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Results of Operations and Financial Condition.
On March 23, 2021, Entasis Therapeutics Holdings Inc., or the Company, issued a press release announcing its financial results for the year ended December 31, 2020. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
Item 7.01 Regulation FD Disclosure
The Company recently updated its corporate investor presentation to provide an updated overview of the Company’s business and growth strategy. A copy of the investor presentation, which is available at www.entasistx.com, is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
Information in the presentation contains forward-looking statements regarding future events and performance of the Company. All such forward-looking statements are based largely on the Company’s experience and perception of current conditions, trends, expected future developments and other factors, and on management’s expectations, and are subject to risks and uncertainties that could cause actual results to differ materially, including, but not limited to, those factors described in the presentation and in the Company’s filings with the Securities and Exchange Commission. The Company disclaims any intention or obligation to update or revise any financial or other projections or other forward-looking statements, whether because of new information, future events or otherwise.
In accordance with General Instruction B.2 of Form 8-K, the information in each of Item 2.02 and Item 7.01 of this Form 8-K and in the press release attached as Exhibit 99.1 and the presentation attached as Exhibit 99.2 is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise be subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any of the Company’s filings whether made before or after the date hereof or any other document under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Financial Statements and Exhibits.
Cover Page Interactive Data File (embedded within the Inline XBRL document).
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.
ENTASIS THERAPEUTICS HOLDINGS INC.
/s/ Michael Gutch, Ph.D.
Michael Gutch, Ph.D.
Chief Financial Officer and Chief Business Officer
Dated: March 23, 2021
Entasis Therapeutics Reports Full Year 2020 Financial Results and Provides Business Update
– Phase 3 ATTACK registration trial more than three-quarters complete –
– Zoliflodacin Phase 3 trial adds clinical trial sites, continues enrollment –
WALTHAM, Mass., March 23, 2020 (GLOBE NEWSWIRE) – Entasis Therapeutics Holdings Inc. (NASDAQ: ETTX), a clinical-stage biopharmaceutical company focused on the discovery and development of novel antibacterial products, announced today its full year 2020 financial results and provided a business update.
“Thanks to the tremendous work of our teams, partners and investigators, and the support of our patients and their families, we are entering 2021 with improved momentum for our Phase 3 registration clinical trials addressing multidrug-resistant Acinetobacter infections and uncomplicated gonorrhea, despite the continued headwinds of the COVID-19 pandemic,” stated Manos Perros, President and Chief Executive Officer of Entasis Therapeutics. “Based on the encouraging progress achieved during the fourth quarter of 2020 and early 2021 in the ATTACK trial and with a better understanding of the impact of the pandemic, we are now able to provide guidance and anticipate completing enrollment in the ATTACK trial in the coming months with a top-line data readout during the second half of 2021. Also during 2020, we continued to advance our early-stage pipeline and strengthen our balance sheet through two private placement transactions. We look forward to an exciting 2021, which we believe will be a transformative year for Entasis as we conclude the ATTACK trial and prepare for a potential NDA filing and commercialization of sulbactam-durlobactam (SUL-DUR).”
Fourth Quarter 2020 and Recent Highlights
|●||The Company saw steady enrollment in the ATTACK trial, despite recruitment headwinds caused by the COVID-19 pandemic. The Company estimates that the ATTACK trial is currently more than 75% enrolled and based on the trailing 12-month enrollment rate, anticipates completion of enrollment in the clinical trial in the coming months with a top-line data readout in the second half of 2021.|
|●||In January, the Company issued a press release regarding its expanded access program (EAP), also referred to as compassionate use, for SUL-DUR, an investigational drug for U.S. patients with Acinetobacter baumannii infections, including potential carbapenem and multidrug-resistant strains. Patients co-infected with COVID-19 are eligible if the treating physician feels the risk benefit supports making SUL-DUR available. In cooperation with the FDA, expanded access is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available. In this circumstance, Entasis can provide a requesting physician with pre-approval access to SUL-DUR for the treatment of the physician’s patient if specific conditions are met and there is adequate availability of drug supply.|
|●||The Company continued enrollment of the ATTACK trial across approximately 95 clinical trial sites in 17 countries, including China. As of March 23, 2021, the ATTACK trial has randomized 160 patients and has had three pre-planned Data and Safety Monitoring Board reviews, including one most recently in February 2021. While the Company remains blinded to the clinical data, all three reviews recommended continuation of the trial without protocol modification. Entasis currently estimates completion of the ATTACK trial will require enrollment of approximately 170 patients to achieve the target of 120 evaluable patients. Based on|
|the observed trailing 12-month enrollment rate, the Company anticipates completion of enrollment in the ATTACK trial in the coming months with top-line data readout in the second half of 2021.|
|●||In February 2021, the Company published “In vitro activity and in vivo efficacy of sulbactam-durlobactam against pathogenic Burkholderia species” in Antimicrobial Agents and Chemotherapy. In addition, the Company presented four posters highlighting SUL-DUR’s potential during the virtual IDWeek 2020 held on October 21-25, 2020. The Company’s presentations highlighted findings which demonstrated activity of SUL-DUR against multidrug-resistant Acinetobacter clinical isolates from the Middle East as well as global Acinetobacter baumannii-calcoaceticus complex clinical isolates, a retrospective review of serious infections caused by carbapenem-susceptible and carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex, and in vitro intrinsic microbiological activity of durlobactam and combinations against multidrug resistant Mycobacterium abscessus.|
|●||The Company continues to support its partner, the Global Antibiotic Research and Development Partnership (GARDP), and its Phase 3 registration trial of zoliflodacin for the treatment of uncomplicated gonorrhea. The trial will assess the safety and efficacy of oral zoliflodacin versus the current standard of care combination of intramuscular ceftriaxone plus oral azithromycin. The trial is actively enrolling patients with uncomplicated gonorrhea, including infections potentially caused by multidrug-resistant strains of N. gonorrhoeae. GARDP plans to activate up to 16 clinical trial sites across the United States, the Netherlands, South Africa and Thailand, with some additional site activations occurring in the first half of 2021. Due to the unique challenges posed by the COVID-19 pandemic to this global clinical trial, the Company remains unable to provide guidance around the timeline for completion or top-line data readout and will continue to actively assess the impact of the pandemic, in consultation with GARDP, and provide updates on guidance when appropriate.|
|●||In March 2021, the Company published “Susceptibility trends of zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in Nanjing, China (2014-2018)” in Antimicrobial Agents and Chemotherapy. The article presents data on susceptibility to zoliflodacin of 986 Neisseria gonorrhoeae isolates collected from men in Nanjing, China between 2014 and 2018. Zoliflodacin demonstrated compelling in vitro activity against these clinical isolates, including those with resistance to ciprofloxacin, azithromycin, and extended spectrum cephalosporins.|
Full Year 2020 Financial Results
The Company reported a net loss of $50.5 million for the year ended December 31, 2020, compared to a net loss of $43.9 million for the year ended December 31, 2019. The increase in net loss was primarily related to a decrease in revenue in 2020 versus the prior year.
