Biotech Strategy Blog

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

Posts tagged ‘Novartis’

The broad and deep protein degradation landscape

It’s a good time to take stock of an early but important niche where the basic concept is the hijacking of the natural ubiquitin-proteasome (waste disposal) system for protein degradation therapeutics.

Traditional targeted therapies involve a small molecule or an antibody (in monoclonal or bispecific format) to inhibit an oncogenic target thereby shutting down the activity of the tumour, at least for a while.

Getting to the centre of things

What if we could find a way to biologically destroy oncogenic proteins instead – especially those which are hard to reach in normal circumstances such as protein-protein interactions?

The inherent potential for this concept would extend what we could do in terms of the proteome, but can it be done in people?

We have, after all, seen the selective estrogen receptor degraders (SERDs) evolve with one drug approved and several companies developing third generation versions in early stage clinical trials, so why not other targets too?

The simple truth of the matter is this elegant idea – while simple in theory – is technically quite challenging involving quite different obstacles from what we have seen with TKIs and antibodies.

Nevertheless, the difficulty has not fazed companies from trying and in looking at the broad landscape, we found 24 companies actively involved in protein degradation research in a multitude of targets and cancers. These span publicly traded biotechs, privately held companies, and of course, big Pharma.

Who are they and what can we learn from them in order to anticipate some of the issues to be addressed?

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New developments in the KRAS landscape

A look through the window at the evolving KRAS landscape

It’s time for an important update on the KRAS landscape and emerging opportunities in this niche.

I’ve mentioned this a few times, but the real kicker is going to come from rational combinations in different settings.  Those companies who figure these out will emerge a stronger player than their competitors who focus on monotherapy.

With this idea in mind it behooves us to be alert and aware of what’s going on in the broader landscape beyond selective KRAS inhibitors against certain mutants.

Here we discuss the latest findings from two such targets, each quite different and yet both could have important roles to play going forward…

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New directions in adenosine axis targeting

Making waves with new directions – there are many possible ways to go when considering targeting the adenosine axis

As we segue between our AACR and ASCO coverage, one topic that straddles both virtual meetings is targeting the adenosine axis.  At AACR19, this pathway was very much front and square with some intriguing and controversial data presented, which caught many people by surprise.

Since then, several companies have opened new trials, others are completing enrollment and waiting for their data to readout before deciding upon next steps.

It’s a good time to take a look at what’s new in this niche and also see things differently through the lens of one company involved in the field.  Yes, it’s time to share our latest expert interview from not one, but two, c-suite executives.

What are their perspectives (they are different), where do they see the field going and why?

In part one of the discussion we focus exclusively on adenosine targeting and how they see themselves differentiated from the crowd… it certainly makes for interesting reading!

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Competition rapidly heats up in the KRAS space!

The calm before the storm as the KRAS competition heats up and also gets more complex in the process

I was very tempted to tease everyone and say something along the lines of… ‘while you were all partying, there was some new KRAS clinical data being presented somewhere in the world’ but that would be rather naughty, I suspect.

Instead, I’ll simply point out that it’s time to take a look at the latest phase 1 data in the KRAS niche.

What more clinical data already?!

Yes there is and what’s more it doesn’t belong to the either of the leading two in the early race to market, aka Amgen and Mirati.  There’s a whole bigger world out there for those interested in following the broader slate runners and riders.  It pays to pay attention because this is not a race about single agent therapies, rather it’s about who figures out the optimal combinations and is able to finesse that better than their competitors.  Like real horse races, an unexpected runner can surprise a few folks by making a strong push on the rails or a bounding leap round the outside like Lester Piggott was famous for doing.

This highly specialised field is moving much faster than the BRAFV600E arena was a decade ago and there’s also more players involved too, plus multiple different approaches and targets to consider, which I expect we will be covering quite a few times during 2020.

Are you ready?

Get set, GO!

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JPM20 Highlights from Day 1

San Francisco – This week is mostly about business news as pharma and biotech companies congregate around the JP Morgan Healthcare conference.

It’s JPM time!

As of today (January 13th) I think a lot of investor and journalistic observers have probably been rather disappointed with no news of any major M&A activity, as this seen as setting the tone for the year ahead. I don’t personally see things that way because there’s always plenty of interesting small deals, new early funding, new science and even newco’s forming.

