Summer is a busy time, if you're one of those busy bees!

It was a big week in pharma-related news, with lots of moving and shaking, which often seems to happen in unison as if the herd truly operates as one when it comes to reorganisation. First up was the news that GSK is definitely beginning to feel the impact of transitioning from Andrew Witty's underwhelming tenure in recent years, to incisive refocusing of the company's pipeline under new CEO, Emma Walmsley. 

Ms. Walmsley has pulled some 30 drug development programs from the table, clearly demonstrating her intent to build upon the brand's expertise in four main areas of business (respiratory, infectious diseases, oncology and inflammation) and probably exiting the rare disease segment completely. No doubt this new focus and vision will sharpen the company's bottom line in years to come, although how likely other pharma are to jump in and snap up assets that GSK has somewhat devalued via their deprioritisation remains to be seen. The R&D refocus is expected to save GSK over $1 billion by the end of the decade. 

The news coming from new Alexion CEO Ludwig Hantson rang a similar tone, with announcement that he too was cutting hard into their R&D programs, resulting in termination of deals with investor darlings Moderna, as well as with Blueprint and Arbitus. These three deals alone cost Alexion over $120 million in upfront cash, so that's quite a bold move, especially given the value seen in the Moderna deal. 

Similarly to GSK, Alexion intends to focus on four main therapeutic areas - haematology, neurology, nephrology and metabolic disorders - and bolster its rare disease business. Clearly, like Walmsley, Mr. Hantson was not necessarily thrilled by the pipeline he inherited upon accepting the top job, but in complementary fashion to Ms. Walmsley he has made decisive moves, and quickly. 

New Eli Lilly CEO Dave Ricks is in a similar frame of mind since arriving in January, and has stated his intent to pull some 10 oncology programs (Phase I and II) from the R&D pipeline, and either partner or out-license them. The company's goal is to sharpen the focus on their immunotherapy and combitherapy franchises, with increased attention to tumour resistance approaches. 

They will not just be looking inward, either, as business development efforts will be directed at new external early stage programs of interest. Mr. Ricks firm intent is to get some shine back on the Lilly logo, which has been somewhat tarnished with various later stage disappointments in recent times. 

In rougher news, AstraZeneca was rocked by a big-time failure and dent in its immunooncology (I/O) pipeline with the news their new I/O drug (durvalumab), alone or in combination with a CTLA-4 drug (tremelimumab), failed to meet its primary endpoint of progression-free survival (PFS). This was a devastating outcome for all involved in the MYSTIC trial of patients with advanced, non-small cell lung cancer, wherein the drugs failed to better chemotherapy in terms of PFS, even in patients selected for expression of PD-L1 on 25% (or more) of their tumour cells. 

This outcome had been rumoured for some time, and that rumour may even have fueled and propagated the rumours that AZ CEO Pascal Soriot was set to leave for the top job at Teva; to date Soriot has denied such rumours and stated that he remains committed to AZ. You can bet that there was frenzied interest in this looking-glass outcome from BMS, Roche and Merck, who are all embroiled in combitherapy I/O clinical trials, but not all in identical fashion. 

Merck (and maybe Roche) look set to make further gains in the space via their Keytruda-chemo combo, while the combos involving CTLA-4 are now in some doubt. BMS feel that there is still hope, and mention the fact that their drug targets PD-1, and not PD-L1 (like AZ's Imfinzi), so there may well be a different outcome. 

As I said, it was a busy week (!) and that includes further developments in the local ecosystem, with news of PreciThera's $36M Series A round garnering attention, not least as one of the founders is the ex-CSO of local biotech Enobia (formerly BioMep);  that company was acquired by Alexion for over $1 billion in the last days of 2011, and represents a rare but spectacular exit by a local Quebec-based biotech. 

The syndicate responsible for the Series A round includes Sanderling, Arix, CTI, Emerillon and FTQ, many of whom are relative veterans of such ventures. The company leverages the power of bioinformatics-based tools to compile data obtained from RNA sequencing as well as that in genomic and clinical databases, to delineate and validate the major pathway responsible for clinical symptoms in selected rare genetic disorders. As far as I am concerned, another new biotech here in the province can only be a very good thing, and here's wishing PreciThera all the very best in their quest to discover new drugs for orphan bone diseases.

That just about does it for this boy on this rather busy week, and now I have a sunny chaise longue and a cold drink crying out my name a few feet from my outdoor office table. Wishing one and all a glorious summer weekend! 

Novartis - a huge horse pulling a massive CAR-T!

The horse and car-t race between Kite, Juno and the behemoth Novartis (among a few others) took a turn in a considerably optimistic direction yesterday, following the news that Novartis had nicely hurdled none other than the FDA, at least for now. An external panel of experts, convened by the agency to assess the usefulness and risks of this groundbreaking new technology, delivered a resounding 10-0 victory to the pharma yesterday.

That technology, referred to as CTL019 (or tisagenleleucel) currently, is the first in a new wave of leukemia treatments that have the potential to revolutionise the therapy of not just leukemias and blood-borne cancers, but ultimately solid tumors as well. We are not there yet though, and for now the focus is on hematological cancers, using a patient's own T-cells to attack the problem, once they have been biomolecularly retuned to seek out signals on the patient's cancer cells. 

The FDA is well aware of the risks inherent to the approach, which has even resulted in patient deaths on several occasions in various clinical trials, but for those individuals who have been through the agony of chemotherapy and stem cell transplants without success, the one certainty in their short term future is death, itself, so anything viable is worth trying. Furthermore, cytokine storms and rare patient deaths aside, the approach has seen resounding responses in many, with Novartis themselves observing >80% of patients remaining in remission some 12 weeks after treatment in a recent trial. 

Unquestionably that kind of success outweighed the considerable safety concerns that the panel had, given the type of patients being treated. The CAR-T field has been in the news for years, in both good and bad ways, but it is the way forward (among other avant garde developments) and I think many are breathing a huge sigh of relief that the FDA is not going to be the elephant-in-the-room on this, and Novartis et al. are being given a green light. That green light won't be official until sometime in October this year, and Kite themselves will be flying high just behind Novartis in November, all being well. 

All of the high-level publicity is good for business, of course, but the practicalities of actually rolling it out and delivering the quality-controlled "product" is a very different matter than simply producing pills, when it comes to autologous cell therapy. Novartis has to ensure safe and robust manufacturing processes that involve taking blood from patients all over the country, shipping it to one of several specialised sites available, manipulating those cells, and subsequently shipping them back to the hospital for direct delivery into the bloodstream of those same patients. 

Clearly there are numerous points where this kind of drug product could vary or go awry from one sample to another, given just the number of different individuals involved in handling the samples from hospital to pharma and back to hospital again. It seems somewhat daunting but Novartis appear confident that they are ready for the task at hand, with reportedly some 30 centres readied for the manufacturing process. Nevertheless, Novartis has estimated a 22-day turnaround on such manufacturing and supply, which is pretty impressive! This scenario is quite different from how things appeared in the third quarter of 2016, when they seemed to be pulling back, if not pulling out of the CAR-T race altogether. 

