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

PARP inhibition in metastatic prostate cancer

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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Crossing the Rubicon

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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ESMO19 Preview 2 – Targeting Synthetic Lethality and Immune Response in GU malignancies

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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Controversies in triple negative breast cancer at ESMO19

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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Overcoming a hostile tumor microenvironment with Siglec-15

We’re continuing our mini-series on cracking the ‘glyco-code’ with an interview with Dr Lieping Chen (Yale), one of the world’s leading cancer immunologists, someone who has taken basic science and translated it into a spin-off company, NextCure (NASDAQ: NXTC) and a new product (NC318) targeting Siglec-15 that’s already being evaluated in the clinic.

Will upregulation of Siglec-15 turn out to be key in some cancer patients?

What happens if you identify a novel target that is expressed in a subset of patients that’s key to resetting the immune response and overcoming the immuno-suppressive tumor microenvironment (TME)?

Not only that, but you can potentially use a biomarker to select the patients most likely to benefit from what we’re calling a ‘targeted immunotherapy’ that’s directed at overcoming a specific immune dysfunction or defect.

Think of it as like when you press the factory re-set button on your iPad or iPhone.

Over the course of the coming year, we expect to hear a lot more about the early clinical data for this novel approach so in this expert interview we’re talking to the founder about the science that’s propelling NextCure forward.

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Targeting Siglecs for Cancer Immunotherapy

One of the innovative areas of cancer immunotherapy is glycobiology, or targeting the sugars found on the surface of tumor cells or immune cells. There is a lot happening in this field around drug development, drug delivery and cell therapies.

Standing out from the crowd

It’s time to take a look at some of the targets around Siglecs (sialic acid-binding immunoglobin like lectins).

We’ve covered Siglecs briefly before in a discussion with Innate Pharma last year about their early pipeline agents, including a Siglec–9 antibody in preclinical development that was subsequently picked up by AstraZeneca.

Since then this space has blossomed with a number of companies rapidly vying for time, space, and attention, making it a good time to take a broader look at the evolving landscape

This primer sets the scene for our coverage on this emerging area in oncology R&D.

In a subsequent post, we have an interview planned with a thought leader at the forefront of translational research into targeting Siglecs.

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Dracarys! How T cell therapy is like Game of Thrones

If you want to meet a believer in the potential of cellular therapy to treat cancer, then look no further than Dr Cassian Yee.

Dr Yee is Director of Solid tumour Cell Therapy at the University of Texas MD Anderson Center in Houston and a Professor in the Departments of Melanoma Medical Oncology and Immunology.

He’s a pioneer in the development of endogeneous T cell therapy (ETC) that uses the peripheral blood as a source of antigen-specific T cells.

If the cells in the immune system are like the participants in “Game of Thrones” then Dr Yee’s eponymous car number plate and Twitter handle (@tcellsrus) strongly declares his allegiance.

He’s also co-founder of Immatics US, a company jointly founded back in 2015 by Immatics GmBH in Tubingen and MD Anderson, to commercialize next generation adoptive cellular therapy (ACT). The US venture secured $60M of first round funding, including $40M of funding from Immatics.

Dr Yee is not someone we’ve heard a lot from on the conference circuit in recent years, so it was a pleasure to catch up with him in person at the recent @C_IMT annual meeting in Mainz.

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Highlights from Plenary Sunday at ASCO19

Chicago: We’ve heard a lot of people say how they think this year’s annual meeting ASCO19 is not as good for data as previous years, and we’re going to have to respectfully disagree.

On Sunday at ASCO19 there was a wealth of data on display in multiple sessions with some noticeable “winners and losers” when it comes to drugs in development.

Dr Hedy Kindler presents phase III POLO trial in Plenary Session at ASCO19. Data simultaneously published in NEJM.

In this post, we’ve some top-line commentary on some of the Sunday sessions we covered, and what caught our attention. As always our detailed analysis comes after the meeting in the “post-game” show.

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Highlights of Day 2 at ASCO19

Chicago – the 2019 ASCO annual meeting is in full swing and it’s plenary Sunday where the jewels in the crown are presented.

Noteworthy this year is the olaparib data being presented by Dr Hedy Kindler.

In this post, we’ve commentary on the data we’ve heard so far, highlights from yesterday’s sessions, and what you can expect to hear today if you’re in Chicago for Plenary Sunday.

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Highlights of Day 1 of ASCO19

The 2019 annual meeting of the American Society of Clinical Oncology (Twitter #ASCO19) is now in full swing, and we’re kicking off our on-site meeting coverage with a review of the some of the highlights of Friday here in Chicago.

In today’s Daily Highlights we offer seven areas of interest and offer commentary on the insights gleaned from the data that is rolling out so far…

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