Indeed, Allogene already announced a new clinical collaboration with SpringWorks Therapeutics to evaluate their investigational anti-BCMA allogeneic CAR-T cell wherapy with their gamma secretase inhibitor in multiple myeloma.  They clearly see this as one way to address the shedding problems that have led to relapse with BCMA therapies.

As in previous years, we have a rolling live blog each day at JPM to highlight some of the scientific and company findings that emerge during the meeting…

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The Evolving Competitive Landscape for TIM-3

The start of a New Year is a good time to take stock of where we’ve come from and where we’re going in the fast-paced world of oncology new product development.

Upregulation doesn’t always mean a protein is a valid target, but in some cases it just might…

In this latest post, we’re revisiting T cell immunoglobulin and mucin domain-containing protein 3 – or TIM-3 in short – and taking a closer look at the evolving competitive landscape in this niche.

One company targeting it is Novartis, who have an anti-TIM–3 antibody MBG453 in development. In this post we have an expert interview with a scientist who is a pioneer in the emerging field of TIM-3 biology.

There’s also a review of some of the recent important scientific papers on TIM-3 biology, as well as commentary on data presented at ASH19 that we expect may feature in presentations at JPM20 next week, not to mention be the focus of future interim updates should the data turn out to show some promise in certain settings.

If you have an interest in targeting novel immune checkpoints and want to find out more about where the field is at with TIM-3, then this post is for you.

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Update on the KRAS Runners and Riders

In Pharmaland it is frequently the case that once a target has been validated there’s always new developments in the form of novel agents that emerge, as well as emerging new related targets to consider.

Standing from the KRAS crowd

Here we combine an update on some new market entrants in the KRAS niche with an expert interview discussing how to address a known area of acquired resistance that has recently been highlighted.  Naturally, that also brings with it yet more novel targets and potential combination strategies that may need to be considered by players in this space.

Yes, KRAS G12C is now a rapidly evolving area with multiple players and many moving parts, whereas even just back in January this year many observers saw it as a three horse race – think again, it’s much deeper and broader than that somewhat naive hypothesis already!

As usual, we follow these races longitudinally with regular updates and explain why new scientific findings need to be considered if we are to make a difference in the clinic with future combination strategies.

Are you ready for the latest game of 3D chess?

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Insights on targeting the oncogene SHP2

Fall in Boston during the AACR-NCI-EORTC Triple meeting

After recent updates on targeting KRASG12C and HRAS, let’s not forget that there are plenty of other elements of the RAS pathway that can be considered, not least is upstream receptor kinases such as EGFR and sideways to SHP2.

What happens when those worlds collide?

Quite a bit it would seem.

If we want to seriously impact patient outcomes for the better then we need to explore rational combination approaches.

Here’s one way to do it…

Please note that this is an early target with not very many competitors, so there’s plenty that can happen here on multiple fronts!

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Where’s the next exciting IO target coming from?

Following the success of anti-CTLA4 and PD(L)1 therapies over the last five years or so, there is much time and attention being focused on addressing a key question, namely – what’s the next viable checkpoint target?

There are quite a few possibilities emerging, although to be fair, some of them will no doubt go by the wayside over the next year or two.  There has already been quite a bit of attrition since 2015/16.  Figuring out which ones will be a target versus being a useful marker is also an important aspect of new product development.

Competition is a fine thing – as long as they’re going in the direction you want to go.

For most of our ASCO coverage over the last few years we have tended to include a variety of approaches in the pre-conference Preview series that can run from a tumour type, a up and coming modality, an emerging target, and various other ways of looking at or making sense of the sea of data.

Here, we take a look at an IO target that is receiving much interest and explore what we know and where this might be headed… and ask whether the early promise is living up to the billing in practice?

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Targeting the adenosine pathway in cancer immunotherapy

The AACR19 ‘mosh pit’ where gems abound

It’s been a while since we looked at the adenosine pathway, where a fog of immunosuppression is thought to cloak the ability of the immune system to induce antitumour immunity.

When we first wrote about the A2A receptor-CD73-CD39 pathway in 2016 there really weren’t very many players in this niche.  Since then the field has expanded quite considerably and there are now more companies and molecules to consider.

As we straddle AACR and ASCO, it’s a great time to offer an update and look at what we learned…

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