Biotech Strategy Blog

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

Posts from the ‘Immunotherapy’ category

It’s that time of the year again – time to highlight key events and talks at the upcoming European Society of Medical Oncology (ESMO) meeting held in Madrid next month.

Over the next two days, we’re going to take a look at five key IO trials (today) and five targeted therapy studies (tomorrow) that are being presented at ESMO.

In short, what should readers know about these oral presentations for greater context, why are they important, and what should you be looking for?

We will cover the hidden gems from the poster halls to watch out for in a separate future post.

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Paris: If cancer immunotherapy is a revolution in how cancer is treated, then Dr Jérôme Galon is a revolutionary.

In addition to being a Research Director at INSERM in Paris, Dr Galon is one of the co-founders of Marseille based HalioDx, an immuno-oncology diagnostics company that is commercializing the research from his laboratory.

Last month, while in Paris, I had the great pleasure to talk with him in his office at the Centre de Recherche des Cordeliers (CRC) on the left bank of Paris.

At the time of the French revolution in 1789, it was the gathering place of the “Club des Cordeliers,” for famous revolutionaries such as Danton, Marat, and Camille Desmoulins. Dr Galon told me it was where the Declaration des droits de l’homme et du citoyen de 1789 (Declaration of the Rights of Man and Citizen) was signed.

As such, it’s a very appropriate place to find a cancer immunotherapy revolutionary…

To learn more insights on what he had to say about a variety of topics in cancer immunotherapy, subscribers can log-in or you can gain access to BSB Premium Content.

Here we are with Part 2 of our latest mini-series on novel ways to jumpstart the immune system so that subsequent therapy can be more effective, leading to improved outcomes.

In Part 1, we looked at the preclinical and scientific evidence regarding a novel approach to modulate a cold or non-inflamed tumour type, thereby turning the phenotype into a hotter or inflamed one.

In principle, this concept sounds quite simple in theory, but in practice it’s actually much more technically challenging to do than many realise, especially when we consider not just the design of the antibody itself and perhaps even efficacy, but also the convenience of administration and tolerability, both as monotherapy and also in combination with other therapies.

What’s up on deck today is not one, but three interviews, offering readers a candid look through the keyhole at varied insights from different perspectives around a central R&D topic, namely…

What do you do when you have a new compound in clinical development and wish to explore how to integrate it – do you use it with an existing framework or try something new and different? What about other compounds that might be competing with it internally?

It’s a question every single oncology company faces when a new molecule moves out of preclinical development into phase 1 trials. What next?

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Paris, France – Last week I had the pleasure of attending a two day Immuno-Oncology Summit, an industry sponsored CME event organized by the European Academy of Tumor Immunology (EATI) and Miltenyi Biotec.

The summit was held at the Centre de Recherche des Cordeliers (CRC) in the quartier Latin on the historic left bank of Paris, a short walk away from Notre Dame cathedral.

Paris Immuno-Oncology Summit 2017

Most of the attendees were French researchers so this opportunity afforded them a chance to hear from leading researchers at the forefront of cancer immunology, including several who travelled from the United States to speak at the event.

CRC Courtyard Statue

I have yet to attend a cancer immunotherapy meeting where I didn’t come away with new insights into what is a fast moving field, where it’s important to see “connections” beyond a tumor type or target.

This post offers top-line commentary highlights on five key presentations at the summit. There were two parallel tracks and a lot of interesting speakers at what was an enjoyable meeting, so think of this like a postcard from Paris.

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Over the years we’ve interviewed folks from numerous pharma and biotech companies here on BSB, including those with targeted therapies (small and large), as well as immunotherapies.

Some companies have small pipelines and may be forced by circumstances to explore what they have or seek collaborations with bigger partners.

For big pharmas with large pockets plus broad and deeper pipelines, the challenge is quite different – how do you prioritise potential combinations and tumour targets given it is impossible to evaluate them all in the clinic? How do you create differential advantage and value when you’re relatively later to market compared to your competitors?

In the BSB spotlight this week we have two researchers in clinical development and R&D from the same company, who happen to have both elements in their pipeline in areas of high competition.

Part one of our latest mini-series explores the IO side of the business as we look ‘Through the Keyhole’ at what’s going on in terms of biomarkers, monotherapy trials, combination studies (both IO-IO and IO-targeted) and what to expect in the near-term future later this year. It’s a wide ranging, candid, and fascinating discussion that highlights a lot of potential in terms of what could happen with a large pipeline.

In all, it makes for rather interesting reading and certainly changed how I perceived the company’s efforts in the IO sphere (for the better, I might add).  So what’s fascinating about their approach and what can we learn from their progress to date?

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We’ve been saying for a while that 2017 and onwards would be when we start to see a few IO combination trials start to shake out. Interestingly, that process seems to have already started, if recent news is any thing to go by.

With this in mind, the annual meeting of the American Association for Cancer Research (AACR) coming up this weekend gives us a timely moment to explore combinations that are looking interesting… or not.

In the last of our AACR 2017 Conference Previews, we take a look at what to expect on this year’s program in the IO and Checkpoint arena. In short, it’s quite a lot and not without some controversy either!

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In the first of our 2017 AACR annual meeting previews, we are taking a look at a particular theme that we expect to hear much more about over the coming months.

Washington DC cherry blossoms

In order to make something better than what it is, we first need to step back and understand the various factors that underpin it. To do otherwise is akin to the proverbial throwing of mud at the wall and hoping something sticks.

