Spero Therapeutics said today it has won up to $54.2 million in grants from two federal agencies, and supporting studies by a third agency, toward further development of the company’s lead candidate SPR994 (tebipenem), an oral antibiotic for complicated urinary tract infections (cUTIs) caused by antibiotic-resistant gram-negative bacteria.

The grants from the Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency (DTRA) come a week after Spero reported positive interim Phase I results from its ongoing single ascending dose (SAD) and multiple ascending dose (MAD) trial of SPR994 (NCT03395249).

The interim results, announced July 9, showed SPR994 to have a favorable safety, pharmacokinetic, and pharmacodynamic profile that supported advancing the candidate to a pivotal Phase III clinical trial at a 300 mg dose administered three times per day. Spero expects to report final data from the MAD portion of the Phase I trial in the third quarter.

SPR994 is Spero’s novel investigational oral formulation of tebipenem, a carbapenem-class antibiotic marketed since 2009 by Meiji Seika Pharma in Japan as Orapenem® (tebipenem pivoxil) for common pediatric infections. SPR994 is a beta-lactam designed to be the first broad-spectrum oral carbapenem-class antibiotic for adults to treat multidrug-resistant (MDR) gram-negative infections by helping patients avoid hospitalizations and/or transition them from hospital care after IV therapy.

BARDA has committed up to $44.2 million in grants to Spero, consisting of $15.7 million upfront, and up to an additional $28.5 million over five years, toward further clinical development of SPR994, should BARDA exercise all options. Pending discussions from a pre-Phase III meeting with the FDA, which Spero plans to request later this year, Spero said it plans to launch the pivotal trial of SPR994 for cUTI “around year-end 2018,” with results intended to support of a new drug application (NDA).

Growing Antibiotic Resistance in UTI

Spero has cited a 2014 report by the Center for Disease Dynamics, Economics & Policy (CDDEP), which found that the most commonly used oral class of antibiotics for UTI, fluoroquinolones, were experiencing resistance at up to 35% in E. coli. The antibiotic resistance more than doubled in the last decade—creating an opportunity, Spero reasons, for a new oral treatment. Carbapenems have become standard-of-care for many MDR gram-negative bacterial infections, but are only available now as intravenous therapeutics.

BARDA is one of three federal agencies collaborating to support development of SPR994. Spero said the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) will conduct a series of studies to assess the efficacy of SPR994 against infections caused by biodefense threats—including anthrax, plague, and melioidosis.

USAMRIID is the lead military medical research laboratory for the Joint Science and Technology Office for Chemical and Biological Defense of the Defense Threat Reduction Agency (DTRA). The DTRA is awarding Spero up to $10 million to fund what the company said were nonclinical biodefense aspects of the inter-agency collaboration. DTRA’s award will consist of $1.25 million in initial upfront support, and up to an additional $8.75 million tied to achieving milestones.

“We look forward to advancing SPR994 through clinical development for public and biodefense use as we target public health needs caused by emerging drug-resistant infections,” says Ankit Mahadevia, M.D., CEO of Spero Therapeutics. “We believe the funding is a validation of the clinical potential of SPR994 across a broad treatment landscape, and of the ability of a small biotech company to work toward bringing these innovative therapies to patients in collaboration with our partners at BARDA and DTRA.”

Spero said the inter-agency collaboration may also include a clinical trial in pneumonia patients—an indication for which tebipenem, SPR994’s active pharmaceutical ingredient, is currently approved in Japan for pediatric use.

In preclinical studies, according to Spero, SPR994 showed potent antibiotic activity against gram-negative bacteria, including E. coli-producing extended-spectrum beta-lactamases (ESBLs) and ESBL-producing Klebsiella pneumoniae, similar to IV-administered ertapenem.

During development of tebipenem in Japan, Meiji conducted clinical and pharmacologic studies in which approximately 1,200 subjects were dosed with tebipenem. The drug showed a favorable safety profile consistent with post-marketing outcomes data on the safety and efficacy of tebipenem in 3,540 pediatric patients with pneumonia, otitis media or sinusitis.

BARDA is an agency of the U.S. Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR). DTRA is the U.S. Department of Defense’s official Combat Support Agency for countering weapons of mass destruction. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command.

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