Millennium Chief Medical Officer Nancy Simonian: An Interview With “The Pink Sheet” DAILY (Part 2 of 2)

Exec discusses Millennium’s key pipeline projects, including the T cell integrin antibody MLN0002 for inflammatory bowel disease.

Millennium Chief Medical Officer Nancy Simonian spoke with "The Pink Sheet" DAILY recently about the firm's most promising pipeline candidates. This is the second of a two-part interview (see ¹ (Also see "Millennium Chief Medical Officer Nancy Simonian: An Interview With “The Pink Sheet” DAILY (Part 1 of 2)" - Pink Sheet, 16 Feb, 2007.)).

"The Pink Sheet" DAILY: Turning to other projects in your oncology and inflammatory disease pipelines, can you highlight the most promising candidates?

Nancy Simonian: I usually think about it, what are the molecules that have already achieved proof of concept or are close to initiating Phase III as being the ones that I would say are the highest priority at this point.

We have an antibody to alpha-4 beta-7, which is [a T cell] integrin. The molecule is called MLN0002. That molecule selectively inhibits the trafficking of inflammatory cells into the gut. [The] cell trafficking mechanism has been validated in multiple sclerosis and inflammatory bowel disease with some of the other agents out there, but what's really unique about what we have is we can selectively target the cell trafficking. … The idea would be that in inflammatory bowel disease you can prevent migration of inflammatory cells into the gut and reduce disease.

We published in the New England Journal of Medicine in 2005 a Phase II study of MLN0002 versus placebo in ulcerative colitis in patients and showed a statistically significant benefit in terms of remission, so twice as many patients went into remission on the drug versus placebo. Because the cell line that we used for that trial was not commercially viable in terms of scale, we had to go back and re-engineer a new cell line, and get it to commercial scale, which we completed. We just completed the preclinical studies, and we're about to go back into the clinic, where we'll do some bridging studies … and then from there we'd launch into Phase III trials.

We're excited about that one because of its selective targeting in immunomodulation. It's already achieved proof of concept, and we are the only ones out there with a drug that's targeted for that disease. That would be the top one.

We also have an antibody [(MLN1202)] to CCR2, which is a chemokine. … That's important because monocytes and macrophages are thought to be very important in the destructive lesions that happen in multiple sclerosis. … Also, if you look at atherosclerosis, the earliest inflammatory cell in the plaque wall is the monocyte. …We announced last year a Phase IIa study where we used [C-reactive protein] as a biomarker. It's a measure of inflammation, systemic inflammation. We took patients at high risk for atherosclerosis, we gave them drug or placebo. After a single dose of 1202 we saw sustained reductions in CRP levels out for many months, and it was very well tolerated, so we were quite encouraged by that finding. We also have ongoing a study in multiple sclerosis, and we expect to have data available in the first half of this year.

We have a CCR1 inhibitor, which is an oral small molecule to another chemokine receptor, and we are in a proof of concept study in rheumatoid arthritis, so adding our drug onto methotrexate versus methotrexate alone. We will have data available from that study by the end of this year.

"The Pink Sheet" DAILY: Are these compounds that you are looking to partner or bring to market on your own?

Simonian: Our strategy has really been, as what we did with Velcade, obviously look for an ex-U.S. partner to share in development and then commercialize it outside the U.S. … In terms of the rest of our pipeline, all of our small molecule inflammation molecules are all partnered with Sanofi-Aventis. We've had a research collaboration with Sanofi-Aventis for many years, and it's both a co-development and a co-commercialization.

Then the small molecule biologics that we have, the 0002 for inflammatory bowel disease and 1202, neither of those are partnered now. With 1202 we are looking for a strategic partnership because one of the indications there is in cardiovascular and that is not a strategic focus area of ours, so we would look for a partner to work with us to develop the molecule broadly. … On the small molecule oncology programs, we have an aurora kinase inhibitor and we also have an RTK inhibitor. Both of those are currently unpartnered. And again, really our goal would be … to get them to proof of concept, then probably look for a partner definitely on the ex-U.S. side from a commercial standpoint.

"The Pink Sheet" DAILY: Millennium has also shown interest in acquiring additional technologies or companies. What is your strategy on that front? Is it mostly an oncology focus?

Simonian: At this point in time, since we have a commercial sales force in oncology, or hematology, that's really our focus, to look at products that would be synergistic with our current commercial organization. Obviously, as 0002 moves forward into Phase III and we start to be moving towards commercialization of that molecule in inflammatory bowel disease and develop a commercial infrastructure, then we would really be also broadening our potential scope for inlicensing, but right now it's really focused on oncology and hematology.

"The Pink Sheet" DAILY: Can you quantify how many compounds you would like to inlicense?

Simonian: We are very aggressively going out and looking for opportunities, but it has to be the right thing. We believe that we have a financial profile of the company that doesn't require that we actually have to go out and find a product from a revenue standpoint. … We would like to have that, but it's not imperative, so we're going to be aggressive, we're going to choose wisely. Just like we did with the AnorMED deal where we figured out what the right price was for that, and when Genzyme came in and bid above that, we just didn't think it was worth that price, we'll step away. You'll see us be very disciplined about [how] we would value those programs.

[Genzyme outbid Millennium for AnorMED, developer of the Phase III stem cell mobilizing agent Mozobil, with a $580 million offer in October (² (Also see "Genzyme Wins AnorMED As Millennium Backs Out Of Bidding War" - Pink Sheet, 18 Oct, 2006.)).]

"The Pink Sheet" DAILY: With the environment getting more and more competitive for new technologies, how do you make those choices?

Simonian: I think it's a very competitive market out there for finding late stage opportunities. I think there's no question about that. Some people out there … are looking only for molecules that are going to have a certain revenue potential. I think we have some different latitude in terms of that, in terms of what we would be willing to look at. Just based on what our financial profile is, something that's not a blockbuster but actually has a reasonable revenue potential with an existing commercial infrastructure that would bring reasonable bottom line growth would be attractive to us. So there's that part, and I think we've also demonstrated a track record in being aggressive at developing drugs like Velcade and have a good relationship with the regulatory agencies, so just in terms of a company looking to partner with somebody that's actually done some of these things before I think we have advantages there.

- Jessica Merrill ([email protected])