Biotech Strategy Blog

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

View from Stars and Stripes life guard hut on Miami Beach

Our latest article is part Journal Club entry for August, part look back at some data from AACR and ASCO plus a part look at a relatively new target from an obscure biotech that caught my attention recently.

To do this, we pose three critical questions and attempt to answer them.

The targets and markers chosen for review here may well surprise a few people.

If we want to understand how to help more people respond to cancer immunotherapy then we need o understand the underlying biology and the tumour microenvironment in greater depth than we currently do.

Gradually, we are getting more clarity on a few areas as new data is being published…

To learn more from our latest review of data as well as companies and targets to get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

Picking a PARPi – what can the biology tell us?

One of the really interesting questions I recently received from a BSB subscriber related to PARP inhibitors – they asked whether the therapies are all the same and can be considered interchangeable as a class?

Around the same time, another reader wrote in asking if there was any new information on what’s happening with PARPi combinations in breast or ovarian cancers?

This got me thinking as there has actually been some useful preclinical and clinical studies reported on both fronts that at least begin to open our eyes to new information based on research that has been reported in several places.

Thus I thought it would be useful to summarise the data and take a look at what we learned in the process.

Fair warning – some of the findings turned out to be a little bit more surprising than you might normally expect to see…

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This week I was fascinated (but not surprised) to learn an interesting snippet from an article in Forbes on Hal Barron and GSK by Matthew Herper. Herper wrote:

“David Schenkein, the chief executive of Agios Pharmaceuticals, worked for Barron at Genentech. He says he’s never worked with anyone who read more of the original scientific literature on a topic before making a decision.”

This should be a given yet… not everyone does that. Dr Scheinkein (whom we interviewed here) is no slouch either, so that’s quite a compliment.  By the way, for an alternative take on the R&D update, check out John Carroll’s article on Endpoints.

Revvin’ up our understanding of the immune system

It is, however, good to see some CMOs and CSOs reading extensively in the literature themselves rather than relying on summaries from project teams, although I highly recommend they should because it’s a great way to keep the brain revved up with new developments and also understand the field more intimately.

This is also one reason why we have regular Journal Club posts on BSB – to highlight important new developments that are worthy of attention and explain why they matter.

It is encouraging that quite a few of our subscribers are c-suite execs, including CEOs, CMOs, and CSOs who often send in links to papers they are curious for an independent perspective on.

It’s time for the latest look at some key research that may have practical impacts in numerous ways…

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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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We have heard much hullabaloo about adoptive T cell therapy approaches with tumour infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cell therapies, but what about T cell receptor (TCR) therapy?

Over the last couple of years, various experts we have interviewed have alluded to TCR approaches in the pipeline that they have been involved in or come across, but this is not a topic we have covered in-depth as we, like many other observers, have been on the sidelines waiting for solid clinical data to mature.

Source: Adaptimmune

That time finally came around at ASCO last month, where we had the opportunity to discuss an NY-ESO–1 based TCR with one of the companies in this space, namely Adaptimmune.

We also covered several other constructs they have in their pipeline.

Inevitably there have been quite a few R&D setbacks with some of the TCR approaches evaluated, going back to Dr Steven Rosenberg and the NIH experiments back in the 1990’s with MART–1 as a target.

I was therefore really intrigued to find out more about how are Adaptimmune faring, what technical and clinical challenges remain, where are the programs going, and what have we learned so far?

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One of the challenges of the short whirlwind period between AACR and ASCO is that many new research papers get published and largely missed or forgotten about in the data tsunami that drops as people eagerly (and almost exclusively) focus on the new abstracts that are available.

This is a real shame since there were many really good pieces of research that were rich in knowledge that were published around then.  My reading pile heading into AACR was much larger than usual, and after wading through it all, it built up rapidly again heading into ASCO, never mind over 20,000 abstracts to consider between those two meetings!

Contemplating new data…

With this in mind, it’s time for a new Journal Club post – these are surprisingly popular on BSB, although on reflection the selections have tended to highlight either new targets and areas of therapeutic potential or offer explanations for some of the phenomena that we are seeing.

New developments often (but not aways) allow us to step back and see results from clinical trials with greater clarity.

With this in mind, here are our latest selections for the BSB Journal Club, all of which should prove to be a useful read…

To learn more from our latest ASCO highlights and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

One of the ongoing challenges with cancer immunotherapy is monitoring response to treatment.

