Biotech Strategy Blog

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

Posts tagged ‘Pancreatic Cancer’

Dr James Gulley is Chief of the Genito-Urinary malignancies branch and Director of the Medical Oncology service at the National Cancer Institute (NCI) in the National Institutes of Health. He’s a world-leading GU cancer expert and at the forefront of pioneering research to make cancer immunotherapy work in prostate cancer.

We last spoke to him at ASCO 2015 (See post: The future of prostate cancer immunotherapy). You can listen to excerpts from this interview on Episode 4 of the Novel Targets podcast (See: The non-inflamed tumour show).

Almost two years on, and new research by Dr Gulley and colleagues from the NCI shows that the STING pathway may have an important role to play in prostate cancer immunotherapy. Activation of this pathway through a novel mechanism could turn a cold non-inflamed tumor into a more inflamed or hotter one in men with advanced prostate cancer. How cool is that?!

At the 2017 annual meeting of the American Association for Cancer Research (AACR) that was recently held in Washington DC, Dr Gulley graciously spoke to BSB about some of the novel trials that are underway at the NCI, with the aim of making cancer immunotherapy work in men with advanced prostate cancer.

Dr Jim Gulley, NCI at AACR17

This is the seventh expert interviews in our series from AACR17 where we explore the conundrum:

How does Dr Gulley plan to light the immune camp fire in prostate cancer?

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Waiting in line for the White House Tour

The 2017 annual meeting of the American Association for Cancer Research in Washington DC (Twitter #AACR17) officially starts tomorrow, but today was a day full of educational sessions and workshops.

After a day of rain yesterday, it was good to have a dry day for the start of the world’s leading cancer science meeting.

In this post we offer some top-line commentary on those educational sessions we attended; the choice reflects personal interests or current fetishes.

By definition, there is far more excellent research at AACR than we can possibly cover on the blog; so we encourage you to check out the AACR webcasts if you have a specific interest or want to check out a particular session.

We’d also like to congratulate AACR for moving with the times and allowing personal photography and the sharing of content on social media, except where a slide or presentation says “Do Not Post.”

The few slides that I saw today that had “Do Not Post” showed unpublished data. Our longstanding unwritten policy has been not to tweet or share on social media data that clearly states it is unpublished, so this was not an unreasonable request and one we heartily concur with in principle.

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The race to the be first to market in the United States with a CD19 directed CAR-T cell therapy is a bit like the America’s Cup Challenge Race Series – one boat/company is ahead and then another is ahead, it’s an ever changing and fluid situation…

Americas Cup Portsmouth

In this post, we’re looking at questions from subscribers – so what’s in the July BSB mailbag?

* CAR T Cell Therapy: Is the recent FDA hold – that came and went in record time, a setback to Juno? Who will win the CAR-T race to market in the United States? What is the market opportunity in Europe?
* Jounce/Celgene Deal: Celgene have a reputation for doing deals with innovative biotech companies, but then what? Is the Jounce deal a good one, or is it a value destroyer?

There are a few other questions in the mail bag, but the above gives you a flavour of some of the commentary in this post.

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For years we’ve followed the trials and tribulations of targeted therapies seeing many approved and quite a few disappear forlornly (and officially) off to dog drug heaven. Many more sit in no-man’s land as companies eagerly wait in a holding pattern for other trial readouts in different tumour types. Sadly, sometimes these studies don’t generate enough compelling data either. With so much competition about, there are no shortcuts or low-hanging fruit in biotech or cancer drug development any more.

ASCO16 Chicago 1

En route to Chicago and ASCO!

Then along came antibody drug conjugates (ADCs), with some encouraging results in a range of cancers in both solid tumours and hematologic malignancies that lead to the approval of several new therapies.

After that, the next big advance was immunotherapies, specifically checkpoint blockade, with encouraging single agent activity in melanoma, lung, and even urothelial bladder cancer. We’ve also seen the promise fo combining two different checkpoints such as nivolumab and ipilimumab together in metastatic melanoma, albeit with an increase in toxicities.

This is all very well and good, although the challenge remains that the majority of patients either respond to therapy and relapse, or do not respond at all, depending on the circumstances, the tumour type and the regimen. We still have a long way to go in moving the needle and creating a new paradigm shift on a broad scale.

