Biotech Strategy Blog

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

Posts tagged ‘innate immunotherapy’

Time to unlock some novel IO targets?

Continuing our latest four part mini-series, this one is on novel targets and agents and we now turn our attention to immuno-oncology in the last two articles pertaining to this particular topic.

You can read the first two articles on targeted therapies here and here.

For the avoidance of any doubt, this latest review is not about T cells, far from it.

Instead we cover six different areas, most of which are related or integrated in some shape of form.

There’s a lot of promising new science now coming out to help us better understand the underlying biology and also think out of the box about ways to enhance or improve on existing research.

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Old Post Office in Barcelona

Barcelona – After the torrential rains that hit here earlier in the month at WCLC, it’s glorious weather in Barcelona for the 2019 Congress of the European Society for Medical Oncology (#ESMO19).

Each day we’ll be providing highlights from the Congress with news, commentary and analysis from various presentations we’ve attended and thought leaders we’ve spoken to.

This ESMO Congress is a really exciting meeting, perhaps one of the busiest we’ve seen in recent years with multiple sessions in parallel to choose from. There are no shortage of data to discuss and review.  In distant years past, ESMO used to be known as the metaphorical dumping ground for negative trials that undoubtedly got lost in hurly burly – no longer! That changed after they started appearing in the Presidential Symposia and having the spotlight shone on the data. It’s now a much more vibrant meeting for clinical development, with an increasing translational focus thrown in too to explain the why and not just the what.  That’s good news for all of us.

To kick off our daily live ESMO coverage, we begin with sharing some useful insights gleaned from what we’ve heard so far plus more will be added throughout the day as we hear from the educational sessions later…

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After extensive – and at times, intensive – preclinical and clinical research on the adaptive immune system and how best to activate the cytolytic T cells in both hematological malignancies and solid tumours, attention is beginning to increase on the innate immune system. In particular, researchers are investigating how approaches in this realm can be incorporated into rational combinations with adaptive therapies, such that outcomes might be improved more than with either alone.

Human NK Cell  Source: NIH

There are a number of ways to activate the innate immune system and direct dendritic or NK cells, for example. Some therapeutics seek to boost the responses via different innate sensing pathways such as cGAS/STING or CD47/SIRPα, for example, while others involve targeting stimulatory cytokines, chemokines, toll-like receptors (TLRs), etc through various agonist molecules.

There are also a myriad of vaccination strategies to consider involving neoantigens or neoepitopes, not to forget NK cell infusions, various NK CARs, bi/trispecifics and even checkpoint blockade of NK related targets.

These development have typically not received the same amount of attention as their T cell cousins, but it’s certainly an active and fertile area of research and one that we are likely to hear more about going forward as new developments start to make their mark.

In a world of ‘T cell chauvinists’ – to quote Dr Adi Diab (MD Anderson) – let’s not forget or ignore the humble NK cells, which also have cancer killing abilities.

Over the next three weeks, we have an extended mini-series focusing on NK cells rolling out with interviews and commentary from academia and biotechs alike across both sides of the pond. It promises to be an interesting and provocative ride with plenty of critical questions to pose and resolve along the journey.

So, hang onto your hats for the first part of the journey…

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In this post, it’s time to put your thinking caps on and empty your minds of any pre-conceived bias in order to play the modern version of Star Trek tridimensional chess aka IO combination trials.

Gems from the Poster Halls

Here we weave now together some important themes and highlight intriguing ideas that at first seem dissimilar, but actually have much more in common than many realise.

Data from bone chillingly cold poster halls of conferences in the distant past can come back and reviewed afresh in the light of new developments. The seasoned observer discards neither these findings or thought leader snippets of insights within nor forgets them in an instant, as many do after the hum of instant live reactions passes.

With oncolytic viruses and cytokines being much in the news of late, what can we learn about where things are likely headed?

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Last week we reviewed some of the promising oral late breaking abstracts and highlighted what to watch out for (W2W4) from our key selections.

National Harbor, DC

This week, it’s the turn of the poster late breakers to be in the spotlight.

There are several approaches worthy of highlighting, but as always, there are also some potential pitfalls for readers to be aware of.

After all, life in the oncology R&D fast lane is as never easy or predictable as the changing of the seasons.

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Orlando, Florida: It’s time for a review of emerging science and clinical concepts.  This post is the final one in our latest series from ASCO-SITC.

Here we take a step back and highlight six key emerging trends and ideas that were either presented in talks and posters, or are sentiments based on conversations with attendees in the poster halls or corridors.

Sometimes those discussions are pretty helpful in giving hints on new dirrections before the actual data eventually comes out.

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Over the last year or two, we have covered a number of different pathways that are involved with the immune system including CD19 and 20, CTLA–4, PD–1 and PD-L1, IDO1, CD40, OX40, TIGIT, ICOS and others.