Research and development expenses were $41.0 million for the year ended December 31, 2020, compared to $40.2 million for the year ended December 31, 2019. The increase of $0.9 million was primarily due to an increase in personnel expenses associated with higher headcount, higher salaries and higher stock-based compensation expense resulting from options and restricted stock units granted during the year ended December 31, 2020 and offset in part by a decrease in preclinical and clinical development expenses related to the advancement of our ETX0282CPDP product candidate and a decrease in clinical development expenses related to the advancement of our SUL-DUR product candidate
General and administrative expenses were $13.2 million for the year ended December 31, 2020, compared to $13.8 million for the year ended December 31, 2019. The decrease of $0.6 million was driven by a decrease in consulting expenses, VAT and other taxes, and legal expenses and were partially offset by an increase in insurance premiums and personnel expenses associated with higher headcount and higher salaries.
As of December 31, 2020, cash, cash equivalents and short-term investments were $53.2 million, compared to $41.0 million as of December 31, 2019.
Based on our current operating plan, we believe that our existing cash, cash equivalents and short-term investments will be sufficient to fund our operating expenses and capital expenditure requirements through the end of the first quarter of 2022.
Entasis is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel antibacterial products to treat serious infections caused by multidrug-resistant Gram-negative bacteria. Entasis’ pathogen-targeted design platform has produced a pipeline of product candidates, including sulbactam-durlobactam (targeting Acinetobacter baumannii infections), zoliflodacin (targeting Neisseria gonorrhoeae infections), ETX0282CPDP (targeting Enterobacteriaceae infections) and ETX0462 (targeting Pseudomonas infections). For more information, visit www.entasistx.com.
Entasis Forward-looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,” “estimate,” “intend” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Entasis’ expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during non-clinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected and changes in expected or existing competition, changes in the regulatory environment, failure of Entasis’ collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. Many of these factors are beyond Entasis’ control. These and other risks and uncertainties are described more fully in the Entasis’ filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Forward-looking statements contained in this announcement are made as of this date, and except as required by law, Entasis assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
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Company Confidential Targeted Solutions for Antibacterial Resistance Precision antibiotics against critical pathogens March 2021
Company Confidential Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements of historical facts, contained in this presentation are forward- looking statements, including statements regarding the plans of Entasis Therapeutics Holdings Inc. (the “Company”) to develop and commercialize its product candidates, the Company's ongoing and planned clinical trials, the timing and availability of data from its clinical trials, advancement of ETX0462 into a Phase 1 clinical trial, the efficacy and safety data from its ongoing Phase 3 trials that, if positive, will be sufficient to support the submission of a new drug application (NDA) to the US Food and Drug Administration (FDA), its ability to obtain grants or other government funding to develop product candidates, its ability to take advantage of benefits offered by current and pending legislation related to the development of products addressing antimicrobial resistance, the timing of its planned regulatory filings, the timing of and ability to obtain and maintain regulatory approval for its product candidates, the clinical utility of its product candidates and the potential advantages compared to other treatments, its commercialization, marketing and distribution capabilities and strategy, its ability to establish and maintain arrangements for the manufacture of its product candidates, its ability to establish and maintain collaborations and to recognize the potential benefits of such collaborations, its estimates regarding the market opportunities for its product candidates, its intellectual property position and duration of its patent rights and its estimates regarding future expenses, capital requirements and needs for additional financing. Forward-looking statements are based on the Company’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, unexpected safety or efficacy data observed during preclinical or clinical trials, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of the Company’s collaborators to support or advance collaborations or product candidates, unexpected litigation or other disputes and the coronavirus pandemic. Many of these factors are beyond the Company’s control. These and other risks and uncertainties are discussed in the Company’s filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections contained therein. Forward-looking statements contained in this presentation are made as of the date of this presentation, and except as required by law, the Company assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. This presentation contains estimates and other statistical data made by independent parties and by the Company relating to market size and other data about the Company's industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of the Company's future performance and the future performance of the markets in which the Company operates are necessarily subject to a high degree of uncertainty and risk. 1
