Editing a blazing trail into a heated trial - daily life in the world of CRISPR!

           

Science and biotechnology continue to push ahead exponentially, and in today's world that means making big bets ahead of truly understanding both the full capacity and potential dangers inherent to certain technologies. It's hard to think of a hotter yet simultaneously controversial example than CRISPR, the next generation gene-editing tool that is capturing not only the imagination of us scientists, but even those in Hollywood!

Yes, believe it or not, even before CRISPR has gotten close to the nail-biting moment of using it on humans, Jenny-from-the-block herself, Jennifer Lopez, apparently wants to produce a TV show centred around the nascent technology. That's quite something for an untested, unproven therapy, and it probably does reflect not only that hardcore science is becoming more and more mainstream these days, but also that CRISPR itself is causing considerable controversy all on its own. I just can't wait to hear the words "clustered regularly interspaced short palindromic repeats" on a TV show; bet you can't say that fast, three times in a row, Jen! 

The potential of CRISPR to change the world of medicine in the post-genomics age is scary-level huge, and of course that potential is not limited to classical medicine but in effect also brings us crashing into a brave (frightening) new world where science can be used to edit something which has evolved over an eternity - our DNA - and messing with that in anything but the most controlled of conditions could have devastating consequences. 

But this is the world we are living in today, and the relentless push of next-generation therapeutic approaches such as CAR-T and CRISPR will continue to revolutionise that world, and only a lack of money could hinder or prevent that. This does not seem to be an issue thus far for the "big three" in CRISPR commercialisation who have now all gone public in recent IPOs; that trio of course consists of Editas Medicine, Intellia Therapeutics and CRISPR Therapeutics. 

Editas ($EDIT) was the first out of the gate back in February, with Intellia ($NTLA) following a few months later, and this week it was the turn of CRISPR ($CRSP). The former two raised about $100M each (on top of considerable VC and pharma money) in their respective IPOs, while CRISPR came in at around $56M, failing to hit their initial target of $90M. Analysts were quick to jump on this, implying that the bottom is already falling out of the market, and this fact had negatively impacted $CRSP's raise. 

While investors may indeed be a little less sanguine on this avant garde and risky bet than a year ago, it is worth pointing out that both $EDIT and $NTLA have seen their market cap nibbled at and all three companies actually have a similar valuation today. In fact, $CRSP is pretty much par for the course, with a current valuation just short of the $500M mark, which is in the same ballpark as the other two after their valuations slipped somewhat and were adjusted post-IPO. 

The confounding factor here is not only which one of these three will get to the first-in-man clinical trial, first, but they are also all facing the reality of the ongoing and explosively contentious patent wars regarding who-owns-what with respect to CRISPR technology. At the heart of the dispute is whether it is indeed UC Berkeley and Doudna/Charpentier who should own key patents in the field, or whether the current status quo should be upheld such that the great majority of the key patents at stake should remain the property of the Broad Institute and Feng Zhang. Additionally, although it garners way less media attention, another prestigious institution, the Rockefeller, is also involved in the fracas and they are claiming that one of their scientists (Marraffini) should be named on specific Zhang/Broad granted patents. 

Apart from egos and bragging rights, there is a vast amount at stake in this patent interference case, and the decision of the USPTO could have staggering consequences for those who do not prevail. At the very least, their bottom line will be affected by being forced to pay no doubt elaborate license fees to use the technology therapeutically. Or, if a decision was made against Zhang, the new owners could license the technology to a competitor of Editas, for example, and the company would be in very deep you-know-what. At worst, if investor and pharma attention swings away from the losers to focus on the (new) owners of the IP, the other companies may struggle to even survive. The temperature during the legal exchanges and between the major scientific players must be a little crisp, to say the least! 

I am in Toronto next week for the Canadian "Gairdner Awards" lectures at the University of Toronto, and you can be sure I will be watching closely as Jennifer Doudna, Emmanuelle Charpentier, and the wunderkinde of the bunch, Feng Zhang all present their work. It will be interesting to see how they position their contributions, with all of the legal shenanigans and inter-institutional fighting still going on in the background. You can be sure I will be looking and listening for any signs of tension or bold claims of ownership during the presentations - watch this space for an update! 

