Biotech Strategy Blog

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

About Pieter Droppert

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Posts by Pieter Droppert

Readers may recall at the 2014 annual meeting of the Society for Immunotherapy of Cancer (SITC) we wrote about the work of Dr Marcel van den Brink (MSKCC) on how the composition of bacteria in the gut can have an impact on graft-versus-host disease (GvHD), and survival post bone marrow transplant. See post: Can you reduce Graft versus Host Disease GvHD by regulating gut bacteria?

At SITC 2015, we heard from Dr Tom Gajewski (University of Chicago) who presented work from his laboratory, recently published in Science, that shows the gut microbiota can also impact the efficacy of checkpoint inhibitors.

Tom Gajewski SITC 2015

Dr Gajweski is one of the foremost cancer immunotherapy researchers in the United States. He previously spoke with BSB about his work on the STING pathway, and how the tumor microenvironment impacts checkpoint inhibitor efficacy. See post: Tom Gajewski takes the STING out of Cancer.

In his extremely busy schedule at SITC, Dr Gajewski found a few minutes to talk about his latest research and future plans.

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Some people may think that if you just give a whole boat load of engineered T cells, and in particular, those modified with a Chimeric Antigen Receptor (CAR), that responders are “cured.”

While some recipients of engineered T cells can have long-term, durable remissions, others may initially respond, only to subsequently relapse.

Resistance to CAR T cell therapy can and does occur.

In this post, we talked with a leading expert about the latest research on how resistance to cell therapy develops, and the potential strategies to overcome it.

CAR T cell therapy is exciting, but remains an emerging field with multiple ways in which the competitive landscape may be shaped moving forwards.

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That’s the $64K question we all want to know, and what’s more is gene editing necessary when it comes to creating an “off-the-shelf” T cell therapy, which instead of modifying a patient’s own T cells (autologous), uses cells from a healthy donor (allogeneic)?

We were really curious too, and sought out one of the world’s leading experts for their opinion on this very issue.

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SITC 2015 National Harbor Gaylord MDNational Harbor, MD.  Today was a busy day with the ASH abstracts coming out this morning, and some ground-breaking data that demanded an immediate #ASH15 preview post.

At the same time we’re here at SITC, and keeping an eye on the AACR-NCI-EORTC Molecular Targets meeting – it’s like three buses come at once!

So what happened at SITC today? In this post we’ve put a quick summary of some of the presentations we heard on Day 2 that stood out.  Sometimes what’s most important is what people don’t say.

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Dr Jerome GalonDr Jérôme Galon is a leading Immunologist and Research Director at INSERM in Paris.

At the recent European Cancer Congress in Vienna he gave an engaging presentation in the scientific symposium on Cellular Immunotherapy of Cancer.

Afterwards, Dr Galon (pictured right) kindly spoke to BSB about:

  • What is immunosurveillance?
  • How the type, location and density of immune cells present within tumors predicts clinical outcome.
  • The potential of the Immunoscore assay to classify cancers based on their immune profile
  • What the future may hold in terms of personalized cancer immunotherapy.

One only has look at the impressive list of companies for which Dr Galon is a consultant or scientific adviser to see how valued his work in the cancer immunotherapy field is; it was a privilege to talk with him. The excerpts of the in-depth interview he kindly gave make for a good weekend read!

Grab a coffee & bagel and enjoy!

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ECC 2015 Dr Sandra Demaria Radiation Immunotherapy Title SlideAt the recent European Cancer Congress in Vienna, one of the Immunotherapy in Cancer Scientific Symposia that caught my attention was on Combining Radiation and Immunotherapy.

When it comes to immuno-oncology, it’s a topic we’ve not heard that much about, although many trials in combination with radiation are planned or in progress.

In the symposium, Dr Sandra Demaria (Weill Cornell Medical College) gave a presentation entitled: “Molecular Basis for Radiotherapy in Synergy with Immunotherapy.”

What are the new concepts on how to combine radiation with immunotherapy?

Dr Demaria shared her thoughts with BSB; excerpts from the interview are included in the following post along with additional commentary.

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Dr Holbrook Kohrt StanfordHolbrook Kohrt MD PhD (pictured right) is a Stanford medical oncologist and clinical researcher who is leading the way in cancer immunotherapy combination strategies targeting CD137 (4-1BB).

He’s a speaker I greatly enjoy listening to at meetings. Earlier this year at The American Association of Immunologists (AAI) annual meeting (Immunology 2015) in New Orleans, he gave a noteworthy presentation on combination monoclonal antibody therapy.

The potential of a combination of an anti-CD137 monoclonal antibody such as urelumab plus an anti-CD20 such as rituximab, was one that he appeared to be particularly excited about.

Dr Kohrt kindly spoke with BSB and shared his thoughts on the potential of immune modulators, which instead of acting as inhibitors to “release the brake,” like checkpoint inhibitors, act as agonists to “step on the gas” and rev up the immune system. This is a concept that many Pharma companies are currently looking to explore for new drug development opportunities, for example:

Roche ESMO Media Briefing Immunotherapy Approach

Source: Roche Media Briefing at ESMO 2014 in Madrid

When it comes to combination strategies, the big unanswered questions are which ones will produce big gains in response rates and survival outcomes, and which ones will be duds?  

After all, much like targeted therapies, not all targets will be relevant in all tumour types – it will depend on the underlying immune system.

