About Entasis Therapeutics Holdings

Entasis Therapeutics Holdings Inc., a late clinical-stage biopharmaceutical company, focuses on the discovery, development and commercialization of targeted antibacterial products that address high unmet medical needs to treat serious infections caused by multidrug-resistant pathogens. In February 2022, the company received a preliminary, non-binding proposal from its majority stockholder, Innoviva Inc. (Innoviva) to acquire all the outstanding equity securities of the company that are not currently owned by Innoviva. The company’s lead product candidate, sulbactam-durlobactam (SUL-DUR) is an intravenous (IV) combination of sulbactam, an IV ß-lactam antibiotic, and durlobactam, a novel broad-spectrum IV ß-lactamase inhibitor (BLI) that it is developing for the treatment of pneumonia and bloodstream infections caused by carbapenem-resistant Acinetobacter baumannii (Acinetobacter). The company initiated ATTACK (Acinetobacter Treatment Trial Against Colistin), its single Phase 3 registration trial in 2019, and announced positive top-line Phase 3 data in October 2021 demonstrating that the primary efficacy and safety objectives had been achieved. SUL-DUR also had a favorable safety profile when compared to colistin with a statistically significant reduction in nephrotoxicity. Based on the success of ATTACK and the totality of the SUL-DUR preclinical and clinical data, the company also announced its intention to file a new drug application (NDA) with the United States Food and Drug Administration (FDA) in mid-2022. SUL-DUR is awarded Fast Track status designation providing potential eligibility for accelerated approval and priority review, if relevant criteria are met, following acceptance of its submission by the FDA. With the support of its partner Zai Lab (Shanghai) Co., Ltd. (Zai Lab), the company enrolled approximately 25% of the ATTACK trial in China and combined with the strength of the overall SUL-DUR data set, the company focuses the data will also support a regulatory submission in China. Zai Lab has an exclusive license to develop and commercialize SUL-DUR in mainland China, as well as the broader Asia-Pacific region. The company’s second late-stage product candidate, zoliflodacin, is a novel orally administered molecule being developed for the treatment of uncomplicated gonorrhea. The bacterial pathogen responsible for gonorrhea is Neisseria gonorrhoeae (N. gonorrhoeae). The Phase 3 registration trial, initiated in September 2019, is sponsored by the company’s nonprofit collaborator, the Global Antibiotic Research and Development Partnership (GARDP), which as the sponsor is also responsible for all Phase 3 clinical trial and pharmaceutical development expenses. GARDP has commercial rights to zoliflodacin in up to 168 low- and select middle-income countries, while the company retains commercial rights in the major markets in North America, Europe and the Asia-Pacific. Based on current enrollment rates, the company anticipates the trial to be fully enrolled in 2023. The company’s third product candidate is ETX0282CPDP, which is a combination of a novel, oral ß-lactamase inhibitor (BLI), ETX0282, with cefpodoxime proxetil (CPDP), which has the potential to address complicated urinary tract infections (cUTIs), including those caused by multidrug-resistant Enterobacteriaceae. The company has reported preliminary Phase 1 trial results, and it is seeking a partner to help further advance ETX0282CPDP through additional clinical trials. The company is also advancing the development of a novel class of antibiotics, non ß-lactam inhibitors of penicillin-binding proteins (NBPs). This novel class of agents is designed to potentially target a spectrum of multidrug resistant bacterial pathogens that are part of the U.S. Centers for Disease Control and Prevention (CDC)/World Health Organization (WHO) list of high unmet medical need or ESKAPE pathogens. The company selected ETX0462 as the initial clinical candidate for this program and with support from CARB-X it is working to complete additional pre-clinical activities to enable the program to advance into a Phase 1 clinical trial. In June 2020, the company was awarded a contract from the National Institutes of Health (NIH) to support research towards developing additional penicillin-binding proteins (NBP) molecules with expanded Gram-negative spectrum from this novel class. This research program, designated NBP2, is attempting to target Klebsiella, Pseudomonas and E. coli from the ESKAPE list of pathogens. In July 2021, the company successfully completed the first milestones for the program and was awarded the Option 1 Period of the program to proceed with further optimization, beginning August 1, 2021. Subject to achieving pre-defined milestones, the contract is expected to sufficiently fund activities to achieve submission of an investigational new drug (IND) application to the FDA. Strategy The key elements of the company's strategy include to advance its lead product candidate SUL-DUR through new drug application (NDA) filing and FDA approval; and advance its existing pipeline of pathogen targeted antibiotics for infections poorly treated by existing generic or branded antibiotics. License and Collaboration Agreements AstraZeneca AB (AstraZeneca): In May 2015, the company entered into a Business Transfer and Subscription Agreement, or the AstraZeneca Agreement, with AstraZeneca, AstraZeneca UK Limited, and AstraZeneca Pharmaceuticals LP, which was amended and restated in March 2016 and further amended in August 2017, pursuant to which the company obtained, among