After all the ballyhoo, it's now toodle-oo to Yahoo!

Back in February of this year, I did predict that Verizon would be a likely top two or final candidate for the acquisition of that tired old dinosaur Yahoo!, and I also stated that even an apparently paltry offer of $5B would have to be taken seriously. No surprise at all to this boy, therefore, that Verizon has indeed acquired the core operations of Yahoo! for a mere $4.8B; for contrast, people, don't forget that this behemoth was once valued at over $200B, and several years ago Yahoo! rebuffed a $45B offer from Microsoft! 

Seeing an Internet pioneer and giant stumbling and falling amidst a rapidly evolving and increasingly competitive ecosystem has not been easy to watch, but in business it is the law of the jungle, and I for one am glad to see the weary, beaten-down beast lying on its side struggling to even breathe while being poked and prodded by passing predators, finally being put out of its misery. It was the only and right thing to do. It had come such a long way from two Stanford PhDs dreaming big in the early days of the earth-changing "world wide web", but ended up as a geriatric has-been, out of fashion, out of touch, and out of time.  

Naturally, the spotlight shines brighter than ever on Google employee #20, and where she goes from here. I think it's a pretty safe bet that she's history, even if rather typically, she is announcing that she's going nowhere and will stay on to finalise the transaction, if nothing more. I am not sure that's a good idea at all, but she has been stubbornly refusing to face reality at Yahoo! for yonks now, so what's six more months?! And the estimates of her ultimate payday ($12M odd at the bottom end, $55M at the mid-zone, and over $120M at the top end) all ensure she will rake it in even after her performance was rated to be sub-par, over and over and over. 

Honestly, the best thing that Tim Armstrong (ex-AOL, and also a former Googler) could do for her, is to talk to the board and arrange her golden parachute, pronto. She failed, let's be frank, and having her around as the beast is now carved open and ripped apart into multiple reusable limbs, is just prolonging that failure and is not going to feel like a fresh start (or fresh anything) for those that are being kept around. Let it go, and let her go, Verizon! 

I actually think she is guilty of hubris at this point, point-blank refusing to walk away from what the entire industry views as an abject failure for a CEO, seemingly hoping that she can somehow rewrite her story in the remaining few months of electronic access to the building, such that she can maybe come out of it looking rosier. Even if the transition from a Yahoo! into a Verizon goes wonderfully, what kind of CV booster is that likely to be? She has got to let go, now; going off on "gardening leave" would be way smarter!

Not unsurprisingly, but rather uncommonly, Ms. Mayer has done some moaning of late about her current predicament, going as far as to accuse the media of gender bias in a recent Financial Times interview that followed the sale of Yahoo!'s core business. It's somewhat ironic in that just a year ago in another interview she stated clearly that gender was not an issue for her as a tech-geek CEO. Perhaps she means that the (sexist) media enjoy seeing women fail, even if that same media did help build her up?!

Just like in Hollywood, you can't have it both ways. If one uses (perhaps even shamelessly) the paparazzi and TMZs of the world to grab attention for oneself as an unknown wannabe, then when one makes it to the big time, one cannot possibly hope that the privacy-invading predators are not going to be following one, 24/7, right? Live by the sword, die by the sword, and all that jazz. 

Now, I have no intention of turning the Yahoo debacle into one of gender bias (Ms. Mayer did that!) and I think it is highly inaccurate to do so. While I agree that life for a female CEO in tech or business cannot be easy, the individual who makes it should normally have seen it all and dealt with it all, if they got there for the right reasons based on both solid experience and stellar performance. So why moan only when it hasn't gone your way, even if being feminine was not an issue in earlier dealings with the media?

Ms. Mayer's provocative pose/photo that adorned the cover of Vogue in 2013 is anything but the typical shot of any male CEO, so she wanted to be seen as different, right?! The shot certainly has more to do with fashion and style (and femininity) than it does tech or business or Yahoo! And why would the CEO of a Yahoo! ever be asked to be on the cover of a Vogue (as opposed to Businessweek or FT)), unless she was known as the epitome of high fashion? Hardly the case for Ms. Mayer, at all. 