Today, it’s the turn of an oncoprotein called NY-ESO–1 that has been garnering quite a bit of attention of late and will also be highly relevant to some upcoming posts and thought leader interviews we have scheduled here on Biotech Strategy Blog. It’s always a good idea to cover the basics first, before exploring the more advanced concepts.

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Marcel R.M. van den Brink, M.D., Ph.D.At the 2014 Society for Immunotherapy of Cancer (SITC) annual meeting at National Harbor, MD, one of the presentations that caught my attention was by Marcel van den Brink MD PhD (@DrMvandenBrink), pictured right, from Memorial Sloan-Kettering Cancer Center in New York. (picture courtesy of MSKCC with permission).

Dr van den Brink, who is Head of the Division of Hematologic Oncology and Alan.N. Houghton Chair, gave a fascinating talk entitled, “The role of the Intestinal Microbiome on GvHD” (Graft versus Host Disease).

Think of the yogurt pots and probiotic drinks we see in the supermarket with “beneficial” bacteria. We’re familiar with the idea that the make up of the millions of bacteria in our gut can make a difference to our digestion and health.

Well, it turns out it can make a difference to our immune system too. Research presented at the recent SITC meeting by Dr van den Brink showed that manipulating the bacteria in the gut could potentially help the thousands of patients around the world who receive a bone marrow transplant (BMT).  BMT is a gruelling procedure that many leukemia, myeloma and lymphoma patients have to face as part of their treatment protocol.

Sadly, about 20%* of people who receive an allogeneic bone marrow transplant from an unmatched donor die from Graft versus host disease (GvHD)

* According to 2010-2011 data from the Center for International Blood and Marrow Transport (CIBMTR), GvHD was the cause of death in 19-23% of people who received an allogeneic hematopoietic stem cell transplant.

After his informative and interesting presentation at SITC, Dr van den Brink spoke with BSB about his findings and what’s on the horizon for the treatment of GvHD.

Over the course of a half hour conversation, he covered some of the new treatment options, one of which may change the standard of care, and the rational some companies are pursuing by targeting the innate immune system.

For those interested in CAR-T cell therapy and the promise of allogeneic CAR-T cells, Dr van den Brink kindly talked about some unpublished data from MSKCC about why we have not seen GvHD in patients who receive allogeneic CAR-T cells.

GvHD is an important topic, and one that deserves more attention. I expect we will here a lot more about it at ASH this year so reading this interview will, hopefully, help you better put that data in context.

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Immuno-oncology is one of the hottest topics, if not, the hottest in cancer drug development at the moment, and every conference seems to advance the field forward. The pace of progress is breathtaking as thought leaders and pharma & biotech seek to maximize how to leverage the body’s immune system in the fight against cancer. It’s exciting times!

Coming up next on the calendar are two cancer conferences, the Society for Immunotherapy of Cancer (SITC) held in Maryland later this week, followed swiftly by the EORTC-AACR-NCI Molecular Targets conference (often referred to as the Triple meeting by industry insiders) in Barcelona just before Thanksgiving.

SITC 2014 Immunotherapy Banner

Whoa, that’s a lot of data yet to come, and then in December we have the American Society of Hematology (ASH) and San Antonio Breast Cancer Symposium (SABCS).

Back home in the Blighty, November is often referred to as the ‘month of the drowned dog’ because it rains a lot… at this rate it’s more like raining data – let’s hope not too many agents are headed for dog drug heaven! The good news for subscribers is there’s a lot of conference coverage to come!

2014 ESMO Congress Poster HallSo here we are, after nearly two dozen posts, it’s time to close out the 2014 ESMO coverage with a final review of the immuno-oncology posters that piqued our interest.

There were 16 in all that fitted that category. Normally, we highlight three or four gems from the poster halls, so more than a baker’s dozen is quite a feast.

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Melanoma oral abstracts at ASCO 2014

A packed theatre in Arie Crown at ASCO

The melanoma oral abstracts session at ASCO 2014 was packed as a full house in the Arie Crown lecture theatre listened to the latest on new immuno-oncology therapies that are leading a revolution in melanoma treatment.

In the Clinical Science Symposium on PD-1 blockade and in the oral session at ASCO 2013 we heard how PD-1 antibodies nivolumab, MK-3475 (now pembrolizumab) and the PD-L1 antibody MPDL3280A had high response rates, long durations of response with favourable toxicity. This led to melanoma suddenly becoming one of the hottest areas of cancer drug development.

Global incidence of stage III melanoma continues to rise, with a high 5 year relapse rate (89% in stage IIIc), so there remains a need for more effective treatment options. It’s particularly sad to see so many young people end up with metastatic melanoma from over-exposure to tanning beds or too much sun! After going to several melanoma sessions, I don’t go out as much in the mid-day sun here in Florida.

So what did latest data show at ASCO 2014? Is pembrolizumab better than nivolumab?

Will combinations be more effective than single agent therapies alone and will toxicities impact the risk:benefit profile?

You can log-in to read more about where these new products stand a year later.

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