Biotech Strategy Blog

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

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ESMO20 Preview 4 – Targeted therapies to watch out for

Not in Madrid – with the global pandemic continuing to exert a significant effect on the cancer conference season, the annual meetings continue apace virtually.

Plaza de Cibeles, Madrid

For this year’s ESMO meeting we have already covered immunotherapies, both early and late stage pipeline highlights and now it’s time to explore what to watch out for over the weekend on the early to mid stage targeted therapy front.

The good news is there is some potentially practice changing data being presented, as well as some novel approaches in preclinical development emerging. These should be hitting the clinic in the near to medium term future.  On the other extreme is the more common problem whereby a few agents are showing signs of not holding up to their early promise/hype.

Let’s now take a look at what we can learn in the fourth and final ESMO Preview for 2020…

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

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ESMO20 Preview 3 Developmental Therapeutics – IO therapies

Remember the good old days at ESMO17 in Madrid? Sadly there’s no face to face networking at this year’s ESMO20 virtual meeting!

In this third ESMO 2020 Preview the focus is on early stage immunotherapies – we’ll cover targeted therapies in a separate review article.

As new regimens evolve involving multiple immune targets, this complexity brings with it a greater need to understand cell-cell interactions – not just immune cell relationships, but also oncogenic, metabolic, and even epigenetic ones. How do they all fit together and what happens when we interfere with those relationships therapeutically?

Often the simple answer is we don’t know until we head into the clinic, I’m afraid.

Beyond the obvious phase 3 IO readouts in the various Presidential symposia and Proffered oral sessions there are quite a few emerging ideas – old ones with a twist as well as entirely new ones – which we can consider and discuss.

Here, we highlight five key IO areas related to cancer immunotherapy and explore the various concepts as preparation for the upcoming meeting…

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

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ESMO20 Preview 2 – New Targets, New Opportunities

Sunset in Puerta del Sol, Madrid

Not in Madrido – In our latest ESMO20 Preview, we take a look at five emerging areas of cancer drug development involving early stage pipelines and highlight some important features and benefits to watch out for.

These topics won’t be on everyone’s radar, especially if the focus is on the big phase 3 trial readouts, yet they can teach us much about new combinations and future pipeline evolution.

Who’s actively moving novel approaches along and who’s sitting on their laurels?

After covering biomarkers to watch out for yesterday, we now take a dive into what’s looking interesting in terms of novel targets and the fresh new opportunities for the not faint of heart…

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

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ESMO20 Preview 1 – Key progress in biomarker development

Scaling the ramparts in Real Madrido

It feels slightly surreal to be writing about this year’s annual ESMO confab instead of attending in person in Madrid, Spain.

While much of the time and attention at ESMO is usually focused on the major phase 3 readouts from various clinical trials, we will be covering these during the meeting as they are presented to avoid repetition since many of the topline company trial results have already been announced.

In this year’s conference Preview series, I wanted to take a step back and explore early new product development in several forms:

  • Biomarkers and potential new ways of predicting outcomes in development
  • Emerging novel targets of interest
  • Developmental therapeutics – trials and tribulations

This initial review will tackle some important developments pertaining to various biomarkers of interest.

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Encouraging progress in immunometabolism

For the final postcard in our 2020 summer mini-series on the potential of immunometabolism in oncology R&D, we’re taking an in-depth look at the ways in which metabolic programming can overcome immunosuppression in the tumour microenvironment (TME), as well as looking at additional novel ways in which the fitness of T cells can be impacted.

We’ve already covered glutaminase, arginine, p38 and others, yet there are other metabolic effects to consider too, as we discover in our latest expert interview.  In the penultimate postcard, we looked at mitochondrial phenotypes and how they can impact both mitochondrial and T cell fitness, which are important aspects in making adoptive cell therapy (ACT) based approaches such as TILs and CAR-T cell therapies more effective.

Deep thoughts on immunometabolism and how it can impact antitumour response

These themes show up yet again, but in a rather different context because T cell fitness can also impact immune checkpoint blockade, oncogenic targeting, as well as transcriptional and epigenetic approaches.

As much as we have been slowing building up the evidence during this series, in the finale it’s now time to kick up things up a notch or two and draw some unifying ideas together.

We accomplish this feat with a rising young star in this particular niche, Dr Ping-Chih Ho, who is at the University of Lausanne.

He kindly spoke to BSB about his pioneering and prolific research, some of the critical questions he has sought to answer, plus what he sees are important future directions to consider in metabolism research.

To learn more from our oncology analysis and get a heads up on insights and commentary emerging on immunometabolism, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Pillars of future strategies in tackling aggressive lymphomas

Are new pillars emerging in DLBCL?

It’s time to take a short break from the immunometabolism mini-series and turn our attention to aggressive lymphomas such as diffuse large B cell lymphomas (DLBCL).

