Biotech Strategy Blog

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

About Pieter Droppert

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Posts by Pieter Droppert

Exploring the immunological links between lung cancer and Covid–19

We are living in exceptionally challenging times and our thoughts are very much with all those healthcare professionals at the front line in the battle against Covid–19.

For people living with cancer, particularly those who have stage IV disease, the stark reality – in the UK and even some States in the US – is an ICU bed may not be available if they come down with the severe form of the disease.

When it comes to cancer research most labs, with the exception of those working on Covid–19, are now closed, but there is still data coming out to keep us all going as we work from home. ASCO20 will be a virtual meeting this year, while AACR will likely have some virtual presentations later in April. There are also plenty of publications coming out in journals from work already completed.

In this post we’re looking at newly published research and one possible immunological link between inflammation related to cancer and certain infectious diseases.

Last week we spoke to Dr Kamal Khanna (@Kamal_M_Khanna), Associate Professor at NYU Langone about research from his lab, which has just been published in the journal Science Immunology.

Although science is important, what matters most in these exceptional times is making sure everyone comes through it safely. Dr Khanna kindly spoke to BSB under embargo on Wed 25th March, where we also spoke about the surreal experience going on around him as we asked, how are things going with you in New York?

“It’s crazy. This has become the epicenter now. It just moved so fast here from having no cases and everyone wondering what’s going on to just explosion. Lab is shutdown, unfortunately. They’re allowing one person to go in at one time, in my lab just to maintain mouse colonies and do very limited experiments.

They’re allowing us to do the Covid–19 experiments, which we started just a few days ago, but also in a limited fashion. Those are the things we’re doing right now is simply plaquing the virus, and we have a few strains and we’re just testing growing them and so. We’re getting some limited human samples, but probably that will explode now. Our hospital has the most amount of Covid patients, so much so that they just made a makeshift morgue with a tent, unfortunately, right next to where we are.

So that’s the reality of where we are right now and hoping that this will peak at some point, they’re predicting in about 2 to 3 weeks that it would reach its apex and then all the social distancing and things that we’ve been doing, hopefully that will start to bring some of the numbers down, that’s the hope.”

In this post we offer an extended interview with Dr Khanna where we explore possible immunological links between inflammation in relation to cancer and infectious diseases and how research from his lab could generate new insights into cancer, as well as some potential impacts for Covid–19.

If you’d like to read our latest in-depth expert interview on cancer-related topics, please do consider supporting independent science journalism in these challenging and exceptional times.

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Unlocking novel IO targets and anti-cancer agents in early development

Time to unlock some novel IO targets?

Continuing our latest four part mini-series, this one is on novel targets and agents and we now turn our attention to immuno-oncology in the last two articles pertaining to this particular topic.

You can read the first two articles on targeted therapies here and here.

For the avoidance of any doubt, this latest review is not about T cells, far from it.

Instead we cover six different areas, most of which are related or integrated in some shape of form.

There’s a lot of promising new science now coming out to help us better understand the underlying biology and also think out of the box about ways to enhance or improve on existing research.

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A delicate question of balance

When should someone receive CAR T cell therapy? How do we identify who will benefit most or who will be most likely to fail? Those are some of the questions we’re considering in our latest expert interview.

As we see the landscapes around aggressive lymphomas and multiple multiple evolve and change with more near-term CAR T cell therapy approvals coming, so too do the clinical questions surrounding the optimising of these novel approaches.

Prof John Gribben, President of EHA (right) at CART2020 in Sitges

At the EHA/EBMT 2nd European meeting on CAR T cell therapy, BSB spoke with Professor John Gribben. He’s the current President of the European Hematology Association (EHA) and holds the Gordon Hamilton Fairley Chair of Medical Oncology at St. Bartholomew’s Hospital, Barts Cancer Institute, Queen Mary, University of London.

One of his messages was when considering CAR T cell therapy, it’s a delicate question of balance.

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In Plain Sight

ASH19 in Orlando, FL

Orlando: In the second of our ASH19 reports, we offer a comprehensive and in-depth look at important data presented over the weekend where we breakdown some of the key findings or trial readouts, which are likely of interest to many readers given the heightened attention on novel therapeutic approaches.