Trying things out just because they seem like a good idea or that’s all you have in your pipeline doesn’t really inspire the greatest of confidence in a clinical trial’s success.

This is also where several factors including tumour biology, cancer genomics, biomarkers, and acquired resistance can intersect to produce some intriguing results.

Please note that our Conference Preview series are never random.  When looking at the abstracts as a whole, we try to organise them around a particular scientific theme or a tumour type. The idea here is that it makes it much easier for our readers to see and grasp emerging concepts and trends. It’s also a deeper dive into the whys; things happen for a reason – why is that?  What can we learn from the process?

These are also not random selections from say, publicly traded or private companies, big or small caps.

It does take more time to roll thematic articles out, but the advantage is that over the course of the next two weeks readers will be better equipped to get a grip on the meeting ahead of the event.

Indeed, a couple of subscribers even told us last year they learned more from our in-depth previews than they did from the meeting itself because it’s easy to miss the important things or become ‘bigly overwhelmed’ as one bio fund manager explained to me.

Strategically, we’ve taken one specific theme today and explored what we can expect based on what we have learned to date, and looked at how that will potentially impact a few things going forward.

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Sunny Day in Orlando, FL

Orlando, FL was the place to be last week thanks to two specialist meetings in town: BMT Tandem 2017 #BMTTandem17 (joint meeting of ASBMT and CIBMTR), and the inaugural ASCO-SITC Clinical Immuno-Oncology Symposium #Immunosym.  Indeed, several speakers spoke at both events!

Throughout this week we’ll be writing about the insights we gained from the two meetings into the latest data and trends in immunotherapy, immuno-oncology and adoptive cell therapy.

We’re kicking off with cell therapy insights from the BMT Tandem Meeting. It’s the joint meeting of the American Society for Blood and Marrow Transplantation and Center for International Blood & Marrow Transplant Research. If you don’t already, do follow the ASBMT President for 2017-2018 Dr Krishna Komanduri, @drkomanduri. He’s actively involved in CAR T cell therapy trials in Miami.

It’s worth remembering that bone marrow transplanters led the way in the use of immunotherapy to provide cures for cancer. Today, the BMT transplant community are pioneering adoptive cell therapy, and in particular  CAR T cell therapy in multiple hematologic malignancies including ALL, NHL, CLL and Multiple Myeloma. This makes the annual BMT Tandem meeting one to watch for some of the latest cell therapy data.

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One of the frequently cited conceptual frameworks in Cancer Immunotherapy is the Cancer Immunity Cycle developed by Drs Dan Chen and Ira Mellman from Genentech.

Ira Mellman Dan Chen Authors of Cancer Immunity Cycle

Ira Mellman and Dan Chen

As we heard Dan and Ira tell us on the Novel Targets Podcast recorded last year at #AACR16, the cancer immunity cycle doesn’t include all the elements that we now know impact the immune system and whether someone will have an immune response. The microbiome is one example that readily comes to mind.

To address this, Chen and Mellman have now published the next installment in the series in Nature:

“Elements of Cancer Immunity and the cancer-immune setpoint.”

The review paper published last month incorporates the latest research into a different framework that looks at the factors that influence what they call the ‘cancer-immune setpoint.’

Anyone involved with cancer immunotherapy knows how fast moving and dynamic the field is, something they draw attention to:

“The pace of cancer immunotherapy clinical studies is such that they have outstripped our progress in understanding the underlying science. However, this situation has created the opportunity to combine emerging scientific and clinical insights in a synergistic fashion that… will also provide guidance for the identification of new targets… and the crafting of a framework for making decisions on a personalized basis.”

Conceptual frameworks such as those proposed by Chen and Mellman will be of increasing importance as we try to make sense of the tsunami of cancer immunotherapy clinical trial data, including combinations, that is coming our way over the next 18 months.

During my recent visit to San Francisco for ASCO GI, I had the great pleasure to catch up with Daniel S. Chen, MD PhD, (Global Head of Cancer Immunotherapy Development, Genentech/Roche) and talk about his latest thoughts on how we should think about cancer immunotherapy.

In writing these review papers he told me:

“We look at this as an opportunity to really think about the field, and try to conceptualize what is happening.”

We also discussed their collaboration with Kite Pharma, something of relevance to conferences this week as we head off to BMT Tandem and the ASCO-SITC meeting.

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gaylord-national-harbour-md

National Harbor, MD

Despite remarkable results with cancer immunotherapy to date, we do need to keep out feet on the ground and remember that response rates are relatively low to modest (10–30%) and the majority of patients do not respond or see a benefit with these approaches.

As we start moving beyond checkpoint monotherapy, the realisation has fast hit many researchers and companies that we really don’t know as much about the tumour microenvironment (TME) as we would like.

No doubt we will learn a lot more about it from the combinatory approaches, but be aware that this also means higher risk associated with such developments – we will likely see a lot of failures – and hopefully, some successes too.

This is where the little biotech companies have an opportunity to shine… they may have some intriguing IO compounds in development but not an anti-PD1/L1 backbone, meaning they can collaborate with a big pharma company to explore novel combinations in small phase 1/2 trials to determine what works or not. This is much lower risk (and R&D costs) for both parties and we get to see more quickly where things shake out.

At the annual Society for Immunotherapy of Cancer (SITC) meeting last week, there was a whole day devoted to New Immunotherapy Drug Development.  

Some of these agents look worthy of watching out for and following their progress.  A variety of data in different targets and MOA were presented from big and small companies alike.  We selected a few of the promising ones for further review and discussion.

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