A bitter biotech brew fermenting into something sweeter - it just needed time!

The word "biotech" of late, while not exactly being a dirty or unholy word by any means, certainly was one which was considered out of time or out of fashion here in the province of Quebec, since 2008 effectively. While there were a myriad of reasons (and even more excuses) for that, the bottom line was that biotech in the Montreal area just didn't work out and the windows were shuttered one after the other, province-wide. Yes, there were one or two noted exceptions, but that didn't save the industry. 

Now if you have never opened a biotech company and then presided over its closing and subsequent gutting of its laboratory and office spaces, then it might be easier to just look at it as a real estate deal gone south. But as someone charged with getting a shiny new but empty space turned into a fully functional modern laboratory facility, and then years later being charged with emptying it out and selling off the parts at firesale-type prices, well, I've been there and done that and would prefer not to live that experience again!

Yes, yes, entrepreneurs have to embrace failure, blah blah, and learn from it, uh huh, but in almost every case of an entrepreneur failing, there are a whole bunch of individuals who by association (and loyalty) must fail alongside them, even after doing their jobs diligently over many dedicated years. The ~350 employees just let go by Theranos, for example, surely know how that feels, today. It's the least fun side of what is typically a brutal business (biotech life) - with what seems like a >95% chance of failure, almost all of the time - even when it's going well!

So why would we at AmorChem even be considering branching out into that milieu once more, after having tasted the bitter brew of biotech business in the past, in previous funds? Well, there is that mantra of "if at first you don't succeed" and of embracing failure, and, of course, the key element of embracing failure is learning from it, and then coming back bigger, better and stronger. Unquestionably, we have learnt valuable lessons from previous endeavours, as have other players in the local ecosystem who are already embracing a return to biotech - 2016 style!

Without going into the details of what went wrong in the business, historically, (there's not enough space in one blog to go into it all!) to cut a long story short we continue to need a vehicle of sorts to nurture and mature our most promising projects. Given that we are a very early-stage life science venture fund, it is completely legitimate to say that 18-24 months of our support rarely leads to that big pharma deal and the much sought after exit for both ourselves as well as our own investors. 

Rather, our support over the typical lifespan of our university-incubated projects leads to a clearer picture regarding which technologies have evolved, and which are ready for further elaboration into a structure that both permits additional investment/development and adds a degree of professionalisation to the team, whilst earmarking the venture as a commercially viable candidate for acquisition. 

It's not as obvious as it may seem to convert what was an entirely academic project and team into a biotech company (real or virtual), as anyone who has lived that experience knows well. But we have made the decision that for chosen exciting technologies which are coupled with talented teams, we will move them forward into their very own (more or less) virtual entities that will be responsible for subsequent development of those technologies towards commercialisation and the marketplace. 

Ergo, and to wit, the recent nucleation and creation of Mperia Therapeutics which arose out of a stellar effort over many years at the University of Montreal, under the auspices of Professor Huy Ong (pictured above) and his dedicated roster of collaborators and researchers. This new entity is being led by local life science serial entrepreneur, Maxime Ranger, who has passionately stepped into the fray to take Dr. Ong's azapeptide technology (focused on age-dependent macular degeneration, for now) to the next level. We wish them the very best and are behind them 100%.

We are not done yet though, and without giving too much away, we have other select technologies from our portfolio that we intend to proceed similarly, some of which have already grabbed attention from local VCs in terms of them joining us in financing such further evolution into the biotech space. There will be more news on that as it happens, but for sure one lesson we have learned is to keep things virtual as long as possible, and spend the money on actual experimentation rather than on infrastructure and top-heavy management teams. 

In many ways this is a continuation of our modus operandi since the debut of AmorChem, whereby we incubated our projects where they began, i.e. in founder's laboratories - to apply maximal funds to pure research - and the interest in the local ecosystem for some of our currently being-positioned newcos is testament to the success of that approach. Mperia was first, but there are others to follow - watch this space!