Drug Discovery Blogs Feed

The Last Post

Fri, 31 Jul 2015 11:51:53 +0000

Update: I've had a lot of people noting that the URL below is asking for a password - that's because the site isn't going live until Monday. All will be well!

Well, the last post here at Corante. I'm going to shut off commenting to all the recent posts, and send the export file over to the people at Science Translational Medicine, and Monday morning we'll start anew at:

http://blogs.sciencemag.org/pipeline

I hope to see everyone over there. The commenting community here is terrific, and provides far more worthwhile content than I could crank out as one person at a keyboard. Here's the to next phase of "In the Pipeline", and I think I can promise that it's not going to be boring!

The GSK Layoffs Continue, By Proxy

Fri, 31 Jul 2015 11:15:32 +0000

You may recall that when GlaxoSmithKline cut down the Research Triangle site, that "up to 450" employees were said to be transferred to a contract organization, Parexel. In many cases, these people were doing the same jobs, in the same buildings, but were now doing it for less money. (Something similar happened a few years back at Eli Lilly, in a deal with Covance).

Now comes word that up to 200 of those Parexel employees are being laid off anyway. So in the end, it bought them a few months on the way to the same destination. According to that story from local station WRAL, the CEO of Parexel had announced the cost-cutting efforts earlier this year, without going into details, under the name of the "Margin Acceleration Program".

So we can now add another one to the long list of euphemisms and doubletalk phrases used to describe the process of dumping hundreds of people out onto the sidewalk. And if you still work for Parexel, remember: you're working for a company that can use a term like "Margin Acceleration Program" and not crack the faintest vestige of a smile. Plan accordingly.

The Move is Nigh

Thu, 30 Jul 2015 15:54:08 +0000

The day for the big Pipeline move is almost at hand! Friday's posts here will be the last on the Corante site, and the new one at Science Translational Medicine will go live on Monday morning. I'll post the new URL shortly.

I wanted to give everyone fair warning that although this domain will soon redirect to the new one, the timing may not be perfect. Any comments posted here after noon on Friday will not migrate - that's when the last update file to the new site will be sent over. I'll be turning commenting off on all the recent posts here, just as a safety measure.

Another Alzheimer's IPO

Thu, 30 Jul 2015 11:04:55 +0000

I've been saying a lot of unkind things about Axovant, the insta-company that's taking a discarded GSK Alzheimer's candidate and running with it. But thanks to Adam Feuerstein, I have another company to roll my eyes about. They have a completely different Alzheimer's plan - they've taken a discarded Pfizer candidate and are running with it. The drug in question is azeliragon, formerly PF-04494700, targeting RAGE (the receptor for advanced glycation endpoints), and the company's press material about it includes a qualifying statement that you don't run across very often:

"Despite the 20mg/day dose being stopped by the DMC due to acute, reversible, concentration dependent cognitive worsening and the study being prematurely stopped for apparent futility, the study achieved its prespecified objective demonstrating a statistically significant 3.1 point different (p = 0.008) favoring azeliragon 5mg/day over placebo at 18 months in patients with mild to moderate AD."

That's in the ADASCog rating, but the overview goes on to say that "the study was not powered to show significant differences for global, functional, cognitive and behavioral secondary endpoints". Here are some publications on the trials themselves. Now, being generous, one could conclude that there's a chance for this to work - after all the 5mg/day numbers are, presumably, what they are. But at a 4x higher dose, big trial-ending trouble was seen, of just the sort that you can't have in Alzheimer's ("acute cognitive worsening"). And we have no idea where that kicks in between the two doses. This is a very, very tight window between what could be a good effect and what is certainly a very bad one, which is surely why Pfizer dropped the compound like it was giving off gamma rays and has not returned to it.

All Alzheimer's clinical candidates are longshots, by definition. But this one is a longshot longshot. I hope that people are only putting money into it that they can afford to lose, but I also hope that when I see elderly customers shuffling up to the lottery ticket register, and I think I'm wrong about that one, too.

So who are these people? The company is vTv Therapeutics (that's how they spell it), and they're heading for an IPO. The bio of their CEO, Stephen Holcombe, says that he brings "brings over 23 years of financial and managerial experience" to the table. Looking closer, though, that experience is with KPMG Peat Marwick, a cell phone company, and an e-commerce provider to the construction industry. Unless he's been hitting the books at night, and perhaps he has, one cannot guess that he knows anything about drug development. Their CSO is Carmen Valcarce, ex-Novo Nordisk. But the chairman of the board, that's the really interesting part: it's one Jeff Kindler, whom many will recognize as Pfizer's onetime CEO. And there are many ex-Pfizer employees who have opinions on how much he knows about drug development, for sure. His departure from the company was the subject of a truly bizarre article the next year, one that I think set off a lot of discontent among the non-executive-suite folks at the company.

