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

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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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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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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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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If the best way to predict the future is to invent it then the poster sessions at the AACR annual meeting are frequently a window into the next generation of cancer drugs and therapies. Regular attendees at AACR will know that there are gems to be found in the posters, and that preclinical research on display may end up being translated into the clinic not long afterwards.

Like wearing a new set of clothes for lunch and dinner, with the exception of the first and last days, there’s a different set of posters in the morning and afternoon – that’s a lot of posters one can get through during a conference!

Indeed, MSKCC Chief Analytics Officer, Ari Caroline, noted on Twitter, “I may have spent more time at AACR this year at the posters than at the sessions.”

Dr Larry Lamb CSO Incysus

One story that we continue to follow this year is the emerging interest in unconventional T cells. The good news was that there was new data at AACR19.

We covered Puretech Health and their posters last week while another related one in the same niche that caught our attention was presented by Dr Lawrence Lamb (right).

On April 1, 2019 Incysus announced that the FDA had approved their IND application for a novel gamma-delta T cell therapy for treatment of patients with newly diagnosed glioblastoma (link to press release).

At AACR19 we met up with Dr Lamb, who is now Chief Scientific Officer of Incysus Therapeutics, to find out more about his research and how Incysus plan to translate it into the clinic.

This is a continuation of our series on gamma delta (𝞬𝝳) T cells exploring the multitude of different ways that illustrate their potential for cancer immunotherapy in hematologic malignancies and solid tumours.

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With the startling news this morning that Poseida Therapeutics are abandoning their IPO plans and pursuing a different tack with a $142M investment from Novartis to fund clinical trials for their BCMA-directed CAR T cell therapy program in multiple myeloma, our attention is focused yet again on the highly competitive BCMA niche.

Poseida’s data was revealed at ASH last December and with an ORR of 63%, the initial efficacy was a bit lower than we have seen from rivals Bluebird Bio and Legend/JNJ, although the Penn/Novartis construct reported disappointingly lower responses in a small cohorts of patients, which may explain Novartis’s interest.

There are also other companies/products in this niche including GSK’s ADC, GSK2857916, and Amgen’s T cell bispecific, AMG 420, plus plenty of others with BCMAxCD3 bispecifics who have earlier skin in this increasingly highly competitive game.

Is BCMA enough though?  Is it really the answer to multiple myeloma or are there other approaches that might be better?

Putting new CARs in the spotlight

What of the future for CAR T cell therapies in myeloma beyond the initial generation 2.0 constructs?

We saw a vision for how this market might evolve and sought out some experts to learn more about what they are doing in this niche – what they had to say was really interesting.

After all, as Wayne Gretsky would say, don’t skate to where the hockey puck is (now) but where it will be… that’s a great analogy one cannot resist borrowing for the future of cell therapy in multiple myeloma.

In our latest article, we go beyond BCMA to explore where we think the field might be going and why a tunnel focus on BCMA might not be such a great thing…

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If we want to help more patients respond to initial immune checkpoint blockade then we not only need to figure out why some people respond initially but stop responding, but also look at why the majority do not respond upfront.

The reasons might take on many forms depending on the defects in their immune system that the cancer might have hijacked to its advantage.

One obvious way is increased immunosuppression and a more hostile tumour microenvironment. In the past, we have looked at the adenosine fog, as well as the cytokine, TGF-beta, as two quite different ways where the tumours might be impacted in terms of their responsiveness to therapeutic intervention.

In our latest mini-series this week, we are going to explore additional ways that cause non-response to cancer immunotherapy due to immunosuppression and how companies – big and small – are investigating novel therapeutic approaches in this niche based on the underlying biology of the disease.

We begin our journey with a look at neutrophils from the eyes of a researcher who is an expert in this field and how an understanding of the science has led to new novel targets with even some early stage compounds in the clinic already…

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Continuing our in-depth oncology pathology interview with Dr David Rimm (Yale), we take a look at some of the new data his lab presented in Atlanta, where we are now with TMB as a biomarker, and what the future may hold for cancer immunotherapy biomarkers.

