Insights from AACR Molecular Targets Meeting

Posted on November 22, 2011 by Daedalus

San Francisco Transamerica Pyramid © Pieter Droppert 225x300 Insights from AACR Molecular Targets Meeting There was a lot of interesting science at the recent AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics international conference in San Francisco.

In particular, the poster sessions offered the opportunity to discuss pre-clinical and early drug development work, and share insights into pathways and mechanisms of action. If you are in new product development, it’s a key meeting to attend.

What was the news at AACR molecular targets?

Sally Church on Pharma Strategy Blog aggregated the live tweets from the joint AACR-NCI-EORTC meeting, although the absence of wifi in the plenary sessions meant that there were fewer tweets than might have been expected.

Sally has written about some of the data presented on breast cancer at the meeting. In her insightful post she reviews the Syndax data for entinostat in second-line ER/PR+ breast cancer, and also asks whether ALK is a new target in inflammatory breast cancer (IBC)?

From what was heard at the meeting, there will be a lot of new breast cancer data at the forthcoming San Antonio Breast Cancer Symposium (SABCS) that Sally will also be attending.

More insights from AACR molecular targets will be available on Pharma Strategy Blog in the next few days.

Meanwhile on Biotech Strategy Blog, Pieter Droppert has written about some of the sessions he attended in San Francisco on:

Next year’s 2012 molecular targets meeting will be in Dublin, good news for all those who like Guinness!

Opportunities and Challenges with Cancer Immunotherapy

Posted on November 11, 2011 by Daedalus

At Icarus Consultants, we help pharmaceutical and biotechnology companies bring new products to market.

When we look at the market opportunity for a new product, it’s not enough to have a great product, key to success is getting paid for it. Pricing and reimbursement are important in the commercial strategy!

Is it better to obtain the highest price for a new targeted therapy or alternatively have a lower price and obtain more market share? From a marketing strategy perspective, there is sometimes a case to be made for a lower price, but it’s a hard sell to convince senior management they are not leaving money on the table.

As to cancer immunotherapy, Dendreon with sipuleucel-T have shown that it can offer a survival benefits to some cancer patients. Other vaccines and immunotherapies are in development.

However, as Pieter Droppert points out in an insightful post on Biotech Strategy blog about a pilot study for PANVAC (Bavarian Nordic, CV-301), there remain a number of challenges that still have to be overcome. These include:

How do we identify upfront which patients will respond to the vaccine?
How do we evaluate how well patients are doing without clinically validated surrogate markers to aid in assessment?

You can read more on Biotech Strategy Blog.

There is a plenary session on cancer immunotherapy at the AACR-NCI-EORTC Cancer Molecular Targets & Therapeutics conference that starts in San Francisco tomorrow.

We look forward to obtaining further insights on the opportunities and challenges with cancer immunotherapy at this meeting.

Neuroendocrine Cancer Awareness Day

Posted on November 10, 2011 by Daedalus

November 10, 2011 is the second worldwide neuroendocrine (NET) cancer awareness day. Pancreatic NET is what Steve Jobs sadly succumbed to.

In recognition of NET Cancer Day, Sally Church has written an insightful post on Pharma Strategy Blog about pancreatic neuroendocrine tumors and new treatment options. It is well worth reading!

Sally highlights two new therapies for pNET approved by the FDA this year:

everolimus (Afinitor) from Novartis that targets mTOR, downstream of the PI3K/AKT pathway
sunitinib (Sutent) from Pfizer, a multikinase inhibitor

Both showed a benefit over placebo with an increase in progression free survival (PFS). They do, however, have some challenges associated with their side effects.

Sally concludes that “in the future, we may well see sequencing studies emerge as well as other targeted therapies to prolong outcomes for patients with this rare disease.”

We hope that the Neuroendocrine Cancer Awareness day achieves its goal of raising awareness about this disease. You can read more on Pharma Strategy Blog.