In New Orleans, Dr Kohrt talked about the potential advantages and concerns around combination strategies and why he’s particularly interested in CD137 as a novel target for immunotherapy.

In-Memorium Holbrook Kohrt 

It is with great sadness that we must report that Holbrook Kohrt is no longer with us. He died, aged 38, on February 24, 2016.

 

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Oxford based Immunocore is an emerging UK biotechnology company that should be on your radar if you’re following companies such as Kite Pharmaceuticals and Juno Therapeutics. If it isn’t already you can expect to hear a lot more about them in the forthcoming year as they start clinical trials with the many leading global pharma companies who have already partnered with them.

Dr Namir Hassan, Immunocore

Immunocore is an immuno-oncology company with an innovative approach to targeting T Cell Receptors (TCR) using their proprietary ImmTAC (Immune mobilising monoclonal TCRs against cancer) technology platform.

Namir Hassan, D.Phil (pictured right) is Director of Translational Research and Head of Development at Immunocore. BSB met with him and Chief Business Officer, Eva-Lotta Allan at the company offices located in a science and business park near Oxford.

Immunocore recently raised $320M in Europe’s largest private life sciences funding. (Link to Press Release)

Earlier this year preliminary clinical data for IMCgp100 their first-in-class novel immunotherapy was presented at the annual meeting of the American Association for Cancer Research (AACR) in Philadelphia by Mark Middleton, Professor of Experimental Cancer Medicine at the University of Oxford.

In the interview, excerpts of which you can read below, Dr Hassan explained why their exciting and innovative approach that targets the T Cell Receptor is different from other companies in the field, what they have learned from the preliminary clinical data, and the potential immTACs may offer in combination with other cancer immunotherapies.

If you’re not a cancer immunologist, this type of science is complex, so the aim of the interview was to put into context the data already in the public domain and gain some insights into the excitement behind ImmTACs and what immunocore are doing. If you don’t understand the potential of TCRs and ImmTACs as immunotherapies, this post is for you!

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LONDON – atezolizumab (Roche/Genentech) is expected to change the standard of care (SOC) for the treatment of metastatic urothelial bladder cancer. That’s the key message I took from a recent interview with Professor Tom Powles (Barts Cancer Institute) on the role checkpoint inhibitors and cancer immunotherapy will play in the treatment of bladder cancer.

Professor Tom Powles BartsReaders will recall the compelling early phase 1 clinical trial data for atezolizumab (formerly MPDL3280A) that Prof Powles (pictured right) presented just over a year ago at the 2014 ASCO annual meeting: “Making a difference in advanced bladder cancer

Although other checkpoint inhibitors are in bladder cancer trials, and we have written about the pembrolizumab (Merck) data first presented at ESMO 2014 (“Breathing New Life into Bladder Cancer Treatment), it is expected that atezolizumab will win the race to market in the US and be the first checkpoint inhibitor to gain FDA approval for the second-line treatment of advanced bladder cancer.

Atezolizumab received breakthrough therapy designation (BTD) in May 2014 from the US Food and Drug Administration for PD-L1 positive metastatic urothelial bladder cancer after progression or intolerance of platinum based chemotherapy.

Earlier this summer Genentech announced in a press release that the IMvigor 210 phase 2 study was positive and met it’s primary endpoint, with a greater response rate associated with higher levels of PD-L1 expression.

European Cancer Congress 2015This data will be presented on Sunday Sept 27 as a late-breaker at the forthcoming 2015 European Cancer Congress in Vienna (Twitter #ECC2015), the European equivalent of the ASCO annual meeting organized in alternate years by ECCO and ESMO:

Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210)

Although we won’t know the trial results until they are presented in Vienna by Dr Jonathan Rosenberg (MSKCC), based on the recent press release it’s widely expected that the positive data from this trial will lead to rapid regulatory approval in the United States.

Subscribers can login below or you can purchase access to read Prof Powles’ opinion on the role checkpoint inhibitors will play in the treatment of bladder cancer, how this may play out in Europe as compared to the United States, and what the future may hold beyond checkpoint monotherapy.

This interview does not discuss the data to be presented at the 2015 European Cancer Congress, the results of which we will have to wait until Vienna to hear.

One of the interesting questions raised by the recently announced and much-discussed Juno/Celgene collaboration is whether you really need a Chimeric Antigen Receptor (CAR) T cell therapy in your portfolio to succeed as a global cancer immunotherapy company?

One leading cancer immunotherapy company that believes you don’t is Roche.  At ASCO 2015 I had the privilege to talk about this with a leading cancer scientist, William Pao, MD PhD (pictured below). Dr Pao formerly worked with Nobel Prize-winning scientist Harold Varmus at Memorial Sloan Kettering, and subsequently led the Hematology-Oncology Division at Vanderbilt. He joined Roche in July 2014 to lead their early development of innovative oncology new products (see press release).

Dr William Pao Roche

I particularly enjoyed Dr Pao’s discussion of the T-cell centric strategic framework around which the Roche/Genentech cancer immunotherapy portfolio strategy is based.

If you haven’t done so already, do listen to Episode 3 of the Novel Targets podcast (ASCO Lung Cancer Show) in which you can hear an excerpt from my interview with Dr Pao.

This is the first in a series of interviews with scientific leaders at companies at the forefront of cancer research.

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