Biotech Strategy Blog

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

Posts tagged ‘AML’

An up and coming new player in CAR T cell therapy

At the recent AACR meeting in Chicago one thing that was a surprise was how many new players seem to be emrging in the CAR-T cell space, not to mention the plethora of targets being evaluated preclinically in both hematologic malignancies and solid tumours.

The CAR-T cell niche is becoming very competitive and gritty

If we thought the market was becoming competitive before with less than a dozen players, imagine how crowded it will get once many of the unknowns start to make their mark?

This situation also presents many challenges and opportunities for the new entrants, not just in terms of merely identifying new targets and preclinical research, but also in the need for quality control and manufacturing expertise plus clinical development.

We should also remember that immunotherapy is designed not to target the tumour per se but unleashes the immune system on the tumour. This means that lessons from one approach (e.g. checkpoint therapy) can be applied to another (e.g. CAR-T cell therapy) and vice versa.

Yesterday, we discussed CD123 from the perspective of a bispecific company, what about approaching the target with a CAR-T cell therapy? What other alternative targets are out that that may be useful to investigate in the clinic?

We decided to explore these issues through the lens of one of the up and coming players in the CAR-T cell niche and find out more about what they are doing, how they see things evolving in this dynamic environment and what their path to market strategy is…

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Targeting NK cells effectively in AML

Continuing our NK cell series, we turn to a different area of work within this niche, namely how cytokines can help boost effectiveness of the clinical responses in hematologic malignancies through their impact on memory-like cells.

Spring is in the air!

This is an important aspect to consider bearing in mind that while NK cells can be useful in attacking cancer cells, they are also notoriously more fickle and less durable than their T cell cousins in sustaining cytlotic effects.

How can this be fixed? What therapeutic approaches might be potentially useful in addressing the problem?

To find out more, we spoke to a learned clinician-scientist involved in research in this arena to learn more about what he had to say and also discover why a molecule they are working on in early clinical development is starting to look quite promising.

The good news is that it may also have utility in solid tumours as well, through the effects that it induces.

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Update on cytokines as novel cancer immunotherapy

In this post, it’s time to put your thinking caps on and empty your minds of any pre-conceived bias in order to play the modern version of Star Trek tridimensional chess aka IO combination trials.

Gems from the Poster Halls

Here we weave now together some important themes and highlight intriguing ideas that at first seem dissimilar, but actually have much more in common than many realise.

Data from bone chillingly cold poster halls of conferences in the distant past can come back and reviewed afresh in the light of new developments. The seasoned observer discards neither these findings or thought leader snippets of insights within nor forgets them in an instant, as many do after the hum of instant live reactions passes.

With oncolytic viruses and cytokines being much in the news of late, what can we learn about where things are likely headed?

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Syros CEO Nancy Simonian looks forward to an exciting 2018

As part of our #JPM18 coverage we like to feature up and coming companies to watch out for, one of these is Syros Pharmaceuticals (NASDAQ: SYRS). In this post we take a look at what’s on the horizon for the company in 2018?

Myelofibrosis has certainly been in the news this week with Celgene acquiring Impact Biosciences for fedratinib and both Celgene and Incyte presenting their annual update at the JP Morgan Healthcare conference in San Francisco.

Yesterday at JPM, Syros and Incyte announced a new collaboration to explore myeloproliferative neoplasms (MPN):

“… The companies have entered into a target discovery, research collaboration and option agreement. Under the agreement, Syros will use its proprietary gene control platform to identify novel therapeutic targets with a focus in myeloproliferative neoplasms (MPNs), and Incyte will receive options to obtain exclusive worldwide rights to intellectual property resulting from the collaboration for up to seven validated targets. Incyte will have exclusive worldwide rights to develop and commercialize any therapies under the collaboration that modulate those validated targets.”

Given the need to find new targets and potential combination agents to partner with JAK2 inhibitors such as ruxolitinib (Jakafi), this deal makes a lot of sense.

It also leaves Syros and Incyte with space to continue developing their existing pipelines in the usual fashion without any undue commitment or conflict.

Syros are a company we have been following for three years now, with several updates on BSB, including thought leader and C-suite interviews.

With new data presented at ASH and SABCS last month, it was a good time for an update on this topic, so we sat down with Dr Nancy Simonian (CEO) for a chat about where they are and where they are going with their current small molecule pipeline ahead of their presentation at JPM18.

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The science behind the venetoclax clinical trial strategy

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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ASH Preview 2 – Developmental Therapeutics

One of my favourite areas to follow in oncology research is Developmental Therapeutics, whether they be targeted, genomic, epigenetic or immune therapies. At some point, even currently approved products started off life in this category, either in preclinical research or in early phase 1 trials.

It’s almost like a primordial soup from which future pipelines spring.