Whether the hematologic malignancy is myeloma, leukemia, or lymphoma, we have been rather spoiled for choice in selections for hot topics to discuss this year, so the series will likely run all week!

Here’s the second of our detailed ASH notes…

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Friday Scientific Workshops are the Perfect Warm-Up act to ASH19

Friday at #ASH19 – remains of the day or hope springs eternal with sunrise on Saturday morning?

Orlando: The annual meeting of the American Society of Hematology or ASH (Twitter #ASH19) is one of the four key Majors on cancer-related related research meeting circuit that BSB attends each year.

Just as golf has the Masters, the US Open, the Open, and PGA championships, so those on the cancer new product development circuit attend AACR, ASCO, ESMO, and ASH.

This year ASH is in sunny Orlando where you have to compete with the tourists for Uber rides if you want to venture to restaurants or events in the area.

Friday at ASH has traditionally been associated with the satellite symposia, colloquially known as “Super Fridays” that CME companies or organizations such as the Leukemia Lymphoma Society have traditionally run, but in recent years ASH has put on its own Friday events to compete with both the industry satellites and also academic events such as the BMT Winter Workshop we have attended in the past.  More choice is good on one hand, but bad on the other in that something has to give way.

Ron Levy (Stanford) and Stephen Ansell (Mayo) blazed the trail a few years ago with their Friday Scientific Workshop on Tumor Immune Interactions in Lymphoid malignancies. Regular BSB readers may recall the interview at ASH16 with Dr Levy where he reviewed some of the data in that year’s workshop (See post: Targeting the tumour environment in lymphomas.)

This year on Friday at ASH19 there were multiple scientific workshops you could attend. What were some of the presentations that caught our personal attention, what can we learn from them and why did they matter?

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The potential of innovative mouse models to recapitulate the microbiome of cancer patients

SITC 2019 Preview: After looking at exciting new developments in targeted therapies last week, it’s now time to switch horses and kick off our annual coverage of the Society for Immunotherapy of Cancer (SITC) meeting, which takes place in a few days time at National Harbor in Maryland.

National Harbor, MD

In the SITC 2019 Presidential Session this coming Saturday, one of the presentations we are eagerly looking forward to is by Dr Vyara Matson, a Post Doc in the lab of Dr Tom Gajewski at the University of Chicago.

Dr Matson will be presenting on “Patient-derived microbiota germ-free mouse model for identifying mechanisms of checkpoint blockade efficacy modulation.”

In our latest expert interview, we spoke to Dr Gajewski about the strategic concepts underpinning his work in the microbiome niche, where he has got to presently and where he plans to go next. It makes for fascinating reading, especially when you realise that as scientists, they are sceptical themselves and yet curious to discover the answers through carefully thought out experiments that could impact future patient care for those people receiving immunotherapy for the treatment of their particular cancer.

One major take home for us in following the cancer immunotherapy niche is that there could well be different mechanisms at play for primary and secondary resistance – where does the microbiome fit in with this, and can it be manipulated to create a more positive benefit?  Is the effect a real one or a spurious correlation?  These kind of questions, along with a host of others, are some of the key topics discussed in the expert interview.

If you have plans to be at #SITC2019 do let us know, as we always look forward to saying “hello” to BSB readers.

Subscribers can read more on why we think this work is innovative and important to our understanding of what’s going on in responders and non-responders by logging in or you can click to gain access to BSB Premium Content.

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Targeting NRG1 Gene Fusions

Boston: The 2019 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics is underway (#Targets19). It’s long been one of our favorite meetings, particularly when held in Boston, and this year there’s a raft of early ideas on offer as to where the targeted therapy field may be going.

Alison Schram, MD. Credit: MSKCC

The success of Ignyta’s entrectinib (acquired by Roche) and Loxo Oncology’s larotrectinib (acquired by Lilly) in targeting NTRK gene fusions has raised interest in targeting other gene fusions, even if they are rare. A new target in a similar vein that has attracted interest recently are fusions involving the neuregulin 1 gene (NRG1).

At this year’s Molecular Targets meeting, Dr Alison Schram, a medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSK) presented clinical proof of concept data for MCLA-128 (Merus), a bispecific HER2/3 antibody therapy in NRG1 fusion positive cancers.

