Rib-X Pharmaceuticals will receive $10 million upfront and could earn another $9 million in near-term research milestones under an agreement it signed with Sanofi July 6 through which the two companies will co-develop novel antibiotics to treat drug-resistant Gram-negative and Gram-positive hospital-acquired infections.

Sanofi also gets the option to license molecules resulting from the research, with structured payouts going to Rib-X.

The deal is structured as an exclusive worldwide research collaboration centered around Rib-X's preclinical RX-04 program, described by CEO Mark Leuchtenberger as a 20-angstrom-wide binding site in one section of the bacterial ribosome where all the biotech's research is focused. Bacterial ribosomes are an internal cell component in which proteins are synthesized. Rib-X's preclinical work indicates that its novel molecules directly impact ribosome function and exert anti-bacterial activity by interfering with protein synthesis.

The agreement initially pertains to four product profiles within the agreed to portion of the ribosome, but the deal essentially gives Sanofi "drilling rights" in that area. The area could potentially yield thousands of candidates, all of which Sanofi will have option rights to. Anything Sanofi does not option, however, will revert fully to Rib-X.

Based in New Haven, Conn., the biotech says the RX-04 program focuses on the ribosome's catalytic region, where many clinically distinct classes of antibiotics bind. "After synthesizing fewer than 200 compounds, we have created five completely novel series of compounds targeting two novel sites that show good antibacterial activity against a number of clinically important multi-drug-resistant Gram-negative pathogens," Rib-X states.

Since its 2002 inception, the company's business model has been based on a pair of technologies licensed from Yale University - a high-resolution crystal structure of a ribosome discovered by company founders Thomas Steitz and Peter Moore and access to a structure-based drug design software application by William Jorgensen ([See Deal]).

Each molecule optioned and developed by Sanofi could yield up to $86 million in development and regulatory milestones as well as more than $100 million in commercial milestones, plus potential low double-digit royalties on sales.

Privately held Rib-X retains rights to the discovery platform and its future programs, other than the specific assets licensed by Sanofi, and the biotech also has the option to co-promote in the U.S. one program of its choosing from the collaboration.

"There is no upper limit on the number of products that can come out of this collaboration," Leuchtenberger said. "What is limited is where these products bind - it's a 20-angstrom-wide binding site in one section of the ribosome. We have not licensed away any part of our broad platform and there are dozens of other sites that remain rich, validated, viable sites for antibiotics and potentially antifungals."

Leuchtenberger asserts that his company attracted the attention of Sanofi with "the broadest-spectrum program out there," one that encompasses Gram-positive pathogens such as various strains of MRSA, as well as what he terms "the big three" of the Gram-negative spectrum - NDM1, acinetobacter and pseudomonas.

Recent FDA Guidance May Allow Quicker Development

With rising concerns about the mortality rates and high hospitalization costs related to these strains, FDA issued guidance last year that may permit more rapid and aggressive development of new antibiotics (Also see "Hospital-Acquired Pneumonia Is Life Or Death, FDA Says; Recommends Sole Primary Endpoint" - Pink Sheet, 7 December, 2010.).

"FDA indicated that it was conceptually open to more aggressive programs for Gram-negatives, specifically even using uncontrolled trials with historical controls as the endpoint," Leuchtenberger said. With the RX-04 programs nearing the end of preclinical development, Rib-X hopes to file IND applications with the agency next year. "There certainly is time enough to think about how to structure conversations [about trial protocols]," he added.

Leuchtenberger said Rib-X has been conducting partnering discussions around three of its programs for several years - beyond RX-04, it has delafloxacin, a next-generation quinolone, nearing Phase III as a treatment for complicated skin and soft tissue infections, and radezolid in Phase II for community-acquired pneumonia and uncomplicated skin and soft tissue infections.

The company's negotiations with Sanofi began last year and grew to fruition through multiple meetings at which Rib-X was able to present data showing significant advancement in the potency of its antibiotics, Leuchtenberger said. "They were able to see the trajectory of the program and really understand that we were on our way toward best-in-class data," he added.

The deal gives Rib-X added runway to advance its two lead programs. Along with a $20 million sale of convertible notes to Warburg Pincus and other returning investors in January, the $10 million upfront should provide Rib-X enough cash to last into late 2012, Leuchtenberger said ([See Deal]). The firm will report Phase IIb data on delafloxacin and Phase II and long-term preclinical data on radezolid in the fourth quarter.

Following those events, Rib-X plans to seek another financing and will consider both the private and public markets. "This is a series of important milestones for us as we enter the fourth quarter and the end of the year, and hopefully we use those as a springboard for a good financing that will allow us to fund our Phase III program," Leuchtenberger said.

- Joseph Haas (j.haas@elsevier.com)

Rib-X Teams With Sanofi To Develop Novel, Broad-Spectrum Antibiotics

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