Reviewing the drug class of 2011

The drug class of 2011 was larger than the past few graduating classes. We count over 30 new “innovative” drugs found among the list of FDA approvals last year. This is in contrast to the 20-something range of the past few years. On the list are some clear breakthrough treatments and a few glimpses of “the future of biotech”. The specific drugs are listed further below, but first a big picture view:

Ten of the approvals were for biologics, six of which came through CDER. Of these six, three were antibodies, two were recombinant fusions, and one was a PEG linked enzyme. The other four biologics came through CBER. The CBER approvals contain blood or serum derived therapies such as the first blood cord stem cell therapy (Hemacord), a mixture of horse derived antibody fab domains for scorpion venom (Anascorp), and an autologous cell therapy for wrinkles (LaViv). One recombinant blood protein was approved by CBER, rFactor XIII (Corifact).

A range of disease areas were addressed by the the approved therapies. Cancer, being the most prevalent with eight approvals. Two of the small molecule new molecular entities (NMEs) are kinase inhibitors for cancers that were approved along side companion diagnostics. We expect to see more of this in the future, as patient identification and responder selection gains more traction in the industry, and regulators welcome the concept. News this week from Biogen, regarding Tysabri, underscores the importance using diagnostics for patient stratification even for approved drugs. News that Roche has bid ~$6B for Illumina also illustrates the imperative for drug developers. Examples of companion diagnostic for negative/positive responder identification, as well as safety profiling, will likely become a major theme in biotech in coming years.

The drugs slated for fast review and decision accounted for over 50% of the approvals. Orphan designated drugs made up a fifth of these approvals, and over a third were priority approvals.

Counting approvals that are new and “innovative”, is not as straight forward as copying and pasting from fda.gov. First, we only include drugs that are being approved for the first time, for a first indication. Second, we do not include imaging agents in our list, like the FDA did in their fiscal year list back in November (note we use a calendar year here). Third, unlike lists published elsewhere online that only count CDER BLA approvals, we include certain BLAs approved via CBER. Fourth, we exclude new formulations, and combinations. However, we do include chemically modified forms of exisiting drugs, such as this year’s addition of PEG to arginase in Erwinase (chemically like what Amgen did for Neulasta or Celltech did for Cimzia). As another example, two drugs with Gabapentin were approved in 2011, but only one was chemically unique (the prodrug Horizant) and made it on our list. The other, Gralise is a once daily reformulation.

Below is the 2011 list of new drugs. The colors denote biologics: Antibody (green), fusion or native protein (blue), blood fraction or cell therapy (orange).

Venture Capital increases in 2011, but…

The National Venture Capital Association (NVCA) has released their 4Q 2011 numbers for biotech venture financing in the US. The report echoes the global numbers already out from BioCentury and BioWorld – a boost in investment for 2011.

The take away, however, is not the total amount, but 1) the drop in the total number of biotech deals, and 2) the drop in start-up, early-stage deals from 2010. The total number of deals near 447 was down 8% from 2010, and the number of start-ups receiving funding dipped 19% from 2010. Biotech 1st round deals fell below 100 for the 3rd time in a decade (see table below). The NVCA defined “Life Sciences” group had the lowest deal number in FIFTEEN years. (They add device companies to biotech to get their “Life Sciences” number, which essentially means things are worse off in the device space.) As is often the case in our sector, the devil is in the details.  So, take the 20% jump in VC $ funding with a grain of salt.*

Here are the 1st round VC financings from NVCA since 1995:

Below is the US biotech venture investment from NVCA, 2005-2011. The second chart shows TOTAL US venture investment and total deals. Note that the second chart shows the total number of deals for all sectors going up, yet biotech (in the first chart) goes down for 2011:

What this implies is that although we did see more investment, the funding is becoming more concentrated. We see fewer deals, but more money invested. There are two possible reasons for why this could be happening. First, VCs are very conscious of capital constraints in a volatile macro environment and want portfolio companies to weather the next storm if need be. Second, later stage assets in biotech require more funding. With LPs demanding closer time horizons for an exit, these companies may have a better chance receiving additional rounds vs. discovery start-ups (without an asset) seeking a first round.

*A point that has been brought up since the NVCA release, see Bruce Booth and Rick Soltero, is the over reaction to the magnitude of the drop in the 1st round deals. Bruce argues that 100 is still a decent turn out, and Rick argues that they get more than they used to, with quality the focus on the VC front. Both are valid points and do not disrupt the thesis that more late-stage rounds deals are occurrring vs. early stage. When we plot the number of biotech deals that are 1st round vs. later round, the divergence is pretty clear (see below). However, when we plot the amount of money going into 1st rounds as a percent of total biotech investment, it is far more consistent (15-20% of all invested biotech VC money). Thus, taken together, this would mean the following:

1. There is no growth in the number of start-ups per year, potentially at a baseline near 100 (the 98 companies in 2011 is off peak levels of 140, by 30%, and below the 15 year average of 105)
2. The VC allocation discipline to early stage is about the same, but off peak allocation of 20% of invested money (typically 15-20% range since 1995)
3. Because there is more VC money invested in 2011, and start-up numbers stagnate, the investment per start-up is increasing (see last chart)

Sizing up the NBI in 2011

How did the Nasdaq Biotechnology Index (NBI) perform in 2011 relative to other sectors?

Second place. Not so bad considering 2011 was the year of defense in the stock market. Like a page out of a textbook on defensive market plays, utilities edged out ahead with a +15% gain, followed by consumer staples with 11%. The NBI squeezed in between at 12%, just above the overall healthcare sector.

Overall, the S&P500 was flat for the year, so the NBI took home double digit alpha for 2011. However, it was not an easy ride for either as this next chart shows. That big drop in August (the AAA crash) meant a -22% drawdown for the NBI (in red below)  and -16% for the S&P500 (in black). The big pop in the spring was in part due to data coming out of Biogen Idec, Pharmasset, and Regeneron, and approval hopes for Vertex. The December pop was a Christmas gift from GILD.

It is also useful to compare the NBI vs the Russell 2000 Small Cap index, given that most biotechs are small caps. The movement of Russell 2000 will give you a better idea of what your typical biotech may have experienced in 2011. (The NBI really shows you the movement of large and mid cap companies, which account for 78% of the market value of the index. It can be hard to imagine this given that 75% of the companies in the NBI are actually small caps. It is just that they comprise such a small weighting.) Below is a month by month breakdown of performance for the Russell 2000. Note the big swing the Russell 2000 took from September to October. The NBI held up (relatively speaking) and avoided ending up in the red for the year. The “R2″ left 2011 down -6%.

Next time we will look at the Amex Biotech Index (BTK) performance in 2011. The BTK was actually down -16%, but why?…