Biotech Strategy Blog

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

Dawlish TrainspottingIt’s Day 7 of our 12 day Countdown to AACR 2016 in New Orleans.  After exploring GITR and OX40, we’re now looking at another stimulatory target for cancer immunotherapy: CD40.

We’ve been writing about CD40 as a cancer immunotherapy target for some time. See posts: “CD40 as a Cancer Immunotherapy Target” and “Targeting CD40 in Cancer Immunotherapy.

Anti-CD40 antibodies are agonists that act on stimulatory signalling receptors on T cells and antigen presenting cells (APCs). Targeting CD40 effectively acts to “put the foot on the gas” and may help generate a better immune response. This could be important in cancers that have fewer natural T cells present.

CD40 is an attractive target because it’s expressed in more than 50% of carcinomas and melanomas and almost all hematological B cell malignancies.  Of particular interest is the potential to combine a CD40 agonist with a PD-1/PD-L1 checkpoint inhibitor.

Multiple companies have CD40 agonists in clinical development including Roche, Apexigen, Alligator Biosciences and Seattle Genetics.  There are others coming too.

In this preview of AACR 2016, we’re looking at the CD40 landscape. New products and companies have entered the scene, so we’re highlighting them and some of the CD40 presentations to look out for at AACR 2016 (and why they matter).

Subscribers can login to read more or you can purchase access below by clicking on the blue box.

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.

Subscribers can login to read today’s Road to AACR 2016 post or you can purchase access below in the blue box.

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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St Charles Streetcar New OrleansIt’s Day 4 of our Road to AACR 2016 mini-series

In the run up to the start of the annual meeting of the American Association for Cancer Research (AACR) that takes place in New Orleans from April 16 -20, we’re highlighting some of the hot topics and interesting targets with data to be presented at the meeting (Twitter #AACR16).

We’ll be providing conference coverage from AACR both during and after the meeting. The program this year offers a veritable smorgasbord of choices, particularly in cancer immunotherapy. It’s going to be hard to cover every session we want to attend!

AACR will be webcasting many presentations, however, much of the work presented and discussed at AACR is unpublished and/or still a work in progress, so do check if a talk you are interested in will be webcast or not. The online meeting calendar indicates whether permission has been given and if all the slides will be included. If you really want to hear something do get to meeting rooms early; we expect the cancer immunotherapy sessions will be especially popular!

In today’s post we’re looking at what’s new at AACR 2016 for cancer immunotherapies that target IDO1 and TDO and their downstream effectors.

Tumor cells and myeloid cells in the microenvironment express high levels of indoleamine-2,3-dioxygenase 1 (IDO1). IDO1 is a rate-limiting enzyme in the degradation of the amino acid tryptophan (TRP). Depletion of tryptophan inhibits T cell responses.

Another route by which the tryptophan metabolic pathway can lead to immunosuppression is via the enzyme TRP-2,3-dioxygenase 2 (TDO), which may be an additional target for cancer immunotherapy. Some IDO1 inhibitors also inhibit TDO, others don’t, which makes for an interesting question as to whether you need a dual-targeted approach or not?

In this post we’re looking at:

  • Some of the companies who have IDO1/TDO inhibitors in development – there is a surprising amount of activity!
  • What is the right combination partner?
  • Who is most likely to benefit from IDO1/TDO cancer immunotherapy?

Data at AACR 2016 may help us answer some of the above questions, and we’ve showcased a few of the relevant sessions and presentations for your AACR “dance card” if this is an area of interest.

Subscribers can login to read more or you can purchase access below. This post is Day 4 of our Road to AACR 2016 mini-series.

Lemons Villa BorgheseThe discovery of a novel target in castration-resistant prostate cancer (CRPC) and the potential of drugs targeting this to delay or overcome adaptive resistance is the subject of today’s post.

Followers of the prostate cancer field know that one of the challenges with drugs such as enzalutamide and abiraterone is that patients stop responding to them over time and they develop acquired resistance.

So imagine that you could give a drug that is not only an effective anti-cancer agent in patients with acquired resistance, but might then allow those treatments to be effective a second time around.  A recently identified druggable target means this is now a possibility.

Of course, it’s early days yet, and the preclinical work has yet to translate into humans, but it’s not hard to see the commercial implications in the prostate cancer landscape for companies such as $MDVN, $JNJ, $TKAI, Bayer and anybody else who wants to be a player.

Interested? Subscribers can login to read more or you can purchase access below. This post is Day 3 in our Road to AACR 2016 series.

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.

Subscribers can read Day 2 of our “Road to AACR 2016” coverage by logging in, or you can purchase access below.

Washington DC Cherry Blossoms

Spring cherry blossoms

It’s twelve working days until the start of the annual meeting of the American Association for Cancer Research (AACR) in New Orleans. This is a meeting we’re especially looking forward to this year, not only for the cool science on offer, but also the Louisiana Coastal Cuisine!

Next year, AACR 2017 returns to Washington DC, at what hopefully will be a perfect time for cherry blossoms along the Tidal Basin.

In this post, I’ve taken a closer look at one cancer immunotherapy approach with new data at AACR – bispecific T cell engagers.  Amgen’s blinatumomab (Blincyto) is interesting because it was the first T cell engager antibody to be approved by the FDA for the treatment of Philadelphia-negative ALL and refractory B-cell precursor ALL, thereby offering proof of concept that such an approach could be safe and effective. There are, however, some challenges associated with it (which you’ll read about).

Can we improve on blinatumomab?

This post will address the question in three parts:

  • A look at what we know about blinatumomab to date
  • Where the competitive landscape is evolving with potential solutions
  • An interview with a scientist actively working in this field for their perspective.

For those attending AACR, I’ve put in links to some of the sessions and presentations to watch out for if you have an interest in bispecifics (there are a surprising number of them in R&D) – we’ll be writing more about some of the noteworthy data after it has been presented.

Subscribers can login below or you can purchase access below to Day 1 of our Road to AACR mini series…..

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 below.

Lindt Gold BunnyWhat questions are BSB readers sending in to us this month?

I wanted to take a moment out of AACR Previews and catch up on some recent news that is intriguing or perplexing subscribers. All questions are anonymous and in many cases, the same questions were actually sent in by multiple people, a testament to what’s top of mind in oncology lately.

Today, we cover a Q&A on a variety of topics on Kite Pharma (the Genentech collaboration and their TCR in solid tumours), a discussion about EGVRvIII in glioblastoma, and Gilead’s woes with idelalisib and an IO pipeline.

So let’s get started – subscribers can sign-in or you can sign up via the blue box below:

New Orleans Jazz

New Orleans Jazz

Most of the abstracts for the 2016 annual meeting of the American Association for Cancer Research (Twitter #AACR16) in New Orleans are now available online, which raises the intriguing question:

What are the top 10 abstracts at AACR 2016? 

If you’re a subscriber, take a moment to think which ones would be on your list, BEFORE you read this post.

Rather than give chapter and verse on a long raft of abstracts, in this second preview post I’ve chosen to focus on a few interesting, intriguing or important issues. Clearly, everyone will have their own way of defining a top 10 list, never mind choosing them! I do hope this starts a debate in your group, it’s always cool discussing science, after all.  Which ones would you choose and why?

What I wanted to do was highlight some of the critical scientific or clinical questions that I have written down in my little black book over the last year or so for which we need solid answers in order to move our understanding of the cancer research along. That list is very long and always seems to be getting longer!  The good news is that we may have answers to some of them at AACR next month. 

Here goes, in no particular order…

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