In a deal potentially worth more than $325 million, Shire plc picked up commercialization rights outside the U.S. and Japan for Alba Therapeutics Corp.'s gastrointestinal permeability inhibitor AT-1001.

The collaboration provides Alba with $25 million up front, which Chief Financial Officer Jeffrey Church estimated could last for about 12 to 16 months. Yet Alba isn't depending on that money alone; the company is also in the process of raising $20 million to $40 million in a Series B financing, which Church said would allow it to complete ongoing and planned Phase IIb trials with AT-1001 for celiac disease.

Alba previously raised $30 million in a Series A round and obtained $10 million in venture debt. (See BioWorld Today, Aug. 24, 2005.)

In its deal with Philadelphia-based Shire, Baltimore-based Alba may also pick up $80 million in clinical, regulatory and launch milestones and $220 million in sales-based milestones. Alba also stands to get royalties on ex-U.S. and ex-Japan sales and, if the current partnership expands beyond gastrointestinal indications, the company could get another $40 million per indication.

Most of the upfront and early milestones, as well as the Series B financing, will support Phase IIb trials. Alba is conducting a 140-patient Phase IIb trial of AT-1001 compared to placebo administered prior to a gluten challenge in celiac disease patients. Data are expected around mid-2008, and Alba plans to start a second Phase IIb trial in the first quarter that will evaluate the addition of AT-1001 to a gluten-free diet in managing celiac disease.

After the Phase IIb trials, Shire will fund half of the global development costs for AT-1001, and the partners will share responsibility for Phase III trials. Shire will manage all commercialization outside of the United States and Japan.

"We've been in discussions with a number of companies over the past year," Church told BioWorld Today. He said Alba chose Shire because of its good reputation as a collaborative partner, its regulatory and manufacturing expertise, its global experience in the gastrointestinal market through sales of the ulcerative colitis drugs Pentasa (mesalamine) and Lialda (mesalamine oral), and the fact that it was willing to let Alba hold onto U.S. and Japanese rights.

In Japan, where the incidence of celiac disease is low, Alba plans to pursue a partnership for AT-1001 in other gastrointestinal indications such as ulcerative colitis and Crohn's disease. In the U.S., Alba plans to build its own gastrointestinal specialty sales force and seek a partner if demand for AT-1001 expands into the primary care market.

Celiac disease, which Church estimated affects about one percent of the population, is an inherited autoimmune disorder triggered by the consumption of foods containing gluten. There are no approved treatments, and most patients must follow a gluten-free diet, which can be difficult considering the protein is found in almost everything containing wheat, flour, barley, rye or oats.

Despite the unmet need, there are few celiac drugs in development. Aside from Alba, Alvine Pharmaceuticals Inc., of San Carlos, Calif., is working on an early-stage product designed to break down and detoxify gluten.

Yet AT-1001 works differently, Church said. It's a short peptide that inhibits the disassembly of intercellular tight junctions. In the intestine, the inappropriate opening of these junctions is referred to as "leaky gut" and is associated with a variety of gastrointestinal diseases including celiac disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome and Type 1 diabetes. By keeping the junctions closed, AT-1001 is designed to prevent gluten or other molecules from slipping through and triggering an autoimmune response.

Celiac disease patents could use the drug as a "safety net" in case they accidentally or unknowing ingest gluten, Church said. Alba is also planning to begin a Phase II trial with AT-1001 in Crohn's disease after the Series B financing.

Outside of the gut, inhibitors of tight junction permeability may be applicable in asthma and chronic obstructive pulmonary disease, Church added. Additionally, Alba is conducting early preclinical work on tight junction permeability inducers for use in drug delivery and vaccine adjuvants.

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