In the third quarter of last year came the news that 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, then in Phase II clinical trials. 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 I/O division. Next came the blow that not just lab hands were being let go, but the bulk of the senior executives running CGTU were also being axed, which didn't look good! 

That sounded 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? The only logical conclusion if they were not in fact pulling out, was that they were demonstrating the belief they had that the major manufacturing issues worked out, and they were confidently restructuring for actual production of the drug product. 

As it turns out, that seems to have been the case, that the R&D was truly done and dusted at that point, and Novartis were indeed gearing up for NDA submission, approval, marketing and rollout. Perhaps simultaneously ruffling the feathers at a few large biotechs who may (still) prefer to have the pharma giant out of their way, if not out of their hair. But healthy competition aside, yesterday's ruling by the FDA panel is good news for everyone, particularly cancer patients desperate for some new regimens to be added to the standard-of-care. 

Those new regimens will ultimately include new technologies with on-trend monikers such as oncolytic viruses, neoantigens, natural killer cells, and of course, CAR-T. Solid tumour therapeutics is where the biggest bank for one's buck is going to come, but you've gotta start somewhere and for now the hot topic remains the fruitful passage of CAR-T out of critical clinical trials and into therapeutic reality. 

To see CAR-T therapy presumably hitting the marketplace in 2018 is a wondrous thing to ponder and hopefully witness, with an advance that truly seems like stepping into the future for anyone older than a Millennial. The entire concept of taking one's own cells out of the body and reengineering them to laser in on and kill tumour cells, is no longer the stuff of science fiction, but it does remain the stuff of pioneering genius, and my hat is off to anyone and everyone who has played a part in this particular aspect of a brave new world in medicine. 

Surfing the waves of the stock market - hopefully there'll be no inclement weather on the big day!

Fresh off the news discussed in my last post on REPARE, what do you know, mere days later we have more good news in the new wave of biotech business here in the city of Montreal! Local bone disease specialist Clementia has filed with the SEC for an IPO of the order of $115M; more than a little irony that the filing first came to light via the team at Renaissance Capital, given that this move represents another significant piece in the renaissance puzzle of the local life science sector. 

The company, which has only been around for seven years or so, was founded by Dr. Clarissa Desjardins, who is also Clementia's CEO, alongside Dr. Jean-Claude Tardif, a local eminent cardiologist. Dr. Desjardins is no newcomer to this business, having founded both Advanced Bioconcept and Caprion, residents both (initially) of BRI here in Montreal. Things have progressed quickly at Clementia, with over $100M USD raised to date, which included an oversubscribed $60M mezzanine round that underlined investor belief in the company and its product.  

That product (their only pipeline asset for now) is their lead candidate for a disease known as fibrodysplasia ossificans progressiva (FOP), an ultra-rare condition that severely debilitates due to extra-skeletal bone growth in muscles, tendons and other soft tissue. Such heterotopic ossification essentially imprisons the patient in a second skeleton, if left untreated. There is no effective treatment nor cure for this horrific condition which results from an overactive BMP signaling pathway, apart from steroids and anti-inflammatories, which ease some of the pain, only. 

This disease affects less than one person in a million, with under 1,000 patients currently living with it; however, companies such as Clementia believe that this type of prevalence should not deter drug developers from investing in such programs and that is a sentiment shared by the entire rare/ultra-rare disease community. Notwithstanding the whole debate ongoing vis-a-vis soaring drug prices, particularly in rare conditions, and what a certain Mr. Trump is going to do south of the border to rail things in! 

Clementia's approach is via palovarotene, an oral RAR-γ agonist (R667) that is proposed to be able to prevent the abnormal bone growth seen in this disease, based on key data obtained in animal modeling of FOP. The compound was not discovered at Clementia, but was in-licensed from Roche as recently as 2014, having been discontinued as a drug candidate for COPD after it's safety had been assessed in several hundred people. 

This potential product is now in Phase II clinical trials in adults and children with FOP, examining different doses of it in patients with flare-ups, and further documenting its safety in patients living with FOP.  The FDA has granted palovarotene orphan drug designation and fast track status, with the equivalent designation being granted by the EMA. The severity of the disease and paucity of adequate therapies underlie such designations. 

In the coming year and with a new boost to the coffers via the intended IPO, Clementia will commence the MOVE Phase III trial of palovarotene in FOP, but additionally, initiate a PhaseII/III trial in multiple osteochondroma. There's a lot of hope in this venture, but it remains a highly risky one, as do almost all biotech financings, but with just one product in the pipeline if something goes awry, I wonder what the back-up plan is that continues to apparently comfort investors. 

One aspect of such confidence seems to be that in animal modeling of the disease, there was a lack of new bone formed even when treatment with palovarotene was inititated even six days post injury. This implies that during flare-ups, an appropriate treatment might be able to nullify the response prior to new bone formation, which is exciting. Further, researchers found that once palovarotene was withdrawn, its effects were maintained and continued inhibition of bone formation was observed. If such results can be repeated in human, this could represent a solid home run for Clementia, and the future would indeed be bright for both the company and patients, alike! 

Like all biotech and drug development ventures, only time will tell, and it is unfortunately an achingly slow process to get from the bench to the clinic to the bedside - but somebody's gotta do it - and I am certain that all FOP patients are delighted that in this case, Clementia is going to try to do it. All the rest of us can do for now is to wish them all the very best, while enjoying their contribution to the revitalisation of Montreal's life science and biotech ecosystem. Bravo!

Good news that helps to further repair the DNA of the local life science ecosystem!

To those of us who were on the factory floors of biotech life back in the late 2000s (here in Montreal or in Quebec more generally), the financial crisis that kicked in more or less simultaneously with the election of Barack Obama in the USA led to some very bitter and difficult pills to swallow. One went from having cut one's teeth in the risky but exciting world of drug development, and garnering some serious career traction in the process, to heading home without even a severance cheque. 

Not having a severance cheque was one thing; but the incineration of other options whereby to exploit the experience gained to date felt like the proverbial nail in the coffin in the heretofore promising careers of so many. The domino effect kicked in seriously in 2008/9 as the doom and gloom whispers spread, until over 100 life science-related companies had evaporated from the province. Here for today, gone tomorrow, as the song goes!

While the talk of eventual rebuilding of the life science cluster that the province was renowned for provided a modicum of comfort, the talk did little to stem the exodus of talent from the Montreal area, and that exodus very significantly included big pharma. Merck, AstraZeneca, Boehringer Ingelheim (among others), and most recently Vertex, all pulled local operations enitrely, sending even greater numbers of skilled local workers home, with departing for the USA as perhaps the only viable option. 

