Q1 2021, pending positive Phase III data, with completion expected in Q2 2021 [11][19] - The focus is on developing oral antibiotics that can keep patients out of the hospital, especially in light of the COVID-19 pandemic [13][32] - The company is also exploring partnerships and funding opportunities, such as the AMR Action Fund, to support antibiotic development [15][82] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the data set for the ADAPT-PO trial, despite challenges posed by COVID-19 [73] - The ongoing pandemic has highlighted the need for effective outpatient treatments to prevent hospital admissions [13] - The company is monitoring the market environment closely and developing a digital strategy to engage healthcare providers [79] Other Important Information - BARDA has committed a total of $44 million in nondilutive funding, with $16.3 million received as of June 30, 2020 [35] - The company is preparing for the commercial launch of tebipenem HBr, emphasizing its potential to meet significant unmet needs in the antibiotic market [27][32] Q&A Session Summary Question: What are the outstanding Phase I studies needed for the NDA submission? - The ongoing Phase I studies include a bioequivalence study, a drug-drug interaction study, and a study in renally impaired patients [42] Question: Can you provide insights on potential pricing for tebipenem HBr? - Pricing discussions are ongoing, with initial estimates suggesting treatment costs could be around $5,000 per course [48] Question: How will the extension on the NDA filing impact commercial build-out? - The company plans to engage with customers early and often, regardless of the NDA timeline, to build demand for tebipenem [64] Question: What are the microbiological endpoints for the SPR720 Phase II study? - The study will focus on safety and pharmacokinetics, with microbiological endpoints measuring changes in bacterial burden via quantitative sputum cultures [50] Question: Are there any data integrity issues for the ADAPT-PO study due to COVID-19? - Management confirmed there are no data integrity issues and expressed confidence in the data set [73] Question: How is the company preparing for the commercialization of tebipenem HBr? - The company is developing a digital strategy and monitoring access to clinicians' offices as part of its commercialization efforts [79]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Commission File Number: 001-38266 SPERO THERAPEUTICS, INC. Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2020 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to (Exact name of registrant as specified in its charter) ( State or other jurisdiction of incorpora ...

Company Overview - Spero Therapeutics has a market capitalization of $247 million as of May 12, 2020, and cash & equivalents of $88.8 million as of March 31, 2020[5] - Spero Therapeutics is focused on developing treatments for multidrug-resistant bacterial infections and rare diseases[6] - The company's lead product candidate, Tebipenem HBr, is the first oral carbapenem, with a single Phase 3 trial required for approval in cUTI[8] Tebipenem HBr (cUTI) - Tebipenem HBr targets a multi-billion dollar market opportunity in complicated urinary tract infections (cUTI)[9] - A Phase 3 trial (ADAPT-PO) for Tebipenem HBr in cUTI is enrollment complete, with topline data expected in 3Q20[13, 14] - Approximately 60% oral bioavailability of Tebipenem HBr[31] - The company estimates that 1.2 million (13%) UTI patients have resistant/recurrent infections or fail oral therapies and have to receive IV antibiotics[41] - The company estimates that 3.3 million UTI patients either require hospitalization or acquire UTI during hospitalization[44] - The US market opportunity for Tebipenem HBr is estimated at $5.4 billion[49] SPR720 (NTM) - SPR720 is a potential oral therapy for Non-Tuberculous Mycobacterial (NTM) infections, with Phase 2 planned for 2H20[8] - More than 75% of NTM patients are non-refractory and lack approved treatment options[72] - Phase 1 data supports advancing SPR720 to Phase 2 trials, with a proposed dose of 500-1000mg once daily[85, 87] SPR206 (MDR Gram-negative Infections) - SPR206 is a novel therapy for multidrug-resistant (MDR) Gram-negative infections, with a Phase 1 BAL study planned for 2H20[8] - Phase 1 data indicates SPR206 is well-tolerated at doses likely to be within a therapeutic range for MDR Gram-negative bacterial infections[98] Financials - Spero Therapeutics reported total revenue of $1.701 million, R&D expense of $20.436 million, and a net loss attributable to common stockholders of $(23.258) million for the three months ended March 31, 2020[105] - The company's cash, cash equivalents, and marketable securities totaled $88.841 million as of March 31, 2020, funding operations into the first quarter of 2021[105, 106]

Spero Therapeutics, Inc. (NASDAQ:SPRO) Q1 2020 Results Conference Call May 8, 2020 10:00 AM ET Company Participants Sharon Klahre - VP of IR and Strategy Dr. Ankit Mahadevia - Chief Executive Officer Dr. David Melnick - Chief Medical Officer Cristina Larkin - Chief Operating Officer Steve DiPalma - Interim Chief Financial Officer Conference Call Participants Louise Chen - Cantor Stephen Willey - Stifel Kevin DeGeeter - Oppenheimer Esther Hong - Janney Ram Selvaraju - H.C. Wainwright Chi Fong - Bank of Ameri ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2020 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38266 SPERO THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) ( State or other jurisdiction of incorpor ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2019 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ____to____ Commission file number 001-38266 SPERO THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) | Delaware | | 46-4590683 | | --- | --- ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2019 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-38266 SPERO THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) ( State or other jurisdiction of inco ...