Opsona, And Pharma Backers, Await Day of Reckoning for Kidney Drug

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overactive immune responses. Most of the mega drugs approved for rheumatoid arthritis or other inflammatory diseases—such as adalimumab (Humira) or etanercept (Enbrel)—work by using an antibody to target and block a molecule called tumor necrosis factor (TNF), which is involved in the inflammatory response that leads to the symptoms associated in those diseases. O’Neill says that TNF, however, is being “driven by” TLRs. So Opsona’s hypothesis has been, “if we block them [the TLRs], we’ll block down everything—we’ll shut down the whole massive inflammatory attack,” O’Neill says.

The hypothesis’ promise caught the attention of investors. Since the Series A round in 2005, a number of other corporate venture entities have jumped in: Amgen, Baxter International, Roche Venture Fund, and Novartis Venture Fund. Other venture groups that provided funds include Fountain Healthcare Partners, BB Biotech Ventures, Inventages Venture Capital, and Sunstone. It all added up to more than 60 million euros ($75 million).

Of course, it’s still a risky investment. Opsona is by no means the only company looking into TLRs. Seattle-based VentiRx, for instance, has been developing a drug that stimulates a specific TLR, TLR8, to boost the immune system’s response to cancer. It cut a big option-to-buy deal with Summit, NJ-based Celgene (NASDAQ: CELG) in 2012. Swiss biotech Novimmune is developing an antibody drug that blocks TLR4. Berkeley, CA-based Dynavax Technologies is developing drugs blocking TLR 7, 8, and 9. No one’s made it to the finish line yet: A TLR4-targeting drug Eisai was developing for sepsis failed a Phase 3 test last year.

“In general there’s been no human documentation to date that blocking a toll-like receptor reduces disease in humans. [But] the lack of efficacy of the TLR4 drug was due to the trial, and not necessarily the concept,” says Charles Dinarello, an immunology professor at the University of Colorado School of Medicine, who has published papers on toll-like receptors, and isn’t involved with Opsona. “Sepsis is a graveyard for very good drugs.”

Even so, Opsona’s first two projects didn’t pan out either. Its first idea was to engineer a certain anti-inflammatory bacterial factor, but O’Neill says the company just couldn’t make the drug. Second came projects focused on different TLRs, which Opsona used to cut a partnership deal with Wyeth and help fund the company. But Pfizer bought Wyeth in 2009 and purchased the IP around those programs. The only thing left standing for Opsona was its TLR2 work. Opsona is the only company targeting TLR2 (“we own all the IP around it,” O’Neill says).

Dinarello says there’s good reason Opsona was able to draw investments from that research: “All these TLR2 pathways have many indications. Probably a list of about 20 things. I think an antibody for TLR2 will have clinical use—I would definitely say it has a pretty good chance of doing well.”

Now, 10 years in, Opsona is about to find out whether that work will lead to something of real value. The specific goal: to show that administering OPN-305 after a kidney transplant will reduce the likelihood that a patient will still be on dialysis after 7 days—without increasing the risk of infection from a suppressed immune system. If it can? “That’s a very valuable drug,” O’Neill says. “There’s 2,000 patients waiting for transplants in each hospital around Europe. And our product would be part of the standard of care.”

Success would also enable Opsona to explore other uses for OPN-305. O’Neill says the company already has encouraging preclinical data in cancer (in combination with chemotherapy), and what’s known as “NSTEMI,” an acronym for a certain type of heart attack.

“Some of these guys have been with us since 2004, so they want to know, when are we gonna cash in our chips here?” O’Neill says. “It’s all about that graph at the end [of the study].”

Photo courtesy of Flickr user Discover Science & Engineering via Creative Commons


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