The Problem of Drug Discovery

Well, this is my last week of employment, and while I am no longer actually working, I’m still having a hard time not thinking about work. It is very difficult to accept that the idea I signed up with at the very beginning ten years ago may be dying. Despite the dissolution of my current employer, a few of us true believers stood a good chance of saving the idea by forming a new entity, with a leaner and more focused organizational structure. This was possible since we had people who seemed willing to give us money. Unfortunately, the party with the most money is probably walking away, which if it does not spell the end, will definitely make putting something together take longer than most of our wallets can tolerate. We are not giving up, but we do need a paycheck.

One of the great difficulties in biotech is that everything is expensive, and you basically can’t operate in this business without venture capitalists, or without cozying up to a company in the Big Pharma club. That’s difficult for a discovery based company. Venture Capitalists are hesitant to invest in companies that are discovery stage, and Big Pharma is reluctant to pay large sums of money for pre-clinical compounds, unless they are hot and difficult targets they themselves have not been able to make any headway on, and even then you’re talking a million or so up-front, typically, with most of the money coming down the road with milestones and royalties.

We figured to run a program to the point where we can partner it it would cost about a million and a half dollars. It might end up being cheaper, but that depends on a lot. A sum such as that is beyond what you can easily finance with angel money, unless you can find an angel, or several angels, with really really deep pockets. Most individuals don’t have that kind of money to drop on a gamble. And because the drug business is a gamble, you will probably need several shots on goal before you’re going to hear the ca-ching of being a winner. Really, you probably want to have enough to do 3 to 4 programs. That means tapping VCs.

Typically how this would work is you develop a compound to a certain stage in the drug life-cycle, then partner it. Obviously, the farther you take it yourself, the more it’s worth when you partner it. It’s feasible for a well financed biotech to take compounds into Phase-II clinical trials. Phase-III is typically the most expensive, since you’re blowing you trials out to large numbers of patients. But going into the clinic is very expensive. Even going into animals like rats isn’t cheap. So the question is where the sweet spot is, where you can make back your cost, have enough to fund another program, but not dump so much money going into the clinic that you assume a large amount of risk yourself. Many biotechs have taken single products into the clinic, had them fall out, and then closed their doors. But taking risk in this business pays, so there’s a balance.

The biggest problem in seeking Big Pharma partners is that the business is so turbulent right now, it’s difficult to work out deals. We had more than several cases of partners either pulling out of deals, or canceling projects in place because of internal politics in the partner, or because management at a higher level in the Big Pharma partner decided to can the work on the project. Internally to Big Pharma, that happens all the time, but if you only have a few partners, and one walks away, it can be devastating to a biotech.

The Venture Capital landscape isn’t much better. VCs seem to prefer investments in companies that have compounds in the clinic. There is money out there for discovery stage compounds, but the bar is set very high for those companies. You won’t raise any money talking about how wonderful your idea is, or how great your people are. They probably won’t understand your idea, and if you don’t have the pedigree to back up how great you are, and by pedigree I mean either you’ve won the nobel prize, have already made million in biotech, or are known in the industry for having produced a blockbuster drug, they basically don’t want to talk to you.

I’ve spent the vast majority of my career in this business, and I’ve been questioning it. The fundamental problem with biotech and pharma is that the barriers to entry are so damned high. Even if you decide to depend on a Big Pharma partner for the most expensive part — clinical trials — experimental science is still awfully expensive. In other technological fields, like software and computers, the barriers are so low it’s not all that out of the question that if you grow lethargic, arrogant, and wasteful, some punk-ass kid right out of college is going to come along an own you. I like that kind of competitive environment, because in businesses like that, people tend to stay sharp, focused, open to new ideas, and open to change. That is not the drug business.

The good reason to stay in pharma/biotech is that if you do it right, there are fortunes to be made. If you produced a drug that people will take every day for the rest of their lives, in areas like cholesterol, blood pressure, or inflammation, you basically have a license to print cash by boxcar load for as long as the patent lasts. Typically in biotech, there’s a provision for a royalty to be paid if the compound is approved by the FDA and makes it to market. This is typically a few percent. But think about this: Lipitor did close to 13 billion dollars in global sales last year. Even one percent of that is nothing to laugh at. But even though the sums of money are huge, you’re going to end up sharing more of it with VCs than you would in many other industries, because of the costs involved.

Erik Estrada and the NRA Election

Because I couldn’t find the voting statistics outside of the NRA Annual Meeting this year (had to run out early to cover the protest), I didn’t do much follow up on the new board members beyond who was actually at the board meeting the following Monday.

I assumed, very wrongly, that Erik Estrada was a top vote-getter who was simply blowing off the organization once he won. I’m not as opposed to celebrities on the board as others, but I do believe that part of what they “bring” to the board in that case is a willingness to at least be known as an actual sworn-in member of the board. (Unlike, say, Karl Malone who, as I understand it, has never even shown up to be sworn in as a board member, never mind even try to symbolically attend a meeting and pretend to give a damn since I’ve been going to these things.)

