Biotech Strategy Blog

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

Posts from the ‘Hematology’ category

The dog that didn’t bark

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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In Plain Sight

ASH19 in Orlando, FL

Orlando: In the second of our ASH19 reports, we offer a comprehensive and in-depth look at important data presented over the weekend where we breakdown some of the key findings or trial readouts, which are likely of interest to many readers given the heightened attention on novel therapeutic approaches.

Whether the hematologic malignancy is myeloma, leukemia, or lymphoma, we have been rather spoiled for choice in selections for hot topics to discuss this year, so the series will likely run all week!

Here’s the second of our detailed ASH notes…

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Friday Scientific Workshops are the Perfect Warm-Up act to ASH19

Friday at #ASH19 – remains of the day or hope springs eternal with sunrise on Saturday morning?

Orlando: The annual meeting of the American Society of Hematology or ASH (Twitter #ASH19) is one of the four key Majors on cancer-related related research meeting circuit that BSB attends each year.

Just as golf has the Masters, the US Open, the Open, and PGA championships, so those on the cancer new product development circuit attend AACR, ASCO, ESMO, and ASH.

This year ASH is in sunny Orlando where you have to compete with the tourists for Uber rides if you want to venture to restaurants or events in the area.

Friday at ASH has traditionally been associated with the satellite symposia, colloquially known as “Super Fridays” that CME companies or organizations such as the Leukemia Lymphoma Society have traditionally run, but in recent years ASH has put on its own Friday events to compete with both the industry satellites and also academic events such as the BMT Winter Workshop we have attended in the past.  More choice is good on one hand, but bad on the other in that something has to give way.

Ron Levy (Stanford) and Stephen Ansell (Mayo) blazed the trail a few years ago with their Friday Scientific Workshop on Tumor Immune Interactions in Lymphoid malignancies. Regular BSB readers may recall the interview at ASH16 with Dr Levy where he reviewed some of the data in that year’s workshop (See post: Targeting the tumour environment in lymphomas.)

This year on Friday at ASH19 there were multiple scientific workshops you could attend. What were some of the presentations that caught our personal attention, what can we learn from them and why did they matter?

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9 up and coming non-T cell based immunotherapy approaches

Orlando

Yesterday we looked at ten innovative approaches centred around T cell-based developments emerging from the American Society of Hematology (ASH) meeting that is taking place in Orlando next month.

Let’s not forget, however, that there are also other immune cells, including NK cells and quite a few others, which can be manipulated into cancer therapeutics for the treatment of hematologic malignancies.

Some of these are intriguing early preclinical research that may form next generation technologies in the future, while others take the form of up and coming early clinical data that readers may be interested to learn more about.

Here we highlight nine emerging immunotherapy approaches to consider that don’t involve T cells…

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New developments in targeting the B cell receptor pathway

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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Eyes on CAR-T Cell Therapy in Europe – Future Directions

One of the delights of going to a major medical/scientific meeting such as the recent European Society for Medical Oncology (ESMO) Congress in Barcelona is that there often meetings going on around it, which offer unique and novel perspectives.

For example, on the Thursday before ESMO19 there was a one-day workshop on “Breaking through emergent immunotherapy and immune targets in cancer.”

Dr Manel Juan Otero presenting at the FLS Science symposium

Organized by FLS Science, it took place at the Casa de Convalescència in Barcelona. The program featured a mix of Spanish immunologists and clinicians, along with some leading US researchers including Dr Tom Gajweski (Chicago) and Dr Antoni Ribas (UCLA).

It was definitely well worth attending and I encourage you to look out to see if the organizers run the again meeting before ESMO20 in Madrid next year.

One of the most interesting speakers at the meeting was Dr Manel Juan Otero (right) who heads up the section of immunotherapy at the Hospital Clinic of Barcelona.

In his talk, he spoke about the “Future Directions for CAR-T Therapy” in Spain, which turned out to be a dramatic one with unexpectedly broad European implications.

During a lunch break at the meeting, Dr Juan Otero kindly spoke to BSB about his plans, which could have an impact on commercial CAR T cell therapy companies such as Novartis and Gilead.

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Key highlights on lymphomas from iCML

Lugano: This post offers a rundown and synopsis of a wide variety of lymphoma trials across different subsets coming out of the 15th International Conference on Malignant Lymphoma (iCML) being in Lugano, Switzerland this week.

Lugano is a glorious place to hold a meeting!

The meeting is held every two years on odd years, usually after the EHA conference.

As such, this review may well turn out to be a useful reference point for later offering background and context for the upcoming ASH meeting in December, since there will likely be additional trial updates and readouts in Orlando.

Some of the updates on the early phase 1/2 trials reference preclinical posters from old AACR meetings circa 2012–2014, which is why the Gems from the Poster Hall series can often turn out to be useful predictors of later clinical trials performance!

There’s a lot to cover and discuss this year and some intriguing developments under the radar…

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The value of biomarkers in rescuing oncology R&D

Amsterdam – this weekend it’s time to showcase some important updates in hematology from the European Hematology Association (EHA).

It’s really hard not to like continental Europe when you see scenes like this from a major conference:

T cell lymphomas is not a topic we cover very often but it looks like it will receive attention here three times in a month with news from Corvus at ASCO and now an update on the intriguing story on CXCL12-positive AML and PTCL from Kura Oncology.

We’ve been following the latter story for a while now and after the previous looks at the rationale behind the translational data, it’s now time to explore what happens in clinical practice from their ongoing phase 2 clinical trial…

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New developments in Multiple Myeloma

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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Potential of CAR T cell therapy in CLL

Standing from the crowd in refractory CLL?

Last year the two FDA approvals of tisagenlecleucel (Novartis) and axicabtagene ciloleucel (Kite/Gilead) CAR T cell therapy for hematologic malignancies such as pediatric acute lymphoblastic leukemia (pALL) and non-Hodgkins lymphoma (NHL) have captured a lot of attention.

It’s worth remembering, however, that back in 2010 the first patient who had a dramatic response to CD19 targeted CAR T cell therapy was actually a gentleman with advanced chronic lymphocytic leukemia (CLL), the case study of which was subsequently published by Porter et al., (2011) in the New England Journal of Medicine.

We’ve been following CAR T cell therapy and its potential in CLL for some time now, with all the successes, trials and tribulations along the way.

Dr David Porter (Penn) told BSB earlier this month:

“The very first patients we treated are now eight years out from their infusion, a little over eight years, and still in remission, still doing extremely well with no evidence of disease or progression, never had any other therapy. So, I think it’s become very clear that for some patients this is effective in the far advanced setting.”

It’s now two years since we last spoke and it was a great pleasure to reconnect with Dr Porter. As he told BSB at ASH in San Diego:

“One way you make it better is to understand why it’s working and why it’s not.”

What have we since learnt about the potential for adoptive cellular therapy in CLL and what new insights did we gain from new data presented at ASH18? The answers may well surprise you.

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