Biotech Strategy Blog

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

Posts from the ‘pancreatic’ category

Packed sessions at AACR19

Atlanta – We’ve had a few requests to discuss the Apexigen anti-CD40 data presented by Dr Robert Vonderheide (Penn) presented at AACR19 on Sunday.

That’s a request we happy to oblige.

There seems to be quite a difference in reactions between researchers and investors on this issue, so it’s a nice opportunity to put the data in appropriate context.

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MD Anderson Cancer Center

Houston, Texas – Advanced pancreatic cancer is a very tough disease to treat, so it is not surprising that by 2030 it will be the No. 2 cancer killer in the United States, according to one of the speakers at the recent 1st Annual Symposium on Pancreatic Cancer held at the MD Anderson Cancer Center earlier this week.

There’s also high unmet medical need for new effective therapies for pancreatic cancer, which is why events that promote collaboration and cross-fertilization among leading experts are important.

I found out about the event from Twitter thanks to tweets by Dr Anirban Maitra (@aiims1742) who shares a lot of information. Do follow him if you don’t already.

Thank you to everyone at MD Anderson for putting on a panel of excellent speakers. The meeting was well worth attending and I hope it will become an annual event.

In this post I’ve captured some of the key take-homes that I took from the symposium.

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At the recent ASCO 2018 Gastrointestinal Cancer Symposium (GI18), Steven. D Leach MD (Dartmouth) gave an excellent Keynote Lecture on “Mapping the Immune Landscape in Pancreatic Cancer.”

Pancreatic cancer has very poor outcomes, with a one-year relative survival rate (across all stages of the disease of 20%) and five-survival rate of 7% according to the American Cancer Society.  In addition, stage IV exocrine pancreatic cancer has a 5 year survival of about 1%, which is utterly dismal to say the least.

When it comes to cancer immunotherapy, so far we’ve not seen the success in pancreatic cancer that we’ve seen in other tumours, there are no FDA approved cancer immunotherapies for this disease.

Which raises a critical question of what is happening in the immune landscape of pancreatic cancer patients, and how will cancer immunotherapy be effective?

In this post, we discuss some of the key points that Dr Leach made in excellent presentation and look at some new developments on the horizon in PDAC.

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Sometimes initial phase 1/1b readouts at cancer conferences produce quite different reactions from a live and remote audience while at other meetings, the Developmental Therapeutics talks produce little or no interest at all. It’s often hard to guage which way they will go.

At SITC this weekend, several talks generated some contentious, and at times quite heated, debate and intense interest.

One of these was an oral presentation by Dr Zev Wainberg on the first-in-man data with the anti-CSF1R and anti-PD1 inhibitors, cabiralizumab and nivolumab, from Five Prime and BMS respectively, in an advanced pancreatic cohort.

Dr Zev Wainberg at SITC 2017

There was a surprising amount of confusion surrounding the initial results and other issues last week, with Five Prime’s stock dropping before we’d even got to Dr Wainberg’s talk.

What became increasingly obvious over the weekend was a clear difference in investors perceptions versus what the scientific community actually thought.

Here we take a look at the data and explain what to watch out for and why…

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The DNA in a human cell undergoes thousands damaging events per day, generated by both external (exogenous) and internal metabolic (endogenous) processes. Unfortunately, some of these changes can generate errors in the transcription of DNA and subsequent translation into proteins necessary for signaling and cellular function. Genomic mutations can also be carried over into future generations of cells, if the mutation is not repaired prior to mitosis.

This DNA damage repair from normal cell cycle activity is a field with a large body of research over the last decade or so. Damage to cellular DNA is ultimately involved in mutagenesis and the development of some cancers.

Clinically, there are a number of different ways that can be utilised to help repair the damaged DNA. One approach that is included in this category is the poly ADP ribose polymerase (PARP) inhibitors, which target the enzyme of the same name. I first wrote about PARPs on PSB way back in 2006 – you can check out the short posts for some basic background information on PARPs (here).  Fast forward to 2014, and another post highlights some of the challenges and issues associated with developing targeted agents, including PARPs.

In 2009, the hot buzzword of the AACR Molecular Targets meeting was ‘synthetic lethality’, a term that is highly relevant to understanding DNA mismatch repair and PARP inhibitors. Hilary Calvert gave a detailed talk on synthetic lethality and PARP inhibition at that meeting, where many attendees, myself included, were struggling to understand quite what he meant.