So what happens when we start to combine modalities – such as targeted therapies with immunotherapies?

Uh-oh, I hear the distant cries of disagreement erupt…

  • Remember vemurafenib plus ipilimumab in metastatic melanoma was scuppered by severe hepatitis?
  • What about osimertinib plus durvalumab in NSCLC and the increased incidence of ILD?

Both of these statements are true, and yet… we should not assume that all mixed therapy combination approaches are doomed on the basis of a mere n of 2. What happens if some are synergistic or additive? What happens of there are hidden gems that teach us new ways of doing things rather than doing the same old thing just because it’s always been done that way?

With this in mind, I’d like to open the door on our first ASCO 2016 Preview series with a look at novel combination approaches in development that caught my eye.

What are the early hints and signals that we can learn from the data? Which companies are evaluating imaginative new ideas that may turn the tables on traditional thinking?  The ideas discussed here may well surprise a few people.

To learn more, Subscribers can log-in below or you sign up for a subscription and join the ever burgeoning BSB club of sophisticated lay people – including investors and commercial/new product development people – who can really understand and appreciate the fundamentals of cancer R&D…

Franciscan Crab Restaurant San FranciscoWe saw at ASCO last year that response to checkpoint immunotherapy is feasible in some patients with colorectal cancer, but what about other gastrointestinal tumours such as pancreatic, duodenal and biliary cancers?

Can their activity extend beyond the obvious hypermutated tumours such as melanoma, lung, renal and bladder cancers?

Many of you will know that most pancreatic cancers, for example, are detected late and prognosis in metastatic disease is generally poor. You also typically don’t see much coverage of the other GI non-CRC cancers from cancer conferences in the medical media outside of pancreatic cancer occasionally.

At the ASCO Gastrointestinal symposium (#GI16) this past weekend, there was some new data of note in these tumour types that is well worth highlighting and discussing because it may have a major impact on the GI landscape.

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There are now several CD40 agonist antibodies in early clinical development from several different companies, including:

  • Roche – RO7009789
  • Apexigen – APX005M
  • Seattle Genetics – SEA-CD40
  • Alligator Bioscience – ADC–1013

This post is the last in our cancer immunotherapy coverage from the European Cancer Congress in Vienna. It features excerpts from an interview with Dr Christian Rommel, head of oncology discovery at Roche in Basle, Switzerland in which he talks about the development of their CD40 monoclonal antibody. Readers may recall we wrote about this from SITC 2014 last year: “Targeting CD40 in Cancer Immunotherapy.

This post is also a new primer on CD40 as we start our coverage of the Society for Immunotherapy of Cancer (SITC) 2015 annual meeting. We’re informed by SITC it’s a sell out conference with 600 more people than last year’s record breaking number. Cancer Immunotherapy is indeed the hottest topic in cancer drug development.

If you have plans to be at National Harbor this week, we hope to see you there!

To learn more insights on this intriguing topic, subscribers can log-in or you can purchase access to BSB Premium Content. 

AB Science confirms the filing for the Marketing Authorization Application to the European Medicines Agency of Masitinib in the treatment of Pancreatic Cancer.

AB Science LogoParis based biopharmaceutical company AB Science announced in an October 16 news release that the company has applied to the European Medicines Agency (EMA) for approval of masitinib in pancreatic cancer.

Masitinib is a tyrosine kinase inhibitor of PDGF, PDGFR, FGFR, FAK, c-KIT. A phase 3 clinical trial (NCT00789633) in pancreatic cancer is underway that compares masitinib with gemcitabine to placebo with gemcitabine.  The trial started in November 2008 with an estimated enrollment of 320 patients at 68 study locations. As far as I am aware no data has yet been presented for this trial.

The phase 2 trial results for mastinib in pancreatic cancer were, however, extremely promising.

Alain Moussy, CEO of AB Science in an interview on Pharma Strategy Blog, A leap of faith: AB Science & mastinib in pancreatic cancer, stated that masitinib “is unique its ability to resensitize the pancreatic cell that has become resistant to gemcitabine.

