Biotech Strategy Blog

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

Posts tagged ‘Multiple Myeloma’

All aboard the BCMA train – or not?

No matter, this was an interesting one with a few twists in the tale. It also offers some additional context as to why GSK’s experimental BCMA ADC therapy, belantamab vedotin, missed out on a late breaker at ASH.

When you read the briefing documents you can quickly see why this might have been the case.

In the latest installment of this story – the last one was the late breaker than wasn’t at ASH19 – things turned out to be rather more intriguing than many may have initially realised…

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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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In the fourth part of our mini-series in novel targets and agents in development we turn to novel cell therapy approaches that are perhaps under the radar for many observers.

While these might seem bleak times during a pandemic, there’s always a silver lining somewhere

While much attention has been focused on antigen loss or downregulation of the target wih adoptive cell therapies, research continues to evaluate various solutions to the problem.

One obvious way is to develop dual CARs or target multiple antigen targets of relevance to the tumour type being investigated.

There are other potential solutions being looked at, both in preclinical animal models and in translational work using cells from people treated with HSCT or CAR T cell therapies.

Here, we look at an alternative immunotherapy approach, which with time may have utility in both hematologic malignancies, as well as solid tumours…

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The annual ASH Dash often ends up with crowds waiting for the poster halls to open up – a daily scene captured from ASH19

With coronavirus and COVID–19 pretty much dominating attention and space in the global news on a daily basis lately, I am vividly reminded that not too long ago in December we attended the annual meeting at ASH in Orlando to experience busy scenes like the one on the right…

Imagine those packed crowds now in the current context – it doesn’t bear thinking about!

Which is why all of the oncology conferences we had been planning to attend this year are one-by-one postponing or outright cancelling their events until next year. This is going to create a lot of challenges for companies in terms of data release and presentations, to be sure, but what matters more is reducing the risk of the infection spread in order to limit the risk of serious cases developing.

The good news is that we do have a huge backlog of oncology data – novel targets, new agents, and emerging companies – to write about and share with our audience. There’s always a silver lining to be had if you look carefully enough.

Here’s one such example – a novel cancer target, agents in development, and an emerging company to highlight too…

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When should someone receive CAR T cell therapy? How do we identify who will benefit most or who will be most likely to fail? Those are some of the questions we’re considering in our latest expert interview.

As we see the landscapes around aggressive lymphomas and multiple multiple evolve and change with more near-term CAR T cell therapy approvals coming, so too do the clinical questions surrounding the optimising of these novel approaches.

Prof John Gribben, President of EHA (right) at CART2020 in Sitges

At the EHA/EBMT 2nd European meeting on CAR T cell therapy, BSB spoke with Professor John Gribben. He’s the current President of the European Hematology Association (EHA) and holds the Gordon Hamilton Fairley Chair of Medical Oncology at St. Bartholomew’s Hospital, Barts Cancer Institute, Queen Mary, University of London.

One of his messages was when considering CAR T cell therapy, it’s a delicate question of balance.

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What do cancer drug development and Sherlock Holmes have in common?

The simple answer is that sometimes you can gain insights by looking at what did not happen.

Will belantamab mafadotin stand out in the crowded BCMA space?

In 1892 Sir Arthur Conan Doyle wrote a short story about the disappearance of a famous racehorse the night before a race. What was curious about the incident was that there was no barking from the watchdog when you might otherwise have expected it, suggesting the dog knew the thief…

Can we follow the same inductive reasoning when it comes to cancer drug development? Are there things we would expect to see, but don’t? If so, what inferences can we draw from them?

In this post we’re taking a closer look at the latest data for GSK2857916 (now belantamab mafadotin), which in many ways was “the dog that didn’t bark” at ASH19.

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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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We have written about a huge variety of different approaches to cancer research since 2006 but few are as intriguing as using pathogen-based approaches involving viruses or bacteria to stimulate or re-activate the immune system. After all, when such foreign bodies break through the physical barriers and enter the bloodstream, the immune system instantly springs into action to tackle them.

Can this knowledge be used effectively in the design of anti-cancer therapeutics?

We have seen some promising initial results with oncolytic viruses, but what about bacterial based approaches?  Can a different approach to drug scaffolds yield improved results?

Here, we look through the window at a novel platform using immunotoxins in early development that may well pique a few people’s interest and offer our latest thought leader interview discussing the approach…

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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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