In its largest deal to date, TransTech Pharma Inc. out-licensed to Pfizer Inc. its portfolio of compounds targeting the receptor for advanced glycation endproducts (RAGE), which includes a Phase II-stage small molecule against Alzheimer's disease and diabetic nephropathy.

In exchange for exclusive, worldwide rights to the RAGE technology, New York-based Pfizer agreed to pay TransTech up to $155 million in up-front and near-term milestone payments, as well as up to $18 million in research funding to support expansion of the portfolio. Beyond that, TransTech said it could receive "significant" milestones for the development and commercialization of RAGE modulators in several potential indications, followed by royalties.

Though TransTech Founder, President and CEO Adnan Mjalli said he couldn't provide further financial details, he called the potential upside "a pleasant shock," for the High Point, N.C.-based firm.

"It's a very significant transforming step" for TransTech, Mjalli said, as its first straight out-licensing arrangement. Prior to the deal, the company, which has turned out an early stage pipeline using its Translational Technology high-throughput discovery platform, formed a number of drug discovery and development collaborations, such as a potential $54 million agreement signed with German firm Boehringer Ingelheim in December 2005. (See BioWorld Today, Dec. 21, 2005.)

"We had extremely fierce competition" for the RAGE portfolio, Mjalli told BioWorld Today. "Pfizer was the winner because of what they bring to the table, in terms of expertise in development, as well as marketing capabilities."

RAGE, a protein that's part of the immunoglobulin supergene family, has been implicated in the initiation and progression of a number of diseases, such as Alzheimer's, inflammation and cancer, but it's also been difficult to address, particularly using a small-molecule approach, Mjalli said. "But we have been successful using our Translational Technology."

The lead RAGE antagonist, TTP488, is an oral small-molecule drug that has completed a Phase IIa study in Alzheimer's patients and is in a Phase II trial in diabetic nephropathy. A second product, TTP4000, is expected to enter the clinic before the end of the year. TTP4000 is a large-molecule compound.

All further development will be handled by Pfizer, though TransTech will participate on a joint development committee.

Meanwhile, TransTech plans to focus on some of the earlier programs in its pipeline, including drugs for obesity, diabetes and cancer, and anticipates moving "four or five drug candidates into Phase I/II in the next three quarters," Mjalli said. "And we have several small molecules behind that in the lead optimization stage."

Those programs all are in addition to ongoing collaboration efforts, such as TransTech's work with Novo Nordisk A/S, of Bagsvaerd, Denmark, which yielded a small-molecule drug candidate.

At this time, Mjalli said TransTech has no plans to develop its own sales force and instead intends to look for partnering opportunities after achieving proof-of-concept data.

"We're going to do what we do best," he said, which is using the technology to "translate an idea of any target through discovery and validation and then taking it into proof of concept in man."

TransTech is a majority-owned affiliate of New York-based MacAndrews & Forbes Holdings Inc.