Company Confidential Accomplished Management Team MANAGEMENT TEAM WITH EXTENSIVE ANTI-INFECTIVE EXPERIENCE Manos Perros, Ph.D. President and Chief Executive Officer Michael Gutch, Ph.D. Chief Financial Officer and Chief Business Officer Ruben Tommasi, Ph.D. Chief Scientific Officer John Mueller, Ph.D. Chief Development Officer David Altarac, M.D. Chief Medical Officer Matt Ronsheim Ph.D. Chief Pharmaceutical Sciences & Manufacturing Officer Elizabeth Keiley, J.D. General Counsel Colleen Tucker Head, Human Resources • Spun out from AZ with 2 early- stage programs in 2015 • Today, advancing 5 novel antibacterial programs • ~50 FTEs Boston BioHub, Waltham, MA 2
Company Confidential Company Highlights Abbreviations: CRE, Carbapenem-resistant Enterobacterales; MDR, Multidrug resistant; cUTIs, Complicated urinary tract infections Leader in targeted antibiotic development ► Multidrug-resistant, pathogen-targeted focus from discovery through commercialization Innovative and robust pipeline ► Two Phase 3 clinical trials against highest-priority pathogens 1. Sulbactam-durlobactam (SUL-DUR) against Acinetobacter 2. Zoliflodacin against N. gonorrhoeae ► Three additional programs in early-stage development 3. ETX0282CPDP against MDR cUTIs, including CRE 4. ETX0462 against Pseudomonas aeruginosa 5. NBP2 for Gram (-) infections Clear commercial opportunities ► Product candidates with significant revenue potential as infections are resistant to generic antibiotics 3
Company Confidential Pathogen Focus We focus on the resistance mechanisms of these multidrug resistant pathogens. Source: Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2019 CDC “Urgent” Threats CDC “Serious” Threat 4
Company Confidential Differentiated Business Model Targeted medicines means streamlined research, development, and commercialization. Abbreviations: FDA, Food and Drug Administration; IP, intellectual property; QIDP, qualified infectious disease product Focused on multidrug resistant pathogens with high unmet medical need Rational drug design Focused development and regulatory strategy Targeted commercialization strategy Targeted-design platform developed at AstraZeneca Novel chemical entities targeting validated mechanisms Acinetobacter baumannii Pseudomonas aeruginosa Enterobacterales Neisseria gonorrhoeae Pathogen targeted single phase 3 pivotal trials FDA Fast Track and QIDP designations for two phase 3 programs Lean infrastructure to address US market Key partnerships to capture value from global markets 5
Company Confidential Robust Pipeline of Novel Antibiotics Fully-integrated research and development. Abbreviations: CRE, carbapenem-resistant Enterobacterales; ESBL, extended spectrum β-lactamases; IV, intravenous; NBP, non β-lactam penicillin binding protein inhibitor. a Zai Lab has licensed Asia-Pacific rights to sulbactam-durlobactam b Global Antibiotic Research and Development Partnership (GARDP) will fully fund the phase 3 development program and has commercial rights in low-income and specified middle-income countries. Entasis has retained commercial rights in all major markets in North America, Europe, and Asia-Pacific. PRODUCT CANDIDATE/ INDICATION PRE- CLINICAL PHASE 1 PHASE 2 PHASE 3 PROGRAM STATUS COMMERCIAL RIGHTS PARTNERSHIPS/ GRANT FUNDING Sulbactam-durlobactam (IV) Carbapenem-resistant Acinetobacter infections Phase 3 top-line data 2H 2021 Worldwide excluding Asia-Pacifica Zoliflodacin (Oral) Uncomplicated gonorrhea Phase 3 trial actively enrolling All developed countriesb ETX0282CPDP (Oral) Complicated urinary tract infections (cUTIs) (Enterobacterales including CRE and ESBL-producing) Post initial Phase 1 work ongoing Worldwide ETX0462 (IV) Multidrug-resistant Pseudomonas Phase 1 enabling work ongoing Worldwide NBP-2 (IV) Gram-negative infections Lead optimization Worldwide 6
Company Confidential Key Metrics - unaudited As of 12.31.2020 Cash and cash equivalents $53.2 M Debt $0 M Common shares outstanding 36,637,357 Common warrants outstanding1 23,345,794 Financial Highlights 1. Five-year warrants; 14,000,000 at $2.50 exercise price and 9,345,794 at $2.675 exercise price. Based on projected operating expenses, cash-runway into 4Q 2021 7
Company Confidential Sulbactam-durlobactam (SUL-DUR; formerly ETX2514SUL) For Acinetobacter Infections Partnered with
