Iterum Therapeutics Stock

Iterum Therapeutics plc, a clinical-stage pharmaceutical company, engages in developing and commercializing sulopenem to be potentially the first oral penem available in the United States and the first and only oral and intravenous (IV) branded penem available globally.

Penems, including thiopenems and carbapenems, belong to a class of antibiotics more broadly defined as ß-lactam antibiotics, the original example of which was penicillin, but which also includes cephalosporins. Sulopenem is a potent, thiopenem antibiotic delivered intravenously which is active against bacteria that belong to the group of organisms known as gram-negatives and cause urinary tract and intra-abdominal infections. The company has also successfully developed sulopenem in an oral tablet formulation, sulopenem etzadroxil-probenecid.

In 2018, the company initiated three clinical trials in its Phase 3 development program, which included: a Phase 3 uncomplicated urinary tract infection (uUTI) clinical trial, known as Sulopenem for Resistant Enterobacteriaceae (SURE) 1, comparing oral sulopenem to oral ciprofloxacin in women with uUTI, a Phase 3 complicated urinary tract infection (cUTI) clinical trial known as SURE 2, comparing IV sulopenem followed by oral sulopenem to IV ertapenem followed by oral ciprofloxacin in adults with cUTI and a Phase 3 complicated intra-abdominal infection (cIAI) clinical trial known as SURE 3, comparing IV sulopenem followed by oral sulopenem to IV ertapenem followed by a combination of oral ciprofloxacin and oral metronidazole in adults with cIAI. The company designed one Phase 3 clinical trial in each indication based on its end of Phase 2 meeting with the U.S. Food and Drug Administration (FDA) and feedback from the European Medicines Agency (EMA).

The company conducted the Phase 3 clinical trials under Special Protocol Assessment (SPA) agreements from the FDA. In December 2019, the company announced that sulopenem did not meet the primary endpoint of statistical non-inferiority compared to the control therapy for the cIAI trial (SURE 3). In the second quarter of 2020, the company announced the results of its Phase 3 clinical trials in cUTI (SURE 2) and uUTI (SURE 1).

Based on discussions with the FDA at a pre-New Drug Application (NDA) meeting in 2020 and previous correspondence with the FDA, the company submitted an NDA for oral sulopenem for the treatment of uUTIs in patients with a quinolone non-susceptible pathogen in the fourth quarter of 2020 and the FDA accepted the application for review in January 2021. It received a Complete Response Letter (CRL) from the FDA on July 23, 2021, in respect of its NDA. The CRL provided that the FDA had completed its review of the NDA and had determined that it could not approve the NDA in its present form. The CRL further provided that additional data are necessary to support approval of oral sulopenem for the treatment of adult women with uUTIs caused by designated susceptible microorganisms proven or strongly suspected to be non-susceptible to a quinolone and recommended that it conducts at least one additional adequate and well-controlled clinical trial, potentially using a different comparator drug. In July 2022 the company reached an agreement with the FDA under the SPA process on the design, endpoints, and statistical analysis of a Phase 3 clinical trial for oral sulopenem for the treatment of uUTIs and it commenced enrollment in that clinical trial, known as REnewed ASsessment of Sulopenem in uUTI caused by Resistant Enterobacterales (REASSURE), in October 2022 and anticipates completing enrollment in the first half of 2024. The study is designed as a non-inferiority trial comparing oral sulopenem and Augmentin (amoxicillin/clavulanate) in the Augmentin susceptible population. Additionally, though not an approvability issue, the FDA recommended in its CRL that the company conducts additional non-clinical Pharmacokinetics and Pharmacodynamics (PK/PD) studies to support dose selection for the proposed treatment indication(s). The company has completed the additional non-clinical PK/PD investigations, as recommended by the FDA, which supports the dosing regimen selected for oral sulopenem.

In November 2015, the company acquired an exclusive, worldwide license under certain patents and know-how to develop and commercialize sulopenem and its oral prodrug, sulopenem etzadroxil, from Pfizer Inc. (Pfizer). Pfizer conducted Phase 1 and Phase 2 clinical trials of sulopenem delivered intravenously in Japan in over 1,450 patients with a variety of hospital and community acquired infections. These clinical trials documented a treatment effect in the indications studied and provided preliminary insights into the safety profile for sulopenem, which will continue to be assessed with additional clinical trials. Pfizer subsequently developed sulopenem into a prodrug formulation, sulopenem etzadroxil, to enable oral delivery. The company has further enhanced this prodrug formulation with the addition of probenecid to extend sulopenem's half-life and enhance its antibacterial potential. Probenecid is a pharmacokinetic enhancer that has been safely and extensively used globally for decades. The company refers to sulopenem delivered intravenously as sulopenem and, together with oral sulopenem, as its sulopenem program.

The company intends to commercialize its sulopenem program in the United States with a commercial partner and/or on its own with a targeted sales force in the community setting.

Sulopenem Program, Clinical and Regulatory Status

The company pursued three initial indications for oral sulopenem and sulopenem in three Phase 3 clinical trials. It designed these Phase 3 clinical trials based on extensive in vitro microbiologic surveillance data, Phase 1 pharmacokinetic data from healthy volunteers, as well as population pharmacokinetic data from patients, animal models in relevant disease settings, Phase 2 data from a program performed with sulopenem by Pfizer in Japan in the early 1990s, and regulatory feedback from the FDA at the company's end-of-Phase 2 meeting, all supported by an advanced commercial manufacturing program which provided clinical supplies.

