Topping Monday's wave of biotech deals, privately held Vitae Pharmaceuticals Inc. procured a potential $336.5 million partnership with Boehringer Ingelheim GmbH to develop 11beta-HSD1 inhibitors for diabetes and other metabolic diseases.

"It's a good way to start the week," said Jeff Hatfield, CEO of Fort Washington, Pa.-based Vitae, a sentiment clearly shared by other firms reporting collaboration or acquisition news, including XenoPort Inc., MedImmune, Crucell NV, Pharmacopeia and Gene Logic Inc.

In its early stage partnership, Vitae and the big pharma firm from Ingelheim, Germany, will "pool our respective programs" targeting 11beta-HSD1 (11beta-hydroxysteroid dehydrogenase Type I), a target that "seems to have tremendous potential" in treating diabetes and might have broad applications across the metabolic disease space, Hatfield told BioWorld Today.

11beta-HSD1 is an enzyme that's responsible for converting inactive steroid cortisone into active cortisol, a hormone known to act as an insulin antagonist. Early research showed that overexpression of 11beta-HSD1 in murine adipose tissue provokes a metabolic syndrome-like phenotype, resulting in hypertension, increased blood sugar, adverse affects on lipid profiles and weight gain. It's a relatively new target and one that has spurred a flurry of research in the biotech and pharma sectors. A few firms already have moved into the clinic with 11beta-HSD1 inhibitors, including Wilmington, Del.-based InCyte Corp., which is in Phase II testing with INCB13739 in Type II diabetes, and Thousand Oaks, Calif.-based Amgen Inc., which is in Phase I with AMG 221 in metabolic disorders.

Vitae began working on its 11beta-HSD1 inhibitor program about 20 months ago, shortly after partnering its lead renin inhibitor program with London-based GlaxoSmithKline plc for a potential $175 million. "Like our experience with our first program in renin, we made incredibly rapid progress" on 11beta-HSD1, Hatfield said, and it wasn't long before the program nabbed the attention of big pharma. Vitae began collaboration discussions in earnest in the spring and, ultimately, decided to work with Boehringer. (See BioWorld Today, June 21, 2005.)

In addition to the compelling economic side of the deal - Vitae will get $36.5 million in up-front fees, equity investments and research funding, plus the chance to earn up to $300 million in milestones - Boehringer also brings to the table its own 11beta-HSD1 program. The companies will work together to conduct preclinical research, leading to the optimization of a lead compound to advance to the clinic. Once a program reaches the clinic, Boehringer will take the lead on further development and commercialization, and Vitae will be eligible for royalties on future product sales.

Vitae, however, does retain the option to pursue compounds emerging from the collaboration in areas outside of metabolic indications, Hatfield said, though details regarding what those programs might include have not been disclosed.

Since the company was established a few years ago, Vitae has focused its resources on one program at a time, first renin inhibitors and then 11beta-HSD1. But with the immediate funding from the Boehringer deal, in addition to other resources, Vitae's cash position should allow it to investigate different opportunities simultaneously, Hatfield said. Possible areas of interest include central nervous system diseases, virology targets, inflammation and cancer.

Vitae also would be able to carry future programs into the clinic on its own, seeking partners later in the development process, preserving value, though the company can't complain about its two early stage collaborations to date.

"We certainly did not expect so much interest so early," Hatfield said, adding that it just goes to show the "intensity of the demand from large pharma."

XenoPort Partners Early Stage Candidate In $147M Deal

Santa Clara, Calif.-based XenoPort partnered a preclinical candidate for menorrhagia with Xanodyne Pharmaceuticals Inc. in a potential $147 million deal.

Xanodyne, a women's health care and pain management company, picks up U.S. rights to develop and commercialize XP21510, a transported prodrug of tranexamic acid, for menorrhagia, a condition described as abnormally long menstrual cycles or heavy menstrual bleeding believed to affect about 9 percent to 14 percent of healthy women. Xanodyne, of Newport, Ky., plans to develop XP21510 as a follow-on product to its own tranexamic acid product candidate, XP12B, which is in Phase III development for menorrhagia.

