Biotech Strategy Blog

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

I’ve heard quite a few people frequently exclaim of late how “ADCs are hot!” Alrighty then, yet this is really only the end of the beginning because old hands know they have actually been around for quite a while.

If one was cynically minded then there’s an obvious reason – chemotherapies are usually generic these days, while ADCs bring in much higher ticket prices.

They won’t all succeed though – we’ve already seen a steadily growing graveyard of failures, which started out promising on paper then unfortunately flopped in the clinic.  Just because an area is suddenly declared hot (again) doesn’t guarantee success because these are complex molecules to design compared to small molecules with a lot of factors impinging on their performance.

What many observers have missed, however, is the deeper and broader opportunities offered beyond the often plain vanilla examples.

This is because the modality has greater flexibility than chemotherapies – you can design them such that other things can be bolted on or even hidden, Trojan horse style.

In other words, what we are seeing is an early trend with few enlightened companies starting to ‘think outside the box’ in this niche.

In the near to medium future we will see a greater volume of clinical data on these emerging approaches, which could lead to improved outcomes and longer lives for people living with cancer.

So what are these new fangled things, how do they work, and which companies are active in the futuristic ADC markets?

In this review we highlight half a dozen emerging areas around ADC technology with examples of products and companies active in these niches…

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All aboard the San Francisco Milan Trolley!

With a number of oncology companies facing substantial loss of exclusivity (LOE) over the next five year strategic review period, we look at who’s at risk, how are they making up the gaps, how convincing are their arguments?  Will the flurry of acquisitions and collaborations announced over the last few months and even days make a difference?

In this series of quick reviews we offer our take aways and insights on what’s happening and whether or not they stand up to scrutiny.

Spoiler alert: some do, others do not!

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New Horizons in CAR-T cell therapies

One important area we are going to focus more on in 2024 is exploring promising up and coming early stage biotechs not yet at the JPM Healthcare conference.

After all, big Pharma companies will be looking to either acquire private biotechs outright or license their clinical stage assets, replenishing pipelines before possible IPOs make them too expensive as a convenient strategy for bolt-on deals.

We have already seen how the IRA changes are driving a switch from oral molecules to iv compounds such as ADCs of late, but what about cell therapies?

In this example, the company have come up a creative CAR-T cell therapy strategy, the first of which is heading into the clinic this year, plus they have a raft of others swiftly following on and currently being put through their preclinical paces.

What do we mean by creative?

Here they a exploring a number of key targets not named CD19/CD20/BCMA or even GPCR5D.  In other words, they’re quite different from the usual CAR-T fare. Some of these were considered tricky in the past, yet by pursuing different scientific angles a viable strategy can result.

It’s time to explore new horizons and opportunities in this niche and discuss where might things be headed?

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Tackling T cell fitness and exhaustion will not be plain sailing, yet they will be an important focus going forward

One of the often ignored challenges in advanced cancers – regardless of whether they are hematologic malignancies or solid tumours – is the quality of the patient’s T cells.

Oftentimes these may be dysfunctional or exhausted, which means responses to any given therapy will be impacted in a negative fashion.

What if we learn more about the underlying biological processes involved – can the knowledge acquired lead to enhancements in the design of CAR-T cell products, the overall quality of the T cells, and hence improvements in outcomes?

While several companies have been active on this front, we went deeper and spoke with an academic researcher keen to leverage research findings, which may uncover novel approaches for future developments.

Rewriting T cells may prove to be an important emerging area of research to watch out for in 2024…

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View from Perdido Bay to Orange Beach

The sun is setting on the year end and the 2023 Holiday season brings our cancer conference coverage to a close until the new year.

Before we go, I wanted to end with a bang and highlight some really stunning and thoughtful research.

It was just published and is an absolutely amazing piece of thinking and execution.

Some of the best ideas come about in oncology R&D when we make the most of what’s already available biologically then borrow the concept so it can be applied therapeutically.

Rather than push the proverbial rock up the hill like Sisyphus, why not simply nudge it off the top and let nature take its course?

Sometimes even scientists are guilty of over-thinking things.

In this elegant work, the findings may well change the way we think about tackling some difficult to treat solid tumours going forward…

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River Walk, San Antonio, Texas

The famous colourful umbrellas on the San Antonio river walk always remind me of cute little hats, which is a rather apt metaphor for today’s post on an emerging new target for breast cancer.

We have seen some success in ER+/HER2-negative breast cancers with the aromatase inhibitors and CDK4/6 inhibitors in first-line treatment of the disease and the SERDs elacestrant and fulvestrant in earlier and later lines, respectively, but there is still plenty of room for improvement.

If we want to seek out new targets to address either resistance or even synthetic lethal relationships, how might we go about finding them?

In our latest post on this niche, we discuss an emerging target of interest, highlight the competitors in the early landscape and also offer some commentary from a couple of the companies involved…

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Immune cells look and act differently

In this latest post from the American Society of Hematology meeting we explore some of the scientific data emerging from San Diego.

Specifically, we are looking at how transcription factors such as TOX2 can drive divergent fates in T and NK cells.

It might be tempting to think it sounds a bit dry, yet the findings could have important implications for future therapeutic developments – especially in the design of novel chimeric antigen receptor (CAR) cell therapies, an area where CAR-NK cells have constantly struggled with poor persistence.

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The quiet of ASH poster hall before the storm

Navigating the American Society of Hematology (ASH) poster halls are almost an art form in themselves.

Whereas at ASCO and AACR tend have select times for poster viewing, with a crowd eagerly waiting for the sessions to open, ASH have essentially two sittings for the daily poster viewings.

In the evening, the hematologists and oncologists have finished the oral presentations and head en masse for the two hour session in the aircraft hangar – hence the infamous ‘ASH Dash’ – whereupon it becomes so crowded you wish you had visited earlier when you had a chance.

The morning is more quiet and sedate, almost like a reference library where you can browse and revere some gems in peace.  It’s also the time when Pharma execs check out the competition, which means the wise ones watch the traffic flows and note which ones are garnering attention each year.

This creates some whimsical amusement for BSB readers – which posters were receiving more attention this year?

A couple in particular were noticeably more popular than others…

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Taking a leaf out of Wayne Gretsky’s book, we’re continuing our theme round seeking to be inspired and highlighting another batch of early developments, which may offer promise in the future.

Don’t skate to where the puck is – skate to where it will be.

Some of the best innovations come about because scientists think deeply about the challenges and issues preventing therapies from working as they should and ignore dogma in their pursuit of innovation.

These may not necessarily be the most popular approaches of the day, yet they can yield satisfying rewards down the road. In fact, I’d argue it is often the few who go an entirely different way from the crowd who end up being successful in the long run.

In today’s post we highlight some of these enlightening developments, as well as others following solutions looking more obvious at first glance, yet could stumble down the road…

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Rise and shine over San Diego

Fridays at ASH is usually the province of the education sessions, although increasingly it is becoming the day to catch some really useful and intriguing translational data.

If we want to know where the next developments are heading to then this is the way to find some emerging gems.

I struck lucky this year – the ones selected kept me listening rather than frantically looking for another parallel session to run to.

What emerged in some cases was a deep appreciation for some well thought out ideas based on novel targets, new CAR constructs, different modalities, or even other diseases altogether.

Here we highlight some excellent talks and how they may offer an impact in the future…

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