8-K
false 0001701108 0001701108 2020-09-08 2020-09-08

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 OR 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported) September 8, 2020

 

 

SPERO THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-38266   46-4590683

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

 

675 Massachusetts Avenue, 14th Floor

Cambridge, Massachusetts

  02139
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code (857) 242-1600

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading

Symbol(s)

 

Name of each exchange

on which registered

Common Stock, $0.001 par value per share   SPRO   The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  

 

 

 


Item 7.01.

Regulation FD Disclosure.

On September 8, 2020, Spero Therapeutics, Inc. (the “Company”), in connection with the positive topline results for its Phase 3 ADAPT-PO clinical trial of oral tebipenem HBr described below, issued a press release (the “Topline Data Press Release”) and provided an investor presentation (the “Topline Data Investor Presentation”), which will be made available on the Company’s website or distributed by the Company in hardcopy or electronic form.

A copy of the Topline Data Investor Presentation and Topline Data Press Release are attached as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K (this “Current Report”). The information set forth in this Item 7.01 and in Exhibit 99.1 and Exhibit 99.2 attached hereto is “furnished” and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section, nor shall such information be deemed incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended.

 

Item 8.01.

Other Events.

Tebipenem HBr – Positive Topline Results from Phase 3 ADAPT-PO Clinical Trial

On September 8, 2020, the Company announced positive topline results for the Phase 3 ADAPT-PO clinical trial of oral tebipenem HBr in complicated urinary tract infection (“cUTI”) and acute pyelonephritis (“AP”). The ADAPT-PO trial is the first ever trial to compare an all oral regimen against an all intravenous (“IV”) regimen for the treatment of cUTI. The pivotal Phase 3 clinical trial of oral tebipenem HBr met the primary endpoint, demonstrating statistical non-inferiority versus IV ertapenem. The primary endpoint of the trial was defined as the overall response rate (combined clinical cure plus microbiological eradication) at the test-of-cure (“TOC”) visit in the microbiological-intent-to-treat population (“micro-ITT”). Favorable overall response rates at TOC were 58.8% versus 61.6% for tebipenem HBr and ertapenem, respectively (treatment difference, -3.3%; 95% confidence interval [CI]: -9.7, 3.2; -12.5% NI margin). Clinical cure rates at TOC were high, at greater than 93% in both treatment groups, and overall response rates were consistent across key subgroups of interest.

In the ADAPT-PO trial, comparative safety data from the 1,372 hospitalized adult patients who enrolled in the trial suggest that tebipenem HBr was well-tolerated, with a safety profile similar to that of ertapenem. Treatment emergent adverse events (“TEAEs”) were reported in approximately 26% of patients in both treatment groups. The most commonly reported TEAEs in both treatment groups were diarrhea (5.0%) and headache (3.8%). Serious TEAEs were infrequent (1.3% for tebipenem HBr versus 1.7% for ertapenem) and no deaths were reported in the trial. Three Clostridiodes difficile-associated TEAEs were observed in the ertapenem group, while none were observed in the tebipenem HBr group.

ADAPT-PO is a global, randomized, placebo-controlled Phase 3 clinical trial that evaluated the safety and efficacy of tebipenem HBr in hospitalized adult patients with cUTI or AP. Patients were randomized (1:1) to receive 600 mg of tebipenem HBr orally every 8 hours, or 1 g of ertapenem IV every 24 hours, for a total of 7 to 10 days. Patients with concurrent bacteremia received up to 14 days of therapy. The primary endpoint was the overall response, defined as the combination of clinical cure and microbiological eradication of the causative pathogen(s), at the TOC visit (Day 19, plus or minus 2 days) and was assessed in the micro-ITT population. The primary analysis and assessment of non-inferiority was evaluated using a pre-specified -12.5% non-inferiority (“NI”) margin. This NI margin was a modification of the original NI margin of -10% that was discussed with the U.S. Food and Drug Administration (“FDA”) because of concern that the COVID-19 pandemic could have an adverse effect on the trial. As a result, the NI margin was modified prior to database lock from the original NI margin. However, as noted by the lower bound of the 95% confidence interval (-9.7), the trial also achieved success according to the original -10% NI margin.

The Company plans to present emerging data from the tebipenem HBr program, including the ADAPT-PO clinical trial results, in detail at future scientific meetings and in publications. The Company intends to initiate a rolling New Drug Application (“NDA”) submission and anticipates completing the NDA submission to the FDA for tebipenem HBr in the second quarter of 2021.


