Continuing our NK cell series, we turn to a different area of work within this niche, namely how cytokines can help boost effectiveness of the clinical responses in hematologic malignancies through their impact on memory-like cells.
Spring is in the air!
This is an important aspect to consider bearing in mind that while NK cells can be useful in attacking cancer cells, they are also notoriously more fickle and less durable than their T cell cousins in sustaining cytlotic effects.
How can this be fixed? What therapeutic approaches might be potentially useful in addressing the problem?
To find out more, we spoke to a learned clinician-scientist involved in research in this arena to learn more about what he had to say and also discover why a molecule they are working on in early clinical development is starting to look quite promising.
The good news is that it may also have utility in solid tumours as well, through the effects that it induces.
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Dr Michael Caligiuri (City of Hope)
In the first of our extended thought leader interviews relating to the latest mini-series, we explore NK cell research through the lens of one of the experts in this niche.
This one is more of a convivial fireside chat than the usual interviews where we discuss data, latest readouts, development blowouts, or clinical trials etc.
So who’s in the spotlight this time around?
It’s none other than Dr Michael Caligiuri (City of Hope) who also happens to be the current President of AACR.
What’s cool is that he has been involved in NK cell research for a couple of decades and has seen a lot of changes in that time. He’s also an engaging and humble researcher who had some interesting perspectives on where success in the future might lie with approaches in this niche.
So grab a cup of joe and settle down to learning an intriguing story…
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After extensive – and at times, intensive – preclinical and clinical research on the adaptive immune system and how best to activate the cytolytic T cells in both hematological malignancies and solid tumours, attention is beginning to increase on the innate immune system. In particular, researchers are investigating how approaches in this realm can be incorporated into rational combinations with adaptive therapies, such that outcomes might be improved more than with either alone.
Human NK Cell Source: NIH
There are a number of ways to activate the innate immune system and direct dendritic or NK cells, for example. Some therapeutics seek to boost the responses via different innate sensing pathways such as cGAS/STING or CD47/SIRPα, for example, while others involve targeting stimulatory cytokines, chemokines, toll-like receptors (TLRs), etc through various agonist molecules.
There are also a myriad of vaccination strategies to consider involving neoantigens or neoepitopes, not to forget NK cell infusions, various NK CARs, bi/trispecifics and even checkpoint blockade of NK related targets.
These development have typically not received the same amount of attention as their T cell cousins, but it’s certainly an active and fertile area of research and one that we are likely to hear more about going forward as new developments start to make their mark.
In a world of ‘T cell chauvinists’ – to quote Dr Adi Diab (MD Anderson) – let’s not forget or ignore the humble NK cells, which also have cancer killing abilities.
Over the next three weeks, we have an extended mini-series focusing on NK cells rolling out with interviews and commentary from academia and biotechs alike across both sides of the pond. It promises to be an interesting and provocative ride with plenty of critical questions to pose and resolve along the journey.
So, hang onto your hats for the first part of the journey…
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As part of our #JPM18 coverage we like to feature up and coming companies to watch out for, one of these is Syros Pharmaceuticals (NASDAQ: SYRS). In this post we take a look at what’s on the horizon for the company in 2018?
Myelofibrosis has certainly been in the news this week with Celgene acquiring Impact Biosciences for fedratinib and both Celgene and Incyte presenting their annual update at the JP Morgan Healthcare conference in San Francisco.
Yesterday at JPM, Syros and Incyte announced a new collaboration to explore myeloproliferative neoplasms (MPN):
“… The companies have entered into a target discovery, research collaboration and option agreement. Under the agreement, Syros will use its proprietary gene control platform to identify novel therapeutic targets with a focus in myeloproliferative neoplasms (MPNs), and Incyte will receive options to obtain exclusive worldwide rights to intellectual property resulting from the collaboration for up to seven validated targets. Incyte will have exclusive worldwide rights to develop and commercialize any therapies under the collaboration that modulate those validated targets.”
Given the need to find new targets and potential combination agents to partner with JAK2 inhibitors such as ruxolitinib (Jakafi), this deal makes a lot of sense.
It also leaves Syros and Incyte with space to continue developing their existing pipelines in the usual fashion without any undue commitment or conflict.
Syros are a company we have been following for three years now, with several updates on BSB, including thought leader and C-suite interviews.
With new data presented at ASH and SABCS last month, it was a good time for an update on this topic, so we sat down with Dr Nancy Simonian (CEO) for a chat about where they are and where they are going with their current small molecule pipeline ahead of their presentation at JPM18.
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Over the last five years we have followed the trials and tribulations of CAR T cell therapies in ALL and aggressive lymphomas as Novartis, Kite, Juno, Cellectis, Unum and others have undertaken the road less travelled towards filing and approval.
The ASH DASH in action!
