Biotech Strategy Blog

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

Posts tagged ‘AstraZeneca’

A smorgasbord of new agents

Every now and then what seems like one player out in left field for the longest time suddenly balloons into a whole new class or niche of agents.

Such is the case for the target in the spotlight in today’s focused review.

Here we look at the challenges and opportunities provided within the emerging landscape, explore where the field is going, and what to watch out for because this is one you’re going to hear a lot more about going forward in a number of ways…

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An unexpected surprise!

Time for a fishing expedition or two

In our fifth preview from the AACR annual meeting being held in San Diego next month, we noticed some intriguing surprises emerging from one class of agents currently being studied both preclinically, as well as in the clinic.

What are they – and why do they matter?

Quite simply, once the implications are understood they may help us understand where the field is headed in the near to medium term – and why some particular combinations might yield some interesting findings…

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Exploring novel targets and modalities in advanced cancer

New waves or on the rocks

It’s not that long ago when a certain tumour type saw several waves of promising new agents emerge, quite a few of which made it past the finish line and commercial approval.

These included novel drugs, fast follow-ons, and even me-toos.

The next batch in new development pipelines were not so lucky with a series of disappointing phase 3 misses.

Then radio silence ensued.

As we take another look at this niche, there are a number of early stage agents being put through their paces – small molecule inhibitors, protein degraders, bispecifics, immunotherapies – they’re all there.

Are we going to see some new waves or will they crash and flounder on the rocks?

To find out, we delved into the latest data to determine the current status…

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Setting the scene

Can TIGIT stand out from the crowd in gastric cancer?

We have seen all sorts of molecules come along in gastric-esophageal carcinomas, from antibodies, ADCs, bispecifics, small molecules, even CAR-T cell therapies.  Some have been more successful than others.

As the competition heats up even in the expanding number of subniches, it’s going to take some stellar data to stand out from the crowd.

We’ve already seen several miss such as Beigene’s much touted Fc-competent anti-TIGIT antibody ociperlimab in the second line setting at ESMO23 last month, while pembrolizumab continued its onward march at the ESMO Plenary back in February.

Now we have three more earlier stage agents to look at across different modalities such as Akeso’s PD1xCTLA4 bispecific cadonilimab, Keymed/AstraZeneca’s Claudin 18.2 ADC CMG901 and Arcus/Gilead’s anti-TIGIT antibody, domvanalimab.

In our latest review, we take a look at how these agents are doing…

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Pointing the IO way

Pointing the way

A few years ago at SITC 2016, we wrote about a raft of early agents, which were then considered all the rage against a variety targets at the time…

  • Modulating MDSCs, M2 TAMs, Tregs
  • TLR agonists
  • Adding MEK or TIGIT to checkpoint blockade
  • Immune agonists from 4-1BB to VISTA
  • And so on…

While some of the trials are still ongoing, a few have fallen by the wayside and still other targets continue to receive sporadic attention.

This year’s crop of emerging agents and targets are a very different bunch altogether and the breathless hype has been replaced by much more quiet determination and optimism.

What to watch out for in 2023? 

We offer eight areas to explore and check out – most of them are up and coming small to medium biotechs focused on oncology rather than big pharma cos with money to burn…

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Precision Targeting of Elusive Cancer Oncogenes

Sunset over Boston Commons

Cancer remains one of the most intractable diseases, with certain types and subtypes continuing to evade effective treatment. While great progress has been made with immunotherapies and molecularly targeted drugs, cancers driven by notorious oncogenes like KRAS, MYC, and p53 remain challenging to drug.

These key transcriptional and signalling proteins play vital roles in normal cell physiology, meaning inhibiting them often causes toxicity. However, the allure of tackling cancers addicted to these oncoproteins keeps researchers striving for more precise, selective ways to target them.

One emerging approach is to inhibit a key transcriptional kinase involved in regulating MYC and other cancer-promoting genes. Several inhibitors of this kinase have been tested clinically, but most were either insufficiently selective or too toxic.

A new compound profiled in the post below shows early signs of being a more optimised inhibitor. It displays high selectivity and a long half-life, enabling sustained target inhibition without excessive toxicity. Early data from a phase 1 trial in solid tumours has demonstrated clinical activity, including exceptional responses in MYC-driven sarcomas.

These promising results highlight the potential of this new wave of inhibitors to tackle MYC-dependent cancers, including aggressive lymphomas. Other companies are advancing selective inhibitors of this kinase into clinical trials for hematologic malignancies.

Overall, these precision inhibitors represent an exciting targeted strategy against transcriptional addictions in cancer. The initial clinical success offers hope for making meaningful advances against once intractable oncogenes…

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Targeted Therapy Trials: Why some drug developers keep missing the mark

Post Banksy exhibition – Wellington has now gained an extra cone. It reminds me of what cell/compartment should we be targeting in oncology trials.

Some of the challenges with personalised medicine is we often see companies either treating a targeted therapy in an untargeted fashion thereby diluting the signal or enriching for one not yet conclusively and clinically established.

In both cases, the results are inevitably suboptimal.

Additionally, not all drugs within the same category are the same.  They often have dissimilar scaffolds or target different cells and compartments, all of which can have a positive or negative impact on clinical outcomes.

In our latest post, we explore and discuss emerging insights around strategies undertaken in clinial trials and how they may offer some clues for certain company readouts over the next quarter…

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The ADC merry-go-round

Unedited, unfiltered – the ‘hey, look at me!’ pink elephant really was this lurid!

It’s time for our second Preview from the World Congress in Lung Cancer being presented in Singapore next month.

In this edition we’re going to focus on the next raft of antibody drug conjugates (ADCs) coming through in early development.

Do any stand out as the next big kahuna or are the numbers too glaringly garish, waiting to be knocked off their coconut shies?

In this review we review the evidence and take some stands…

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The scudding clouds of freedom

All too often the noise and attention is thrust upon the latest flashy or shiny new lures rather than on refining or redirecting the sails based upon changes in the wind patterns as more data become available.

In the book Dracula, Bram Stoker wrote:

“…the passing gleams of the moonlight between the scudding clouds crossing and passing, [are] like the gladness and sorrow of a man’s life.”

He might just as well been referring to drug company pipelines, where early stage agents rise and fall in favour as we follow their trials and tribulations from discovery and preclinical development through to evaluation in the clinic.  Success is fleeting and more often than not, many will fizzle and disappear in the blink of an eye.

Sometimes though, new information or intelligence comes together to point a different way forward.  It’s not necessarily going to be ‘better’, but like other aspects of life, taking action and moving forward is usually a sounder strategy than standing still.

Here, we look at a couple of developments that seemingly hit the skids a few years ago, but new evidence may offer some more focused direction forward…

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From far away you see more

The ‘Friendly Alien’

Von weit weg sieht man mehr (from far away you see more) is the title of an exhibition at the Kunsthaus Graz, an iconic modern art museum known as the “Friendly Alien” for its cutting edge design akin to a space ship which has landed in the city.

The same concept could also apply to cell therapy, as well as oncology new product development in general.

It’s all too easy to get bogged down in the weeds and   overwhelmed by detail – sometimes you need to step back to look from the distance to see more clearly and, in particular, the innovation or evolution currently happening in the field.

Some developments might look relatively small or even curious in nature, yet can turn out to be surprisingly ahead of their time, while others may portend issues ahead for the wise.

In this latest post, we take a look at a variety of novel CAR-T cell therapies involving some more unusual targets or designs and discuss some of the challenges and opportunities they face.

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