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Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts from the ‘Inflammation’ category

New Orleans – one of the presentations of note at Immunology 2015 (the annual meeting of the American Association of Immunologists) was by Thomas J. Gajewski MD, PhD from the University of Chicago. His presentation on “Innate immune sensing of cancer via the STING pathway” was well worth the trip to New Orleans.

Presentation by Dr Gajewski at Immunology 2015

Readers may recall the post we wrote in March on “What is STING and why does it matter in cancer immunotherapy?” It followed the news that Novartis were collaborating with Aduro Biotech (NASDAQ: ADRO) on agonists that activate the STING (Stimulator of Interferon Genes) signaling pathway in immune cells.

I had the privilege to talk with Dr Gajewski (pictured below) after his presentation at AAI.

Dr Tom Gajewski AAI 2015

Excerpts from the interview will feature on Episode 2 of the Novel Targets podcast (@TargetsPodcast). (Do sign up for the Novel Targets Newsletter if you want to be among the first to know when this will air). Subscribers can read more from the interview below.

You should read and/or buy access to this post if you don’t know the answers to the following:

  • What role does the tumor microenvironment play in response to cancer immunotherapy?
  • How could the tumor microenvironment be a biomarker of response to checkpoint inhibitors?
  • Why target the STING pathway?
  • Reasons Novartis are collaborating with Aduro Biotech?
  • How may a STING agonist be brought to the clinic?

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T cell activation has been very much to the fore over the last couple of years with many companies looking at different ways to use them against cancer cells, with chimeric antigen receptor (CAR) T cell therapy, vaccines or monoclonal antibodies. There are situations though, where T cells are not necessarily a good thing.

Graft versus Host disease (GvHD) is an area of tremendous unmet medical need that is triggering the interest of a number of biotech and rare disease companies such as Alexion Pharmaceuticals (ALXN).

Houston based Bellicum Pharmaceuticals (BLCM), whose IPO raised around $140M last month, have said they plan to spend most of the funds on bringing to market a new cell therapy that could make stem cell transplants more effective and reduce GvHD. They also have a CAR-T therapy in early development.

Indeed, at last month’s ASH 2014 annual meeting in San Francisco, GvHD was very much a hot topic, with data presented in the plenary session by Dr Wei Li (pictured below) on a novel biomarker for GI GvHD.

Dr Wei Li ASH 2014 GvHD Plenary

This post discusses one of the GvHD oral sessions at ASH 2014, and includes post-presentation commentary from Dr Marcel van den Brink, who is an expert in the area. The related interview Dr Brink kindly gave BSB at the SITC annual meeting is well worth reading if you missed it.

Subscribers can read more by logging in or you can purchase access to Biotech Cancer Conference coverage by clicking on the blue icon at the end of the post.

At the recent 2014 annual meeting of the Society for Immunotherapy of Cancer (SITC), it was surprising to see how many people stayed till the bitter end of the conference to attend the Hot Topic Symposium on Accelerating Tumor Immunity with Agonist Antibodies.

Readers are well aware of the potential of cancer immunotherapies that block immune checkpoint receptors. After all, the FDA has already approved antibodies that block CTLA–4 (ipiliimumab) and PD–1 (pembrolizumab) in metastatic melanoma, with nivolumab (Opdivo) currently being reviewed for advanced melanoma and lung cancers.

These antagonists, and others in development targeting the PD-L1 signalling pathway, such as MEDI4736 and MPDL3280A, act to reduce the engagement of inhibitory receptors on the T-cell. This results in a releasing of a brake on the T cell response, enabling killer T cells to attack the tumour(s).

CD40 in cancer Source: Costello et al., 1999

However, in order to stimulate an immune response, particularly in tumors with few natural T cells, it is likely that agonist antibodies will be required that act on stimulatory signalling receptors on T cells and antigen presenting cells (APC’s).

In a previous post from SITC, we discussed the potential of agonists targeting OX40, and the rational for combining an anti-OX40 antibody with an anti-PDL1. This is one of the hottest targets that thought leaders are excited about from our discussions.

It isn’t the only one of interest though. Another potential stimulatory target that might be suitable for combination with anti-PD–1/PD-L1 is an antibody against CD40 (not to be confused with OX40). The pathway (shown right) is quite complex.

Subscribers can login to read more about another fascinating talk from SITC 2014 on where the cancer immunotherapy may be heading.

National Harbor MarylandThe Society for Immunotherapy of Cancer (SITC) annual meeting promises to be a most interesting one, if the first day is anything to go by. It’s being held this week at National Harbor, Maryland on the banks of the Potomac River just south of Washington DC.