Even if you are one of the minority of people who do respond to cancer immunotherapy, many responders go on to develop acquired resistance or experience immune escape resulting in a loss of response to therapy, which means we need to be able to detect what is happening in the immune system of a cancer patient in order then identify the next treatment option.

Dr Whiteside in the poster hall at #AACR18

Could the proteins and nucleic acids carried by virus sized microvesicles called exosomes – present in their billions in blood plasma – provide insights into biomarkers of response to therapy and what is happening in the tumour?

Some people think they can, while others remain skeptical.

We think it’s cool area of research, worthy of consideration and following as we continue to explore various biopsy and blood/plasma approaches.

One person at the forefront of exosome research is Dr Theresa Whiteside from the University of Pittsburgh, where she’s a Professor of Pathology, Immunology and Otolaryngology.

At the recent 2018 annual meeting at AACR, she kindly spoke about her innovative work over the past year in what is now an exploding field of research…

To learn more from our latest thought leader interview and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

The #ASCO18 poster hall scrum

Wrapping up our cytokine mini-series, we have our latest expert in the BSB hotseat discussing concepts and future developments, as well as strategically drawing things together in a way that makes sense.

It has become increasingly clear that a hostile tumour microenvironment may account for one of the reasons why many patients don’t respond to cancer immunotherapy.

How do we go about figuring out the whys and wherefores in order to significantly improve on the results seen to date with monotherapy treatment?

There are quite a few angles to look at this conundrum, so we decided to explore some concepts and analogies, as well as look at what’s going on under the hood of IO clinical trials to address the thorny issue of tumour heterogeneity.  We also discuss some of the top-line data in the cytokine niche presented at ASCO and look at the outcomes in the context of what we learn and where we going next.

There’s a lot to take in and process here, but that’s part of the fun!  As often is the case, some of the best gems are in the poster halls or poster discussion sessions…

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The potential of cytokines in cancer immunotherapy is now attracting a lot of attention with many in industry assessing whether they need a cytokine in their pipeline and if so which one may make the optimal combination partner.

We’ve been writing about cytokines for several years now and have been following several cytokine molecules, including Nektar’s novel pegylated IL–2 (NKTR–214) approach and Armo’s pegylated IL–10 (AM0010). Other technologies in early development include an IL–8 agonist from BMS and an IL–15 superagonist fusion protein from Altor Bioesciences.

#ASCO18 Blisterwalk to Developmental Therapeutic sessions

What does the future hold for cytokines – are they really the “best thing since sliced bread,” as we say in England or will they fizzle out and not prove to induce additive effects over and above monotherapy with checkpoint blockade?

For a view of where the field is at and where it might be going, while in Chicago we spoke with Dr Mario Sznol, who is a medical oncologist at Yale Cancer Center in New Haven, where he treats melanoma and kidney cancer patients.

He’s one of the leading translational researchers in cytokine drug development and is also the in-coming president of the Society for Immunotherapy of Cancer (SITC).

Readers of Biotech Strategy will recall that we last spoke with Dr Sznol at the 2015 SITC annual meeting where he talked about his renewed interest in cytokines, and in particular, interleukin–2 (IL–2) (See post: Novel immunotherapies and combinations). Since then, much has happened and there are now even more targets being investigated, as well as a wider cadre of researchers actively involved in this field.

Being president of a medical or scientific association takes up a lot of time, so it was a privilege to talk with Dr Sznol again, before he takes up his new honorary position in 2019.

To learn more from our latest thought leader interview and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

Palace guard in Stockholm

Stockholm, Sweden – The annual meeting of the European Hematology Association (EHA) is in full swing with updated data from two blue companies, Blueprint Medicines and bluebird bio of interest to BSB readers.

There is often beauty and simplicity to be found in nature that also applies to oncology R&D.

One of those aspects can be found in the concept of targeting particular aberrations or molecular rearrangements that driven oncogenic activity.  Once you connect the dots to arrive at these key targets, you can develop therapeutics that inhibit the activity, resulting in cessation or reduction in proliferation.

In our latest post, we focus on an update on Blueprint Medicine and take a look at their various programs in early clinical development, as they have quite a lot going on with multiple targeted compounds in different areas, including hematology.

To learn more from our latest analysis and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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