Biotech Strategy Blog

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

About MaverickNY

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Posts by MaverickNY

Kicking ADCs up a notch

Orchid at Vizcaya Museum in Miami – always thought they looked like chemical structures showing us the gaps!

We highlighted a number of different types of antibody drug conjugates (ADCs) recently – yes, there’s much more to this category than simply dropping a chemo cargo on cancer cells!

In this review, we explore one of those flexible functionalities in more depth.

The cool thing about having an antibody base is creative chemists can bolt different things onto them, depending on what their goal is.

There are some really cool technology ideas being explored in research right now, which may improve not only what we can do with ADCs but also another modality.

If we think of the ADC as a modern day Trojan Horse to hide or mask the real payload in some way, the possibilities become limited only by our imagination.

The good news is there’s more than one example of this new genre to explore…

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Shining a beacon

Shining a beacon on key GI trials

After covering a lot of science of late it’s now time to review some recent clinical data, discuss some of the implications of the findings, and their potential impact.

After all, science doesn’t exist in a vacuum and how it translates into outcomes in people living with cancer is an important part of the process.

Can we help them live longer and feel better are two important questions to ask when looking at study readouts.

Let’s not forget there’s quite a difference when considering the exposure of light from a lighthouse beacon versus a typical torch.

The former is designed to produce an extremely powerful, far-reaching beam that can propagate over long distances. A torch has much more modest lighting capabilities suitable for short-range use. The exact brightness difference depends on the specific lighthouse and torch, but it can reasonably be assumed the lighthouse beam is orders of magnitude more intense.

In a similar fashion, we need to look at phase 1 and 3 trials through different lenses, just as we ought to do with the potential 14th agent to market versus the first…

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A oncology biotech to pay attention to

We are still on a quest – a patient journey, if you like – to find new agents capable of addressing the inherent issue of why do some patient’s tumours lack immune infiltrate and how do we go about fixing it?

Chihuly Glass sculptures always remind me of upregulating MHC

Over the last decade on BSB we have explored a veritable telephone directory of immune agonists, cancer vaccines, cytokines, bispecific and trispecific antibodies, additional inhibitory checkpoints, oncolytic viruses, small molecules, chemotherapy, CAR-T cell therapies, and various others.

Few have got the job well done in advanced solid tumours. Once MHC is downregulated, it becomes much harder to generate an immune response.

Stop and think about this for a moment.

It’s been a long slog to find the next big thing and a frustrating one at that for cancer researchers slaving away at the coal face. A lot of promising agents have come and gone – some quietly, others loudly – to end up in what Dr Patricia LoRosso wittily described as ‘dog drug heaven’. It is also dispiriting to write about so many ending in failure.

The good news is there are some new signs of life coming through, although it’s too early to declare a spring rennaisance. Over the next couple of weeks we’re going to highlight a number of young biotechs with encouraging or fresh ideas being explored in the clinic.

I also don’t want to raise too many hopes – especially as I have long been sceptical about some approaches with all their breathless hype – but here’s something to keep an eye on with an open mind because if it holds up where others failed then the company could be on to something…

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Thinking outside the box

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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Key oncology take aways and insights from Days 1 and 2 at JPM24

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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Wow I wished I’d thought of this!

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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An emerging new target for ER positive breast cancer

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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Same Controller, Opposite Outcomes

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 mystery ASH posters receiving a lot of attention

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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Next generation of T and NK cell therapies

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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