Biotech Strategy Blog

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

Posts tagged ‘CLL’

Cambridge from Bay Bay Boston

Back Bay Boston

With the TARGETS meeting ending and ESMO soon to be starting up, I wanted to offer up a change of pace completely by highlighting some important new cell therapy research presented at the AACR Tumour Immunology and Immunotherapy meeting in Boston.

The CAR-T cell therapy space has certainly seen a lot of developments this year since we wrote about what was coming down the pike in February and here we are in the fourth quarter and the researchers in this niche continue to execute.

I suspect a lot of folks dismissed the first round of gene editing attempts for various reasons without really thinking deeply about why this might be the case and how the issues can be overcome.

This is not the case for the folks at the top of their game – they don’t give up, they go away and find out why things don’t work as expected, how we can overcome them, and importantly, improve on clinical trial execution…

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The first day of the 5th annual CAR- T cell meeting in Rotterdam turned out to be rather interesting indeed with a number of key presentations highlighting novel developments across a range of hematologic malignancies.

If we want to see some progress then we need to start developing new constructs with other targets beyond CD19 and CD20, which are applicable to B cell malignancies, CD123 and CD33 in AML, and BCMA in multiple myeloma.

By the way, sometimes gene edited allogeneic products might make sound scientific sense in the context of the disease being studied, but getting these through the various regulatory hoops and hurdles isn’t as easy as some might think.

Necessity is often the mother of invention requiring alternative strategies to creatively address the underlying challenges.

Here we highlight some of these developments and put them in a broader context of the evolving CAR-T cell therapy field…

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What’s ahead – a smooth journey or a slow moving train wreck?

One thought struck me quite vividly at ASH – what is old is new again.

This certainly seems to be the case in the niche at the centre of today’s story where we explore new developments emerging in the context of both what’s happening now and also what might lie ahead.

Pharma and biotech companies are always seeking to claim their sparkly new anti-cancer agent is both novel and better than what’s available, meeting some unmet medical need and improving on prior performance etc, but is the truth a reflection of their claims or not?

Positioning, as Ries and Trout taught us all years ago, isn’t so much about what companies try to spin tell us about their product, but rather it’s how a product’s identity is perceived in the mind of potential customers – in this case oncologists – in contrast to other products in the niche.

The way the problem itself is framed also tells us much about how the company view the situation, especially when they conveniently ignore other factors in their story.

There’s a lot going on this particular example, with various types of agents, different mechanisms of action, not to mention a variety of resistance patterns emerging.

Here we explore the latest clinical and translational data and evaluate where the opportunities are going forward…

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I can’t believe it’s two years since we last attended a medical or scientific meeting in real life, but the last time we had “boots on the ground” was in pre-Covid times, at a CAR T cell meeting held in Sitges, a small coastal town and former fishing village south of Barcelona with phenomenal light.

Organized jointly by the European Hematology Association (EHA) and European Society for Blood and Marrow Transplantation (EBMT), their annual CAR T meeting attracts “the great and the good” of cell therapy and back in 2020 we were able to interview luminaries such as Carl June, Stan Riddell, John Gribben, and Crystal Mackall in person.

This year’s CAR T meeting, now in its fourth iteration, offers a mix of clinical practice, practical advice for those running CAR T units, as well as offering keynote lectures and posters on new developments in the field. Attracting speakers from the US, EU and UK (sadly no longer part of the EU thanks to Brexit, a decision that is unlikely to make Britain great again), it has an inclusive feel about it with physicians, scientists, nurses, and patient advocates all part of the program.

Thanks to Omicron, EHA/EBMT had to pivot to a virtual meeting at the last minute, so everyone missed out on a jolly to Nice. The organizers are to be congratulated for making the meeting happen rather than postponing to the Autumn, as many have done recently thereby adding to what is already looking like a busy conference schedule for late 2022, presuming another Covid variant doesn’t come along to cause disruption…

So, what were the highlights from Day 1 of the 4th annual EHA/EBMT CAR T meeting and what did we learn about the direction of the CAR T cell field?

