ASH19 Targeted Therapies Preview: This year’s ASH in Orlando is very much dominated by new developments on the immunotherapy front in terms of both T and NK cell therapies, with some passing interest in BTK inhibitors as well.
It’s not always sunny in Florida…
What about targeted therapies and the science behind those developments?
It was not that long ago that these were the main lifeblood of the meeting across many, if not most, hematologic malignancies. How times have changed!
That said, outside of the CARs (T and NK cells), as well as bispecific immunotherapies, and BTK inhibitors there are still some gems to be found amongst the rest of the ASH19 abstracts.
Here we highlight an additional 10 abstracts involving early pipeline areas that encompass some novel targets, new combination approaches, or emerging science.
Please note that the novel targets can take the form of classic targets or IO ones since they didn’t fit in the prior ASH Preview topics already reviewed under separate cover…
Curious to find out more about these intriguing selections and get a heads up on additional insights from our ASH19 commentary?Subscribers can log-in or you can click to gain access to BSB Premium Content.
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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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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No ASH pre-conference coverage would be the same without a shout out to Dr John Leonard (Weill Cornell). For 10 days prior to the annual meeting he counts down each day with a lymphoma study that caught his attention and tags it #LeonardList. The first one went up yesterday:
Do follow Dr Leonard and his lymphoma selections on Twitter – there are usually surprising ones in the middle that are quirky or interesting that makes you stop and think more carefully. He also appeared on the #ASH16 Novel Targets podcast in Season 2 explaining his choices and why they mattered if you want to get a flavour.
Our #ASH17 series we have already covered aggressive lymphomas and also developmental therapeutics.
Atlantic Olympic Sculpture
Up next in our third ASH17 Preview, we take a broad look at the wealth of abstracts available and highlight ten key presentations, irrespective of tumour type, which readers should be watching out for.
Some of these ‘Champions’ may not be immediately obvious and include interesting preclinical findings, intriguing new products in development, as well as eagerly awaited mature data from recently approved therapies. It’s an eclectic mix, to be sure.
There are definitely some early trends and interesting new molecules emerging from company R&D pipelines that are worthy of further consideration in this year’s batch of abstracts.
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One of my favourite areas to follow in oncology research is Developmental Therapeutics, whether they be targeted, genomic, epigenetic or immune therapies. At some point, even currently approved products started off life in this category, either in preclinical research or in early phase 1 trials.
It’s almost like a primordial soup from which future pipelines spring.
Following these initial approaches over time can be useful in many ways – you can pick up new trends and emerging drugs earlier than most, and can also step back to see a broader picture of the landscape as it evolves.
While there are no formal developmental therapeutics sessions at the American Society for Hematology (ASH) annual meeting per se, that doesn’t stop the intrepid scientist from creating their own selection, in fact it’s a lot more fun this way!
That’s exactly what I’ve attempted here…
Be warned though, this year, the mix is much more complex and intriguing with a lot of interesting and, in some cases, novel targets to explore and consider, including the deeper and tricky protein-protein ones to hit, which are now receiving more attention as researchers find more creative and indirect ways to tackle the problem.
Our second ASH 2017 Preview goes deep into what for many BSB readers will be intriguing, yet for others… completely unknown.
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Over the last five years the face of the chronic lymphocytic leukemia (CLL) landscape has changed quite dramatically with the advent of new approvals in several categories. These include anti-CD20 antibodies, BTK inhibitors, PI3K inhibitors and apoptotic Bcl–2 inhibitors.
In yesterday’s wide ranging interview we explored in-depth how these therapies are impacting the broader landscape, as well as emerging trends in how these regimens might be used.
In Part 2 of the ongoing series, we spoke with another CLL expert and explored promising new and earlier agents in development for a different perspective on how outcomes might be improved further.
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Targeted therapy and Chemo-Immunotherapy in CLL
At last December’s 2016 annual meeting of the American Society of Hematology, one of the areas that attracted attention was the latest clinical data on the treatment of chronic lymphocytic leukemia (CLL).
