ASH16 in San Diego
Today we resume our coverage from the recent American Society of Hematology (ASH16) annual meeting with a look at some fascinating and highly compelling science that was presented in an obscure and hard to find tiny hall in San Diego.
This story is also about how a small biotech company that many casual observers may not even be aware of, is taking advantage of advances recent research to grab a clinical lead in a very specialised field in oncology that may yield a novel approach worthy of taking notice of..
Genomics is increasingly becoming a core element of cancer research. Think of it as the alphabet soup of molecular biology concerned with the structure, function, evolution, and mapping of genomes.
Once we understand and identify the genomic landscape in health and diseases such as cancer, it allows numerous platforms to evolve whereby those unique differences can be identified (as driver vs. passenger mutations, for example), explored in depth, and later key ones targeted with therapeutics. Inevitably, there are many ways to do this.
Much of the focus in genomics has been on DNA, but what about RNA?
RNA is important because a mistake – even a single nucleotide – can be devastating to the cell, and a reliable, repeatable method of RNA processing is necessary to ensure cell survival. Mis-splicing can thus lead to the development of new point mutations and genomic instability deep in the cell nucleus, potentially causing the evolution of certain cancers.
Paradoxically, these aberrations also offer novel therapeutic targets – but are they druggable?
What we are exploring here is a completely different approach, both in terms of how a fledgling company is funded and also the type of research that is conducted.
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Yesterday sudden and unexpected news from Seattle Genetics caused quite a stir…
“Seattle Genetics Announces Clinical Hold on Several Phase 1 Trials of Vadastuximab Talirine (SGN-CD33A).”
Part of the Seattle Genetics exhibit booth at #ASH16, taken with permission
In short, over 300 patients have been treated with the ADC and six experienced hepatotoxicity, including several cases of veno-occlusive disease, with four fatalities.
We’ve written about AML several times recently and also received a number of reader questions on this latest development, so it’s time to explore the issue in more depth and look at the implications. We also include some expert commentary from a leukemia specialist for their take on the issue.
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The 2016 annual meeting of the American Society of Hematology with over 27, 000 attendees, a record high, was the venue for the announcement of a major new initiative by the Leukemia Lymphoma Society (LLS), called Beat AML.
It is lead by three well respected researchers in the Hematology/Oncology field:
- Dr John Byrd (Ohio State)
- Dr Brian Druker (OHSU)
- Dr Ross Levine (MSK)
Beat AML is a special project at LLS, who have developed a broad collaboration with academic researchers, pharmaceutical companies, a genomic provider, and a clinical research organization:
Initially, there will be five trial sites, which will each offer all arms of the trial. The centers are:
- Memorial Sloan Kettering Cancer Center in New York
- The Ohio State University Comprehensive Cancer Center in Ohio
- OHSU Knight Cancer Institute in Oregon
- Dana-Farber Cancer Institute and
- Massachusetts General Hospital Cancer Center, both in Massachusetts.
Further sites and (hopefully) also other drugs from pharma companies will be added in due course, so if you’re interested in joining this project, do contact them after checking out more details here!
For our industry readers, this would be a great opportunity to get involved in an exciting and landmark study for AML, whether you are a researcher or a company with a promising drug in early development. These types of trials can help speed up drug development if a therapy graduates in a particular subset.
Here, we offer an in-depth analysis of the scientific and clinical rationale behind this important landmark study and the targets/drugs selected to date.
BSB also spoke with Dr Brian Druker, Director of the Oregon Health and Science University (OHSU) Knight Cancer Institute in Portland, Oregon, who offers additional insights on the special project.
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Oncology R&D is tough and there are many more failures than successes, despite the FDA approving more than they’ve rejected over the last two years. That’s quite unusual in my experience.
As Dr Mario Sznol (Yale) told us at SITC recently, sometimes these things are sometimes more whimsical. He was referring to different types of modalities that can be used in conjunction with cancer immunotherapies, but the sentiment is also highly relevant to the FLT3 AML space.
The critical questions we need to think here about are:
- What’s different about the various approaches?
- What can we learn from the FLT3 experiences to date that give us clues about the changing landscape in AML?
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We have followed the roller coaster development of the Bcl2 inhibitor, venetoclax (ABT–199/GDC–0199), for several years now. There have been some lowlights along the way, but lately, things have been much rosier for AbbVie and Genentech as a more sensible dosing and patient management approach has been paying off.
Recently at ASCO and ASH, we have seen encouraging new data emerge in leukemia (AML and CLL), lymhomas (NHL), and even multiple myeloma.
New data has now emerged that looks quite interesting in another blood disorder. Today, we took a look at the data and also the potential implications for venetoclax’s development program.
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Much has been written about the success of checkpoint blockade in solid tumours over the last couple of years with the advent of anti-CTLA4 therapy (ipilimumab/Yervoy) for metastatic melanoma followed by the more recent approval of the anti-PD-1 antibodies in advanced melanoma (pembrolizumab/Keytruda and nivolumab/Opdivo) and lung cancer (nivolumab).
