Biotech Strategy Blog

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

Posts tagged ‘OX40’

We’ve come a long way over the last two years in the oncology market, with several novel approaches approved, numerous major phase 3 trials evolving and a huge turnaround for many companies in terms of early pipeline activity.

ASCO 2016 Posters 3

The melée at the ASCO 2016 Poster Hall

Unfortunately, this also means that the tendency of lemming activity also increases in the rush to copy everyone else and not be left behind.  Just a couple of years ago, some industry friends grumbled that there were over 20 checkpoint inhibitors chasing them in development; they may be surprised to know that now there are nearly 70!  This is both unprecedented and unsustainable, and yet it’s also a function of the perceived success these agents have had on the cancer R&D landscape to date.  Everyone wants one for fear of being left behind… except that many are indeed way behind already.

You can imagine the tall guy on the left of the picture looking at his watch and wondering, “Ah so many new posters, so little time!”

Meanwhile, as the rate of approved cancer therapies increases, so does the inexorable march in terms of hyper-aggressive basket pricing.  I would argue that at some point, it no longer acceptable or even conscionable to change a premium or even market rate for drugs that give an incremental improvement of a mere 2 months of extra life.

Equally, one thing that many industry observers and the media love to do, and wrongly in my view, is to compare the individual drug prices on an annualized basis.  This is silly for several reasons:

  1. So far, not all patients are treated for a full year
  2. If patients are treated until progression and that happens early, then therapy is stopped
  3. What people should be looking at is the average treatment cost based on the length of therapy – some people will receive a few months and some much more than that
  4. What’s the true cost of a cure or remission to a patient and their family?
  5. How do we quantify the impact of the long lasting durable remissions?

These questions will become increasingly important as we see a more aggregated therapy approach emerge over the next few years.

By this, I mean that we are now going beyond monotherapy and even combinations; those trials have already long started and are the low hanging fruit that has been rapidly snapped up by the early players, as we eagerly wait for their data readouts.

If you have new agents coming-out of preclinical and into phase 1 development over the next year, there are a number of important questions to consider:

  • What are you going to do and where do you start?
  • How do you gain an edge when coming from (way) behind?
  • How do you develop unique positioning that could sustain your molecule in a sea of similar competitors?
  • Is it realistic to expect the 17th and 50th checkpoint to have equivalent efficacy as what went on before and will all of these seriously make it to market?

You can see now why even the FDA’s Dr Richard Pazdur was moved to grumble about the surfeit of me-toos here and company expectations that the FDA should consider them – it’s on a massive scale that we haven’t seen before.  For once I agree and empathize with him over that dilemma, it’s madness to think they will all be as good as pembrolizumab or nivolumab.

What we are starting to see emerge now is a surprising synthesis of ideas and a merging of disparate approaches. How will this affect oncology R&D over the next 1–5 years?

A couple of smart readers wrote in asking about these emerging trends, what have we identified so far, and where do we see the oncology space going in the near to medium term future. Now that AACR and ASCO are behind us, what can we learn about the new developments and where they all fit in the oncology landscape strategically?

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Lung cancer, along with metastatic melanoma, has been very much to the forefront of attention in cancer immunotherapies with both nivolumab (Opdivo) and pembrolizumab (Keytruda) garnering approval as monotherapy from the FDA in second line treatment of NSCLC. A third molecule, atezolizumab (Tecentriq) has also been submitted to the authorities for this indication and a decision is expected soon.

Morgan Grafitti Wall

Street art in the Chicago West Loop

While no one is in any doubt that the response rates with monotherapy are low (in the 20% range) and the majority of people do not respond, the important thing so far is that when they do, they appear to be very durable responses. People are living longer, much longer than the 2–3 months of incremental improvement we are used to seeing with chemotherapy or targeted therapies.

The race is now on to see how we can improve things for the 80% of people with lung cancer who don’t respond to single agent therapy:

  • What can we do to help them?
  • Which combinations look more encouraging?
  • Should we treat beyond progression?

To answer these questions, we interviewed Dr Stephen Liu and discussed his views on some of the cancer immunotherapy combination studies presented at ASCO last week.

Dr Stephen Liu

Dr Stephen Liu at ASCO 2016

Dr Liu is a lung cancer expert at the Lombardi Cancer Centre at Georgetown University, and is actively involved in numerous clinical trials, particularly in Developmental Therapeutics.

Georgetown’s founding principle is Cura Personalis, which translates as care of the whole person. It “suggests individualized attention to the needs of others, distinct respect for unique circumstances and concerns, and an appropriate appreciation for singular gifts and insights.”

Dr Liu embodies this ideal, advocating for his patients for access to the best research advances, including genomics and clinical trials of promising agents.  At ASCO, he kindly highlighted some of the important findings from Chicago and offered context on why they matter to the field.

He told us one combination was “potentially transformative” and could be “practice changing” in lung cancer with more data.

Intrigued? To find out what these important trials are and which ones to watch out for, subscribers can log-in to read the article or you can sign-up by clicking on the Blue Box below.

Chicago ArchitectureChicago – the ASCO 2016 annual meeting is in full swing. This is the third and last day of our rolling blog where we’re providing updates with top-line commentary throughout the data.

If interested, you can also check out the many updates from Day 1 and Day 2.

There’s a lot happening at ASCO today, including a presentation by Vice President Joe Biden later this morning. Allow extra time for security checks if you plan to listen to him in person, and I expect there’ll be delays to the hotel shuttle buses around Chicago as roads are closed to accommodate the VP’s motorcade.

Many people chose not to come to ASCO this year – but it’s turned out to be a great meeting. We’ve heard a lot of new data which are likely to have an impact on future clinical trial strategy, as companies look to bring new products to market in what is a competitive field, particularly in cancer immunotherapy. There are how many PD-1 checkpoints in development now?

A word of warning to the wise – not all these IO molecules are going to win – some are going to fail, some will be useful tools in various subsets and some are going to be new home runs.

If you’d like to read our coverage of Monday at ASCO 2016, you can login if already a subscriber, or you can purchase access below by clicking on the Blue Box below.

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.



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 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

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.

If you’re not already a subscriber, you can purchase access to AACR posts and also our immuno-oncology coverage by clicking on the blue icon below.

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 below.
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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