Now that we have seen the first two CAR T cell approvals in pediatric ALL (Novartis) and aggressive lymphomas (Kite), with tisagenlecleucel widely expected to be the next one in aggressive lymphomas following presentation of the 6-month JULIET data at the recent American Society of Hematology (ASH) meeting in Atlanta, a key question remains to be addressed:
Is there a threat on the horizon that might be potentially used prior to CAR T cell therapy in refractory lymphomas?
We say ‘yes, there is’ and thus it was interesting to see where this approach might go… including discussion with an expert.
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Buried amongst the intense hurly burly of a major medical meeting such as the American Society of Hematology (ASH) are the unsung preclinical researchers whose work largely makes clinical development possible. After all, few sensible companies would bet on an expensive clinical trial program, especially in combination, without first knowing whether such an approach is rational or not and has a decent shot of working efficaciously.
At stake here is the potential for building a blockbuster cancer drug niche by niche.
Venetoclax (BCL-2 inhibitor) got off to a somewhat slow start compared to say, ibrutinib (BTK inhibitor), which had a much broader initial indication and a lower risk of tumour lysis syndrome (TLS), yet it may actually have a wider application across multiple hematologic malignancies. This could well end up as one of those classic tortoise versus hare stories in the long run.
Back in 2013, we posted five interviews conducted with a range of experts including:
- Dr Oliver Sartor (prostate cancer)
- Dr Susan O’Brien (CLL)
- Dr Deepak Sampath (BCL-2 and ABT-199)
- Dr John Jenkins (then deputy director at the FDA)
- Dr Renier Brentjens (CAR-T cell therapy)
To put this in context, consider that we just recorded 15 interviews at ASH this year alone!
As regular readers know, we like to follow people and R&D stories over time, so while in Atlanta at ASH17 we took the opportunity to move a particular story forward – we wanted to learn where Dr Sampath and his colleagues are now and also where they are headed next. This gives readers a head start on anticipating what future clinical developments might be mentioned at JPM18 by either Genentech/Roche or AbbVie.
In our latest expert interview, we pick up and continue the discussion with Deepak Sampath to find out what’s happening with venetoclax four years on… it turns out quite a lot and makes for very interesting reading indeed.
Dr Deepak Sampath (Genentech)
Curious to now more about what this scientist and his work in BCL-2 targeting is all about? Check out this short excerpt:
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In our latest thought leader interview from the annual meeting of the American Society of Hematology (ASH) Dr John Leonard (Weill Cornell) provides a lesson on how to interpret key lymphoma data such as ECHELON–1, CAR T cells, and other topics at ASH, as well as what he’d like to see more of in lymphoma clinical trials.
In this hard-hitting interview, Dr Leonard reminds us that the media should not be a mere extension of the PR of companies. Instead he offers his real world insights into what may or may not be practice changing, and how we should interpret CAR T cell therapy data.
Dr John Leonard (Weill Cornell)
It’s a must read for anyone with an interest in lymphoma… here’s an excerpt to give you a flavour of the wide ranging discussion:
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As we continue rolling out our ASH coverage, we now move on to the in-depth analyses and thought leader interviews post meeting… What do experts really think about the critical questions that arise from new data? What is practice changing versus a nice to have in a small subset of people?
Someone said to me recently, “You seem very picky about who you interview. Why’s that?”
You betcha we are!
ASH17 in Atlanta
There are hem/oncs, thought leaders, and true experts whose opinions we value and know are solid and fair balanced in their commentary. There are also others who have major COI and will say whatever needs to be said about a particular individual study they are involved in, but are not reliable in a strategic perspective of the broader landscape or the impact of a study in terms of future trends.
I’d rather talk to people in the first category and learn from them – they don’t have to know everything or even agree with our own viewpoint, but they do need to be independent and fair balanced.
In the first of our ASH interview series, we posed some tough questions to a CLL expert and here’s a snippet on what he had to say:
Hah, at least we are thinking along the same lines!
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After the snow flurry in Atlanta that induced much panic and minor frustration in equal measure after the trials and tribulations of a tiring travel day with delays and cancellations galore. Then you see attendees waking up to a veritable winter wonderland in the south:
Meanwhile, things soon settled down somewhat and life got back to normal at the American Society of Hematology (ASH), as this quick time lapse that 3NT recorded showed down the main thoroughfare :
It’s time for our annual meeting daily highlights and lowlights because after all, oncology R&D is not a rose tinted garden and thus not every session or compound you highlight pre-conference will turn out as expected and sometimes, there are pleasant surprises that few see coming so you could end up at sixes and sevens if you don’t watch out…
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For the last couple of years at every annual meeting of the American Society of Hematology (ASH) conference, I have posted an extensive Preview of the CAR T cell therapy landscape and looked at which abstracts piqued my interest.
The roaring 30s CAR
This year the review is the most extensive to date, with more companies, more research groups, more tumour types and way more preclinical research coming through. It’s like a kaleidoscope of ideas cascading through R&D.
The other thing to take note is how fast the field is moving – it’s warp speed now and so much comes through the literature every month on top of that.
So here we go – hold onto your hats as there is a LOT to contemplate this year!
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