Biotech Strategy Blog

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

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An up and coming biotech not at JPM

New Horizons in CAR-T cell therapies

One important area we are going to focus more on in 2024 is exploring promising up and coming early stage biotechs not yet at the JPM Healthcare conference.

After all, big Pharma companies will be looking to either acquire private biotechs outright or license their clinical stage assets, replenishing pipelines before possible IPOs make them too expensive as a convenient strategy for bolt-on deals.

We have already seen how the IRA changes are driving a switch from oral molecules to iv compounds such as ADCs of late, but what about cell therapies?

In this example, the company have come up a creative CAR-T cell therapy strategy, the first of which is heading into the clinic this year, plus they have a raft of others swiftly following on and currently being put through their preclinical paces.

What do we mean by creative?

Here they a exploring a number of key targets not named CD19/CD20/BCMA or even GPCR5D.  In other words, they’re quite different from the usual CAR-T fare. Some of these were considered tricky in the past, yet by pursuing different scientific angles a viable strategy can result.

It’s time to explore new horizons and opportunities in this niche and discuss where might things be headed?

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Powering up CAR-T cells

Tackling T cell fitness and exhaustion will not be plain sailing, yet they will be an important focus going forward

One of the often ignored challenges in advanced cancers – regardless of whether they are hematologic malignancies or solid tumours – is the quality of the patient’s T cells.

Oftentimes these may be dysfunctional or exhausted, which means responses to any given therapy will be impacted in a negative fashion.

What if we learn more about the underlying biological processes involved – can the knowledge acquired lead to enhancements in the design of CAR-T cell products, the overall quality of the T cells, and hence improvements in outcomes?

While several companies have been active on this front, we went deeper and spoke with an academic researcher keen to leverage research findings, which may uncover novel approaches for future developments.

Rewriting T cells may prove to be an important emerging area of research to watch out for in 2024…

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What will novel CAR-T cells look like in the future?

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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Cool and emerging new concepts to watch out for in Gliomas

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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Diet as a drug

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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Thinking outside the Box

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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Catamaran Bio sets sail in 2022

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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Shoreline rides the CAR-NK wave at AACR22

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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What to watch at AACR22 on NK cells

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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Is the future of CAR T cell therapy beyond Oncology?

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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