Our Promise

Responding to medical need

Iterum was founded with one over-arching goal: to develop an antibiotic that addresses the growing crisis of multi-drug-resistant pathogens and meets the specific needs of physicians, their patients and other important stakeholders.

Among the most important demands were new treatments for common, often serious conditions, including urinary tract infections (UTI), and intra-abdominal infections (IAI). Increasingly, these are caused by pathogens that have evolved resistance to today's antibiotics.

Clinicians and medical groups are looking for new therapies that can be used outside as well as inside hospitals. First, in-patient care is more expensive. Second, admission can increase the spread of infection and puts patients at risk for hospital-acquired infections.

Together, these demands pointed to an agent that remains effective against resistant pathogens and can be administered in oral as well as intravenous (IV) forms.

Iterum responded with its experimental medicine, sulopenem.

Sulopenem is the first oral and IV penem antibiotic demonstrating a potent spectrum of activity against multi-drug resistant gram-negative infections in both the hospital and community settings

Sulopenem and Iterum

Iterum's major achievements are three-fold;

1. Recognizing and rescuing a shelved experimental medicine, with significant potential value against multi-drug resistant infections.
2. Overcoming scientific and technical challenges to manufacture and deliver this compound as an antibiotic available in oral and IV forms.
3. Managing an efficient, fast-moving development program that recognizes urgent medical need.

Sulopenem was discovered in the laboratories of Pfizer Inc. in the 1980s and was first developed with an intravenous (IV) formulation only. The company completed an extensive pre-clinical program, followed by human studies. Later, an oral formulation was developed and tested in Phase 1 and Phase 2 trials.

Although the results were encouraging, development of sulopenem was abandoned when Pfizer shifted focus towards other therapeutic areas.

In November 2015, Iterum successfully negotiated the license of sulopenem and its prodrugs and restarted the development program. The company is now planning its Phase 3 program.

Sulopenem is the first oral and IV penem antibiotic demonstrating a potent spectrum of activity against multi-drug resistant gram-negative infections in both the hospital and community settings

Sulopenem Properties

Sulopenem is an orally bioavailable, broad-spectrum penem β-lactam antibiotic which is being developed for the treatment of infections caused by multi-drug resistant bacteria.

If approved, this penem-class antibiotic will help address the significant clinical and economic need for oral antibiotics that enable the avoidance of hospitalization in the treatment of community infections and, for those requiring admission, facilitate early hospital discharge by providing continuity-of-care step-down therapy.

Although there is an alarming increase of antibiotic resistance in bacteria that cause either community or hospital-acquired infections, of particular concern are the multi-drug resistant, gram-negative pathogens, Escherichia coli and Klebsiella species.

Production of extended-spectrum β-lactamases (ESBLs) by these organisms can make treatment with beta-lactams more likely to fail. Many ESBL producing organisms are also harboring resistance to other classes of antibiotics such as trimethoprim/sulfamethoxazole and the quinolones.

Carbapenems are an important class of intravenous antibiotics frequently regarded as the drugs of choice for the treatment of severe infections caused by ESBL-producing Enterobacteriaceae. Their utility across multiple treatment settings is limited, however, due to the lack of an oral formulation.

Sulopenem can, however, be administered orally (e.g as a tablet) or by intravenous (IV) infusion. This makes it an attractive option for the treatment of patients with uncomplicated and complicated urinary tract infections (UTI) and complicated intra-abdominal infections (cIAI) caused by susceptible organisms.

Trials have shown that oral sulopenem shows very promising biovailability (see table)

The IV formulation is intended for the initial treatment of severe infections in a hospital setting, and the oral prodrug will provide the option for IV-to-oral switch, thereby potentially minimizing in-hospital patient stay. The oral prodrug is also intended for the treatment of uncomplicated infections where a patient can tolerate an oral drug in an outpatient setting.

The development approach for sulopenem includes its evaluation for the treatment of uUTI, cUTI and cIAI.

The safety profile of intravenous sulopenem has been documented in a Phase 2 program.

Qualified Infectious Disease Product (QIDP) designation was granted by the U.S. FDA for both intravenous and oral formulations in the treatment of complicated urinary tract infections (cUTI), uncomplicated urinary tract infections (uUTI) as well as complicated intra-abdominal infections (cIAI).

Sulopenem is the first oral and IV penem antibiotic demonstrating a potent spectrum of activity against multi-drug resistant gram-negative infections in both the hospital and community settings

References and Further Reading

http://www.cdc.gov/drugresistance/about.html
https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf

Shaikh S, Fatima J, Shakil S, Rizvi SMD, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment. Saudi Journal of Biological Sciences. 2015;22(1):90-101. doi:10.1016/j.sjbs.2014.08.002.

Kassakian and Mermel. Changing epidemiology of infections due to extended spectrum beta-lactamase producing bacteria. Antimicrobial Resistance and Infection Control 2014 3:9. doi: 10.1186/2047-2994-3-9

Sulopenem Studies

Sulopenem's global development efforts to date confirm its safety and efficacy. The IV formulation has been studied in more than 1,450 subjects in Japan. The oral prodrug was studied in a Phase 2a study in community-acquired pneumonia (CAP) in the U.S. Iterum anticipates commencing three Phase 3 studies under Special Protocol Assessment (SPA) with the United States Food and Drug Administration (FDA) and Scientific Advice from the European Medicines Agency (EMA) in the initial indications of uUTI, cUTI and cIAI by the end of 2018 and filing a new drug application (NDA) and marketing authorization application (MAA) in the second half of 2019.

Sulopenem is the first oral and IV penem antibiotic demonstrating a potent spectrum of activity against multi-drug resistant gram-negative infections in both the hospital and community settings

Appropriate Use

Iterum is led by highly experienced Medical, Scientific and other professionals who strongly recognize the privilege and responsibilities associated with the development of a novel antibiotic, for use against multi-drug resistant infections.

At all stages of development, the company will seek expert opinion and encourage dialog with stakeholders responsible for individual patient care and the health of broad populations.

Iterum is confident that it can develop a novel antibiotic that addresses urgent medical needs and will promptly demonstrate its value within appropriate clinical management guidelines.