SPR720 – FDA Acceptance of IND Application

On August 31, 2020, the Company announced that the FDA accepted its investigational new drug (“IND”) application for SPR720. With the IND accepted, the Company expects to initiate a Phase 2a clinical trial evaluating SPR720 in patients with nontuberculous mycobacterial (“NTM”) pulmonary disease by year-end 2020. The planned Phase 2a clinical trial is designed as a multi-center, partially blinded, placebo-controlled proof-of-concept clinical trial that will enroll approximately 90 treatment-inexperienced patients with NTM pulmonary disease due to Mycobacterium Avium complex. Patients will be randomized to receive either 500mg or 1,000mg of oral SPR720, placebo or standard of care consisting of a macrolide and ethambutol, plus the option of adding a rifamycin. The objectives of the trial are to evaluate plasma pharmacokinetics, safety, tolerability, and microbiological response of SPR720 compared with placebo and standard of care over 28 days of treatment.

Forward-Looking Statements     

This report, including the exhibits hereto, may contain forward-looking statements. These statements include, but are not limited to, statements about the initiation, timing and submission to the FDA of a 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. 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. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important 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; and other factors discussed in the “Risk Factors” set forth in filings that the Company periodically makes with the U.S. Securities and Exchange Commission. The forward-looking statements included in this report, including the exhibits hereto, represent the Company’s views as of the date of this report. 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 report.

 

Item 9.01.

Financial Statements and Exhibits.

(d) Exhibits.

The following exhibits relate to Items 7.01 and 8.01, and shall be deemed to be furnished, and not filed:

 

Number

  

Exhibit Description

99.1    Topline Data Investor Presentation, dated September 8, 2020.
99.2    Topline Data Press Release, dated September 8, 2020.
104    Cover Page Interactive Data File (embedded within the Inline XBRL document)


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

               SPERO THERAPEUTICS, INC.
Date: September 8, 2020      

/s/ Stephen DiPalma

      Stephen DiPalma
      Interim Chief Financial Officer and Treasurer
EX-99.1

Slide 1

ADAPT-PO Phase 3 Topline Data Conference Call September 8, 2020 Exhibit 99.1


Slide 2

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.  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; 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.


Slide 3

ADAPT-PO Phase 3 Results Tebipenem HBr Building Spero as the leader in the field of antibiotic drug development Trial met primary endpoint of non-inferiority of oral tebipenem HBr versus IV ertapenem for the treatment of complicated urinary tract infections and acute pyelonephritis


Slide 4

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


Slide 5

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 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 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


Slide 6

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 ≥ 1 mcg /mL


Slide 7

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


Slide 8

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


Slide 9

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%


Slide 10

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


Slide 11

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)


Slide 12

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)


Slide 13

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 high agreement that relapsed, failed cUTI patients could be treated at home Payers expect to broadly cover tebipenem HBr due to unmet need for new oral therapy “We need more drugs for UTI beyond Macrobid for lower UTI, Keflex and Cipro. There is a lot of resistance to FQ, so if we want an oral, we need something new.” - Urologist “Switching to PO would be far preferable to a PICC and Home Health or having them return to an infusion center...” - KOL “We don’t have any oral carbapenems now to send them home. This would shorten length of stay markedly and it covers ESBLs for hospital and community!” – Hospitalist “The value proposition here is that you can avoid using the IV which I think certainly has some clinical benefit and may be even some economic benefit as well.”- National Payer Source:: IQVIA 2019; Precision Payer Landscape Research 2020; Key Opinion Leader Interviews, 2020


Slide 14

Tebipenem HBr Well Positioned to Recognize Significant Market Opportunity Value-Based Pricing Consistent with other unmet need antibiotics Favorable Payer Coverage Primarily reimbursed as a pharmacy benefit and not under hospital DRG Largest Unmet Need in Infection Today 2.7 Million resistant or failed cUTIs Robust IP Coverage through 2038; Granted QIDP and Fast Track designation Targeted Commercial Footprint Urology is primary treater for relapsed, refractory or failed cUTI patients in the community or hospital Commercial Support: Tebipenem HBr for the treatment of cUTI


Slide 15

Next Steps for Tebipenem HBr Complete NDA package - Meeting with FDA and completing Phase 1 trials Exploring lifecycle management opportunities – Microbiological surveillance and clinical studies Manufacturing readiness – Process validation and launch planning Launch readiness – Market development work, pricing research, distribution strategy, key hires


Slide 16

Multiple Catalysts Planned 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     As of September 8, 2020

EX-99.2

Exhibit 99.2

Spero Therapeutics Announces Positive Topline Results from its Phase 3 ADAPT-PO Clinical Trial of Oral Tebipenem HBr in Complicated Urinary Tract Infection and Acute Pyelonephritis

Pivotal Phase 3 clinical trial of oral tebipenem HBr met primary endpoint, demonstrating statistical non-inferiority versus intravenous ertapenem in patients with complicated urinary tract infection and acute pyelonephritis

Well-tolerated with comparable safety profile to intravenous ertapenem

Spero intends to complete NDA submission for U.S. regulatory approval of tebipenem HBr in the second quarter of 2021

