Biotech Strategy Blog

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

Have you ever sat in a freezing cold scientific session and been so engrossed in the compelling presentations that followed, you simply forgot to take notes? Not one. That actually happened to me at the American Association for Cancer Research (AACR) in Philadelphia this year in one of the many fringe sessions that I attended.

Reading Terminal Clock

Reading Terminal Clock, Philadelphia

Granted, the hot topic of the conference was undoubtedly checkpoint inhibition, but I was anxious to escape to the comfort of some meaty and familiar basic and translational science, namely MYC.  MYC is largely thought to be a difficult to target, even undruggable protein, and along with RAS and p53, represents a formidable challenge for cancer researchers.  These three oncogenic proteins alone are probably responsible for more drug resistance developing and even death from cancer than any other proteins in a patient with advanced disease.

For cancer patients with advanced disease, the clock is ticking on time they have left.

Solve these three problems (MYC, RAS and p53) and we may have a shot at dramatically improving outcomes. As Dr Gerard Evans (Cambridge) noted:

“I think it’s fair to say that we don’t really know why interruption of any oncogenic signal actually kills cancer cells, but one of the reasons that we’re interested in MYC is because it seems to be a common downstream effector of many, maybe all cancers.”

Sure, the road to success is paved with an enormous graveyard of failures, just as metastatic melanoma was before checkpoint blockade came along, ironically.  What I heard at AACR both inspired and filled me with greater confidence… we’re finally getting somewhere.

To learn more about these intriguing new developments, you can login or sign-up in the box below.

Multiple myeloma (MM) has been very much in the news this week after the American Society of Clinical Oncology (ASCO) abstracts were released to much anticipation.

Myeloma is largely thought to be an incurable disease despite the option of an autologous stem cell transplant for newly diagnosed patients. That said, I have actually met some people who have had two or 3 transplants over several decades, a testament to their strength and fortitude in enduring such a challenging procedure.

This year, the news media have focused on elotuzumab (BMS/AbbVie), a CS1/SLAMF7 inhibitor that has previously shown clinical activity in earlier trials, after it was showcased in the ASCO Presscast last week. This why you see many articles on the data reported from this particular abstract.

New Orleans American QueenIt’s not the most exciting new data in this disease for me though, that honour goes to two other therapeutics of an entirely different kind. They come completely out of left field and what we saw over the last two months really caught our attention and may surprise you too.

Indeed, we saw hints of some of this data at the American Society for Gene and Cell Therapy (ASGCT) meeting last week in New Orleans.

To learn more about the exciting new developments in the field of multiple myeloma and what a leading thought leader had to say, you can sign in or sign up in the box below.

Medivation-LogoNew Orleans – in today’s plenary session at the 2015 annual meeting of the American Urological Association (Twitter: #AUA15), Dr Celestia Higano (Seattle), presented the results of the STRIVE trial (NCT01664923) – a multicenter phase 2 study of enzalutamide (Xtandi) versus bicalutamide in men with nonmetastatic (M0) or metastatic castration-resistant prostate cancer (M1). These were men who were asymptomatic or mildly symptomatic.

Dr Celestia Higano STRIVE AUA 2015

Dr Higano noted that this was a very late breaking abstract; topline results were only announced a little over a month ago on April 2.

The TERRAIN trial also compared the efficacy of enzalutamide head-to-head against bicalutamide. We’ve updated our EAU 2015 TERRAIN post with the additional data presented here at AUA 2015 in New Orleans.

Subscribers can login to read more about the STRIVE trial results presented at AUA 2015 or you can purchase access by clicking on the blue icon below.

Gumbo Shop New OrleansThe annual meeting of the 2015 American Urological Assoication (AUA) is being held in New Orleans… Yes, we’re on the third and final leg of our Louisiana trip encompassing AAI, ASGCT and now the triumvirate of AUA-SBUR-SUO.

This morning, I attended the Urologic Oncology Research Symposium, “High impact science in urologic oncology and progress in biomedical imaging.”  In particular, I was keen to hear about the latest research in urothelial bladder cancer (UBC) with regards to checkpoint blockade with anti-PDL1 and PD-1 therapies.

In the past, any session on bladder cancer guaranteed the lucky (or hapless) presenters with an audience of a dozen or so people.  Not any more – the room was packed with standing room only very quickly – a nice change for a disease that has seen no new therapies for 30 years.

Part of this renewed enthusiasm is due to the excitement for the checkpoint therapies making a huge impact in this disease, at least in clinical trials to date. While waiting for the session to start, one urologist I spoke to told me he bought the ASCO Virtual Meeting last year just to hear Dr Tom Powles talk on anti-PDL1 therapy with MPDL3280A in advanced urothelial cancer. What did you think of it, I asked?

“Wow, just wow!”

Later this month an update on the more mature data from that phase I trial is due at the American Society of Clinical Oncology (ASCO) from Dr Daniel Petrylak (Yale)… who just happened to be one of the presenters at AUA this morning.

He discussed the checkpoint data with MPDL3280A in urothelial bladder cancer, as well as the pembrolizumab data from ESMO last fall and what’s happening with nivolumab. These drugs are quite different in many ways, not just in terms of the efficacy, but also in terms of the biomarker data, as we discovered today.

To learn more about the latest checkpoint data, including an update on biomarkers, you can login in or sign up in the box below.

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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