Biotech Strategy Blog

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

Whew, after posting the interview with Dr Tom Gajewski this morning from the American Association of Immunologists (AAI), we headed across town to the American Society for Gene and Cell Therapy (ASGCT) morning session and then dashed back to complete the first of the American Society of Clinical Oncology (ASCO) Previews for 2015!

What a busy week it’s been, never mind the hurly burly of today.

The ASCO 2015 abstracts went live at 5pm ET, with the exception of the late breaking abstracts, which are usually embargoed to the day of the actual presentation.

ASCO 2015 Abstracts

There are a number of topics well worth highlighting this year, so today kicks off the first of our annual Preview series on BSB. There will be much more to come – we wrote nearly 30 articles before, during and after the conference last year – this year will probably be similar with so much data to review and discuss.

New Orleans – one of the presentations of note at Immunology 2015 (the annual meeting of the American Association of Immunologists) was by Thomas J. Gajewski MD, PhD from the University of Chicago. His presentation on “Innate immune sensing of cancer via the STING pathway” was well worth the trip to New Orleans.

Presentation by Dr Gajewski at Immunology 2015

Readers may recall the post we wrote in March on “What is STING and why does it matter in cancer immunotherapy?” It followed the news that Novartis were collaborating with Aduro Biotech (NASDAQ: ADRO) on agonists that activate the STING (Stimulator of Interferon Genes) signaling pathway in immune cells.

I had the privilege to talk with Dr Gajewski (pictured below) after his presentation at AAI.

Dr Tom Gajewski AAI 2015

Excerpts from the interview will feature on Episode 2 of the Novel Targets podcast (@TargetsPodcast). (Do sign up for the Novel Targets Newsletter if you want to be among the first to know when this will air). Subscribers can read more from the interview below.

You should read and/or buy access to this post if you don’t know the answers to the following:

  • What role does the tumor microenvironment play in response to cancer immunotherapy?
  • How could the tumor microenvironment be a biomarker of response to checkpoint inhibitors?
  • Why target the STING pathway?
  • Reasons Novartis are collaborating with Aduro Biotech?
  • How may a STING agonist be brought to the clinic?

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AAI LogoNew Orleans – At the 2015 annual meeting of the American Association of Immunologists (AAI) leading experts came together to share their insights on the Promise of Cancer Immunotherapy.”

The audience at #AAI2015, in an artic chilled hall, heard from an outstanding panel of speakers, many of whom flew in specially:

  • Immunologic Checkpoint Blockade: Combinations and Mechanisms, Jedd Wolchok (MSKCC)
  • Immune Checkpoint Therapy: Clinical Success and Next Steps, Padmanee Sharma (MD Anderson)
  • Improving Cancer Treatment Through Immunotherapy Combinations: Combination MAb Therapy: Dual tumor & Immune Targeting, Holbrook Kohrt (Stanford Cancer Institute)
  • Curative Potential of T-Cell Transfer Immunotherapy for Cancer, Steven Rosenberg (Surgery Branch, NCI)
  • PD-1 pathway blockade in cancer therapy: new frontiers, Suzanne Topalian (Johns Hopkins)
Dr Steven Rosenberg (NCI)

Dr Steven Rosenberg (NCI)

Cancer Immunotherapy is such a fast-evolving field that at Immunology 2015, we heard data that wasn’t at the annual meeting of the American Association for Cancer Research (AACR), just a few weeks ago.

Several presenters also put in context data that will published at the forthcoming ASCO annual meeting.

If you’d like to hear more about some of the checkpoint inhibitor data at AACR15, do listen to the first episode of the Novel Targets podcast (if you haven’t already done so).

It’s available as a free download on SoundCloud and on iTunes.

This post offers a top-line summary of some of the key messages we heard in the #AAI2015 symposium.

Subscribers can login below to read more or you can purchase access to premium content by clicking on the blue icon at the end of the post.

As we wrap up our AACR coverage, I can’t believe it’s already time to discuss the annual American Society of Clinical Oncology (ASCO) meeting already – it seems to come around way too fast.

Over the last few years, we’ve reported on the rapid and impressive rise of innate, adoptive and adaptive immunotherapies in cancer research and wondered how long it would take before we see such data presented in the plenary session.  That actually happens this year… finally!

Fireworks River Thames

A checkpoint trial makes the ASCO 2015 Plenary!

It does look like 2015 is the year that checkpoint inhibitors cannot be ignored for plenary selection with the wealth at data available at first AACR and now ASCO emerging.

This is no bad thing, especially given these drugs can affect the long tail of survival and are really starting to impact the dismal 5-year survival rates in metastatic melanoma and non-small cell lung cancer (NSCLC).

Beyond those two tumour types, what else can we expect to see and how is the data likely to shape up?  We took a look at the abstracts available based on the titles only, the actual abstracts themselves come out next week.

What did we find?

You can check out our first Preview on the Top 10 immunotherapy trials with checkpoint blockade by signing up or logging in the box below…

We know from preclinical research that immunosuppressive tumour microenvironments can restrain anti-tumour immunity, thereby making subsequent therapeutic interventions less effective than expected. CD40 activation has been shown to reverse immune suppression and drive antitumor T cell responses, which in turn could lead to potentially better outcomes.

What happens when patients with advanced melanoma are given a checkpoint inhibitor plus an immune agonist such as anti-CD40?

Can we help the non-responding patients to checkpoint blockade improve their outcomes and shift the long tail in survival curves up using this approach?