Management to host conference call and live webcast at 8:00 a.m. EDT today

CAMBRIDGE, Mass., September 8, 2020 — Spero Therapeutics, Inc. (Nasdaq: SPRO), a multi-asset clinical-stage biopharmaceutical company focused on identifying, developing and commercializing treatments in high unmet medical need areas involving multidrug-resistant (MDR) bacterial infections and rare diseases, today announced positive topline results from ADAPT-PO, the pivotal Phase 3 clinical trial evaluating Spero’s oral antibiotic candidate, tebipenem HBr, for the treatment of adults with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP). Topline data from the trial demonstrate that oral tebipenem HBr was statistically non-inferior to intravenous (IV) ertapenem in the treatment of patients with cUTI and patients with AP.

The global Phase 3 ADAPT-PO clinical trial evaluated the safety and efficacy of oral tebipenem HBr versus IV ertapenem for the treatment of adults with cUTI or AP. Results demonstrate that tebipenem HBr was non-inferior compared to ertapenem with respect to the trial’s primary endpoint, overall response (combined clinical cure plus microbiologic eradication) at the test-of-cure (TOC) visit in the microbiological-intent-to-treat (micro-ITT) population.

 

   

The favorable overall response rates at TOC were 58.8% (264/449) versus 61.6% (258/419) for tebipenem HBr and ertapenem, respectively (treatment difference, -3.3%; 95% confidence interval [CI]: -9.7, 3.2; -12.5% NI margin).

 

   

Clinical cure rates at TOC were high (>93%) in both treatment groups.

 

   

Overall response rates were consistent across key subgroups of interest, including age, baseline diagnosis, and presence of bacteremia. Per pathogen microbiological response was balanced across treatment groups for most prevalent uropathogens.

“The results of ADAPT-PO are truly exciting and welcome news for the medical community and for the millions of U.S. patients suffering from cUTI and AP annually,” said Dr. Keith Kaye, Director of Research in the Division of Infectious Diseases at the University of Michigan Medical School. “Due to the increasing prevalence of antibiotic-resistant bacteria, many patients with cUTI now receive intravenous antibiotics as their only available treatment option. The much-anticipated data from this head-to-head comparison against an IV standard-of-care carbapenem antibiotic suggest that in many instances oral, outpatient treatment of these complicated bacterial infections is a viable option.”


Comparative safety data from the 1,372 hospitalized adult patients who enrolled in the trial suggest that tebipenem HBr was well-tolerated, with a safety profile similar to that of ertapenem.

 

   

Treatment emergent adverse events (TEAEs) were reported in approximately 26% of patients in both treatment groups.

 

   

The most commonly reported TEAEs in both treatment groups were diarrhea (5.0%) and headache (3.8%).

 

   

Serious TEAEs were infrequent (1.3% for tebipenem HBr vs. 1.7% for ertapenem) and no deaths were reported in the trial.

 

   

Three Clostridioides difficile-associated TEAEs were observed in the ertapenem group, while none were observed in the tebipenem HBr group.

Dr. Ankit Mahadevia, Chief Executive Officer of Spero Therapeutics, commented, “The ADAPT-PO trial is a landmark trial that is the first ever to test an all oral regimen against an all IV regimen for the treatment of cUTI. We are thrilled to announce positive ADAPT-PO results that we believe demonstrate the value of tebipenem HBr for healthcare providers, payers and patients. These results bring us one step closer to delivering a new oral therapeutic option that could potentially address an expanding unmet need for patients with cUTI and AP. If approved by the FDA, tebipenem HBr would be the first oral cUTI drug to earn approval in 26 years, which would be an important achievement given the high levels of resistance to currently available oral therapies. We want to express our gratitude to the patients and investigators who participated in the trial.”

Emerging data from the tebipenem HBr program, including the ADAPT-PO clinical trial results, will be presented in detail at future scientific meetings and in publications. Tebipenem HBr has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA) for the treatment of cUTI, which may result in expedited review and an option for rolling submission of a New Drug Application (NDA). Spero intends to initiate a rolling NDA submission and anticipates completing the NDA submission to the FDA for tebipenem HBr in the second quarter of 2021.

Conference Call and Webcast

Spero will host a conference call and webcast today at 8:00 a.m. EDT. To access the call, please dial 1-877-705-6003 (domestic) or 1-201-493-6725 (international) and refer to conference ID 13709990. The conference call will also be webcast live and a link to the webcast can be accessed (here) and also on Spero’s website at www.sperotherapeutics.com in the “Investors and Media” section under “Events and Presentations.” An archived webcast will be available on Spero’s website for 30 days following the presentation.

