With various acquisititions occurring in the wake of #JPM18 plus CAR T cell therapy being back in the news this morning following the proposed Juno acquisition by Celgene following on from the recent Kite/Gilead deal, not to mention some recent publications on the role of checkpoints in enhancing the technology, I wanted to explore a related area:
It’s time to talk about ICOS…
Before you think I’ve gone completely over to the dark side talking about blockchains, rest assured that we do not refer here to Initial Coin Offerings i.e. an unregulated means by which funds are raised for a new cryptocurrency venture, but rather to an inducible co-stimulator of T cells that is structurally and functionally related to CD28.
In short, it’s an immune stimulatory rather than inhibitory checkpoint target that is gaining attention of late and is something we are likely to hear a lot more about over the near term.
Related to this is highlighting up and coming biotechs in the IO space who are exploring novel targets beyond the obvious anti-PD(L)1 focus since we need to see what might happen with IO-IO combinations as a way to improve responses and outcomes such that more people with cancer can receive benefit from immunotherapy.
Here, we offer a look at a biotech active in this space to learn what their approach is and where their pipeline is going in the near to medium term future.
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SITC 2017 at the Gaylord Hotel, MD
It’s that time of year already and it has come around so fast in 2017… yes it’s the annual meeting for the Society for Immunotherapy of Cancer (aka SITC).
This year there are several eagerly anticipated presentations, one of which is Juno’s ill-fated ROCKET trial in adult ALL using their JCAR015 CAR T cell therapy.
While Novartis and Kite both successfully made it to market recently in pediatric ALL and aggressive lumphomas, respectively, Juno were left languishing in a poor third place after a series of lethal cerebral oedemas scuppered the program. In the meantime, Novartis are relentless chasing Kite with their JULIET trial in DLBCL and could well have the third CAR T cell therapy indication.
Finally, we heard for the first time today what the company learned from the recent analysis of the deaths, which they shared with the field this morning. BSB was on the spot to hear more about what the CMO, Dr Mark Gilbert had to say and we also have some thought leader sentiments on their perspective of the findings.
That’s not all though, as there was also new data on checkpoint blockade and other immunotherapies that are in early development as well as developments on the biomarker front.
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With so much data to cover recently, we haven’t have time for a perennial favourite, the monthly mailbag to answer BSB reader Q&A on hot oncology topics.
October has brought out quite a lot of controversy to consider, most of it happening in the last week!
Here, we consider questions on Immune Design’s phase 3 trial with their NY-ESO-1 vaccine, CMB305, which attracted both a lot of market attention and also questions from readers.
We also review a bunch of questions relating to 1L NSCLC and the upcoming readouts. This niche is probably potentially one of the most competitive spaces in oncology R&D at present and readers seem almost insatiable for information on this topic.
It is quite a turnaround considering the last decade of numerous failed trials or even non-inferiority studies that were being conducted.
Like many readers, I can well remember sitting in freezing cold, half empty halls wondering if the latest chemo or targeted therapy doublet was going to offer a mere 2-3 months improvement in PFS and no OS benefit or not. It was that binary and also depressing.
With the possibilities offered by immune checkpoint blockade, in a short space of time 1L NSCLC has gone from graveyard to uber intense with several companies vying to demonstrate improvements in overall survival by 6 months or more.
There’s a lot more to come here and not all of the lung trials will be positive – that’s expecting too much against the game of chance. Here, we look at numerous factors that could make a difference, both positive and negative.
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Last week we reviewed some of the promising oral late breaking abstracts and highlighted what to watch out for (W2W4) from our key selections.
National Harbor, DC
This week, it’s the turn of the poster late breakers to be in the spotlight.
There are several approaches worthy of highlighting, but as always, there are also some potential pitfalls for readers to be aware of.
After all, life in the oncology R&D fast lane is as never easy or predictable as the changing of the seasons.
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One of the biggest challenges that many people have in cancer research is spottng opportunities in a cosntantly swelling sea of data.
That situation gets ever more difficult as the year and cancer conference season goes on and a raft of new data evolves from not just monotherapy studies, but also combination trials.
Add in numerous tumour types and patient subsets…
And then there’s another layer (or five) of additional sophistication from newly emerging targets, different approaches undertaken and novel ideas explored.
Who want’s to play 3D chess?
It’s a little bit like slowly peeling an onion, strip by strip, until we get to the heart of the matter. This can take time. Meanwhile, preclinical data at previous meetings that many barely noticed at the time comes back to be looked at in a fresh light with newly emerging clinical data. And we start to see things quite diffferently with this new information.
Talking on the onion, we decided to kick off our annual SITC series ahead of the event next month with a look at five key presentations that should be interesting and advance the field in terms of potential impact.
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Cancer immunotherapy has been very much focused on T cells of late, but perhaps we shouldn’t ignore the importance of the innate aspect of the immune system and how that might help generate cytolytic activity to help kill cancer cells.
Regular readers will know that we’ve been following the potential of Natural Killer (NK) cell therapy and targeting NK checkpoints.
Sculpture in Mainz
At the recent CRI-CIMT-EATI-AACR international cancer immunotherapy conference in Mainz, we spoke with a scientist active in NK cancer immunotherapy research.