Company Confidential Carbapenem-Resistant Acinetobacter: Overview Global carbapenem-resistant Acinetobacter rates exceed 50%. Abbreviations: CRAB, carbapenem-resistant Acinetobacter baumannii; EU5, European Union Five (France, Germany, Italy, Spain, United Kingdom); Sources: 1. Data on file. Decision Resources. 2. Chung DR, et al; Asian Network for Surveillance of Resistant Pathogens Study Group. Am J Respir Crit Care Med. 2011;184:1409-1417. 3. Du, et al. American Journal of Infection Control 00 (2019) 1-6. 4. Poirel L, et al. Antimicrob Agents Chemother. 2010;54:24-38. 5. Karageorgopoulos DE, Falagas ME. Lancet Infect Dis. 2008;8:751-762. 6. Raible KM, et al. Ann Clin Microbiol Antimicrob. 2017;16:75. 7. Data on file. Entasis Therapeutics. IHMA (2014-2017). 8. CARSS (China Antimicrobial Resistance Surveillance system), 2017 Annual Report. ► Estimated annual CRAB incidence1,7,8 ► Limited therapeutic options Polymyxin-based polypharmacy Mortality rate: ~50%2,3 ► Resistance to β-lactams mediated by Classes A, C, and D β-lactamases4-6 20,000-40,000 (United States) 45,000-60,000 (Europe and Middle East) Global Percentages of Carbapenem Resistance in A. baumannii 7 *Local surveillance studies >150,000 (China) 9
Company Confidential Durlobactam: Overview Durlobactam has broad Class A,C & D β-lactamase coverage. Abbreviations: IV, intravenous; SUL-DUR, sulbactam-durlobactam. ► A novel IV broad-spectrum β-lactamase inhibitor Differentiator is its broad Class D β-lactamase coverage, essential for the treatment of carbapenem-resistant Acinetobacter infections ► Extensive preclinical and clinical studies demonstrate antibacterial activity and favorable safety profile Extensive pharmacokinetic and pharmacodynamic modeling employed to project efficacious SUL-DUR dosing regimen Well tolerated in a phase 2 and three phase 1 clinical trials, including at doses that are well in excess of phase 3 clinical trial dose ► Has the potential to restore the antibiotic activity of sulbactam against multidrug-resistant Acinetobacter ► Phase 3 clinical trial ongoing 10
Company Confidential SUL-DUR: Pre-Clinical Data Preclinical data potentially differentiates SUL-DUR from existing therapies, including colistin. Abbreviations: CFU, colony-forming unit; MIC, minimal inhibitory concentration; SUL-DUR, sulbactam-durlobactam a Extensively drug-resistant (XDR) Acinetobacter baumannii ARC3486 (OXA-72, OXA-66, TEM-1, AmpC) in neutropenic mice; MIC (sulbactam) ≥32 mg/L, MIC(SUL-DUR) = 0.5 mg/L. b Durlobactam, sulbactam, and colistin were dosed subcutaneously. Colistin was injected to maximum tolerated dose. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 % of Strain Inhibited MIC (mg/L) In Vitro Activity Against 6,426 Acinetobacter Strains SUL-DUR Colistin Sulbactam Amikacin Imipenem Meropenem 90% of Strains Inhibited 0 2 4 6 8 10 Pretreatment Vehicle 2.5/0.625 5/1.25 10/2.5 20/5 30/7.5 40/10 80/20 Colistin 40 mg/kg Bacterial Load (Log CFU/g) In Vivo Activity Against XDR Acinetobacter Infection in Mouse Lung Modela,b 1-Log Reduction Sulbactam-durlobactam (mg/kg) 11
Company Confidential SUL-DUR: Clinical Data Summary We have conducted extensive clinical trials to optimize SUL-DUR heading into phase 3. Abbreviations: cUTI, complex urinary tract infection; FDA, Food and Drug Administration; PK, pharmacokinetics; QIDP, qualified infectious disease product; SUL-DUR, sulbactam- durlobactam. Phase 1 (n=188) Demonstrated favorable safety profile & dose proportional PK No dose-limiting toxicities up to 8 grams in single dose No drug-drug interactions Predicted therapeutic levels achieved in urine, plasma, and lung Renal dosing study completed to inform phase 3 dosing Phase 2 (n=80) Favorable safety profile in 53 cUTI patients receiving SUL-DUR PK was consistent with PK observed in phase 1 Successful eradication of imipenem- nonsensitive strains (n=3) Phase 3 Phase 3 ongoing Received Fast Track and QIDP designation by the US FDA 12
Company Confidential SUL-DUR: Single Global Phase 3 Pivotal Trial The ATTACK trial supports the basis for regulatory submissions in the US, Europe, and China. Abbreviations: BSI, bloodstream infection; CFDA, China Food and Drug Administration; DOT, days of therapy; EMA, European Medicines Agency; FDA, US Food and Drug Administration; HABP, hospital-acquired bacterial pneumonia; ICU, intensive care unit; LOS, length of stay; NDA, new drug application; PK/PD, pharmacokinetics / pharmacodynamics; RIFLE, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease; SUL-DUR, sulbactam-durlobactam; VABP, ventilator-associated bacterial pneumonia. ► Regulatory plan based on a series of discussions with the FDA • Design reviewed by EMEA and CFDA (now known as China National Medical Products Administration) • Dose selection informed by robust PK/PD and extensive phase 1 and phase 2 clinical trials • Flexibility on the size of the NDA safety database once target enrolment has been reached for Part A ► Trial designed with 80% power to demonstrate between-group noninferiority with a 20% margin 120 patients Carbapenem-resistant Acinetobacter Primary efficacy analysis: 28-day mortality SUL-DUR + imipenem Colistin + imipenem Patients with documented or presumed Acinetobacter infections (HABP, VABP, BSI) 1:1 Exploratory endpoints* Primary safety analysis: Nephrotoxicity (RIFLE criteria) *Include ICU days, ventilator days, total LOS, and DOT vs. colistin 13
