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

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ciml40-marseille-luminyThere is a lot of interest in manipulating the microbiota to improve clinical outcomes – there was a whole session dedicated to it earlier this week at the CRI-CIMT-EATI-AACR international cancer immunotherapy conference in New York.

At the recent scientific meeting to celebrate the 40th anniversary of the Centre d’Immunologie de Marseille-Luminy (CIML40) in the South of France, Dr Eric Pamer spoke about his research into microbiota-mediated defense against intestinal infection.

Dr Eric Pamer presenting at CIML40

Photo Credit: ATGC Partners

Dr Pamer is an infectious diseases expert at Memorial Sloan Kettering Cancer in New York, where he runs a laboratory (The Eric Pamer Lab) focused on the role of the microbiota in immune system development and in defense against antibiotic resistant pathogens.

The gazillions of bugs in our gut, collectively the microbiota, interact with the innate immune system.

Researchers have shown that the effectiveness of antibiotics and the type of immune response we generate depends on the type of bacteria and their diversity in our gut.

ciml40Readers may recall the interview we did with Dr Marcel van Brink (@DrMvandenBrink) at the Society for Immunotherapy of Cancer (SITC) 2014 annual meeting, where he talked about his research into how gut bacteria can impact survival post allogeneic bone marrow transplant. See post: Can you reduce Graft Versus Host Disease GvHD by regulating gut bacteria?

Almost a year ago in November 2015, researchers and the pharmaceutical industry were both galvanized by work from Laurence Zitvogel and Tom Gajewski labs, published simultaneously in Science. See post: Gut Bacteria Impact Checkpoint Inhibitor Efficacy.

Not only could the results from mice experiments be influenced by the gut bacteria they had, but the microbiome could also impact the effectiveness of checkpoint inhibitors.

You can listen to Dr Gajewski on Novel Targets Podcast summarize the research from his lab published in Science. Link to Episode 9: Targeting the Microbiome.

ebmt17

Next year’s European Society for Blood and Marrow Transplantation Congress (#EBMT17) will be held in Marseille.

Given the impact the microbiome has on post-transplant GvHD and survival, I expect we’ll hear more about this at the Congress. Marseille is well worth a visit if the opportunity presents.

Marseille Vieux Port

In case you missed them do check out our recent posts from the Marseille Immunopôle and #CIML40:

In the meantime, our latest expert interview with Dr Pamer covers his wide ranging thoughts on a number of issues, including the impact of the microbiota on the innate and adaptive immune systems and where he sees the field going in the future.

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Cellular immunotherapy with Natural Killer (NK) cells is emerging as a potentially effective treatment option for older patients (more than 60 years of age) with Acute Myeloid Leukemia (AML).

AML remains a disease with high unmet medical need, particular for those patients who relapse and are ineligible for a stem cell transplant (SCT).

There’s considerable buzz around adoptive cellular therapy and, in particular, chimeric antigen receptor modified T cells (CAR T cells). It is important, however, to note that there are other approaches worthy of consideration. See post: Could a Novel Cell Therapy replace CAR T cell therapy?

Cancer immunotherapy targeting NK cells has already shown some early promising results in AML. We await the read out of the EFFIKIR trial data for lirilumab (Innate Pharma/BMS), an anti KIR (killer inhibitory receptor monoclonal antibody. See post: Innate Pharma at an Inflexion Point, an interview with Hervé Brailly.

357-cover-sourceRizwan Romee, Maximilian Rosario, Melissa Berrien-Elliott and colleagues at the Washington University School of Medicine in St Louis (@WUSTLmed) recently published the results of a clinical trial with a novel NK cell therapy: “Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia.”

The paper was published on 21 September, 2016 in Science Translational Medicine (link).

Melissa Berrien-Elliott, PhD. Photo Credit: Fehniger Laboratory, Washington University

To better understand the trial results and what they tell us about NK cell therapy in AML, BSB spoke with one of the joint first authors, Melissa Berrien-Elliot, PhD (pictured right) and senior author, Todd A Fehniger MD PhD, Associate Professor of Medicine at Washington University.

This post is part of our series on the innate immune system.

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New York – at the CRI-CIMT-EATI-AACR international cancer immunotherapy conference (Twitter #CICON16) that’s currently underway, one of the plenary oral presentations and posters that attracted my attention was for CPI-444, a small molecule inhibitor of the adenosine 2 A receptor (A2AR). It is in development by Corvus Pharmaceuticals (NASDAQ: CRVS).

Corvus Pharmaceuticals Logo

Stephen Willingham, PhD a Senior Scientist at Corvus presented data yesterday on CPI-444, “A potent & selective inhibitor of the A2AR that induces antitumor responses alone and in combination with anti PD-L1 in preclinical and biomarker studies.”  

Corvus announced a collaboration with Genentech back in October 2015. A phase 1 trial with CPI-444 alone and in combination with Genentech’s anti-PD-L1 checkpoint inhibitor atezolizumab (Tecentriq) is now underway.