In 2018, the company initiated three clinical trials in its Phase 3 development program, being the SURE 1 trial, the SURE 2 trial and the SURE 3 trial. The company designed one Phase 3 clinical trial in each indication based on its end of Phase 2 meeting with the FDA and feedback from the EMA. It conducted the Phase 3 clinical trials under SPA agreements from the FDA. In December 2019, the company announced that sulopenem did not meet the primary endpoint of statistical non-inferiority compared to the control therapy for the cIAI trial (SURE 3). In the second quarter of 2020, it announced the results of its Phase 3 clinical trials in cUTI (SURE 2) and uUTI (SURE 1). Based on discussions with the FDA at a pre-NDA meeting in September 2020 and previous correspondence with the FDA, the company submitted an NDA for oral sulopenem for the treatment of uUTIs in patients with a quinolone non-susceptible pathogen in the fourth quarter of 2020 and the FDA accepted the application for review in January 2021.

The company received a CRL from the FDA on July 23, 2021 in respect of its NDA. The CRL provided that the FDA had completed its review of the NDA and had determined that it could not approve the NDA in its present form. The CRL further provided that additional data are necessary to support approval of oral sulopenem for the treatment of adult women with uUTIs caused by designated susceptible microorganisms proven or strongly suspected to be non-susceptible to a quinolone, and recommended that the company conducts at least one additional adequate and well-controlled clinical trial, potentially using a different comparator drug. In July 2022 the company reached an agreement with the FDA under the SPA process on the design, endpoints, and statistical analysis of a Phase 3 clinical trial for oral sulopenem for the treatment of uUTIs and it commenced enrollment in that clinical trial, known as REASSURE, in October 2022. Additionally, though not an approvability issue, the FDA recommended in its CRL that the company conducts additional non-clinical PK/PD studies to support dose selection for the proposed treatment indication(s). It has completed the additional non-clinical PK/PD investigations, as recommended by the FDA.

Strategy

The company's strategy is to develop and commercialize its sulopenem program for multiple indications, and in the long term to build a market-leading anti-infective business. The key elements of the company's strategy are to obtain regulatory approval for oral sulopenem in the United States; consider regulatory strategy outside the United States; maximize commercial potential of its sulopenem program; pursue the development of oral sulopenem and sulopenem in additional indications; and build a portfolio of differentiated anti-infective products.

Pfizer License Agreement

In November 2015, the company and its wholly owned subsidiary, Iterum Therapeutics International Limited, entered into a license agreement with Pfizer (the Pfizer License), pursuant to which it acquired from Pfizer an exclusive, royalty-bearing license under certain patent rights and know-how to develop, manufacture, and commercialize sulopenem and related compounds, including, among others, sulopenem etzadroxil and three other sulopenem prodrugs, globally for the treatment, diagnosis and prevention of infectious diseases and infections in humans. The licensed patents include two U.S. patents, one of which covers the composition of matter of sulopenem etzadroxil, one patent in Japan, one patent in Hong Kong and one patent in Mexico. All patents directed to the compound sulopenem expired prior to the company entering into the Pfizer License. Pursuant to the Pfizer License, the company's exclusive license from Pfizer includes certain know-how, data and regulatory documents that will support the development of sulopenem.

Intellectual Property

As of February 28, 2023, the company exclusively licensed from Pfizer two U.S. patents and three foreign patents, including one U.S. patent directed to composition of matter of sulopenem etzadroxil, which is projected to expire in 2029, subject to potential extension under the Drug Price Competition and Patent Term Restoration Act of 1984, or Hatch-Waxman Act, to 2034, and three foreign patents related to sulopenem etzadroxil. It also owns two U.S. patents, with one patent directed to the composition of the bilayer tablet of oral sulopenem and its related uses and the other directed to the method of use of oral sulopenem in treating multiple diseases, including uUTIs. Both patents are projected to expire in 2039, excluding any additional term for patent adjustments or patent term extensions. The company also owns three U.S. patent applications and twenty-seven foreign patent applications, which collectively cover uses of sulopenem and probenecid and bilayer tablets of sulopenem etzadroxil and probenecid. Any U.S. or foreign patents issuing from the pending applications are projected to expire between 2039 and 2041, excluding any additional term for patent adjustments or patent term extensions. In addition, the FDA has designated sulopenem and oral sulopenem as Qualified Infectious Disease Products (QIDP) for the indications of uUTI, cUTI, cIAI, community-acquired bacterial pneumonia, acute bacterial prostatitis, gonococcal urethritis, and pelvic inflammatory disease pursuant to the Generating Antibiotic Incentives Now Act (the GAIN Act).

Regulations

The company's operations are subject to anti-corruption laws, including the U.S. Foreign Corrupt Practices Act (FCPA), the Irish Criminal Justice (Corruption Offenses) Act 2018, and other anti-corruption laws that apply in countries where it does business and may do business in the future.

History

Iterum Therapeutics plc was founded in 2015. The company was incorporated under the laws of the Republic of Ireland in 2015 as a limited company and re-registered as a public limited company in 2018.