Roche Teams With Spero To Target Gram-Negative Pathogens

Roche gets an option to acquire program addressing drug-resistant gram-negative infections when it reaches IND-filing status. Spero is working on a novel target found originally in infected tobacco plants.

Spero Therapeutics LLC, launched in 2013 with seed funding from Atlas Venture with a focus on developing novel antibiotics for gram-negative infections, has signed its first partner. The Cambridge, MA-based biotech announced April 9 that it will partner with Roche on preclinical development of a molecule addressing an undisclosed novel target that has shown the ability in preclinical studies to shut off the effects of gram-negative pathogens. [See Deal]

Roche is providing non-dilutive R&D funding to Spero, which is about halfway through the IND-enabling work for the candidate, said Ankit Mahadevia, MD, a partner at Atlas Venture and acting president of Spero. The Big Pharma will then will have the option to license the program at the time an IND is filed at FDA, at pre-negotiated terms including up-front cash and potential milestones.

Mahadevia founded Spero in April 2013 with a $3 million Series A funding from Atlas, along with Partners Innovation Fund and SR One, the venture arm of GlaxoSmithKline PLC. Spero’s initial program stems from research by Laurence Rahme, PhD, a plant biologist at [Massachusetts General Hospital] who discovered the target in infected tobacco plants and then switched her focus to the impact on gram-negative pathogenesis in humans.

At the time Atlas raised its ninth fund, the venture firm was looking proactively for new areas of research to invest in, Mahadevia said. Given his background as a clinician, he was interested in start-ups focused on addressing unmet medical needs in drug-resistant bacterial infections, an area of high unmet medical need that has been de-emphasized by many Big Pharmas in the last decade due to regulatory and commercial challenges in the field.

This R&D gap has created an opportunity for smaller start-ups and specialty pharmas that are developing antibiotics, especially now that Congress has stepped up incentives to drive more antibiotic development. FDA also is looking to pave the way for faster approval of new antibiotics.

Antibiotics for resistant gram-negative infections have become a particularly dire unmet medical need. Several antibiotics targeting resistant gram-negative pathogens are now moving through the later stages of development from companies like Forest Laboratories Inc., Cubist Pharmaceuticals Inc., and Achaogen Inc. (See (Also see "Market Snapshot: Gram-Negative Antibiotics Progress As Urgency Grows" - Pink Sheet, 3 Mar, 2014.).) But all of the antibiotics in late-stage development work through existing mechanisms of action and entirely novel approaches remain very much in need.

“We had had a reasonable success in a previous fund in antibiotics with Novexel SA, which we’d sold off to AstraZeneca PLC,” Mahadevia said in an interview. [See Deal] “Concurrent with starting fund nine, the regulatory environment in anti-infectives really changed significantly for the better. Secondly, there was a series of data published by the CDC [US Department of Health and Human Services’ Centers for Disease Control & Prevention] and by the Infectious Diseases Society of America that highlighted in stark numbers the huge unmet need, especially for gram-negative infections.”

Congress passed the Generating Antibiotic Incentives Now (GAIN) Act in 2012 in an effort to encourage drug manufacturers to develop novel antibiotics. Since then, the regulatory environment for bringing novel antibiotics through development and to market has grown more clear, he said. (See (Also see "Antibiotic Development Incentives Face Critical Test As NDA Reviews Begin" - Pink Sheet, 20 Jan, 2014.).)

“What Rahme devised was a very novel way of identifying compounds that inhibit a particular target within gram-negative bugs, Pseudomonas aeruginosa, but also other gram-negative infections, and that control their ability to make people sick,” Mahadevia said. “It doesn’t kill the bacterium if you inhibit this target, what it does is essentially shuts them off. This target controls at least a quarter of the entire genome of these bugs and shuts them off.”

Hitting the target also inhibits the persistence of bugs that become quiescent in the presence of antibiotics and wait until the antibiotic’s affects disappear to resume their pathogenicity, he said.

Spero’s “startling” in vitro and in vivo data drew partnership interest from multiple suitors, according to Mahadevia. The company determined that Roche was the right partner for its first program, based on its “legacy in antibiotics,” he added. “If you look at some of the deals Roche has done, they have a clear roadmap for where they want to go,” he said.

The partnership with Spero marks the fifth anti-infective deal for Roche and its large-molecule unit Genentech Inc. since mid-2012. Roche’s recent interest in the space speaks to a resurgence on the part of Big Pharma in antibiotic R&D.

In June 2012, Roche in-licensed exclusive global rights to a discovery-stage polymerase inhibitor for influenza from Australia’s Savira pharmaceuticals GMBH.[See Deal] Roche took over sole development responsibility for that program last November.

In February 2013, Genentech signed a discovery and development agreement in drug-resistant infections with RQx Pharmaceuticals Inc.[See Deal] Then, that November, Roche licensed global rights to Phase II macrocycle antibiotic POL7080 for P. aeruginosa infections from Polyphor Ltd.[See Deal] Most recently, the Swiss pharma paid a $16 million up-front to UK drug-discovery start-up Discuva Ltd. for global rights to its candidates for drug-resistant gram-negative pathogens. [See Deal]

“We have a lot of data to sift through and a lot of decisions to make before we go into the clinic, but we have data showing that as a single agent [our candidate] improves mortality in animal models and in combination it makes existing antibiotics work better,” Mahadevia noted. An IND filing is still likely a couple of years off, however. Rahme serves as a consultant to Spero, which currently has a headcount of five but is expanding slowly. Mahadevia plans to bring in a chief scientific officer in the near term.

As for cash, he thinks the remainder of Spero’s seed funding plus what Roche is providing should be sufficient to bring the first program to IND-filing status. If additional cash is needed, Mahadevia believes the firm can raise it from its existing investors.

Adapted from “The Pink Sheet” DAILY, April 9, 2014.