Miscellany

Forbes, with an assist from In the Pipeline thinks BMS and Sanofi shouldn't pair up. I'm really surprised that more people haven't looked at the historical performance of pharma M & A - it's overwhelmingly not pretty.

Somewhat related, Forbes comments on IMCL - "Nowhere to go but up." Gotta think that IMCL's future hinges on what happens with BMS. Another point: this article reflects thinking that IMCL's valuation is solely based on financial performance, meaning no one really is putting any value on the pipeline.

Research and Markets says Discovery to IND takes 6.5 years and 40% of the total R & D budget for a program. Gotta think these numbers reflect the requirement to discovery a target, as well as a compound.

Speaking of Gleevec....

Long term study results from early targeted therapies are starting to come in. In CML, some 95 percent have survived the cancer after five years due to treatment with Gleevec. (I don't have the pre-Gleevec survival rates, but will try to track them down.)

Also: "Even high-risk patients have close to a 70 percent chance of getting to what we call a complete cytogenetic response, which is an optimal response to the drug. That is still six or seven times better than they ever could have hoped for with the previous standard therapy. So, even for high-risk patients, the likelihood of responding is quite high."

Gleevec is being followed by nilotinib (NVS) and dasatanib (BMS), and will hopefully improve these numbers. What I can't make sense of, though, is the choice of this disease (and these drug targets) as the main focus of a number of other biotech companies.

I understand and appreciate the scientific merit, and there is perhaps a business boost thru the validation that the preceeding therapies provide, but just off the top of my head, I can name several entrants:

Ariad
BMS (dasatanib)
Breakthrough Therapeutics
Chemgenex
Curagen/Topotarget
Innovive
Merck/Vertex
Novartis (Nilotinib)
Structural Genomics
even a DoD funded team at VCU
(plus, I feel like I'm blanking on one or two more)

I really hope this effort results in the eradication of the disease, but surely, even if that is accomplished, 3 to 5 companies will swing hard and create a drug therapy, but ultimately wish that they'd spent their time on something else instead of coming in 3rd or 4th in a 2-horse race.

Is this a call for government regulation of R & D targets? Not quite, especially since I'm a raging libertarian, but you can't help but make parallels to the days before government regulation of the electricity distribution business (early 1900's) when as many as 20 different companies' wires serviced some neighborhoods, pre-regulation.

Exelixis is like butter.....

because they're on a ROLL!

In addition to last month's BMS deal ($60M upfront + $20M each for 3 INDs selected by BMS.) EXEL has just optioned to Genentech XL518 - a MEK inhibitor just filed as an IND last month.

From the press releases, this looks like a great deal for both sides. It appears that EXEL is on the hook for all phase I expenses, and DNA can then decide whether to execute a pre-negotiated license prior to phase II. Assuming conversations have been going on for a while, DNA waited until IND-ready, and still is only obligated to spend the upfront payment on the program - depending on terms, DNA might be thinking it's worth the upfront fee just to control the rights to see the Phase I data on a compound targeting a 'new' kinase.

From EXEL's side, their financial risk is the phase I trials expenses, which I'm sure that they can handle financially (if it's not less than the DNA upfront), while booking a partner early on for a pioneering program. (It seems a law of biotech that I'll have to put some more thought into before writing too much that you should partner early on novel leads to novel targets, and partner later for novel leads to established targets.)

DNA is offering $40M in upfront and milestone payments. I'd REALLY like to know the split on that - $20M signing (based on BMS precedent last month) + $10M @ exercise + $10M for P2 milestone?)

(It could be as high as $40M upfront and after nominal milestones, as the press releases speak of additional payments should DNA exercise (after phase I).)

Kudos to EXEL for retaining US sales rights. They've drawn a top-notch partner to XL518, without tieing themselves so tightly to the partner that they become a single-buyer M&A candidate (like ImClone or Onyx.)

(EXEL seems to have done a great job to date in spreading around their connections (and future M & A interest) via partnerships with BMS, DNA, and GSK, to name a few.)

Handicapping targeted drugs

Though not the main conclusion, this article suggests that dasatanib may be an even better therapy than gleevec for CML patients because dasatanib also inhibits Src signaling in addition to Bcr-Abl.

If so, from a business perspective, BMS just became a bit more valuable. Analysts predict annual sales of $500M for dasatanib (Sprycel), but it if this article is right, may be more like Gleevec's $2.2B annual revenue.

Does this suggest a Novartis buy-out of BMS?

BMS is trading at $24.50.