As the meeting started with some intensive workshops yesterday, the American Society for Hematology (ASH) annual meeting abstracts were released at 9am, giving up a choice between writing up SITC in situ or switching gears and analysing the initial hematology abstracts. In the interests of sanity, we have decided to focus on SITC for the next week, then move onto the AACR-NCI-EORTC conference, before reviewing the ASH data in detailed previews.

SITC is mostly a translational science meeting with a little bit of relevant clinical data through in here and there. It’s also not for the faint hearted, especially given the sheer intensity and pace of some of the talks – keeping up with pen and paper to hastily scribble notes is surprisingly quite hard!

It was an honour to attend as one of the few members of the media here. The excitement is palpable, with speakers reminding us of how only a few years ago, few people attended immunotherapy sessions at ASCO. SITC is rapidly becoming a major meeting with a record-breaking 1500 expected for the first time! It is the immuno-oncology meeting to attend for those interested in understanding the emerging trends, landscape and direction that research is taking us.

Yesterday SITC fielded two workshops with impressive line-ups from the immuno-oncology space that included Drs Carl June, James Allison, Tom Gajewski, Susan Topalian, Stephen Hodi and Mario Sznol, to name a few. The workshops focused on different topics:

  • A basic one on understanding the immune system
  • A more advanced one on combination strategies in immunotherapy

Rather than summarise all the talks from both sessions that ran a full day each, we’ve decided to focus on some themes, ideas and concepts that catch our attention each day. Here’s the first of our daily reviews from the SITC 2014 annual meeting. Thanks to all our subscribers whose support enabled us to attend this meeting for the first time.

To learn more about our impressions from the SITC immunotherapy workshops yesterday, you can sign in or sign up below.



“Nothing lasts forever, because nothing ever has.”

James Shelley, The Caesura Letters

This year’s annual AACR meeting was so good, we could probably write another 50 posts and still not be done! With ASCO fast approaching, however, it’s almost time to draw it to a close and the final post conference note will be published on Monday.

Today is the penultimate report and focuses on the key highlights that caught my attention in immuno-oncology, which covers the gamut from checkpoint inhibitors, co-stimulants, innate immunotherapy and CAR T cell therapy to bispecific antibody TCRs.

To learn more about our insights on the highlights and lowlights, you can sign in or sign up below.

Today I thought it would be a good idea to answer a question sent in by a premium subscriber.  He asked,

“What’s the deal with TIL and how does that relate to checkpoint inhibitors and PD-L1 expression?”

This is a good question and there were some interesting top-line debates about this at AACR recently, which are well worth discussing and highlighting.

To learn more about this emerging trend, sign in or sign up below to read our insights.

Sometimes you get lucky before a conference and catch an interview with a thought leader ahead of time when it’s more relaxed and less fraught with all the demands of meetings etc while there.

rick young

Dr R Young, Source: WI

That good fortune happened to me on the Friday before the recent AACR conference in San Diego, when I recorded an interview with Dr Richard Young, (Whitehead Institute & MIT and scientific co-founder of Syros), who was giving a plenary talk on the Sunday at AACR entitled, “Transcriptional and Epigenetic Control of Tumor Cells.”

Epigenetics and transcriptional changes are fascinating concepts to me because they get right to the heart of what’s going on deep in the oncogenes and how they control processes in cancer. Clearly, in simplistic terms, if we can understand how things change and evolve, then we can potentially devise better strategies to overcome them. Instead of targeting a protein kinase with a small molecule or a cell surface antigen with a monocloncal antibody, this is an altogether different approach. Protein-protein interactions such as MYC, RUNX1, p53/TP53 etc have long been the bugbear and frustration of many good researchers, precisely because they are challenging to target with conventional approaches.

So what’s new and why am I really excited about these new developments?

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We’ve been hearing and writing about a substantial amount of news and information on various immuno-oncology developments over the last year, especially in metastatic melanoma and lung cancer, but despite renal cell cancer (RCC) being a proven immune-sensitive disease with known PD-L1 expression, it seems to be the poor cousin to the other two tumour types given the lag in data and relative media attention.

There’s actually quite a lot going on in this disease though, from biomarker work to phase I to III trials that are either ongoing or just started accruing.

We should be hearing much more about the role of anti-PD–1 and PD-L1 antibodies in RCC over the next couple of years, including data from some large randomised controlled trials, but what’s the current state of play?

With that in mind, I was deligted to catch up with David McDermott’s (DFCI) in-depth presentation at ASCO GU in San Francisco over the weekend.  It’s always unfortunate when an interesting talk is left for the final presentation on the last day of a conference, as only a few diehards will be there to catch it!  It was a well thought out discussion though and he covered a lot of interesting ground in this space.