Company Confidential SUL-DUR: Single Global Phase 3 Pivotal Trial The ATTACK trial also includes a Part B to provide safety and supportive efficacy data. Abbreviations: AP, acute pyelonephritis; cUTI, complicated urinary tract infection; HABP, hospital-acquired bacterial pneumonia; SUL-DUR, sulbactam-durlobactam; VABP, ventilator- associated bacterial pneumonia ► Part B non-randomized cohort up to 80 patients • Open-label arm with patients randomized to SUL-DUR plus imipenem • Supportive efficacy data not included in Part A primary analysis • Primary safety analysis will include patients in Parts A and B ► Part B patients are not eligible for Part A but will include: • HABP, VABP, and bacteremia due to colistin-resistant Acinetobacter • cUTI/AP, surgical, or traumatic wound infections due to colistin-resistant Acinetobacter • Patients with known intolerance to colistin SUL-DUR + imipenem Patients with documented or presumed Acinetobacter infections (not eligible for Part A) Safety and supportive efficacy Part B Non-Randomized Cohort: Study Design 14
Company Confidential SUL-DUR: Regulatory Update FDA willing to collaborate with Entasis to ensure meaningful and successful outcome. Several interactions with FDA from 2016 to present to discuss clinical development plan During August 2020 Type C meeting, Entasis sought flexibility on alpha level used in Part A statistical analysis FDA expressed interest in working with Entasis to complete the ATTACK trial FDA indicated they would consider a smaller safety database with a positive overall benefit risk profile In December 2020, FDA and Entasis’s agreed on several program modifications: Part A change in NI margin from 19 to 20% Removal of interim sample size analysis – Changes resulted in primary efficacy population reduction from 136 to 120 – Statistical robustness maintained Part B enrollment will continue until primary efficacy population target is met 15
Company Confidential The ATTACK Trial Projected Timeline We currently anticipate top-line data 2H 2021. 16 ► As of March 15, 2021 we have randomized 159 patients into Part A • 90 clinical trial sites active across 17 countries, including China • 107/112 (96%) were carbapenem-resistant; 13/112 (13%) were colistin-resistant ► 91/129 patients (21 pending) meet criteria for inclusion in evaluable population • Current evaluable rate of ~70%, higher than originally projected (60%) ► To reach our target of 120 evaluable patients in Part A, approximately 170 patients will need to be enrolled • At current enrollment rates, top-line data should be available in 2H 2021
Company Confidential DSMB Meeting 1 Feb-2020 No safety findings Recommended that the study continue without modifications Initiate Part B of the study after review of PK data in the first 30 patients DSMB Meeting 2 Jul-2020 No new safety findings Recommended that the study continue without modifications DSMB Meeting 3 Feb-2021 No new safety findings Recommended that the study continue without modifications ATTACK Data and Safety Monitoring Board (DSMB) 17
Company Confidential Commercial Model: Streamlined Execution A lean, targeted sales force can efficiently reach key customers with compelling data. Abbreviations: DOT, days of therapy; LOS, length of stay; LTACs, long-term acute care centers. ► Carbapenem-Resistant Acinetobacter can be found in very targeted settings • 300 Large Intensive Care Units (ICUs) (moderately cost sensitive) • 200 Transplant / 50 Cancer / 25 Burn Centers (least cost sensitive) • Outpatient LTACs and Home Infusion [life cycle management opportunity] ► Messaging will focus on Acinetobacter 24/7 Efficacy 28-day mortality vs. colistin 1 Safety Nephrotoxicity vs. colistin 2 Cost Savings ICU days, ventilator days, LOS, DOT vs. colistin 3 18
Company Confidential Commercial Model: Product Positioning SUL-DUR aims to replace colistin and polypharmacy in carbapenem-resistant Acinetobacter. Current Treatment Protocols Future Treatment Protocols Nephrotoxic Neurotoxic Slow onset, complex pharmacodynamics Cumbersome dosing protocol and AE monitoring Dosing limited by safety Day 1: Carbapenem + Suspected Acinetobacter Days 2-14 or longer Colistin + Polypharmacya Day 1: Carbapenem + Suspected Acinetobacter ✓ No SAEs observed in phase 1 or 2 trials ✓ Well tolerated ✓ Well-understood pharmacodynamics ✓ Easier dosing protocol ✓ Dosing optimized for efficacy a For CRAB treatment, drugs used in combination with colistin come from the following classes: carbapenems, cephalosporins, tetracyclines, penicillins, and aminoglycosides. Abbreviations: AE, adverse event; CRAB, carbapenem-resistant Acinetobacter; SAEs, serious adverse events; SUL-DUR, sulbactam-durlobactam. Confirmed CRAB Confirmed CRAB Replaced by Days 2-14 or longer SUL-DUR 19
Company Confidential Commercial Model: Minimal Competition Unlike the CRE market, the CRAB market has no labeled competition for 5-10 years. Abbreviations: CRAB, carbapenem-resistant Acinetobacter; CRE, carbapenem-resistant Enterobacterales Source: 1. https://clinicaltrials.gov/ct2/results?cond=Acinetobacter+Infections&term=&cntry=&state=&city=&dist= CRE: Branded Antibiotics Used CRAB: Branded Antibiotics Approved Other than SUL-DUR, according to ClinTrials.gov1, there are no new antibiotics in Phase 1, 2, or 3 trials for CRAB. 20
