Biotech Strategy Blog

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

Posts tagged ‘TIGIT’

Remember the good old days at ESMO17 in Madrid? Sadly there’s no face to face networking at this year’s ESMO20 virtual meeting!

In this third ESMO 2020 Preview the focus is on early stage immunotherapies – we’ll cover targeted therapies in a separate review article.

As new regimens evolve involving multiple immune targets, this complexity brings with it a greater need to understand cell-cell interactions – not just immune cell relationships, but also oncogenic, metabolic, and even epigenetic ones. How do they all fit together and what happens when we interfere with those relationships therapeutically?

Often the simple answer is we don’t know until we head into the clinic, I’m afraid.

Beyond the obvious phase 3 IO readouts in the various Presidential symposia and Proffered oral sessions there are quite a few emerging ideas – old ones with a twist as well as entirely new ones – which we can consider and discuss.

Here, we highlight five key IO areas related to cancer immunotherapy and explore the various concepts as preparation for the upcoming meeting…

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Sadly not the #blisterwalk this year

Not in Chicago – Breast cancer has been a hot topic again on several fronts after a bit of a lull on the R&D front.

Writing about such trials across ESMO Breast, ASCO and the second AACR meeting is all very well, but what about some KOL commentary and reactions to some of the data we get to see?

If this has been a burning question for you, this is a handy article to catch up on. Of course, to be clear – not all the trials will be positive or biomarker analysis helpful, so here we tackle the issue and look at what’s what though the lens of a specialist…

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Not in Chicago: We continue our ASCO coverage with a look at the evolving TIGIT landscape and the initial tiragolumab data in lung cancer.

With all the breathless hype of late one wonders if some observers believe (accompanied by loud trumpeting of horns) this is the next big checkpoint target after CTLA-4 and PD(L)1, but is it?  The field has barely got started with a raft of new trials opening to evaluate several molecules in different combinations across solid tumours, and yet we have something of a fanfare already.

Will TIGIT roar and fire up the immune system in some people with cancer or will it fizzle out?

To those of us familiar with new product development and early stage development the ‘hot’ status is likely leaving us somewhat bemused at the noise around the emerging targets, after all it’s going to be a long while before we see those all important phase 3 readouts with appropriate head-to-head comparisons.

In this latest article, we take a look at the Genentech antibody, tiragolumab, and also discuss the development with a company executive to gain their perspectives, insights and rationale on what was behind the recent trial expansions beyond the phase 1 study in advanced solid cancers.

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Time for some additional colour commentary!

There has been some incredibly intense interest surrounding TIGIT as a new therapeutic target in oncology of late, to the point where some observers have been wildly claiming this is the new universal checkpoint everyone has been waiting for.

But is it?

It’s early days yet with little data presented from people with cancer, so at this point it could well be a bit of a stretch to find another anti-PD–1/PD-L1 equivalent, but this doesn’t mean there isn’t utility in seeing clinical activity in some tumour types, far from it.

In our latest post, we take a look at what’s coming up in the TIGIT niche, along with an interview from a company active in this niche.

What do the company have to say and how do they see this panning out?

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And we’re off!

Rays of hope during dark days

No, no, not to the races – and certainly not to Cheltenham – but rather it’s that time of the year when the first of our annual AACR Preview series drops.  While some cancer conferences have been postponed and even cancelled, others such as AACR and ASCO are proceeding with virtual meetings, proving that even dark times can offer hints of hope.

This is good news for both young researchers and companies alike in getting data out there and shared because life goes on as time and tide wait for no man.

The actual abstracts themselves won’t be revealed until later in the month on April 27th, but for now we get a taster of this year’s truncated event since the titles available for the first virtual meeting.

Often time, this glimpse is sufficient to garner some useful clues, so what does this year hold in store for us all?

This Preview series will be in multiple parts – a review of some of the key oral sessions from the first virtual program (targeted agents, immunotherapies, cell therapies, novel targets, translational studies etc) followed by a review of the posters in the final part.

To get started, let’s take a look at some of the important presentations we can expect to hear on the first day…

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ASH19 Targeted Therapies Preview: This year’s ASH in Orlando is very much dominated by new developments on the immunotherapy front in terms of both T and NK cell therapies, with some passing interest in BTK inhibitors as well.

It’s not always sunny in Florida…

What about targeted therapies and the science behind those developments?

It was not that long ago that these were the main lifeblood of the meeting across many, if not most, hematologic malignancies. How times have changed!

That said, outside of the CARs (T and NK cells), as well as bispecific immunotherapies, and BTK inhibitors there are still some gems to be found amongst the rest of the ASH19 abstracts.

Here we highlight an additional 10 abstracts involving early pipeline areas that encompass some novel targets, new combination approaches, or emerging science.

Please note that the novel targets can take the form of classic targets or IO ones since they didn’t fit in the prior ASH Preview topics already reviewed under separate cover

Curious to find out more about these intriguing selections and get a heads up on additional insights from our ASH19 commentary?Subscribers can log-in or you can click to gain access to BSB Premium Content.

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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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Port Sunglight SpringSpring has arrived in many parts of the world, and with it I am always reminded of William Wordsworth’s classic poem, “I Wandered Lonely as a Cloud:”

I wandered lonely as a cloud 
That floats on high o’er vales and hills, 
When all at once I saw a crowd, 
A host, of golden daffodils; 
Beside the lake, beneath the trees, 
Fluttering and dancing in the breeze.

 

So what does the future hold for cancer immunotherapy?

Inspired by Wordsworth, I’ve sat on my cloud and have looked at some of the recent review papers and thought pieces published by experts in the field. Do they offer a Jerry Maguire – like mission statement: “The Things We Think and Do Not Say: The Future of Our Business” or will we have to wait till AACR 2016 in New Orleans to learn more?

 

This is the latest in our pre-AACR 2016 annual meeting series. Subscribers can login to read more or you can purchase access.

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Picture Credit: @gene_antibody

Picture Credit: @gene_antibody

For much of the last two years, one of the hottest topics around has been T cell manipulation, which can happen in many different forms.

This is just one area that we have covered extensively in the immuno-oncology space from Chimeric Antigen Receptor (CAR) T cell therapies to checkpoint inhibitors, as well as various antibodies, including the first bispecific T-cell engager (BiTE) to CD19 that recently approved by the FDA called blinatumomab (Blincyto) from Amgen.

Not all cancer patients respond to all these approaches though.

Why is that and what approaches or novel targets can we explore next to address this vexing issue?

At the SITC and SABCS meetings, I saw some really interesting and unusual presentations, together with some recent publications on topic, that really piqued my interest in this challenge. They are early signs of the new directions some of the research in this field could go. Overcoming resistance and understanding different aspects of immune escape will likely be very instructive in developing the next generation of combination studies that could make a positive impact on patients.

Today’s post touches on some of these exciting developments and includes an in-depth interview with Dr Ira Mellman, the scientist behind Genentech’s immunology research program at gRED.

Interested readers can log-in to read more about the exciting new developments that are happening with different types of antibodies in the immuno-oncology space.

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