The lead scientist at KuDos, Dr Mark O’Connor, (note: KuDos was subsequently bought by AstraZeneca) had a nice poster on their PARP inhibitor in development at that very same meeting.  I’ll never forget our animated discusson and his simple analogy of a three-legged coffee table, removing one of the legs to cause instability and falling over as a great metaphor for what happens with synthetic lethality.

To this day, every time the leading British researchers in this field, Profs Hilary Calvert or Alan Ashworth, mention ‘synthetic lethality’, I immediately think of the unstable and wobbly coffee table visual!

Incidentally, the KuDos/AZN PARP compound in preclinical development back in 2009 subsequently became olaparib… is now Lynparza, marketed by AstraZeneca, and available on both the US and EU markets for refractory ovarian cancer with germline BRCA mutations. The EU approval is specifically in platinum-sensitive disease.

Since then, we’ve seen iniparib (Sanofi) fail badly in phase 3 in a poorly designed catch-all study that didn’t screen or test patients with triple negative breast cancer (TNBC) for BRCA mutations (doh!) and three new promising next generation PARP inhibitors emerge – veliparib (AbbVie), rucaparib (Clovis) and talazoparib / BMN 673 (Biomarin).  All three of these have received attention on this blog in the past (check the links).

In this article, we discuss what’s happening with Biomarin’s PARP program based on their latest update at the recent San Antonio Breast Cancer Symposium (SABCS) last month.

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San Francisco – In the ASCO GU prostate cancer session yesterday morning one of the most interesting presentations was by Andrew J Armstrong, Associate Professor of Medicine and Surgery at the Duke Cancer Institute.

I previously referenced Dr Armstrong’s excellent education presentation at ASCO 2012 in my piece on Xconomy about the emerging challenges of prostate cancer drug development.

He’s a speaker that I particularly enjoy listening to, so my attention was immediately drawn to his presentation at ASCO GU on, “Beyond Enzalutamide and Abiraterone: What’s Next in Androgen Therapy.

Looking at this title, at first glance the question that comes to mind is do we really need new treatments that target the Androgen Receptor (AR), after all we’ve heard this week about the PREVAIL trial with enzalutamide?

Based on Dr Armstrong’s presentation the answer is a resounding yes!

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The 2014 ASCO Gastrointestinal (GI) Cancer Symposium takes place in San Francisco from Jan 16-18 and is the second meeting in this year’s oncology conference calendar. GI cancers include oesophageal, gastric, colorectal and pancreatic cancers, as well as hepatocarcinoma or HCC (liver).

You can follow any tweets from ASCO GI using the hashtag #GI14.

This year, the topics that most caught my eye in the program were pancreatic and gastric cancers.

This post provides insights on the key studies that looked interesting to me at this event, based on the schedule available.  The abstracts will be available on January 14th and can be accessed here.

Companies mentioned: Celgene, Lilly, Roche/Genentech, Aduro Biotech
Drugs mentioned:  Abraxane, Gemzar, ramucirumab, Avastin, Herceptin, GVAX

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Boston – at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference today, preclinical data was presented on a first-in-class antibody-drug conjugate (ADC) targeting guanylyl cyclase c (GCC) expression in pancreatic cancer.

Petter Veiby, Ph.D, Global Head of BioTherapeutics, Oncology DDU at Takeda Pharmaceuticals International Co. in Boston, MA took the assembled press corps through data that showed MLN0264 demonstrated antitumor activity in GCC-pancreatic cancer xenograft models.

In drug development, as in life, timing is everything. The recent FDA approval of Celgene’s nab-paclitaxel (Abraxane) has changed the standard of care in pancreatic cancer.

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At ASCO 2013 Daniel D. Van Hoff, MD, Physician-In-Chief of the Translational Genomics Research Institute (TGen), presented the data for the phase III pancreatic cancer MPACT trial that compared weekly nab-paclitaxel (Abraxane) plus gemcitabine (Gem) versus gemcitabine alone (ASCO 2013 Abstract 4005).

The results were first presented at the ASCO GI meeting earlier this year, so what’s new here?

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