Anyway, I’m glad I never posted about it because it turns out that Estrada did the right thing. He would have come in sixth place by votes, however, according to the report from the Secretary, he contacted NRA to let them know that his schedule would no longer allow him to participate. So he actually withdrew from the election. Seriously, kudos and applause all around for him doing the responsible thing.

This year, that effort is especially noteworthy because we lost some very experienced board members who bring unique skills to the board. I cannot tell you how many people on the board, on staff, and who are just highly involved in the organization were lamenting the loss of seriously dedicated and talented board members, partially due to the sheer number of celebrities up in one year. With Estrada actually withdrawing from the election, it means that the next highest vote-getter was elevated to the top 25 winners. It helped ease some of the displacement issues.

I figure it’s worth mentioning when someone does the right thing. Tomorrow’s topic: how NRA members participate in the elections. There were actually measurable differences this year, but not for reasons you might think.

Ray Nagin is as Crazy as a June Bug

It turns out Ray Nagin is completely off his rocker, at least according to his new book:

“And after several rounds of going back and forth, our unwelcome visitors got the message that we were not going to allow them to take over or gain access to my room to plant bugging devices.” […]

“I thought to myself, ‘I’m a dead man! I have just publicly denounced the governor, U.S. Senators, FEMA and the president of the United States,’” he writes. “I started wondering if during the night I would be visited by specially trained CIA agents. Could they secretly shoot me with a miniature, slow-acting poison dart? […]

Nagin admits he also suffered pangs of paranoia on the Monday after the storm, when he visited the USS Iwo Jima, an amphibious assault ship that docked near the Ernest N. Morial Convention Center and served as a base of federal operations.
There, he was escorted to an infirmary where two medical staffers “had orders to examine me and give me shots.”

“I was still a little paranoid and again started imagining a secret CIA plot where in six months I would be gone,” he writes. “After thinking for a minute, I said to them, ‘Okay, you can give me shots, but I want you to do the same for my two security guys.’

“My thinking was it would have been easier to spin that stress ultimately took me out, but it would be much harder to explain all three of us suddenly dying mysteriously,” writes Nagin, who said during Wednesday’s briefing that his sense of suspicion abated shortly after his visit to the ship.

And this is before he goes into the conspiracy to rid New Orleans of black people. Now I understand why this guy doesn’t trust anyone with firearms. It’s projection. He probably doesn’t trust himself, and assumes everyone else is as much a loon as he is. He has good judgement for himself. I’m not sure Ray Nagin is the kind of guy I want having a gun either, let alone running a city.

Isn’t it amazing how off balance so many of our opponents are? At least he was kind enough to document his delusions for posterity.

80s Flashback

Somehow I ran across this video of the 2003 Gumball 3000, which is a 3000-mile international race that happens on public roads:

Made me think of this classic 80’s movie, which was a giant middle finger extended to Tricky Dick’s 55MPH speed limit, along with a desire to leave the malaise of President Peanut behind:

For those who know the movie, I’ve always thought of our opponents as reminding of Mr. Arthur J. Foyt.

Unpacking the Pack Rat

Since I’m home, I’m making a concerted effort to clean and organize around the house. Every once in a while it’s time to go through all the stuff that’s been pack ratted away and make some hard, and not so hard choices.

It’s never hard to throw away PC power cords. They are like coat hangers, in that they seem to get together when you’re not looking and multiply. Ethernet patch cables are like that too. But some things are harder to part with. SCSI has been replaced by SATA and SAS by now, yet I bitterly cling to my last remaining SCSI cables and terminators for fear I may need it. I also was bitterly clinging to some remaining 10-Base-2 cabling , connectors and terminators for the same reason. When am I ever going to set up a 10-Base-2 network again? How many people reading even remember those? Another thing that are like coat hangers? Gun cases. I need to get rid of a lot of them, but I don’t want to throw them out and advertise to anyone who drives by there’s guns for a stealing. I would imagine everyone else who collects guns is in the same boat. How to get rid of them?

I’m still sitting on three NeXT cubes, and a slab in my attic I’d love to find a home for, but don’t want to throw out. Pack ratted along side is my Mac IIsi from college, a prototype Newton I found that still works, and a 30 gallon aquarium set. I think I’ve decided it’s about time to toss the aquarium, or sell it. I’m tired of the room it’s taking up. I don’t see myself ever getting back into keeping fish.

Also on the way out, several previous generations of digital cameras, the 8mm SCSI tape drive, and all my backups from 1998 to 2001. I’m pretty sure if I haven’t needed those by now I won’t ever need them, and even if I did, I encrypted all my backup tapes and doubt I even remember the passphrase.

