Biotech Strategy Blog

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

About Pieter Droppert

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Posts by Pieter Droppert

Iraj Ali leads the way at Achilles Therapeutics

There is a lot of interest of late in targeting neoantigens in cancer therapeutically.

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 private UK 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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Why are the SOLO1 data so compelling?

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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Can we use exosomes for immune monitoring?

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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In a Prudential Light

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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Fitting it all together – what does the post ASCO Lung Cancer Landscape look like?

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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Will KEYNOTE-042 change the standard of care in lung cancer?

Chicago June 3, 2018: The data for the phase 3 KEYNOTE–042 trial has just been presented in the plenary session of the 2018 annual meeting of the American Society for Clinical Oncology (#ASCO18).

Data for this positive phase 3 study was presented by Dr Gilberto Lopes (@GlopesMd), Associate Professor at the Sylvester Comprehensive Cancer Center at the University of the Miami.

The trial in previously untreated patients with metastatic non-small cell lung cancer (NSCLC), who didn’t have an ALK translocation or EGFR mutation, sought to answer the question of whether the anti-PD–1 checkpoint inhibitor pembrolizumab (Keytruda) would be better than chemotherapy in patients whose tumours had an expression of PD-L1 between 1–49%.

Readers may recall that pembrolizumab has already received FDA approval for the treatment of first-line NSCLC in patients with greater than 50% PD-L1 expression, based on data for the KEYNOTE–024 trial that was presented back at ESMO 2016 by Dr Martin Reck.

So what’s the verdict? 

Dr Lopes kindly spoke to Biotech Strategy and shared his perspective on the trial data he shared with ASCO. Will the KEYNOTE–042 trial change the standard of care, and how does it fit in with the KEYNOTE–189 trial data that we heard about at the 2018 AACR annual meeting back in April?

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Development of Next Generation CAR T cell therapies

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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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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Stacking up evidence from IO clinical trials

What we wanted to accomplish in our latest thought leader interview was to peek under the hood with someone active in this field who is an experienced participant in phase 2 and 3 trials, as well as being a solid translational researcher capable of thinking outside the box critically.

Stacking up the evidence from IO trials

Today we cover a global KOL’s perspectives on cancers of the lung, renal, bladder, and even melanoma, in a wide ranging discussion about immunotherapy trials and some of the pitfalls and opportunities to watch out for.

It makes for an intriguing read as there are likely a few issues that many have not thought about in great depth.

This is an important discussion in the context of not just data that was recently presented at several conferences including AACR, but also with the upcoming monotherapy and chemo combination trials (including squamous and non-squamous lung cancer) expected at ASCO in a few weeks time.

We discuss quite a few of the key challenges and opportunities relating to the broader picture and highlight some of the important issues to watch out for…

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How Charles Swanton plans to revolutionize treatment of Lung and Renal cancers

At the 2018 AACR annual meeting, one of the noteworthy talks given to the 22,000+ attendees in Chicago was a plenary lecture by Charles Swanton from the Francis Crick Institute in London. He’s a Professor of Personalized Cancer Medicine at University College London and chief clinician for Cancer Research UK (CRUK).

Professor Swanton is the leader of a landmark clinical study, TRACERx (TRAcking Cancer Evolution through therapy (Rx)) study, which involves analyzing how cancers and in particular, lung and renal cancers, evolve over time.

There’s a lot of heavy science and jargon inherent in this niche that often frightens off people, but that need not always be the case.

What is fascinating, though, is the very idea that tracking the development of early stage cancers might teach us new insights and lessons about alternative approaches to oncology R&D.

We have all seen the limitations of chemotherapy, targeted therapies and even immune checkpoint blockade, so what other approaches can be considered that link back to the biology of the disease and how it evolves over time?

What we wanted to achieve here was a clear and elegant story about what Prof Swanton and his colleagues are doing, as well as a simple grounding on the basics of disease progression and how that can translate clinically into new therapeutics that might make a real difference to the lives of people with cancer.

It’s a fascinating story and may well be one of the most underappreciated recent developments in cancer research…

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