Biotech Strategy Blog

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

About Pieter Droppert

Here are my most recent posts

Posts by Pieter Droppert

Potential of Immunometabolism to Enhance CAR T cell therapy

One only has to look at the number of clinical trials to recognize that cell therapies are one of fastest growing areas in terms of cancer new product development.

Over the past several years we’ve seen many changes and improvements in continuous innovation regarding the development of CAR T cells.

What metabolic “treats” do T cells like?

There has been no shortage of novel ways to enhance their targeting, durability, efficacy, or ease of administration. Most of the early strategies have yet to translate into commercial products, but it remains an area an attractive area to investors hoping to repeat the returns seen with Juno and Kite as more competitors enter the field.

In the fifth post in our mini-series on novel approaches in the emerging immunometabolism niche, we’re looking at ways to metabolically reprogram CAR T cells, as well as what the future may hold for the next generation of CAR T cells in this context.

Like a postcard from one’s summer holiday, it’s an opportunity to offer a snapshot at a moment in time from our journey.

We were fortunate to have the opportunity to talk with a researcher who is actively at the forefront of this area. Dr Roddy O’Connor is working with Carl June along with various colleagues at the University of Pennsylvania, and he kindly spoke to BSB about his work.

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A novel way to target KRAS mutant lung cancer

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.

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Targeting Glutamine for Cancer Immunometabolism

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.

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Looking for Signals in Cancer Immunometabolism

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.

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A Journey into Immunometabolism and its Potential for Cancer Immunotherapy

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.

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Putting NK cells to work

Last week we talked about finding ways to make the T cells work harder and smarter – there are numerous ways to do this, but cytokines might be one interesting way to begin the search.

What about NK and other immune cells though, can we do the same with these too?

This week we are focusing on various cell therapy approaches with some academic and industry interviews to share, along with some analysis of arising issues as well as some new developments to review and discuss.

In the first of the series, we have an academic thought leader in the spotlight who had a few interesting points to make on novel cell therapies…

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

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Are gamma delta T cells ready yet for prime time?

Not in San Diego: We took a close look at the potential for targeting gamma delta (𝞬𝝳) T cells early last year in an extended mini-series looking at the landscape including some of the early companies leading the way in this niche.

Since then there’s been a raft of company related announcements and collaborations in recent months, highlighting the ongoing interest in this field.

In this post, it’s time to revisit the original landscape (link), as well as explore how well some of the biotech companies who are active in this space are navigating the R&D roller coaster.

We will also be discussing recent data presented at the AACR20 virtual meetings.

So what did we learn about gamma delta T Cell therapies at AACR20 – who stands out from the increasingly crowded pack?

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

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Will a novel way to target IL–18 be a winner?

Not-in-San Diego: The second part of the 2020 virtual annual meeting of the American Association for Cancer Research (AACR VM2) is over, and now the fun part of looking at some of the key data presented commences.

If you listened in to some of the sessions live like BSB did then you would have heard many of the chairs say how surprised they were to have 1,200 to 1,500 or more people listening live – AACR are to be congratulated on promoting access to science from around the world.

We all miss the personal interaction of a meeting but given the high cost of attending an annual conference, a virtual meeting does promote the democratization of science, and we are all for that. Given the ongoing uncertainties around the control of Covid–19, with all the travel and large crowds involved, it remains uncertain when we’ll all feel comfortable going to major conferences again.

One presentation that caught the attention of many at AACR VM2 including ourselves was data on a novel way to target IL–18 from the lab of Dr Aaron Ring (Yale), which was presented by his postdoc, Dr Ting Zhou at the meeting. A paper was also published simultaneously in Nature last week.

We’ve been following Dr Ring’s work on IL–18 for some time so it was good to finally see it published.

As part of our ongoing AACR20 coverage, Dr Ring kindly spoke to BSB to explain how his research led to the discovery of a novel way to target IL–18 for cancer immunotherapy as well as the plans to translate this into the clinic through a spin-off company, Simcha Therapeutics.

Will this novel way of targeting IL–18 be a winner? We take a closer look in this post.

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

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The Potential of CAR-NK Cells for Cancer Immunotherapy

This week the conference cycle continues with the annual meeting of the American Society of Gene and Cell Therapy (ASGCT) (Twitter #ASGCT20).

Due to the ongoing travel challenges and need for social distancing as result of Covid–19, one key annual immunology meeting originally slated for this month was AAI in Honolulu, which was sadly cancelled. Fortunately, ASGCT is being held as a live virtual meeting instead, so do check it out if you have a keen interest in this field.

One area we’re hoping to learn more about at ASGCT20 is cell therapy using natural killer (NK) cells. It’s an exciting and emerging area, which is attracting a lot of interest of late.

Those following the NK cell space will no doubt have seen the recent announcement of the collaboration between Kite/Gilead and Melbourne based oNKo-innate, co-founded by Prof Nick Huntington (@Dr_Nick_Bikes) and Dr Jai Rautella (Link to PR).

Other NK focused companies in the news include the licensing by Avectas of the CAR-NK cell therapy from Galway based ONK Therapeutics, founded by Prof Mike O’Dwyer (@MichaelodwyerMD) (Link to PR).

It’s definitely an exciting time to be an NK cell biologist!

In our ongoing series of expert interviews, we caught up with Prof Huntington from Melbourne to talk about the potential of CAR-NK cell therapies.

To learn more from our oncology analysis and get a heads up on insights and commentary emerging in the NK cell niche, including our latest expert interview subscribers can log-in or you can click to gain access to BSB Premium Content.

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Postcard 2 on Adoptive Cell Therapies from the AACR20 Virtual Meeting

The American Association for Cancer Research (AACR) is to be congratulated on turning their annual in-person meeting into a virtual meeting at short notice.

With over 60,000 registered attendees, the meeting is a success and has set the standard for others to follow this year. While we all miss the opportunity to meet and network in-person, a virtual meeting does democratize access to science for scientists and researchers who can’t afford to travel or attend every year and we hope that live-streaming will continue in 2021 and beyond.

Since the sessions are available to watch for free on demand, we’re not repeating the data but like a postcard are instead focusing on what stood out for us, adding some pertinent commentary or context, as well some of our key take homes from a cancer new product development perspective.

Whether you agree, disagree, or thought differently about the presentations, we’re here to provoke thinking and critical discussion.

In this latest postcard from AACR20, we’re focusing on highlights from the adoptive cell therapy session taking place earlier today.

To learn more from our oncology analysis and get a heads up on insights and commentary emerging from the first annual AACR virtual meeting subscribers can log-in or you can click to gain access to BSB Premium Content.

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