Biotech Strategy Blog

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

Posts tagged ‘Incyte’

Potential of Immunometabolism to Enhance CAR T cell therapy

One only has to look at the number of clinical trials to recognize that cell therapies are one of fastest growing areas in terms of cancer new product development.

Over the past several years we’ve seen many changes and improvements in continuous innovation regarding the development of CAR T cells.

What metabolic “treats” do T cells like?

There has been no shortage of novel ways to enhance their targeting, durability, efficacy, or ease of administration. Most of the early strategies have yet to translate into commercial products, but it remains an area an attractive area to investors hoping to repeat the returns seen with Juno and Kite as more competitors enter the field.

In the fifth post in our mini-series on novel approaches in the emerging immunometabolism niche, we’re looking at ways to metabolically reprogram CAR T cells, as well as what the future may hold for the next generation of CAR T cells in this context.

Like a postcard from one’s summer holiday, it’s an opportunity to offer a snapshot at a moment in time from our journey.

We were fortunate to have the opportunity to talk with a researcher who is actively at the forefront of this area. Dr Roddy O’Connor is working with Carl June along with various colleagues at the University of Pennsylvania, and he kindly spoke to BSB about his work.

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Lining up new developments in the treatment of GVHD

January is inevitably a month where several worlds collide for us.

There might be initial data from SITC and solid data from ASH that bears the advantage of showcasing in the context of corporate presentations at JPM or company announcements of competitor trial progress.

That’s very much the case today.

Earlier this month, Incyte announced the phase 3 trial miss for their JAK1 inhibitor in acute graft versus host disease (GVHD), perhaps coming as a surprise to a few observers familiar with the positive ruxolitinib result, but not so much to clinicians.

In the latter case, one transplanter in the itacitinib study told me at ASCO that he hadn’t noticed any difference between the steroid only and steroid plus itacitinib arms in his SCT patients. Although admittedly that was a small sample of the whole, it did make me wonder if the trend was repeated then it wouldn’t augur well for the overall readout expected year end. Come January, his observation turned out to be rather prescient.

Incyte are presenting on the JPM20 slate in San Francisco today and we’ll be keen to learn if they have anything to add beyond the terse Jan 2nd announcement on the itacitinib miss.

More importantly though, there are still plenty of other agents in development are being investigated for the treatment of acute GVHD, one of which from Alpine Immune Sciences in Seattle we are particularly enthused about following discussions at the recent ASH meeting last month.

In our latest expert interview, we learn more about that development and explore the context for the evolution of a novel molecule likely not on many people’s radar. If the results turn out to be encouraging that situation could well change in the future.

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JPM19 Highlights from Day 2

San Francisco

While much of the focus has been on the mergers and acquisitions at this year’s JP Morgan Healthcare conference, seeing what a few companies have up their sleeves is also intriguing.

In today’s round up we address reader Q&A as well as highlight some presentations and announcements of interest in the cancer research space.

2019 is going to turn out to be a rather critical year for some companies…

If you missed the first day’s highlights and lowlights – check them out here!

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ASCO 2017 Preview 2 – IDO1 Inhibitors

IDO/TDO inhibition is a topic we’ve been following the progress on for several years now with various updates along the way. It’s also one of our most requested Previews for this year’s ASCO meeting taking place next month.

The Bean, Chicago

In Chicago next month, initial data from several trials is due to be presented.

  • What can we expect?
  • How are the main players in this landscape doing?
  • Will this combination be the next big thing in the oncology IO space?

In our latest #ASCO17 Preview, we take a hard look at IDO/TDO inhibitors.

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ASH16 Preview on Acute Myeloid Leukemia AML

Post 2016 US Election, we move on and get back to business with an in-depth review of some new science and clinical data.

ash-2015Yes, it’s time for another Bushidō – “Way of the Warrior” – guide to the key ASH abstracts!

Here we focus on acute myeloid leukemia (AML), a difficult and challenging disease to treat with a high unmet medical need for new effective therapies.

In this Preview we look at key companies in the AML space, as well as a look at what’s happening in classic targets and also some new ones that are receiving notable attention, both preclinically and also in the clinic.

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The BET Bromodomain Landscape in Cancer Research

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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Gems from the Poster Hall at AACR16 – Part 1

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

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OX40 immune agonists at AACR 2016

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:

…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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AACR 2016 GITR Cancer Immunotherapy

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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Did the epacadostat combo data disappoint at SITC?

SITC Day 3 Highlights

There were a couple of late breakers presented in the oral session yesterday that are worth discussing for several reasons, not least the controversy surrounding the stock action afterwards.

Dr Tara Gangadhar (U Penn) presented epacadostat, Incyte’s IDO1 inhibitor, in combination with pembrolizumab, Merck’s anti-PD1 inhibitor in a phase 1/2 trial with selected solid tumours.

Will combining these agents lead to better responses and outcomes than with pembrolizumab alone?

Dr Naiyer Rizvi (Moffitt) presented the combination data of AstraZeneca’s anti-PDL1 (durvalumab) plus anti-CTLA4 (tremelimumab) in patients with non-small cell lung cancer (NSCLC).

Neither of these agents have yet been approved in any indication, so the only relative comparators we have here are nivolumab and pembrolizumab as single agents in NSCLC and ipilimumab plus nivolumab in metastatic melanoma. There are no data approved for the BMS combo in lung cancer.

This review looks at both trials, in terms of the controversial data presented, and also in a broader context of the ever-changing landscape.

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