Targeting the tumor microenvironment to lower the immunosuppressive adenosine and improve checkpoint point effectiveness could be a big win for both Corvus and Genentech if CPI-444 is able to significantly improve the response rates to atezolizumab.

Corvus Senior Scientist Stephen Willingham, PhD and Chief Business Officer Jason Coloma, PhD kindly spoke to BSB about what the data presented in New York means and the company’s clinical development strategy.

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At the recent scientific meeting to celebrate the 40th anniversary of the Centre d’Immunologie de Marseille-Luminy (#CIML40), Professor Ton Schumacher from the Netherlands Cancer Institute gave an informative presentation on “T cell recognition and tumor resistance in human cancer.”

Professor Ton Schumacher at CIML40

Picture Credit: ATGC Partners

Schumacher started his talk at CIML by saying, “I guess by now I should consider myself a cancer immunologist…”

Cancer immunologist ‘wannabes’ should take note of the level of expertise required to be considered one!

Neon Therapeutics LogoHe is one of the co-founders of Neon Therapeutics and a leading researcher into antigen-specific T cell immunity.

Several companies are seeking to develop personalized cancer vaccines against patient-specific neoantigens.

We previously wrote about the approach Neon Therapeutics is following based on expert interviews with the interim CEO Cary Pfeffer and scientific co-founder Dr Cathy Wu.

BioNTech LogoYesterday the field heated up when it was announced that German biotech BioNTech AG had entered a strategic collaboration with Genentech to develop individualized mRNA cancer therapies (Sept 20, 2016 press release).

This post continues the BSB mini-series on targeting neoantigens that we started last month. Do check out previous posts if you missed them:

After his #CIML40 presentation, Prof Schumacher kindly spoke to BSB.

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mimabs_logoOne of the partners of the Marseille Immunopôle cluster is an immuno-technology center focused on translational research called MI-mAbs (“MI” for Marseille Immunopole, and “mAbs” for monoclonal antibodies).

It aims to bridge the gap between industry and academia by accelerating the development of novel monoclonal antibodies for new targets.

MI-mAbs is based in the Parc Scientifique et Technologie de Luminy.

It’s a stone’s throw from the Centre d’Immunologie de Marseille-Luminy (CIML), which this year celebrated its 40th anniversary (1976-2016).

Panoramic view from CIML

Panoramic view from CIML

Luminy is also the home to several companies focused on immuno-oncology, including Innate Pharma and HalioDx. Marseille has the ambition to become a world leader in the development of immune-based therapies

MI-mAbs is funded by a €19M award from the French Government, as part of their Investissments d’avenir/Investments for the Future program.

The Scientific Director of MI-mAbs is Professor François Romagné. He’s a co-founder of Innate Pharma and for 14 years was the company’s Chief Scientific Officer (CSO). He’s one of the inventors of lirilumab and monalizumab, both of which are in phase 2 clinical trials.

mi-mabs-pr-francois-romagne

Professor Romagné kindly spoke to BSB about MI-mAbs and how it plans to accelerate innovation and develop new drug candidates for the treatment of cancer or inflammatory disease.

For our French speaking audience, here is a brief excerpt from the interview with Pr. Romagné, where he introduces himself and MI-mAbs.

It’s an incredible time for immunologists like Prof Romagné, where the clinical results we are seeing with new cancer immunotherapies have validated a lifetime of work.

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While in Marseille for the scientific meeting to celebrate the 40th anniversary of the Centre d’Immunologie de Marseille-Luminy (CIML), I had the pleasure to interview Hervé Brailly PhD, the CEO of Innate Pharma, a leading biotech company in the Marseille Immunopôle.

dr-herve-brailly-innate-pharma-ceo

Innate Pharma (@InnatePharma) was founded in 1999 by six immunologists: Hervé Brailly, Eric Vivier, Marc Bonneville, Alessandro Moretta, Jean-Jacques Fournié and Francois Romagné.

Yesterday’s blog post on “Why Target the Innate Immune System? An interview with Eric Vivier” sets the scene for today’s post.

Innate Pharma, as the name suggests, has pioneered targeting the innate immune system. The company has leveraged the research undertaken at CIML by Professor Vivier and others in the field of innate immunity.

Innate is leading the way in immuno-oncology by targeting checkpoint receptors on natural killer (NK) cells. In 2011 Innate signed a licensing deal with Bristol-Myers Squibb for the development and potential commercialization of lirilumab.

In a recent financial report (link to Sept 8 press release) the company announced that several clinical trials would read-out in the forthcoming months.

Without disclosing any material non-public information, Dr Brailly kindly spoke with BSB and talked about his vision for Innate, what data readouts we are expecting, and the inflexion point the company is now at.

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Eric Vivier, DVM PhD (@EricVivier1) is a leading French immunologist whose research has focused on understanding the innate immune system, and in particular, the role natural killer (NK) cells and innate lymphoid cells (ILC) play.

prof-eric-vivier

He is Director of the Centre d’Immunologie de Marseille-Luminy (CIML) and a Professor of Immunology at Aix-Marseille University.

