Biotech Strategy Blog

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

Posts tagged ‘DLL3’

WCLC25: The wow factor in SCLC wasn’t an ADC after all

And no, it wasn’t one of the hot bispecific antibodies either!

Finding gold at WCLC25

If you’ve been following the small cell lung cancer (SCLC) space, you’ve probably heard the same refrain; ADCs are the future…

Higher response rates, validated targets, new Topo-I payloads, precision medicine at its finest.

Many in the investment community certainly seems to think so, with every new agent sparking fresh excitement about who might capture market share based on the most tumour shrinkage.

But what if everyone’s been looking in the wrong direction?

In this review, we look at a dozen developments across multiple targets and modalities to find the most promising ones to watch out for in SCLC…

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How Merck plans to succeed where others failed

Innovation comes in many shapes and sizes

In an industry littered with discontinued programs and dashed hopes, Merck is placing some contrarian bets on therapeutic approaches that others have abandoned.

While competitors retreat from challenging modalities or write off entire target classes after early setbacks, Merck’s strategy centres on a simple premise: the first attempt rarely gets it right.

By focusing on next generation agents with improved therapeutic windows and enhanced combinability, they’re revisiting the graveyard of oncology development with fresh eyes and deeper pockets.

The question isn’t whether their pipeline agents will work in isolation, but whether they can succeed where previous iterations failed spectacularly and leverage the science to generate approaches, which could make their competitors irrelevant…

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T Cell Engager Comeback: Why solid tumors may finally yield

While most eyes at ASCO will be on the marquee phase 3 ADC readouts, a quieter revolution may be unfolding in the T cell engager space.

Created by Wall-E from a Blue Ice Publishing prmpt

After years of struggling to replicate hematologic successes in solid tumours – and several high-profile failures that nearly killed the field – a new generation of engineered bispecifics is finally showing signs of life.

The question is whether these sophisticated molecular machines can overcome the fundamental challenges, which have made solid tumour bispecifics such a graveyard for promising compounds.

In this latest review we take a look at some early-stage agents, some of which are looking quite encouraging while others might struggle with headwinds…

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Critical Analysis of the Emerging Trispecific Landscape

Dawn of a new era or a setting sun on a tricky approach…

Three is a magic number – except when it isn’t.

Trispecific antibodies are one of the emerging stars on the multispecific stage, promising to hit not one, not two, but three targets with a single swing. It’s a tempting idea – who doesn’t love a good triple play?

With great ambition also comes great complexity, and not every design is ready for primetime.

At this year’s AACR, the trispecific party got a little louder.

From PD-1/CTLA-4/VEGF mashups to CD3-based T cell whisperers, the posters are brimming with innovation – and more than a few eyebrow-raisers.

So before we get swept up in the hype, let’s pause and ask a provocative question: is this a triple threat or a triple headache waiting to happen?

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AACR25 Preview 2 – Curiosities

This year’s American Association for Cancer Research (AACR) annual meeting in Chicago is rich in early targets and agents coming along through a multitude of company pipelines.

It’s too early to say whether they will provide a beacon of light or indicate another crop of agents heading for the rocks.

The good news is there are plenty to choose from and look at in the context of what’s coming next.

Here, we take a bunch of curiosities and put them through their paces to see what looks promising or not…

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Biotechs beating ADCs at the own game

For all the hullabaloo around M&A and licensing deals from China especially for antibody-drug conjugates (ADCs) of late, it’s easy to forget they have many inherent challenges in their design, which may lead quite a few to fall short down the road – despite high expectations.

Recently we asked ourselves is there a different way to go about killing cancer cells in late stage tumours more effectively?

In our latest company interview, the answer, at least in some instances could well be yes.

It’s also a lot of fun going off the reservation to hear more about next generation approaches from up and coming young biotech companies with well thought out approaches to watch out for…

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A novel bispecific ADC to watch out for

Companies think they see gold in the distance, while ignoring the narrowing, darker hazards close by

If 2024 was the year of topoisomerase-I antibody-drug conjugates (ADCs) then 2025 is likely to herald a different series of trends within this niche.

Adding on extra payloads or targets may seem like a logical extension – as witnessed by the flurry of bispecific and dual-payload ADCs. This approach often ignores the many underlying complexities and challenges involved because these are highly complex and sophisticated agents to develop.  It’s not simply a matter of swapping out different elements akin to Lego bricks and hoping for the best.

In this article, we discuss a number of issues facing companies chasing the ADC dream, as well as an early example of an intriguing novel ADC target to pay attention to going forwards.

In the long run, the near and far might turn out to be relative, depending on your perspective…

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A Turning Point for IO at SITC 2024?

Choices, oh so many choices!

We’ve been following the IO wave for over a decade now and one of the questions that comes to my mind is whether we are about to experience what the Germans would call a change in times, or ‘Zeitenwende.’

The Duden German dictionary describes Zeitenwende as “the ending of an epoch or era and the beginning of a new time.”

Readers may recall it was famously used by Germany Chancellor Olaf Scholz after the Russian invasion of Ukraine in 2022 to describe how this was a turning point in European and Germany history, albeit in not necessarily a good way.

Are we at a turning point in IO for the better rather than worse?

After the initial wave of success with low hanging fruit, we’ve sadly seen more failures than successes although we’re starting to see signs that new strategies may yet deliver the promise and potential we all hoped for way back when.

In this post we take a look at 10 presentations to watch out for at SITC 2024 around the theme of Zeitenwende. Check it out!

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The Nexus Frontier

Futuristic image created with WALL-E   Source: Blue Ice Publishing

The Nexus Frontier stands as a bold and groovy movement at the intersection of discovery and understanding, where complexity meets clarity.

It’s a frontier where scientific rigour and human relatability converge.

In other words, it’s time for a collaborative guest post from a physician CMO to learn about his perspectives and reactions to recently presented data.

What jumped out?

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How bispecific antibodies are reshaping cancer treatment

Rolling into Madrid!

One of the challenges we are starting to see more attention on is what happens in later lines of treatment for advanced solid tumours, regardless of whether prior therapy involved chemotherapy, immunotherapy, or hormonal therapies.

How can we provide new options for treatment of refractory disease and help more people live longer?

Finding active drugs with both a reasonable safety profile and demonstrable solid activity in a situation with more complexity in terms of the underlying biology coupled with a much higher tumour burden has long been a challenge for many oncologists and companies.

In previous years we saw how poorly checkpoint inhibitors did in this setting compared to using them upfront and while chemotherapy is very effective at shrinking tumours, the effects are rarely long lasting.

What’s next then?

One approach involves bispecific antibodies where the tumour cells and T cells are literally dragged into closer proximity, enabling the serial killers to do their job more effectively.  They worked rather nicely in blood cancers, so why not in solid tumours?

After nearly a decade of trying out many permutations of this approach, we are finally starting to see some light at the end of the tunnel with several different agents in diverse tumour types…

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