Biotech Strategy Blog

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

Copenhagen – it’s the end of Day 2 of the European Society for Medical Oncology (ESMO), which this year had a record-breaking 20,239 attendees.

esmo16-posters

Three of the presentations in today’s plenary Presidential Symposium were simultaneously published in The New England Journal of Medicine – I haven’t seen that happen before.

All three were also featured in this morning’s media briefing in Copenhagen.

  • Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer (NEJM link)
  • Prolonged Survival in Stage III Melanoma with ipilimumab Adjuvant Therapy (NEJM link)
  • Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer (NEJM link)

In today’s daily digest there’s top-line commentary and insights from some of the sessions we attended. In a separate post, we have already discussed the niraparib data.

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Copenhagen – PARP inhibitors are creating quite a lot of controversy here at the 2016 ESMO Congress.

Yesterday, we heard the data for rucaparib (Clovis Oncology) as monotherapy treatment for the advanced ovarian cancer patients with BRCA mutations who have been treated with 2 or more chemotherapies.

In a totally different ovarian cancer indication, today at #ESMO16 we heard the results of the phase 3 trial for niraparib, the PARP inhibitor from Tesaro, that many thought was superior to the rucaparib data, ignoring the fact you can’t make comparisons for maintenance versus relapsed/refractory treatment.

The niraparib ENGOT trial was presented in today’s plenary Presidential Symposium by Dr Mansoor Mirza and simultaneously published in The New England Journal of Medicine (link). It was also featured in a media briefing earlier today in Copenhagen.

esmo-2016-press-briefing

In this piece we’ve taken a critical look at the Tesaro (NASDAQ: TSRO) niraparib data and the controversial claim made by their principal investigator, Dr Mirza, that the data shows there is no need for a companion diagnostic to be associated with this drug.

In other words, the intent that regulatory approval will be sought for this drug as maintenance therapy for platinum-sensitive ovarian cancer patients, irrespective of whether they have a BRCA mutation or homologous recombination deficiency (HRD).

This post provides commentary on this and offers the perspective of a leading ovarian cancer expert with deep experience of companion diagnostics in this field.

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Copenhagen – today was day one (Day 1) of the 2016 Congress of the European Society for Medical Oncology (Twitter #ESMO16).

esmo-2016-registration

ESMO 2016 Registration

The meeting is a few weeks later than last year’s European Cancer Congress in Vienna, and it definitely feels as though autumn has arrived in Europe.

copenhagen-cycling

Cyclists in Central Copenhagen

This year we’re providing a daily digest at the end of each day at ESMO 2016 in Copenhagen.

The aim is to provide some top-line commentary around the sessions we attended earlier in the day. Think “Match of the Day” for those in UK or “Sports Center” for those in the US. We’ll be writing more in-depth pieces after the meeting.

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Cancer Immunotherapy will require personalized treatment based on the type of cancer you have, and the immune response your body has generated to the cancer.

Dr Holbrook Kohrt Stanford

Dr Holbrook Kohrt at Immunology 2015

The sadly missed and visionary Dr Holbrook Kohrt was very prescient when he told BSB in New Orleans back in May 2015:

“Today when I see a patient or you go to a cancer center, the first thing they ask is what type of cancer do you have? Most patients respond – breast cancer, a colon cancer – unfortunately we are not in position where patients can say I have a deficiency in my cytotoxic CD8 cells or I have overly active regulatory T cells.

I actually envision a day when patients will know both sites, they will know they have breast cancer and they’ll also know it’s because there’s a lack of effector cytotoxic CD8 T cells. That combination knowledge, of what your immune system is lacking and what tumor you have, that combination will allow you to identify what type of immunotherapy you need.

Patients may need CAR directed T cells and those will be for patients who have completely non-functional T cells themselves, no matter what therapy you give them, you’re not going to create those cells within the body, therefore you need to do it ex-vivo in a petri dish and give it back to them.

Other patients may have T cells that just need to be turned on and so all they need is a checkpoint modulator and that combination is going to be effective enough for them.

So it’s this dual diagnosis, diagnosing their immune system and diagnosing their tumor that’s going to allow us to identify one, two, or three therapies that’s going to be the right cocktail.” 