So vTv is going to be interesting to watch. The Alzheimer's program isn't their only shot, as opposed to Axovant, I will give them that. But some of their other assets have been kicking around for a while, too, such as the ones from when the company was known as TransTech Pharma (like TTP339, a glucokinase activator). Azeliragon itself was originally a TransTech compound, licensed to Pfizer, but it boomeranged back to them after the Phase II results. The company has changed its name and rebranded itself as an Alzheimer's therapy play, and so off to the NASDAQ they go.

Cutbacks at C&E News

Wed, 29 Jul 2015 13:09:33 +0000

Word is this morning that Chemical and Engineering News has let at least 8 staff members go in a reorganization, including former editor-in-chief Maureen Rouhi. The magazine outsourced its advertising sales some months ago, rather than drumming these up internally, and what I'm hearing is that their projected ad revenues are way off since the changeover. I don't know if that's the main reason for these staff changes, but it certainly has to be a factor. . .

Sanofi Pays to Get Back Into Oncology

Wed, 29 Jul 2015 11:49:58 +0000

You may recall that Sanofi basically threw its hands up in the air some time back about its entire oncology R&D efforts. Or, since they're so relentlessly French over there, perhaps it was the Gallic Shrug instead. Either one would fit - the company just wasn't seeming to get anywhere. So when that happens, what you do is you pay someone else to do it for you, and in this case, that would be Regeneron. The two companies announced a deal in immuno-oncology this week, and they are indeed paying:

Sanofi is committed to pay at least $1.8 billion in the rich deal, including a $640 million upfront, $750 million of the first $1 billion in costs to reach proof-of-concept data, half of the $650 million tab for developing the PD-1 drug REGN2810, with another $75 million being reallocated to this deal from another pact. The partnership also includes a special $325 million bonus milestone if they hit a high sales target.

There are two ways to look at this, and (at this point) a case can be made for either one. With all the money and effort being thrown around in this area, it's quite possible that Sanofi is late to the party here. On the other hand, it's a wide field, and there are surely surprises left in it, so this may be one of the "end of the beginning" situations instead. I lean a little more towards the latter, since I always have immunology filed away in my mind under "hideously complex with many key aspects unknown". But in that case, it's still true that Sanofi is, to some extent, hoping to get lucky in order to be a strong player in this area, and that's never a good thing to have as an explicit step in a business plan.

And while they would have been even further behind if they'd tried to catch up on their own, this deal does emphasize how much the company felt that their internal R&D had come up short. They let a lot of people go, took a lot of loss on the whole effort, and now they're reaching in for at least another billion dollars more. . .

An Irresponsible Statement About Curing Cancer

Tue, 28 Jul 2015 14:09:39 +0000

OK, let's stop doing this. Here's the head of the Fred Hutchinson Cancer Institute, telling people that "It is actually plausible that in 10 years we will have cures and therapies for most, if not all, human cancers". I object, on several grounds.

(1) Most, if not all? Although some great progress has been made in the last few years, we still face a number of all-too-common cancers for which a diagnosis is very bad news. Glioblastoma, renal cell carcinoma, hepatocellular carcinoma, the various pancreatic cancers - what do we have to offer? And although immunotherapy is great stuff, these aren't all good candidates, or not yet (and it's not like people haven't been looking at them in view of the latest techniques, either).

(2) Ten years is not a very long time, at least when you're talking about drug discovery and development. It would be best, to meet that timeline, if someone had something in hand right now. Maybe they get another year or so to find it, but that requires everything downstream to go pretty much perfectly. My guess is that Gary Gilliland, the Hutch president, is not sitting on a handful of potential cures that were found last week.

(3) This statement (as reported, anyway) leaves out the diagnostic angle. There has been progress here (a potential early diagnostic for pancreatic cancer was reported recently in Nature, for example), but a lot more is needed. Look at the case of Oliver Sacks: here is an extremely competent and acute physician, but the first diagnosis he had of liver cancer was when it was already metastatic. Not much we can do about that. Without better diagnostics, it's hard to see how we're going to achieve really impressive cure rates.

(4) Finally. . .no. You don't go around telling people that you're going to cure cancer, or Alzheimer's, or what have you. Cures are hard to find, and hard to prove, and most of the things that look like they're going to work actually don't. It is irresponsible to talk as if we're going to solve all these problems in such a way. Sure, tell people that we're making a lot of progress, tell them that we've opened up whole new avenues of therapy in the last few years and that we're excited about what could happen as we explore them, tell them that there's more potential than there's ever been. All true! But telling people that "most, if not all, cancers" are going to be cured in ten years? Over the line.

Oliver Sacks on Turning Back to Chemistry

Mon, 27 Jul 2015 14:30:38 +0000

If you haven't seen it, Oliver Sacks has written a sort of self-elegy in the New York Times. As he announced some months ago, he has been diagnosed with metastatic liver cancer, which as most people know has an extremely poor survival rate at almost any time point you look at.

I have tended since early boyhood to deal with loss — losing people dear to me — by turning to the nonhuman. When I was sent away to a boarding school as a child of 6, at the outset of the Second World War, numbers became my friends; when I returned to London at 10, the elements and the periodic table became my companions. Times of stress throughout my life have led me to turn, or return, to the physical sciences, a world where there is no life, but also no death.

