Biotech Strategy Blog

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

About Pieter Droppert

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Posts by Pieter Droppert

In a few years time the next generation CAR-T cell therapies are going to look and behave very differently from the somewhat crude versions we use in the clinic today, making them more akin to the homemade wooden go-carts of our misspent youth.

This is what science and technology is all about improvisation and innovation to create something bigger, better, faster, or even safer than what went before.

It’s a rite of passage just as many Dads and siblings went through numerous iterations of building go-carts, so too will we see a similar evolution in this cell therapy niche, although obviously more rapidly and on a much grander scale than those humble efforts to improve the speed or manoeuvreability we were all ardently obsessed with. Brakes, I have to admit didn’t even come into the equation until much later when a near-miss got us all grounded, but oh the fun we all had in the process!

If we want to improve the selectivity and killing capacity of the new CARs in both liquid and solid tumours, what practical aspects ought to be considered and how is synthetic biology going to get us there?

In our expert interview, we sought to learn how an expert in the field saw how things might be changing and where they could be shifting…

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Rotterdam harbour where even the architecture can look like CAR-T cell constructs!

For decades four tumour types always seemed to be considered the ‘graveyard’ of drug development with many a promising therapy hitting the skids and being banished to dog drug heaven…

  • Metastatic melanoma
  • Small cell lung cancer (SCLC)
  • Acute myeloid leukemia (AML)
  • Glioblastoma (GBM)

Of these, melanoma has been dramatically transformed by targeted therapies and checkpoint blockade, while AML has come of age with novel targeted therapies being approved for specific subsets and many more in development, and even SCLC has seen some success with both immunotherapy and targeted approaches.

This leaves us with refractory GBM as the main holdout and a 5% survival rate at five years post diagnosis.

The good news is there are various novel approaches coming through the clinic and more in preclinical development, some of which might well move the survival needle if all goes well.

In order to see improved success in the clinic though, we first have to marry the novel ideas with a greater understanding of the inherent challenges and hurdles we wish to address.  There are plenty of smart and articulate people quietly working at the coal face in various brain tumours with some intriguing ideas being evaluated going beyond the obvious.

In our latest BSB interview we talk to one of the experts in this niche and discuss the challenges, opportunities, and importantly – where is the field moving towards…

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We have heard much over the last decade or so about the impact of the microbiome on responses to hematopoeitic stem cell transplant (HSCT) and checkpoint blockade, but what about other immunotherapies such as CAR-T cells?

This could well be one of the unexpected X factors accounting for some of the differences in outcomes seen in clinical trials in this niche.

Increasingly, scientists and physicians are starting to see how we really might be what we eat as well as how diet might impact response to therapeutic intervention.

How then should we go about learning more about this issue and – and just as importantly – figuring out the next steps to improve function ahead of such treatment in order to maximise the survival outcomes for patients undergoing stem cell or CAR-T cell therapies?

To learn more about progress, we interviewed one of the pioneers in this field to see what he had to say…

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Innovation at the cutting edge, cube houses in Rotterdam designed by Piet Blom

Continuing our CAR-T cell therapy mini-series, we take a look at how some creative preclinical studies helped uncover a new mechanism of resistance to CAR-T therapy.

This then led to a novel enhancement or tweak in the engineering of the CAR-T cells in order to make them resistant to being killed themselves. These twin findings could lead to the enhancement of performance in the clinic for patients needing such treatment.

If we want to help more lymphoma patients get to the 6 month mark and beyond then we need greater understanding of the underlying issues combined with practical thinking skills.

In our latest expert interview, we discuss an innovative new cell therapy approach with an unusual strategy currently in preclinical development, which is heading towards the clinic …

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One of the hottest areas of cancer new product development is adoptive cell therapy and, in particular, the development of CAR modified natural killer cells (CAR-NK).

Which company will win the CAR-NK race?

We’re all familiar with CAR modified T cells, several of which are now FDA approved, while the next group of immune cells to receive renewed attention as a therapeutic are natural killer cells. They have unique properties and may have a role to play in the next generation of cancer immunotherapies.

While it’s still early days for CAR-NK cell therapy, if we have learnt anything from the first era of cancer immunotherapy it’s that we won’t know what will or won’t work, or even how durable any responses may be until we go into the clinic. Even then, it will probably not be until phase 2 multi-center trial readouts before we gain a sense of the real potential.

In the meantime, several companies are looking to ride the CAR-NK wave, and in this post, we’re highlighting a relatively recent newcomer, Catamaran Bio, who launched in November 2020 with a $42M series A round funding.

Recently, BSB spoke with Chief Scientific Officer, Vipin Suri PhD, about their preclinical data at AACR22 and the science behind their approach.

This is the second in our latest mini-series on CAR-NK cell therapy, where we explore the various challenges and opportunities in this emerging field.

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Deckchairs in Regent’s Park, London

It’s the dog days of summer and time for a mini-series with some expert interviews to enjoy while sitting in your “strandkorb” (classic German beach deck chair) in a Baltic sea resort, or wherever you’re chilling out.

It’s remarkable to see how the field of cell therapy continues to grow. Today and in coming weeks, we are taking a closer look at innovative ways companies are seeking to leverage the unique properties of Natural Killer (NK) cells.

Who will build the best CAR-NK construct?

Cell therapy remains one of the hottest areas for innovation. At this year’s annual AACR meeting (AACR22) we saw a lot of new data from companies in the field of CAR modified Natural Killer (NK cells).