About ADAPT-PO

The global, randomized, placebo-controlled ADAPT-PO Phase 3 clinical trial evaluated the safety and efficacy of tebipenem HBr in hospitalized adult patients with cUTI or AP. Patients were


randomized (1:1) to receive tebipenem HBr (600 mg) orally every 8 hours, or ertapenem (1 g) IV every 24 hours, for a total of 7 to 10 days. Patients with concurrent bacteremia received up to 14 days of therapy. The primary endpoint was the overall response, defined as the combination of clinical cure and microbiological eradication of the causative pathogen(s), at the test-of-cure (TOC) visit (Day 19 ±2 days) and was assessed in the micro-ITT population. The primary analysis and assessment of non-inferiority was evaluated using a pre-specified -12.5% non-inferiority (NI) margin. This NI margin was a modification of the original NI margin of -10% that was discussed with the FDA because of concern that the COVID-19 pandemic could have an adverse effect on the trial. As a result, the NI margin was modified prior to database lock from the original NI margin. However, as noted by the lower bound of the 95% confidence interval (-9.7), the trial also achieved success according to the original -10% NI margin.

About Tebipenem HBr

Tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994) is Spero’s novel investigational oral formulation of tebipenem pivoxil, a carbapenem antibiotic of the ß-lactam class marketed by Meiji Seika Pharma Co. Ltd. (Meiji) in Japan as Orapenem® since 2009 for pediatric infections limited to pneumonia, otitis media and sinusitis. Carbapenems are an important subclass of antibiotics because they have been observed to be safe and effective in the treatment of drug-resistant Gram-negative bacterial infections. Tebipenem HBr is being developed for the treatment of complicated urinary tract infections, including acute pyelonephritis. The Company expects that the favorable ADAPT-PO clinical trial results, once finalized, will support completion of a New Drug Application submission to the FDA in the second quarter of 2021. If approved, tebipenem HBr would be the first oral carbapenem antimicrobial to receive marketing approval in the United States. Tebipenem HBr has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the FDA for the treatment of cUTI and AP.

About Complicated Urinary Tract Infection (cUTI)

In 2007, in the United States alone, there were an estimated 10.5 million office visits for urinary tract infection (UTI) symptoms and 2-3 million emergency department visits. Most cases of cUTI and acute pyelonephritis are caused by Enterobacteriaceae, with Escherichia coli being the most common pathogen in the majority of infections across care settings. According to the Centers for Disease Control (CDC), drug-resistant Enterobacteriaceae, or commonly called extended-spectrum beta lactamase (ESBL) producing Enterobacteriaceae, is considered to be one of the most serious antibiotic-resistant bacterial threats in the United States. Antimicrobial resistance rates across most U.S. regions to fluoroquinolones, the most commonly used antibiotic for UTI, are >30% among Escherichia coli. Currently, there are few oral options to treat these patients. There is a need for strategies to avoid preventable cUTI-related inpatient and emergency department visits and potentially an opportunity to shift site of care for a proportion of hospitalized patients with cUTIs.


Tebipenem HBr Research Support

This project has been funded in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201800015C.

About Spero Therapeutics

Spero Therapeutics, Inc. is a multi-asset, clinical-stage biopharmaceutical company focused on identifying, developing and commercializing novel treatments for multidrug-resistant (MDR) bacterial infections and rare diseases.

Spero’s lead product candidate, tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994), is anticipated to be the first oral carbapenem antibiotic for use in adults to treat serious bacterial infections, including those caused by MDR Gram-negative infections.

Spero is also advancing SPR720, its novel oral therapy product candidate designed for the treatment of rare, orphan pulmonary disease caused by non-tuberculous mycobacterial (NTM) infections.

Spero also has an IV-administered next generation polymyxin product candidate, SPR206, developed from its potentiator platform that is being developed to treat MDR Gram-negative infections in the hospital setting.

For more information, visit https://sperotherapeutics.com.

Forward-Looking Statements

This press release may contain forward-looking statements. These statements include, but are not limited to, statements about the initiation, timing and submission to the FDA of a 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 IV to oral administration. 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. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including Spero’s ability to timely complete related Phase 1 trials for NDA submission, taking into account the possible effects of the COVID-19 pandemic; Spero’s need for additional funding; the lengthy, expensive, and uncertain process of clinical drug development; Spero’s reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; the ability to develop and commercialize Spero’s product candidates, if approved; the potential impact of the COVID-19 pandemic; Spero’s ability to retain key personnel and to manage its growth; and other factors discussed in the “Risk Factors” set forth in filings that Spero periodically makes with the U.S. Securities and Exchange Commission. The forward-looking statements included in this press release represent Spero’s views as of the date of this press release. Spero


anticipates that subsequent events and developments will cause its views to change. However, while Spero 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 Spero’s views as of any date subsequent to the date of this press release.

Spero Investor and Media Contact:

Sharon Klahre

Senior Director, Investor Relations

857-242-1547

IR@sperotherapeutics.com