Company Confidential Commercial Opportunity: Addressable Market At launch, annual worldwide addressable market for CRAB treatments should exceed $1 billion. Abbreviations: CRAB, carbapenem-resistant Acinetobacter; RoW, rest of world. Sources: 1. Data on file. Decision Resources. Note: Addressable market projections are for year 2022 based on Company estimates and assumptions, including estimated patient populations, market share and pricing, made as of the date of this presentation. These parameters could differ materially at the time of commercialization. 20,000-40,000 Annual CRAB Infections1 Global Addressable Market $1B + 150,000-200,000 Annual CRAB Infections1 U.S. RoW Pneumonia Bloodstream Skin and skin structure Urinary tract Wounds Inpatient Outpatient 21
Company Confidential Commercial Opportunity: China Our Zai Lab partnership will help address CRAB in China. Abbreviations: CRAB, carbapenem-resistant Acinetobacter ► CRAB presents a significant unmet medical need in China and Asia-Pacific territory ► Partnership with Zai Lab (Nasdaq: ZLAB) provides potential accelerated path for commercialization in China Co-enrollment of ATTACK pivotal phase 3 clinical trial If successful, provides path for regulatory approval Direct economic benefits to Entasis (milestone and royalty payments) in addition to partially offsetting phase 3 clinical trial costs ► Entasis maintains 100% economics outside Asia- Pacific, including North America and Europe 22
Company Confidential Zoliflodacin Zoliflodacin For Gonorrhea Infections Partnered with
Company Confidential Gonorrhea: Overview Only one drug remains effective for gonorrhea—intramuscular ceftriaxone. Sources: 1. Rowley J, et al. Bull World Health Organ. 2019;97:548-562P. 2. Unemo M, et al. Microbiol Spectr. 2016;4. 3. Gonorrhea - CDC fact sheet (detailed version). CDC website. https://www.cdc.gov/std/gonorrhea/stdfact-gonorrhea-detailed.htm. Reviewed October 25, 2016. Accessed September 23, 2019. 4. CDC Sexually Transmitted Disease Surveillance 2018, Table 1. 5. Unemo M, et al. Sex Health. 2019;16:412-425. *includes China and Australia Currently, no oral antibiotics are recommended as an alternative to ceftriaxone for the treatment of N. gonorrhoeae infections ► The only recommended treatment option today is ceftriaxone (intramuscular [IM] injection), but resistance has emerged5 Ceftriaxone 250mg administered via 21- gauge 1.5-inch needle ► 87 million worldwide annual cases1 35.2 million in Western Pacific2* 1.14 million in the United States3 Growing >10% per year since 20094 24
Company Confidential Gonorrhea: Overview The CDC has changed its STD Guidelines five times in the last 18 years1 due to resistance. Sources: 1. CDC: Sexually Transmitted Diseases Treatment Guidelines, MMWR, May 10, 2002; Sexually Transmitted Diseases Treatment Guidelines, MMWR, August 4, 2006; Update to Sexually Transmitted Diseases Treatment Guidelines, 2006, MMWR, April 13, 2007; Sexually Transmitted Diseases Treatment Guidelines, 2010, MMWR, December 10, 2010; CDC No Longer Recommends Oral Drug for Gonorrhea Treatment, August 9, 2012; 2. CDC, Sexually Transmitted Disease Surveillance 2017, Figure 33 Abbreviations: STD, sexually-transmitted disease Distribution of Primary Antimicrobial Drugs Used to Treat Gonorrhea Among Participants, 1988–20172 25
Company Confidential Zoliflodacin: Phase 2 Trial Results Landmark phase 2 trial results were published in the New England Journal of Medicine. Source: Taylor SN, et al. N Engl J Med. 2018;379:1835-1845. ► Phase 2 trial results showed urogenital efficacy in 47 out of 47 patients ► Zoliflodacin was generally well tolerated at clinically effective doses ► Phase 3 trial initiated in Sept 2019 Anatomic Site Zoliflodacin (3 g) Ceftriaxone Urogenital 47/47 (100%) 21/21 (100%) Pharyngeal 7/9 (78%) 4/4 (100%) Rectal 6/6 (100%) 3/3 (100%) 1Represents results for the per-protocol population. Microbiological Efficacy1 26
Company Confidential Zoliflodacin: Single Global Phase 3 Pivotal Trial The phase 3 trial supports the basis for regulatory submissions in the US and Europe. Abbreviations: DSMB, data safety monitoring board; EMA, European Medicines Agency; FDA, US Food and Drug Administration; GARDP, Global Antibiotic Research and Development Partnership; IM, intramuscular; TOC, test of cure ► Phase 3 trial sponsored and funded by our partner GARDP Regulatory plan based on a series of discussions with the FDA and EMEA Dose selection informed by robust PK/PD and extensive phase 1 and phase 2 clinical trials ► Trial designed with 90% power and a 10% between-group noninferiority margin ► Global phase 3 trial with up to 16 clinical sites planned across the US, EU, Africa and Asia Trial temporarily paused in March 2020 due to COVID-19; now actively enrolling DSMB in March 2020 recommended to continue the clinical study without modification 603 patients with confirmed uncomplicated gonorrhea Primary efficacy analysis: Microbiological cure at urethral or cervical sites (urogenital) at TOC (day 6 ± 2) Oral dose zoliflodacin (3g) Ceftriaxone IM injection (500mg) + oral azithromycin (1g) Patients with documented or presumed uncomplicated gonorrhea 2:1 Secondary analyses: Microbiological cure at rectal or pharyngeal sites at TOC (day 6 ± 2); safety 27
