Intrexon In-trouble?

Ever used Google Alerts? They're a great way to keep tabs on interesting companies without the press appeal of, say, Apple or Pfizer. One such company that I follow is Intrexon - a company that aims to be to synthetic biology what Microsoft or Google are to software or the internet - broad, dominant, and in certain regards the 800-pound gorilla of the sector.

Usually my Intrexon alerts are full of Halozyme and Ziopharm references - they're small-cap partners of Intrexon and never shy about touting their connection to Intrexon and RJ Kirk. This weeks' alert, though, linked to a message board post from an Intrexon employee who's position was being eliminated in a bad way. Not a huge deal, but it did prompt me to check the Intrexon management page and some LinkedIn connections. Turns out  there's been leadership turnover and layoffs at the extremely well funded company. At least two long-term leaders at the company have been booted (COO who was formerly CEO, and the head of the AgBio division), and the number of open positions on their career page has been reduced to a trickle.

Intrexon is highly secretive, so what has happened will probably never reach the press. I'll guess, though, that somebody realized that a time-out was necessary since 1) the company probably has/had a seven-digit monthly burn rate, while intentionally foregoing revenues, and that 2) the company's core technology is over a decade old. Other guesses might be that an expected partnership didn't materialize, or, possibly the Prometheus, Myriad, and other legal cases prompted doubt over whether Intrexon's synthetic biology IP strategy was defensible.

One other possibility: the realization has taken hold that synthetic biology is just a new name for cool(er) genetic engineering, and that a category-killer company in this segment just isn't in demand.

Transgenic (& biosimilar!) FDA approval!

Congrats to Protalix and Pfizer for receiving FDA approval for Elelyso, a drug to treat Gaucher's disease. The Protalix product will compete with the insanely expensive Genzyme product, Cerezyme.

What makes this approval especially noteworthy is that Elelyso is produced in carrots, making it the first FDA-approved transgenic drug.

Transgenics have been in development for two decades, but the challenges of the science have been significant, as has been reluctance on the part of regulators and payers, as they wondered if transgenics could really be bio-identical.

Also interesting, but not noted in the article: Elelyso may have also broken ground as the first biosimilar approved by the FDA. In this case, the resulting molecule is the same, though the expression system is obviously very different. I wonder if we'll see biosimilar makers trying this backdoor approach as well.

Now that Protalix has burst both the transgenic and biosimilar dams, it will be interesting to see the industry response. For starters, I think we'll see Genzyme cutting their price on Cerezyme to match Protalix/Pfizer, in spite of all of their previous protestations that the current price of $200,000/year is justified.

Personally, I'm happy to see this transgenic enzyme for Gaucher's disease receive approval. Approximately 15 years ago I was mildly involved with a research team trying to do the same thing using tobacco as an expression system, with the same goal of a massive price reduction for Gaucher's patients. We never succeeded, for a variety of reasons, but I've always been hopeful that someone else would.

DNA, RNA, and….XNA?

A UK team synthesized DNA-like and RNA-like chemicals with similar properties, though using never seen-before chemistry to act as the structure for the nucleobase genetic information. (In other words, traditional A's, G's, T's. and C's, but novel structures in place of the ribose or deoxyribose sugar scaffolding. Good scientific over views can be found here or here.)

The resulting molecules are referred to as XNA - xeno nucleic acids. The implications of XNAs are profound, and I'm not even counting the conclusion that it now seems that life need not be based on DNA or RNA. (I can't wait to see how the evolutionists and creationists spin this news.)

The UK team's research represents the dawn of a new research modality or at least a re-definition of the science of biochemistry. XNAs could be a new source of therapeutic compounds or a source of new biomaterials. XNAs could be a key component of quantum computing (it would seem that XNAs could represent organic memory storage).

My first thought, as I contemplate how to explain the significance of XNAs to a non-bio-geek, is to suggest a mainstream analogy: DNA & RNA are traditional operating systems that we have grown up with and almost mastered, like Linux or Windows. The development of XNA is like the establishment of a different but ubiquitous operating system like Java. Like Java, XNA could enable exciting new applications in a breadth of industries or operating systems.

I think XNAs will kickstart a wave of interest in chemistry and synthetic biology research, not just in traditional biochemistry groups, but probably as far afield as NASA (XNAs as an analog for extraterrestrial life?) and Dow Chemical (why synthesize a chemical when you can express it?)

A couple of questions to chew over as a result:

1) while XNAs represent a change in the basics of life's chemistry, is an improvement possible, or has evolutionary biology optimized our chemistry?

2) what does this mean for large synthetic biology ventures like Intrexon? Their existing IP likely just became less relevant (or valuable), but their core capabilities are now more relevant. (I'm probably getting ahead of things - the XNA technology is still a long way from commercialization.)

3) what groups will be the first to incorporate XNA in their grant proposals? Will it be drug discovery groups, who would consider XNA another lead class on the order of siRNA or aptamers or will it be chemical engineers?

4) what can be down to mitigate the inevitable new, larger, louder round of synthetic biology fear-mongering among bioethicists and bio-Luddites, as XNAs could possibly do very bad things - intentionally or unintentionally.


Of course, XNA was not the biggest scientific advance this week. That prize goes to the research team who discovered the cause of brain freeze. I wonder if the research was underwritten by Slupree Corp.