Those times were truly funereal in nature in the industry, and while they are in the past now, the memory of them  should never be too far in the back of the mind, such that they serve as a stark reminder of what can go wrong, and/or act as a guide on which mistakes should not/must not be repeated again. But, thankfully, it is 2017 today, and we are in an enormously improved condition and amidst a new dawn in the life science ecosystem once more, and it sure feels like one very welcome breath of fresh air. 

Even just one example from the news of last week serves to illustrate the reemergence of Quebec life science and biotech as key components and drivers of the local economy, and that was the announcement that REPARE Therapeutics was opening for business in Montreal. The founders closed a whopping $68M US Series A that was co-led by the Versant Ventures powerhouse alongside MPM Capital. Other investors in syndication included Montreal's FTQ, BDC Capital's Healthcare Venture Fund, as well as Celgene. Heady company, indeed! 

This ~$90M CDN Series A (!) round is indicative of an ongoing restoration or indeed a repair of the Canadian life science sector in general, with over $1B of cash splashed out in some 74 companies by the end of 2016. This set a new record since the last peak seen in the year 2000, and it looks like 2017 is following suit with close to $500M already deployed in 26 different enterprises. 

The REPARE deal is simply an underlining of the thinking that a more robust venture capital infrastructure is not only needed but is already firmly in place, and is willing to part with sufficient cash to bring such companies out of stealth mode into preclinical development, and to maybe even have enough funds to get them to an exit without a need to raise more money. The fact that this deal raised more money than the recent IPO of Vancouver's Zymeworks sort of says it all in that regard. 

REPARE is being championed by a figure who is well known here in Montreal, and who in fact has been one of the AmorChem heavyweights in our annual KNOCK OUT pitch competition - Lloyd Segal -  who is taking the reins as CEO after 18 months of stealth while developing their tour de force CRISPR-enabled synthetic lethality drug discovery platform. Two of the founders (Drs. Daniel Durocher and Frank Sicheri) are from Toronto's Lunenfeld-Tanenbaum Research Institute, and the third (Dr. Agnel Sfeir) is from NYU's Skirball Institute. 

While it appears that there are several new targets discovered while in stealth mode, REPARE’s first program targets the DNA-directed DNA polymerase theta (PolQ), a key component of a pathway that repairs double-stranded DNA breaks in cancer cells. That this polymerase is highly expressed in ovarian, breast and certain other cancers means that REPARE is likely to have multiple options for this newly identified target, and they have made the bold claim to have their first compound in the clinic in 2019. 

We are delighted to see this company emerge into the public eye, further raising the Canadian flag along with the likes of Zymeworks, BlueRock Therapeutics, and EnGene, among others. At AmorChem we have seeded several newcos ourselves over the past year (Mperia, SemaThere, Corbin, with three more to come in 2017!), even if our more limited resources preclude us from the type of investments typical of say, a Versant or an FTQ. But the placement of REPARE's HQ on Montreal soil further adds to the critical mass being built here, and unquestionably the team at FTQ is to be credited for such efforts in the life science sector. 

As far as I am concerned, whether we are talking about DNA repair and the restoration of a healthy cellular infrastructure, or about repairing the DNA of the local (and Canadian) life science ecosystem, and rebuilding the Quebec cluster's infrastructure and international reputation, well, it's all good! Wishing nothing but success and some serious repair by the talented people kicking off REPARE! Oh, and by the way, go Dan! :)

Talk about canned heat - Pepsi bubbles bursting with troubles!

If you have been even remotely alive and connected to the world this past week, there are probably two names that were impossible to miss - Pepsi and Kendall Jenner - even overshadowing the increasingly attention-getting antics of he who is known to his buddies as the Trumpster. 

Now don't get me wrong, there are already far too many words written and way too much attention showered on the entire Kardashian Klan, primarily for the wonderful job they all do of being, well, Kardashians. Not to be confused with those extraterrestrial long-necked humanoids known as the Cardassians, of course; although they too move to establish a dominant presence in any social setting, so the two species do have that in common!

It never ceases to amaze me how much furore, fire and brimstone can be stirred up by as innocuous a prospect as a TV ad for a soft drink that has been even more globally ubiquitous than the Kardashian brand itself. I mean, how seriously are we supposed to peer in, examine, digest and draw conclusions from an ad for a can of soda?

Well, if the reaction is anything to go by, make that very seriously indeed! Unquestionably, the pervasion (invasion) of social media into not only our personal lives, but also as a power tool for business and marketing purposes, today means that nothing is hidden for long and once the machine rebels, then you better get ready! The very machine that can fuel a feeding frenzy on a company's latest hot product can turn cancerously against its creators, and sink them in the process. Social media were the marketer's wet dream, but the tide can turn against one in a heartbeat, showering one in this case with a deluge of warm, flat cola. 

While social media may have evolved into an aspect of everyday life, they have simultaneously become the medium for (sometime so-called) social conscience, where any offender can be singled out and word spread to tens of millions in an instant, with the right support. If there is photographic evidence to go along with it, even better. The President of the free world himself has come under fire for his endless twittering on questionable subjects in even more questionable fashion, but somehow, it didn't stop him from getting the big job. 

The new rule seems to be that one must make absolutely sure one's new ad (or whatever else, including the underwear) is squeaky clean before ever risking public dissemination, and then, and only then, does one release it out into the twitterverse or facebookfray or instagramdram. So, what the hell was Pepsi thinking?! Surely they had not only expensively expert campaign creative/marketing/management personnel behind the ad, but presumably had road-tested it in some discreet fashion with focus groups or the like?

Now as I said, and not being a Millennial, I am not sure I am a fan of social-media-as-real-life, and everything must be shareable/shared and watch out if it can't or shouldn't be, because we will find it and get you. This is not a social conscience, it is social media shaming, and there is a massive, gaping difference between the two! It's one thing for young people living under a far-off archaic third world regime to be posting about war, torture and inequality on their streets, yet it's entirely another to be using the same media to troll a famous golfer for his various extra-marital affairs or a teen pop star who started acting up whilst growing up. 

However, this point is kind of a moot one, because Pepsi are using that very social media with great success, and they just had to know that the Millennial masses are watching every move they make, and are primed to jump up and down in celebration at an "incredible new ad!" whilst being completely capable of growing horns and becoming the cancerous beast eating them alive for their "abhorrent and disgusting new excuse for an ad!"

What's the lowdown and what's all the fuss about? Well, our gal Kendall, representing any typical young person today (cough!) is in the middle of a photo shoot (ahem!) when she spots her peers out-and-about protesting major issues of the day, and lo-and-behold, she has a lightbulb moment and decides to forgo her lucrative modeling career (splutter!) so she can join the Millenial masses in fervent protest over some great social injustice her peers are upset about. And also, lo-and-behold, she miraculously went from platinum blonde to decidedly duskier tones in the process; I wonder what point that is supposed to make?!

