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

A tale of 3 cellular therapy companies

London – last week a half day event at The Francis Crick Institute looked at three UK cell therapy companies that have been spun out of academic research from partner institutions, UCL and King’s College London.

Medicine at Crick Welcome

Professor Julian Downward welcomes everyone to The Crick

We heard from the CEOs of Achilles Therapeutics, GammaDelta Therapeutics and Autolus Therapeutics on how they are translating science into new adoptive cellular therapies.

There were also presentations from leading scientists whose research they are commercializing.

All three companies were founded in 2016, so the event was a fascinating snapshot as to where are they now, roughly 3 years on, what have they achieved and where are they going.

They vary in terms of their vision, innovation and their adoptive cellular therapy approach.

Autolus are developing autologous CAR-T cell therapies, GammaDelta Therapeutics are focusing on allogeneic Vδ1 gamma delta (ϒδ) T cells, while Achilles Therapeutics are targeting patient-derived clonal neoantigens.

If you couldn’t make this Medicine at the Crick event, what were some of the take home messages, and how do we think these companies compare to some of their competitors?

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TC BioPharm leads the way in allogeneic gamma delta T cells

For the final post in our mini series on the potential of gamma delta (γδ) T cells for cancer immunotherapy, we’re traveling to Scotland with a visit to a company that is a poster child for Scottish enterprise.

TC BioPharm Office Building

TC (as in T cell) BioPharm are leading the way in development of allogeneic γδ T cell therapies. They’ve already completed a trial of autologous γδ T cell therapy to establish safety and now have an allogeneic phase 1 trial underway in Prague.

TC BioPharm logoCEO and Founder, Dr Michael Leek, has built a company that already counts bluebird bio (NASDAQ: $BLUE) as one its partners (Link).

Co-Founder and Chief Operating Officer, Dr Angela Scott was part of the team that cloned the first mammal, “Dolly the Sheep.”

Angela Scott COO and Co-Founder of TC BioPharm

Dr Angela Scott, COO

She was recently profiled in The Herald (Link) and her cell therapy experience has been instrumental in the development of the company’s own GMP manufacturing facility in Scotland.

As the Herald article notes, the company is being positioned for a possible NASDAQ IPO in 2020, so is definitely one to watch out for.

We all remember catchy advertising slogans, and one I remember well is for the now defunct Orange mobile phone network in the UK: “The future is bright, the future is orange.”

If you’re TC BioPharm then maybe this could be construed as: “The future is bright, the future is allogeneic” (γδ T cells).

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Emerging Gamma Delta T Cell Cancer Immunotherapy Landscape

Aerial View Thames Estuary

Aerial View of Thames Estuary

There’s a lot of interest in the potential for γδ T cells for cancer immunotherapy with multiple US, UK and EU companies already active in the area, not to mention the Chinese too.

Now that we have a grounding in the science behind what role γδ T cells play in our immune system, what they ‘see’ and do, we can better consider how companies are translating basic research into therapeutics.

In this third post in our mini-series, we’re taking a closer look at the emerging new product development landscape.

This post is not intended to be a definitive analysis or report on the whole γδ T cell therapy landscape, instead we’ve chosen to highlight a few leading companies and use them as examples to illustrate different translational approaches that are being investigated. A report on developments in China will follow separately tomorrow.

Some companies are looking at adoptive cell therapy, others have monoclonal antibodies or bispecific antibodies in development.

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Are gamma delta T cells the next wave of cell therapies?

In the first post in our mini-series about the potential for gamma delta (γδ) T cells in cancer immunotherapy, Prof Adrian Hayday took us on a voyage of discovery through the pioneering research he and colleagues did at MIT, Yale, King’s College London (KCL) and The Francis Crick Institute in London.

Prof Adrian Hayday FRS

Prof Adrian Hayday FRS

Along the way he highlighted how our current understanding of γδ T cells has developed over the last thirty years.

“All truths are easy to understand once they are discovered, the point is to discover them.”