And now, at this juncture, when death is no longer an abstract concept, but a presence — an all-too-close, not-to-be-denied presence — I am again surrounding myself, as I did when I was a boy, with metals and minerals, little emblems of eternity. . .

Readers of his memoir, Uncle Tungsten, will recognize some of the themes of that book. Sacks himself gave me some early encouragement in the first years of this blog, in a letter I'm very happy to have (we talked about how much we each enjoyed copper sulfate). I know just what he means about seeking companionship in the nonhuman, too.

Different people react to the physical sciences in different ways, as I'm reminded these days while I go over the copy-editing for The Chemistry Book. What one person finds beautiful and timeless, another can find sterile and uninteresting. (The book's actually going well, by the way). Perhaps a proxy for this might be to look at the sorts of photographs someone takes on vacation, or out on a camping trip: how many of them feature people, versus objects and scenes? My own photography, I can say pretty definitively, tends towards the abstract: cloudscapes, algae, lichens, closeups of things like weathered rock faces and tree bark. That's not to say that I haven't taken many people-pictures over the years, too, but given a choice between (say) four people grinning in front of a tree and just the tree itself, I'm always going to work in a couple of shots of the latter, too.

Stanley Kubrick once said in an interview that "The most terrifying fact about the universe is not that it is hostile but that it is indifferent". I like that about it. There are bigger and older things out there than people.

The Biopharma Funding Boom

Mon, 27 Jul 2015 11:38:04 +0000

As Bruce Booth noted on Twitter on Friday, the drop in Biogen's stock that day represents a loss of more money than all the venture capital funding in biopharma over the last four years. Here he is with more on the current funding boom, which is probably a bit different than it seems.

For one thing, the majority of the money has been provided by people other than than actual venture capitalists, and this money is going (quite disproportionately) to the larger players. (This makes figures on the "average funding" per company even more meaningless than usual). Booth is too nice a guy to say it in as many words, but the strong impression you get is that a lot of investors in this area are not willing (or able) to do the legwork of vetting and forming new companies themselves. Instead, they're very willing indeed to throw money at the big-name deals that others have already (implicitly) given the seal of approval to. It's a "me too" boom.

And as the post shows, it's really not leading to as many new companies as one would have expected - just richer ones. Is this a good thing? Probably not, to be honest. It is possible to throw too much money at an early-stage company, a (perhaps surprising) lesson that has been demonstrated numerous times. Big piles of cash make it easier to paper over problems that otherwise might get usefully addressed. Business plans that otherwise could have been stronger don't get the chance to improve, because hey, we've got the money anyway, so clearly things are fine.

Another problem is that the whole VC business is based on spreading around the risk. You fund a whole range of startups, in the full knowledge that most of them won't make it, and in the hope that the ones that do will more than make up for those losses. You know, kind of like drug development. But what about the people who aren't following that prescription, who are investing in early-stage biopharma, but in only a couple of the big ones? Those companies have (sad to say) pretty much the same chances of failure as everyone else. It's just that their failures are going to take a lot more money down with them.

So a lot of fresh money has flowed into biopharma, and not necessarily in an intelligent way. It could flow right back out again if something scares everyone - a couple of big unexpected clinical wipeouts, the threat of price controls, what have you. I can't blame people for taking the money that's on offer, but the punch bowl is not going to be refilled forever.

Biogen's Bad Week

Fri, 24 Jul 2015 15:45:47 +0000

If you're a Biogen shareholder, you don't need me coming along to tell you that this has been a bad week. The Alzheimer's antibody news was just the warmup for the company's earning numbers, which made no one happy.

So what's going on over there? Reality, I'd say. The drug industry is ferociously competitive, and no one's earnings are safe. Clinical trials are still coming in with about a 10% rate of success overall, which is the sort of risk level that would send a lot of other industries fleeing in terror. Time and chance happeneth to them all. (And no, I'm not religious at all, but a lot of Ecclesiastes is just good common sense).

So yeah, Biogen as I write this is down about $70 a share, a solid 18% whacking. By the month, by the year-to-date, by the previous year, you're probably not happy if you've been holding the shares. But over the last five years, even with today's debacle, Biogen has beaten all the indices savagely. The five-year NASDAQ is up about 126%, and the five-year S&P 500 is up 90%. Note: earlier figure was incorrect (typed something wrong into the database!), and these figures, as noted in the comments, do not reflect dividends. But then, they don't reflect taxes on those dividends, either. . . Biogen is up 485% over that span, and you know what? Hardly anything ever goes that well in this business for that long, on that large a scale. That's a terrific run.

So if you're a Biogen shareholder right now, sure, you're wondering about the company's earnings prospects, its pipeline, whether or not it's going to do some sort of acquisition (rumors are out there about Isis, and probably others). Worthy questions, and I don't know the answer to any of 'em. If you bought the company's stock back early this year on the basis of (say) those Phase I Alzheimer's results, well. . .you know what happens, most all the time, when you live by the sword, right? If you didn't, well, you do now. But if you've been a longer-term shareholder, you really don't have much to complain about.