Company Confidential Zoliflodacin: Commercial Opportunity Zoliflodacin has the potential to be the oral product of choice for gonorrhea. Abbreviations: MIC, minimum inhibitory concentration. a 49 states allow patients diagnosed with gonorrhea to provide medications to take to his/her partner without the health care provider first examining the partner (https://www.cdc.gov/std/ept/legal/default.htm) Sources: 1. McLenon J, et al. J Adv Nurs. 2019;75:30-42; 2. Chisholm, J Antimicrob Chemother 2010; 65: 2141 –2148. Single-dose treatment (oral suspension sachet) Alternative to intramuscular ceftriaxone 20% of the population are “needlephobes”1 Ceftriaxone injection is notorious for its pain Increasing ceftriaxone MIC creep2 Oral sachet allows “expedited partner therapy” (EPT)a 28
Company Confidential Zoliflodacin: Partnership with GARDP The Phase 3 trial is sponsored by the Global Antibiotic Research & Development Partnership. Abbreviations: R&D, research and development Source: GARDP website, Entasis press release (July 6, 2017) ► Developed and fully funded in partnership with: ► GARDP is not-for-profit R&D organization that addresses global public health needs by developing and delivering new or improved antibiotic treatments while endeavoring to ensure their sustainable access ► GARDP will have zoliflodacin commercialization rights in most low- and select middle-income countries, while Entasis retains commercial rights in high-income markets 29
Company Confidential Commercial Opportunity: Worldwide Addressable Market With over 85MM gonorrhea infections annually, the worldwide market could exceed $1 billion. Abbreviations: RoW, rest of world. Sources: 1. Centers for Disease Control and Prevention; 2. Rowley J, et al. Bull World Health Organ. 2019;97:548-562P Note: Addressable market projections are for year 2022 based on Company estimates and assumptions, including estimated patient populations, market share and pricing, made as of the date of this presentation. These parameters could differ materially at the time of commercialization. 1,000,000 Annual Gonorrhea Infections1 Global Addressable Market $1B + >85,000,000 Annual Gonorrhea Infections2 U.S. RoW 30
Company Confidential Zoliflodacin: Competition GSK’s gepotidacin is the only near-term competitor in phase 3 development. Sources: 1. ClinTrials.gov: NCT04010539; 2. Taylor, CID 2018:67 (August) 4 tablets (750mg each) taken at clinic 4 tablets 750mg taken at home 6-12 hours later After food, with water Gepotidacin Dosing Regimen1 In Phase 2 study, there were 3 failures (out of 69), and 2 failures were due to resistance2 Side Effect: 36% diarrhea2 31
Company Confidential ETX0282CPDP (ETX0282 + Cefpodoxime Proxetil) for Complicated UTIs APPENDIX
Company Confidential ETX0282CPDP: Initial Target Addressable Market ETX0282CPDP will initially target the 1 million hospital cUTIs resistant to oral treatments. Abbreviations: CPDP, cefpodoxime proxetil; cUTI, complicated urinary tract infections. Sources: 1. Decision Resources and HCUPNet claims data 2. Decision Resources 3. CDDEP (weighted average fluoroquinolone resistance for E. coli and Klebsiella) 0 1 2 3 4 cUTI In Hospital cUTI Enterobacterales Addressable Infections Infections (MM) ETX0282CPDP US Addressable Market 85%2 cUTIs Caused by Enterobacterales 33%3 Resistant to Existing Oral Treatment Options 3.5M1 Hospital-Treated cUTIs 33
Company Confidential ETX0282CPDP ETX0282 is a novel broad-spectrum oral β-lactamase inhibitor. Abbreviations: CPDP, cefpodoxime proxetil; CRE, carbapenem-resistant Enterobacterales; ESBL, extended-spectrum β-lactamases; MDR, multidrug-resistant; UTIs, urinary tract infections. ► ETX0282CPDP could be the first oral therapeutic option for the treatment of complicated UTIs with broad coverage of MDR Enterobacterales including CRE Opportunity for expansion into the broader community setting ► ETX0282 is designed to have both high oral bioavailability and broad Class A and Class C β-lactamase inhibition No other orally bioavailable treatment covers both Class A and Class C β-lactamases, including ESBL-producing bacteria and CRE ► Initial phase 1 data trial in healthy volunteers supports further progression Investigated safety, pharmacokinetics, drug-drug interaction (DDI), and food effect Interim phase 1 data indicate ETX0282 is generally safe and well tolerated ► Potential for use in additional indications where multidrug-resistant Enterobacterales are commonly found 34
Company Confidential ETX0282CPDP Oral ETX0282CPDP shows in vitro and in vivo activity against multidrug-resistant E. coli. a ETX0282CPDP is an oral prodrug which is metabolized into ETX1317, the active BLI, and cefpodoxime. The in vitro activity is of ETX1317 + cefpodoxime. bARC2687 = multidrug-resistant E. coli (AmpC+; CTX-M-14+), levofloxacin-resistant (MIC >4 mg/L), cefpodoxime-resistant (MIC >64 mg/L), cefpodoxime-ETX1317–sensitive (MIC <0.03 mg/L). c ETX0282 and cefpodoxime were dosed orally. Meropenem was dosed subcutaneously. Abbreviations: BLI, β-lactamase inhibitor; CFU, colony-forming unit; CPDP, cefpodoxime proxetil; CRE, carbapenem-resistant Enterobacterales; IV, intravenous; MIC, minimal inhibitory concentration. 0% 20% 40% 60% 80% 100% 0.031 0.0625 0.125 0.25 0.5 1 2 4 8 16 32 64 Percentage of Strains Inhibited, % Concentration (mg/L) In Vitro Activity of ETX0282CPDP Against 54 Enterobacterales Strains, Including CREa ETX0282CPDP Oral Agent 1 in Development Oral Agent 2 in Development Vabomere (IV) Avycaz (IV) 0 2 4 6 8 10 12 Pretreatment Vehicle Cefpodoxime 50 mg/kg ETX0282 10 mg/kg 10 mg/kg 25 mg/kg 100 mg/kg Meropenem 600 mg/kg Bacterial Load (Log CFU/g) In Vivo Activity of Oral ETX0282 + Cefpodoxime Proxetil in Mouse Thigh Modelb,c 1-Log Reduction 90% Inhibition Pretreatment Vehicle Cefpodoxime 50 mg/kg ETX0282 10 mg/kg 10 mg/kg 25 mg/kg 100 mg/kg Meropenem 600 mg/kg ETX0282 + Oral CPDP 50 mg/kg 35