See post: Holbrook Kohrt leads the way in Targeting CD137, you can also listen to excerpts on the Novel Targets Podcast: Episode 6: Stepping on the Gas

ICYMI do listen to the tribute to Dr Kohrt on the Novel Targets Podcast from two people who knew him at Stanford: Dr Ron Levy and Dr Dan Chen (@DanChenMDPhD). It’s at the start of Episode 11: Cancer Immunity Cycle.

Immunoscore® — a diagnostic test based on the immune profile of a patient is based on the pioneering work of INSERM scientist Dr Jérôme Galon.

Dr Jerome Galon at ASCO 2016

Dr Jérôme Galon at ASCO 2016

We are fans of his work, and interviewed him at the 2015 European Cancer Congress. See post: Immunosurveillance, Immunoscore & Personalized Cancer Immunotherapy – an interview with Jérôme Galon.

Over 10 years ago, Dr Galon’s research published in The New England Journal of Medicine and Science showed that the type, location and density of immune cells within a tumor predicts clinical outcome in early stage colon cancer.

These findings led to the development of an assay called Immunoscore® that’s based on an analysis of cytotoxic T cells, the ones that kill cancer.

In the process, it has led to a new way of classifying stage 2/3 colon cancer patients: those with a high Immunoscore® (good prognosis), and those with a low Immunoscore® (poor prognosis). Dr Galon’s work has shown that irrespective of whether you are MSI high or MSS, colon cancer prognosis correlates with Immunoscore.

Dr Bernard Fox at #AACR16

Dr Bernard Fox at AACR 2016

As we heard from Dr Bernie Fox (@BernardAFox) at AACR 2016. See post: AACR Cancer Immunotherapy Insights from Dr Bernard Fox, listen to excerpts on Novel Targets Podcast Episode 12: Of Mice and Men:

“What I teach the first year medical students is that if you have metastatic cancer, the only thing that makes a difference in your life is whether you’ve got your immune system turned on. If it’s not turned on, it doesn’t make a difference what you get, chemo, radiation, surgery, you aren’t going to do well.”

Immune response is key to outcome, which means that knowing what your immune profile is will be key to deciding which of the many immunotherapy options, either alone or combination will achieve the desired effect.

A large multinational phase 3 clinical trial sponsored by the Society for Immunotherapy of Cancer (@SITCancer) was set up to validate Immunoscore® as a biomarker in Stage 2 colon cancer.

Dr Galon and co-authors reported the results at ASCO 2016. See post: immunoscore validated as an important biomarker for colon cancer. He featured on the ASCO 2016 episode of the Novel Targets Podcast: Immunotherapy or Bust.

Immunoscore® is now being commercialised by Marseille based HalioDx(See post: HalioDx CEO Vincent Fert outlines commercial strategy for Immunoscore in US and Europe).

ciml40During a recent visit to the Marseille Immunopôle for #CIML40, I had the pleasure to do an impromptu tour of the HalioDx lab.

When listening/watching this, do bear in mind this was not a scripted tour, and also the people I spoke to were speaking English as a second language.

It’s not intended to be a definitive guide; if you are a patient you should talk to your doctor about any questions you have about diagnostic assays such as Immunoscore.  At the moment, it’s only available for research or clinical trial use, but HalioDx has plans to make the assay commercially available on the US and Europe.

The company has more information on their website and also recently published a paper in the Journal for Immunotherapy of Cancer (open access) that describes how the test is done in more scientific detail.

In the meantime, subscribers can login to join me for a lunch-time tour, or you can purchase access below. The audio-slideshow tour was for several weeks open access and available to all, but is now for subscribers only:

After some relatively quiet summer months, we have been deluged with questions and requests this month for commentary on some hot topics of late. This seems like a good time to take stock and reflect on some of most frequent ones sent in.

west-acton-tubeThe original Journal Club post slated for today will appear next week instead.

Here, we address numerous queries on the following five topics readers are interested in:

  • APHINITY trial in HER2+ adjuvant breast cancer
  • Array’s BRAF plus MEK data in metastatic melanoma
  • Kite’s interim ZUMA–1 phase 2 announcement
  • Amgen’s Kyprolis in newly diagnosed multiple myeloma
  • BMS nivolumab data in 1L lung cancer (CheckMate-026)

The last two in particular seem to be causing a lot of hand-wringing!

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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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