Dr Nicholas Huntington (@Dr_Nick_Bikes) leads a laboratory at the Walter and Eliza Hall Institute (WEHI) of Medical Research in Melbourne, Australia. He’s also co-founder of oNKo-innate, a startup company focused on developing innate immunotherapies.
After his presentation in Mainz, he kindly spoke to BSB about his NK cell research and its potential as a novel target for cancer immunotherapy.
Here’s a short excerpt from our discussion:
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Pancreatic adenocarcinoma is a tough disease to deal with given that it is portends poor clinical outcomes, aggressive tumour biology, and early metastatic spread. Not surprisingly, we have seen very little improvements in terms of clinical outcomes with anti-cancer therapeutics. Surgery (for early stage disease) and intense chemotherapy (for metastatic disease) remain the bedrocks of treatment to this day.
From an immunotherapy perspective, there are also additional barriers and hurdles to overcome including, for example, lack of high mutational load, a complex inhibitory tumour microenvironment, and even a physical barrier in the form of the stromal layer.
Not surprisingly, all of these factors combine to make companies reluctant to rush into clinical trials with immune checkpoint blockade, accepting that we really need to understand the underlying tumour biology better before attempting such an endeavour.
At a recent cancer conference we heard an uplifting talk from a research group who are attempting to tackle this issue and offer some pointers on where there may be some near-term opportunities that are worthy of discussion.
Before we can even consider what delivery system or adjuvant to use, we first have to do the scientific investigations into what’s special about exceptional responders and characterize those.
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Mainz – At the recent CRI-CIMT-EATI-AACR international cancer immunotherapy conference in Germany, one of the underlying themes of the conference that attracted considerable attention from speakers and poster presenters was neoantigens, and how to generate cancer vaccines directed against them.
One of the European leaders in the field is Professor George Coukos who is Director of the Department of Oncology at the University of Lausanne Hospital and Director of the Lausanne branch of the Ludwig Institute for Cancer Research.
Lausanne is an exciting place for innovative translational oncology work with the Swiss Cancer Center, that Coukos also directs, creating synergy between partner institutions co-located in the Lausanne University Hospital (CHUV).
We last spoke to Prof Coukos 18 months ago and much has happened since then. In Mainz, he kindly agreed to speak to BSB again and provide an update on progress.
This time we talked about the cancer vaccine research that he and collaborators such as Dr Lana Kandalaft are pioneering in Lausanne, and how this could best be applied in ovarian cancer. It was exciting to hear him discuss his vision and some of the ambitious goals he hopes will be possible within the field.
Here’s a short excerpt from the interview – he has an interesting story to tell:
This expert interview is part 5 of our onging mini-series on the Future of Cancer Vaccines.
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Mainz: At the third CRI-CIMT-EATI-AACR international cancer immunotherapy conference held in Mainz recently, one of the emerging themes from an exciting and interesting meeting was novel cancer vaccines.
Despite the announcement last month that the Bavarian-Nordic phase 3 PROSTVAC trial in prostate cancer was futile (See post: PROSPECTing for nuggets with PROSTVAC in CRPC), therapeutic cancer vaccine research is experiencing a renaissance.
In this new mini-series, we’re featuring interviews with leading scientists and clinical researchers at the forefront of cancer vaccine research.
It’s not meant to be an exhaustive list of the “good and great,” as not all leaders in the field were actually in Mainz, but nonetheless we hope this series, like a series of postcards, captures some of the excitement along with challenges and opportunities facing researchers at present.
Up next is Professor Cornelius “Kees” Melief, who is Emeritus Professor at Leiden University in the Netherlands and Chief Scientific Officer of ISA Pharmaceuticals – where ISA stands for Immune System Activation.
Earlier this year, Professor Melief received a lifetime achievement award from the Association for Cancer Immunotherapy (CIMT) for his work in research in this niche.
He’s a global expert on cancer vaccine research. Ironically, back in July he published an editorial in Nature entitled, “Cancer: Precision T-Cell therapy targets tumors” that discussed some two letters on neoantigen cancer vaccine research from other thought leaders we have interviewed in this current mini-series, namely Dr Cathy Wu (Link) and Prof Ugur Sahin (Link).
While, in Mainz, Professor Melief kindly shared his thoughts on the field, where it is going, and how ISA Pharmaceuticals are looking to make a difference. Here’s an audio postcard for those interested in hearing a sample of what he had to say…
This is the fourth interview in our mini-series on the Future of Cancer Vaccines.
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One of the pioneers and leading entrepreneurs in the development of personalised cancer vaccines is Professor Ugur Sahin.
In addition to being CEO of the privately-held biopharmaceutical company, BioNTech, he holds an academic appointment at the University of Mainz and is Managing Director of the translational research institute TRON.
This makes Mainz the perfect location for a cancer immunotherapy conference. It’s also where the Association for Cancer Immunotherapy (CIMT) is located. They were the local organisers of the 3rd annual CRI-CIMT-EATI-AACR cancer immunotherapy conference that we recently attended along with over 1400 people from around the world.
One of the underlying themes of the meeting and the posters was the development of personalised cancer vaccines, which is why we’re doing an extended mini-series based on interviews we did in Germany with leaders in the field.
Prof Sahin is a busy man, but we tracked him down in the poster hall. Here’s a brief excerpt from the impromptu interview he kindly gave to BSB.
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