We’re all familiar with the concept of putting a chimeric antigen receptor (CAR) on a T cell (CAR-T), so why not put a CAR on a NK cell to target it against tumors as well?

There’s certainly a lot of interest in this approach and as a result, the CAR-NK cell therapy landscape is fast-moving. We expect to see a lot more data and news roll out in the coming years, as companies look to bring new products into the clinic.

Recently we spoke with experts at three CAR-NK companies who had data at the 2022 AACR annual meeting – to be clear we’re not endorsing any of them, but each company offered a different scientific approach and perspective offering insights into the challenges and opportunities of this emerging field.

First up in our latest mini-series is Dr Bob Hollingsworth, Chief Scientific Officer of Shoreline Biosciences, a company who are looking to develop induced pluripotent stem cell (iPSC) derived NK cell therapies.

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I confess in the days when I watched TV if I was short on inspiration then I’d check out the TV guide in a newspaper to see what they recommended for the evening’s viewing.

Such guides are by definition, the eclectic, subjective choice of the reviewer and they are designed to showcase programs catching their interest and, in the process, persuade you to see something you might otherwise not have watched.

This post is written in the same spirit.

For the past several years now we’ve been writing about the potential of harnessing the unique properties of Natural Killer (NK) cells for cancer immunotherapy and even produced a podcast episode on it back in 2018!

Since the publication of a landmark NEJM paper on CAR modified NK cells in 2020, we’ve seen even more interest flourish in the field.

This year’s annual meeting of the American Association for Cancer Research (AACR) has something for everyone involved in cancer research. It’s a veritable smorgasbord and just like watching TV there are multiple channels simultaneously going on over several days.

In this post we’ve taken a look at some of the NK cell presentations at AACR22 which caught our attention and why. You can find all of our ongoing AACR22 coverage here.

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At the #CART22 meeting jointly run by EHA/EBMT, one of the sessions yesterday attracting a lot of interest and attention was one on the application of CAR T cell therapy beyond hematologic malignancies and solid tumours.

In a world where academic medicine is increasingly the domain of sub-specialists, as it is in many professions, it was refreshing to see the organizers of the meeting think ‘outside the box’ and offer the opportunity to hear speakers you wouldn’t typically expect at a meeting organized by hematology focused organizations.

Is the future of CAR T cell therapy, to paraphrase the oft-quoted Star Trek introduction, to seek new frontiers and boldly go where T cells have not gone before?

In this post we take a look at some of the data presented and offer our perspectives.

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I can’t believe it’s two years since we last attended a medical or scientific meeting in real life, but the last time we had “boots on the ground” was in pre-Covid times, at a CAR T cell meeting held in Sitges, a small coastal town and former fishing village south of Barcelona with phenomenal light.

Organized jointly by the European Hematology Association (EHA) and European Society for Blood and Marrow Transplantation (EBMT), their annual CAR T meeting attracts “the great and the good” of cell therapy and back in 2020 we were able to interview luminaries such as Carl June, Stan Riddell, John Gribben, and Crystal Mackall in person.

This year’s CAR T meeting, now in its fourth iteration, offers a mix of clinical practice, practical advice for those running CAR T units, as well as offering keynote lectures and posters on new developments in the field. Attracting speakers from the US, EU and UK (sadly no longer part of the EU thanks to Brexit, a decision that is unlikely to make Britain great again), it has an inclusive feel about it with physicians, scientists, nurses, and patient advocates all part of the program.

Thanks to Omicron, EHA/EBMT had to pivot to a virtual meeting at the last minute, so everyone missed out on a jolly to Nice. The organizers are to be congratulated for making the meeting happen rather than postponing to the Autumn, as many have done recently thereby adding to what is already looking like a busy conference schedule for late 2022, presuming another Covid variant doesn’t come along to cause disruption…

So, what were the highlights from Day 1 of the 4th annual EHA/EBMT CAR T meeting and what did we learn about the direction of the CAR T cell field?

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The annual meeting of the American Association for Cancer Research (AACR) is an event we at Biotech Strategy Blog really enjoy writing about due to the outstanding depth and breadth of the scientific content.

The 2021 organizers led by program committee chair Prof Charles Swanton FRS are to be congratulated in putting together a meeting that has something for everyone involved with cancer research, whether you’re in academia, industry, or clinical practice.

While we may miss the personal contact of real life meetings there are many advantages to the virtual format, including the avoidance of scheduling conflicts, the ease of hearing and seeing presentations without worrying about the person in front or poor room audio quality, not to mention the ability to stop and rewind a presentation if you didn’t quite catch what was said. The virtual format definitely improves accessibility for those who are disabled or for whom English may be a second or third language.

When the world moves on to hybrid virtual/live meetings as looks likely in 2022 then we hope we won’t lose all the advantages of the virtual meeting concept. It’s outside the scope of BSB, but there is an opportunity to reimagine the medical/scientific meeting rather than simply go back to what we had before.

Spring flowers herald the start of a new cancer conference season

In this preview post we’re taking a look at the “on-demand” sessions available starting on April 9, 2021 – we’ve selected fifteen presentations which caught our attention. Some are by researchers we’ve interviewed on BSB, others are stories we’ve been following around a particular topic or target.

If you’re looking to go outside your own area of interest at AACR21 and are overwhelmed with choice then this post offers a few suggestions and explains why they should be worth watching.

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