SouthShore

Isis Pharmaceuticals' Obesity Buster an Enormous Finding

Re: Bioinvestor. Actually, big pharma invests in most promising new platforms in a rather unique way - in a press release, with a transfer of money, rights to regional distribution, and in exchange for a percentage of the company they're investing in. So they do share in the profits of the successful ventures, and they also lose their investment in those platforms that are not viable. Even the big pharma's were taken during dot.com bubble.

As you correctly said, upstart biotechs must partner away early products in order to build a revenue stream that will power growth of their future pipeline. Most fail. Also, AMGN and DNA are now struggling as they've picked most of the low hanging fruit.

A non-oral form of Mipomersen will discourage its wide spread use, but if the formulation can be produced in an extended release form or packaged in a pen-style injection similar to AMLN's Byetta, then this might change.
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Specifically regarding Mipomersen, a reversal of plaque would be a significant benefit and would provide ISIS with an expanded use. Prevention of cardiac disease surgeries would be a significant savings to the HMO system (not to mention the impact on patients and families).
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Generally regarding ISIS, they have a potential platform that applies a new drug type to old and new disease targets. The old targets are the most promising since these are already validated, have probably come off patent, and are abundant. Plus, ISIS will not have to spend much money or time on early-phase discovery or legal. Targeting PTP-1b with small molecules for instance was tried to death by every pharma and is the poster child for each new drug platform. The platform for ISIS is the bull case for investing here. Mipomersen is the proof-of-principle product.

Toxic side effects, drug-delivery issues, competition, and production costs are the bear points.

Long-term, ISIS is a speculative buy - to me. IMO.

Isis Pharmaceuticals' Obesity Buster an Enormous Finding

First, let me say that when AMGN and DNA were just small start ups, the large pharma companies whose focus was on traditional small molecule drugs probably didn't foresee the success of the protein-based drug market. That's likely because a single success doesn't prove a "platform's" potential. Of course, AMGN and DNA over a long time "have" proven themselves to have pursued a successful platform bringing many new drugs to market using it.

Since it is not the individual drug that will make a start-up or the investment in one have great potential but rather the ability to bring many new drugs forward, then it is important to assess the platform more than the individual drug.

With that said, companies like ISIS, and to a lesser extent MNTA, stand today at the forefront of a new "platform" for drug discovery and the strength of each remains to be be seen.

My specific comments are:

1) Mipomersen is an injectable (not oral) preparation. Thus, the ability to expand its market share to Lipitor-like sales could be held back until ISIS launches an oral formulation. It is my understanding that ISIS intends to pursue this, but that doesn't mean it will be easy, cheap, and/or safe. Competition from generic statins should make marketing shy of attempting to expand here unless the clinical data shows benefits not seen in the statins in general. Perhaps the efficacy in reducing the plaque as stated in your blog will offer cardiologists a new tool used prior to arterial stents and/or bypass surgery.

The counter argument (a positive) would be that a once per month injection would be preferable to the patient over taking 3 pills a day, every day, along with 3 or 5 other daily medications. This would increase patient compliance. And since many seniors already visit their doctor/HMO frequently, then an injectable formulation might not be black-listed by the HMO's/insurance co's because of increased office visits per patient.

2) Bayer brought to market (thus passed the FDA clinical trials) the anti-cholesterol drug Baycol, which was later recalled for toxic side effects. Baycol was highly bioavailable (meaning it could be found throughout much of the body's tissues) whereas all of the other statin drugs including Lipitor were retained in the liver. Retaining the drug in the liver prevents the toxic side effects of sterol inhibition elsewhere in the body. As yet, it is unclear if ISIS can effectively produce an oral formulation that is retained by the liver (for Mipomersen) or the reverse, if their formulation technology can be engineered to make other potential drugs highly bioavailable (as they might need to be).

Thus, can ISIS make oral formulations that are tailored to the needs of the tissue target? This has implication as to how successful the ISIS platform will be - not just how Mipomersen can be advanced or its use expanded.

Having demonstrated proof-of-concept with Mipomersen and many of the patents in the area is a good sign, though.

Just my 2 cents,