Biotech Strategy Blog

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

Posts tagged ‘LAG-3’

One of the (many) highlights for me at the recent annual meeting of the American Association for Cancer Research (AACR) was a “Meet the Expert” session presented by Professor George Coukos.

Prof George Coukos AACR 2016

Prof George Coukos AACR 2016

Professor Coukos is Director of Oncology at the University Hospital of Lausanne and Director of the Ludwig Institute for Cancer Research in Switzerland.

Ovarian cancer is becoming a fascinating battleground for cancer immunotherapy, with multiple challenges that must be overcome before we see improvements in outcomes, especially for women advanced disease.

The interview with Prof Coukos is a follow-on to the one we did on advanced ovarian cancer and checkpoint blockade at ECCO 2015 in Vienna with Dr Nora Disis.

After his AACR presentation, Prof Coukos kindly spoke with BSB and in a wide ranging discussion, highlighted some of the innovative clinical trial strategies he is working on to move the cancer immunotherapy field forward in ovarian cancer.

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Iwakuni Bridge

Cherry Blossoms and Iwakuni Bridge

We’re continuing our countdown to the 2016 AACR annual meeting in New Orleans with a look at anti TIM-3 and LAG-3 inhibitory checkpoints and highlighting some of the companies with noteworthy abstracts.

In case you missed it, yesterday AACR announced that Vice President Biden will be delivering remarks on the final day of the meeting, Wednesday, April 20th in the “Highlights 2016: Vision for the Future” Plenary Session. As conference diehards, we will be there in person, but AACR have announced they plan to livestream it to the world. It’s a fitting finale to what is set to be a “must attend” meeting for those with an interest in cancer new product development and in particular, cancer immunotherapy.

What can we learn from AACR abstracts on TIM–3 and LAG–3?

There is some early clinical data that we will be checking out (no pun intended) on TIM-3 and LAG-3.

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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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Over the last couple of years we have heard much about targeting various checkpoints that exert an inhibitory effect on the immune system and the T cells, in particular.  The main targets where we have a growing body of evidence to date are CTLA-4, PD-1 and PD-L1, but there are others including LAG-3, TIM-3, ICOS etc.

Earlier this year at AACR, we saw new evidence that combining two checkpoints (anti-CTLA4 and anti-PD1) was superior to monotherapy in metastatic melanoma, albeit with a concomitant increase in toxicities.

What about the other inhibitory signals though?  Are they bystanders, much like passenger mutations that have little effect, or do they matter, at least in some tumor types?  If so, which ones?

We took a look at some of the emerging data associated with targeting TIM-3 – the results may well surprise some observers.

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After yesterdays post on Gems from the Poster Halls at the American Association for Cancer Research (AACR) in Philadelphia where we took a look at new developments in targeted therapies, several subscribers asked for a repeat, but with a focus on immuno-oncology.

AACR 2015 Checkpoint Inhibitor PostersThere are a number of elements that many people are interested in, especially given the Merck and BMS clinical data at AACR, where we clearly saw that:

  • Anti-PD–1 therapy with pembrolizumab is superior to anti-CTLA4 with ipilimumab in metastatic melanoma (expect nivolumab to show the same thing at ASCO)
  • Combined PD–1 plus CTLA4 blockade (with nivolumab plus ipilimumab) was superior to anti-CTLA4 alone, but with higher grade 3/4 toxicities, also in advanced melanoma

Sadly though, we still see that 70-80% of patients don’t respond to these therapies.

  • How can we improve on that?
  • What happens when we explore other factors, tumour types and different aspects of the immune system?
  • What can we learn about novel sequencing or combination approaches?
  • Which ones look interesting?

Endless questions can be asked – to which we still have too few answers – although there were some encouraging signs and hints of possibilities at AACR.

The 2015 AACR program was particularly challenging this year with lots of really good symposia and general sessions, making it tough to whizz round the vast poster hall spread out around the exhibits as well.  To give you an idea of scale, it was pretty typical to cover 17K to 18K steps a day, approximately 7 to 8 miles.  For many people, fitting in a quick lunch and the posters was certainly a challenging feat, depending where you were in the complex.  With a morning session ending at 12.30pm, the afternoon session starting at 1pm and 2,000 steps between the Grand and Terrace Ballrooms, you sure had to get your skates on, Beep Beep!

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“Nothing lasts forever, because nothing ever has.”

James Shelley, The Caesura Letters

This year’s annual AACR meeting was so good, we could probably write another 50 posts and still not be done! With ASCO fast approaching, however, it’s almost time to draw it to a close and the final post conference note will be published on Monday.

Today is the penultimate report and focuses on the key highlights that caught my attention in immuno-oncology, which covers the gamut from checkpoint inhibitors, co-stimulants, innate immunotherapy and CAR T cell therapy to bispecific antibody TCRs.

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