This is going to be a long process, but I need to get in the mood of putting the past behind me, and throwing crap out is a good way to do that.

Reasoned DiscourseTM, Part CCXLII

I can sympathize somewhat with Joan Peterson here, because I remember when I first decided I needed to implement some basic ground rules for comments. My one paragraph ground rule basically amounts to, “Don’t be a jackass,” and those of you who have been around for a while know I probably tolerate a good bit more jackassery than could be classified under my guidelines. I probably only remove or partially redact, at most, ten posts a year, and the majority of those are rambling nonsense from people who I think found me on Google and have mental health issues.

But Joan’s comment policy reads like a Hammurabi’s Code of blog commenting. What’s more, my, and most of our default is to allow comments generally, and only remove or redact ones that cross the line. It’s hard for me to understand how facts that are in dispute can be corrected if they aren’t published and discussed. There’s an old saying that you’re entitled to your own opinion, but you’re not entitled to your own facts. One thing I’ve learned from observing Ms. Japaete is that she often thinks she is, in fact, entitled to her own facts. Common Gun Sense has been much more open to dissenting ideas than many other blogs run by folks on the other side of this issue, and she deserved credit for that, but it seems as time has worn on, there’s been more and more Reasoned DiscourseTM going on. One of the other side’s greatest weaknesses has been not forming a credible response to our grassroots new media efforts, and their unwillingness to engage in open debate has been one of those.

Signs of Discord at Brady

Dave Hardy reports this interesting tidbit:

Even after deciding to leave his role as president, Helmke said he still wanted to stay with the Brady Campaign. He said that he and the organization could not agree on a suitable role, however, so the two sides mutually decided to part ways.

So basically, his previously agreed upon term was up, and they did not appear to want to renew. The question would be is Helmke’s expense a problem? It very well may be. Or is it possible they are unhappy with his leadership?

As an objective critique, I don’t think Helmke was a bad spokesman for the group, but I never got the impression he had a whole lot of passion for the cause. I would imagine, in looking for a replacement, the Brady Campaign is going to want someone with a bit of fire in the belly. Not the kind of fire that can get your Twitter account suspended, but someone who can fire up people like Joan Peterson and get them to open up their checkbooks.

They probably don’t have the money for someone like Daley or Rendell, as I’ve seen some speculating about. Even if they did, Daley and Rendell are both the kind of guys who revel in the spotlight. I can’t see them spending their time as just another small cog in the D.C. machine.

Remember that whoever replaces Helmke probably needs to be a particularly good fundraiser. Colin Goddard strikes me as someone who’s inexperienced, and not connected in that kind of way. If the speculation that he’d be next in line is correct, I’m going to suggest a Brady deathwatch, because that tells me they can’t afford or recruit anyone with experience in the areas they desperately need.

Head of Chicago PD Says Gun Laws are Racist

It’s generally well known that the the vast majority of gun control laws have a racist origins, so I was surprised to see the headline here. But this one can’t be filed under the category of winning:

“I want you to connect one more dot on that chain of African-American history in this country, and tell me if I’m crazy: Federal gun laws that facilitate the flow of illegal firearms into our urban centers, across this country, that are killing black and brown children,” he said according to an WMAQ-Channel 5 story that aired Thursday.

I hate to tell you, chief, but it’s not the guns, it is, unfortunately, mostly other black and brown children who are killing black and brown children. You don’t get to dodge that by blaming federal gun laws. He suggests “everybody is afraid of race. I’m not afraid of race.” No, I think you’re quite afraid of it, because you’re helping these communities find scapegoats for their problems, rather than helping them look within. Violence, with guns or otherwise, is symptom of a much larger and more difficult to solve problem. He ends with this bit of twisted logic:

In a statement Thursday, McCarthy said “strong gun laws against illegal firearms are critical in order to maintain public safety and private rights.”

If they are illegal firearms, wouldn’t that suggest there are already strong laws against them? I mean, the federal penalties are generally ten years for illegal trafficking, and handguns were illegal in Chicago for more almost 30 years. This guy would do well to remember the fence.

UPDATE: See Illinois State Rifle Association’s response here.

Brady Campaign on Hunt for New President

It looks like the board of the Brady Campaign is shaking things up. Paul Helmke’s contract wasn’t extended, and he doesn’t have any future plans for work. Dennis Henigan will be the acting president while the search is conducted, which indicates they don’t even have anyone in mind. It would seem that means they just wanted Helmke gone.

So, any nominations to suggest for the Brady family? They recruited a Republican in 2006 thinking that they could somehow appeal to more GOP leaders in switching over to the dark side. That didn’t work, and the Democrats haven’t done them any favors, either. If they follow the same strategy, maybe they will try to find a far left leader to try and earn back the attention of the party in the White House.