Social media depend on an engaged society - now they might just make us healthier in return!

As far apart as the technological worlds of social media and drug discovery may well seem to be, there is a new trend that marries the vast wealth obtained by pioneers in the former to funding the forefront of the latter. When we consider the dizzying digital world that we now live in, trying to remember what life was like before email, social media and smartphones, well, somehow all roads tend to be lead back to that single word and entity - Facebook. 

Things have changed, of course, and today Facebook's biggest challenge has less to do with connecting people both locally and globally, but given that they are a publicly traded company, they have to make enough money to keep the boardroom and shareholders happy. In that vein, Facebook is as much an advertising and marketing tool today for many companies, rather than simply a social media outlet. Monetizing Facebook, particularly on mobile, has been one of Mark Zuckerberg's greatest challenges, and by all accounts he is doing rather well at it; even if their monetization strategy has not always been clear. 

Irrespective of how Facebook founders intend to continue to make money, the clearest thing about them is that they are already incredibly wealthy and are generously spreading some of that wealth into the healthcare arena. Peter Thiel, the legendary investor who discovered Facebook, has put cash into some 25 biotech start-ups to date. Sean Parker (famously played by Justin Timberlake in the movie) made a donation of some $24M a while back, to found the Sean N. Parker Center for Allergy & Asthma Research at Stanford University, which is one of the biggest private donations for allergy research ever in the USA. 

Further, just this summer, it was announced that Parker would be funding the first ever clinical trial of the controversial gene-editing technology known as CRISPR, as part and parcel of his Parker Institute for Cancer Immunotherapy - an initiative that involves six leading cancer centres - spanning some 40 laboratories and more than 300 researchers all focused on immunotherapy. He will shell out an extremely cool $250M on that one!

Given such contributions, and the humanitarian efforts of other technology pioneers and social leaders such as Bill Gates, well, it was inevitable that it would draw other big dogs to the table. Ergo, and to wit, the announcement this past week that Facebook CEO Zuckerberg and his wife, pediatrician Dr. Priscilla Chan, were donating a massive $3B to "cure, prevent or manage all disease within our children's lifetime."

That is an ambition as equally massive as their donation! That amount, coming from a private couple, is probably one of the biggest medical research donations ever, anywhere, and if any kind of "sibling" rivalry between Parker and Zuckerberg helped fuel that monster donation, well, researchers and clinicians are not going to complain about it! $600M of that money will be doled out over the next decade under the auspices of the Chan Zuckerberg Initiative which intends to invoke a multidisciplinary approach in addressing human disease. 

You know, as scientists we tend to snigger at over-hyped announcements by tech execs claiming they will "eradicate" or "cure" this disease or that disease or even all disease, as if money was the only object in the way.  It is a major obstacle, yes, but if that was the only thing in the way, then we would have cured HIV and cancer already, right? Entities like Microsoft and Facebook tend to face some backlash for over-hyped claims of how they will set medical research on the right track, as if having a PhD or MD and a decade's laboratory experience has little to do with it. 

But in this case it is worth pointing out that Zuckerberg is talking "patience" and the idea is to achieve the Initiative's goals over the next century (yes, 100 years!) and they are not claiming that they will cure cancer in a mere handful of years. The media laps up major donations from big Silicon Valley names such as the Chan-Zuckerbergs, and it is often they, not the donors, who inflate the story into a de facto mission impossible. Doomed from the start, by all the hype. 

Having said that, they have chosen a bigtime neuroscientist as the President of the new venture, none other than Cori Bargmann, who is currently a professor at Rockefeller studying C. elegans neurobiology. This coupled with oversight from a stellar scientific advisory board should pave the way to some big science, which according to Bargmann, will incorporate academia, biotech and engineering. 

Social media have been very pervasive in our lives, it's almost impossible not to have been touched by them in some way today, and another most pervasive aspect of daily life is human disease; so in many ways the application of the successes of one technological advance that depends on society's involvement towards the ongoing health of that society somehow seems entirely appropriate.