I am not going to get into all the accusations or various ways this can be interpreted, overinterpreted, or misinterpreted, but suffice it to say that cultural appropriation (another fave subject of social media shaming today) is a major concern, and indubitably, Pepsi's positioning of a glamorous (blonde-turned-brunette) white model in some kind of alignment with the "Black lives matter" movement caused the pot to boil over. One can of Pepsi at a time. Our gal Kendall apparently changing the world with one can of Pepsi handed to a police officer is not what the Millennial masses want to see, it seems. 

Pepsi got this whole thing entirely wrong. I am not sure I agree with the level of horror expressed and leveled at them, as I am pretty certain they were trying to express the importance of even brief moments of "love and  unity" between opposing sides of an issue. But they should have known this would backfire, and surely someone in the entire creative team and process, especially their social media gurus and staffers, told them it would?

In the end, Pepsi did what everyone must do today in this world of social media shaming - they apologised - even expressing regret at what they have done to Kendall Jenner herself, who apparently is "devastated". In this new world, one is allowed to make even horrific mistakes, as long as one acknowledges it within 24-72 hours, and then expresses sincere regret thereafter. Now everyone can go back to being seen exiting the store with a Pepsi in hand, instead of covering it with a brown paper bag!

The whole politically correct thing is not something I am a huge fan of, not least because it is often a hypocritical political correctness. In that, as long as it's someone else who has sinned, then it's fine to raise absolute bloody hell and shame them, but let's not talk about what may be in one's own head or related mistakes one may have made in the past. The Internet is an unforgiving place with a permanent memory, and there have been a few social media shaming celebrities who got caught out by people questioning their motives, upon finding similar sins in their pasts. 

The one thing that the Trumpster and I do agree on is the way that political correctness now makes it impossible to speak one's mind, or even open one's mouth, without the risk of being nailed to the cross of social media and subsequently stoned for it. Even if in his case he should keep some of his more questionable opinions to himself! But for example, one headline responding to the Pepsi ad and accusing the company of being "tone deaf" drew ire from other individuals, claiming that this response was further insulting, to the hard of hearing. Where does it end? Have we become so keen to blame and shame on social media, that we let go of common sense in the process? We strive to take offence even when clearly none was intended? Every single group on the planet must be considered, in advance, and our thoughts edited, in case someone might be able to draw offence? Again, where does this end?

Nevertheless, I bet that Pepsi learnt a tough lesson this week about trying to market directly to the Millennial masses via social issue-based social media and ads, and the lesson is that the message still counts, regardless of which currently-in-vogue Millennial face they use to promote their brand. Today, the Pepsi can and brand has been sorely dented, and it will need hammering back into place again. 

Unless, wait, they knew exactly what they were doing all along, and they got preciesly their desired result - people all over the globe speaking that magic five letter word - PEPSI! ;)

Being chased around by your fitness tracker?!

That we are definitively living in a new era of personalised health and medicine is evident from the proliferation of "wearables" on the market and being developed; the most obvious testament to this being the number of people who now carry around a monitoring device in place of their old wristwatch, maybe even replacing an already somewhat passé smartwatch with it. 

The concept of wearing clothes made of materials that can sense and respond to activity, temperature and moisture is no longer new, and specialised materials were credited with the breaking of over 100 world swimming records between 2008 and 2009 alone, for example! But I am referring more specifically to activity trackers, and the role that they are currently playing in our lives, and the potential contribution they make in improving our overall health. 

Now I have been pretty active all my life, and still run on the mountain or around the track (in the stadium that is home to the Montreal Alouettes) four or five times a week, so I don't really need to monitor my activity, right? But it seems that could be wrong! First up, it is pretty true that after a day in the office, then getting home to change and go run, followed by a shower and making dinner, well, it's real easy to spend the remainder of the day pretty immobile in front of the TV and a good documentary.  

That appears to be fairly natural after a day of work and exercise at the end, but a study I heard of actually suggested that sitting is the new smoking, and it was just as dangerous in the physically active as in the proverbial couch potato. The "sitting is the new smoking" idiom was coined by Dr. James Levine of the Mayo Clinic, who also happens to the inventor of the standing desk. He believes that we are "sitting ourselves to death" and that the effects of such behaviour are actually permanent, and cannot be reversed by subsequent return to activity. 

I find that kinda hard to believe, personally, but the message is clear - sitting is a killer - and we need to get off our backsides and move more! There's no clear answer yet, but I would love to know if staying mobile more of the time, even or especially in the absence of vigorous exercise, is actually better for us than working out and then collapsing on the sofa, feeling justified in our end-of-day sloth. If simple movement is king, then can we forgo the torture on the treadmill? 

Even considering all of the above, I wasn't really convinced of the need or use for wearables, and even as typically a quite early adopter, I resisted the urge to have an activity tracker strapped on my arm, 24/7. Apart from anything else, I like to sleep with nothing on (I mean on my wrist, people!), and you can't do that if you want your sleep patterns monitored. If I go in, I go all in, or not at all, I felt. But this was suddenly challenged and changed by a family member who sent me a Fitbit at Christmas, and I had to consider facing my failings on my smartphone, every single day. 

I admit, it took me a few days to charge it up and strap it on, especially with some people stating that it was a prison, and a shamer of the lazy, and was only the beginning of a new form of healthcare mind (and body!) control; a modern day Big Brother that was threatening to take over our very lives, and even predict our deaths. Perhaps unsurprisingly, the naysayers were largely those that hate working out or going to the gym! 

But I went with it, and got used to having my every move, and activity, and heartbeat, and snore, monitored by the deadly device that now watched over me, 24/7. At the end of each day, my smartphone would tell me "It's time to begin winding down for bed", and I would awaken to some gentle pulses on my wrist, and a summary of the activitty of the day before on my screen. Before you even think a clear thought, you get to see how inactive you were yesterday.

Of course, it's a lot of fun on your big days, seeing you did over 12,000 steps and 30 floors of stairs, during almost 90 minutes of activity, and that your resting heart rate is the 50s. However, after a lazy weekend day, seeing the stats that show "You are a sloth, who did almost nothing in the last 24 hours" is well, not quite so much fun! Like everything else in life, I feel that the happy medium is in moderation, and getting the best out of what is supposed to be a fun addition to life, not a prison guard or roving doctor barking at you. 

It can be kind of addictive to see good stats, and then want to reach that level every day (or most days), but how much danger is there in that? If it does make one more active, then fine! The key is not taking it all too seriously, and not letting it rule one's life. "No, I can't go to the movies tonight, because I was in the office all day and had lunch there, so I am only at 1939 steps for today. I need to go walk or run this evening, or else I will have horrible stats first thing in the morning!"

Thus, use the device to encourage one to do more, but not get in the way of or ruin the quality of life. If it assists on obtaining generally improved numbers even five or six days a week, and then a bad day occurs on a Sunday, fair enough! One is still further ahead of the game than without it. In fact, for me personally, the most valuable use of my Fitbit is not truly as an activity tracker, per se, but more as a sedentary time tracker. If I go run or climb some stairs, I know what I did, but it can be much harder to take note of one's sitting time or lazy periods. 

