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

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The 10 abstracts selected here are actually not in order of magnitude, preference or weight… with the lone exception #1, an incredible piece of work that was a decade in the making.

Chicago!

Chicago!

Few of these choices are in the press briefing, none are in the Plenary session – they’re often hidden gems that many will miss in the hurly burly of the data drop and noise.

They’re also 10 abstracts that I feel are worthy of highlighting with some additional commentary.

Some of the ideas here illustrate some intriguing trends that are emerging, others may have a big impact on the cancer immunotherapy space, either because of the novel concept idea, or because the data are very compelling, if you understand the science.

You can decide for yourselves – which ones would you pick and why?

Subscribers can log-in or you can sign up in the Blue Box below to learn more about the important cancer immunotherapy abstracts at ASCO 2016…

After a long lull on the targeted therapies front – outside of EGFR T790M in lung cancer – this year’s ASCO has plenty to be cheerful about with new data across multiple tumour types.  We can’t cover them all here, but more will be discussed in the Daily Live Blogs starting on Saturday.

Which drugs are going to be in roaring back after a quiet period?  Which ones will be having a more muted meeting?

ASCO16 Chicago 4For those of you who are working in the targeting therapy world, take heart, there is a future beyond cancer immunotherapy; it is not the universal panacea and will likely not cure every cancer, at least for now.

There’s still a market opportunity for targeted therapies in cancer, and as we mentioned in yesterday’s ASCO Preview, there is also potential for the combination of targeted therapies with immunotherapies, so long as the combined toxicity is manageable and doesn’t outweigh the benefits.

In this post we’re looking at a selection of targeted therapies in a variety of tumour types. There’s a lot to choose from at ASCO this year.

Here’s a few we think are worth highlighting upfront.

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For years we’ve followed the trials and tribulations of targeted therapies seeing many approved and quite a few disappear forlornly (and officially) off to dog drug heaven. Many more sit in no-man’s land as companies eagerly wait in a holding pattern for other trial readouts in different tumour types. Sadly, sometimes these studies don’t generate enough compelling data either. With so much competition about, there are no shortcuts or low-hanging fruit in biotech or cancer drug development any more.

ASCO16 Chicago 1

En route to Chicago and ASCO!

Then along came antibody drug conjugates (ADCs), with some encouraging results in a range of cancers in both solid tumours and hematologic malignancies that lead to the approval of several new therapies.

After that, the next big advance was immunotherapies, specifically checkpoint blockade, with encouraging single agent activity in melanoma, lung, and even urothelial bladder cancer. We’ve also seen the promise fo combining two different checkpoints such as nivolumab and ipilimumab together in metastatic melanoma, albeit with an increase in toxicities.

This is all very well and good, although the challenge remains that the majority of patients either respond to therapy and relapse, or do not respond at all, depending on the circumstances, the tumour type and the regimen. We still have a long way to go in moving the needle and creating a new paradigm shift on a broad scale.

So what happens when we start to combine modalities – such as targeted therapies with immunotherapies?

Uh-oh, I hear the distant cries of disagreement erupt…

  • Remember vemurafenib plus ipilimumab in metastatic melanoma was scuppered by severe hepatitis?
  • What about osimertinib plus durvalumab in NSCLC and the increased incidence of ILD?

Both of these statements are true, and yet… we should not assume that all mixed therapy combination approaches are doomed on the basis of a mere n of 2. What happens if some are synergistic or additive? What happens of there are hidden gems that teach us new ways of doing things rather than doing the same old thing just because it’s always been done that way?

With this in mind, I’d like to open the door on our first ASCO 2016 Preview series with a look at novel combination approaches in development that caught my eye.

What are the early hints and signals that we can learn from the data? Which companies are evaluating imaginative new ideas that may turn the tables on traditional thinking?  The ideas discussed here may well surprise a few people.

To learn more, Subscribers can log-in below or you sign up for a subscription and join the ever burgeoning BSB club of sophisticated lay people – including investors and commercial/new product development people – who can really understand and appreciate the fundamentals of cancer R&D…

The BET Bromodomain market is a meaty epigenetics topic we have followed for several years now, including a look at the space back in 2013 on the old Pharma Strategy Blog (Link). The last update on this was ironically at AACR last year when we discussed MYC and bromodomains (Link).