The Chan Zuckerberg Initiative is an extremely admirable one, and you can be sure that I will be watching and commenting on it as things roll out and develop, and hopefully one day we will be discussing the solving of a major health problem for mankind. I just hope that it's not in the latter part of that 100 years, because by then this blog (and I) will he dead and buried - and probably the Chan-Zuckerbergs as well! ;)

One big Go CAR-T less in the vigorous race towards T-cell immunotherapy?!

These days barely a week seems to go by without some big news on the CAR-T front, and given the complexities in manufacturing/production of a distinctly personalised T-cell medicine, it is not surprising that the news is more often bad than good. That's pretty much par for the course for the evolution of a truly groundbreaking new therapy, and it is still advancing at a rather incredible rate!

After recent events that have included the clinical hold placed on Juno's Phase II trial of JCAR015 by the FDA, well, things have been a little shaky. The death of three patients under 25 was subsequently ascribed to the combination of fludaribine into a regimen that previously used only cyclophosphamide for pre-conditioning, though Juno's proposal to restart the trial using only cyclophosphamide was extremely rapidly approved by the FDA. 

Some believe that it was too rapid a turnaround given the deaths, but Juno executives appear to have been extremely persuasive in their arguments, and the shares that had plunged on the bad news soared back up once more when the clinical hold was lifted. The FDA is not known for being particularly expeditious or pharma-friendly especially when people are dying in clinical trials, so the mere days required to get the clinical hold lifted are indicative of a collective enthusiasm at the agency to get this novel treatment tested and approved - apparently, at least.

Not long before the Juno problems, top competitor Kite announced that the NIH were going to review their cell therapy manufacturing facilities at the National Cancer Institute, even if such intervention was not anticipated to impact their pivotal multi-centre Phase II trial of Kite-C19 CAR-T product. However, they were not permitted to enrol more patients until such review will be completed, and the ecosystem bristled at the prospect of more bad news. 

On top of all of this came the somewhat stunning news last week that pharmaceutical giant Novartis was "pulling back" from the forefront of the CAR-T race, and would be disbanding the cell and gene therapies unit (CGTU) that was behind their CTL019 treatment, currently in Phase II clinical trials. While this might have seemed a natural step to take if they were announcing it as an aspect of their success in having jumped all of the manufacturing hurdles and having flown threw the various regulatory hoops, in actuality this was hardly the case. 

Au contraire, in fact. First came the news that 120 workers at CGTU were being axed, with the pharma stating that the rest of the outfit was simply being reintegrated back into the mothership as part and parcel of their immuno-oncology division. That sounds truly bizarre to me; take something that is as unique and uniquely challenging as manufacture of CAR-T therapeutics, back out of a specialised unit charged with so doing, and stick it right back into the pharmacological parent giant from which it was extruded in the first place? Right in the middle of critical clinical trials? Things that make you go "hmmm"!

Next came the news that it wasn't just laboratory hands that were being let go, but the bulk of the senior executives running the cell therapy unit were also being axed, and that doesn't sound optimistic at all. The job is not done, as far as we are aware at any rate, and why would you not let the team stick around to at least get credit for successfully applying for an NDA and having CTL019 approved for marketing?! Apparently that's not to be, as outlined in a leaked memo from Oz Asam himself:

"Unfortunately a number of colleagues will be impacted by this change as many positions are being eliminated. Impacted US-based associates are being notified in meetings today. Associates based in Basel will learn more about their individual circumstances on Thursday. The majority of the CGTU Leadership Team members, who are among the best I have worked with, are also impacted."

"Among the best that I have worked with" yet you are eliminating them? Are you kidding me? Especially given that Novartis restated their commitment to CAR-T technology and that they intend to file with the FDA in early 2017 and with the EMA later the same year? They are either confident that the job is done and no more tweaking will be needed or they know something that we don't. Rumours that some of the 120 axed job are based at their 173,000-square-foot manufacturing facility in Morris Plains, NJ, are hardly comforting in that regard.  

So what is it that Novartis might know that we don't? At worst, one could imagine that there is extremely bad news coming out of their current clinical trials, and Novartis is preparing their exit bit-by-bit, in advance, to soften the blow when the hammer falls. They have invested heavily already, including $43M for the ex-Dendreon facilities in Morris Plains, but why put more good money after bad, if the news is indeed bad? A scary prospect! 

