Biotech Strategy Blog

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

Posts tagged ‘AACR 2018 Chicago’

An up and coming IO target to watch out for

Summer time always seems a good opportunity to explore new cancer targets or approaches on BSB and we’ve covered quite a few interesting concepts over the last couple of years.

ASCO18 Gems from the Poster Halls

This particular approach is an up and coming immuno-oncology target that I noticed is quietly gaining increased interest amongst pharma companies and not all the usual players either.

Consider typing in [target] + cancer in PubMed…

What I got was one single paper in 2000, nothing until 2006 (two more papers), then one to four new ones a year dribbled out until 2014 when nine appeared, followed by a big jump to 17 in 2015, over 20 the following year, then finally more than 30 last year.

At the current rate there will likely be 40–50 such articles in 2018, making for a typical sigmoid growth rate of interest.  Boom!

Clinical trials (montherapy and combinations) are already in early phase studies in the clinic, so this is a good time to take stock and look at progress to date. It also makes for interesting reading when put together as a whole!

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A different take on targeting cancer

While many observers attentions have recently been focused on immuno-oncology of late, particularly with respect to checkpoint blockade and CAR T cell therapies, these are not the only class of drugs that are being investigated in the clinic.

Field of dreams or crowded marketplace?

We saw a lot of early preclinical data and especially got to see quite a few new targets at AACR, while next month ASCO offers a new opportunity to see inital phase 1 data presented in several developmental therapeutic sessions and in the poster halls.

There is no doubt that the oncology R&D niche is becoming increasingly competitive and crowded, which means that companies need to think carefully about how they can clearly differentiate themselves and position their platform much more assertively than before.

For small biotechs, this also means going beyond offering great preclinical packages to demonstrating proof of concept in the clinic, hence phase 1/2 trials are receiving a lot more attention these days, as potential collaborators and acquirers flock to the poster halls.

Today we have a CEO from one of these emerging biotech companies in the BSB hotseat with a candid discussion about their approach, why they are different, and importantly, where they are heading…

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A new inhibitory checkpoint target hits the clinic

The hurly burly in Chicago between sessions

We have written about the positive and negative effects of various inhibitory checkpoints such as PD-L1, PD-L2, ICOS, and even B7-H3, but there are also other targets within the B7 family that might be worthwhile exploring in the clinic.

Beyond the hullabaloo surrounding the phase 3 anti-PD(L)1 data in 1L NSCLC, there were actually a lot of interesting new and emerging molecules that caught our attention from small biotechs that we plan to highlight throughout the rest of this week. They all have different targets, approaches and rationales, but offer a window into the world of oncology R&D and where things might be headed in the next couple of years.

Today we take a look at one of the long forgotten checkpoint targets and explore a number of aspects that can be considered, given that several companies have preclinical or clinical molecules in early development.

Is this an IO target to watch out for – or not?  What are the challenges and opportunities to consider?

It turns out that there could be more than one way to unleash T cells on cancer… as this interview with a company scientist and researcher demonstrates.

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Stacking up evidence from IO clinical trials

What we wanted to accomplish in our latest thought leader interview was to peek under the hood with someone active in this field who is an experienced participant in phase 2 and 3 trials, as well as being a solid translational researcher capable of thinking outside the box critically.

Stacking up the evidence from IO trials

Today we cover a global KOL’s perspectives on cancers of the lung, renal, bladder, and even melanoma, in a wide ranging discussion about immunotherapy trials and some of the pitfalls and opportunities to watch out for.

It makes for an intriguing read as there are likely a few issues that many have not thought about in great depth.

This is an important discussion in the context of not just data that was recently presented at several conferences including AACR, but also with the upcoming monotherapy and chemo combination trials (including squamous and non-squamous lung cancer) expected at ASCO in a few weeks time.

We discuss quite a few of the key challenges and opportunities relating to the broader picture and highlight some of the important issues to watch out for…

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Bench to bedside and back again

Can we break through the barriers of a hostile tumour microenvironment?

Who would have thought that after 30 years of no new therapies that urothelial carcinomas would suddenly be almost constantly in the spotlight with enticing words like cancer immunotherapy, biomarkers, tumour microenvironment, translational immunology etc?

And yet it has happened – with a lot more to come in this highly competitive niche too.

Prior to AACR in Chicago, we highlighted TGFβ in our Preview series as an important emerging target that is gathering attention and may be relevant in tumour types, such as urothelial carcinoma and ovarian cancer.

After the meeting, Dr Paul Rennert (CSO, Aleta Biotherapeutics) noted:

I don’t disagree with either of these sentiments – there was a reason we interviewed a lot of NK cell enthusiasts recently and we have since been rolling out our thought leader mini-series focused on TGFβ. Yesterday, we kicked off with perspectives from an academic researcher active in this field and tomorrow will showcase some practical clinical perspectives.

On deck today, we have a interview with a research scientist who has conducted both basic and translational work for a discussion about how he sees the learnings that have arisen from bench to bedside and back again.

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Targeting TGF-β and the tumour microenvironment

We know that not every patient responds to checkpoint therapy and some may respond but then stop responding, so what can we learn about the tumour microenvironment in order to fix it?