Early morning in Atlanta en route to the GWCC and AACR19

In an engaging discussion, Dr Rimm discussed many of the details behind PD-L1 and TMB in terms of what really matters when thinking about these tests and their practical applications. He also shared his candid thoughts on the lung cancer blood TMB data presented at AACR by Prof Solange Peters.

If you missed the first part of the interview with Dr David Rimm, a leading oncology pathologist at Yale, on the various challenges associated with PD-L1 as a biomarker on tumour and immune cells in triple negative breast cancer than you can catch up and read it here.

The second half of the interview with Dr Rimm focuses on TMB, with some more details on the challenges of reading PD-L1 on immune cells and why that is the case…

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One of the emerging challenges of the IMpassion130 trial of the combination of nab-paclitaxel and atezolizumab versus nab-paclitaxel alone in triple negative breast cancer (TNBC) is that pathologists can’t reliably read PD-L1 on immune cells.

Georgia State Capitol in Atlanta

This issue came up in an insightful talk by David Rimm MD PhD (@RimmPathology), Professor, Departments of Pathology and Medicine (Oncology) at Yale in an education session at this year’s AACR annual meeting in Atlanta where he spoke about, “Predicting immunotherapy response with protein-based tools: PD-L1 and beyond.”

BSB readers will recall Dr Rimm was a hard hitting discussant of the CheckMate–227 trial data for the combination of nivolumab and ipilimumab in first-line non-small cell lung cancer (NSCLC) at AACR18. He correctly predicted that tumor mutational burden (TMB) as a biomarker would predict PFS but not overall survival, based on an analysis of their cohort at Yale. He turned out to be right!

The implication of this was that BMS subsequently withdrew their EU/US regulatory filings for CM227 in 1L NSCLC when the hazard ratios (HR) for high and low TMB turned out to be identical.

If you missed it, do listen to the episode 22 of the Novel Targets Podcast we produced from AACR18 (Link), where we took a closer look at TMB as a biomarker, and the phase 3 lung cancer clinical data presented at the meeting.

Will we see challenges emerge with the Ventana SP142 assay?  What about the implications for Merck’s KEYNOTE-355 trial in TNBC?

In this BSB post, we discuss these issues and explore many of the nuances that readers should be aware of in TNBC.

In addition to Dr Rimm’s candid and hard hitting interview, we also invited Professor Sherene Loi (@LoiSher) to review Dr Rimm’s commentary and offer a clinical perspective on the points he raised.

She’s a consultant medical oncologist at the Peter MacCullum Centre in Australia, where she holds the National Breast Cancer Foundation of Australia Endowed Chair and is head of the Translational Breast Cancer Genomics and Therapeutic Laboratory.

Professor Loi is also one of the authors of the paper published in The New England Journal of Medicine that reported the results of the IMPassion130 trial.

If you’d like to read Dr Rimm’s candid interview and Professor Loi’s clinical perspective, become a subscriber to BSB and support independent science journalism. As of today, 75% of our subscribers are repeat buyers – do consider joining them!

In the second part of the interview with Dr Rimm (to be published separately), we’ll hear about some of the new data his lab presented at AACR19 and where he sees the future for TMB and other immune biomarkers.

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Centennial Olympic Park, Atlanta

In the first part of our preview we looked at the cancer immunotherapy related program from Friday through Sunday at the AACR 2019 (#AACR19) annual meeting at the Georgia World Congress Center (GWCC) in Atlanta.

This post looks at the program from Monday to Wednesday – you can find a review of the IO track for Fri-Sat here.

Don’t forget you can review the precise room details via the AACR meeting app prior to attending sessions as these are sometimes subject to change. We’ve based our posts on the preliminary program and it is highly likely there will be changes to meeting rooms, based on past experience.

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