Honeslty though, I don't think that's it. My take on it is that Novartis have been somewhat rocked by the recent turbulence in the field in general, and probably have come up against technical issues or clinical challenges that have convinced them that CAR-T might be too great a developmental and commercial challenge today. Given the equally turbulent political arena in the USA (hell, everywhere!) right now, and the heavy-duty governmental surveillance of the drug pricing wars, well, this could be another factor that might force a serious reconsideration of the commercial prospects for such a personalised medicine. 

CAR-T manufacturing is a much more 24/7 complexity-filled process than producing tablets or even a routine (today) biologic such as a monoclonal antibody. It is clearly a high-risk venture, and in many ways, that may define it as something that only large biotech should take on and hurdle, given their increased capacity (hunger?) for such risk. Pharma tend to be more conservative, and there's not much about CAR-T therapy that aligns with with the word "conservative". 

One pharma's loss is another pharma's gain, and even though he has nothing but respect for Novartis, Kite's Arie Belldegrun clearly sees added opportunity in the reported Novartis withdrawal from the CAR-T race. Ditto Hans Bishop at Juno, although Beldegrun stated that Kite has gotten both the number of cells infused and the doses of both chemotherapeutic agents (fludaribine and cyclophoshamide) worked out so as to avoid the problems experienced at Juno. So maybe Kite has the edge, in September, 2016. 

I quote the month, above, because things are moving, shaking and changing on a monthly basis in this horse race to the finish line, and who knows what will happen next? Speaking personally, it is now time for this horse to put the car-t behind him, get out into the fresh air of a blustery, autumnal Sunday morning and put in some solid laps on the racetrack of Molson Stadium! 

One big Go CAR-T less in the vigorous race towards T-cell immunotherapy?!

These days barely a week seems to go by without some big news on the CAR-T front, and given the complexities in manufacturing/production of a distinctly personalised T-cell medicine, it is not surprising that the news is more often bad than good. That's pretty much par for the course for the evolution of a truly groundbreaking new therapy, and it is still advancing at a rather incredible rate!

After recent events that have included the clinical hold placed on Juno's Phase II trial of JCAR015 by the FDA, well, things have been a little shaky. The death of three patients under 25 was subsequently ascribed to the combination of fludaribine into a regimen that previously used only cyclophosphamide for pre-conditioning, though Juno's proposal to restart the trial using only cyclophosphamide was extremely rapidly approved by the FDA. 

Some believe that it was too rapid a turnaround given the deaths, but Juno executives appear to have been extremely persuasive in their arguments, and the shares that had plunged on the bad news soared back up once more when the clinical hold was lifted. The FDA is not known for being particularly expeditious or pharma-friendly especially when people are dying in clinical trials, so the mere days required to get the clinical hold lifted are indicative of a collective enthusiasm at the agency to get this novel treatment tested and approved - apparently, at least.

Not long before the Juno problems, top competitor Kite announced that the NIH were going to review their cell therapy manufacturing facilities at the National Cancer Institute, even if such intervention was not anticipated to impact their pivotal multi-centre Phase II trial of Kite-C19 CAR-T product. However, they were not permitted to enrol more patients until such review will be completed, and the ecosystem bristled at the prospect of more bad news. 

On top of all of this came the somewhat stunning news last week that pharmaceutical giant Novartis was "pulling back" from the forefront of the CAR-T race, and would be disbanding the cell and gene therapies unit (CGTU) that was behind their CTL019 treatment, currently in Phase II clinical trials. While this might have seemed a natural step to take if they were announcing it as an aspect of their success in having jumped all of the manufacturing hurdles and having flown throw the various regulatory hoops, in actuality this was hardly the case. 

Au contraire, in fact. First came the news that 120 workers at CGTU were being axed, with the pharma stating that the rest of the outfit was simply being reintegrated back into the mothership as part and parcel of their immuno-oncology division. That sounds truly bizarre to me; take something that is as unique and uniquely challenging as manufacture of CAR-T therapeutics, back out of a specialised unit charged with so doing, and stick it right back into the pharmacological parent giant from which it was extruded in the first place? Right in the middle of critical clinical trials? Things that make you go "hmmm"!