In fact, a study in the UK in 2016 found that out of 82 technologies useful for monitoring activity, only 9 of them actually functioned as sedentary period monitors. This is where there is a gap in the market. In many ways, I don't need my butt kicked for activity inandof itself, but I probably do need it kicked to keep moving and do so more regularly. So I get my Fitbit to buzz my wrist and make sure I do a minimum number of steps per hour, every hour if possible, and that's a definite benefit to me, I feel. 

If sitting is the new smoking, then I need to do less of it! Not least as I never even tried smoking! The future of such devices is clearly in taking more responsibility for one's personal health, and even getting pre-diagnosed with characteristics of a sedentary lifestyle (before disease), as well as the integration of increasing quantities of useful data and analytics being uploadable to one's doctor and healthcare records. It's kind of a scary new world in that regard, but we aren't quite there yet. And I certainly have no intention of inputting my water intake and dietary habits to my Fitbit, that just ain't going to happen!

As invasive as biosensors and wearable technologies threaten to be, if they catch something before it kills one, how evil can they be? More significantly, if they actually provide something that might be missing - a guilty conscience or a kick in the butt or silent encouragement - and get us moving more which ultimately prevents lifestyle-related diseases from taking hold in the first place? Then they could even be a godsend, and something to enjoy rather than dread. Taking more personal responsibility for our health in this new era of personalised medicine just seems to be the appropriate thing to do. 

For this boy? My tracker deets page tells me that even though I have climbed 10 floors and done 2,000 steps, zero real activity has been detected thus far today. Guess who's going running this afternoon? :) 

This Wednesday belongs to the women of the world!

So here we are at March 8th, which of course means the annual celebration of all things female, and given that we here at AmorChem are led by two women, well, I didn't have much choice but to acknowledge the significance of this day. No, my job does not depend on it - I hope! :) 

You know, I am all for the recognition that any gender or minority receives for their contribution to the world, but I can't help but feel that some of it is becoming rather old-fashioned in feel, or may even be outdated in today's world. Yes, I can hear the screaming hordes of abuse coming my way for that suggestion, and okay, I would have to try being a woman for a day (a month, a year?) to truly get it, I guess. But still. 

It just doesn't seem to me in the western world at least, that women are not recognised for their hugely significant place in the world, whether that world is one of being a wife and mother, or working at a place of business, or both. There is no doubt that historically, things were on a much less level playing field than they are today, but do we still actually need to somehow imply that women are so distinct from men, even in 2017?

I imagine that the answer is a resounding "yes" even in spite of women being more prevalent in previously male-only bastions such as the military, the police force or even high-level politics. But for every almost-the-first-female-POTUS-in history, there are presumably millions of others who don't feel they get a fair shake of the tree, just like the outgoing first-black-POTUS-in history did not necessarily change the perception of life as a young black adult in the USA. 

But I am not a fan of the "prize for everyone" philosophy that seems to be rampant in schools today, even in sports competitions, nor am I a fan of rich, famous celebrities being further pampered for their work at huge awards galas, and especially not if they show tantrums at not having won. Don't even mention Kanye West in that regard! Not everyone deserves or needs a prize, and not everyone has to feel they won even if they lose. 

I actually kind of admired the gutsy move by our very own first lady, Sophie Gregoire Trudeau, who chose to take an alternative stance on the day by drawing attention to the men and boys in (her) life and co-celebrating them. 

"This week, as we mark International Women’s Day, let’s celebrate the boys and men in our lives who encourage us to be who we truly are, who treat girls & women with respect, and who aren’t afraid to speak up in front of others."

She also encouraged women to take a picture holding the hand of a "male ally" and post it using the hashtag "TomorrowInHand". Rather remarkably,  but totally predictably, this approach drew both appreciation as well as howls of horror from those who chose to see the move as somehow anti-feministic. Comments ranged from "I've never had to have my hand held!"to "Celebrating Women's day by celebrating men?" to "Allies are important but they don't get to be part of our day!", and so on. 

I mean, really? No, I mean, reallyyyyy? Honestly, this type of thing just makes one want to leave social media forever, because the whole shaming-by-social-media thing is completely out of control, even when it comes to someone who clearly has nothing sinister up her sleeve and nothing but the best of intentions. People with simply too much time on their hands choose to troll on social media rather than trying to actually contribute something useful to society, and by so doing often distort the original purpose and meaning to a positive post. 

In some ways, in part because of stupid social media shenanigans such as those outlined (very briefly) above, a negativity begins to permeate what are supposed to be societally positive initiatives. Ms. Trudeau was simply illustrating a point that reflects my overriding feeling on this, which is that it takes two, or all of us, to make the world go round. She has her own version of success in this life, but sees it as an inclusive success, not an exclusive one, and wants to celebrate those who contribute(d) to it. What the hell is so wrong with that?

Maybe the best way around the problem is to cancel the day altogether, or, we have to introduce an International Men's Day! This would be a great idea, if someone else hadn't thought of it first; apparently there is one, and it's on November 19th this year. I had no idea it even existed, which perhaps says a lot. I know I don't feel any need whatsoever for an international day recognising my gender, but that may be because I am a man, right?  Wrong!

I believe in men and women, period. It's how we all ended up here, even if that statement could almost get me in trouble today for its implications. The political correctness pervasive in the media (not just social media) and the endless shaming of those who err (almost exclusively via social media) is rampant, and it's gotten to the point where saying nothing at all is the safest route forward. I personally hate that, and I think it does not bring us forward. 

Lest I am misunderstood, in conclusion, I am all for celebrating the women in our lives, at home, outside, and in the workplace, yet I don't feel (at least in North America) that we need a special day to acknowledge them. Just like I don't need any silly-sounding men's day. I prefer to celebrate women year-round, not just on some artificially created special event day; ditto St. Valentine's day. And if you ask most women, they much prefer year-round appreciation rather than roses and chocolates ordered online at the last minute on Feb. 13th from the office, after hearing someone mention tomorrow's big day!

Next we will be asking for a special day to commemorate just us Irish?! Hmm, I think we already have that one, too, and it's only a week or so away! On that note, I better get back to my desk and focus on the needs of two of the women in my life, before they begin to ask themselves whether they really need any men in the office anymore and label me as superfluous to requirements! Have a great International Women's Day (to all those who do celebrate it) but just remember, tomorrow is as much a day to celebrate women everywhere as is today! 

[Photo courtesy of Tony Caldwell/Postmedia Network and the Toronto Sun]

Dare to meet the need in rare!

Coincident with the lengthening of daylight hours and the imminent forwarding of the clock, both signs that we are nearing the beginning of March, comes Rare Disease Day. This worldwide series of events occurs on the last day of February each year and is organised by EURORDIS, the European organisation for rare diseases. 