If I think of two recent and very prominent in-the-news female CEOs of our time, it would be Mayer and Elizabeth Holmes of Theranos. While I am not truly in a position to ascertain whether the media apparently enjoy their slide to ignominy because of their gender, I think it's the case that the media elevated them above their male counterparts, in many, many ways., in the first place. That's fair enough, as there are so few female CEOs in the tech world, or even business in general. A mere few percent of Fortune 500 companies are led by women, in fact. 

So I think it kind of balances out: the media may gush more over prominent female CEOs when they first make it, but unless one rejected the attention and glossy fashion magazine covers on offer, one shouldn't moan about "gender-charged reporting" (Mayer quote) on their writing of one's failure. Schadenfreude has been around for a while, and I don't think it is gender-specific; rather, it's human-specific!

Mayer and Holmes were darlings of both the media and their boards, alike, and each CEO should have been ousted a long time ago. I honestly feel that a male CEO would have been removed sooner, in each case, especially as they are both still sitting CEOs who have everyone except their boards asking for their heads. In the end, it was the boards who remained starstruck even in the face of evaporating value and imploding scandals, respectively. They are responsible ultimately, and it is to them that shareholders should look to for fault. 

Marissa Mayer's failure to turn around Yahoo! had nothing to do with her being a woman. Just as her being a woman had nothing to do with her being hired by Yahoo!. She failed because she never should have been hired in the first place. Being Google employee #20 and a talented product engineer/manager does not a CEO make, particularly of a (struggling) giant such as the behemoth that now was Yahoo! She transparently refused to face reality, repeatedly, and the board correspondingly refused to face her/their reality, repeatedly. It was a most unhealthy combination and outcome. 

It's far from clear if anyone could have turned it around, but failing at doing so at Yahoo! has tarnished her reputation, and should serve as a warning sign to those considering taking the helm at dying public companies. It must be very tempting being offered the top slot at some huge corporation (primarily due to one's star power rather than previous relevant experience) but if one says yes to an impossible task in return for a bucketload of cash, then one can be left with just that, a bucketload of cash, at the end, when one fails. 

But to each their own; maybe a bucketload of money is enough to make up for being blamed for tanking a legendary company, and the clinging tarnished reputation and subsequent career crater are just the ultimate means to an end? Mayer sails off richer than ever, as the Yahoo! brand is evaporated into the vapour trails of Internet history. 

[PS - For those that are wondering, the blue upside-down dress in the photo above is a Michael Kors number!] :)

CIHR - Chaos in Health Research?!

Having spent centuries (well, okay, decades - but it felt like centuries!) at the bench in academic and biotech laboratories, and currently being in a position to invest in transformative research in universities, if there's one thing one gets used to it's listening to griping about having to write grants, the outcome of such applications, and even tales of doom and gloom about the entire process itself. That's business as usual in academia. 

However, of late, there have been much more turbulent rumblings and aftershocks over dysfunction at the Canadian Institutes of Health Research (CIHR), the $1B agency to whom Canadian researchers look for funding primarily of their basic research programs. Such dysfunction has led to usually behind-the-scenes scientists risking their neck by speaking out about the problems, demanding changes. 

It takes a deep breath to stand up and shout out that CIHR is screwing up, when one's own laboratory and future may in large part be dependent on CIHR funding - but that's exactly what some scientists are doing - which inandof itself is a sign of how desperate the situation has become. Back in 2015, stem cell bigwig Michael Rudnicki did just that, going as far as to suggest that not only should heads roll at the agency but that Alain Beaudet, its president, should be replaced. 

“I can tell you that the vast majority of Canadian scientists think Alain Beaudet should be replaced with more progressive leadership."

This is a highly vocal and unusual move to bite the hand that feeds one, but it seems that he has the backing not only of some very prominent Canadian scientists,  but the rank and file as well. In fact, in many ways it is the rank and file (more junior, less well established researchers, and female scientists, in particular) that have been hit hardest, and it is only right and proper that some big names step up to the plate and lend their weight (and relative security) to the debate.

