Biotech Strategy Blog

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

Posts tagged ‘AstraZeneca’

One of the surprise controversies at ESMO16 was the fall-out between Myriad Genetics (NASDAQ: MYGN) and Tesaro (NASDAQ: TSRO) over whether the company’s PARP inhibitor, niraparib, should require a companion diagnostic for the treatment of women with platinum-sensitive ovarian cancer in the maintenance setting. We previously wrote about this from Copenhagen (Link).



Tesaro were so keen on controlling their message, in the run-up to ESMO, they even went to the trouble of taking out a legal injunction against Myriad Genetics in an attempt to prevent them publishing their own press release discussing the niraparib data.

We knew about this “off the record” at ESMO, but it’s now a matter of public knowledge and John Carroll admirably reported the story on Endpoints last week (Link).

It is a sad reflection on any biotech partnership or pharma alliance if you can’t reach an agreement in private, and have to resort to an injunction in US Federal Court. Doubly unfortunate when you lose the injunction too!

As many readers are already aware, back in June 2014 AstraZeneca failed to convince an FDA ODAC about the merits of olaparib in the same indication that Tesaro are seeking. This is why the data for Tesaro and their regulatory/commercial approach justifies careful scrutiny.

What’s more, data from Myriad Genetics was key to AstraZeneca obtaining a subsequent indication for olaparib in more advanced ovarian cancer, so their experience in this space cannot be dismissed.


Johnathan M. Lancaster MD PhD

At ESMO, the Myriad Genetics Laboratory Chief Medical Officer, Dr Johnathan Lancaster kindly spoke to BSB.

He shared his perspective on the niraparib data and why a companion diagnostic should be considered based on the NOVA trial data presented by Dr Mansoor Mirza. You can read more about the data in The NEJM paper that was published simultaneously (Link).

Dr Lancaster was formerly Director of the Center for Women’s Oncology, and Chair of the Department of Women’s Oncology at Moffitt Cancer Center in Tampa.

While he does bring a corporate bias based on his position at Myriad Genetics Laboratories – and Myriad clearly have a vested interest in selling diagnostic tests – his clinical perspective is worthy of consideration and it’s one that is shared by other GYN oncology thought leaders we have spoken to (see: earlier post, “what Tesaro aren’t telling you about niraparib”).

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The 2016 Congress of the European Society for Medical Oncology (ESMO) is fast approaching. It takes place next month from October 7th to 11th and we will be on site covering the meeting for Biotech Strategy Blog. We’re looking forward to a great meeting!

ESMO 2016 CongressIf you are sitting on the fence as to whether you should go to Copenhagen, then hopefully our series of Previews will help you decide.

Be warned that accommodation is in already in short supply and ESMO are now putting people up across the Oresund bridge in Malmo, Sweden.

The Congress App has a lot of useful information and is well worth downloading, if you haven’t done so already.

Last week many of the late breaking abstract (LBA) titles were announced, although there are still some placeholders. While we won’t know the actual late-breaking data until the meeting, the LBA titles offer insights into what will be presented in Copenhagen.

In the second in our ESMO 2016 Preview series, we’re highlighting the lung cancer late breakers that we’re looking forward to hearing, providing some background on why they may be of interest, and a look at how some of subset landscapes may be a-changing in the future.

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September 1st… as the hot summer floats away from London town and cooler autumn days draw in, it’s time to think about the upcoming fall cancer conference season – it’s quite a busy one this year!

In the coming weeks, I will be rolling out our series on the ESMO 2016 Previews (Twitter #ESMO16) and taking a more in-depth look at various topics of interest. The Copenhagen meeting is later than usual and also more compressed, with numerous sessions now held simultaneously. It used to be that you could take a break between key sessions, but not any more – there’s a lot going on this year.

View of Thames BarrierOne of the things that jumped out to me from a preliminary review of this year’s hectic ESMO program is an interesting novel target that had some early preclinical data at AACR, but that sadly got lost in the tsunami of data there.

It is good to have that reminder and be able to return to it in the context of broader data because overcoming barriers to drug resistance with targeted therapies is still an important issue that is worth researching.

You likely won’t see it in many analyst reports or previews, however, although it’s a hidden gem of great interest and well worth exploring in terms of what we know so far. This means that readers will be both prepared and intrigued – don’t be surprised to hear about some BD&L deals in this niche in the future.

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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.

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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.

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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.