To do this may well require retrospective analyses of the existing trials in order to learn what happened and figure out an improved design of the next wave of clinical trials with rationally based combinations (as opposed to randomly testing two molecules simply because that’s what a company has in its pipeline).

The other thing to consider is that while some people might have a high level of a particular marker or inhibitory factor up front, others may see rise on treatment as an adaptive response to immunotherapy. Those two situations may well require quite different approaches or regimens to address, making things much more complicated than originally thought.

Dr Kunle Odunsi (Roswell Park) at #AACR18

One topic that caught our attention in the run-up to AACR and subsequently during the meeting was a cytokine called transforming growth factor beta (TGF-β). We have covered IL–2, IL–6 and IL–15 developments quite extensively on BSB, but what of TGF-β?

As such, we decided to investigate this little known target further and explore the concept from different perspectives in both academia and industry.

Today, we begin this latest mini-series with a thought leader interview from an academic institution who is researching a novel approach to combination therapy based on TGF-β – here’s what he had to say about the topic…

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How Charles Swanton plans to revolutionize treatment of Lung and Renal cancers

At the 2018 AACR annual meeting, one of the noteworthy talks given to the 22,000+ attendees in Chicago was a plenary lecture by Charles Swanton from the Francis Crick Institute in London. He’s a Professor of Personalized Cancer Medicine at University College London and chief clinician for Cancer Research UK (CRUK).

Professor Swanton is the leader of a landmark clinical study, TRACERx (TRAcking Cancer Evolution through therapy (Rx)) study, which involves analyzing how cancers and in particular, lung and renal cancers, evolve over time.

There’s a lot of heavy science and jargon inherent in this niche that often frightens off people, but that need not always be the case.

What is fascinating, though, is the very idea that tracking the development of early stage cancers might teach us new insights and lessons about alternative approaches to oncology R&D.

We have all seen the limitations of chemotherapy, targeted therapies and even immune checkpoint blockade, so what other approaches can be considered that link back to the biology of the disease and how it evolves over time?

What we wanted to achieve here was a clear and elegant story about what Prof Swanton and his colleagues are doing, as well as a simple grounding on the basics of disease progression and how that can translate clinically into new therapeutics that might make a real difference to the lives of people with cancer.

It’s a fascinating story and may well be one of the most underappreciated recent developments in cancer research…

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The PD-1 Gorilla is Back!

At AACR last week we had the long awaited initial readouts for three key phase 3 studies in lung cancer, namely CheckMate–227, IMpower150, and KEYNOTE–189 in the same session on the same day.

This had me thinking about how it might end up being, “a killer and a chiller and a thriller when I get the (PD–1) gorilla in Manila,” with sincere apologies to Muhammed Ali and Dr Jean-Charles Soria for (mis)appropriating their past themes 😉

Chicago River Bridge at #AACR18

For those attending the event, you might well be forgiven for thinking from the first two adjectives that I’m referring to the weather, as it was certainly cold enough (!), or even the results this week from AstraZeneca’s unfortunately named ARCTIC study exploring the IO-IO combo of durvalumab plus tremelimumab in the third line setting with a miss in both PFS and OS endpoints.

In reality, we should be warmed and heartened to see three positive immunotheraopy trials appear at once and presented in the same session at the same meeting.  It isn’t always the case as regular attendees at ASCO well know.

When all is said and done, what do thought leaders specialising in lung cancer really think about the data that was presented in Chicago, and what were the convergence and discord on the various key issues under consideration?  There is, after all, a lot of subtlety and nuance to consider in 1L NSCLC.

To find out more, we interviewed not one, but four, lung cancer specialists in Chicago for their personal perspectives.  What they had to say as a group was both candid and absolutely fascinating, so it made sense to curate their insights around various key topics together into one detailed post for easy reading… 

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Can TMB help select patients for lung cancer therapy or not?

Chicago!

One of the key topics arising out of probably the hottest session (lung cancer clinical trials plenary) at AACR last week was tumour mutation burden (TMB).

An important question to be addressed was whether or not the nivolumab plus ipilimumab combination from the CheckMate–227 study will be useful in previously untreated non-small cell lung cancer (NSCLC) patients with a high TMB?

There are a number of questions that occurred to us that need careful consideration:

  • Is TMB ready for prime time?
  • What are the challenges and issues involved?
  • How useful are the data from CheckMate–227 and CheckMate–568?
  • Where are we going next?

To find out more, we had some fascination discussions at AACR with two up and coming young researchers from industry (Dr David Fabrizio of Foundation Medicine) and academia (Dr Nicky McGranahan from UCL in London), who are both experts intimately involved in measuring TMB.

What did they had to say and what does it all mean?

Their candid answers may well surprise a few people…

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AACR18 Red and Green Flags in 1L NSCLC

Chicago: It’s been a crazy busy day here at BSB, with embargoes, key data, thought leader interviews around town, the poster hall and plenty other things to think about.

What I wanted to do here was take a step back after the dramatic 1L NSCLC session and pull together some pros and cons that oncologists will be thinking about going forward.

There’s a lot going on in this market that is worthy of further discussion and debate…

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