Biotech Strategy Blog

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

Posts tagged ‘KRAS’

The annual meeting of the American Association for Cancer Research (AACR) is an event we at Biotech Strategy Blog really enjoy writing about due to the outstanding depth and breadth of the scientific content.

The 2021 organizers led by program committee chair Prof Charles Swanton FRS are to be congratulated in putting together a meeting that has something for everyone involved with cancer research, whether you’re in academia, industry, or clinical practice.

While we may miss the personal contact of real life meetings there are many advantages to the virtual format, including the avoidance of scheduling conflicts, the ease of hearing and seeing presentations without worrying about the person in front or poor room audio quality, not to mention the ability to stop and rewind a presentation if you didn’t quite catch what was said. The virtual format definitely improves accessibility for those who are disabled or for whom English may be a second or third language.

When the world moves on to hybrid virtual/live meetings as looks likely in 2022 then we hope we won’t lose all the advantages of the virtual meeting concept. It’s outside the scope of BSB, but there is an opportunity to reimagine the medical/scientific meeting rather than simply go back to what we had before.

Spring flowers herald the start of a new cancer conference season

In this preview post we’re taking a look at the “on-demand” sessions available starting on April 9, 2021 – we’ve selected fifteen presentations which caught our attention. Some are by researchers we’ve interviewed on BSB, others are stories we’ve been following around a particular topic or target.

If you’re looking to go outside your own area of interest at AACR21 and are overwhelmed with choice then this post offers a few suggestions and explains why they should be worth watching.

To learn more about the hot topics at AACR21 and get a heads up on our oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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It feels weird to be covering the WCLC from Singapore remotely after remembering the rain in Spain at WCLC19!

If we look at the more mature phase 2 data now available for Amgen’s sotorasib (AMG 510) in KRAS G12C driven lung cancers, we learn there are quite a few nuances and subtleties at play. These aren’t always obvious in top line press releases or even in presentations until we consider the broader niche in which they are competing.

Amgen submitted the sotorasib applications to both the US and EMA health authorities in December.  With breakthrough designation status and clinical evidence of activity in an area of high unmet medical need, it’s hard to believe the approval won’t be forthcoming sooner rather than later, at least in the US.

Mirati is expected to showcase their phase 2 data later this year, so I would highly encourage people to hold off with cross-trial comparisons until we see how their more robust data look at the RP2D.

In the meantime, we can take a careful look at the latest Amgen data.  We do those not only from a BSB review but also through the lens of a company perspective and consider some of the key strategic issues we need to start thinking about…

To learn more about the WCLC20 data and get a heads up on our latest oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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The first day of ASH oral presentations brought some unexpected surprises from several quarters, both good and not so good.

In this second review of the highlights, we cover some important translational research, as well as various clinical studies in both AML and multiple myeloma.

The latter focuses on discussing some subtleties and nuances to watch out for in the BCMA CAR T cell space.  A number of people have been declaring ‘wins’ to different products across the board, but it’s way too early to call at this stage given phase 1 trials do not always predict what will happen in pivotal registration trials.  There are also some challenges to address along the way so we put these findings in context.

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

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A look at upregulated targets outside of the BCR signalling pathway and what small molecules are looking promising

In our final preview of ASH 2020 exploring key abstracts and what to watch out for this weekend, we offer the second half of our discussion around small molecules in early stage development.

There’s always a roller coaster ride in any early stage drug development and small molecule inhibitors are no different from antibodies, bispecifics, or even immunotherapies in this respect.

There are certainly some unexpected and surprising overlaps discussed and uncovered here plus also some novel combination approaches either being considered or which may potentially need to be considered in the future.

So what’s in store this time around?

To learn more from our oncology analysis and get a heads up on the latest insights and commentary pertaining to the ASH meeting — including our final Preview ahead of the meeting this weekend, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Gaudi Cathedral, Barcelona

It seems oddly surreal of my photo editor to remind me that on this day in the past we were in Barcelona (right) for some conference or other and this year’s EORTC-NCI-AACR Molecular Targets meeting (aka the Triple in industry parlance) was cancelled in Spain in favour of a virtual meeting, thanks to the ongoing pandemic.

There is no doubt that thinking big in cancer research is vitally important, but sometimes we have to consider the difference between building cathedrals for the long-term rather than building simple walls as short-term fixes.

Here we consider some examples in the context of oncology drug development and also open the monthly October BSB mailbag…

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

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What’s the elephant in the KRASi room?

It’s time to look at the latest update on KRAS mutation specific agents in clinical development as we turn the spotlight from the Amgen sotorasib data at ESMO to Mirati’s G12C selective agent, MRTX849, now known as adagrasib.

At the Targets meeting last year in Boston, Dr Pasi Jänne presented the initial findings from phase 1/1b the lung cancer cohort.  This time around we get to hear him provide an update on the combined phase 1/1b plus phase 2 results, plus there’s an additional presentation from Dr Melissa Johnson on the non-lung cancer cohort i.e. GI and other cancers.

Ahead of the presentation this morning (US east coast time), BSB caught up with Dr Jänne for his perspectives on the progress made and where things are headed in the near-term.  He offers a thoughtful and candid approach to tackling a hard to treat cancer subset with targeted therapy.

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

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We have two stories to share today from the EORTC-NCI-AACR Molecular Targets conference, which are posted separately owing to different embargo times.

The second posting later focuses exclusively on KRAS and Mirati’s turn in the spotlight.

Due to the embargo, it will not be available until 1545 hrs CET (1045 hrs ET) and will include some thought leader perspectives on the data.  I’ll add the link here in due course.

Developmental Therapeutics is often a cases of sunny days or stormy waters ahead…

Meanwhile, in the first post (below) we take a keen look at some of the new developmental therapeutics approaches coming through company pipelines.

Which ones shine might brightly and which ones lose their lustre?

As is often the case with early stage trials, translating rational science in preclinical setting doesn’t always translate well into the clinic when humans receive a therapy or particular combination of agents.

To this end, you might be surprised at how much PK/PD issues, half life, dosing/scheduling and other many other factors can severely impact the therapeutic window.

In this post, we look carefully at several targets we have been following preclinically for a while and finally initial clinical is either available or they are heading into the clinic – what can we learn from the presentations?

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

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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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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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A graceful white swan serving as an antidote the current COVID19 pandemic (black swan event)

In our the third of our AACR 2020 Preview series, we turn to the KRAS pathway to look at some new aspects, whether they be new targets, novel agents in development or even twists on the biology of the disease.

There’s quite a bit to discuss here, certainly more than I was expecting considering it was expected to be a down year by some after all the excitement of last year’s revelations and developments in the clinic!

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

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