Corbus Believes A Different Inflammation-Fighting Approach Will Serve All CF Patients

The start-up asserts that agonizing the CB2 receptor will “resolve” inflammation, a different approach than used by anti-inflammatory drugs, and one that would pertain to the entire cystic fibrosis patient population.

“Resolving” inflammation may offer a safer and more broadly applicable approach to treating inflammatory disease – and that is the value proposition on which start-up Corbus Pharmaceuticals Holdings Inc. is betting, with financial backing from the Cystic Fibrosis Foundation.

Having received a $5 million development award from the funding arm of CFF for a Phase II study of resunab, a first-in-class, oral molecule that binds to and agonizes the CB2 receptor on immune cells, Corbus hopes to demonstrate over the next year and a half that targeting a natural process by which the body regulates immune response will provide a new, powerful therapeutic option for the entire cystic fibrosis patient population.

Corbus, which raised $10.3 million last year in an early-stage private equity financing headed up by Aegis Capital, is also developing resunab, its lone clinical candidate at present, for diffuse scleroderma [See Deal].

In an interview, Corbus CEO Yuval Cohen claimed that agonizing the CB2 receptor could provide a safer approach to battling inflammatory disease than the entire armamentarium of anti-inflammatory drugs, which take a completely different therapeutic approach than resunab.

“CB2 does two things in the body: in our brain it’s an analgesic receptor that makes pain go away, but in our immune system, it’s an anti-inflammatory receptor,” he explained, “so CB2 is one of the triggers that the body presses when it wants to go from heightened inflammation back to normal.”

“What we are doing in technical terms is resolving inflammation, and that is completely different than being an anti-inflammatory.” – Corbus CEO Yuval Cohen

Cohen pointed out that inflammation basically is a positive, natural process by which the human body fights infection. The whole host of inflammatory diseases stem from situations in which the inflammatory response does not shut off, with the immune response becoming a disease itself.

“Think about a healthy individual who, for example, gets infected with a cold virus,” he said. “The immune system is activated, the patient exhibits inflammatory symptoms, [but] you can turn it back off. Why? Because CB2 was engaged. In chronic inflammation, that never happens. And so by binding to CB2, what we are doing in technical terms is resolving inflammation, and that is completely different than being an anti-inflammatory. When we think about anti-inflammatories, [those are] drugs that jam the inflammatory system – what we’re doing is simply resolving it.”

Because all CF results from an overstimulated inflammatory process, resolution of inflammation theoretically should apply to all CF patients, Cohen said, meaning resunab stands to be much more broadly applicable than Vertex Pharmaceuticals Inc.’s Kalydeco (ivacaftor), the first disease-modifying drug for CF but one that addresses a small subpopulation with a specific mutation to the cystic fibrosis transmembrane conductance (CFTR) regulator.

Vertex is aiming to expand that population with the combination of ivacaftor, a CFTR potentiator, with its experimental lumacaftor, a CFTR corrector. The combination goes before FDA’s Pulmonary-Allergy Drugs Advisory Committee on May 12 (Also see "Return Of Vertex’s Ivacaftor To FDA Panel May Signal Efficacy Concerns" - Pink Sheet, 2 Apr, 2015.).

Safety Benefits Of Inflammatory Resolution

Resunab is not the first attempt to create an inflammation-resolving drug, but it is the first to advance into Phase II study, Cohen noted. Corbus plans to start a 70-patient Phase II trial beginning this quarter, after demonstrating a strong safety profile in 126 healthy Phase I volunteers. Data are expected by the end of 2016.

Besides broad applicability in CF, another benefit would be safety, in that this approach so far does not show any potential for immunosuppression, as is seen frequently with various anti-inflammatory agents.

“The problem with a lot of anti-inflammatories is they work too well,” he said. “They knock out the immune system, and that’s a very dangerous, nasty side effect. We’re not seeing that with resunab.”

The CEO added, “What we’ve seen to date in terms of preclinical and clinical safety and tolerability has been very satisfactory.”

Cohen believes resunab, if it achieves proof-of-concept in Phase II, could offer the same kind of advance in inflammatory disease that previously was provided first by aspirin, later by steroid therapy. The drug will be investigated at four doses over a three-month treatment period in 70 CF patients.

In addition to the development award, CFF also provided invaluable assistance in helping to design the trial protocol, Cohen said. CFF also helped finance the development of Vertex’s ivacaftor and lumacaftor, along with a host of other CF drugs and candidates (Also see "Cystic Fibrosis Market Snapshot: Disease-Modifying Drugs Elusive 24 Years After Discovery Of Root Cause" - Pink Sheet, 11 Mar, 2013.). After receiving a single-digit royalty from Vertex in exchange for roughly $75 million in funding of its CF discovery work, CFF sold those royalty rights in November 2014 to Royalty Pharma for $3.3 billion .

The $5 million is not a grant, but is very de-risked financing for the trial. Corbus must pay the money back six-fold, but only if resunab reaches market for cystic fibrosis and then meets certain sales thresholds. If those conditions are met, the company would be required to pay $30 million in installments as certain sales levels are achieved.

“This is a very attractive form of non-dilutive financing,” Cohen said. “It’s hugely de-risked, and the other thing that comes with this award, which I would argue is even more important than the financial aspect, [is that] the CFF represents the world’s top experts in cystic fibrosis, the world’s top clinical sites, top recruitment personnel, top protocol designers, so working hand-in-hand with them is literally valuable.”