Biotech Strategy Blog

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

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Posts by Pieter Droppert

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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SITC 2019 Preview: After looking at exciting new developments in targeted therapies last week, it’s now time to switch horses and kick off our annual coverage of the Society for Immunotherapy of Cancer (SITC) meeting, which takes place in a few days time at National Harbor in Maryland.

National Harbor, MD

In the SITC 2019 Presidential Session this coming Saturday, one of the presentations we are eagerly looking forward to is by Dr Vyara Matson, a Post Doc in the lab of Dr Tom Gajewski at the University of Chicago.

Dr Matson will be presenting on “Patient-derived microbiota germ-free mouse model for identifying mechanisms of checkpoint blockade efficacy modulation.”

In our latest expert interview, we spoke to Dr Gajewski about the strategic concepts underpinning his work in the microbiome niche, where he has got to presently and where he plans to go next. It makes for fascinating reading, especially when you realise that as scientists, they are sceptical themselves and yet curious to discover the answers through carefully thought out experiments that could impact future patient care for those people receiving immunotherapy for the treatment of their particular cancer.

One major take home for us in following the cancer immunotherapy niche is that there could well be different mechanisms at play for primary and secondary resistance – where does the microbiome fit in with this, and can it be manipulated to create a more positive benefit?  Is the effect a real one or a spurious correlation?  These kind of questions, along with a host of others, are some of the key topics discussed in the expert interview.

If you have plans to be at #SITC2019 do let us know, as we always look forward to saying “hello” to BSB readers.

Subscribers can read more on why we think this work is innovative and important to our understanding of what’s going on in responders and non-responders by logging in or you can click to gain access to BSB Premium Content.

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Boston: The 2019 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics is underway (#Targets19). It’s long been one of our favorite meetings, particularly when held in Boston, and this year there’s a raft of early ideas on offer as to where the targeted therapy field may be going.

Alison Schram, MD. Credit: MSKCC

The success of Ignyta’s entrectinib (acquired by Roche) and Loxo Oncology’s larotrectinib (acquired by Lilly) in targeting NTRK gene fusions has raised interest in targeting other gene fusions, even if they are rare. A new target in a similar vein that has attracted interest recently are fusions involving the neuregulin 1 gene (NRG1).

At this year’s Molecular Targets meeting, Dr Alison Schram, a medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSK) presented clinical proof of concept data for MCLA-128 (Merus), a bispecific HER2/3 antibody therapy in NRG1 fusion positive cancers.

What did we learn about MCLA-128 and NRG1 at Targets19?

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Oncology R&D is very much a tale of two cities. At one end you have all big pharmas and biotechs with significant resources in the form of very large budgets, (hopefully) an extensive pipeline, plus many hands on deck to efficiently spread the workload, while at the other end you have what I call the ‘baby’ biotechs with completely the opposite situation coupled with a much greater need for prudence in how those scarcer resources are managed.

A failed drug development may not affect big pharmas very much, it’s written in to the strategic plans after all, and a 90% failure rate is very much de rigeur so you’re looking for the rare gems that will shine and carry the rest. In small biotechland, such inherent risks are much more prominent – and drastic – because a failed program can wipe out the stock overnight such that future endeavours to raise money are greatly hampered, putting the very life of the company at risk of not only delisting (if publicly traded) from stock exchanges such as NASDAQ, but also the ultimate doom.

The constraint that both bookends have in common, however, is familiar to many readers – how to get the best shots on goal given the time, energy, and resources available?

At BSB we don’t write just about big Pharma – we also try to highlight the roller coaster experienced at the other end of the spectrum and showcase some cool science in the process. Given our interest in stapled proteins as well as the various challenges associated with both tumour suppressors and MDM2, it seemed like a good idea to catch up with the folks at Aileron Therapeutics (NASDAQ: ALRN) and learn more about their progress since they combine all three elements in one go…. it’s time for some gems from the ESMO19 poster hall.

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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.

To learn more from our coverage on breast cancer and get a heads up on insights from our latest thought leader interview, subscribers can log-in or you can click to gain access to BSB Premium Content.

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It’s time to talk about new developments in breast cancer.

@3NT with Dr Dennis Slamon at ESMO19

This week we will be featuring thought leader interviews with two breast cancer specialists as we look at new data in different subsets of this disease, in both early and metastatic settings.

We like to ring the changes with invited guests on BSB who comment on trial results and offer broader perspectives on their specialist field as well.

One expert is someone neither of us has ever interviewed before, while the other returns for an update on an early trial that is showing promise. Both interviews were conducted under embargo ahead of their presentations in Barcelona.

