Biotech Strategy Blog

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

Posts tagged ‘CTLA-4’

Autumn leaves in Munich

We have increasingly seen how oncologists like the efficacy associated with the immune checkpoint combination of ipilimumab plus nivolumab, but are leery of the increase in side effects, including immune related events.

Are there practical ways to reduce this phenomenon, other than dose reductions?

CytomX are one company who are focused on engineering a different concept with their monoclonal antibodies, bispecifics and ADCs to try and mask the effects, thereby reducing the treatment emergent toxicities.  Their main idea is that the therapeutic window can be widened, thereby improving the tolerability profile.

It’s a nice idea, but what happens in practice?

To find out, we took a look at the recent early clinical data and interviewed executives from the company…

To learn more from our latest assessment and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

The hurly burly in Chicago between sessions

We have written about the positive and negative effects of various inhibitory checkpoints such as PD-L1, PD-L2, ICOS, and even B7-H3, but there are also other targets within the B7 family that might be worthwhile exploring in the clinic.

Beyond the hullabaloo surrounding the phase 3 anti-PD(L)1 data in 1L NSCLC, there were actually a lot of interesting new and emerging molecules that caught our attention from small biotechs that we plan to highlight throughout the rest of this week. They all have different targets, approaches and rationales, but offer a window into the world of oncology R&D and where things might be headed in the next couple of years.

Today we take a look at one of the long forgotten checkpoint targets and explore a number of aspects that can be considered, given that several companies have preclinical or clinical molecules in early development.

Is this an IO target to watch out for – or not?  What are the challenges and opportunities to consider?

It turns out that there could be more than one way to unleash T cells on cancer… as this interview with a company scientist and researcher demonstrates.

To learn more and get a heads up on our latest thought leader interviews and oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

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?

To learn more about our strategic analysis, subscribers can log-in.

This content is restricted to subscribers

One of the (many) highlights for me at the recent annual meeting of the American Association for Cancer Research (AACR) was a “Meet the Expert” session presented by Professor George Coukos.

Prof George Coukos AACR 2016

Prof George Coukos AACR 2016

Professor Coukos is Director of Oncology at the University Hospital of Lausanne and Director of the Ludwig Institute for Cancer Research in Switzerland.

Ovarian cancer is becoming a fascinating battleground for cancer immunotherapy, with multiple challenges that must be overcome before we see improvements in outcomes, especially for women advanced disease.

The interview with Prof Coukos is a follow-on to the one we did on advanced ovarian cancer and checkpoint blockade at ECCO 2015 in Vienna with Dr Nora Disis (Link).

If you missed it, you can still listen to highlights in Episode 7 of the Novel Targets Podcast (Link).

After his AACR presentation, Prof Coukos kindly spoke with BSB and in a wide ranging discussion, highlighted some of the innovative clinical trial strategies he is working on to move the cancer immunotherapy field forward in ovarian cancer.

Subscribers can login to learn more about this important topic or you can purchase access.

This content is restricted to subscribers

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.

This content is restricted to subscribers

One of my favourite sessions at any cancer conference is the science symposia, although they go under many different guises and names. At the European Society of Medical Oncology (ESMO) they are known as Special Symposia and conceptually are very similar to Clinical Science Symposia at ASCO.

ESMO 2014Here at these sessions, top thought leaders in the space debate and lecture on key issues of the day. They’re usually packed with information and are well worth attending, even in a hectic schedule.

Interestingly, immuno-oncology has a dominant focus on the program for the first time since I’ve been attending ECCO/ESMO events over the last dozen years or so, demonstrating how quickly it is being assimilated into the scientific and clinical consciousness.  Years ago, I attended a session on autologous cell therapies (ACT) and there were maybe a handful of us in the room.  In Madrid, I doubt if there will be 12 empty seats in the theatre and it will probably be what Pharmaland calls SRO – standing room only.

So what can we learn from the announced sessions this year?

To learn more about our insights and thoughts, you can log-in to read this review.

This content is restricted to subscribers

1 Comment

Today I thought it would be a good idea to answer a question sent in by a premium subscriber.  He asked,

“What’s the deal with TIL and how does that relate to checkpoint inhibitors and PD-L1 expression?”

This is a good question and there were some interesting top-line debates about this at AACR recently, which are well worth discussing and highlighting.

To learn more insights on this intriguing topic, subscribers can log-in or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

Free Email Updates
Subscribe to new post alerts, offers, and additional content!
We respect your privacy and do not sell emails. Unsubscribe at any time.
error: Content is protected !!