Biotech Strategy Blog

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

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In wave 3 of the immuno-oncology surge things have slowed down, partly due to a raft of combination trials yet to read out and partly because the reality has finally hit that tumour heterogeneity means there will be variable patient responses.

Just getting from room to room on time can be a real challenge with 40,000 other people present!

This complexity can come about in many forms… immunosuppression, alterations in gene functions, resistance and immune escape, to name a few.

If we want to help more people respond to these therapies then before we can rush headlong into another round of combination trials, we first have to go back to looking carefully at the underlying biology of the diseases and listen to what the patient’s tumours are telling us in order to fix things.

To accomplish this feat requires considerable time, energy, effort, and a lot of bioinformatics.

In this post we explore five key talks that highlight different aspects of biomarkers of response and mechanisms of resistance.  From there, we may see additional validation and prospective testing to determine how best to segment people so that they have the greatest chance of responding to the therapy administered.

One thing that most people don’t have these days is time, which is how we can help you because here’s a handy short cut to finding out more about five complex and diverse areas on biomarkers or IO resistance quickly and easily…

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Chicago – Having stayed until the last morning of the last day for a final expert interview and sessions on CAR-T therapy and metastatic breast cancer, there were certainly some interesting targets and findings to discuss in the post meeting analysis.

I particularly wanted to post some thoughts and commentary on the ongoing Macrogenics story around margetuximab, an anti-HER2 antibody that binds with elevated affinity to both the lower and higher affinity forms of CD16A, an Fc receptor.

In our last review in February, we noted that the company “could miss on PFS and have to wait for OS down the road,” which wasn’t far off given the rather weak PFS benefit of 0.9 months announced on May 15th.

We finally got to see the initial SOPHIA data presented at ASCO this morning by Dr Hope Rugo (UCSF), so what did we learn?

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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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Chinatown Chicago

One of the things we try to do on BSB is tread paths that aren’t well travelled.

It’s a bit like coming to Chicago and visiting areas such as Chinatown that are beyond the common tourist sights. It can take a bit of effort, but often delivers a memorable experience in the process.

In this final preview of #ASCO19 before the educational sessions start tomorrow, we’re offering up 10 abstracts that we think are underrated and noteworthy of closer attention.

Like any guide book our recommendations are subjective, but if you’d like to read more then subscribers can login or you can purchase access.

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Bispecifics in the garden? Who knows!

We’re continuing our preview of the ASCO 2019 annual meeting (Twitter #ASCO19) with a look at a fast-paced area of drug development that is attracting a lot of interest, namely the potential of bispecifics as novel cancer treatments.

On BSB we’ve been following this emerging field for the past five years or so, but at this year’s ASCO we expect to hear clinical data that may offer new insights.

If you’ve been in London this past week, then you may have been at the annual Royal Horticultural Society (RHS) Chelsea Flower Show, which features impressively designed show gardens built around a theme or location. They’re built with great attention to detail just for Chelsea, then at a few days they’re dismantled.

Large cancer meetings like ASCO19 are a bit like that too. We all come together for a few days to mix and mingle then go our separate ways again.

In the spirt of Chelsea, in this post we’re taking a look at what to watch for in the “ASCO19 bispecific garden,” if one were to be made.  There’s certainly a surfeit of choice to consider and like flowers, some may flourish under certain conditions, but not others.

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River Rhine, Mainz

Mainz, Germany: We’re back for Day 2 highlights from the 2019 Association for Cancer Immunotherapy (CIMT) annual meeting with a look at some insights emerging from some academic and industry talks, as well as gems emerging from the poster halls.

Much attention is focused on cancer immunotherapy clinical data, yet it’s also important to watch out for new developments.

These can take many different forms such as what are companies doing to meet those challenges with novel therapeutics, as well as understanding more detail about immune mechanisms, including evasion and escape as well as defining phenotypes based on different immune cell populations.

As we head into ASCO, let’s not forget that there’s some important learnings to be had elsewhere in the world before we get there…

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Mainz, Germany: A grey and gloomy day by the river Rhine has been brightened up by the quality of science on display at the 2019 annual meeting of the Association for Cancer Immunotherapy (CIMT) (Twitter: #CIMT2019).

Dr Nicky McGranahan presenting at CIMT 2019

We were last here in Mainz 18 months ago for the EACR-CIMT-AACR Immuno-Oncology conference.

Cancer immunotherapy remains a work in progress, however.

What’s increasingly becoming more important is understanding the science, in particular finding answers to critical “why” questions that help us to not only understand the biology of cancer, but also why some people respond and others don’t.

In this post, we describe some of the key highlights and have penned some thoughts on some of the oral talks and posters presented today.

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Following the success of anti-CTLA4 and PD(L)1 therapies over the last five years or so, there is much time and attention being focused on addressing a key question, namely – what’s the next viable checkpoint target?

There are quite a few possibilities emerging, although to be fair, some of them will no doubt go by the wayside over the next year or two.  There has already been quite a bit of attrition since 2015/16.  Figuring out which ones will be a target versus being a useful marker is also an important aspect of new product development.

Competition is a fine thing – as long as they’re going in the direction you want to go.

For most of our ASCO coverage over the last few years we have tended to include a variety of approaches in the pre-conference Preview series that can run from a tumour type, a up and coming modality, an emerging target, and various other ways of looking at or making sense of the sea of data.

Here, we take a look at an IO target that is receiving much interest and explore what we know and where this might be headed… and ask whether the early promise is living up to the billing in practice?

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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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