Nawlins Mardi GrasIn a remarkable tale of two cities in real life, two companies we discussed in those posts – Constellation Pharma and Tensha Therapeutics – have had markedly different fortunes since then. Roche decided to end their collaboration with the former and went on to acquire the latter instead.

Since we first wrote about bromodomains and BET inhibitors, the niche has exploded in a wildly stunning way… More drugs in the pipeline, more tumour targets being explored, and even novel combinations being evaluated preclinically for synergistic or additive effects. Even I was surprised by how competitive this niche has become based on the offerings at AACR this year.

With all the wealth of new data at the AACR annual meeting and also some other recent presentations I’ve attended elsewhere, it’s time for a more in-depth look at the BET/Bromodomain landscape.

Who are the new players, which tumour targets are now being evaluated, which combinations might be useful?

A word to the wise – this is neither a nerdy science post nor a comprehensive literature review – instead we take a look at the emerging landscape from a new product development perspective.

Science has been absolutely critical to success in all of the cancer therapeutics from targeted therapies to immunotherapies that have emerged in the last decade.

It really doesn’t matter whether you come from a marketing and commercial organisation or the investment community – if you want to make great decisions, you need to understand the basics of the science underpinning the R&D, where the strengths and weaknesses are. The alternative is play Roulette and put everything on Black 11 as a euphemism for whichever company/product/target you have an interest in.

To learn more about this burgeoning niche in epigenetics, subscribers can log-in or you can sign-up via the Blue Box below:

If you had told me several weeks ago that we would write over 28 posts on #AACR16 and become very interested in mouse models, then most likely I would have laughed out loud and told you not to be so ridiculous!  Here we are with the 29th one and, another, on the bromododomain landscape yet to go.  Such was the vast richness of data and concepts being discussed or presented in New Orleans for those who chose to look.

Today, I want to start the segue from AACR to ASCO coverage.

Nawlins MGRAS FIOne way to do that is through the second part of the Gems from the Post Hall series. This latest one looks at a range of intriguing new targeted therapies and novel targets that are emerging, including a pharma company with a particularly interesting early pipeline.

Several pharma companies presented interesting data on their very early compounds currently in development, plus I noticed a trend for a new class of targeted therapies to emerge, MNK inhibitors, which we will also discuss.

Companies mentioned: Bayer, Orion Pharma, Lilly, Novartis, Pfizer, Agios.

Targets mentioned: PI3K, CDK, Akt, TWEAK, FGFR, BUB1, IDH1, SMYD2, MNK

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Miami Beach

Miami Beach Lifeguard Tower

This week I’ve been at an American Association for Cancer Research (AACR) conference in Miami on “Targeting the Vulnerabilities of Cancer,” part of their Precision Medicine Series (Twitter #AACRpm16).

What’s interesting about AACR small specialist meetings is as well as listening to high quality talks, they create a relaxed atmosphere for networking and catching up with experts informally. The conference this week was relevant to anyone with an interest in cancer drug discovery.

Dr Bernie FoxAlthough cancer immunotherapy remains the hottest topic in cancer drug development, we shouldn’t forget that there are other therapeutic targets worth exploring; several potential new opportunities were highlighted in Miami.

As readers know we don’t share unpublished data on the blog, so what I’ve done is provide a top-line summary of some of the strategic themes and key take homes I took from several of the presentations.

As an aside, If you haven’t already done so, do listen to the latest episode of the Novel Targets podcast – Of Mice and Men – it features excerpts of interviews recorded at the recent AACR annual meeting in New Orleans. I was surprised by some of what I heard!

For more information on forthcoming AACR meetings and workshops, check out the events calendar on the AACR website.

If you would like to read my commentary from the AACR Precision Medicine Conference in Miami on Targeting the Vulnerabilities of Cancer, subscribers can login below or you can purchase access.

After looking at one important poster yesterday on multiple myeloma, it’s time to explore other equally interesting targets in other tumour types.

Some years reflect the inertia that hit oncology R&D with a lot of old data rehashed or they can be flooded with many me-too compounds.  Not this year, there’s a lot to talk about and review… so much so that we may well have enough for three rounds of Gems from the Poster Halls, time permitting as ASCO is fast approaching!

Without much further ado, for round 1 we have explored eight posters spanning four companies with a variety of different targets including chemotherapy, targeted therapies and immunotherapies.  I will say though, that the lines are being blurred as all of these modalities can impact the immune system, sometimes in unexpected ways.