other things, worldwide rights to SUL-DUR, ETX0282, and zoliflodacin. Intellectual Property Durlobactam: The company’s intellectual property portfolio for its durlobactam program contains patent applications directed to the compositions of matter for durlobactam and other chemical analogs, as well as the methods of making, referred to as synthetic methods, and the methods of use and the modes of treatment using durlobactam in combination with one or more antibiotic compounds. As of December 31, 2021, the company owned four issued U.S. patents, one pending provisional application, and 69 issued foreign patents, as well as 12 pending foreign patent applications, of which two are allowed. The issued foreign patents are in several jurisdictions, including Australia, the European Union, Canada, China, Hong Kong, Israel, India, Japan, Macau, Mexico, New Zealand, the Philippines, the Russian Federation, Singapore, South Africa, South Korea, Taiwan and the United Kingdom. The issued U.S. and foreign patents and patents issuing from pending U.S. and foreign applications will have expiration dates of April 2033 and November 2035. Zoliflodacin: The company’s intellectual property portfolio for zoliflodacin contains patent applications directed to the compositions of matter for zoliflodacin and other chemical analogs, as well as synthetic methods and the methods of use and modes of treatment. As of December 31, 2021, the company owned 7 issued U.S. patents, and 71 issued foreign patents, as well as six pending foreign patent applications. The issued foreign patents are in several jurisdictions, including Australia, Brazil, Canada, China, Eurasia, the European Union, Hong Kong, India, Israel, Japan, Mexico, New Zealand, the Philippines, Singapore, South Africa, South Korea, Taiwan and the United Kingdom. The issued U.S. and foreign patents and patents issuing from pending U.S. and foreign applications have expiration dates of October 2029, January 2034 and May 2035. ETX0282: The company’s intellectual property portfolio for its ETX0282 program contains patent applications directed to the compositions of matter for the prodrug ETX0282, the active molecule, ETX1317, and other chemical analogs, as well as synthetic methods, and the methods of use and the modes of treatment using ETX0282 and ETX1317 in combination with one or more antibiotic compounds. As of December 31, 2021, the company owned one issued U.S. patent, one pending U.S. application, two issued foreign patents, four allowed foreign patents and 15 pending foreign patent applications, of which one is allowed. The issued U.S. and foreign patents and patents issuing from pending U.S. and foreign applications will have expiration dates of September 2037. ETX0462: The company’s intellectual property portfolio for its ETX0462 program contains patent applications directed to the compositions of matter for ETX0462 and other chemical analogs, as well as synthetic methods, and the methods of use and the modes of treatment. As of December 31, 2021, the company owned one granted U.S. patent application, one pending U.S. patent application, three issued foreign patents, and 17 pending foreign patent applications. The issued U.S. and foreign patents and patents issuing from pending U.S. and foreign applications will have expiration dates of May 2038. Provisional Patents: In addition to the issued and pending patent applications covering its most advanced product candidates, the company’s portfolio includes one pending PCT application relating to an early stage discovery project. Trademarks The company’s trademark portfolio consists of registered trademark and service mark rights for ENTASIS THERAPEUTICS in several jurisdictions, including the United States, the European Union, Japan, Argentina, Australia, Brazil, Canada, India, Mexico, Norway, the Russian Federation, South Korea, Switzerland, Taiwan, Turkey and the United Kingdom, and pending applications in other jurisdictions. In addition, it has registered trademark and service mark rights for ENTASIS THERAPEUTICS (plus design) in the United States, the European Union, Argentina, Brazil, Canada, Japan, Australia, India, Norway, the Russian Federation, South Korea, Switzerland, Taiwan, Turkey, Mexico and the United Kingdom, and pending applications in other jurisdictions. It also has registered trademark rights for XACDURO and XULDURO in the United States, the European Union, Brazil, China, Hong Kong, India, Macau, New Zealand, the Philippines, Taiwan, the United Arab Emirates, Argentina, Albania, Australia, Egypt, Macedonia, Mexico, Malaysia, Saudi Arabia, the United Kingdom, Belarus, Bosnia-Herzegovina, Cambodia, Indonesia, Israel, Laos, Japan, Moldova, Montenegro, Norway, the Russian Federation, Serbia, Singapore, South Korea, Switzerland, Turkey, Ukraine and Vietnam, and pending applications in other jurisdictions. Research and Development The company’s research and development expenses were $37.1 million for the year ended December 31, 2021. Government Regulation In addition to the U.S. Food and Drug Administration (FDA) restrictions on marketing of pharmaceutical products, several other types of state and federal laws restrict the company’s business activities, including certain marketing practices. These laws include, without limitation, anti-kickback laws, false claims laws, and data privacy and security laws, as well as transparency laws regarding payments or other items of value provided to healthcare providers. History Entasis Therapeutics Holdings Inc. was founded in 2015. The company was incorporated under the laws of the state of Delaware in 2018.