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

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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Pointing the way

Over the last decade chimeric antigen receptor (CAR) T cell therapies have demonstrated success in hematologic malignancies such as certain acute leukemias and lymphomas, yet they have struggled to gain traction in advanced solid tumours.

What can we learn from the ASCO Breakthrough meeting in Japan?

There are many reasons for this, not least are overcoming issues such as physical barriers, a hostile tumour environment, tumour heterogeneity, on-target, off-tumour toxicities, immune escape, difficulty in trafflicking and homing to the lesions, limited CAR-T cell persistence and exhaustion, etc.

It’s not all bad news though because there’s one tumour type where we are making some progress with CAR-T cells, namely gliomas.

What’s interesting is there has been a variety of tumour-associated antigens investigated in gliomas, including B7-H3, EGFRvIII, GD2, HER2, and IL–13Rα2.

Last week some new CAR-T cell therapy data of interest was presented at the ASCO Breakthrough meeting in Yokohama, Japan.

In this review we look at high grade gliomas in adults to explore how some new data against one target stacks up with what we’ve recently see reported for other targets. We also discuss future directions and where the field might be headed for further new product developments…

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New opportunities for Menin inhibitors

Tree of Hope

Some recent research in a specific area has provided some helpful and stimulating findings, which may lead to some unexpected combination trials in the future.

We all know cancer is best beaten with combinations and regimen approaches, but a key question always remains the same no matter which company is doing the R&D – which are the best options to evaluate together given the limited time, resources, and budget available?

Even large pharmas cannot explore every single possibility.

Suppose a company has the luxury of five early stage agents either in-house or available to them in a partnership. This would give 10 potential phase 1 doublets they could evaluate. If we include triplets as an option then we can add a further 60 possibilities on top.

It might sound like a tree of hope, yet these are unrealistic scenarios because few companies will run 70 phase 1 trials just to figure out the optimal regimen to go forward with in a phase 3 study. In fact, I seriously doubt if anyone would seek to attempt this number in mice studies either!

Despite all the misgivings people have about translating preclinical data to humans with advanced cancers, we often need to be reminded to keep our feet on the ground.

It’s not a matter of alchemy where chemists and translational researchers seek the ’elixir of life,” or a pill that would cure all cancers. Instead we have to use some common sense based on what we know and how things might shake out.

In today’s post we look at what some future combinations might look like and who the key players might be…

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And the relentless ADC march goes on…

Are ADCs the new smart bomb or likely to blow up company pipelines without a bye or leave?

We highlighted a number of issues and challenges facing the ADC field in our first ESMO Preview last month.

I really wasn’t expecting to be covering the topic again before the conference next month – how wrong I was in this assumption!

This is an active niche with much going on from one month to the next.

Thie thing is are the next generation versions going to blast through sufficient cancer cells with less toxicities than before or are they going to blow up a few early stage pipelines instead?

After all, it’s easy to forget more early stage agents will fail than succeed.

What kind of features ought we to be looking for and what can we learn from the latest round of company announcements ahead of the ESMO meeting next month?

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Riding the next IO wave or a damp squib at ESMO24?

Old Post Office in Barcelona

We’ve reached the point in the oncology R&D conference season where it’s hard to predict the outcomes of quite a few trial readouts.

Some folks might well reckon a correction is needed while others are focused one future.

Either way, we put a baker’s doxer of studies under the microscope to see which ones are destined for good data while others crash and burn.

Which agents fall into into which category?

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ESMO24 Preview 2 – Hurdles and Prospects

The Basílica i Temple Expiatori de la Sagrada Família in Barcelona

I’ve always found Gaudi’s gothic cathedral in Barcelona beautiful and inspiring inside despite its ugly gothic facade.

The way the light and space combine to produce a sense of awe and wonder is a nice way to forget the trials and tribulations in the outside world.

In our latest ESMO Preview we look at a particular niche, which has seen many changes in its landscape over the last few years, including some ugly data as well as areas giving greater hope for investigators and patients alike.

This year looks like continuing both trends in equal measure…

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ESMO24 Preview 1 – ADC challenges and opportunities

What’s on the other side of the window in Barcelona?

With the initial ESMO abstract drop, it’s time for our first Preview of this year’s conference from Barcelona.

Spain as a venue is rather apt considering they just won the European finals against England in Germany.

They have a thrilling and highly talented young side, is the same equally true of early stage drug development?

Part of the fun of the first ‘data’ drop is there are no data since only the titles are available for the following:

  • Mini orals (95 abstracts)
  • Proffered papers (60)
  • Regular posters (1742)
  • Trial in progress posters (97)
  • Posters (1589)

We usually cover a wide variety of topics over the summer, so it’s time for the first one on deck – let’s roll!

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Novel strategies for taking on advanced cancers

Signalling intentions… Tall Ships Race 2024 Turku, Finland

It’s an unfortunate truth very few currently available cancer therapies are capable of inducing durable complete responses in people with advanced solid cancers.

This is largely due to challenges such as tumour heterogeneity and acquired resistance or immune escape.

How can we change this situation for the better?

There are only so many targets to go around and existing modalities have their limits, thus what we need is some more innovative and creative strategies.

In this post we hone in on two such examples to explore what they and how they might make a difference…

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Red and green flags for RevMed’s RMC-6236

Is everything as bright and sunny as it first appears?

One of the many challenges associated with oncology R&D is picking out the red and green flags associated with early stage trials in order to handicap phase 3 outcomes.

The road to success is paved with many failures along the way.

KRAS has been a hot topic for a while now, yet much of the initial enthusiasm has finally been tempered of late thanks to shorter outcomes than some folks expected with the first generation of targeted therapies – with monotherapy no less!

It’s all too easy to forget KRAS was widely considered ‘undruggable’ or intractable until recently. This doesn’t mean the agents in this space get an easy pass though, far from it.

With new data now out on the first RAS multi agent in the clinic, what’s the story behind the results and what should we be looking for or wary of?

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Postcards on early oncology drug development

Mailbox by the Polar Museum, Trømso

It is the dog days of summer in many places, and as thoughts turn to vacations and time away from the office it seemed a good idea to write five postcards around topics catching our attention in the science and biotech/pharma news this past week.

Issuing a press release on a phase 3 trial on July 4 in America is never a signal of good news and in this post we’ve some analysis and commentary on why the trial was doomed from the start and what lessons companies can learn from it.

For scientists among our readership we also have some thoughts on potential new targets and for those in translational research,there are some early data readouts to contemplate, as well as some heartwarming news to finish.

The postcards also span a variety of topics from CAR-T cells to epigenetics, IO, and protein degradation.

Happy reading!

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