What about hematologic malignancies though?
At the recent American Society of Hematology (ASH) conference, we heard about the first clinical data for anti-PD1 antibodies in patients with refractory classic Hodgkins Lymphomas (cHL) and saw some impressive results. Interestingly, though, the early preclinical work was conducted in mice looking at CTLA4 blockade in a variety of tumours, both solid and liquid.
Is there a rationale for targeting CTLA4 in leukemias, lymphomas and even myeloma? New data presented at a medical meeting in patients with heavily pre-treated and relapsed disease post stem cell transplantation suggests that this might be feasible.
Check out to today’s article to learn more about this clinical opportunity in more detail – you can log in or subscribe in the box below.
The 2015 Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2015) was held in Istanbul from March 22-25, where it offered a European perspective on some of the latest developments in cancer immunotherapy.
We’ve heard a lot in the United States about the early CAR T cell therapy clinical trial results from institutions such as UPenn, CHOP, MSKCC, Fred Hutchinson, Seattle Children’s, the NCI, and MD Anderson to name but a few, so it was good to see a leading a European center join the club: University College London (UCL).
While completing a Masters degree in Human and Applied Physiology at King’s College London, I spent several weeks training at UCL and particularly enjoyed the intercollegiality of the University of London.
At EBMT15, Dr Sara Ghorashian Clinical Training Fellow at the Insitute of Child Health at UCL, presented data on a phase 1 trial of Epstein Barr virus (EBV) specific T cells transduced with a first generation CD19 Chimeric Antigen Receptor (CAR). The trial data was first reported by Dr Ghorashian (pictured below) in an oral presentation at #ASH14 (Abstract 383).
Dr Ghorashian stated at EBMT that UCL have several CAR T cell therapy trials planned.
Readers will be aware that earlier this year that UCL spun-off a series A funded company, Autolus, to commercialize their CAR T cell therapy research.
Although £30m from Syncona (a subsidiary of the Wellcome Trust) is not a lot of money by US investment standards, UCL is nonetheless a European center to watch if you have an interest in the CAR-T competitive landscape.
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The announcement earlier this week that Cellular Biomedicine Group (NASDAQ: CBMG) has acquired rights to the Chimeric Antigen Receptor T cell (CAR-T) therapy of the PLA General Hospital in Beijing (pictured right) should come as no surprise to industry watchers. (Link to Press Release).
The share price in $CBMG has risen from $16.31 on February 4 to $23.60 as of close of business on Feb 10, 2015 in what looks like a poorly kept secret! It looks like most of the rise in share price took place immediately prior to the company’s formal Feb 9, 2015 announcement of the Chinese deal.
Those following the cancer immunotherapy space have known for some time that several Chinese groups are working on CAR-T cell therapies that could be a threat if licensed or acquired.
Given the significant investor interest in this space, which is almost bordering on “tulip mania,” it’s entirely foreseeable that companies looking to share in this opportunity would go looking towards China.
One investor on Twitter in response to this news asked should Chinese data be trusted?
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After last week’s post on therapeutic tumor infiltrating lymphocytes (TILs), we received a bunch of questions from readers.
I don’t have time to answer them all in detail individually (sorry!), but it does provide an opportunity to review the evolving landscape and address some of them within the latest article.
It seems to be a good time to take a broader look at T cell manipulation, especially as it pertains to the application of TILs, chimeric antigen receptors (CAR), and T cell receptors (TCR).
We’ve certainly come along way since the historic lecture in 1991 pictured right (photo: National Institutes of Health), but there’s still some way to go before the full potential of cancer immunotherapy is reached.
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A couple of years ago we had a lot of fun here on BSB following the progress of ibrutinib (Imbruvica), obinutuzumab (Gazyva), and idelalisib (Zydelig) in CLL and indolent NHL. It seemed back then that the stunning trio were the hot topics for some time at ASCO and ASH meetings. Exciting times! All three target different entities (BTK, anti-CD20 and PI3K-delta) and made it past the tape to market, with Gazyva leading, Imbruvica a close second and Zydelig a slightly more distant third. I was reminded of the race again over the last week or so as the 4Q earnings were announced, with Pharmacyclics reporting almost $500M for Imbruvica last year and estimating sales to hit $1B in 2015. In contrast, Zydelig revenues for 2014 were $23M, reflective of their much later market entry in the US.
Still, that was a pretty impressive set of drugs all in development at the same time.
Two other agents we also reported on regularly were Infinity’s IPI-145, a PI3K delta-gamma inhibitor, and ABT-199/GDC-0199 (now known as venetoclax). I haven’t heard much about the former of late, but after a few missteps, the next big question to consider is whether venetoclax is coming back strongly or destined for dog drug heaven?
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