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Are we putting the cart before the horse – yea or neigh?

We’ve been following and writing about the CAR-T cell therapy space for over a decade now, with plenty of trials and tribulations along the way for both products and companies alike.

With the fanfare around the latest Penn data on Friday, we’re going to take a slightly different approach from the lay media and explore some of the ins and outs around the big strategic picture.

We’ll also be looking at some new data on multiple myeloma and CAR-T cell therapies. The latter are seeing the emergence of some interesting early studies of late…

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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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Orlando bound for ASH!

What is old is new again…

I have that distinct feeling of deja vu with the ASH asbtract drop yesterday on several fronts. It’s quite a few years now since we wrote about the runners and riders in the BTK/PI3K race to market in CLL and by weird coincidence a topic I was covering by interview yesterday on the RAS pathway came up in one of the first ASH asbtracts I was reading, which was rather spooky. Clearly Halloween came slightly late to Florida this year!

So how do all these disparate topics hang together and why are we excited about a small cap biotech company that is largely under many people’s radar?

They have some unexpected unifying threads…

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For today’s post, we’ve curated our individual highlights from the tsunami of data that flew thick and fast yesterday between science sessions, oral presentations and poster hall gems.

There were some pleasant surprises in the mix, to be sure, plus the weather brightened up immeasurably!

Yesterday’s lunch time ASH Dash was quieter than usual

Having whittled the number of trial highlights for review and critique down to thirteen key insights and learnings, what made our joint list?

To find out more, check out the post below!

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A warm welcome for Nobel Laureate Dr Jim Allison at CICON18

With all the furore and excitement over Dr Jim Allison’s Nobel prize award that hit CICON18 on Monday, it would be fair to say it was the highlight of the conference for many and it was pretty cool to be there in New York at the time.

Aside from the external news, there were also some intriguing developments to report on the CAR T cell therapy front – you might be forgiven for thinking that there’s not much new to say with two products now approved, but I have to point out that this is a very active area of research and there’s much going on here that is well worth highlighting.

Cell therapy is a bit like the twilight zone in the city that never sleeps – there’s a different vibe and energy about this particular research niche in oncology and quite a few new developments to discuss…

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Buried amongst the intense hurly burly of a major medical meeting such as the American Society of Hematology (ASH) are the unsung preclinical researchers whose work largely makes clinical development possible. After all, few sensible companies would bet on an expensive clinical trial program, especially in combination, without first knowing whether such an approach is rational or not and has a decent shot of working efficaciously.

At stake here is the potential for building a blockbuster cancer drug niche by niche.

Venetoclax (BCL-2 inhibitor) got off to a somewhat slow start compared to say, ibrutinib (BTK inhibitor), which had a much broader initial indication and a lower risk of tumour lysis syndrome (TLS), yet it may actually have a wider application across multiple hematologic malignancies. This could well end up as one of those classic tortoise versus hare stories in the long run.

Back in 2013, we posted five interviews conducted with a range of experts including:

  • Dr Oliver Sartor (prostate cancer)
  • Dr Susan O’Brien (CLL)
  • Dr Deepak Sampath (BCL-2 and ABT-199)
  • Dr John Jenkins (then deputy director at the FDA)
  • Dr Renier Brentjens (CAR-T cell therapy)

To put this in context, consider that we just recorded 15 interviews at ASH this year alone!

As regular readers know, we like to follow people and R&D stories over time, so while in Atlanta at ASH17 we took the opportunity to move a particular story forward – we wanted to learn where Dr Sampath and his colleagues are now and also where they are headed next. This gives readers a head start on anticipating what future clinical developments might be mentioned at JPM18 by either Genentech/Roche or AbbVie.

In our latest expert interview, we pick up and continue the discussion with Deepak Sampath to find out what’s happening with venetoclax four years on… it turns out quite a lot and makes for very interesting reading indeed.

Dr Deepak Sampath (Genentech)

Curious to now more about what this scientist and his work in BCL-2 targeting is all about?  Check out this short excerpt:

 

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