To learn more about the latest combination data with immuno-oncology therapies and where they are going next, you can sign up or sign in in the box below.

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!

To learn more about the latest data in these areas, especially from the small up and coming biotechs, you can sign up or sign in below.

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With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:

“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”

Good question.

There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.

Reading Market Philly Chocolate TowerTo maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.

When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!

I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research.  Thank you for joining our conference coverage service, we really appreciate it.

To learn more about the hot topics in targeted therapies for cancer research, you can log in or sign up in the box below.  Read on…

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One of the obvious learnings from the American Association of Clinical Research (AACR) meeting earlier this week was that we are coming to the end of the low hanging fruit opportunities for checkpoint inhibitors as monotherapies.

Speaking with numerous company people in this space, there was wide consensus on that point. As one clinical lead put it succinctly, “From here on out, it’s going to get way more complicated – had a low grade headache develop after the very first science session I attended – and it’s still there after two days!”

How many of us know that feeling all too well?  AACR always has the heaviest science load of any cancer conference we attend each year. Sure there’s some nice clinical data, but that is like nibbling on the light appetizers before the 20 course banquet. You need much stamina and fortitude to survive the brain fog at AACR. Then there’s the glee at snagging some key poster handouts at the meeting, only to be rapidly diminished when you try to read the 4pt print post hoc and realise your eyes cannot focus easily.

Looking at the long list of topics I want to cover in the in-depth post meeting analysis for a ‘lighter’ post, especially given that it’s Friday after a very long week, that sinking feeling hit home hard – there are no lightweight topics at AACR.

The other day, we posted about the promising data in triple negative breast cancer (TNBC), following on from the Genentech and Merck presentations at the San Antonio Breast Cancer Symposium (SABCS). These data surprised many folks, mostly because they didn’t consider breast cancer to be an immunogenic tumour – nor is lung cancer in the broader scheme of things for that matter – yet we are seeing some nice durable responses in both tumour types with checkpoint inhibitors.

In other words, our definition and perceptions must change as we redefine how we identify and think of possible ‘responsive’ cancers to these agents.

So where are likely heading next?

To learn more about future directions with checkpoint inhibitors, you can sign in or sign up below.

Quick Reminder: Today is the last day for the AACR Special – the discount ends at midnight ET tonight. We may not offer this rate again as it’s a limited time only deal!

With the news hot off the press at the 2015 annual meeting of the American Association for Cancer Research (AACR) that Merck’s pembrolizumab (Keytruda) beat out BMS’s ipilimumab (Yervoy) in advanced melanoma, quite a few readers wrote in asking whether this signals the end for ipilimumab?

The short answer is no, and here’s why…

To find out why, you can sign in or subscribe to our Conference Coverage service in the box below.

Philadelphia – it’s the final day of the American Association of Cancer Research (AACR) annual meeting, and it’s been one of the best AACR annual meetings of recent years, with cancer immunotherapy very much at the fore.

This morning, the plenary session at the meeting was: Oncology Meets Immunology: Not Just Another “Hallmark.”

Cancer immunotherapy is changing the paradigm of cancer treatment in many ways, which is why the title of today’s plenary was clever….

Readers will be aware of the classic Hallmarks of Cancer paper (open access) by Douglas Hanahan and Robert Weinberg, which provides a framework for understanding how how tumors develop (e.g. sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis). This landmark paper provides a way to understand where new cancer treatments could act.

Today’s plenary featured four presentations from leaders in the field of cancer immunotherapy:

  • Engineering Improved Cancer Vaccines, Glen Dranoff, Novartis Institutes for Biomedical Research
  • Leukocytes as targets for therapy in solid tumors, Lisa M. Coussens, OHSU Knight Cancer Institute, Portland
  • Fatal Attraction: A new story featuring the immune system and pancreatic cancer, Elizabeth M. Jaffee, Johns Hopkins University, Baltimore
  • The mechanistic basis of cancer immunotherapy, Ira Mellman, Genentech, Inc. South San Francisco.

The first three speakers I have to say did not live up to the promise of their billing, spending far too much time on “My Pet Project,” delving into the weeds of the research from their lab or group, rather than putting the landscape in context, providing strategic direction of where things are going and including fair balance across the work in the field, which is what I expected a plenary presentation to be about.

One of our highlights of the plenary (and the conference) was the presentation by Ira Mellman, Vice President at Genentech who along with Dan Chen, Cancer Immunotherapy Franchsise Head at Genentech, are the author of the paper that is fast becoming the equivalent of the classic Hallmarks paper for Cancer Immunotherapy: Oncology meets immunology: the cancer-immunity cycle. (open access).

Dr Ira Mellman Dr Leisha Emens Dr Dan Chen AACR 2015

Earlier in the meeting, I had the privilege to chat with Drs Ira Mellman (pictured left), Leisha Emens (Johns Hopkins) and Dan Chen (pictured right) for the Novel Targets podcast. They are three of the many “rock stars” of the cancer immunotherapy world.

What were our highlights of AACR 2015?

We’ve carefully selected our Top Ten presentations of this year’s AACR for subscribers – Ira Mellman’s was one of them – but who are the others?  Some of them could be found outside the main sessions in the fringe rooms.

You can login in below or can purchase access to read them in the box.

For the week of the AACR meeting, there’s $50 off the price of a quarterly subscription, that will get you not only our post-AACR conference coverage, but access to the library of content we’ve written for example on immuno-oncology.

We’ll be at four meetings, including ASCO in the next two months, so to paraphrase Frank Sinatra, “The best is yet to come”…….

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