Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

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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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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Everyone loves a deal, and we at BSB are no different, so here’s a Cyber Monday Flash Sale for you all.

For 24 hours only (until 7am US Eastern Time on Tuesday Nov 28) we’re offering $100 off a 3 month subscription to Biotech Strategy Blog Premium Content. 

This offer is only available to individuals and not to anyone who plans to use our content for business purposes. Please do read our Terms of Use before purchasing.

If you have any questions please feel free to contact us.

Buying now will give you access to most of our coverage of #ASH17, the forthcoming annual meeting of the American Society of Hematology.

Fountain of Rings, Atlanta Centennial Olympic Park

Fountain of Rings, Atlanta Centennial Olympic Park

We’ll be rolling out more #ASH17 previews in the next few days and will have on-site coverage in Atlanta, then post-conference analysis.

If you want additional colour on what we wrote about last year, check out the page with our #ASH16 coverage. You can also listen to Episode 16 of the Novel Targets Podcast, “Controversies in Hematology.

Nearly 80% of our current subscribers are repeat purchasers so we must be doing something right. If you’ve been sitting on the fence, now is a great time to buy and try us out.  We won’t be offering another discount this year!

How to get the Cyber Monday discount rate?

Click here to purchase this offer and use the discount code CYBER100 at checkout to obtain your $100 discount.

[This Offer has Expired]

Non-small cell lung cancer (NSCLC) is big news this morning with the announcement from Genentech/Roche that the IMpower150 trial exploring whether adding atezolizumab to the standard of care Avastin plus chemotherapy hit it’s first co-primary endpoint of PFS. The data will be presented at European Society for Medical Oncology (ESMO) Immuno Oncology Congress in Geneva, Switzerland next month. The other co-primary endpoint, overall survival, is expected in a couple of months.

I’m delighted that this trial hit a positive note, especially after a few folks were surprised at our emphatic positive prediction for both the PFS and OS outcomes in reviews this year when we looked at it in the summer and again in the fall – see: predictions in 1L NSCLC trials followed by red and green flags.

In the meantime, recently there was some very important news in the lung cancer niche relating to the field of genomics and our understanding of how tumours develop and evolve.

It’s easy for many folks to forget that even in a tumour type that is considered to be a hot/inflamed one due to the high tumour mutation burden (TMB), not all patients respond to checkpoint therapy upfront and not all will achieve lasting durable responses that go out five years. Resistance (primary and acquired), as well as immune escape, will inevitably have a large impact on many patients.

Understanding the underlying biology of the disease will not only help us figure out the causes of non-response and relapse, but also explore rational combination approaches that might improve outcomes.

Just as the triplet of atezo/bevacizumab/chemo has now been show to be superior to the control doublet, we may well see other approaches evolve in the near to medium term future.

The Dynamic Duo at #TARGETS17

Up on deck today is a timely yet rare joint interview that explores the science behind how cancers (including lung cancers) evolve and adapt to try and evade not only detection, but also being destroyed, by anti-cancer therapeutics.

Professor Charles Swanton (Crick and UCL) and Dr James Gulley (NCI) make for a thoughtful and compelling double act.

It was an absolute delight and a privilege to conduct our latest BSB fireside chat with them together. What they had to say was fascinating.

Often we have jested about putting researchers in the BSB hotseat, but frankly when it comes to people of this calibre, the tables are usually turned and the interviewer is the one in the hotseat with some selective pressure to keep up and maintain a flow of intelligent questions!

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SITC2017 Poster Halls

National Harbor, MD: It’s time for the first of our Gems from the Poster Halls following the Society for Immunotherapy of Cancer (SITC) annual meeting over the weekend.

It’s time for a look at biomarkers of response and some novel approaches in development. In the past we have covered circulating tumour cells (CTCs), cell free DNA (cfDNA), circulating tumour DNA (ctDNA) and even exosomes.

As Monthy Python would say — now for something really different…

What about a more integrated approach?

Yes, it’s possible and no, I’m not talking about the classical nonogram either.

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Sometimes initial phase 1/1b readouts at cancer conferences produce quite different reactions from a live and remote audience while at other meetings, the Developmental Therapeutics talks produce little or no interest at all. It’s often hard to guage which way they will go.

At SITC this weekend, several talks generated some contentious, and at times quite heated, debate and intense interest.

One of these was an oral presentation by Dr Zev Wainberg on the first-in-man data with the anti-CSF1R and anti-PD1 inhibitors, cabiralizumab and nivolumab, from Five Prime and BMS respectively, in an advanced pancreatic cohort.

Dr Zev Wainberg at SITC 2017

There was a surprising amount of confusion surrounding the initial results and other issues last week, with Five Prime’s stock dropping before we’d even got to Dr Wainberg’s talk.

What became increasingly obvious over the weekend was a clear difference in investors perceptions versus what the scientific community actually thought.

Here we take a look at the data and explain what to watch out for and why…

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SITC 2017

Treatment with checkpoint blockade has undoubtedly improved the lives of some people with advanced cancers such as melanoma and lung cancer, however the number who do achieve complete remission with single agent therapy is low (typically <20%).

In addition, not all people will respond up front while others achieve an objective response then relapse as acquired resistance or immune escape hits.

One challenge facing the field is identifying these mechanisms of resistance and finding the optimal combination approaches that lead to improved outcomes.

This weekend at the Society for Immunotherapy of Cancer (SITC) annual meeting, there were quite a few interesting new combination developments with early data.

Here, we take a look at one such combination to explore the data, the biomarker research that is ongoing and also some of the challenges associated with finding needles in the proverbial haystack…

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We’re at a crossroads in the IO space, where much of the low hanging fruit has been already plucked and now we could be in limbo for the next 2–5 years while we wait to see which of the IO-IO or IO-other combos pan out as winners.

Part of the problem is that we don’t yet know all the potential mechanisms of resistance or immune escape involved, so imagine figuring out how best to optimally modulate the tumour microenvironment on top is going to be challenging – each tumour type is heterogeneous and highly complex.

In addition, the field has heavily skewed towards obsessing almost exclusively over T cells, which may or may not be a good thing.  There are alternative approaches that are starting to generate interest and results.

As Andrew Shepherd, the fictitious leader of the free world in the American President famously said:

“We have serious problems to solve, and we need serious people to solve them.”

One promising company in this space is Nektar Therapeutics.  At SITC this week they had some elegant and intriguing early data that combined an innate immunotherapy approach with checkpoint blockade.  We have been following their progress for a while now and it’s a great time for an update!

Dr Adi Diab NKTR-214 #SITC2017

Here we explore the data and have our latest expert interview that is not merely a couple of paragraphs long with a few platitudes or topline quotes… this is, quite frankly, a comprehensive review and strategic roadmap of what Nektar Therapeutics are doing in the IO space, why they are doing things a certain way, and where they are headed – in their own words…

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National Harbor, MD – Day 2 of #SITC17 brought some interesting highlights on a number of fronts, not all of which may be apparent at present, but there are a few readouts that will have a broader impact going forward.

SITC 2017 Stars?

As we move into an era where we see more combinations evolve in immuno-onology, things are likely to get more confusing rather than less so and it could well be another 3-5 years before things truly settle down and more concrete trends emerge.

Here, we reviewed 10 different areas of interest with a strong clinical relevance and explored the topics further.

Please note that some of these will also have follow-on posts with thought leader interviews and related poster reviews.

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