Biotech Strategy Blog

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

Posts tagged ‘Biomarkers’

Bench to bedside and back again

Can we break through the barriers of a hostile tumour microenvironment?

Who would have thought that after 30 years of no new therapies that urothelial carcinomas would suddenly be almost constantly in the spotlight with enticing words like cancer immunotherapy, biomarkers, tumour microenvironment, translational immunology etc?

And yet it has happened – with a lot more to come in this highly competitive niche too.

Prior to AACR in Chicago, we highlighted TGFβ in our Preview series as an important emerging target that is gathering attention and may be relevant in tumour types, such as urothelial carcinoma and ovarian cancer.

After the meeting, Dr Paul Rennert (CSO, Aleta Biotherapeutics) noted:

I don’t disagree with either of these sentiments – there was a reason we interviewed a lot of NK cell enthusiasts recently and we have since been rolling out our thought leader mini-series focused on TGFβ. Yesterday, we kicked off with perspectives from an academic researcher active in this field and tomorrow will showcase some practical clinical perspectives.

On deck today, we have a interview with a research scientist who has conducted both basic and translational work for a discussion about how he sees the learnings that have arisen from bench to bedside and back again.

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Innate Pharma – converting science into the clinic

Every year for our annual AACR Preview coverage we like to mix things up and explore what’s happening with different targets, pathways, and even companies.

In this latest post for #AACR18, we take a look at a company that has historically been involved in R&D associated with the innate immune system. As new molecules have evolved against different targets, researchers have begun to realise that we can actually target both the innate and adaptive immune systems together rather than one or the other.

We have covered several clinical developments from Innate Pharma on lirilimumab, but they are actually more than a one compound biotech and have a growing pipeline of antibodies against several novel targets, some of which are unique to the company.

This isn’t just about the science behind the pipeline as we also explore facets of corporate strategy and where the company is headed in the near to medium term future.  While in London earlier this month, we caught up with Dr Mondher Mahjoubi (CEO) and Prof Eric Vivier (CSO) for a candid and detailed fire side chat.

There was plenty to discuss and some interesting new developments to highlight…

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New Horizons in Pancreatic Cancer

MD Anderson Cancer Center

Houston, Texas – Advanced pancreatic cancer is a very tough disease to treat, so it is not surprising that by 2030 it will be the No. 2 cancer killer in the United States, according to one of the speakers at the recent 1st Annual Symposium on Pancreatic Cancer held at the MD Anderson Cancer Center earlier this week.

There’s also high unmet medical need for new effective therapies for pancreatic cancer, which is why events that promote collaboration and cross-fertilization among leading experts are important.

I found out about the event from Twitter thanks to tweets by Dr Anirban Maitra (@aiims1742) who shares a lot of information. Do follow him if you don’t already.

Thank you to everyone at MD Anderson for putting on a panel of excellent speakers. The meeting was well worth attending and I hope it will become an annual event.

In this post I’ve captured some of the key take-homes that I took from the symposium.

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The death of PD-L1 in urothelial cancer

Prof Tom Powles GU18 Title SlideAt the 2018 ASCO Genitourinary Cancer Symposium, one of the standout keynote lectures was from Professor Tom Powles, Director of the Bart’s Cancer Cancer Center in London who talked about “Immune checkpoint inhibitors in Urothelial Cancer: which one and why?”

We’ve been following the highs and lows around checkpoint inhibitors in bladder cancer for some time, so it was interesting to hear what Prof Powles had to say in San Francisco.

How does he see the landscape evolving for immune checkpoint inhibitors?

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Going beyond PD-L1 expression as a immune biomarker

One of the things that I’ve heard repeatedly over the last year is that many researchers want a better biomarker of response for checkpoint therapies than PD-L1 expression by IHC.

National Harbor

Indeed, we could expand that statement more broadly to say that there’s a real need for a better predictive biomarker of response to any immunotherapy, since there are more approaches out there now and not just checkpoint blockade. Plus combinations are evolving, complicating things further.

Fair enough, but what’s happening in this space?  Anything, Bueller?

We’ve covered a few emerging ideas in the past, although they were based on retrospective analysis – usually with a small N – and remain to be validated in prospective clinical trials.

There’s quite a few groups now much more active in research in this space, from academia to industry.  This is a good time to take stock and look at some of the emerging technologies that might be making a splash later if the data pans out.

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Do Exosomes Matter?

At AACR17 one of the fascinating topics that came up in several presentations was exosomes, what they are, and how the information they contain can be used to best effect.

One of the evangelists of exosomes, and their potential in cancer research is Theresa Whiteside, PhD who is a Professor of Pathology, Immunology and Otolaryngology at the University of Pittsburgh.

At the recent 2017 American Association for Cancer Research (AACR) annual meeting, Dr Whiteside gave two fascinating talks in education symposia.  Afterwards, she kindly spoke to BSB about her research.

Love them or hate them, exosomes were a hot topic in Washington DC and something you should be aware of, if you aren’t already.

This post continues our volley of expert interviews from AACR17 and is the ninth in the series.

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Understanding the Cancer-Immune Set Point

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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A manifesto for immuno-oncology research

Two of the most intriguing developments in cancer research over the last 5 years have been checkpoint blockade and CAR T cell therapies. There’s no doubt that they work – in some patients – or that toxicities can be challenging to manage at times, but what has been very interesting to me has been physician reactions to the rise of immunotherapies.

There has been much noise about biomarkers, including whether they work or not in this niche, as well as how do we go about selecting patients for therapies and combinations?

Ultimately, immunotherapies will be no different from targeted therapies in that we need to better understand the underlying biology in order to move forward beyond the low hanging fruit and figure out how we can best select appropriate therapy for each individual based on their particular characteristics.

The worry that many researchers have is that we could end up making the same mistakes with immunotherapies as targeted therapies, i.e. treat them in a broad fashion akin to throwing mud at the wall. Indeed, some companies are already doing this, much to the consternation of the research community.

So how do we go about doing things better and thinking more strategically about what needs to be done?

Up next is the first in a two-part interview series with a global thought leader who is a scientist-clinician with expertise in both immunology and oncogenic pathways. What does he have to say about where we are now and importantly, what does the future hold?

This is the penultimate article in our coverage from the Triple meeting in Munich, held in November 2016.

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The future of our cancer research business

The Future of our (cancer research) Business

Happy New Year! No one really wants to spend too much time in the past dwelling on the negatives, what didn’t work, and in some spectacular cases, who’s to blame for it.

What we do want to know is what are the learnings from such endeavours and where are we going next.

Let’s look forward rather than backwards then and see what the Maverick’s crystal ball is showing in terms of fresh clarity and new trends we can learn from …

In today’s post I want to take a moment to look at some of the trends we can expect to see occuring in cancer research in 2017.

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Insights from biomarkers in ovarian cancer

esmo-poster-hallThis post started out as a look a one of the Gems from the Poster Halls at ESMO, including an interview with a thought leader in biomarkers, then morphed into a broader Op Ed that includes a strategic analysis of where we are, where we are going, and how we could get there more effectively and efficiently.

It’s time to turn tables to start challenging the status quo and slow pace of development if we really want to make a difference in advanced ovarian cancer.  I was recently challenged by a well respected GYN oncologist to delineate how we could do things differently so here are some ideas, along with the scientific rationale in my response to his gauntlet.

Is the ideal situation one where multiple companies randomly throw mud at the wall hoping something sticks the best approach? Or are there more effective ways to make a difference?

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