In exchange, XenoPort will receive an up-front cash payment of $12 million, with $6 million payable upon execution of the agreement and the remaining $6 million due on the one-year anniversary, plus be entitled to development, regulatory and commercial milestones of up to $130 million for XP21510. The firm also could receive $5 million in milestones related to Xanodyne's XP12B. Beyond that, XenoPort would receive tiered, double-digit royalty payments on any future sales of XO21510, as well as escalating single-digit royalties on future sales of XP12B.

XenoPort CEO Ronald Barrett said in a press release that the deal allows XenoPort to leverage its discovery engine while "we concentrate our internal resources on the development and commercialization" of its internal central nervous system disease drug pipeline. That pipeline includes lead program, XP13512, which completed a Phase III program in restless legs syndrome and completed a Phase IIa trial in postherpetic neuralgia. A second product candidate, XP19986, recently yielded positive Phase IIa data in patients with gastroesophageal disease.

Shares of XenoPort (NASDAQ:XNPT) closed at $49.77 Monday, down 53 cents.

MedImmune, Crucell In Antibody Deal Of Up To $40M

MedImmune and Crucell are joining forces to address hospital-acquired bacterial infection. The firms agreed to an exclusive license and research collaboration to develop and commercialize one of Crucell's panels of bacterial antibodies.

Under the terms, Gaithersburg, Md.-based MedImmune, a wholly owned subsidiary of London-based AstraZeneca plc, agreed to provide Crucell up-front, annual and milestone payments potentially exceeding $40 million. In addition, Crucell, of Leiden, the Netherlands, also is entitled to research and development funding and an undisclosed royalty on product sales. MedImmune, meanwhile, will have rights to antibodies within one of Crucell's MAbstract technology programs.

The partnership with MedImmune builds on Crucell's work, started in 2005, focused on antibody discovery programs in the field of hospital-acquired infections. Crucell used its MAbstract platform to discover drug targets and identify human antibodies against those targets.

Shares of Crucell (NASDAQ:CRXL) gained 38 cents Monday to close at $20.86.

Pharmacopeia Adds SARM Program In BMS Deal

Pharmacopeia bolstered its pipeline with a selective androgen receptor modulator (SARM) program from New York-based Bristol-Myers Squibb Co.

That program includes PS178990, a nonsteroidal SARM designed to provide the benefits of testosterone without its unwanted side effects on the prostate. PS178990 has completed a Phase I single-ascending dose study, and it becomes the seventh clinical-stage program in Princeton, N.J.-based Pharmacopeia's portfolio. The deal also includes back-up compounds.

Instead of the customary up-front payment, Pharmacopeia agreed to provide its medicinal chemistry resources to a separate BMS discovery program for up to three years. That allows the firm to preserve its cash for moving its new SARM compounds forward. Pharmacopeia also will pay BMS milestones associated with submission and approval of any therapeutic product for marketing, plus a stepped royalty rate on any product sales.

Pharmacopeia's stock (NASDAQ:PCOP) closed Monday at $5.97, unchanged.

Gene Logic Sheds Genomics Assets

As the firm continues to shift its efforts to drug repositioning and development, Gene Logic agreed to sell its genomics assets to Ocimum Biosolutions Ltd. for $10 million cash.

Charles Dimmler, president and CEO of Gaithersburg, Md.-based Gene Logic, said in a press release that the deal marked a "transforming event of significant strategic proportion," and allows the firm to focus on its drug development business. The company is developing GL1001, a small-molecule candidate that it has repositioned to treat gastrointestinal disease. That program is gearing up for clinical testing in that indication. GL1001 previously yielded promising in vivo results in inflammatory bowel disease.

Under the terms of the deal, Ocimum, of Hyderabad, India, will pay $7 million at closing, with the remaining $3 million payable pursuant a promissory note due 18 months after closing. Ocimum also agreed to take on certain liabilities associated with the genomics assets and business. Closing of the sale is subject to certain conditions, including the approval of Gene Logic shareholders.