Biotech Strategy Blog

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

Posts tagged ‘BCMA’

In the second part of our cell therapy series this week, we take on three quite different issues.

These include the following:

  • A new dual CAR in development
  • Where cell therapy may be heading and how to address the limitations
  • The Cellectis CS–1/SLAMF7 clinical hold

Not all CAR T cell therapies are going to end up as a bridge to transplant – some of them are clearly intended to be more efficacious than their predecessors – but along the way the trials, tribulations and clinical challenges continue apace.

These are all meaty topics to consider, so with out much further ado, let’s roll…

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Continuing our ASCO20 coverage with another Preview in the pre-meeting series, we turn our attention to a particular modality of keen interest to many of our readers.

In this latest article, we highlight ten areas within the niche and include an array of companies, both big and small, across Pharma and Biotechs.

Some of them have some nice data to share, others will be footnotes to the meeting, but who fits into what category and what can we learn from the abstracts upfront?

To find out more, we looked very carefully at the hints and nuance which inevitably grace the writer’s pen – it’s time to hone in on where are the flourishes and the crossings out this year?

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At the start of the New Year, Dr Carl June (@carlhjune) who needs no introduction as one of pioneers of Chimeric Antigen Receptor (CAR) T cell therapy tweeted that, “2020 will be the decade of cell therapy and genome engineering.”

So what does the next decade hold for CAR T cell therapy?

At the recent 2nd European CAR T cell meeting, jointly organized by EHA and EBMT, we asked the man himself to tell us more about his vision.

In Sitges, Dr June kindly spoke to BSB and shared his thoughts on where he sees the CAR T field going, some of the key challenges that will need to be overcome, as well as some of the opportunities to watch out for.

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Breathing fire into cancer immunotherapies with novel approaches

It would be all to easy an exercise to pick out our top 10 abstracts of any particular conference and share them, which tends to create a somewhat skewed perspective because there are often many pieces of research that we may wish to highlight for entirely different reasons, making the exercise rather limited in scope.

Instead, how about 10 cool or next generation approaches that could have an impact in oncology in the future?

This approach generated a quite different and really eclectic list that can also have existing approaches referenced in context, so that we can see where the puck is moving towards as opposed to merely following it.

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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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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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With the startling news this morning that Poseida Therapeutics are abandoning their IPO plans and pursuing a different tack with a $142M investment from Novartis to fund clinical trials for their BCMA-directed CAR T cell therapy program in multiple myeloma, our attention is focused yet again on the highly competitive BCMA niche.

Poseida’s data was revealed at ASH last December and with an ORR of 63%, the initial efficacy was a bit lower than we have seen from rivals Bluebird Bio and Legend/JNJ, although the Penn/Novartis construct reported disappointingly lower responses in a small cohorts of patients, which may explain Novartis’s interest.

There are also other companies/products in this niche including GSK’s ADC, GSK2857916, and Amgen’s T cell bispecific, AMG 420, plus plenty of others with BCMAxCD3 bispecifics who have earlier skin in this increasingly highly competitive game.

Is BCMA enough though?  Is it really the answer to multiple myeloma or are there other approaches that might be better?

Putting new CARs in the spotlight

What of the future for CAR T cell therapies in myeloma beyond the initial generation 2.0 constructs?

We saw a vision for how this market might evolve and sought out some experts to learn more about what they are doing in this niche – what they had to say was really interesting.

After all, as Wayne Gretsky would say, don’t skate to where the hockey puck is (now) but where it will be… that’s a great analogy one cannot resist borrowing for the future of cell therapy in multiple myeloma.

In our latest article, we go beyond BCMA to explore where we think the field might be going and why a tunnel focus on BCMA might not be such a great thing…

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We have been following the progress of various classes of molecules in the myeloma space here on BSB since 2010. These include traditional approaches (e.g. HSCT and proteasome inhibitors/IMiDs and various antibodies or ADCs), as well as immunotherapy (checkpoint blockade, CAR T cell therapy, oncolytic viruses etc).

Brick Lane Grafitti

There’s much going on in this space and it’s not only becoming extremely crowded and competitive (akin to 1L NSCLC), but there is a gradual trend towards convergence on many fronts, be they targets or modalities.

In our latest look at the myeloma space, we focus on several key areas of development – antibodies, CARs, and also highlight a new target that may be of interest…

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Continuing our up and coming biotech series, we now switch our focus from small molecules to immuno-oncology.

While big Pharma has garnered the lion’s share of attention (and revenues) from checkpoint inhibitors and CAR-T cell therapies, if we want to make a serious impact on solid tumours, especially the colder ones, then we are going to need to devise ways of jumpstarting the immune system where there are far fewer immune cells around to help do this.

There are many ways to achieve this aim, although the count is still out on how best to optimise combinations.

We’ve looked at various approaches over the last couple of years including chemotherapy, immune agonists, cytokines, STING/PARP/TLRs, NK cell checkpoints, T and NK cell bispecifics, and many many more.

Fortunately, most small biotechs have been focused on alternative targets that mght be seen as complementary to existing established therapeutics.

As we move forward towards a more regimen-based approach some of these will succeed while many will not, such are the challenges of oncology R&D where 90% of compounds unfortunately fail.

One challenge that has long been obvious though is that once clinical proof of concept has been established, another 10 companies will wade in quickly and dust down old molecules lurking in screening libraries that have been languishing in darkness waiting for their call-up. In the old days, a lead time of 5+ years before a competitor caught up with a rival drug was not uncommon.

Increasingly, it now seems there are mere months rather than years between approvals in the same class, an astonishing feat in a highly competitive and cut-throat business driven by generic erosion, noticeable pipeline gaps and the urgent need for continued topline sales growth.

In today’s hot seat, we have a small biotech CEO discussing his company’s IO pipeline and progress…. they caught my attention at AACR last year and I’m delighted to have the opportunity to learn more about what they are doing and how they are different from the existing competition.

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What latest ASH18 data jumps to our attention?

San Diego – It’s time to put another dozen studies in the spotlight and review what we can learn from the existing data with a view on where we’re headed in the future.

Today’s list covers a whole gamut of targeted therapies, bispecific antibodies, CAR-T cell therapies and other immunotherapies, what’s more we have a range of targets in the list too, and not the obvious ones either.

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