Executive Summary

The discovery of antibiotics in the first half of the 20th century reduced the mortality from infectious diseases in the developed world by 95%, and by the 1970s it was widely believed that bacterial diseases had been conquered. That prediction was overly optimistic; the infectious disease mortality rate jumped by 75% in the period 1980 – 1995, largely due to antibiotic resistance.  About 2 million people acquire bacterial infections in U.S. hospitals each year, and 90,000 die as a result.  About 70% of those infections are resistant to at least one of the major classes of antibiotics.   Despite increased resistance to antibiotics, the development of new antibiotics has slowed to a crawl and only two new antibiotics with novel mechanisms of action have been approved since 1998.

Synereca’s scientific founder, Professor Scott Singleton, and his colleagues screened over 130,000 compounds yielded five separate chemical classes of antibiotic potentiators, and Synereca’s SAR campaign has synthesized over 400 novel compounds that have demonstrated potentiation of multiple classes of antibiotics including polymyxins, carbapenems, aminoglycosides, and fluoroquinolones.

Synereca’s first program focuses on compounds that enhance the activity of Colistin against gram-negative bacteria without enhancing its toxicity.  Colistin is current used as a drug of last resort against difficult to treat serious Gram-negative bacterial infections. The use of Colistin has increased as the incidence of multi-drug resistant Gram-negative bacteria has grown, despite its adverse effect profile. Unfortunately, as Colistin use increases, resistant strains are now emerging. Synereca’s small molecules have the potential to broaden the use of Colistin for serious in-patient bacterial infections, reduce the doses required to induce bacterial killing, and improve the treatment of multi-drug resistant pathogens.

Synereca has identified Colistin potentiators that have demonstrated enhancements of up to 4,000-fold in the potency (MIC100) of Colistin against a number of susceptible and resistant strains of Gram-Negative bacteria: A. baumanii, K. pneumoniae, E. coli, and P. aeruginosa.  Candidate compounds showed a 4-fold reduction in the protective dose of Colistin in vivo in a murine bacteremia model using an extensively multi-drug resistant strain of Acinetobacter baumanii  (Ab23; MIC >32 ug/ml for Colistin, Meropenem, Ciprofloxacin, Tobramycin, and Levofloxacin). Lead candidate compounds are currently being assessed for in vivo safety, pharmacokinetics, and efficacy to determine a final IND candidate.

Colistin potentiation has clinical application in several contexts. Initially, parenteral products containing Synereca’s potentiator compound at 2 concentrations (e.g. standard and 25% of standard) would be developed.  These products will be tested in patients with complicated Urinary Tract Infections (cUTI) and Intra-Abdominal Infections (cIAI) caused by Gram-Negative bacteria including Acenitobacter, Psuedomonas, Klebsiella, Enterobacter, and E. coli.

Colistin is also used clinically as last-line of care against multi-drug resistant Gram-Negative organisms in nosocomial and Ventilator-Associated Pneumonia (HAP/VAP), bloodstream infections, and skin, surgical-site, and skin-structure infections (cSSSI/SSTI). Thus, additional clinical indications provide the potential for broad label coverage in Gram-Negative bacterial infections. Similar combination products for inhalation use in cystic fibrosis patients could then be developed as line-extensions, where inhaled Colistin therapy is common for CF patients with lung infections associated with Gram-Negative organisms.

Synereca has partnered with Accele BioPharma, Inc., a biotechnology accelerator. Accele Venture Partners and additional investors have provided seed capital to Synereca in the amount of $2.5 million.  Accele BioPharma is interested in discussing this program with relevant commercialization partners and potential investors.

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