What did we learn about MCLA-128 and NRG1 at Targets19?

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What did we learn about ALRN-6924 at ESMO19?

Oncology R&D is very much a tale of two cities. At one end you have all big pharmas and biotechs with significant resources in the form of very large budgets, (hopefully) an extensive pipeline, plus many hands on deck to efficiently spread the workload, while at the other end you have what I call the ‘baby’ biotechs with completely the opposite situation coupled with a much greater need for prudence in how those scarcer resources are managed.

A failed drug development may not affect big pharmas very much, it’s written in to the strategic plans after all, and a 90% failure rate is very much de rigeur so you’re looking for the rare gems that will shine and carry the rest. In small biotechland, such inherent risks are much more prominent – and drastic – because a failed program can wipe out the stock overnight such that future endeavours to raise money are greatly hampered, putting the very life of the company at risk of not only delisting (if publicly traded) from stock exchanges such as NASDAQ, but also the ultimate doom.

The constraint that both bookends have in common, however, is familiar to many readers – how to get the best shots on goal given the time, energy, and resources available?

At BSB we don’t write just about big Pharma – we also try to highlight the roller coaster experienced at the other end of the spectrum and showcase some cool science in the process. Given our interest in stapled proteins as well as the various challenges associated with both tumour suppressors and MDM2, it seemed like a good idea to catch up with the folks at Aileron Therapeutics (NASDAQ: ALRN) and learn more about their progress since they combine all three elements in one go…. it’s time for some gems from the ESMO19 poster hall.

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Eyes on CAR-T Cell Therapy in Europe – Future Directions

One of the delights of going to a major medical/scientific meeting such as the recent European Society for Medical Oncology (ESMO) Congress in Barcelona is that there often meetings going on around it, which offer unique and novel perspectives.

For example, on the Thursday before ESMO19 there was a one-day workshop on “Breaking through emergent immunotherapy and immune targets in cancer.”

Dr Manel Juan Otero presenting at the FLS Science symposium

Organized by FLS Science, it took place at the Casa de Convalescència in Barcelona. The program featured a mix of Spanish immunologists and clinicians, along with some leading US researchers including Dr Tom Gajweski (Chicago) and Dr Antoni Ribas (UCLA).

It was definitely well worth attending and I encourage you to look out to see if the organizers run the again meeting before ESMO20 in Madrid next year.

One of the most interesting speakers at the meeting was Dr Manel Juan Otero (right) who heads up the section of immunotherapy at the Hospital Clinic of Barcelona.

In his talk, he spoke about the “Future Directions for CAR-T Therapy” in Spain, which turned out to be a dramatic one with unexpectedly broad European implications.

During a lunch break at the meeting, Dr Juan Otero kindly spoke to BSB about his plans, which could have an impact on commercial CAR T cell therapy companies such as Novartis and Gilead.

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New directions in HR-positive breast cancer

It’s time to talk about new developments in breast cancer.

@3NT with Dr Dennis Slamon at ESMO19

This week we will be featuring thought leader interviews with two breast cancer specialists as we look at new data in different subsets of this disease, in both early and metastatic settings.

We like to ring the changes with invited guests on BSB who comment on trial results and offer broader perspectives on their specialist field as well.

One expert is someone neither of us has ever interviewed before, while the other returns for an update on an early trial that is showing promise. Both interviews were conducted under embargo ahead of their presentations in Barcelona.

One of the myriad of challenges in oncology R&D is the tendency to begin exploration in the most advanced form of the disease with monotherapy to determine single agent activity and then work up to earlier lines of therapy with combinations evolving over time.

While it is always good to see proof that people are living longer with particular approaches, there is a real need to keep one’s eyes out on the horizon for new developments that may extend overall survival further.

What should those regimens look like and what are rational choices based on the underlying biology of the disease rather than being explored because that’s what a particular sponsor happens to have in their pipeline? We were delighted to have the opportunity for a much broader discussion some of these opportunities with today’s key opinion leader, Dr Dennis Slamon of UCLA, who presented data in an ESMO Presidential symposium and also talked about other topics in breast cancer research with BSB.

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