Biotech Strategy Blog

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

Posts tagged ‘neoantigens’

La Tour Eiffel par nuit

Paris, France:  It’s the dog days of summer and my reading stack of interesting science and cancer research papers is particularly high at the moment despite reading voraciously over the last few weeks…

So much excellent research keeps on piling up as fast as one can get through it.

It’s beginning to feel like Ravel’s Bolero…

Still, there’s one particular batch of important papers that draws together some interesting findings in an area we have been following for a little while now and these data most certainly advance the field in more ways than one.

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Gritstone Oncology hit the ground running with a $102M Series A financing round back in October 2015. Any company that raises that amount of initial funding is on the radar as a company to watch, especially one in the cancer immunotherapy space.

Since the AACR meeting in DC, Gritstone have also hired Genentech’s Dr Raphael Rousseau as CMO (Link) and appear to be an exciting young company going places.

As attention on neoantigens increases, what is Gritstone’s strategy and where could they fit into the cancer immunotherapy landcaspe?

At AACR17 in DC last month, Dr Andrew Allen, President and CEO of Gritstone Oncology kindly spoke to BSB about his vision for the company.

This post is part of expert interview series (Link) and also forms part of our ongoing series on neonatigen based immuno-oncology.

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In the first of our 2017 AACR annual meeting previews, we are taking a look at a particular theme that we expect to hear much more about over the coming months.

Washington DC cherry blossoms

In order to make something better than what it is, we first need to step back and understand the various factors that underpin it. To do otherwise is akin to the proverbial throwing of mud at the wall and hoping something sticks.

Trying things out just because they seem like a good idea or that’s all you have in your pipeline doesn’t really inspire the greatest of confidence in a clinical trial’s success.

This is also where several factors including tumour biology, cancer genomics, biomarkers, and acquired resistance can intersect to produce some intriguing results.

Please note that our Conference Preview series are never random.  When looking at the abstracts as a whole, we try to organise them around a particular scientific theme or a tumour type. The idea here is that it makes it much easier for our readers to see and grasp emerging concepts and trends. It’s also a deeper dive into the whys; things happen for a reason – why is that?  What can we learn from the process?

These are also not random selections from say, publicly traded or private companies, big or small caps.

It does take more time to roll thematic articles out, but the advantage is that over the course of the next two weeks readers will be better equipped to get a grip on the meeting ahead of the event.

Indeed, a couple of subscribers even told us last year they learned more from our in-depth previews than they did from the meeting itself because it’s easy to miss the important things or become ‘bigly overwhelmed’ as one bio fund manager explained to me.

Strategically, we’ve taken one specific theme today and explored what we can expect based on what we have learned to date, and looked at how that will potentially impact a few things going forward.

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View of Cambridge and Charles River

Neon Therapeutics is based in Cambridge, MA

One of the much anticipated cancer immunotherapy presentations at the 2017 JP Morgan Healthcare conference was by Neon Therapeutics CEO Hugh O’Dowd.

As readers know we’re riding the Immuno-Oncology wave on Biotech Strategy Blog, and one of the exciting new topics to emerge is whether we can target neoantigens to create personalized immunotherapy.

Our mini-series last year on neonatigens received a lot of attention. It included a primer and three interviews. We were very much of the opinion that Neon Therapeutics is a company to watch out for.

In case you missed them, here are the links:

I highly recommending reading these articles as background on the science and new product development as a prelude to the latest commercialisation update we will cover in today’s post.

What did we learn from the 2017 JP Morgan presentation of the Neon Therapeutics corporate strategy?

If you didn’t make it to the presentation at JPM17 in San Francisco (it wasn’t webcast), you may be interested in this post. This is the latest update in our on-going series on neoantigens and why they matter in cancer immunotherapy.

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As we continue our journey exploring neoantigens in the context of novel cancer research in Part 3 of our latest mini-series, today we focus on the commercialisation side of the business through an interview with a leading investor, Dr Cary Pfeffer, who is a partner in Third Rock Ventures, as well as being ad interim CEO of Neon Therapeutics.  We’ve written about other Third Rock companies in the past; Agios, Foundation Medicine and bluebird bio come to mind, for example.

neonlogoHow does an exciting early product in development move from academia to industry? There are many ways to do this, so here is the story through the eyes of one young company with strong academic connections, as a way to illustrate what can be done. It isn’t the only way, by any means.

To be sure, there are other competitor companies in the neoantigen space – Gritstone and Moderna come to mind as examples – we will cover companies in the broader landscape in a future post. There is also an incredible amount of promising research going on in academia right now, which may lead to more companies or products being licensed and developed.

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Westminster Hall Stained GlassThis week we’re focusing on neoantigens, what role they have to play in cancer immunotherapy and novel approaches that identify and use them as a therapeutic modality.

When you look at the cancer immunotherapy landscape it’s like looking at a stained glass window – it’s not only about the light but seeing the patterns and way the glass is aesthetically arranged in order to make it effective.

Today’s post, the second in a mini-series of three, features an interview with a thought leader doing pioneering work at the forefront of how neoantigen based vaccines can be used to target solid tumors.

The field of vaccine based cancer immunotherapy research is attracting renewed interest from VCs, angel investors and academics because of it’s potential to be used in combination with other immunotherapies.

If you’d like to learn why, then you can purchase access below. Subscribers can login to read more.

Great Fire MonumentThe Great Fire of London started 350 years ago in September 1666 following a fire in a Pudding Lane bakery.  It highlights the potential of what a small fire can do once it takes hold – over the course of 3 days, 13,000 houses and 436 acres were destroyed.  It forever changed the landscape of medieval London.

The Monument (pictured right) to commemorate the Great Fire was designed by Sir Christopher Wren. Constructed from 1671 – 1677, it is 202 feet in height, the distance to the bakery where the fire started. You can even walk up it, if you are in the area.

When we think about cancer immunotherapy, one of the emerging important trends is the need to “inflame” or set fire to the immune system, especially in those cancer patients who don’t have a pre-existing immune response.

We want to ignite the immune system, in the hope that it will create the equivalent of the Great Fire…

Great Fire of London Plaque

In this post we’re starting at mini-series looking at neoantigens, beginning with a primer on what they are and why they matter in cancer immunotherapy.  In subsequent posts we’ll look at some of the innovative ways companies are identifying and targeting them.

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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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We have selected five key strategic trends that are emerging that will be critical to follow, understand, and even implement if you are on the coal-face of clinical research and new product development.

ASCO16 Chicago 5We aren’t talking about financial things such as cost toxicity, or even how doctors should be paid, but meaty scientific aspects that we need to watch out for. If we are going to improve on cancer research and R&D in the future, these issues will be important.

For companies and academic researchers alike, there is much to learn from the tsunami of data that hit this week if you have a keen interest in the field and a bent for making sense of patterns out of an amorphous mass of data.

Not paying attention to evolution in clinical development can mean the difference between being in the winners circle, on the outside looking in, or falling way behind your competitors. Playing catch up is never anyone’s idea of fun in this market – oncology moves at a lightning fast pace compared to many other therapy areas.

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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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