So who is EURORDIS and what is Rare Disease Day exactly? Well, EURORDIS is a non-governmental patient-centric alliance of almost 750 individual rare disease organisations; that number alone says a lot about the magnitude and scope of the problem and movement that is rare disease advocacy. It's underlined by the fact that some 50% of existing rare or orphan diseases affect children. 

In many ways, given the low prevalence of rare diseases (by definition, less than 200,000 patients in the USA), the best way to focus serious attention on the issue is to join forces and create a larger footprint between big pharma and their desire to fill their pipelines with blockbuster drugs for major diseases. Although there has been unquestionable progress in steering big pharma R&D in the direction towards rare disease drug discovery, the current controversy is primarily on how much those exciting new treatments should cost.

The political landscape for both big pharma and patient advocacy groups has been shaken (to see the least!) by recent administration changes south of the border, and given that Obama and Trump are not even as similar as chalk and cheese, no one is sure what will happen next. Apart from some occasional bleating, Obama was always pretty friendly to big business such as the big banks and big pharma, and it's far from clear how Trump is going to impact things. 

Some of these treatments for extremely rare diseases can cost exorbitant amounts while also being difficult to access here in Canada, which doesn't strictly have a rare/orphan disease policy or set of regulations. In fact, Health Canada doesn't even have a definition of rare diseases, even though they say they are working on developing an orphan drug regulatory framework that will encourage drug development and provide better access to existing drugs.

As stated above, the US-based criterion for orphan status is a current number of 200,000 patients at a given time. In Europe it is categorised differently, wherein a prevalence of less than 1 in 2,000 people is identified as a rare disease or disorder. The spectrum is pretty wide even inside that narrow-sounding category, such that in the EU one rare disorder could affect a mere handful of individuals while another may impact around 250,000 people. Further, it is estimated that in Europe as many as 30 million people suffer from one of a staggering 6,000 existing rare diseases. 

Canada's lower population in part explains lack of organisation around this issue, but by any measure Health Canada is lagging behind, badly, and needs to get some policy around this problem if patients are to have a chance at accessing such drugs at a remotely affordable price. In a recent example of the problem in Canada, the announcement by Marathon Pharmaceuticals that they were raising the price of a generic drug (deflazacort) for Duchenne Muscular Dystrophy (DMD) to almost $90,000 USD was only part of the problem. 

Marathon isn't even intending to market the drug in Canada, because the USA represents their target market, and it probably isn't worth their while promoting it's use north of the border. But $90,000 for a generic drug that costs mere hundreds for a year's supply, imported from elsewhere? So much for the era of Shkreli and Pearson being over! For their efforts, Marathon also received a voucher from the FDA, which inandof itself could be worth hundreds of millions of dollars. So it's (big) business as usual, in other words.

Donald Trump does have strong views on the whole pricing question, but he also loves big business and has no problem with savvy businessmen (himself included!) making bucketloads of money. The recent get-togethers with the CEOs of big pharma at the White House must have been fascinating in terms of such conversations, not least as essentially everyone is quaking at the prospect of Trump's take on not only big pharma drug pricing but also his choice of the next leader of the FDA. Moreover, tomorrow morning he sits down with the big healthcare insurers, such as Aetna, Signa and UnitedHealth, and that's another conversation with far-reaching implications.  

In any case, Tuesday is all about increasing global awareness of the rare disease phenomenon, and spreading the word on a cause that affects a relatively small group of people to the wider population at large. Improved access to existing medicines, at an honest cost, as well as stronger health policies and education around rare diseases, combined with increasing incentives  for focused R&D and drug development by pharma are all goals of the initiative. Last year's Rare Disease Day involved events in some 84 countries, and that's a pretty healthy level of participation. 

On that note, I will end this particular blog by sharing the video for this year's Rare Disease Day 2017, and wishing everyone involved their most successful event day yet!

Oak Island is a blessing, not a curse!

Although reality TV has become the scourge, if not the curse, of trends in television in recent years, every cloud indeed has a silver lining, and one can actually find some sapphires in the mud if one looks hard and digs deep enough. Speaking of curses and jewels and digging deep enough, one diamond in the rough (for me) is the fascinating "The Curse of Oak Island" on the History Channel.  

The story is essentially as much one of brotherly love as it is a treasure hunt, but the basic premise is that Marty and Rick Lagina set out to solve the 200-year-plus mystery of Oak Island in Nova Scotia, while hopefully becoming very wealthy in the process. For all of us who are still in touch with the younger boy (or girl!) inside of us, the story has much to offer - pirates, buried treasure, gold bullion, the awe-inspiring Knights Templar - and all this with a dreaded curse thrown in as the icing on the cake! 

I actually have my own frustrations regarding Oak Island because I drove from downtown Montreal to St. Margaret's Bay in Nova Scotia for a family vacation, and spent a wonderful time there, but sadly without any knowledge of such an intriguing mystery a few miles down the road from our oceanfront repurposed fish store. We drove through the Mahone Bay area several times, and must have seen Oak Island, but it was before the current reawakening of the mystery, so nothing was evident to the uneducated eye. It is a given that I would have taken the Jeep onto Oak Island to explore it, had I known!

We are now onto the fourth season of the show, and the elusive treasure remains, well, as elusive as ever. The brothers have been furiously digging deep into Oak Island areas with evocative names such as the Money Pit, 10-X, and the Swamp, among others. But as one false hope has turned into another real disappointment, it has become clearer and clearer that the brothers (and other team members) are having to dig deep within themselves, as much as into Oak Island soil. 

As predictable as the show can be in terms of producers ramping up drama with a potentially explosive find, the camera zooming rapidly down a dark, watery hole to hopefully reveal the discovery, and then, right into a commercial about Tide detergent! As appropriate as that is given the dirt all over the brothers, so far, the tension built up is inevitably evaporated within seconds of return to the show and one sees it was yet another false alarm. This trick might work the first few times, but with repetition it totally loses power, and one just heads to the kitchen to put the kettle on. 

Where am I going with this? Well, the thing that probably keeps me watching is both the human aspect of the production, and the relationship and (occasionally wavering) belief between the brothers, and team members, as well as the investment in both money and time that is being poured down 10-X or the Money Pit. No, I didn't say being poured down the drain!

Investment is investment, almost irrespective of the endeavour being invested in; nothing is ever certain and considerable risk is taken in placing money in harm's way, with no guarantee nor even the faintest signs of a return. And yet, in this case the two brothers continue on with pervasive passion, endless enthusiasm, tireless travails and a brotherhood borne of belief. This is what investors do on a daily basis, and at AmorChem we are not so different from the Lagina brothers. 

We are also a tightly knit team founded on belief; and while drug discovery might not quite equal a 200-year-old hunt for the truth, well, the 10-20 year hunt for new drugs is no sprint either! And even if we don't have to believe in any actual curse around our endeavours, it is an unquestionable truth that drug discovery and development is littered with failures, and many, many tombstones lie in the so-called "valley of death" between discovery and late stage clinical trials and subsequent marketing. Drug discovery percentage success rates are not that much better than sea turtle survival from egg to adulthood, and that's not even 1%! 

