By Aaron Lorenzo

Millennium Pharmaceuticals Inc. made some major moves Monday, forming a pair of partnerships in an effort to enhance its product line.

The Cambridge, Mass.-based company and XOMA Ltd. reached an agreement to further develop a pair of Millennium¿s biotherapeutic agents, CAB-2 and LDP-01, for certain vascular inflammation indications. Also, Targeted Diagnostics and Therapeutics Inc. granted Millennium a license to TDT¿s intellectual property surrounding guanylyl cyclase C (GC-C), a protein uniquely expressed on the cell surface of colorectal tumors, and its related ST ligand, for use in colorectal cancer therapeutics.

¿I would characterize both of these moves as consistent with Millennium building its pipeline,¿ said Alan Crane, Millennium¿s vice president of corporate development. ¿It¿s two different approaches that we¿re using. This is part of an ongoing process to really scour the world for what we feel are the best therapeutic opportunities out there, and then to license those.

¿We¿ve developed a fine degree of synergy between what we¿re doing from a business development perspective and our unique insights into pathways and biology in the core franchise areas that we focus on ¿ oncology, inflammation and metabolic disease ¿ so that we can really pick licensing opportunities that we feel are likely to be winners.¿

Millennium picked up a number of positives in both agreements.

¿The XOMA deal really represents a way for us to manage a portfolio of products and still have very significant rights to those products, but not have to develop those products internally through proof of concept, or Phase II,¿ Crane said. ¿In this case, our partner, XOMA, is developing these products through Phase II, and they can use their development infrastructure while we focus our development infrastructure on our major products.¿

XOMA is responsible for development costs through the completion of Phase II trials. It also will make initial payments to Millennium, as well as after reaching certain clinical milestones. After successful completion of Phase II, Millennium retains commercialization rights, while XOMA will have the option to choose between further participation in the development program and eventual profit sharing, or future royalty and milestone payments.

Under an investment agreement, Millennium committed to purchase, at XOMA¿s option, up to $50 million worth of XOMA common shares over the next three years, through a combination of convertible debt and equity, at prevailing market prices.

Further financial details were not disclosed.

¿XOMA moves these products forward in a more accelerated way than we would be able to do internally,¿ Crane added. ¿This is really a way to tap into the development capabilities of another organization, have them drive CAB-2 and LDP-01 forward. But we retain significant rights to step into further development and then to commercialization.¿

Peter Davis, chief financial officer of Berkeley, Calif.-based XOMA, said the agreement follows along the lines of two other similar deals the company has entered.

¿We have the opportunity now to take advantage of our manufacturing capabilities,¿ he said. ¿Rather than discovering our own lead products, we can take someone else¿s products and work with them.¿

XOMA is involved with South San Francisco-based Genentech Inc. on the Xanelim antibody for psoriasis (Phase III), organ transplant rejection and other indications. Earlier this year, XOMA signed with Richmond, Calif.-based Onyx Pharmaceuticals Inc. to develop and manufacture Onyx-015 for various cancers (Phase II and III).

¿We look for ways to leverage our development capabilities,¿ Davis continued. ¿We do it in a way that¿s self-financing, investing our own efforts to have equity in the product going forward.¿

That background made XOMA an appealing partner for Millennium.

¿We look for partners that have proven clinical capabilities, and preclinical capabilities to the extent that that¿s relevant,¿ Crane said. ¿XOMA has an excellent track record, having worked with a number of partners in doing exactly these kinds of deals and successfully driving products forward.¿

CAB-2, a recombinant fusion protein that inhibits complement activation, is in preclinical testing for the treatment of reperfusion injury. Data have shown that CAB-2 may reduce ischemic damage following reperfusion in a number of model systems and may be useful in cardiopulmonary bypass surgeries. Preclinical data have shown that LDP-01, a humanized monoclonal antibody, inhibits inflammatory responses by blocking the attachment of Beta 2 integrins to their adhesion molecules, thereby limiting the recruitment of leukocytes essential to the inflammation process. LDP-01 was well tolerated in Phase I studies.

¿These are early stage products,¿ Davis said. ¿But we¿re enthusiastic about them and about the agreement.¿

In the other deal, TDT granted Millennium an exclusive worldwide license for development of human cancer therapies targeting GC-C and using the ST ligand. Millennium will pay milestone fees and potential royalties to West Chester, Pa.-based TDT after reaching specific development goals. In addition, Millennium will make an initial equity investment in TDT.

Additional financial terms were not disclosed.

¿Our whole process of licensing involves identifying key pathways and saying these are the things we¿re going to go after,¿ Crane said. ¿So very much the way earlier in the year we licensed our anti-PSMA molecule, which is bearing out now as a very exciting opportunity clinically, the GC-C was one of the highest priority opportunities when we identified it because we believe that it has some very interesting properties for colon cancer, and potentially for GI cancer, more generally.¿

In April, Millennium paired with BZL Biologics LLC, of New York, to develop the antibody-based therapeutics targeting PSMA.

¿It¿s been an incredibly busy year,¿ Crane said.

Millennium¿s products include both therapeutic (small-molecule and antibody) and predictive programs. The company has three additional candidates in clinical trials for inflammatory conditions. LDP-02, a humanized monoclonal antibody, is currently in Phase II trials for Crohn¿s disease and Phase I/II and Phase II trials for ulcerative colitis. LDP-977, an orally active small-molecule compound, is in Phase II trials for asthma. LDP-519, a proteasome inhibitor with anti-inflammatory properties, is in Phase I trials for stroke.

In other recent dealings, Millennium pulled out of a 50-50 joint venture, Millennium & ILEX Partners LP, giving ILEX Oncology Inc. Millennium¿s 33 percent share of the approved product Campath. (See BioWorld Today, Oct. 31, 2001.)

XOMA is involved in several late-stage programs. In addition to its deals with Genentech and Onyx, it is involved in one with Baxter Healthcare Corp., of Deerfield, Ill., to develop Neuprex (rBPI-21) for Crohn¿s disease (Phase II) and other indications. Earlier-stage development programs include compounds to treat cancer, retinopathies, autoimmune diseases and infections.

Privately held TDT is pursuing preclinical testing in animal models of targeted imaging agents for metastatic colorectal cancer. Also, a highly sensitive and specific molecular marker is undergoing Phase I testing for patients with colorectal cancer and for detecting recurrent cancer in the blood of patients undergoing postoperative surveillance.

Millennium¿s stock (NASDAQ:MLNM) closed at $33.50 Monday, up $2.29. XOMA¿s stock (NASDAQ:XOMA) closed at $8.58, down 14 cents.