Next came the news that it wasn't just laboratory hands that were being let go, but the bulk of the senior executives running the cell therapy unit were also being axed, and that doesn't sound optimistic at all. The job is not done, as far as we are aware at any rate, and why would you not let the team stick around to at least get credit for successfully applying for an NDA and having CTL019 approved for marketing?! Apparently that's not to be, as outlined in a leaked memo from Oz Asam himself:

"Unfortunately a number of colleagues will be impacted by this change as many positions are being eliminated. Impacted US-based associates are being notified in meetings today. Associates based in Basel will learn more about their individual circumstances on Thursday. The majority of the CGTU Leadership Team members, who are among the best I have worked with, are also impacted."

"Among the best that I have worked with" yet you are eliminating them? Are you kidding me? Especially given that Novartis restated their commitment to CAR-T technology and that they intend to file with the FDA in early 2017 and with the EMA later the same year? They are either confident that the job is done and no more tweaking will be needed or they know something that we don't. Rumours that some of the 120 axed job are based at their 173,000-square-foot manufacturing facility in Morris Plains, NJ, are hardly comforting in that regard.  

So what is it that Novartis might know that we don't? At worst, one could imagine that there is extremely bad news coming out of their current clinical trials, and Novartis is preparing their exit bit-by-bit, in advance, to soften the blow when the hammer falls. They have invested heavily already, including $43M for the ex-Dendreon facilities in Morris Plains, but why put more good money after bad, if the news is indeed bad? A scary prospect! 

Honeslty though, I don't think that's it. My take on it is that Novartis have been somewhat rocked by the recent turbulence in the field in general, and probably have come up against technical issues or clinical challenges that have convinced them that CAR-T might be too great a developmental and commercial challenge today. Given the equally turbulent political arena in the USA (hell, everywhere!) right now, and the heavy-duty governmental surveillance of the drug pricing wars, well, this could be another factor that might force a serious reconsideration of the commercial prospects for such a personalised medicine. 

CAR-T manufacturing is a much more 24/7 complexity-filled process than producing tablets or even a routine (today) biologic such as a monoclonal antibody. It is clearly a high-risk venture, and in many ways, that may define it as something that only large biotech should take on and hurdle, given their increased capacity (hunger?) for such risk. Pharma tend to be more conservative, and there's not much about CAR-T therapy that aligns with with the word "conservative". 

One pharma's loss is another pharma's gain, and even though he has nothing but respect for Novartis, Kite's Arie Belldegrun clearly sees added opportunity in the reported Novartis withdrawal from the CAR-T race. Ditto Hans Bishop at Juno, although Beldegrun stated that Kite has gotten both the number of cells infused and the doses of both chemotherapeutic agents (fludaribine and cyclophoshamide) worked out so as to avoid the problems experienced at Juno. So maybe Kite has the edge, in September, 2016. 

I quote the month, above, because things are moving, shaking and changing on a monthly basis in this horse race to the finish line, and who knows what will happen next? Speaking personally, it is now time for this horse to put the car-t behind him, get out into the fresh air of a blustery, autumnal Sunday morning and put in some solid laps on the racetrack of Molson Stadium! 

After the joys of summer have gone....

Well, as far away as it seemed back in gloriously early June, here we are once again at the Labour Day long weekend, which both unofficially and officially signals the end of the summer. Or the end of the summer as we know it and I (don't) feel fine, to paraphrase a certain musical voice from Athens, Georgia. 

Even though it's been a long time since the end of summer held its prior darker meaning in our lives, i.e. the dreaded loss of freedom that was the return to schooldays and homework, the end of summer still tends to draw wistful sighs from one and all, and a yearning to go back to the start again. It's not that different from how many feel on a Sunday afternoon and evening after a weekend of freedom, in their adult lives! 