This maxim attributed to Galileo Galilei in a 1632 publication, is very pertinent to Prof Hayday’s research which was a fascinating journey of discovery.

For the second post in our mini-series we have a Q&A with Prof Hayday that takes the story forward and looks at how our understanding of the science behind γδ T cells has opened the door to translational and clinical opportunities such as adoptive cellular therapy.

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A Voyage of Discovery

This is the first part of our latest mini-series, which takes a closer look at the potential of gamma delta (γδ) T cells for cancer immunotherapy.

Prof Adrian Hayday FRS

Prof Adrian Hayday FRS

In this post, we’re focusing at the voyage of discovery made by one of the pioneers in the field, Professor Adrian Hayday, FRS.

We’re living in a golden age of immunology. Basic research conducted over the past thirty years is beginning to pay dividends as it is translated into new cancer treatments that leverage the power of the immune system.

As things stand today, however, the majority of cancer patients do not respond to approved immunotherapies such as checkpoint blockade, either as single agents or in combination with chemotherapy. This means that we still have a long way to go to make these therapies an effective and widely available modality for the majority of cancer patients.

Despite the “hype and hope” surrounding the approval of two cell therapies based on CD19 directed CAR T cell therapies for certain types of blood cancers, there remain many challenges before more widespread use is likely. These include long term durability and persistence, overcoming antigen loss/immune escape, developing safe and effective allogeneic (off-the-shelf) treatments, as well as finding suitable targets for solid tumours.

The cellular therapy landscape is undoubtedly still emerging. While many companies have jumped on the CAR T cell bandwagon, others are looking at new and novel opportunities, one of which is the potential of unconventional lymphocytes, such as γδ T cells.

The Francis Crick Institute viewed from The British Library

The Francis Crick Institute viewed from The British Library

Someone who is a pioneer and leading researcher in the γδ T field is Professor Adrian Hayday. He’s a Senior Group Leader and Assistant Research Director at The Francis Crick Institute and has been the Kay Glendinning Professor of Immunobiology at King’s College London since 1998. He was elected a Fellow of the Royal Society (FRS) in 2016.

Prof Hayday kindly spoke to BSB about his γδ T cell research and the voyage of discovery that have taken him from basic biology to translation into a novel cancer immunotherapy.

What is the potential of γδ T cells for cancer immunotherapy?

BSB readers will, hopefully, have a clearer idea after reading our latest four part mini-series.

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Book Review – L’Immunothérapie des cancers

The latest addition to the burgeoning list of books on the advent of cancer immunotherapy comes from two French immunologists, Éric Vivier and Marc Daëron.

The timing of the award of the 2018 Nobel Prize for physiology or medicine to Jim Allison and Tasuko Honjo, certainly seems to have acted as a catalyst for the publication of several books about the field.

There are a variety of ways to approach the cancer immunotherapy story, ranging from the personal portraits of researchers behind the science to narrative storytelling based on the “Hero’s journey” where the intrepid hero embarks on a quest, overcomes challenges or tests along the way and then finally emerges triumphant. One could certainly fit Jim Allison’s life and accomplishments into that mold.

We don’t normally review books on BSB, but were very curious to see how immunologists themselves would approach their specialist area and tell the cancer immunotherapy story. After all, everyone views the world through the lens of their own experiences and the bias that creates.

L’Immunothérapie des cancers, histoire d’une revolution médicale’ offers the reader a journey through the history of science.

Marc Daëron is a researcher at INSERM, the Institut Pasteur in Paris and Centre d’Immunologie de Marseille-Luminy (CIML). He’s also an associate member of the Institute for History and Philosophy of Science and Technology.

Prof Éric Vivier at 40th Anniversary of Centre d’Immunologie de Marseille-Luminy

BSB readers are already familiar with Éric Vivier (Twitter @EricVivier1) who is a Professor of Immunology at the University of Aix-Marseille and was previously Director of CIML.

