Painting in Broad strokes or a Crispr whitewash?!

                        

Not so long ago I posted some comments on very recent developments in the game-changing field of CRISPR technology, coming out of the lab of Feng Zhang et al. at the Broad Institute in Cambridge, Mass; if anyone needs reminding, Zhang is a pioneer in the field and currently holds the bulk of the patents originating from the discovery of CRISPR. 

Well, last week, CRISPR, Zhang and the Broad all made the headlines again, not because of the upcoming (and longtime-simmering) patent interference case over the technology, but rather due to a published attempt by the high profile head of the Broad Institute, Eric Lander no less, to write (and lay down in stone, perhaps?) the history of the discovery of CRISPR. 

However, far from being seen as the modern day and scientific equivalent of the decalogue and its two stone tablets, Lander has caused a firestorm of controversy over what many similarly prominent figures claim is a self-serving and inaccuracy-laced attempt to actually rewrite the history of CRISPR! Apart from the fact that the very facts themselves are in question, Lander's case is not helped by having a clear axe to grind in the current controversy over who-discovered-what; he is after all, Zhang's de facto boss at the Broad. 

The timing really couldn't be worse in my opinion. If this had been written even six months ago, or had issued during/after the patent interference hearings at the USPTO, it may have appeared less loaded or strategic. But it being cranked out a month or so before the landmark hearings are set to begin, and it coming from a figure who is sufficiently prominent as to be an advisor to President Obama on science and technology, well, it certainly appears to be an attempt to put the argument to bed before the legal shenanigans fully commence - from an individual with skin in the game and definitively something huge to lose - even if not personally, but certainly professionally and institutionally. 

A major issue science has faced in recent years is that of reproducibility of results and research findings, or the lack thereof. It seems to have become almost normal, if not quite acceptable, that a team in one institution or location has trouble reproducing the work of another, following prominent publication. Although there have been controversial accusations, and some cases of apparent fraud, it seems that a large part of the problem resides in the various cell lines teams use for their experiments, and how truly similar a given cell line may be in two different corners of the scientific world at any given time.  

As reported on this blog last year, the heretofore anonymous outfit known as PubPeer is front and centre in the war on irreproducible results, and ostensibly allows researchers a safe place to call out questionable publications by competitors. However, while scientists are loathe to accuse one another of outright fraud and prefer to believe more generous conclusions, when it comes to not giving credit where it's due and even seemingly eliminating or downplaying the role of certain key players in a major discovery while elevating others, inappropriately, the claws do come out and the responses are a lot less guarded or gracious. 

Such as it is with this Lander "Perspective" in Cell, emotively entitled "The Heroes of CRISPR" and published on January 14, this year. Normally such retrospective pieces may raise a few eyebrows at the coffee machine or in a lab's journal club, and then disappear under the weight of more important everyday matters and endless newer publications. But this Lander piece lit up even the Twitterverse; not exactly a place that your typical scientist spends much or any of their precious time! 

When you start seeing heated Twitterrage over an esoteric subject such as #CRISPR, then you know it must be 2016, and not 1984, right?! In some ways I found the social media outburst most entertaining because it sure beat the usual nonsense surrounding the Biebs or the Kardashians or the Real Housewives of Thetford Mines (insert your fave frnachise of that TV show/excuse for grown women behaving like vicious, spoilt teenage brats). For once we had something of real substance and import to fight over, and the financial stakes are higher in all likelihood as they probably run into the billions, ultimately. 

There was more than one problem with Lander's use of Cell as a personal platform for his take on the story, not the least (and probably the most glaring) of which was the omission of any disclosure of potential conflict(s) of interest that he may have had. It's not just that he has a clear professional interest in seeing Zhang and the Broad retain ownership of a dozen or more patents at the expense of UC Berkeley, Jennifer Doudna and Emmanuelle Charpentier. Additionally, there are huge amounts of money involved in the success of Broad-associated Editas Medicine (estimated to likely raise as much as $100M in an IPO), and Lander also has close ties to a major VC company (Third Rock) that funded that biotech.  
To say he is conflicted is an understatement, and the omission of some/any kind of disclosure statement simply pushed coarse-ground sea salt deeper into already painful wounds, and the response was to be expected. "Scientific propaganda at its most repellent" is how one prominent scientist at UC Berkeley put it, while another star researcher located at the Mount Sinai Hospital (Toronto) referred to the perspective as "Orwellian doublespeak at its very best". The mercury has been rising ever since. 

