Biotech Strategy Blog

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

About Pieter Droppert

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Posts by Pieter Droppert

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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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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The keynote address at the 2018 CRI CIMT EATI AACR International Cancer Immunotherapy Conference in New York last month was given by Ignacio Melero (Pamplona). Professor Melero gave an engaging and informative presentation entitled, “The immunotherapy faces of Interleukin–8 and CD137.” He also had a related talk on “4–1BB and Metabolism” at the Society for Immunotherapy of Cancer (SITC) meeting this weekend.

Pinning down new opportunities in IL-8 and 4-1BB

The late and sadly missed, Dr Holbrook Kohrt (Stanford), worked closely with Prof Melero on targeting CD137 or 4–1BB, as it’s more commonly known.

Regular readers may recall our interview wth Dr Kohrt back at Immunology 2015 in New Orleans (Link).

If you missed it, we also shared some excerpts from this discussion on Episode 6 of the Novel Targets Podcast, “Stepping on the Gas” (Link). There was also a tribute to Dr Kohrt from Dr Ron Levy (Stanford) at the start of Episode 11 of the podcast (Link).

Professor Melero kindly spoke to BSB at SITC 2018 and shared his thoughts on where we are three years on and where his research is currently focused in relation to cytokines, and in particular, IL–8.

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Autumn leaves in Munich

We have increasingly seen how oncologists like the efficacy associated with the immune checkpoint combination of ipilimumab plus nivolumab, but are leery of the increase in side effects, including immune related events.

Are there practical ways to reduce this phenomenon, other than dose reductions?

CytomX are one company who are focused on engineering a different concept with their monoclonal antibodies, bispecifics and ADCs to try and mask the effects, thereby reducing the treatment emergent toxicities.  Their main idea is that the therapeutic window can be widened, thereby improving the tolerability profile.

It’s a nice idea, but what happens in practice?

To find out, we took a look at the recent early clinical data and interviewed executives from the company…

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There is a lot of interest of late in targeting neoantigens in cancer therapeutically. If you missed it do listen to Episode 20 of the Novel Targets Podcast, which features several pioneers in the field.

At the recent European Society for Medical Oncology (ESMO) meeting, we heard Dr Patrick Ott from the Dana-Farber Cancer Institute present the latest clinical data for Neon’s cancer vaccine approach (See: interview with Dr Ott).

If you have an interest in neoantigen based cancer treatments, however, then a company on the horizon that we’re excited about is Achilles Therapeutics.

It’s an early stage company, in what is very much still a developing and emerging field. Founded just over two years ago, it has a strong academic pedigree. The scientific co-founders are Professors Karl Peggs, Mark Lowdell, Charles Swanton and Sergio Quezada.

BSB readers will recall our prior interviews with Prof Charlie Swanton FRS (See: here and here), where he talked about the groundbreaking TRACERx study he’s leading, some of the insights it is generating regarding neoantigens, and their importance in cancer evolution.

Achilles Therapeutics was established to commercialise the intellectual property being generated from the TRACERx program.

While in London en-route to ESMO18, the CEO of Achilles Therapeutics, Dr Iraj Ali kindly spoke to BSB about where the company is, and some of its future plans.

From what we heard, it’s definitely a company we can expect to hear a lot more about in the cancer immunotherapy space. Check it out!

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Dr Moore at ESMO18

At the recent European Society of Medical Oncology (ESMO18) Congress in Munich, arguably the data of the meeting – if the audience reaction is anything to go by – were the results from the phase 3 SOLO1 trial that were presented by Dr Kathleen Moore (right).

The results were simultaneously published in The New England Journal of Medicine in an article entitled: “Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer” (Link).

As Moore and colleagues note in the abstract:

“After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan–Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P < 0.001).”

Dr Moore is an Associate Professor of gynecologic oncology and the Jim and Christy Everest Endowed Chair in Cancer Research at the University of Oklahoma Stephenson Cancer Center.  She kindly spoke to BSB after her presentation in the Presidential Symposium.

In addition to Dr Moore’s personal commentary on what these results mean for women with ovarian cancer, we also have some additional insights on what this data may mean for other players in the PARP space such as Tesaro and Clovis.

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One of the ongoing challenges with cancer immunotherapy is monitoring response to treatment.

Even if you are one of the minority of people who do respond to cancer immunotherapy, many responders go on to develop acquired resistance or experience immune escape resulting in a loss of response to therapy, which means we need to be able to detect what is happening in the immune system of a cancer patient in order then identify the next treatment option.

Dr Whiteside in the poster hall at #AACR18

Could the proteins and nucleic acids carried by virus sized microvesicles called exosomes – present in their billions in blood plasma – provide insights into biomarkers of response to therapy and what is happening in the tumour?

Some people think they can, while others remain skeptical.

We think it’s cool area of research, worthy of consideration and following as we continue to explore various biopsy and blood/plasma approaches.

One person at the forefront of exosome research is Dr Theresa Whiteside from the University of Pittsburgh, where she’s a Professor of Pathology, Immunology and Otolaryngology.

At the recent 2018 annual meeting at AACR, she kindly spoke about her innovative work over the past year in what is now an exploding field of research…

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The #ASCO18 poster hall scrum

Wrapping up our cytokine mini-series, we have our latest expert in the BSB hotseat discussing concepts and future developments, as well as strategically drawing things together in a way that makes sense.

It has become increasingly clear that a hostile tumour microenvironment may account for one of the reasons why many patients don’t respond to cancer immunotherapy.

How do we go about figuring out the whys and wherefores in order to significantly improve on the results seen to date with monotherapy treatment?

There are quite a few angles to look at this conundrum, so we decided to explore some concepts and analogies, as well as look at what’s going on under the hood of IO clinical trials to address the thorny issue of tumour heterogeneity.  We also discuss some of the top-line data in the cytokine niche presented at ASCO and look at the outcomes in the context of what we learn and where we going next.

There’s a lot to take in and process here, but that’s part of the fun!  As often is the case, some of the best gems are in the poster halls or poster discussion sessions…

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It is always a pleasure to talk with experts who have a clear vision of not just what the current treatment landscape looks like, but where the field is going.

Dr Stephen Liu at ASCO18

Dr Stephen Liu is a medical oncologist and assistant professor at Georgetown University Medical Center in Washington DC, where he specializes in thoracic oncology.  He’s also actively involved in clinical trials and developmental therapeutics.

We last interviewed him at ASCO 2016 – you can also hear him on Episode 13 of the Novel Targets Podcast – where he shared his thoughts on some of the early lung cancer immunotherapy combination trials underway.

As regular readers know, we like to follow stories over time and also catch up with thoughtful, intelligent people we’ve talked to in the past whose opinions we value.

Dr Liu kindly shared his highlights of ASCO 2018 in lung cancer, and in a wide ranging discussion, also offered some thoughts on what the future may hold and where we may be going next.

There was a lot to learn from Chicago this year, with plenty of nuances and subtleties to consider. If you read only one post on lung cancer from ASCO18, this interview tells you all you need to know!

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Now that at two CAR T cell therapies have been approved by the FDA in two indications, what does the future hold for new developments in both hematologic malignancies and solid tumours?

It was astonishing to explore the poster halls at AACR last month and see just how many new players and targets are emerging left, right and centre.

Last week we highlighted an up and coming new player on the scene, Mustang Bio, but what about the original pioneers in this niche and what are they up to these days?

To answer this question, we tracked down Dr Renier Brentjens at Memorial Sloan Kettering while in Chicago to learn more about his latest work and where he sees the future of CAR T cell therapy heading. It makes for a very interesting, and at times, surprising read…

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