 

Daniel Durocher‏@durocher1

Daniel Durocher Retweeted Jim Woodgett

There has to be accountability for this catastrophe. The honorable thing is for A. Beaudet to resign.

Daniel Durocher added,

Jim Woodgett @jwoodgett

Now results are released, there needs to be an external investigation of CIHR Project Scheme. It’s done, but this can never be repeated.

This recent exchange on Twitter between one of the story's top protagonists (big Jim Woodgett) and a (relatively) more junior (but no less highly esteemed) colleague, both of Toronto's Lunenfeld-Tanenbaum Research Institiute, is quite telling indeed. Both individuals have done rather well in Canada's research system, but both are quite clearly outraged by what has transpired at the hands of Beaudet, who by the way had his positioned renewed for five more years by the exiting Harper government last April. 

Such conversations were of course commonplace back in the day, but that was back in the day before social media existed and one's comments were essentially coffee area chatter, and anything but public. In today's world things have changed, and scientists (perhaps unexpectedly but not totally surprisingly) are not only on social media, but are using such platforms to reach out, vent or even to rebel, for the whole world to see. 

Beaudet's reforms, particularly the change-up of the classic (beloved?!) peer review process, are viewed by almost one and all as an unmitigated disaster. Under enormous pressure recently, due to a massively supported open letter to Health Minister Jane Philpott from Woodgett and some 1300 scientist supporters, CIHR agreed to meet with Canadian researchers to hear their concerns. But somehow, Beaudet's statement that "CIHR cannot be successful unless it has the confidence of Canadian researchers" comes across more as a swansong (if not an outright admission of defeat) than anything else. 

"Them's retirement words, buddy!"

As if removing the face-to-face aspect of peer review was not bad enough, and with grant success rates hovering around the 15% mark, CIHR rather unbelievably added more salt to the wound and more saltpetre to the flames this past week with yet another simply shocking screw-up. Last Thursday CIHR released results (a day early) on its website for a recent competition, but while informing various scientists of the funding decision, they also named the reviewers of those grants and revealed confidential comments they had made; this  might even be an inglorious first in CIHR history, but even (or especially) if it's not, it is one contemptible cock-up. 

This monumental blurting out of confidential information will probably have more impact in Canada than Hillary Clinton's personal email server had on the United States! Complete anonymity is vital to the peer review process for both grants, and publications arising thereof, and now both the grant reviewers and the scientists they commented on know that the other knows.  You can just imagine the repercussions of that, and how it compromises the integrity and functionality of the CIHR reviewing and granting process. 

What is there left to say? I don't hear anyone defending CIHR, or Beaudet especially, for whom the writing must surely be on the wall. If you lose the support of the scientific community, whose research is funded by taxpayers, and those scientists are taxpayers themselves, and things go from rumblings in the dark room all the way to social media and onto public forums and letters to the health and science ministers, then the government simply has to step in and realign the use of hundreds of millions of dollars of taxpayers hard-earned money with the values and ambitions on which that government was elected. Trudeau's - not Harper's! 

Trials and tribulations of CAR-T cells - too much, too soon?!

Immunotherapy is revolutionising the world (of cancer) as we know it, and unquestionably, huge progress has been made by targeting the checkpoint inhibitor pathways and retooling the immune system to attack instead of ignore tumour cells. This is an approach that is spreading across the field of cancer, and is quite literally changing patient lives in a most hopeful fashion.

Further elaboration of such immunotherapy is to extend it to actual whole cells of the immune system, modifying them outside of the body, and then reintroducing them again to seek out and destroy the cancer nemesis. It's a fascinating concept in this brave new world of rapidly changing modern medicine, but as exciting as the few positive outcomes observed thus far are, we don't know as much biology as we would love to and it remains a dangerous game. 

This was emphasised in the past week with the news that the FDA had halted Juno's CAR-T trial (ROCKET) for patients with adult lymphoblastic leukemia (ALL) in response to the tragic loss of three patients enrolled in the study. It's a crushing blow for Juno who have JCAR015 lined up as their first product to market, and that's on hold now. They are not alone in the CAR-T race, with Cellectis, Kite and pharma giant Novartis all pushing hard. 