Agents mentioned:
ipilimumab, nivolumab, MK–3475, MPDL3280A, LAG–3, TIM–3, PD-L2, IL–2, sunitinib, everolimus, bevacizumab

Companies mentioned:
BMS, Roche/Genentech, Merck, GSK, Novartis, Pfizer

You can sign in or sign up below to read my analysis of the state of play of immuno-oncology in the kidney cancer market.


A scientific meeting that I would have liked to have attended and one where I think attendees will obtain a lot of insight into the future of prostate cancer research is the forthcoming American Association for Cancer Research (AACR) Advances in Prostate Cancer Research meeting.

AACR Advances in Prostate Cancer Research Meeting 2012Chaired by Charles Sawyers (MSKCC) and Arul Chinnayan (Michigan) it has an impressive line-up of speakers and sessions.  The meeting takes place next week (Feb 6-9) in Orlando.

There are two presentations on cabozantib (XL184) that may offer new insights into the mechanism of action of the drug and its potential:

Cabozantinib (XL-184) and prostate cancer: Preclinical and clinical profile of a novel agent

Maha Hussain, University of Michigan Medical School, Ann Arbor, MI

Cabozantinib (XL184) inhibits androgen-sensitive and castration-resistant prostate cancer in the bone and increases bone formation in non-tumored bones
Eva Corey, University of Washington, Seattle, WA

A few of the presentations at the meeting that caught my attention include:

  • Role of inflammation (William Nelson)
  • Influence of tumor microenvironment on progression and resistance (Christopher Logothetis),
  • Novel therapeutic targets in prostate cancer (Arul Chinnaiyan)
  • Overcoming castration-resistant prostate cancer 
(Charles Sawyers)

If you have in an interest in prostate cancer research, February 6-9 in Orlando is the place to be.

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The Oncologist Journal of the Society for Translational Oncology (STO) has published a video recording on prostate cancer that is well worth watching for those with an interest in this area.

At their Sept 8, 2011 CME symposium held in Belfast, a roundtable was held entitled “Prostate Cancer: Progress & Promise.”

Moderated by Bruce A. Chabner (Mass General/Harvard), the panelists were Joe O’Sullivan (Queen’s University, Belfast), Johann De Bono (The Institute for Cancer Research) and David Waugh (Queen’s University, Belfast).

Professor de Bono in the video comments that”

“with regards to our dream of eventually treating men with prostate cancer without castrating them, which must be our ultimate goal and curing them of cancer. I think we will have to focus on for example drugs targeting ERG or ERG signaling.”

Chabner then asks the good question of whether ERG is a druggable target?

To which De Bono replies that you can drug ERG by inhibiting PARP and references a paper by the Chinnaiyan group published in the May 2011 issue of Cancer Cell.

PARP inhibition represents an interesting area of prostate cancer research.

If you would like to know more, Sally Church, PhD has written about this on Pharma Strategy Blog.  See posts on “TMPRSS2: ERG may be a more useful marker than PSA in prostate cancer” and “Personalized Therapy for Prostate Cancer – is it possible?

In the STO video, De Bono discusses why he would like to replace bone scans in prostate cancer with another imaging modality that more accurately reflects the activity of the disease. Future possibilities include use of diffusion weighted magnetic resonance imaging and novel PET tracers.

There’s also a good discussion about Alpharadin for those interested in some anecdotal commentary on experiences with it.

Another notable comment by De Bono is his belief that “taxanes work in prostate cancer primarily by targeting androgen receptor signaling.” Taxanes have typically been thought to target mitosis.

De Bono goes on to say that clinical trial data being submitted for publication shows that patients who are refractory to abiraterone, are also refractory to docetaxel when they progress on it.  The suggestion is that there may be cross resistance between abiraterone and taxanes with a subgroup of patients who just don’t do well on androgen receptor (AR) targeting drugs.  The reason for this isn’t yet clear.

A new phase 2 clinical trial is starting soon that will look at the sequencing of abiraterone and cabazitaxel.  One group will receive abiraterone followed by cabazitaxel, the other cabazitaxel followed by abiraterone.

The Belfast STO symposium was the second in a three part series. The next one will be held during ASCO GU in San Francisco next year.

Another potentially useful meeting in this area is the February 2012 AACR workshop on “Advances in Prostate Cancer Research” chaired by Arul Chinnaiyan & Charles Sawyers.

Prostate cancer remains an exciting therapeutic area to watch with tremendous progress and promise of late.

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