This week heralded the latest AACR virtual meeting on Advances in Lymphoma in conjunction with iCML.  There were plenty of science focused talks to listen to and learn from, including new developments in oncogenic targeting.

What if we can learn from what the patients underlying biology can teach us in terms of more rationally designed clinical trials?

We know these are diverse and heterogeneous tumours, but this doesn’t mean we can’t take a more precision medicine approach to treating patients.  What can we learn from early trial readouts and genetic analyses?

It turns out, the answer is quite a bit and more information might be available at the forthcoming ASH meeting, so let’s look at what we can piece together from the available data now…

To learn more from our oncology analysis and get a heads up on insights and commentary emerging on aggressive lymphomas, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Building up a storm against resistant solid tumours

Can we build up a storm against hard to treat cancers?  The initial evidence suggests, yes we can!

Today’s focus is on an emerging new biotech company with potential to make an impact in difficult to treat solid tumours with a more selective and focused approach to oncology drug development.

We’ve talked about the so-called ‘drugging the undruggable’ targets in the past, but what if we could circle back and use a different approach in combination with existing selective inhibitors currently in the clinic?

These possibilities – and others – caught my attention and they may pique yours too, so what’s this all about?

To learn more from our oncology analysis and get a heads up on insights and commentary emerging on protein degradation, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Controversial developments in pancreatic cancer

It’s the dog days of summer and time for some meaty controversy to read!

For the longest time there have been several cancer types which have been incredibly difficult to treat therapeutically.

Metastatic melanoma and non-small cell lung cancer (NSCLC) both used to be in this category, as did glioblastoma and advanced pancreatic ductal adenocarcinoma (PDAC).

We have made great strides in changing the face (and more importantly outcomes!) for people with both metastatic melanoma and lung cancer, so what’s happening on the pancreatic cancer front?

The last two years gave certainly thrown up a series of disappointing clinical trial readouts such as RESOLVE, HALO–301, CanStemIIIP, and SEQUIOA, for example, where in each and every case the findings favoured the control arm of gemcitabine plus nab-paclitaxel over the experimental arm in terms of improving survival.  Not one of them was able to raise the bar and show a significant improvement over standard therapy, which is pretty disappointing.

So what can be done to change the face of PDAC?

If we want to improve further then we need to go back to basics and enhance not only our understanding of the funadamental biological mechansisms and processes, but also the models we use to interrogate the systems involved.

In this post, we look at six key new areas of research in PDAC and explain what we’ve learned and why they matter if we are to see new therapeutic developments arise from the ashes of the past…

To learn more from our oncology analysis and get a heads up on insights and commentary emerging on pancreatic cancer, subscribers can log-in or you can click to gain access to BSB Premium Content.

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What’s the skinny on a new IO target in oncology R&D?

When the boat comes in

Much has been written about new and emerging immuno-oncology targets where we can add new targeted agents to existing immunotherapies – after all, quite a few have already tried and failed in clinical trials to shift the survival curve upwards and to the right.

Can it be done?

I firmly believe so, but this endeavour is going to take the whole field much time and energy, as well as quite a few iterations in molecule and trial design.  No one knows what the next big target is though, but when they do it will be a bit like when the boat comes in – you know it when you see it.

In the spotlight today is a relatively obscure target we have written about perhaps once or twice before and now there is suddenly burgeoning interest in this subniche with a couple of players already active in the space.  Will there be others? Maybe, it will likely depend on how the phase 1 trials pan out.

We have attempted to cover a couple of key questions:

  • What can we learn about the science and research conducted thus far?
  • Why is a big biotech company suddenly interested in this target?
  • Which tumour types look like being important?

Most importantly, though, a long time reader wrote in and asked why on earth is there sudden interest?  Will start a new stampede?  Who are the competition?

Good questions, and now we get to set the scene to explain what’s what and why the target matters…

To learn more from our oncology analysis and get a heads up on insights and commentary emerging on an emerging IO target, subscribers can log-in or you can click to gain access to BSB Premium Content.

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A new dawn for epigenetic therapy in oncology

A new dawn or a rapid sunset for epigenetics in oncology R&D?

Epigenetic therapies have had somewhat of a chequered history in oncology R&D, but new targets are always cropping up to tempt us to look further.

One emerging target we’ve come across – this is only the fourth mention here since January 2019 – is starting to gather steam with new players entering the landscape, as well as emerging preclinical and clinical evidence suggesting it might be well worth a serious look.

Here we look at the potential role this epigenetic target may have to play in a variety of difficult to treat cancers, as well as how it could enhance existing therapies in new combination approaches.

Could we combine these inhibitors with chemotherapy, with immunotherapy or DNA repair approaches?  How does the therapeutic window stack up?

We look at the latest evidence from several sources and discuss where the opportunities might lie…

To learn more from our oncology analysis and get a heads up on insights and commentary an emerging area of epigenetics, subscribers can log-in or you can click to gain access to BSB Premium Content.

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