One of the myriad of challenges in oncology R&D is the tendency to begin exploration in the most advanced form of the disease with monotherapy to determine single agent activity and then work up to earlier lines of therapy with combinations evolving over time.

While it is always good to see proof that people are living longer with particular approaches, there is a real need to keep one’s eyes out on the horizon for new developments that may extend overall survival further.

What should those regimens look like and what are rational choices based on the underlying biology of the disease rather than being explored because that’s what a particular sponsor happens to have in their pipeline? We were delighted to have the opportunity for a much broader discussion some of these opportunities with today’s key opinion leader, Dr Dennis Slamon of UCLA, who presented data in an ESMO Presidential symposium and also talked about other topics in breast cancer research with BSB.

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Who’s King of the PARP castle?

After yesterday’s review and expert commentary on the phase 3 PROfound trial presented in the Presidential Session at ESMO 2019, we’re continuing our look at PARP inhibitors in advanced prostate cancer.

Perhaps surprisingly, there were a lot of insights to be found in the posters that were presented and discussed at the meeting for other PARPs in clinical development.

How do these stack up against olaparib? We’re not fans of cross-trial comparisons as they always come with a mandatory health warning, but if you want to consider the emerging landscape, it is important to be aware of the different patient populations, lines of therapy, and details of the trial designs.

For additional perspective at ESMO19, we spoke to a European prostate cancer expert who kindly talked about his clinical practice and also offered insights into a PARP clinical trial he and colleagues presented in Barcelona.

Who will be King of the PARP castle in advanced prostate cancer?

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We’ve heard much about the role of PARP inhibitors in ovarian and breast cancers where there is sensitivity to these agents in women with DNA damage repair defects, but what about advanced prostate cancer?

Following the publication of the phase 2 trial TOPARP in the NEJM in 2015, we’ve been eagerly awaiting the outcome of a series of phase 3 studies with these agents in metastatic prostate cancer in multiple different lines of therapy.

Dr Oliver Sartor at ESMO19

Following on from our daily coverage from ESMO in Barcelona last week where we looked at some of the pros and cons as they appeared during the presentation by Dr Maha Hussain (Chicago) from the PROfound trial, it’s time to share some expert opinions.

The study she presented evaluated the PARP inhibitor, olaparib, versus next generation AR anatgonists abiraterone or enzalutamide in refractory metastatic castrate-resistant prostate cancer (mCRPC).  Interestingly, it soon became rapidly clear that many casual observers missed some important nuances from the myriad of top-line news articles and summaries.

The devil, as always, is in the details.

To further our readers education on this important topic, BSB interviewed a prostate cancer thought leader, Dr Oliver Sartor (right) for his personal perspectives and look at the take homes from the lens of an experienced triallist in this niche.

Let’s see what he had to say about PARP inhibitors in advanced prostate cancer, as well as the PROfound and TRITON studies…

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We’ve been writing about PARP inhibitors since 2006!  Who knew this target would have multiple legs over a dozen years on?

Barcelona

In this post we’re taking a look at some of the noteworthy presentations at ESMO19 around targeting DNA damage repair (DDR) and how they act through synthetic lethality and/or the generation of immune response to kill cancer cells in GU cancers.

It’s a fascinating area where we are seeing convergence between immunotherapy and genomic instability, one of the hallmarks of cancer.

The abstracts for ESMO19 are not yet available, so in this post we’re only providing context and setting the scene for some of the presentations we are looking forward to, as well as raising some key questions that we hope will be answered in Barcelona.

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One of the expected highlights of the forthcoming European Society for Medical Oncology (Twitter #ESMO19) will be data for breast cancer immunotherapy.

In the first of our pre-ESMO19 previews we are taking a closer look at three breast cancer immunotherapy presentations that we think are noteworthy.

As a reminder, the abstracts are not yet available, so we’re not writing about data that’s not yet been presented, but instead are looking at why the presentations may be of scientific/medical interest, and what the questions we hope they will answer. In cancer biology as we heard from Professor Gerard Evan in a recent expert interview, it’s not about “what” happened, but “why”?

We have “boots on the ground” in Barcelona from Sept 27th to October 1st providing daily posts for BSB subscribers with our unique blend of data, analysis and commentary.

Do download the ESMO19 app if you want to check out what already looks like it will be a busy, informative and interesting congress in Barcelona. Hopefully the rain that struck the recent World Lung meeting in Barcelona will have gone away, leaving us with a sunny and dry spell one normally associates with Spain!

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