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 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.

If you’d like to read more about our current conference preview on cancer immunotherapy, subscribers can log-in to read our latest review of what’s going on or you can click to gain access to BSB Premium Content.

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We’re starting our review of the program for the forthcoming 2019 annual meeting of the American Association for Cancer Research (Twitter hashtag to follow: #AACR19) with a look at the cancer immunotherapy program.

One of the challenges of a large meeting is that it’s like a smorgasbord or buffet in a hotel that’s resplendent in choices, but you can’t possibly eat it all.

Choices!

Some choose to follow a research area, others a target or tumor type. There’s a lot of ways to segment the program depending on your specific interests.

However, it’s a good idea to have a plan in place ahead of a large conference such as AACR, even if you modify it as you go to take into account evolving needs.

Seasoned conference goers will be familiar with the maxim known as “the law of two feet” – if a session you are in doesn’t live up to expectations or meet your needs and something else looks more to your taste from the tweets, then simply dash off to another!

In our latest conference preview, we’ve taken a careful look at the cancer immunotherapy track.

What are some of the key sessions to put on your calendar if you’re following this track or have an interest in this area?

In Part 1, we review the IO sessions from Friday to Sunday then tomorrow in Part 2, we’ll review the schedule from Monday to Wednesday.  Yes, it’s that intense this year! Just think, five years ago you had to search the program really quite hard indeed to even find much on immuno-oncology, as it was very much in its infancy then.

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Casa Milà, Barcelona

One of the pleasures of going to international cancer immunotherapy conferences is the opportunity to meet great scientists such as Sergio Quezada, PhD. He’s a Professor of Cancer Immunology and Immunotherapy at University College London (UCL) Cancer Institute.

After his PhD, he joined the laboratory of Jim Allison at MSKCC in 2004, and as we heard from Nobel Laureate Sir Richard Roberts FRS on the last episode of the Novel Targets Podcast (Link), working in the laboratory of a future Nobel Laureate is one of his 10 tongue in cheek suggestions to improve your chances of winning a Nobel prize!

Professor Quezada kindly spoke to BSB last week at the European Association for Cancer Research (EACR) “Defense is the Best Attack” conference.

In Barcelona, we talked about the research done by his UCL group into regulatory T cells (Tregs) that led to the development of a novel first-in-class Treg depleting anti-CD25 antibody.

As Prof Quezada told BSB:

“This was the dream. It was basic biology, a big curiosity, lots of basic biology and being very stubborn and lots of luck. And now we have something that came out of PhD students and postdocs that some medic or nurse is gonna be injecting at the end of the year into a patient, so it’s really exciting. It’s really, really exciting!”

We enjoyed talking with Prof Quezada and appreciated the perspicacious insights he shared on where we’ve come from and where we may be going.

If you’d like to read more about the science and potential for this approach in cancer immunotherapy, subscribers can log-in to read our latest thought leader interview or you can click to gain access to BSB Premium Content.

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Barcelona: What makes a great scientist is not accepting conventional wisdom or dogma but instead thinking differently, pursuing what data generated truly means, and asking if we can do things differently as a result?

Gaudi architecture, Barcelona

Current success in immuno-oncology new product development has been built on basic research done twenty and thirty years ago, when many didn’t believe in leveraging the power of the immune system therapeutically.

At the ongoing European Association for Cancer Research (EACR) “Defense is the Best Attack” meeting in Barcelona this week, many experts in the IO field are sharing novel findings on what may lead to future insights.

What were some of the key take-homes?

Subscribers can read our notes from some of the presentations that stood out at the meeting.

If you’re not yet a BSB subscriber and are interested in learning from our science and clinical commentary/analysis then come join a growing band of enthusiastic readers!

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Gaudi’s Casa Milà/La Pedrera, Barcelona

Barcelona: There’s a lot of choice when it comes to cancer immunotherapy conferences, but an event that caught our attention this year as one that merited coverage is the European Association for Cancer Research (EACR) meeting, Defense is the Best Attack – Immuno-Oncology Breakthroughs taking place in Barcelona this week.

The conference is being held in the basement of La Pedrera, Gaudi’s famous Casa Milà modernist building in Barcelona (right).

It’s such an old building that you’re actually forbidden to plug in any phones or computers to charge them for fear of over-loading the electrics, so it’s an event that requires you to be fully charged upfront!

What were some of the highlights from Day 1?  There were some key data and concepts being presented that will grab folks involved in cancer research…

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