Company Confidential ETX0282CPDP Phase 1 Status Oral ETX0282CPDP has completed initial phase 1 testing. Abbreviations: CPDP, cefpodoxime proxetil Fit-for-purpose formulation ► Drug substance in capsule (no excipients) First in Human study completed ► 99 healthy subjects were enrolled into 12 cohorts ► 26 subjects received a single dose of ETX0282 ► 51 received at least 2 doses of ETX0282 ► 22 received matching placebo Part A Single ascending dose, fasted Dose range: 100 mg-800 mg Part B Food effect: fasted vs high fat meal Dose range: 100 mg-300 mg Part C Multiple dose with regular meals Dose: 200 mg Part D Drug-drug interaction with regular meal Doses: ETX0282 400 mg and cefpodoxime proxetil 400 mg Part G Simulation of PK profile associated with high fat meal Dose range: 300 mg single dose vs 75 mg x 4 doses 36
Company Confidential Key Pharmacokinetic (PK) and Safety Findings Oral ETX0282CPDP’s plasma concentrations are in predicted therapeutic range. Abbreviations: Cmax, maximum plasma concentration; CPDP, cefpodoxime proxetil. ► ETX0282 is rapidly converted to ETX1317 at all doses evaluated ► Plasma concentrations of ETX1317 are potentially in the desired therapeutic range ► Minimal accumulation of ETX1317 with multiple dosing ► No drug-drug interaction (either way) with cefpodoxime ► Mild-to-moderate emesis reported in 11 out of 77 receiving ETX0282 ► A high fat meal (but not normal diet) and Part G (75 mg x 4 doses) both resulted in a modified PK profile with no emesis observed Decrease in peak concentration (Cmax) Decrease in absorption rate to peak concentration Broader exposure window We are currently prioritizing our resources on completing the ATTACK trial and supporting the ongoing Phase 3 clinical trial with zoliflodacin, while we evaluate options for further clinical development of ETX0282CPDP 37
Company Confidential ETX0462 ETX0462 for Pseudomonas Infections APPENDIX
Company Confidential P. aeruginosa Infections Pseudomonas infections remain a key priority due to high resistance rates and mortality. Sources: 1. ECDC/EMEA Joint Working Group. ECDC/EMEA Joint Technical Report. The bacterial challenge: time to react. https://www.ecdc.europa.eu/sites/default/files/media/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf. Published September 17, 2009. Accessed September 23, 2019. 2. Entasis triangulated estimate from Decision Resources, CDC, AMR, CDDEP, and literature reviews. Abbreviations: CDC, Centers for Disease Control and Prevention; CR, carbapenem-resistant; MDR, multidrug-resistant; WHO, World Health Organization. Note: Brand Resistant includes Avycaz, Zerbaxa, Vabomere, Recarbrio ~10,000 extra deaths + ~800,000 extra hospital days caused by carbapenem-resistant P. aeruginosa1 ~600,000 – 750,000 cases/year2 ~30% MDR rate by 2040 WHO: Critical Priority 1 CDC: “Serious” Threat 120 90 35 0 20 40 60 80 100 120 140 MDR CR Brand Resistant Infections (000s) Estimated US Pseudomonas aeruginosa Infections by Resistance2 39
Company Confidential ETX0462 ETX0462 is a first of a novel class of PBP Inhibitors unaffected by all types of β-lactamases. Abbreviations: MDR, multidrug-resistant; MIC, minimal inhibitory concentration. ► Penicillin Binding Protein inhibitors (PBPi) are β-lactam antibiotics representing some of the oldest and most widely used antibacterial agents but are vulnerable to degradation by β-lactamases ► Novel class of non–β-lactam PBPi (NBPs) is shown to be impervious to all classes of b-lactamases tested ► Excellent potency observed against multiple MDR Gram-negative pathogens with no β-lactamase inhibitor (BLI) needed, creating a potential new IV monotherapy Class A Class B Class C Class D Compound No β-lactamase CTX-M-15 SHV-2a KPC-3 TEM-1 PER-1 VEB-1 GES-11 NDM-1 VIM-1 IMP-1 AmpC P99 OXA-1 OXA-10 OXA-48 Piperacillin 4 64 4 64 >64 8 32 4 >64 >64 >64 64 64 >64 >64 >64 Ceftazidime 0.5 32 16 16 1 64 >64 32 >64 >64 64 8 32 1 1 0.5 ETX0462 1 1 2 1 2 1 1 1 2 1 1 2 2 2 2 2 MIC (mg/L) Against E. coli Isogenic Strains Expressing Individual β-lactamases 40
Company Confidential Entasis: A Leader in Targeted Antibiotics We have hit all major milestones in our first 5 years. Two phase 3 programs (SUL-DUR, zoliflodacin) Phase 1 data (ETX0282CPDP) Fourth candidate selected (ETX0462) Initial Public Offering Second partnership Spinout from AstraZeneca with $23.5M and 14 employees Two clinical programs (SUL-DUR, zoliflodacin) >$100M raised First partnership Phase 3 data on two lead programs (SUL-DUR, zoliflodacin) Commercial launch preparation Sustainable pipeline 2015 2016-17 2018-19 2021 and Beyond 41