Some of this is just conditioning and comes from deeply ingrained memories from our childhoods, I feel. As a kid growing up in church-dominated Ireland, for example, there was a (un)holy doom and gloom that clung to Sundays like white on rice, and almost nothing could shake it off. Even when we did have a long weekend or were on never-ending lazy summer holidays, with no school on Monday, there was still a blackness oozing out of every empty closed shop that was matched only by the color of the priest's robes at the front of the packed pews. 

I can still smell the hissing starchy steam of my mother's iron pressing on the ironing board on dark, wet Sunday afternoons of childhood, with nothing to rescue me from either gloomy Sunday or the looming Monday ahead. As distant as that reality has become today, the steam apparently has still not evaporated from my senses! Maybe I should simply let off some steam?!

Was there ever anything as desolate as grey, wet street corners in a small Irish town on a Sunday afternoon, we would ask. For young teenagers it felt like death itself and we were jealous of adults for once in our lives because they got to get up on Monday morning and escape the house and go off into town and see their work pals, while we got securely shuffled off to prison for another week of indoctrination and rigorously scheduled shuffling around from one (padded) cell to another. 

Imagine if we had known back then, that we were destined to live the same thing for the next 50-60 years?! For many, I guess that's exactly how it feels, and that's got to be one rough life, living and working just for Friday night and Saturday, and then the dread of Sunday evening or end of summer comes along and the stress levels start to rise again. But you know, even those of us who are lucky enough to love our jobs still carry part of that longing in us, which resurfaces on Labour Day or on occasional Sunday nights; the question is why?!  

As I said, certainly for an Irish schoolboy (or girl!), a lot of it is simply permanently etched into our souls and muscle memroies that Sunday was a day as boring, bleak and black as sin itself, and nothing could be done about it. For us adults, with all of our experience, we know that not to be the case even if we still get the Sunday blues occasionally, and you know, I think that just stems from our innate desire to be free. We are free, in so many interpretations of that word, but we are not free to just go off and walk around the lake on Monday after a nice breakfast in town. 

Much as we do love our job and our work, there is a building desire to be set free, particularly as the number of years left falls below the number of those that have already been lived, and that is probably entirely natural. To rub against the grain, and kick against the fray, to rebel, and refuse to go to the office on Monday morning, instead heading for the hills without a worry in the world and embracing freedom - it's a lovely thought - but we would probably get anxious by early afternoon. 

I often think it might only take a few days or at most weeks of kicking against the fray and playing hooky to remind us of precisely why work is so important in our lives. We derive so much more out of it than our salary, and that is often overlooked when we are facing a tough week ahead on a Sunday night, or are dreaming of never going back again. Last week I chatted with a guy who apparently had and has it all - retired by 52 and free as a bird - and when I pushed him for how he feels about it today, his answer surprised me. He wishes he hadn't -  retired - and feels that 52 was too young. What are you supposed to do when you don't have to go to school but all of your friends are incarcerated there?!

As precious as our weekends, and our holidays, and our summers truly are, we enjoy them all the more because we work the rest of the time, at least in part, to be able to afford and enjoy those precious free hours. To see life through the other side of the coin, from someone who is free to enjoy every day as a free man in Paris (evoking a certain billionaire entertainment mogul seen through the eyes of a legendary Canadian songstress) and who, well, seemed kind of bored, most definitely opened my eyes up to the "free"  life. 

Yes, if you have enough money to do anything/everything you want, then being free all year probably is a great experience. But even then, after a year or two, most of us would return to "what's the point?" Overall, we already have (close to) the right balance, because in the end nothing beats jumping out of bed to go off to do work that stimulates and challenges us, and that produces something that we believe in. That is the holy grail, when it compensates you by providing a lifestyle that is both comfortable and rewarding at the same time. 

So, on this gorgeous (again!) Sunday morning of Labour Day weekend, there are no blues on this street corner, or in this summer office, but rather a most definite sense of freedom that I can stay in bed a little later this Monday morning and Labour Day, and then when Tuesday morning rolls around and I am due back in the office for work, I am going to consider myself one of the lucky ones to be able to go do so. Summer might be (almost) over, but it's going to be an awesome Autumn, and I can't wait for that! The big question after Tuesday of course is whether we can still wear white?!