R&D efficiency

Forbes' Matt Herper takes a look at the cost to develop a new drug, and now current estimates put that figure at $1B-$4B.

While the current estimate is newsworthy, folks at places like Tufts have been conducting this exercise for years, and the numbers are always eye-popping (and debatable.)

What makes this particular article interesting is how you can also use the analysis conducted by Herper to compare pharma productivity over the last 15 years. Take a look at the R&D productivity of the top 12 pharmas:

Here's my takeaways:

-There's two tiers of productivity in the analysis: the "productive" cluster (AMGN, NVS, BMS, MRK, ABT, and LLY) all cluster between $3.7B and $4.6B in cost per new drug, while the "less productive" ranged from $5.9B to 11.8B per drug. While half of the companies studied, the "productives" account for 66 of the 135 drugs (49%) these 12 companies introduced in the last 15 years. So you can't say that higher R&D productivity is also a factor of scale - the productive and less-productive companies produced roughly the same number of drugs. 

-The "less-productive" companies tend to be the product of mega-mergers. Each of these companies has done deals to one extent or another, but think of the "biggies" and you're generally thinking of the "less productive" group. Careful, though, when thinking about the time element here - MRK, for example, only did their big SGP acquisition in late 2009. This brings up the question: do mergers depress R&D productivity, or is it mostly companies with declining R&D productivity that have the urge to merge? (My guess: a bit of both, but considering that the 6 most productive companies are generally considered the least involved in the M&A game due to a bias towards internal efforts, it may be a moot point. M&A either distracts from focus, or results in sub-efficient R&D orgs.

(I'm being charitable to NVS, which is a product of a mega-merger (Sandoz and Ciba-Geigy), but that occurred in 1996 - prior to the analysis period. Either NVS did a much better job of integrating R&D, or it takes 15 years to overcome the M&A inefficiencies.)

-I think it would be appropriate to believe that these results also project future R&D efficiency and likely future stock performance.  (e.g. over the next 15 years, AMGN is likely to be much more productive than AZN.) The 15 year period (and $75B in R&D spend) should account for short-term spikes and likely demonstrates which companies have the best R&D people and organizations. I am especially impressed with Novartis (21 products over 15 years) and most disappointed by AstraZeneca (5 products over the same period.) Perhaps this reflects one company choosing easier/harder targets, but I think it more likely reflects capabilities.

-For all of the news and criticism, Pfizer's R&D isn't too bad. The criticism that failures like torcetrapib reflect diminished R&D productivity due to repeated mergers seems misplaced, as Pfizer was almost middle-of-the-pack in R&D efficiency over the last 15 years.

-You might expect that the broadest R&D portfolios would have the smoothest results (success in one area, say cancer, making up for failures in another, say neuroscience.) However, the more productive companies are to me the least broad. Rightly or wrongly, I think of BMS & AMGN biased towards cancer research, while GSK and JNJ are the most diversified. Does this mean that there is R&D value in specialization?

Any other insights to be gleaned from the Forbes analysis?

A couple of caveats to the analysis: 

-The best analysis would weight productivity with resulting product sales. (In other words: you'd accept lower R&D spending efficiency if the output were blockbusters.)

- I can't tell from the Forbes analysis exactly what is included in the figures. I suspect that Roche data includes historical Genentech R&D spending and output. I think DNA has been one of the most efficient AND effective R&D organizations, so I would be very curious to see DNA split out from pre-merger Roche.

More on Warp Drive Bio

I analyzed the Warp Drive Bio (WDB) launch here (Warp Drive launched with a stunning $125M in financing.)

Even better,  BioIT World has more detail on Warp Drive Bio, including an interview with the CEO.

Interesting to see that the 'put' of WDB to Sanofi is actually formally agreed to - hit certain milestones, and Sanofi has to pay a pre-determined price, so there's more risk on Sanofi's part that I assumed was being carried by the VCs.

Either directly or indirectly, this results in reduced risk for Sanofi, the VCs, and WDB company management - a win all-around - pretty smart. Consider:

-WDB & company management doesn't have as much financing risk as most biotech's - they can concentrate on discovery productivity, instead of chasing next round financing.

-VCs get a liquidity put. There's even less downside, as VC's are providing less than 100% of the start-up capital. (Assuming more than the VC's $75M was required to launch.)

-Sanofi gets exclusive (I assume) access to a novel technology platform, gets R&D expenses off of their income statement, and locks in discovery productivity and the cost of acquiring WDB technology at 2012 prices. As long as SNY's R&D agenda is matched by WDB's, and the value of leads does not go down, this is great.


I think most VCs and company executives would LOVE to do this sort of deal, especially at company founding, but pharma's aversion to risk prohibits most deals of this sort. Big Pharma's usual game plan is to wait to see more data, as they would rather trade potential financial upside for reduced product or program risk. Let's hope that this deal represents Big Pharma's willingness to take a little more risk, especially when a company at start-up has such a great pedigree.