Following these initial approaches over time can be useful in many ways – you can pick up new trends and emerging drugs earlier than most, and can also step back to see a broader picture of the landscape as it evolves.

While there are no formal developmental therapeutics sessions at the American Society for Hematology (ASH) annual meeting per se, that doesn’t stop the intrepid scientist from creating their own selection, in fact it’s a lot more fun this way!

That’s exactly what I’ve attempted here…

Be warned though, this year, the mix is much more complex and intriguing with a lot of interesting and, in some cases, novel targets to explore and consider, including the deeper and tricky protein-protein ones to hit, which are now receiving more attention as researchers find more creative and indirect ways to tackle the problem.

Our second ASH 2017 Preview goes deep into what for many BSB readers will be intriguing, yet for others… completely unknown.

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Some simply stunning cancer research for Journal Club

Over the last four or five weeks we have seen some truly remarkable research published by numerous cancer researchers around the globe… which means that it’s time for another Journal Club review of key research to feature some cool science.

Here, we have selected half a dozen key papers of interest in both solid tumours and hematological malignancies that are well worth reading and digesting.  The impact from many of these may well lead to new molecules being explored.  We also include at least one review paper for BSB readers to peruse.

While much of the focus is inevitably on lung cancer and melanoma of late, we also highlight important research in pancreatic cancer, aggressive lymphomas and AML.

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Update on CD123 and other viable targets in AML

Coney Island Roller Coaster

In the roller coaster of life that is oncology R&D, molecules come and molecules go… a rare few reach blockbuster heights while many others are quietly packed off to dog drug heaven, never to be seen or heard of again.

This is also very true of targets as well…

What about the in-between space?

Unfortunately, that’s where most molecules and cancer targets end up – into a deep black nothingness where we seek the high affinity targets with low grade side effects – and fall short in some way. It’s a frustrating place to be, to be sure.

One of these conundrums is compounds against CD123 (IL3Rα), which have been in the spotlight on and off this year and are turning out to be a rather mixed bag.

After our recent update on Cellectis and their CD123 direct CAR T cell therapy (UCART123), I wasn’t expecting to write any more on this until ASH in mid December. How wrong that prediction turned out to be!

Today we have quite a few things to discuss on this topic, so if interested in CD123 in hematologic malignancies and going beyond that to find better targets in AML then this is the poster for you…

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The dawn of a new beginning for Cellectis?

Paris – amazingly it’s now 3 years since we interviewed Cellectis (NASDAQ: $CLLS) CEO André Choulika and CSO Philippe Duchateau (See post: Can Cellectis revolutionise CAR T cell therapy):

Cellectis CSO CEO

Cellectis Senior Management – Drs Duchateau and Choulika

Since then, we’ve followed the company over time, including an interview with one of their leading scientists, Dr Julianne Smith at ASH 2014, followed by the initial results of their first allogeneic CAR T cell therapy UCART19 presented at #ASH15 by Professor Qasim.

It’s hard to believe 3 years have gone by so quickly! As regular readers know what we often do on BSB is follow stories longitudinally, so while in Paris for an Immuno-Oncology Summit we thought it a rather timely opportunity to revisit Cellectis and take stock of where they’re at and ask what the future may hold for them?

With the recent news that Gilead have acquired Kite Pharma, there’s going to be a lot of interest in what companies such as Cellectis are doing to bring allogeneic “off the shelf” CAR T cell therapy to market.

This is the penultimate post in our summer mini-series on gene editing and allogeneic CAR T cell therapy and features a candid interview with Dr Philippe Duchateau, Chief Scientific Officer, at Paris based Cellectis.

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BMT Tandem Cell Therapy Insights

Sunny Day in Orlando, FL

Orlando, FL was the place to be last week thanks to two specialist meetings in town: BMT Tandem 2017 #BMTTandem17 (joint meeting of ASBMT and CIBMTR), and the inaugural ASCO-SITC Clinical Immuno-Oncology Symposium #Immunosym.  Indeed, several speakers spoke at both events!

Throughout this week we’ll be writing about the insights we gained from the two meetings into the latest data and trends in immunotherapy, immuno-oncology and adoptive cell therapy.

We’re kicking off with cell therapy insights from the BMT Tandem Meeting. It’s the joint meeting of the American Society for Blood and Marrow Transplantation and Center for International Blood & Marrow Transplant Research. If you don’t already, do follow the ASBMT President for 2017-2018 Dr Krishna Komanduri, @drkomanduri. He’s actively involved in CAR T cell therapy trials in Miami.

It’s worth remembering that bone marrow transplanters led the way in the use of immunotherapy to provide cures for cancer. Today, the BMT transplant community are pioneering adoptive cell therapy, and in particular  CAR T cell therapy in multiple hematologic malignancies including ALL, NHL, CLL and Multiple Myeloma. This makes the annual BMT Tandem meeting one to watch for some of the latest cell therapy data.

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