Biotech Strategy Blog

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

Posts tagged ‘SCLC’

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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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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Pointers to consider in SCLC developments

Wait, what did you say?!

How many times in the past have we seen gaudy initial high response rates from traditional chemotherapies in small-cell lung cancer (SCLC) only for people to experience early relapse due to lack of persistence and durability?

Are we doomed to repeat this process with ADCs?

The initial attempts with Stemcentrx/AbbVie’s Rova-T, a DLL3 directed ADC ended in abject failure.  Proving the target wasn’t the issue, this hasn’t stopped a bispecific T cell engager (tarlatamab) from Amgen gaining approval in extensive stage disease (ES-SCLC).

Suppose we tweak a few elements with the next generation of ADCs and try swapping out the linker, payload, and antibody target – what then?

Perhaps another target with a chequered history to date has been B7-H3, with several modalities tested and a number of companies giving it a good go without much to show for their efforts.

This weekend we saw some new clinical data with a B7-H3 ADC. First reactions were positively rosy, yet there are a number of early warning signs and nuances to watch out for, as we explain in our latest review…

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Breathing fire into novel combinations

Dragon sculpture at ⁨Kiyomizu-dera Temple⁩, ⁨Kyoto

Cancer cells can exhibit a dynamic ability to change their identity in response to environmental pressures or treatments. This flexibility allows them to adapt by taking on different characteristics, enabling them to survive in challenging conditions.

A tumour cell that initially depends on a specific growth pathway can shift its traits to rely on alternative mechanisms when the pathway is blocked therapeutically.

Much as a magician can conjure up an illusion, the nifty cellular shift can contribute to resistance to cancer treatment.

In some cases, tumour cells may alter their surface markers or acquire features typical of another cell type, making them less susceptible to targeted therapies.

Understanding this behaviour – and the molecular underpinnings of the changes – is crucial for developing more effective strategies to counteract tumour evolution, escape, and resistance.

What if the targets also change in the process?

Ah, but what if we can adapt a treatment regimen to aim at the evolved targets, assuming we know what they are?  After all, if we put a blindfold on an archer then he likely won’t be able to see what and where the target is, whereas if they can see then the chances of success is much higher.

In our latest review we look at a number of targets and novel combinations based on key findings around the underlying molecular changes…

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Breaking down doors at ASCO24

One of the themes we have been watching out for at ASCO this year is new targets and novel combination strategies.

In each of the daily highlights we have selected five examples which jump out – for various reasons.

The early phase 1/2 trials obviously won’t be practice changing in the way a major global pivotal trial will be, yet they often offer useful clues for some of the new direections coming through company pipelines.

Today’s selection are a mix of early and late stage trials to ponder…

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What science tells us about future directions in lung cancer

The World Conference on Lung Cancers (WCLC) annual meeting in Singapore showcased important scientific findings illuminating new directions against these deadly diseases.

While some clinical presentations fell a little short of expectations, smaller sessions revealed some important gems illustrating the intricacies of lung cancer biology where art and science intersect.

In the end lung cancer remains complex, heterogeneous, often aggressive, and evolving. Emerging translational research undoubtedly brings hope towards guiding more targeted therapeutic strategies.

The art is in creatively leveraging emerging science to tackle these lethal diseases from every angle.

Here we highlight seven areas where we ought to be paying attention to when considering future directions in lung cancer…

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WCLC21 Preview of key data to watch out for

Time for some new directions in lung cancer?

It seems only a few months ago we covered WCLC20 and here we are again with another lung cancer conference.  This is because the pandemic certainly made an impact last year in more ways than one since the meeting was split into two, with the second half of the sessions being showcased in January.

This time around we highlight quite a few presentations on the IO and KRAS related pathway fronts, as well as some updates on various targeted therapies – with a few unexpected surprises in store.

There are also some important genomic and biomarker presentations to watch out for…

BSB subscribers can read more on our latest cancer conference preview  – you can log-in or click to access our latest expert interview.

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Which early phase agents look promising – or not – ASCO21?

New product development and early phase anti-cancer agents have been very much a focus on BSB (and PSB before it) since their inception.

It’s fascinating to realise one of the compounds selected for review in this article has its origins in a much one earlier trial with serious incidents we saw in a trial in novel volunteers with a different company and product and originally inspired the beginning of our scientific writing in 2006.

By an interesting quirk of history, the first time we wrote about PARP inhibition was in the same year and now it is one of the selections in the ASCO plenary today.  You can read more about the olaparib OlympiaD trial write-up here, proof that all successful products eventually started off in developmental therapeutics at some point in their early career!

In this latest review, we selected eight anti-cancer compounds currently undergoing phase 1/2 trials and put them through their paces… some are more positive than expected, some were downright disappointing, some were off to an encouraging start, others the count is out until we see more robust data.

How is the report card looking this year?  Some reflections and thoughts to consider…

To find out, BSB subscribers can read more on our perspectives regarding Developmental Therapeutics and various early stage compounds, subscribers can log-in or you can click to read our ongoing ASCO21 coverage.

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Tooting the DDR horn

Every year the sweet spot sandwiched between AACR and ASCO comes around all to quickly, as we’re wrapping up interviews conducted at one and preparing the previews for the other, never mind ESMO Breast, AAI, and ASGCT all coming in May as well.

Cambridge Botanical Gardens

This year is no different and I’m delighted to say they segue rather nicely for once!

It’s hard to believe we’ve been writing about DNA damage repair and PARP inhibitors since 2008/2009 or so, and still this topic just keeps growing and growing!

We’ve certainly come a long way since those early days and now the broader DDR niche is also expanding as more targets are identified and evaluated, both in animal models as well as the clinic.

This list will also increase as CRISPR screens continue to identify synthetically lethal targets – some will be useful, others will fall by the wayside due to lack of efficacy or poor tolerability. Finding a balance between the two will therefore be a big key to success.

In this post we’re going to start with an update on the PARP1/2 inhibitors then catch up on data from other DDR family targets and finally explore a pipeline discussion with an industry expert who is well versed in the DDR field.

To learn more about our ongoing post AACR21 and pre ASCO meeting analysis and expert interviews to get a heads up on key oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Putting some colour on the TIGIT niche

Time for some additional colour commentary!

There has been some incredibly intense interest surrounding TIGIT as a new therapeutic target in oncology of late, to the point where some observers have been wildly claiming this is the new universal checkpoint everyone has been waiting for.

But is it?

It’s early days yet with little data presented from people with cancer, so at this point it could well be a bit of a stretch to find another anti-PD–1/PD-L1 equivalent, but this doesn’t mean there isn’t utility in seeing clinical activity in some tumour types, far from it.

In our latest post, we take a look at what’s coming up in the TIGIT niche, along with an interview from a company active in this niche.

What do the company have to say and how do they see this panning out?

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