Biotech Strategy Blog

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

Posts tagged ‘OX40’

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?

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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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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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UNO SignIn our post AACR analysis, I noticed some consistent observations across multiple talks and informal discussions with thought leaders.

Some of these ideas are pretty important and help us see the big picture for the near and medium term future in the cancer immunotherapy space.

The “Claws” sign we saw at the University of New Orleans sums things up!

Without much ado, it seems a good point to capture and summarise these ideas so that readers can compare notes and debate their thoughts too.

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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.

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Dr Mario Sznol

Dr Mario Sznol at SITC 2015 Patient Forum

Novel Immunotherapies and Combinations” was the title of the talk by Dr Mario Sznol (Yale) at the recent Immunotherapy Patient Forum co-hosted by Global Resource for Advancing Cancer Organization (GRACE) and the Melanoma Research Alliance at the 2015 SITC annual meeting.

At the forum, Dr Sznol also led a breakout session, where he reviewed what is melanoma, the treatment of primary melanoma and management of advanced disease, as well as answering questions from the patients and patient advocates.

Often at medical meetings you hear the results of a clinical trial that is but one piece of the jigsaw, so it was interesting to hear a more comprehensive overview of the disease.

Dr Sznol kindly spoke with BSB about his vision for the future of cancer immunotherapies. This post includes excerpts from the interview along with additional commentary.

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There can be no doubt that immuno-oncology is a hot topic in cancer research of late with checkpoint inhibitors, immune agonists, immunocytokines, CAR T cells, TILs, TCRs, not forgetting innate immunotherapies.  We’ve written extensively about many of these topics, but what about the companies behind them and their strategies?

One thing subscribers tell us they love reading about here on BSB is not only fireside chats with thought leaders, but also interviews behind the scenes with company personnel, be scientists, clinicians or CSOs.

Recently, we’ve posted some interviews with Roche and Genentech scientists/physicians about their IO platform that were well received. Today, it’s the turn of AstraZeneca and MedImmune, who are also developing checkpoint inhibitors and immune agonists against various cancers.

With the anti-PD1 antibodies i.e. Merck’s pembrlizumab (Keytruda) and BMS’s nivolumab (Opdivo) already approved by the FDA, and Roche/Genentech’s atezolizmuab well on the way to filing in advanced urothelial bladder cancer with the announcement this week that the IMvigor 210 trial in relapsed/refractory disease met its primary endpoint, the big question now remains is what’s happening with the fourth element of the quartet? How well is progress coming along there and what is the main focus we can expect in the near future?

Cambridge PuntingLike most Brits, when AstraZeneca noted back in 2013 that they expect to establish their global R&D hub in Cambridge, I assumed they meant in the Golden Triangle and not Massachusetts. This is a burgeoning area for European biotech research, which is somewhat ironic after the KuDos scientists working on olaparib (Lynparza) moved to Alderley Park in Cheshire with the acquisition and will likely face moving back again!

At ASCO, we had the pleasure of a chat with Dr Rob Iannone, the head of the AstraZeneca Immuno-oncology development program.  The company also published a number of interesting abstracts and posters that were on show in Chicago, as well as a burgeoning pipeline in this area beyond their lead compounds, the anti-PDL1 inhibitor, durvalumab (MEDI4736) and tremelimumab (anti-CTLA4).

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There has been a lot of enthusiasm in the immuno-oncology space since ASCO about the possibility of combining a checkpoint inhibitor with an immune stimulator.  There are several ideas behind this approach since:

a) Not all patients respond to checkpoint inhibitors
b) Some patients only partially respond, although they can achieve an attenuated response before relapsing

An important question in many people’s mind is what is different about these subsets of patients compared to exceptional responders? How can we change that situation for the better?

Two approaches that have been mooted of late include the following:

  • Using a cancer vaccine to ‘prime’ the tumour
  • Combining a checkpoint inhibitor with an antibody agonist to stimulate the immune system

CrowdAt SITC in Maryland this weekend, there were plenty of packed presentations and discussions on both of these classes of agents, so this is a good time to explore the idea of immune stimulators further based on the latest data we heard.

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TWashington DC in Fallhis week sees the start of the 2014 annual meeting of the Society for Immunotherapy of Cancer (SITC) at National Harbor, MD.

Given the rapid progress that is taking place in the field of cancer immunotherapy, we’re excited to be flying up to DC to attend the meeting for the first time as part of our conference coverage.

SITC 2014 ProgramMany of the leading translational scientists in immuno-oncology will be at SITC to discuss the current landscape, challenges and opportunities.

For all the promising results we’ve seen so far, harnessing the body’s immune system to fight cancer is very much a work a progress.

Don’t expect much from SITC on social media, most of the data is likely to be unpublished, which is why you have to go to meetings like SITC, ARVO and AACR in person. An important part of attending is the in-person conversations and connections that take place.

SITC 2014 Conference AppYou can download the preliminary program on the SITC 2014 Annual meeting website. There’s also an iphone/android app for those attending.

 

 

Conference Highlights: 

  • Addresses by the 2014 Richard V. Smalley, MD Memorial Award recipient, Giorgio Trinchieri, MD – National Cancer Institute and the Annual Meeting keynote speaker, Olivera J. Finn, PhD – University of Pittsburgh
  • News on important initiatives and updates in cancer immunotherapy by key stakeholders in the field
  • Workshop on Combination Immunotherapy: Where Do We Go From Here?
  • Primer on Tumor Immunology and Cancer Immunotherapy™
  • Hot Topic Symposia on Managing Engineered T-Cell Toxicities & Accelerating Tumor Immunity with Agonist Antibodies.

If you haven’t already seen it, this educational video from Roche/Genentech, narrated by Dan Chen MD PhD (Cancer Immunotherapy Franchise Head) is not only educational in discussing the mechanism of action of their anti-PDL1 monoclonal antibody, MPDL3280A, but is highly fun and entertaining to watch. Enjoy!

Sally interviewed Dr Chen at ASCO this year for a blog post from the meeting on “Making a difference in advanced bladder cancer.”

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“Nothing lasts forever, because nothing ever has.”

James Shelley, The Caesura Letters

This year’s annual AACR meeting was so good, we could probably write another 50 posts and still not be done! With ASCO fast approaching, however, it’s almost time to draw it to a close and the final post conference note will be published on Monday.

Today is the penultimate report and focuses on the key highlights that caught my attention in immuno-oncology, which covers the gamut from checkpoint inhibitors, co-stimulants, innate immunotherapy and CAR T cell therapy to bispecific antibody TCRs.

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