Biotech Strategy Blog

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

Posts tagged ‘T cell engagers’

Continuing our up and coming biotech series, we now switch our focus from small molecules to immuno-oncology.

While big Pharma has garnered the lion’s share of attention (and revenues) from checkpoint inhibitors and CAR-T cell therapies, if we want to make a serious impact on solid tumours, especially the colder ones, then we are going to need to devise ways of jumpstarting the immune system where there are far fewer immune cells around to help do this.

There are many ways to achieve this aim, although the count is still out on how best to optimise combinations.

We’ve looked at various approaches over the last couple of years including chemotherapy, immune agonists, cytokines, STING/PARP/TLRs, NK cell checkpoints, T and NK cell bispecifics, and many many more.

Fortunately, most small biotechs have been focused on alternative targets that mght be seen as complementary to existing established therapeutics.

As we move forward towards a more regimen-based approach some of these will succeed while many will not, such are the challenges of oncology R&D where 90% of compounds unfortunately fail.

One challenge that has long been obvious though is that once clinical proof of concept has been established, another 10 companies will wade in quickly and dust down old molecules lurking in screening libraries that have been languishing in darkness waiting for their call-up. In the old days, a lead time of 5+ years before a competitor caught up with a rival drug was not uncommon.

Increasingly, it now seems there are mere months rather than years between approvals in the same class, an astonishing feat in a highly competitive and cut-throat business driven by generic erosion, noticeable pipeline gaps and the urgent need for continued topline sales growth.

In today’s hot seat, we have a small biotech CEO discussing his company’s IO pipeline and progress…. they caught my attention at AACR last year and I’m delighted to have the opportunity to learn more about what they are doing and how they are different from the existing competition.

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Cancer cells Source: Dr. Cecil Fox, NCI

As part of our ongoing mini-series on small emerging companies to watch out for, we have two quite different biotechs focusing on different aspects of immunotherapy on deck today.

We look at what we know, what we recently learned and where things are likely headed in the near to medium term future.

As always, there’s good and bad news along the way, so what are the pitfalls and what’s to be cheerful or encouraged about?

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Sometimes research topics that we’ve researched and covered for several years, including interviews with thought leaders, suddenly become ‘hot’ or are seen as the latest shiny silver lures by sceptics when a new bandwagon starts rolling. They don’t always end well, but some do and take off and become embedded in new standards.

Checkpoint blockade and CAR T cell therapies are two such approaches, which we wrote about in 2010 and 2012, respectively.

When I included what was then known as MDX–1106 and MK–3475 in an ASCO 2010 or 2011 preview video, folks scoffed at highlighting phase 1 data in advanced solid tumours with obscure compounds – “too early to tell” apparently. They subsequently went on to become nivolumab (Opdivo) and pembrolizumab (Keytruda) and are indisputely multi-billion blockbusters. Now it’s hard to imagine a discussion about cancer immunotherapies without them mentioned as a bedrock therapy to build on.

I mention this story because it’s easy to follow the herd and dismiss early promising developments as ‘too early’ – fortune favours the brave, even if it means that many approaches need to be tested and evaluated along the way before finding the best solution.

Pathway to success

There is no doubt that the path to success in oncology R&D is paved with many challenges and hurdles – it is rarely a straight road.  Some drug classes will inevitably fail and fall by the wayside, others will need tweaking, incorporated into more optimal trial designs or even evaluated with other combination partners. And let’s not forget those twin issues of dosing and scheduling, which are no slouches when it comes to providing tricky or even exasperating hurdles for hitting an optimal therapeutic window, as many early phase PIs will no doubt be all too familiar with.

We currently live in a very T cell centric world despite the fact that they aren’t the most numerous of the various killing machines available to the immune system. They do happen to be extremely potent and highly effective fire power though, much as a machine gun is over, say, a combat knife or Samurai’s sword. That doesn’t mean that knives or other approaches aren’t effective, far from it, they’re just different and can even be more useful in appropriate situations.

Our heads were first turned by the potential for NK cell engagers a couple of years ago at ASH and we’ve keenly followed their progress since then, documenting the challenges and successes as we went.

With the Affimed-Genentech collaboration announced last night, it’s time to consider where we are with this approach and what this all means…

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Here we are with Part 2 of our latest mini-series on novel ways to jumpstart the immune system so that subsequent therapy can be more effective, leading to improved outcomes.

In Part 1, we looked at the preclinical and scientific evidence regarding a novel approach to modulate a cold or non-inflamed tumour type, thereby turning the phenotype into a hotter or inflamed one.

In principle, this concept sounds quite simple in theory, but in practice it’s actually much more technically challenging to do than many realise, especially when we consider not just the design of the antibody itself and perhaps even efficacy, but also the convenience of administration and tolerability, both as monotherapy and also in combination with other therapies.

What’s up on deck today is not one, but three interviews, offering readers a candid look through the keyhole at varied insights from different perspectives around a central R&D topic, namely…

What do you do when you have a new compound in clinical development and wish to explore how to integrate it – do you use it with an existing framework or try something new and different? What about other compounds that might be competing with it internally?

It’s a question every single oncology company faces when a new molecule moves out of preclinical development into phase 1 trials. What next?

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We have a two part mini-series this week exploring an approach on how to boost T cells in cold tumours. There are a number of different ways to do this, including adding them ex vivo such as via CAR T cell therapies, although this technique has yet to yield durable benefit in solid tumours.

So how else can it be done?

We’ve discussed immune agonists, oncolytic viruses and cancer vaccines in the past so now it’s time for something different…

In Part 1 of the series today, we explore the science behind the technology and some of the early clinical data that was recently presented at medical meetings.

In Part 2 tomorrow, we have not one but three, different voices exploring some researchers thoughts on where the approach might go.

It should make for interesting reading!

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ASCO 2014 Chicago Contemplation

Contemplation in Chicago ahead of #ASCO17

As part of our ongoing American Society of Clinical Research (#ASCO17) Preview series (we’re on number 5 already), we turn our attention to an upcoming area of cancer research that is expected to play an important role in future clinical trials and combination regimens because of the mechanism of action involved.

It may also turn out to be a very handy and important approach for turning cold into hot tumours.

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Washington DC Cherry Blossoms

Spring cherry blossoms

It’s twelve working days until the start of the annual meeting of the American Association for Cancer Research (AACR) in New Orleans. This is a meeting we’re especially looking forward to this year, not only for the cool science on offer, but also the Louisiana Coastal Cuisine!

Next year, AACR 2017 returns to Washington DC, at what hopefully will be a perfect time for cherry blossoms along the Tidal Basin.

In this post, I’ve taken a closer look at one cancer immunotherapy approach with new data at AACR – bispecific T cell engagers.  Amgen’s blinatumomab (Blincyto) is interesting because it was the first T cell engager antibody to be approved by the FDA for the treatment of Philadelphia-negative ALL and refractory B-cell precursor ALL, thereby offering proof of concept that such an approach could be safe and effective. There are, however, some challenges associated with it (which you’ll read about).

Can we improve on blinatumomab?

This post will address the question in three parts:

  • A look at what we know about blinatumomab to date
  • Where the competitive landscape is evolving with potential solutions
  • An interview with a scientist actively working in this field for their perspective.

For those attending AACR, I’ve put in links to some of the sessions and presentations to watch out for if you have an interest in bispecifics (there are a surprising number of them in R&D) – we’ll be writing more about some of the noteworthy data after it has been presented.

Subscribers can login below or you can purchase access to Day 1 of our Road to AACR mini series…..

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