The word "game" used above in a non-literal sense is however an appropriate one, because in many ways the biotech space has been seen somewhat as a sport by both investors and many executives alike, in that it's all about creating (even perceived) value and then choosing the right time to jump ship with the spoils, before the ship sinks or just floats off into oblivion, adrift. It's a game many have played, but once you get to clinical trials and begin to hear of people dying as a result of the therapy that's supposed to treat (and ideally cure) them - it suddenly becomes very serious business indeed. 

For their part, the ~$4B biotech Juno have been very quick (some say, too quick) to come out with an explanation, and an eagerness to continue the trial after modification of the protocol. The offending component, they say, was the inclusion of the chemotherapeutic agent, fludarabine, added in after the trial had begun. This agent is an extremely potent lymphodepleting drug and Juno believed that it would further help the seeding and expansion of their modified T-cells after introduction into patients. 

However, after three patients died with cerebral oedema, there was no choice as far as the FDA was concerned but to put a clinical hold on the trial, which had some 20 patients enrolled with closer to 100 planned. Juno's CEO Hans Bishop was quick to state that they know what the problem was - fludarabine - and that they will stop using it and go back to using cytoxan, which had proved very efficacious in a previous JCAR015 trial run at the Memorial Sloan-Kettering Cancer Center. 

It does sort of beg the question as to why they did not just settle for cytoxan, which works, instead of endlessly trying to better previous results by changing-up protocols. But it seems that Juno have used fludarabine very successfully with JCAR014 and JCAR17 in other indications, which prompted the move. In any case, Juno will rapidly respond to the FDA, including submission of a new investigator's brochure for JCAR015, and Bishop appears confident that they will be back on track shortly. The markets were not quite as sanguine, with a 28% drop in share price inside a few days. 

I haven't read all the news articles on this subject as yet, but I have to say that from those that I did see, I couldn't help but feel that Juno, and Bishop in particular, are in too much of a hurry to please investors and appease the FDA, with a shockingly business-like attitude to the human beings lost in their trial. Now, I am acutely aware of the fact that these patients were very ill already, and that life must go on even in the face of death, but when it is your treatment that terminated those lives prematurely?! Showing sensitivity and compassion is not a sign of weakness, particularly when you are 100% responsible, and Juno's urgency to blame fludarabine and race onwards into the ROCKET trial appears hasty to some, if not many. 

This is groundbreaking science that we are talking about here, and Juno do know more about it than most, investing heavily in understanding the biology, as well as having some eight CAR-T programs in their pipeline. While death is part of life in cancer trials, particularly those that use such revolutionary new treatments, safety for the patient must remain an absolute priority, and one must never get too used to seeing patients die, and one simply must suitably acknowledge and respond to the unquantifiable loss of patients who die as a result of that treatment. 

This brave new world of science fiction-like science as modern medicine makes for massive leaps forward, but those leaps are often deep into the dark and further into the unknown. As much we do know, human biology remains remarkably complex, and running before we can walk can be a case of putting the CART before the horse. The patients that died are heroes for the cause, and what is learned from their tragic loss must be credited to them, even (or especially) as champagne is corked upon later successes.  

Rushing things is not always productive, and slowing down to consider all the possibilities before proceeding further might be a better way to go. Speed may be a key driving factor for investors, boards and executives alike, but dropping down a gear (or two!) can be educational, ultimately benefiting both patients as well as relationships with regulatory agencies.  But kudos to Juno for how far they have come in developing T-cell therapies to date, and let's hope they can jump this hurdle with not just the necessary scientific rigour but also while exhibiting the appropriate level of class.   

[PS - Just prior to the publishing of this blog, and still only mere days after the Juno disappointment, Kite Pharma announced enrollment has been completed for a Phase II (ZUMA-1) trial of their CAR-T candidate, KTE-C19, Rather remarkably, their regimen includes fludarabine, which surely will raise some eyebrows given the Juno outcome.]

[PPS - Just after publishing this piece, and mere days after the clinical hold by the FDA, Juno got what they wanted, and the hold was lifted so the ROCKET trial can continue with no further use of fludaribine - that was rocket-like fast!]