Biotech Strategy Blog

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

The past year has seen hype and hope over targeting KRAS mutant cancers and many challenges still remain to be addressed. We’ve seen the emergence of selective G12C inhibitors, as well as others targeting SOS1:RAS upstream and even related pathways to address cross-talk such as SHP2 and ULK1, for example. The oncology R&D ecosystem is beginning to motor again as new competitors start entering the niche.

Riding the KRAS wave

To put things into broader perspective, however, despite all the positive news in lung cancer, consider the colorectal carcinoma data was less impressive than lung because of more complex, heterogeneous disease.

Meanwhile, Lilly recently announced the discontinuation of their selective G12C inhibitor, LY3499446, due to adverse toxicity, so clearly it is not all going to be plain sailing in this landscape!

Let’s also not forget the G12C mutation is not the only viable target in this context. People with advanced lung cancer can also present with one or more of several co-occurring mutations such as the serine/threonine kinase 11 gene (STK11) and kelch like ECH associated protein 1 gene (KEAP1), for example.

Unfortunately those presenting with both STK11 and KEAP1 mutations – independent of KRAS status – often have a poorer prognosis and there remains an unmet medical need for effective new treatments.

In this fourth postcard in our summer mini-series on the potential of immunometabolism for cancer immunotherapy, we’re taking a look at a novel way to target KRAS mutant lung cancer and, in particular, those with an STK11 and KEAP1 mutation who tend to do poorly on current therapies.

To learn more about the emerging area of immunometabolism and its translational potential, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

 

What do T cells want?

In the third post in our summer mini-series on immunometabolism, we’re continuing our journey by taking a look at glutamine as a target, and in particular, the potential of glutaminase inhibitors.

Cancer cells compete with immune cells for glucose and glutamine in the tumor microenvironment, and if the cancer cell wins then immuno-surveillance and anti-tumour immune response can be diminished. Of interest, glutamine addiction is commonly seen in cultured cancer cells.

This begs a critical question – can we target glutamine therapeutically in patients, and if so, what happens?

In this article we highlight an expert interview with Dr Jeffrey Rathmell, who is Professor of Pathology, Microbiology and Immunology at Vanderbilt, where he directs the Vanderbilt Center for Immunobiology.

Dr Rathmell is at the forefront of research into T cell fuels such as glutamine and has published preclinical work on early compounds in this niche, including Calithera’s glutaminase inhibitor, CB-839, for example.

He kindly spoke to BSB after the AACR20 virtual annual meeting where he chaired a session on Metabolism and the Tumor Microenvironment.

To learn more about the emerging area of immunometabolism and its translational potential, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

This is the second postcard in our mini-series on the emerging field of immunometabolism and the translational potential for cancer new product development.

Over the course of three weeks, we’ll be sharing six postcards from our journey, three of which are based around interviews with scientists at the forefront of research in this niche.

What did we learn about immunometabolism at AACR20?

In this latest post we’re taking a look at some of the signals at this year’s virtual AACR annual meeting, which as usual had a wealth of data on offer, offering as it does a window into the future of cancer drug development.

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

This content is restricted to subscribers

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.

This content is restricted to subscribers

It’s the dog days of summer in August, traditionally a time when many of us go on holiday and while that’s more challenging in the uncertain times of COVID-19, we at BSB are taking a break for the next three weeks as we recharge/renew for a busy autumn of virtual meetings.

We won’t be writing much about topical news or recent data for the next few weeks, but instead, while we’re taking time out we’ve prepared a six-part mini-series looking at immunometabolism and its potential for cancer immunotherapy.  We’ve run this kind of series every summer over the last couple of years and they’ve worked out rather well.

One of the things we did on Seasons 3 and 4 of the Novel Targets Podcast was to look at topics involving emerging areas of complex research, where we often didn’t know all the answers yet there were emerging data worthy of time and attention. Immunometabolism is certainly a topic which meets those criteria – it’s been on our list to do a deeper dive into for a while and here we are now, with some extended time to make the most of the opportunity to do it some justice.

We’re obviously dating ourselves in that we used to write letters or send postcards to friends and family from our holidays, this mini-series is very much in that style.

To be clear, this is not intended to be a comprehensive review of absolutely everything in the landscape, instead we’ll be reviewing some of the key concepts, showcasing important papers, and highlighting data at AACR20 that caught our attention. There will also be mention of a few emerging biotech companies in the field and for good measure we have three interviews with scientists at the forefront of research, which may have excellent translational potential to the clinic.

By the end of our three-week journey together, hopefully you’ll gain a greater understanding of the new product development potential for cancer immunometabolism and be better placed to put into context new data as it steadily emerges over the coming months.

In this first post, let’s set the scene by looking at immunometabolism and the role it plays in the fate, function, and fitness of T cells.

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

This content is restricted to subscribers

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.

This content is restricted to subscribers

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.

This content is restricted to subscribers

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.

This content is restricted to subscribers

In our latest company interview we continue our ongoing AACR series on various protein degraders and how they may be useful in hitting difficult targets where small molecule TKIs have struggled mightily for various reasons, which we discuss in detail.

The protein degraders are what we might call large small molecules – they have a large molecular weight in Dalton terms – yet despite their unwieldy size they do offer a number of distinct benefits, which could potentially lead to improved efficacy, reduced toxicity, and enhanced outcomes in the setting of both cancer and autoimmune disease.  At least this is nice in theory, but what actually happens in practice?

Can we learn from the preclinical rationale and experiments to get a sense of what might happen in the clinic?

Find out more about what one emerging young biotech are accomplishing on the protein degradation front in both hematologic malignancies and solid tumours…

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.

This content is restricted to subscribers

All aboard the BCMA train – or not?

No matter, this was an interesting one with a few twists in the tale. It also offers some additional context as to why GSK’s experimental BCMA ADC therapy, belantamab vedotin, missed out on a late breaker at ASH.

When you read the briefing documents you can quickly see why this might have been the case.

In the latest installment of this story – the last one was the late breaker than wasn’t at ASH19 – things turned out to be rather more intriguing than many may have initially realised…

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

This content is restricted to subscribers

Free Email Updates
Subscribe to new post alerts, offers, and additional content!
We respect your privacy and do not sell emails. Unsubscribe at any time.
error: Content is protected !!