In parallel with Oak Island entrepreneurs, in many ways we are also investing time and money in what can appear to be deep, black holes, but there are jewels in there amongst the rocks and mud, and we believe that we can find one or two of them. This takes both belief and teamwork not only within, but also and primarily with our talented researchers in whose laboratories we invest in; we are all aligned in our very own quest to find new truth - truth that benefits mankind - and yes, to share in the profits of our collective labours if we get there. 

Notwithstanding the fact that we do and will face failures, we remain optimistic - why would one invest if one had a pessimistic view of the outcome? - and patient. Patience is a key word among investors, but my version of that characteristic would perhaps best be described (somewhat oxymoronically) as a patient impatience! There's nothing wrong with being impatient, when it comes to success we all are to some extent, but it must be tempered with a solid dose of Rome-not-being-built-in-a-day. Easy to say, harder to live by! 

I think what's important is acknowledging from the get-go that something is going to take a few years (big picture) to mature, and accepting that, but being pushy and even a little impatient on a daily/weekly basis (small picture) by trying to achieve the maximum possible. It's always surprising how quickly a blank canvas can evolve into something so much bigger when it is diligently worked on each and every day. Let the head deal with the big picture, while the heart pumps out daily energy and lifeblood for the small picture tasks and challenges. 

Perhaps surprisingly, one overarching take-home lesson learnt from watching Oak Island or while working at AmorChem is actually one and the same: as cliched as it sounds, it is the journey that matters. Success and wealth are great driving forces, of course, but if one is miserable for the several years (decades?!) it took to get there, was it worth it? When I watch the brothers on Oak Island face flooded digs due to the legendary booby trap flood tunnels laid down centuries ago, it remains clear that everyone is still enjoying themselves! 

The only way to be able to get out of bed and go get cold, wet and muddy on a frigid, desolate island is because you are filled with a passion; one that is not diluted by small defeats, and by realising that you wouldn't want to be anywhere else. Ditto investing in life science projects that will take many years to get there; frankly, the only realistic way of doing it is because you love what you do, on the daily basis, not just because of some defrayed dream of wealth in say 13 years. The journey may be a frustrating one but nothing worth having ever comes easy, as my Dad used to say, and the journey just has to be valued to its maximum. All the real fun is in the getting there! 

The journey is where all the shiny, bejeweled lessons reside, and one must take the time to see them and treasure them, even if they are obscured by the cold black earth of defeat and failure. Embracing failure may appear to be such a contradictory concept, but how many winners have never lived defeat? So many winners have stated that it was the bitter taste of failure that drove them ever harder towards the sweet smell of success. Ergo, failure can (or should) be seen as instructive. It's all about the attitude in the end!

Now then, it is Sunday today, which means tonight I get to escape for an hour with my team at Oak Island, and let the boy in me go off on an East Coast treasure hunt with the Lagina brothers; it certainly is therapeutic before another week in the office. I am fully behind the Laginas in their hunt for the truth about Oak Island; this is Season 4 now, so I am hoping that they find that truth some day soon and then maybe can return to warm offices instead of frigid swamps on Monday mornings. 

Ironically, I can only imagine how romantically they are all destined to look back on their days in the trenches of Oak Island if/when that day finally comes. Maybe that will be the real curse of Oak Island in the end - the solving of the mystery - leaving behind a hole almost as deep as the Money Pit or 10-X that fascinated them all so much!

Repatha Will Test the NewRepatha Will Test the New Drug Pricing Realiax Nisen Drug Pricing Reality

By Max Nisen

Telomeres and teloyears on my television?!

A little while ago I spoke on the proliferation of opportunities to interrogate one's own genes via the offering from the equally proliferative spate of new-age companies providing kits to peer into the murky depths of our individual genomes. As fun as it may be to learn certain things about one's ancestry and genetic make-up, there are clear dangers in coming to diagnostic and prognostic conclusions based on non-physician interpretation of such data. Especially when physicians are in fact not trained to analyse such data in the first place!

While watching TV on the weekend, my attention got suddenly grabbed by an advertisement berating us all to "Redefine your age in 2017!"; the name of the provider had the extremely intriguing moniker of "TELOYEARS" which I knew just had to mean telomeres!  I was kinda taken aback to be honest - while the terms DNA, and human genome, and personalized medicine have become quite commonplace in (social) media these days - is the general public now ready to be asking questions about their telomeres?!

I find it fascinating that something as specialised or even esoteric as telomere research is already out there in the public domain, with a tantalising little test on offer to inform you how well (or not) you are aging. Is the public sufficiently educated to truly understand what it is they are buying and what can of worms they may be opening, or is Teloyears just another biotech venture destined to make some serious money while simultaneously courting considerable controversy?

So what's the story? Well, briefly, telomeres are the protective nucleotide caps that keep the ends of our chromosomes intact and protected, via multiple repeats of the TTAGGG hexanucleotide sequence, with one hexanucleotide overhang at the very end. We are born with a few thousand of such repeats at the ends of our chromosomes, but this number is reduced with aging, due to the replication process not being complete at each cell division. Thus, a gradual shortening of our telomeres is part and parcel of the natural aging process, or even (as Teloyears imply) an unnaturally accelerated aging process. 

It's an enticing little story, even if it's the usual soft focus lens take on things, with glamorous, healthy, active people young and old simply  bursting with vitality, no doubt due to very sexy telomere counts! And that's all very well, in fact it is likely to be those active, fit, middle-aged folks who will be the major clients of such companies. In other words, I am fit and healthy, and the test confirmed my telomere length to be like ten years younger than me! 

That will feel good, no doubt. But what about those that felt they were doing great, and the test informs them they are actually older than their years? If their lifestyle is already top notch, what are they to do next to stop the onslaught of telomere shortening? So much of it is probably in the genes already, that if it's low, then it's low! Are people who have let themselves go, and can see it in the mirror and/or on the scale, likely to pay for a test that confirms their worst fears or what they already know? Will such a test be the single factor that will cause them to overhaul their lifestyle?

Again, what are physicians supposed to do when their patients come to them with the results of their Teloyears test? Maybe I am misinformed, but it's my opinion that if you stroll in all newly educated and tested to your doctor's office, exclaiming woe due to criminally short telomere repeat numbers, the doc is likely to say "Telo-whaaaaat?!" I just don't think the medical profession is ready to truly interpret and prognosticate based on such data, and at best one is likely to be told to eat less, exercise more, stress less and sleep more. Business as usual, in other words. 

Telomeres have been and are the focus of intense research, and not just in terms of cellular aging. Clearly, one advantage of shorter telomeres would be that it is not compatible with the cell division/growth seen in cancer, and in fact, maintenance of telomere length is a hallmark of cancer cells. Like almost everything in life, too much of a good thing is often a bad thing. So, overly short telomeres is a sign of cellular aging and contributor to cellular senescence, and overly long telomeres is a sign of cellular "youth" and contributor to cancer.