In addition to his academic work, he also co-founded the biotech company Innate Pharma back in 1999. Through the company, he is actively involved in the translation of basic research into new cancer immunotherapy treatments.

New clinical data is eagerly expected for one of these, a first-in-class monoclonal antibody against KIR (lirilumab). It is in phase 2 clinical trials with Innate Pharma and Bristol Myers Squibb.

At the recent scientific meeting to celebrate 40 years of CIML (#CIML40), Professor Vivier kindly spoke to BSB about his research into innate immunity and the Marseille Immunopôle, for which he is also a co-founder.

It is an immunology cluster that brings together academic/clinical research with innovative biotech companies looking to bring new drugs and diagnostics to market.

This is the second post in our mini-series from the Marseille Immunopôle and CIML40. It also sets the scene for forthcoming posts on targeting the innate immune system, something you can expect to hear a lot more about in cancer immunotherapy.

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Marseille – When it comes to biotech clusters for immunotherapy, Marseille, the second city of France, has to be right up there along with Boston, San Francisco in the United States and the “Golden Triangle” of Oxford, Cambridge and London in the UK.

ciml40I’m here in Marseille thanks to an invitation from Professor Eric Vivier to attend the 2-day scientific conference that the Centre d’Immunologie de Marseille-Luminy (CIML) have organized as part of their fortieth anniversary celebrations (1976-2016). It starts today (Twitter #CIML40).

Surrounding CIML in the picturesque national park (Parc National des Calanques), just outside the city, are innovative biotech companies focused on immunology and cancer immunotherapy. The combination of companies, research institutes and academic hospitals in the region has created the Marseille Immunopôle (@Immunopole). The area should already be on your radar if you are following the field.

haliodx

Yesterday, I visited HalioDx (@HalioDx), a start-up company a stone’s throw from CIML. It was founded in 2015 to commercialize Immunoscore, a novel biomarker in colon cancer that can be used to stage patients based on their immune response.

Vincent Fert CEO HalioDx

Vincent Fert, CEO of HalioDx

We’ve been following the work of Dr Jérôme Galon on the blog for some time (see posts from European Cancer Congress 2015 and ASCO 2016), so it was a pleasure to talk to Vincent Fert, CEO (pictured right) and co-founder of HalioDx, about his plans to commercialize Immunoscore in Europe and the United States.

If you want to know more about the science behind Immunoscore, do listen to the recent Novel Targets Podcast (@TargetsPodcast) interview with Dr Galon, where he talks about the data he presented at ASCO 2016 (link to Episode 13: Immunotherapy or Bust).

The field of cancer immunotherapy is making rapid progress. It is already reaching the point where — in order to optimize the chance of a durable response — doctors need to know what a patient’s underlying immune response to cancer is, in order to direct therapy.

Vincent Fert and HalioDx are leading the way with the commercialization of a new diagnostic approach for colon cancer based on a patient’s immune profile. He kindly spoke with BSB about his plans for the company and making Immunoscore available in the US and Europe.

haliodx-marseille-luminy

This is the first post in a mini-series from the Marseille Immunopôle.

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Prof Fran Balkwill Barts Cancer InstituteWhen it comes to cancer immunotherapy drug development, one of the challenges is that we can’t accurately predict from preclinical mouse models what will happen in people. The result is a rush into the clinic to test in human subjects.

We do need better preclinical models, which is why it was interesting to hear recently on an episode of Health Check (BBC World Service) about a 3D tumour model that is being developed at Barts Cancer Institute.

Professor Fran Balkwill (pictured), who leads the Centre for Cancer and Inflammation, kindly spoke to BSB about the work she and colleagues are doing to model the tumour microenvironment (TME) in high-grade serous ovarian cancer.

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Like the Battle of Britain, the cancer immunotherapy landscape is a dynamic one where tactical decisions can make the difference between “winning” and “losing.”

As Bristol Myers recently found out in first-line NSCLC, if you choose the wrong trial design or adopt an overly-aggressive strategy, you can end up losing badly (see post: Detailed thoughts on BMS CheckMate 026 1L trial in NSCLC)

A recent trip to the operations bunker at former RAF Uxbridge, from where the fighters of 11 Group were directed, shows how close we came to losing the Battle of Britain.  Had the German Luftwaffe continued to target RAF airfields instead of diverting their efforts on London, the outcome of the war is likely to have been quite different.

History provides a valuable lesson that strategy and tactics can and do matter; in R&D the targets you choose and how effectively you execute on a plan can make a big difference to outcome.

Battle of Britain Bunker Plot

Pictured: the RAF 11 Group Operations plot as it looked on September 15, 1940.

In Part 2 of the BSB interview with PsiOxus Therapeutics CEO Dr John Beadle, we discuss corporate strategy, and some of the challenges faced by an emerging Biotech company, many of which are likely to be shared by other small companies in the field.

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