It probably irks Lander and the Broad that Doudna and Charpentier already shared a multimillion prize for their discoveries on CRISPR, as recipients of the Breakthrough Prize in San Francisco last year. The subtext of that award being that these two are the true discoverers of CRISPR, which was compounded by Doudna herself giving a TED talk wherein she described herself (and her colleague) as having discovered the phenomenon. Ouch! So, both sides have been edgy and self-promotional over who-discovered-what, and it's not all just bad boy Lander and the big old, bad old Broad. And who wouldn't expect a(n) (un)healthy amount of podium hugging, Gallo vs Montagnier-style, over a monster genome editing breakthrough such as CRISPR - it's only human nature - even if the human ego can edit us into monsters, sometimes! 

This will all play out at the hands of the USPTO soon enough, and there will be chilled champagne flowing in the winning institution's halls and laboratories, while the losing side will belch bituminous bile down the corridors of theirs - but it's all in the game. The world will keep on turning. All the players will survive. Some will get a lot richer. Some will simply get richer. And the people with the least to lose - the lawyers - will all come away with another extremely healthy tab of extravagantly billed hours and expenses. Win-win. Except for the credit. 

The thing that intrigues me having watched this story is how the Internet and social media have now changed the scientific process irreversibly; from a situation where publication in journals was the only real way to raise issues or contest results or statements made (and even that had to be peer reviewed, so was protective for the accused and risky for the accuser), to one where players at any and all levels (lab technician all the way up to lauded professor) can use social media to ignite a conversation about publication, data, prominent personalities, or even the very scientific process itself. 

The good old days of keeping everything quiet, and brushing science's dark matter under the rug, with the big names ultra-protected and closeted, well, they no longer exist. The darker underbelly of fiercely contested science, and its equally fierce contest for recognition and funding, is being exposed and pushed out onto the Internet for all to see - Joe Public included. The stars of this ecosystem are beginning to find themselves forced out onto the very same social media public stage previously reserved for the "real" stars of the world of entertainment, and that is another game-changer. It's only going to get more interesting in this amazing world of science, folks! 

It's less about resolutions and more about decisions - onwards and upwards in 2016!

Well, 2016 is now very firmly with us, and it's shaping up to be another very interesting year ahead! Personally speaking, this is the beginning of my fourth year at AmorChem, and while it is true to say that occasionally it still feels like yesterday, a lot of water has flowed under my bridge in that time corresponding with a lot of new challenges faced, much new experience gained, and many solid lessons learned - and that's what it's all about! 

This is a big, big year for us at AmorChem, having reached the end of the investment cycle of our first fund, and various key projects now having matured from early stage discovery assets into those that are increasingly the focus of business development (BD) activities, garnering enthusiasm from BD personnel working for various potential external partners. This is both an exciting as well as rewarding development in that it underlines that we must be doing something right - right?!

We are poised to do it again this year, bigger and better, having learned a lot about the complexities and challenges in investing in life science discovery projects that remain housed in the laboratories of inventors. This experience is fairly unique to us (province-wide if not Canada-wide), the need for such translational funding isn't going away anytime soon, and this is why we are ideally positioned to expand on our success and therefore are currently fundraising for an AmorChem 2. We weren't totally sure at the outset or early on during the vesting period of our first round whether the submission of new opportunities and deal flow would significantly slow down after 3-4 years, or would be sustained. While it's always easy to be cynical or pessimistic, we were in on the inside, busier each passing year, with confidence that the need for our presence in the local ecosystem was not about to dry up. And guess what - it didn't!

In fact, our thermometer remained on the warmer side consistently, and it is accurate to say that the door has never really stopped knocking. Word of mouth has spread about our fund and what we do, and increasingly, people come to us now in a fashion typified by classical inbound marketing campaigns. This trend has been facilitated by our annual KNOCK OUT™ competition, whereby local hopefuls enter the ring in front of our panel of biopharma heavyweights and duke it out for a chance at a grand prize of a $500,000 AmorChem investment. The quantity and quality of our applicants has steadily improved and last year we found ourselves in the somewhat luxurious (bot not enjoyable!) position of having to turn down projects that were just a little too early - even for us. 

The take-home message here is that demand remains high, the need for external funds to get early stage projects across the "valley of death" is deeper than ever (like the valley itself) , and it is apparent that academic granting agencies can only do so much in this regard. This is why we exist, and I don't think it is a stretch to suggest that the need for our continued existence is palpable - given the number of calls we receive from local tech transfer offices asking about our rumoured next round of financing, with a hot new project to put forward for it - it's more than evident that we meet a key, urgent need. 

As exciting a time as it is for us, 2016 presents many challenges in the life science and pharma sector, and recent or upcoming elections can be expected to impact those challenges further. Here in Canada, we have Justin Trudeau as a newly elected Prime Minister, representing a shift of government from Conservative to Liberal, while south of the border, we have the raucous (and occasionally trainwreck) presidential campaign trail that will see Obama sail off to early retirement and the lucrative dinner speech circuit by year end.

