Biotech Strategy Blog

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

Posts tagged ‘AMG 510’

ESMO19 Preview 3 – Tackling immune suppression

It has to be said that this is one of the most jam-packed ESMO schedules that I’ve seen in a while!

Usually one has a few sessions they are interested in and lots of ‘free’ time to conduct interviews. That is definitely not the case this year with even parallel sessions at the same time as the Presidential (plenary) symposia, making for some very hard choices that need to be made.

Barcelona

Immune suppression can take the form of many targets – just taking out one of them may not be enough

As we start to see a renewed focus evolve on how to make immunotherapy work in or help more patients, there has been much attention on what we can learn from the addition of chemotherapy, additional checkpoint targets, immune agonists, various innate targets from KIR and NK cell checkpoints to TLRs and STING, neoantigen and dendritic cell vaccines, a telephone directory of cytokines, oncolytic viruses, etc etc to name a few, all with varying degrees of success.

What about exploring the inhibitory factors that induce immune suppression?  If we can reduce the cloaking and hostile tumour microenvironment, would that lead to more effectiveness with checkpoint blockade?  Maybe, maybe not.

In principle, it’s a sound idea yet these factors are both broad and incredibly varied in scope as a topic as to seem overwhelming at first.  The good news is that there are some emerging targets and hints of activity to come that are slowly beginning to emerge, making ESMO a good place from which to take stock of some new early stage developments.

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Targeting KRAS – Highlights from WCLC 2019

Chariots of Fire in Barcelona?

Barcelona – Gosh, what a weekend chock full of lung cancer data at the World Congress on Lung Cancer hosted by the IASLC!

There’s nothing like a bit of controversy to get riled up or crash with disappointed hopes under the weight of expectation, but if we go under the hood and look carefully, what do we find?

There was a lot of topics that we’re going to cover the important highlights and learnings in a two parter series – today we focus on KRAS with targeted therapy, while tomorrow we look at other topics of interest, both targeted and immunologic.

Without much ado, let’s roll with the Amgen update as there are many subtleties and nuances to consider…

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A look at Amgen’s early oncology pipeline

Continuing our bispecific mini-series, we now switch from small to large biotech with a look at what Amgen are doing in this niche. They have both regular bispecifics, as well as T cell bispecifics in their early pipeline.

Our latest company interview focuses on several early phase 1 new product developments.

Aside from the BiTEs, we also discuss the clinical program with one of their most promising small molecules, AMG 510, a KRAS selective inhibitor that has been drawing much attention since the chemical structure was unveiled at AACR earlier this year.

There was much ballyhoo and yet more garish headlines in the media at ASCO regarding ‘Amgen showed it had developed a medicine that shrank tumors in 50% of lung cancer patients’ – in 10 patients. Was it really 10 people or a much higher number if we consider intent to treat amongst evaluable patients? Then of course, taking a small sample size into consideration, the next 10 might produce quite different results. We might also see resistance set in down the road (e.g. at 9 to 12 months as we have with BRAFi), so these are really very early days, something we pointed out during the daily ASCO coverage.

To be clear, I can say that both companies included in yesterday’s (Neon Therapeutics) and today’s (Amgen) articles were sensible, thoughtful, and well measured in how they handled the data rollouts, but the media frenzy that occurred with each is quite something else.

Since we had quite a few BSB readers ask about both sets of data, having discussed Neon’s yesterday, today we offer an interview with an Amgen exec at the heart of their early stage programs…

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Manic Monday at ASCO19!

Chicago – here we are with highlights and insights from Day 4 of #ASCO19 and time is running down on this meeting with just half a day to go – whew!

One of the highlights of medical and scientific meetings we go to is meeting early career researchers, especially those who are doing translational research.

On Monday at ASCO19 we particularly enjoyed talking with Dr Wungi Park (@W_Park_MD) from Memorial Sloan Kettering Cancer Center who presented a poster on homologous recombination deficiency (HRD) as a biomarker in pancreatic cancer (abstract 4132).

We look forward to hearing more from him and colleagues as data is generated from the clinical trial they plan to start later in this year to investigate this further. Translational research in action!

What were some of our other highlights of Manic Monday at ASCO19? We’ve shared a few in the post below for BSB subs.

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Challenges of targeting KRAS G12C and why Amgen’s AMG 510 may not be a winner

Henry Moore sculpture – looks like a protein binding pocket!

Cambridge, UK – It’s somewhat ironic that we headed across town today to chat with one of the world’s leading cell biologists on MYC and RAS with a post on KRASG12C inhibitors almost ready in the bag. More on that interview in a future mini-series.

There are a number of nuances and subtleties involved in this niche, which have been somewhat lost in the frantic hype over hope melêe of late.

This review discussing KRAS and various other co-mutations such as LKB1/STK11 is a long and thorough one,, and perhaps rather contrarian in nature.

That said, I do feel that it is very important to highlight a lot of issues that are being ignored in the rush to declare the latest expected winners and losers or even potential blockbusters, if the breathless signals are to be believed.

If nothing else, there are certainly several key issues that could have a bearing on the clinical results in patients that are worthwhile highlighting for discussion and adding to the watch list because some of these factors may well take time to develop.

This is one of those ‘Ground Control to Major Tom – take your protein pills and put your helmet on’ moments… Actually, I may well be needing the helmet as protection if the analysis and commentary turn out to be unpopular!!

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