Replies to post #85430 on Biotech Values

[DewDiligence]

VRTX IDIX VRUS etc.

I found the argument against [nukes] being any better by Mueller to be informative.

Mueller evidently hasn’t heard about—or he pretends not to have heard about—the monophosphate nucleotide prodrugs from IDIX and VRUS (#msg-42396728).

[dewophile]

VRTX

it's always been the case that companies favor a point of view that suits their commercial enterprise, and the uncertainty surrounding future HCV therapy - particularly given how early we are in drug development and how many players are in the game - is highlighting this point most acutely. some examples:

1. vrtx doesn't think a nuke is necessary - their argument is a non-nuke has lower resistance but can still mop up the resistant variants from proteases and that is enough. convenient since they have a protease and now a non-nuke in development

2. idix thinks soc (or at least some component therof) will be eliminated in the future, but they think it will take a combination of 3 direct acting agents..interesting, they are one of the only companies with all 3 classes in late preclinical to clinical develoopment

3. zgen - they think interferon will remain the backbone of therapy for the foreseeable future - how convenient given lambda is a cornerstone of their pipeline

i could go on - clearly no one knows and one has to take what these companies say with a heavy grain of salt. personally i think all these drug classes will find their way into the treatment paradigm in some way or another - it's a heterogenous disease (and heterogenous pt population) that will require multiple options without a one size fits all (although when the smoke clears there probably will be some regimen that has dominant market share and becomes a megablockbuster)

[DewDiligence]

Gilead’s John Martin Speaks of Nucleotides and Other Things

[For background, please see #msg-39680718, #msg-42396728, and #msg-36507844.]

http://www.forbes.com/2009/10/30/gilead-pharmaceuticals-hiv-intelligent-technology-martin.html

›by Kerry A. Dolan
10.30.09

BURLINGAME, Calif. -- John Martin is Chief Executive of Gilead Sciences, a drug company that has helped to transform HIV from a death sentence into a chronic disease in the developed world. Some 80% of Gilead's $6 billion in revenue comes from drugs to treat HIV, the virus that causes AIDS. Forbes met up with Martin to discuss managing success, maintaining productivity and what lies ahead.

Forbes: Gilead has been one of the most successful drug companies in the last decade. What have you done to really disrupt the treatment of HIV?

Martin: Well, we've done two things. From the early stages of Gilead, we worked on nucleotide antivirals [i.e. nucleotides rather than nucleosides, as explained in #msg-42396728]. It's just a unique chemistry class that other people were skeptical about. So we were the only company working in the area. And we've developed three nucleotide drugs and no other company, to this day, has one to treat viral infection. Those products turned out to be very important, especially Viread for the treatment of AIDS.

The other thing that was important, AIDS patients need to take three drugs to completely suppress the virus. And so we simplified therapy. We got a second product when we acquired Triangle Pharmaceuticals [Emtriva—see #msg-34008977] and combined that with Viread to put two drugs in a single pill [Truvada]. Then we collaborated with Bristol-Myers Squibb with their single drug [Sustiva] and added that to our two-drug pill. So we have all three drugs in one pill, given once per day [Atripla].

Forbes: Some of the other regimens that patients might choose from would be one pill two times a day, or more than one pill two times a day. If you can just do one pill with three drugs in it once a day, you're more likely to take that pill?

Martin: Yes, absolutely. It's been shown in studies. In fact, [with drugs from other companies], it's not only taken multiple times per day on different schedules for different drugs; it's also with and without food before bedtime. So the regimens are very hard to stick to, day in and day out.

Forbes: If you're an HIV patient and you miss a drug, what are the consequences?

Martin: Resistance can develop. It's been shown in scientific studies that a patient would need to take 95% of their medicines in the course of a year. If they miss more than 5% of the pills, resistance can develop, and the drug no longer works.

Forbes: So, as a result of having this patient-friendly, you know, three drugs in one pill, you've really increased your market share, right?

Martin: Absolutely. About 80% of our total revenues come from HIV.

Forbes: Have any of the other big pharma tried to replicate this, putting two drugs in a pill?

Martin: There's been a three-drugs-in-one pill [Trizivir from GSK, which consists of three nucleosides and is rarely used today], but it was given twice a day and it's shown to have lower efficacy. There's another product that's two drugs in a single pill that competes with our two-drug pill [GSK’s Combivir/Kivexa, which consists of two nucleosides and has been crushed in the marketplace by Truvada: #msg-43082174]. But there have been scientific studies that have showed our products to be the preferred regimens.

Forbes: You're looking at putting four drugs in one pill? What's the timeline on that?

Martin: That's correct. We started a few years ago. We have one Phase III trial started and we need to start three more Phase III studies. [This refers to “Quadro”: a combination of Truvada, the integrase inhibitor Elvitegravir, and the PK booster called GS9350: #msg-39680718].

Forbes: Another method that you've taken to grow is acquisitions. How do you decide when to make an acquisition and what's a good acquisition?

Martin: It's actually quite opportunistic. We'll think about, over the course of years, a potential acquisition. But only under the right circumstances does it happen. A recent example is CV Therapeutics, a company in Palo Alto, Calif., that we acquired this year.

It was a company formed in 1992. We first did an internal business development review of it over a decade ago. But a company went hostile on them and put them in play. And we were able to complete the acquisition.

Forbes: How would you describe Gilead five years from now? Ten years from now?

Well, we'd be a more diversified company. And I personally, every day that I come to work, I want to make a difference in the health of people. And everyone else at Gilead feels that way too. We're proud of what we're doing, of what we're doing and how we're doing it. And we want to have more successes.‹