Strangely, the AB Science news release today offers no top line results, and merely states the “communication of results was delayed to allow the filing for patent applications aimed at extending the period of marketing exclusivity.

The presumption from the filing and today’s announcement is that the data for mastinib in pancreatic cancer is positive, which is good news for patients. I look forward to hearing more about the overall survival benefit for masitinib when more data becomes available.

This news also adds to the excitement building in pancreatic cancer, with the Celgene Abraxane data expected before year end.

Update November 1, 2012: Phase 3 Trial Results Announced

In an October 30, 2012 news release, AB Science finally shared the data for their Phase 3 clinical trial (NCT00789633): A Study to Compare Efficacy and Safety of Masitinib in Combination With Gemcitabine, to Placebo in Combination With Gemcitabine, in Treatment of Patients With Advanced/Metastatic Pancreatic Cancer.

I don’t plan to rehash the self-explanatory news release, but the results are mixed. The Principal Investigator, and leading pancreatic cancer experts I contacted (who were not involved with the trial) did not respond to requests for comment. This suggests that we will have to wait till the data is presented at the ASCO GI symposium in San Francisco next year to fully understand the implications for clinical practice.

Bad news: Study failed to meet it’s primary endpoint of showing that masitinib increased overall survival (patients lived longer) when used in combination with gemcitinabine versus gemcitabine alone.

  • Median OS was 7.7 months in the masitinib plus gemcitabine treatment arm versus 7.0 months in the placebo plus gemcitabine treatment arm (p=0.74; hazard ratio=0.90).

The company news release states:

“This finding of a non significant survival improvement in the overall population is explained by the fact that masitinib is not indicated when Gemzar® is highly efficient.”

However, there is some positive news for AB Science, and that is a subset of the 320 patients in the study did significantly live longer with masitinib.

Good news: a subset of pancreatic cancer patients with a novel genetic biomarker for tumor aggressiveness, identified using RNA expression from whole blood samples, lived significantly longer with masitinb.

  • Patients in the subset with this biomarker (65% of the study population) had a median overall survival (OS) of 5 months on gemcitabine alone, while those on masitinib and gemcitabine had an OS of 11.0 months (hazard ratio of 0.29, p=0.000038).

A survival advantage of 6 months with mastinib is a dramatic result!

If mastinib can be used in conjunction with a predictive biomarker that identifies those patients who may likely respond, it is hard not to imagine that some form of regulatory approval would be forthcoming, despite the failure of the trial to meet it’s primary endpoint. However, more clinical data and another clinical trial may be needed to validate the biomarker, if as it appears, the biomarker was identified retrospectively.

There are also many unanswered questions:

  • what is the technology needed to detect the biomarker?
  • is this a test that can be routinely performed?
  • is there a diagnostic kit available?
  • How might such a genetic biomarker be used in clinical practice by non-academic physicians?
  • What is the extent to which the biomarker has been shown to be valid and reproducible?

I look forward to hearing more about the masitinib data at the ASCO GI 2013 meeting.

Update November 6, 2012: Skuldtech identified as diagnostics partner

Another piece of the jigsaw has been provided in a November 3 news release from AB Science that french company, Skuldtech is the company they are working with on a companion diagnostic test for masitinib in pancreatic cancer. As usual, I found the news out first on Twitter:

The AB Science news release states that:

Skuldtech and AB Science plan to exploit these new markers for commercialization of a future companion test associated with masitinib, a molecule developed by AB science for treating pancreatic cancer.

It goes on to say:

“From a simple drop of blood, Skuldtech and AB Science were able to identify specific markers – transcriptomic markers – that can distinguish between the different populations treated during the phase III study and select the predictive markers for pancreatic cancer survival associated with masitinib treatment.”

We await further information on the cost, availability and validation of the companion diagnostic.

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Following on from yesterday’s news that Gilead had acquired Calistoga and CAL-101, another company that is exploring the interface between cancer and inflammation is Paris based AB Science.

Pharma Strategy Blog has an excellent interview with the CEO, Alain Moussy.  AB Science is an emerging French biopharmaceutical company, and I previously wrote about its IPO.