We all need some light relief now and then, and the Republican nomination soap opera has been both excruciating and fascinating to watch, with the almost inconceivable notion that the Trumpster is poised to nail his party's nomination for President. Many shrieked or laughed in horror at the return of Sarah Palin yesterday, offering her support of Trump for President. This was seen as a critical step for Trump inside the party, and no doubt Sarah would love another shot at being Mrs. VP., even if once again, personal issues (this time the arrest of her son on domestic violence charges on the eve of the day she endorsed Trump, no less) continue to surround her. 

This could all be seen as a sideshow to the daily world we all live in, but one mustn't forget pricing practices and pricing wars in the pharmaceutical industry have been top-of-mind in the latter part of 2015, with the issue being escalated both into the hands of Congress, as well as being a hot topic for Democratic hopefuls Hillary Clinton and Bernie Sanders. Given that one of these two likely is the next President of the United States, the scrutiny isn't going away anytime soon. The taunting of both by a certain prominent (for all the wrong reasons) ex-pharma CEO hardly helped the situation. 

Lawmakers remain focused on addressing the issues they see, and various corporate names such as Valeant, Turing, Ovation, and Questcor (among others) have all felt some heat from Congress, which is also zooming in on the price-gouging fake pharmacy phenomenon, including the so-called "gray marketers". Valeant's affiliation with Philidor was one such relationship that came under a load of scrutiny. In terms of individuals who made the news for these wrong reasons, well, one cannot possibly forget either Martin Shkreli (Turing) or J. Michael Pearson (Valeant); the latter ending up in hospital with pneumonia and on indefinite medical leave from his post, which sort of says it all regarding his particular 2015. 

Just today in fact, I heard of the latest subpoenas to both Valeant and Shkreli, who will be forced to appear next week before the House Committee on Oversight and Government Reform regarding price-hiking shenanigans. For this one, Pearson is off the hook due to his extended medical leave, so it will be up to Howard Schiller to take the heat, and prove he meant what he said about pricing reform at Valeant during the recent JPMorgan Healthcare Conference in San Francisco. Shkreli, for his part, seems to be taking it in his stride or as seriously as ever (you can choose which!) with his usual response to the Twitterverse. 

House busy whining to healthcare reporters about me appearing for their chit chat next week. Haven't decided yet. Should I? @RepCummings

— Martin Shkreli (@MartinShkreli) January 20, 2016

One currently red hot drug development area is the immuno-oncology space, which saw some record-breaking fundraising in a dealmaking record year in 2015. Perhaps most prominent are companies like Juno, Kite, Cellectis, Bluebird, and making the news more recently was the UK's Immunocore,  which scored a European record-breaking financing round of $320M for their T-cell-mediated attack approach on cancer. This type of huge fundraising is reminiscent of North American record-breaking rounds such as Cambridge's (MA) Moderna, which raised a whopping $450M in 2015 for their mRNA therapeutic approach. In fact, since 2011, Moderna has raised an amount just shy of $1B, which is staggering. 

Speaking of immunotherapy, AmorChem bought into this overall approach early on, having invested in a personalised cancer immunotherapy program that uses minor histocompatibility antigens (MiHAs) as T-cell targets in cancer. This exciting program is about to enter Phase I clinical trials here in Canada, and we are already fielding multiple inquiries from potential partners who see the huge potential in the approach, and we are optimistic that the future for MiHA-directed immunotherapy is looking very bright indeed. Watch this space!

Although the general trend in 2015 was that big money went to many fewer players than in previous years, the upshot was that those fewer players raked in a record-breaking amount of investment. According to Evaluate Pharma, almost $9B poured into some 366 companies (US, Europe, Asia) in 2015, which is about $2B more than was seen in even 2014 by most estimates, so although the number of residents inside the bubble may have been reduced, the bubble itself not only didn't shrink (and definitely didn't burst) but actually expanded. 

Things look optimistic in spite of various challenges the pharma industry faces; such issues will probably sort themselves out in the coming year or so, once corporations find out who the next President is, and how ahead of the game they want to be in order to avoid greater scrutiny. Having said that, an industry with a global revenue stream in the hundreds of billions of dollars (and predicted to be in the trillions before very long!) is a juggernaut that barrels forward with considerable force, and even lawmakers can only hope to do so much to slow it down. Time will tell on the outcome of big pharma pricing wars and the increasing accusations of price gouging from the public, payers and governments alike. Until then, let's stay optimistic and look forward to an amazing 2016 ahead!

From the hot seat, to the cold hands of Congress, then into a warm hospital bed - a melodramatic year for both Pearson and Valeant!