Besides the novel Sanofi partnership, WDB has a very traditional lead discovery value proposition  - their expectation is that their technology platform will generate novel lead compounds quicker/better/or more efficiently.

I'm in no positon to evaluate the technology, but from a business strategy perspective, it is another example of over-valuing lead discovery. (That is, if you believe as I do that preclinical leads are over-valued.)

Consider the typical drug discovery & development timeline, as put forth in Nature:

WDB's value proposition affects only the first two years of the timeline (up to lead selection.) Presumably WDB is more efficient (either in time or cost) during the early stage. Let's say they're 25% more efficient in terms of time, which equates to 6 less months of development over 8 years, assuming that the drugs have the same downstream risks of other R&D programs. (i.e. a WDB-sourced lead is just as likely to succeed in Phase II as any other pharma lead.)

The net effect is WDB's entire discovery advantage is in 1/16th of the total effort required to produce a drug, and does not seem to impact the probability of success. Sure, there's financial value in getting a product to market 6 months earlier, but bringing $250M in revenue forward by six months 7.5 years from now is only worth $31M in present value (25% WACC, 30% OPM).

The same $31M in NPV could be generated just by increasing the probability of a programs success by a small amount. (In other words, quality over quantity.)

For this reason, I'm a fan of investing not in more early leads, but rather any IND leads or technologies, especially if I'm a risk-averse pharma.

Thoughts? Reactions?

Interesting deals......

Two transactions from the last month that intrigued me:

Transgenomic (TBIO) raised $22M from a group of investors. Congrats to TBIO, as they attracted new capital equal to about 40% of their market cap including from a very serious investor (RJ Kirk's Third Security.) This financing allows TBIO to rise above the small cap services/genomics/diagnostics crowd, and lets them focus more on business than on financing. Gaining the imprimatur of RJ Kirk isn't bad either.

(Also an acknowledgement of TBIO's very nice 3-yr stock performance.)

What made me curious about the deal is:

1) the size. While one blogger calls the raise too large relative to their $1M/yr cash burn, I'd expect that TBIO has some really good uses in mind for the fresh capital, perhaps to shop around earlier, younger diagnostics plays to plug assays into their sales channel. My perception is that acedemics are asking for stiff terms to commercialize novel diagnostic IP, bargains can be found among capital starved start-ups.

2) the fact that Kirk/Third Security are injecting equity into TBIO.......to repay the debt owed to Third Security by TBIO. (TBIO owes ~$8M as part of their prior deal to buy Clinical Data/s (i.e. Kirk's) prior PGx assets.

This isn't anything unscrupulous, like, say Elan's early 2000's Enron-esque equity investments to get R&D expense off of their books while pumping their book value. (Wish I could find a link for this.) Instead, it's an interesting way for Kirk to continue to bet on pharmacogenomics while also returning some value on the investment in the short run. (The definition of "short run" is liberally applied here. Kirk's PGx investment interest goes all the way back to the purchase of Genaissance (2004?)) Kirk & team have turned over a tertiary asset from their Forest Labs/Clinical Data deal into an interesting chunk of a publicly traded company. (albeit OTC BB)

One of these days I'll have to dive deeper into Kirk's activity, particularly Intrexon, his synthetic biology company, and affiliates such as Ziopharm and Adeona.....

The other transaction that caught my eye:

Warp Drive Bio founded with $125M in seed financing.

When I first heard of this deal, I was stunned by its' size. I've come down a bit after learning more details, but I still can't rationalize it. (Never mind the realization that the headline science of Warp Drive combines two absolute graveyard priorities: natural products and genomics. That's a conversation for another day)

It looks like only $75M is committed cash financing. My guess is that Sanofi is contributing $50M in research support, less any research assets contributed. The press release suggests that this will cover 5 years of operations. (Let's ignore that business plans & research agendas change over 5 years.)

If you're an early stage VC, you're targeting a 40% annual ROI, but you won't pull the trigger that doesn't look like a potential 10X return. If the VCs behind the deal expect 10X liquidity in 5 years, then they'd target an enterprise value for Warp Drive in 5 years of $1.25B (158% IRR), but be happy with  5.4X (40% IRR on $675M EV in 5yrs.)

These figures are nuts, but I guess that's how Third Rock (not Third Security) does it - they also started Foundation Medicine with an enormous seed round ($34M last year.)

I really hope this isn't the only way that start-ups will get off the ground in the future. By now it is apparent that there's a big gap between start-up requirements and VC interest - VCs really need to deploy large amounts of capital ($5M chunks minimum, likely in syndicate with other firms resulting in rounds of $10-$20M in new capital. Only deploying capital at this level makes their VC models economical, while most early stage discovery companies think in terms of $1M-$5M rounds, otherwise their interests are diluted to nothing.

If Warp Drive is the rule, rather than the exception, only big ticket discovery efforts with star quality SABs and pharma partners at launch will draw financing, meaning that pre-clinical discovery will slow significantly.

My guess is that Warp Drive and Foundation are the exception rather than the rule, and that their VC parents have the 'curse' of too much capital to manage.

Or at least I hope so.