ASH 2016 in San Diego
In recent years, we’ve seen tremendous advances in the field with several new agents approved such as obintuzumab, ibrutinib, idelalisib, and venetoclax. There are also new treatment options available for CLL patients with high risk disease such as 17p deletions (Del17p).
Other new targeted therapies such as acalabrutinib are now in clinical development, plus we have CAR T cell therapies and combination strategies also being evaluated in the clinic.
So what was the hot news from #ASH16 in CLL?
- Does chemotherapy still have a role or is it a targeted therapy world?
- Are we further forward towards a cure?
- Have we worked out how to identify those at risk of relapse?
- Will CAR T cell therapy be a game changer in CLL?
- Is financial toxicity going to be an issue with combination strategies?
BSB interviewed two experts in CLL while in San Diego who kindly shared their thoughts on which CLL data impressed them at the ASH annual meeting and discussed some of the big strategic issues facing the field right now. These interviews are being posted in a two-part series.
Part 1 today answers some of the questions highlighted above and explores the changing face of the broader CLL landscape.
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San Diego – after “Flying Friday” where I flew from Munich to San Diego, Biotech Strategy Blog coverage of the 2016 annual meeting of the American Society of Hematology (ASH) is now done for another year.
With over 27,000 attendees – it’s the largest ASH annual meeting I’ve seen in 20 years of coming here! ASH is definitely the pre-eminent global meeting for hematology and blood cancers.
As you might expect, the thought leaders at this event are super-busy, but we’ve already managed to catch up with a few, and we’ll be rolling out interviews in the “post-game show.”
Subscribers have been asking what’s really hot at ASH this weekend, so reflecting my interests and the sessions I went to, here are my seven highlights/learnings of ASH 2016 (so far). There’s a lot more data to come!
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Post 2016 US Election, we move on and get back to business with an in-depth review of some new science and clinical data.
Yes, it’s time for another Bushidō – “Way of the Warrior” – guide to the key ASH abstracts!
Here we focus on acute myeloid leukemia (AML), a difficult and challenging disease to treat with a high unmet medical need for new effective therapies.
In this Preview we look at key companies in the AML space, as well as a look at what’s happening in classic targets and also some new ones that are receiving notable attention, both preclinically and also in the clinic.
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The BET Bromodomain market is a meaty epigenetics topic we have followed for several years now, including a look at the space back in 2013 on the old Pharma Strategy Blog (Link). The last update on this was ironically at AACR last year when we discussed MYC and bromodomains (Link).
In a remarkable tale of two cities in real life, two companies we discussed in those posts – Constellation Pharma and Tensha Therapeutics – have had markedly different fortunes since then. Roche decided to end their collaboration with the former and went on to acquire the latter instead.
Since we first wrote about bromodomains and BET inhibitors, the niche has exploded in a wildly stunning way… More drugs in the pipeline, more tumour targets being explored, and even novel combinations being evaluated preclinically for synergistic or additive effects. Even I was surprised by how competitive this niche has become based on the offerings at AACR this year.
With all the wealth of new data at the AACR annual meeting and also some other recent presentations I’ve attended elsewhere, it’s time for a more in-depth look at the BET/Bromodomain landscape.
Who are the new players, which tumour targets are now being evaluated, which combinations might be useful?
A word to the wise – this is neither a nerdy science post nor a comprehensive literature review – instead we take a look at the emerging landscape from a new product development perspective.
Science has been absolutely critical to success in all of the cancer therapeutics from targeted therapies to immunotherapies that have emerged in the last decade.
It really doesn’t matter whether you come from a marketing and commercial organisation or the investment community – if you want to make great decisions, you need to understand the basics of the science underpinning the R&D, where the strengths and weaknesses are. The alternative is play Roulette and put everything on Black 11 as a euphemism for whichever company/product/target you have an interest in.
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