The term "Happy New Year!" is primarily an optimistic one with wishes for health, happiness and success in the coming twelve months, but they take on a greater significance when one has been through (and survived!) a particularly rocky and challenging channel of raging whitewater, sliding out to still, calmer waters at the other end, "Deliverance"-style. 

Thus it has been for J. Michael Pearson of Laval-based Valeant Pharmaceuticals, who had a turbulent 2015, to say the least. However, and sadly, while he did survive the ups-and-downs of his 2015, in a business sense, it now appears that he is in a battle for his very survival with the news of his indefinite medical leave. It has been reported that he is still hospitalised with an aggressive pneumonia, and no indication of his return has been implied to date. 

The six month journey from the highs of Valeant's very own Everest - record highs for stock prices this past summer - all the way down to the lows of the latter part of the year - price gouging accusations, apparent alignment in business model with Martin Shkreli (seen by many as the Devil himself), subpoenas to appear before Congress, and the revelation of their previously hidden relationship with mail-order US pharmacy Philidor - was clearly an extremely challenging one, and one that took a serious toll on "Big Mike".  

The Pearson name has become synonymous with that of Valeant and mid-last year it would have seemed inconceivable that a three-man "Office of the CEO" executive committee would be in place to run the company a mere six months later, and worse, today, that a new interim CEO has been put in place to take over from that executive committee. While it appeared that investors took some comfort that it was trusted former Valeant CFO Howie Schiller (along with Robert Ingram taking over as Chairman of the Board) who was returning to take the helm, not everyone kept smiling. 

One of the most prominent investors involved in Valeant's acquire-and-hike (or acquire-and-slash) approach - no, wait, the most prominent investor in the entire story - Bill Ackman, no less, didn't seem that comforted. He has been one of Pearson's and Valeant's most staunchest allies, and it was Ackman who heavily co-drove the move for Valeant to swallow up Allergan in 2014, and even after that failed he remained firmly on board. 

In fact, even while criticising them for having a "public relations problem", he increased his stake in Valeant! So the recent news that Ackman sold off a swathe of Valeant stock on the last trading day of 2015 seemed a touch ominous. The New Year's Eve date could be seen as simply a tough decision put off until the very last moment possible, if one is kind, or rather it was a move to use the hullabaloo associated with the 31st of January date as a smokescreen and distraction, if one is cynical. 

Ackman's Pershing Square sold off some 5 million shares, reducing their stake in Valeant from 9.9% down to 8.5%, which is hardly deserting the sinking ship, but still. Ackman weathered all the other storms and stood firmly behind Valeant, or maybe more fully behind Pearson, during what was one tumultuous 2015. But perhaps the fact that he is not as confident about a Valeant led by someone other than Pearson caused him to moderate his exposure a little. Anyway, the story goes that he sold off to help generate a tax loss for investors in his on-shore holdings, and it seems he is sticking to that story - for now. Pershing Square and its investors lost billions on Valeant by year's end, so Ackman probably had to do something. 

It is unquestionable that Pearson has done big things for Valeant and most certainly raised their profile (albeit not always for the right reasons) along with their stock, but as Martin Shkreli found out, it's simply not true that any publicity should be considered good publicity. "Talk about me - good or bad, it doesn't matter - as long as you are talking about me", as a certain well-known senior scientist used to say to me from time to time. While that might work for a senior academic scientist or the CSO of a private biotech company, it works less well for the boss of an extremely public company, with a board, investors, the public and even Congress all breathing down your neck! 

Adding some salt into his current wounds comes the news that the particularities of Pearson's contract mean that if he walks away for medical reasons, he will lose his golden parachute. That's close to $10M, right there! On top of that it is estimated that such early departure, as opposed to sticking around long enough to see the stock recover and rebound by around 2020, could cost him as much as hundreds of millions of dollars in stock-as-compensation when they vest. There's no doubt that it is in his best interest to return to Valeant, pronto, before someone else starts steering the ship in directions new; directions which may send stock soaring once more, and it is very hard to remove even an interim head coach or quarterhack, when they are on a brash winning streak. 

Well, it is a new year, and if we take our business hats off for a moment, I think everyone would agree that we can't wait to hear that Big Mike is out of hospital, back home, and on the mend. When he is fully recovered, and if he returns to the helm, he has another very challenging year ahead. One major hill he will have to climb is repairing the damage to the company's reputation that occurred in the latter half of 2015; he will also have to repair the damage to the share price (from $260 in high summer down to $101) that also occurred in the latter half of 2015.

He is probably more than capable of correcting the latter - he's done it before - but whether he can impact the former (and some would say that requires a new face at the helm) remains to be seen. But we wish him well and we all will be watching his 2016 very closely indeed!