The company has adopted a unique market entry strategy of obtaining approval first in animal health for their tyrosine kinase inhibitor, masitinib.  In 2008, AB Science gained European approval for canine mast cell tumors and in December 2010 FDA approval.

The company recently announced that on February 8, 2011 it had its first US sale of masitinib to vets.

Masitinib is in fact a multi-kinase inhibitor that inhibits wild type and mutant forms of stem cell factor receptor (c-KIT, SCFR), platelet-derived growth factor (PDGFR), fibroblast growth factor 3 (FGFR3) and to a lesser degree, focal adhesion kinase (FAK).

Sally Church on the Pharma Strategy Blog has written about how AB Science’s strategy makes sense – if you look at Pfizer, they obtain more revenue from animal health than they do from oncology.  AB Sciences’ Masivet® in Europe, Kinavet® in the United States competes against Pfizer animal health’s tyrosine kinase inhibitor, Palladia® (toceranib), which also targets mast cell cancer in dogs.

Not only does this growth strategy generate revenue for an early-stage company like AB Science, it also allows the company to build a sales and marketing infrastructure in the United States and Europe while waiting for the results of pivotal phase 3 studies in humans.

The phase 2 clinical trial data for masitinib in combination with gemcitabine in pancreatic cancer were impressive (28% survival at 18 months).  The phase 3 clinical trial results are expected this year.  The clintrials.gov listing shows the date for the estimated primary completion date (Overall Survival) as November 2010 with study completion in November 2011.  Obviously the exact timing depends on how fast subjects were accrued, but I would be surprised if we didn’t see some data presented at ASCO or ESMO, especially if positive.

In terms of targeting inflammation, masitinib is in phase III development for mastocytosis, rheumatoid arthritis (RA) and asthma.  AB Science announced on January 27, 2011 the first patient recruited into their phase 3 study in severe asthma.

The company’s new product development strategy is way ahead of many of its competitors in identifying the links between cancer and inflammation, and choosing to target market opportunities in both areas.

AB Science is an exciting company to watch, and I expect that we will see important new data come out at major scientific meetings this year.

Arc De Triomphe (Paris) in 1000 MegaPixels (Zo...Image by Anirudh Koul via Flickr

An emerging French biotech company, AB Science has plans for an IPO on the Paris based Euronext exchange.  The company is reported to be seeking €50 million.  What makes AB Science interesting is not only that it has a tyrosine kinase inhibitor that has particular promise in pancreatic cancer, but the company has grand designs to follow the growth strategy of biotech companies such as Genentech, Celgene and Biogen Idec.

In the initial company filing with the French Autorité des Marchés Financiers (AMF), the stated corporate strategy is to become a “fully integrated pharmaceutical company (FIPCO)” in order to preserve as much of the potentlal value of the drugs in the pipeline.  Very few biotech companies have been able to succeed with this busienss model, so it will be interesting to see if AB Science makes it.

The CEO of AB Science, Alain Moussy provided insight on his plans for the company in the interview he did last year with Sally Church of the Pharma Strategy Blog.

In the interview he states why AB Science has not pursued alliances or partnerships with large pharma companies:

“Biotechs are owned by venture capitalists, who have a 5 to 7 year cycle to make money, but the cycle of drug development is 10-12 years, so in the middle of the cycle they have to sell where the risk is not too high. Typically, venture capitalists do not care whether the product ends up being approved or not.  Most biotechs end up following this strategy because they are owned by VC firms.  AB Science is owned by entrepreneurs, and we have chosen to dedicate our life to developing products that make a difference.  We have to stay independent, because if we try to make money in the middle of the drug development cycle, then we will just select drugs that we can sell to a big pharma, and this is not what we want.  What we want is stability for the long-term to have time to take the necessary risks to make the right products.”

AB Science is a company to watch, not only because the CEO has a passion for wanting to make a difference to the lives of patients, but their business model is different from many other biotech companies who instead have adopted a licensing and shared risk approach with major pharma companies.

Ultimately, AB Science’s success will rest on clinical data and in particular the phase 3 clinical trial results for mastinib in pancreatic cancer. Recruitment is set to end in this study in mid-2010 with results in 2011.

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