With success in a 28-day preclinical safety and tolerability study, Synthetic Biologics Inc. believes it is on the cusp of bringing the first drug to prevent Clostridium difficile infections into clinical development, with an ambitious timeline to move into Phase II testing during the first half of 2015.

Based in Rockville, Md., Synthetic Biologics’ SYN-004 is an oral, second-generation anti-infective based on a prior compound licensed from now-shuttered Finnish biotech Ipsat Therapies Oy. The company plans to file an IND within the next two months for ’004 and then begin Phase Ia and Ib trials during the fourth quarter, CEO Jeffrey Riley said in an interview.

“We did a one amino acid change on the molecule and we had to discuss [that] with the FDA,” he explained. “They were okay with all of the clinical data that had been generated but they requested a bridging study, which is basically just a canine toxicity study. The results were the same and the drug is completely benign in a dog model.”

In that study, Synthetic Biologics tested repeated doses of ’004 exceeding those it expects to test in human subjects over a 28-day period.

The company expects that ’004, an oral biologic, will protect a patient’s gastrointestinal microflora – also known as the microbiome – from the side effects of intravenous beta lactam antibiotic therapy. Specifically, antibiotics from the penicillin and cephalosporin families can alter the microbiome, killing off beneficial bacteria and making the patient more susceptible to C. difficile infections, Riley said.

Ipsat worked with the first-generation compound, P1A, a decade ago hoping to reduce the diarrhea complications that can present from antibiotic therapy Also see "Antibacterials: Biotechs Fill the Big Pharma Void" - In Vivo, 1 May, 2004..

Now, Synthetic has the second-generation molecule about ready for clinical development, along with an oral therapy for constipation-predominant irritable bowel syndrome (SYN-010) that should enter clinical development next year. The biotech also is working on monoclonal antibodies for pertussis (SYN-005) and Acinetobacter infections, as well as an oral estriol candidate (Trimesta) to treat relapsing-remitting multiple sclerosis and cognitive dysfunction related to MS.

Riley said it would be more accurate to call Synthetic Biologics a “pathogen-focused” company rather than one centered on anti-infective therapeutics.

“Irritable bowel syndrome isn’t in the classic anti-infective mold, pertussis really doesn’t fit either,” he said. “What we’re trying to do is target diseases and specific bacteria that we can take out or fix or mitigate in some way without causing disruption to the rest of the human system. That’s the philosophy of the company.”

“The IBS drug does that by reducing methane gas, by interrupting an energy cycle of a little bug called a methanogen that lives in your intestinal tract,” the exec continued. “The C. difficile drug works the same way but we’re actually protecting the entire microbiome – the 9 trillion that live in your gut – essentially from being disrupted, and if you protect them, a lot of other diseases are seriously mitigated.”

Different Anti-Infective Approach Than Vaccination

Synthetic Biologics’ strategy will be to promote co-administration of ’004 with beta lactam antibiotics, a point-of-care preventative approach that it says it vastly different from mass vaccination to prevent infection.

“When you go into a hospital, a nursing home or a dentist’s office, if they’re going to give you an I.V. antibiotic which is a beta-lactam, you would pop one of our little pills at the same time, and that would protect your microbiome from being damaged by the antibiotic,” Riley said.

He doesn’t think the development path will be all that difficult even though there is no currently approved preventive therapy for C. difficile infection. The company already has discussed a development approach with the Centers for Disease Control & Prevention, he said.

“It’s fairly typical, unlike a vaccine, which is incredibly difficult just because of the sheer volume and diversity of patients that you’re trying to deal with,” Riley noted.

Because the IND has not been filed yet, Riley declined to divulge any expected trial design characteristics, but said Synthetic Biologics expects to have proof-of-concept for ’004 by about this time next year. He anticipates quick-moving trials and says the firm should have a good idea if the candidate is working as expected by the end of the Phase Ib study.

Riley thinks C. difficile infection is an ideal indication to pursue because such infections have surpassed methicillin-resistant Staphylococcus aureus (MRSA) as the most prevalent hospital-acquired infection in the U.S. The company notes that C. difficile infections affect 1.1 million Americans annually, leading to 30,000 deaths, an estimated four-to-seven additional hospitalization days on average per case, and $8.2 billion in annual hospitalization costs.

Synthetic Biologics most recently raised funds through a follow-on public offering in December, netting $12.4 million by selling 13.2 million common shares at $1 each [See Deal].

C Diff. Prevention Candidate Heads Into Clinic With Ambitious Timetable

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