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British Javelin TrainIt’s Day 6 of our Countdown to the AACR 2016 annual meeting in New Orleans. We’re at the halfway, 6 posts written and 6 more to go!  Then it will be daily Live blogs from the meeting.

There’s a lot of cancer immunotherapy at AACR this year, so after yesterday’s post on GITR we’re continuing our mini-series with a look at another immune agonist.

Today, we’re moving onto OX40 (CD134) as a novel immuno-target. Regular readers will know that we’ve been following this target for some time.

Immune agonists such as GITR, OX40, CD40, CD27 and 4-1BB help to rev up T cells. As Dr Tom Gajewski (Chicago) told us last year, in an interview published on the blog and excerpted in Episode 6 of the Novel Targets Podcast: Stepping on the Gas:

…there are inhibitory receptors on activated T cells that are involved with shutting immune responses down. There are also activating receptors that help to rev up those T cells. You might question whether you can push an activator and block an inhibitor, and maybe get a good anti-tumor response going as well.

When we drive a car, we both lift our foot off the break and we step on the accelerator. We have really beautiful data in animals that that this is exactly the case, that if you hit one of those strong positive regulators, and block just one of the negative regulators, you can have complete disappearance of the tumors in mice.

Several of those positive agonistic antibodies against costimulatory receptors are in the clinic. One of them is anti-OX40 that a couple of groups have in the clinic. We’re working with Genentech, that has one of those agents in phase I.

What does the OX40 competitive landscape look like?

In those post we’ve provided commentary on some of the new products in development from companies and highlighted a surprising number of abstracts that you’ll want to watch out for at AACR 2016 if you’re on the cancer immunotherapy track.

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Macarons in shop windowWe’re all familiar by now with the idea of checkpoints that can be inhibitory (release the brake) or stimulatory (put the foot on the gas) on the immune system.

There are multiple checkpoint modulators in development, it’s becoming a bit like buying a macaron – which flavour do you want?

As the late Holbrook Kohrt said on the Novel Targets Podcast last year:

There are two types of checkpoint inhibitors, one checkpoint inhibitor are these series of markers that each of them when you target them, they will slow down the function of that cell. Now that’s a good thing if that cell is a suppressor cell, such as a regulatory T cell. Anti-CTLA-4, ipilimumab, the first approved immunotherapeutic monoclonal antibody targets these regulatory T cells. Essentially is this concept as you said of taking off the brake .

Now if you want to press on the gas pedal, you want to find a target that is essentially that actually increases the function of a cell you want to make work better…….

…. these ideas of the different checkpoint inhibitors, essentially we should really call them, checkpoint modulation, because the checkpoints can either be gas pedals or they can be brakes.

And ultimately, it’s a question about how do you combine them in a rational way so that way you’re not either pushing the car too hard or taking the brake off at a time when the car is rolling in the wrong direction.

So essentially, you need to do checkpoint modulation in a setting where you still have the steering wheel on your car to ensure it’s directed against the right cells, otherwise you’re going to get significant toxicity.”

Which is a good introduction to Day 5 of our Road to AACR 2016 mini-series.

Over the course of 12 days in the run up to the 2016 annual meeting of the American Association for Cancer Research (AACR), we’re taking a look at some of the areas we expect to hear more about in New Orleans.

In today’s post, which continues our look at some of novel cancer immunotherapy targets, we’re look at the modulation of GITR (glucocorticoid-induced tumor necrosis factor receptor related gene) and companies that are targeting this.

GITR was named as the 12th most promising cancer immunotherapy target by the National Cancer Institute (NCI) back in 2006.  Interestingly, high GITR expression can be found on both T cells and NK cells.

There are now several agonist antibodies in development and entering the clinic that seek to activate GITR, and new data is expected at AACR 2016.

What GITR pathway data is worth looking out for at AACR 2016?

If you want to know more about why GITR matters, and where it fits into the cancer immunotherapy landscape then do read more. 

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San Francisco JPM16 Day 2It’s Tuesday at the 2016 JP Morgan Healthcare conference in San Francisco (Twitter #JPM16).

Each day of #JPM16 we’re doing a rolling blog post which we’re updating throughout the day with commentary and insights on the company presentations we’re covering.

While we’re not giving a blow-by-blow account, many companies have the slides readily available, we will be commenting on noteworthy news, and what we learn about corporate strategy going into 2016.

For those of you who like to catch up with the final summary of each day’s highlights, you can read yesterday’s Day 1 synopsis here and our interview with Seattle Genetics CEO, Clay Siegall here.

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