There are several key players in regulation of this process, including TERT (telomerase reverse transcriptase), the shelterin complex (including TRF1 and TRF2), and the newly discovered TZAP (telomeric zing finger-associated protein) which was the subject of a groundbreaking paper published in SCIENCE just this past week. In this case, rather than the currently fashionable issue of shortened telomeres, the authors studied the question of how longer telomeres would actually be a cancer risk, and how do healthy cells avoid the problem. 

It turns out that not only do our telomeres shorten with age, but we do have a mechanism in place to prevent them from becoming overly longas well, and that is driven by TZAP.  So, when telomere length becomes too long, the concentration of the shelterin complex goes down, permitting association of TZAP with telomeres, resulting in a trimming of telomere ends. Clearly, telomere shortening can also be considered a good thing, too! 

Almost certainly, telomere shortening is a factor associated with age-dependent diseases but the cause-and-effect relationship is far from clear, if it exists at all. Is it the shortened telomeres that caused the disease, or is it that the shortened telomeres are just another marker of aging process that inandof itself led to the disease? It's the chicken and egg question, again. Much more research is needed, of course, and one has to be careful about the claims being pushed at us by various companies making money off of our genes. 

The world of personal health and fitness is unquestionably a brave new world, with various wearables poised to revolutionise healthcare as we know it. Now you can have a device on your wrist that can measure your activity, your resting heart rate, your sleep patterns, stairs climbed, and some even offer blood pressure monitoring. So we are more and more likely to be monitoring such parameters, and sharing that information with our doctors. But I feel we are still some way off from discussing the results of 23andme's inherited genetic risk factor data or our telomere length issues with them! 

Happy new year to two newly minted newcos!

             

What better way to kick off the new year than with news of a couple of key AmorChem investments converting into full-blown but virtual (for now!) biotech companies?! It's only early January but we are starting the year in the fashion in which we intend to continue, i.e. putting our money and support behind those prior investments that have succeeded in their early endeavours and now merit/need additional help to cross the great divide. 

First up, we were delighted to launch Corbin Therapeutics, a new company focused on the USP15 deubiquitinase (DUB) target discovered by Dr. Philippe Gros of McGill University. With a seed financing of $1M in place, the team is now poised to begin screening for small molecule inhibitors of USP15 as novel candidate therapeutics for neuroinflammation, with multiple sclerosis as the primary indication. 

There's a lot of buzz in the UB/DUB space in general, with many referring to the them as the next generation of drug targets, in correlation with kinases/phosphatases, but of course specificity is always going to be a key factor in developing inhibitors. USP15 itself is seeing quite a bit of attention in the literature, and seems to play key roles not only in neuroinflammation, but additionally in viral replication/stability as well as in p53 biology and cancer.  

This exciting new target's role in inflammation was identified by Dr. Gros and his team in an elegant genome-wide mutagenesis screen in which a single point mutation was sufficient to be protective in various animal models of neuroinflammation. In a recent paper published in Nature Immunology, the team demonstrated that USP15 regulates the type I interferon response and is directly involved in the pathogenesis of neuroinflammation. 

Essentially, we see huge potential not only in the USP15 target but also in the team that discovered it, and so we wanted to capture that potential and further nurture it, allowing the program to mature and evolve such that it may become an acquisition target for a larger biotech or big pharma interested in the UB/DUB (and inflammation) space. In fact, given not only the expanding role of USP15 as outlined in recent literature, but also discovery of other targets by Dr. Gros and his team, Corbin is positioning itself as a drug discovery platform. On that note, best of luck to Corbin, the first 2017 spin-off from our AmorChem fund - here's hopiung that we are on the c-usp of something big! 

Next up is another spin-out newco, SemaThera, via the pioneering work of Dr. Mike Sapieha of the Maisonneuve-Rosemont Hospital (HMR). Dr. Sapieha has been working on the involvement of a key new target (SEMA 3A) in diabetic macular edema (DME), and his team have generated a series of ligand-based traps that permit investigation of the roles of both SEMA 3A and VEGF in animal models of disease. 

The team has demonstrated that SEMA 3A is linked to vascular leakage that is z hallmark of DME, but importantly, they have shown that the levels of SEMA 3A rise earlier than those of VEGF in disease modeling, which may facilitate earlier intervention in the disease than the current standard of care. This is a most pertinent point in that almost half of all DME patients do not respond well to treatments targeted at VEGF, and thus the targeting of SEMA 3A may provide new hope for those living with the condition. 

SemaThera is also the recipient of $1M seed financing from AmorChem, and this financing will permit the company to select a lead candidate for preclinical development, from their bank of SEMA 3A traps. This is a hot target already getting a lot of attention from big pharma, and we believe that a lead trap which has been through preclinical development will be very much on the radar both in terms of pharma partnering and/or acquisition. 

When one considers that DME is a very common feature of many retinopathies, and that as many as a quarter of diabetes sufferers exhibit some degree of DME, then the significance of an earlier, targeted therapy is ultra-clear. We wish SemaThera a very happy new year and all our best wishes for an action-packed year with no blurred lines! 

Although it may appear that we are reverting back to the older Quebec biotech model that crumbled back in the late 2000s, it's worth noting that we learnt serious lessons from previous failures. These newcos are being seeded by AmorChem to elongate their runway, whilst existing within the confines of a virtual newco that remains housed in founder labs and institutions. 

One socioeconomic positive arising from such newcos is that it allows the retention of highly skilled and trained research personnel who become central to the chances of success of our funded projects. So even though we are not creating new infrastructure, we are contributing to maintenance of such jobs and growth of a skilled life science workforce here in Quebec, and that's a very important bonus in our newco strategy.

There will be a degree of both professionalisation and further development within these newcos that should augment their chances of success, and it will be both their ongoing evolution and various market forces that will dictate the outcome. We are fine with that! With these two spin-offs, we are now at #4 from our AmorChem fund, with one major announcement still to come - we have Mperia, Corbin and SemaThera thus far - for more info on the mysterious missing link, watch this space! 

Hitting the ground running in 2017!

Well, 2017 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 fifth 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), and the need for such translational funding isn't going away anytime soon, so 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. You only have to mention the acronym "CIHR" to researchers young and old, to be hit with a barrage of tales of woe about lack of funding or even basic trust in the process. 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, 2017 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 had the raucous (and occasionally trainwreck) presidential campaign trail that ultimately saw the Trumpster seeing off Obama and the Dems. 

One currently red hot drug development area is the immuno-oncology space, which saw some record-breaking fundraising and dealmaking in 2016. 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. This year should see new, susbtamtial investment in the assets of this program and for updates on that, watch this space!

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 exactly who and how the next President is, in a business sense. 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 2017 ahead!