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!