An expert on innate lymphoid cells, natural killer cells and innate immunity, he’s also a co-founder of Innate Pharma and is currently the company’s Chief Scientific Officer (CSO).

If you want to hear them in person, the authors discussed their book on a recent France Inter talk show, which also includes a couple of patients doing well on immunotherapy phoning in.

Assuming you have a reasonable level of French, is L’Immunothérapie des cancers, histoire d’une revolution médicale well worth a read? Who is the audience? What did we make of the approach taken by two eminent immunologists?

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Potential of CAR T cell therapy in CLL

Standing from the crowd in refractory CLL?

Last year the two FDA approvals of tisagenlecleucel (Novartis) and axicabtagene ciloleucel (Kite/Gilead) CAR T cell therapy for hematologic malignancies such as pediatric acute lymphoblastic leukemia (pALL) and non-Hodgkins lymphoma (NHL) have captured a lot of attention.

It’s worth remembering, however, that back in 2010 the first patient who had a dramatic response to CD19 targeted CAR T cell therapy was actually a gentleman with advanced chronic lymphocytic leukemia (CLL), the case study of which was subsequently published by Porter et al., (2011) in the New England Journal of Medicine.

We’ve been following CAR T cell therapy and its potential in CLL for some time now, with all the successes, trials and tribulations along the way.

Dr David Porter (Penn) told BSB earlier this month:

“The very first patients we treated are now eight years out from their infusion, a little over eight years, and still in remission, still doing extremely well with no evidence of disease or progression, never had any other therapy. So, I think it’s become very clear that for some patients this is effective in the far advanced setting.”

It’s now two years since we last spoke and it was a great pleasure to reconnect with Dr Porter. As he told BSB at ASH in San Diego:

“One way you make it better is to understand why it’s working and why it’s not.”

What have we since learnt about the potential for adoptive cellular therapy in CLL and what new insights did we gain from new data presented at ASH18? The answers may well surprise you.

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ASH18 Highlights from Day 3

What latest ASH18 data jumps to our attention?

San Diego – It’s time to put another dozen studies in the spotlight and review what we can learn from the existing data with a view on where we’re headed in the future.

Today’s list covers a whole gamut of targeted therapies, bispecific antibodies, CAR-T cell therapies and other immunotherapies, what’s more we have a range of targets in the list too, and not the obvious ones either.

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Pinning down potential new opportunities for IL–8 and 4–1BB

The keynote address at the 2018 CRI CIMT EATI AACR International Cancer Immunotherapy Conference in New York last month was given by Ignacio Melero (Pamplona). Professor Melero gave an engaging and informative presentation entitled, “The immunotherapy faces of Interleukin–8 and CD137.” He also had a related talk on “4–1BB and Metabolism” at the Society for Immunotherapy of Cancer (SITC) meeting this weekend.

Pinning down new opportunities in IL-8 and 4-1BB

The late and sadly missed, Dr Holbrook Kohrt (Stanford), worked closely with Prof Melero on targeting CD137 or 4–1BB, as it’s more commonly known.

Regular readers may recall our interview wth Dr Kohrt back at Immunology 2015 in New Orleans (Link).

Professor Melero kindly spoke to BSB at SITC 2018 and shared his thoughts on where we are three years on and where his research is currently focused in relation to cytokines, and in particular, IL–8.

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Can CytomX’s Probody checkpoint beat the competition?

Autumn leaves in Munich

We have increasingly seen how oncologists like the efficacy associated with the immune checkpoint combination of ipilimumab plus nivolumab, but are leery of the increase in side effects, including immune related events.

Are there practical ways to reduce this phenomenon, other than dose reductions?

CytomX are one company who are focused on engineering a different concept with their monoclonal antibodies, bispecifics and ADCs to try and mask the effects, thereby reducing the treatment emergent toxicities.  Their main idea is that the therapeutic window can be widened, thereby improving the tolerability profile.

It’s a nice idea, but what happens in practice?

To find out, we took a look at the recent early clinical data and interviewed executives from the company…

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