Biotech Strategy Blog

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

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Posts by MaverickNY

The CAR-T cell beat goes on

The first day of the 5th annual CAR- T cell meeting in Rotterdam turned out to be rather interesting indeed with a number of key presentations highlighting novel developments across a range of hematologic malignancies.

If we want to see some progress then we need to start developing new constructs with other targets beyond CD19 and CD20, which are applicable to B cell malignancies, CD123 and CD33 in AML, and BCMA in multiple myeloma.

By the way, sometimes gene edited allogeneic products might make sound scientific sense in the context of the disease being studied, but getting these through the various regulatory hoops and hurdles isn’t as easy as some might think.

Necessity is often the mother of invention requiring alternative strategies to creatively address the underlying challenges.

Here we highlight some of these developments and put them in a broader context of the evolving CAR-T cell therapy field…

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An unexpected renaissance

Rotterdam, Feb 2023

With so much focus on T cell fitness and exhaustion of late I wanted to highlight an area in the CAR-T cell space, which was all the rage a decade ago then quietly fizzled somewhat, leading many observers to wonder if it was great in theory, but not so much in practice.

This subniche is going through a renaissance of sorts as more research is conducted and we learn enough from the experiments and past mistakes to start moving forward again.

In this post, we’re gimng to focus exclusively on one of these aspects and see what’s new and where things might be headed because this isn’t an isolated incident…

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New directions in lymphomas

The landscape in various lymphoma subsets has changed in ways many may not have expected a decade or so ago and will continue to evolve further as new treatments against novel targets start to show their true colours.

Let’s not forget the original emergence of BTK inhibition caught a lot of people by surprise, so if we think about the next five years ahead, where might some of the next innovations come from and how might different segments potentially look in terms of new regimens?

In our latest expert interview, we take a look at an emerging pipeline in this hematologic niche and discuss where some of the early stage data might lead us to going forward.

Of course the caveat in oncology is most products will not actually make it to phase 3 development or even succeed there, yet the big attraction is in exploring emerging products to see where the trends might lead, because you never know which ones will shine down the road…

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Will targeting KRAS G12D prove more successful than G12C?

Are scientists and observers taking a distorted fish eye view of the KRAS world?

I’ve often wondered if in putting so much focus on ripping the progress of the G12C inhibitors to shreds, people simply lose focus of the progress being made elsewhere especially with different, yet related targets.

Here we offer some emerging highlights on several fronts, some of which ought to be well worth watching out for and others perhaps not so much…

Curious to learn more?

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Cracking the code to the MYC oncogene

Sunrise or sunset for therapeutics against an intractable oncogene?

In our perpetual search for cool and interesting new developments coming through in cancer research we stumbled upon an unexpected surprise.

The good news is it’s aimed at an intractable target where there is a high unmet medical need across a range of different cancers and recently entered clinical evaluation.

The bad news is the outcome is uncertain (as yet), plus there are some key challenges we have identified.

Somewhere in between lies the truth of the matter, although there are a few clues where we can put some stakes in the ground as reference points to come back to.

In our latest assessment, we take a look at what is known as well as some of the potential unknown unknowns, and how they might impact the eventual outcome.

We weren’t as excited as many were at ENA22 with an entirely different approach, yet this one piqued our interest and may have more promise…

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Keeping an eye on the ball in AML

Every once in a while a new approach comes along in acute leukemias, which turns everyone’s head.

CAR-T cell therapies certainly achieved this in pediatric ALL, as did the FLT3 and Bcl2 inhibitors in AML before them.

What are the next potential novel developments to think about?

Recently at ASH we explored progress with the Menin inhibitors, although they aren’t the only targeted therapy on the horizon.

In our latest in-depth analysis, we turn our attention to a very different kind of therapeutic intervention, which also happens to have a potential near-term binary event to consider.

This particular review includes an interview with company executives for their perspective on a late stage clinical program…

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Pointing the way forward

Continuing our series on Kaizen in cell therapy, we now switch both angles and companies to explore a different round early stage developments.

It was clear at ASH that to some, these were perceived as a head scratcher, while for others they were considered the best thing since sliced bread in the niche, so opinions on the controversy clearly differ quite broadly!

What’s the skinny then – and why does it all matter?

Curious to learn more?

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Kaizen in action

Taken on Jan 1st 2023 – a bright new path forward?

Kaizen is the Japanese word for continuous improvement.

It’s all very well companies producing their first blockbuster in oncology, but what then?

The real mark of success in my view is being able to sustain their effort to build a life cycle management portfolio lasting over time, so in effect you generate many more options and opportunities for success over the long run.  This is much harder to achieve.

I think many folks were quite curious to see what would happen to the promising early stage Celgene pipeline once it transferred to BMS. Would the march continue beyond the IMiDs, or would it all wither and die on the vine?

We last took stock of their progress at ASH20 prior to the approvals of ide-cel and liso-cel.  In the two years since then much has happened – both on the approval front and also with the products coming along further behind.

It’s time for a look at how things are progressing, with some surprises in store…

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Tipping the TIGIT balance

Are we experiencing a sunrise or sunset for TIGIT?

TIGIT has certainly generated significant positive and negative reactions over the last few years, as it wenders its way through the Gartner hype cycle.

Sometimes people think things are much more clear cut than they actually are in practice; the complex TIGIT pathway is a great example of this fallacy.

With targeted therapies we have consistently seen the emergence of acquired resistance over time – a similar phenomenon happens with immunotherapies too as the tumour adapts in response to selective pressure.  These changes can lead to immune evasion, which means less tumour cells are being killed, leading to relapse.

We haven’t seen much data on what the mechanisms of resistance are, in part because the anti-TIGIT trials are starting to read out and it takes time to figure out what’s happening.

There’s some new data from academia to consider, which may shine a light on one potential solution as well as offering an opportunity for another NewCo to rise.

Here’s a look at the science behind the story…

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Shining the light

Shining a light

There’s always a newcomer coming out of stealth in the oncology field given the sheer breadth and depth of novel research being published in academia of late.

The latest example has a dramatic name, which made me smile. It may well have come from the ancient Greek word meaning “burning”, “blazing” or “shining.”

I’m inclined to think the last one is particularly apt, since this approach essentially shines a beacon for T cells to see their way more accurately.

So what’s the story and why is this one a potential standout?

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