What’s in store for today?  A focus on biotech companies doing intriguing cancer research.

Companies mentioned: Infinity, Innate, Incyte, Agenus

Jounce Poster AACR 2016

The AACR Poster Halls get packed quickly!

It’s time to change direction and take a look at some of the Gems from the Poster Halls at the recent American Association for Cancer Research (AACR) meeting.

One particular abstract that looked interesting related to the Aduro compound, BION–1301, which is a monoclonal antibody targeting the B cell Maturation Antigen and its ligand, A Proliferation Inducing Ligand (BCMA-APRIL) in multiple myeloma.

Increasingly, there has been a lot of clinical interest in the BCMA target, but what about APRIL?

We spoke to one of the scientists involved in the research about this novel agent:

“It is very effective at abrogating the activity of APRIL and, in particular, in our models blocks the growth, survival, drug resistance, migration and adhesion of myeloma cells both in-vitro and in-vivo in our murine models. These models have been predictive for clinical activity of other novel targeted therapies including lenalidomide and bortezomib, and so we think targeting APRIL represents a very promising strategy.”

Sounds pretty good, right?

To learn more about what they had to say about this approach, subscribers can log-in or you can sign-up in the blue box below.

New Orleans American Queen

New Orleans, American Queen

After yesterday’s enlightening conversation on novel ways to jumpstart the immune system including OX40, vaccines, and STING with a self-confessed radicalist aka cancer immunologist (Dr Bernard Fox), we now turn to a self-described optimist for an industry perspective on oncology R&D and Part 2 of our anti-OX40 mini-series:

  • What ideas and challenges need to be considered in order to develop a new agent against a novel target, alone or in combination with another unapproved agent?
  • We know that mouse models and biomarkers aren’t optimal yet, so how do those issues and other factors influence decision making and clinical trial design?
  • It’s not so easy as many think – there are way more unknowns than knowns – so how do companies go about tackling them?
  • What can we learn from the readouts?

To learn more, subscribers can login or you can click on the blue box below to purchase a subscription and read the OX40 mini-series, as well as our comprehensive AACR coverage…

At the recent annual meeting of the American Association for Cancer Research (AACR), one controversial area that arose was centred around targeting OX40, a stimulatory checkpoint. We’ve written extensively about anti-OX40 checkpoint agonists on the blog in the past.

Targeting OX40 is an area of interest to several companies looking to improve the effectiveness of checkpoint inhibitors. As a result, several companies have OX40 agonists in development, including AstraZeneca/MedImmune, Roche/Genentech, Pfizer, GSK and Incyte/Agenus, for example, making it a competitive target and interesting race to market.

Meanwhile, in their recent 1Q earnings call, Roche announced that they expect to present clinical data on their PD-L1/OX40 combination at the forthcoming American Society of Clinical Oncology (ASCO) annual meeting in Chicago from June 4th to 7th. This therefore makes it a timely moment to reflect on the data generated so far and what we can expect next month.

In New Orleans, we spoke to several researchers who are active in the OX40 field, since there were both mouse and human data presented at this year’s conference.

The interviews conducted were wide-ranging and informative, so in our latest mini-series we explore Part 1 today with Part 2 tomorrow.  They are relaxed fireside chats with different experts included in each to discuss their data (and other relevant topics) presented in New Orleans.

This way, you’ll be able to follow along and find out where the common areas are, as well as the differences in perspectives, and even where we could be headed in the near future.

This latest series on OX40 agonists raises many intriguing questions that we hope may be answered at ASCO and other clinical meetings going forward. We also discuss the challenges and opportunities associated with research into cancer immunotherapy combinations.

Dr Bernard Fox at #AACR16

Dr Bernard Fox at #AACR16

Intriguing preclinical data in mice models were presented by Dr David Messenheimer (Portland). We spoke with the senior author of that abstract, Dr Bernard Fox.

He is the Harder Family Chair for Cancer Research and Chief of the Laboratory of Molecular and Tumour Immunology at the Earle A. Chiles Research Institute in Portland, Oregon, and a leading cancer immunotherapy expert. He’s also the CEO of UbiVac, a biotech spin-off from Chiles in 2005 to develop therapeutic vaccines for cancer and infectious diseases.

Subscribers can login to read more on where “the rubber is hitting the road” in cancer immunotherapy clinical research.

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