Macrophage Cell Surface Protein S100A10 may be new target

Posted on November 10, 2011 by Daedalus

Sally Church, PhD on Pharma Strategy Blog has written about research on macrophage cell surface protein S100A10 and the role this plays in cancer metastasis and tumor growth.

As Sally notes, “macrophages are critical in driving tumour growth, invasion and metastasis. Macrophages are like the Pacmen of cells…” What a great visual metaphor!

Recently published research now shows that the macrophage cell surface protein, S100A10 plays an important role in how macrophages move to the site of tumor growth, a process that is key to tumor development and angiogenesis.

Is S100A10 a potential druggable target? You will have to read Sally’s insightful blog post to learn more.

PARP inhibition in Prostate Cancer

Posted on November 9, 2011 by Daedalus

The Society for Translational Oncology (STO) recently held a prostate cancer symposium in Belfast.

In a post on Biotech Strategy Blog, Pieter Droppert reviews the STO video discussion on “Prostate Cancer: Progress & Promise”

One of the key insights is that targeting ERG signaling may be key to treating prostate cancer, and that ERG becomes a druggable target by inhibiting PARP.

Sally Church has written about the work of Arul Chinnaiyan’s lab on TMPRSS2:ERG and how this may be a more useful marker than PSA in prostate cancer.

You can read more on Pharma Strategy Blog about whether personalized therapy for prostate cancer is possible?

Sally will be attending the American Association for Cancer Research (AACR) special conference on “Advances in Prostate Cancer Research” in Orlando from February 6-9, 2012.

Co-chaired by Arul Chinnaiyan and Charles Sawyers, the meeting features plenary sessions on genomic and molecular profiling, prognostic signatures, androgen receptor signaling, drug development, ETS gene fusions, prostate cancer initiation and progression, and imaging.

If you have an interest in prostate cancer drug development and translational research this meeting looks well worth attending.

MDV3100 in Advanced Prostate Cancer

Posted on November 9, 2011 by Daedalus

The fast moving prostate cancer market took another leap forward last week with the announcement of positive phase III data for Medivation’s MDV3100.

As reported by Sally Church on Pharma Strategy Blog, Medivation announced that the interim analysis of the AFFIRM trial showed a 4.8 month increase in overall survival (OS) compared to placebo.

Although this is only interim and not final data, Sally observed:

“the 4.8 month improvement in OS in post-chemo setting is superior to that previously seen reported for abiraterone (Zytiga), which had a 3.9 month advantage over placebo.”

Pieter Droppert on Biotech Strategy Blog noted, MDV3100 and Zytiga have completely different mechanisms of action in advanced prostate cancer.

MDV3100 is an androgen receptor blocker, while Zytiga is an androgen biosynthesis inhibitor. This distinction is key. Zytiga inhibits the CYP17 enzyzme complex required for androgen biosynthesis. However, a consequence of CYP17 inhibition is an increase in mineralocorticoid levels, which can lead to hypokalemia, hypertension, fluid retention.

The result is that Zytiga requires coadministration of a corticosteroid (prednisone) to reduce the incidence and severity of potential mineralocorticoid adverse reactions.

MDV3100 does not require the administration of a steroid, which is a big advantage to patients. Instead it blocks the androgen receptor (AR) that is highly expressed on prostate cancer cells.

Cora Sternberg presents Prostate Cancer Educational Symposia at EMCC 2011 in Stockholm

There are a lot of new products in the pipeline for prostate cancer including TAK-700, Cabozantinib (XL184), radium-223 chloride (Alpharadin), BPX-101, Prostvac-VF, ipilumumab, Custirsen (OGX-011), dasatinib (Sprycel), lenalidomide (Revlimid) and ARN-509 to name a few.

The prostate cancer market is forecast to grow from $1B to $5B by 2015 as new products are approved and new treatment options become available. This is good news for advanced prostate cancer patients.

Understanding Cancer Metabolism may lead to new Molecular Targets

Posted on November 8, 2011 by Daedalus

Future advances in cancer drug development may come from targeting cancer metabolism and the pathways associated with this.

Image Source: Tak W Mak, Stockholm EMCC 2011

That was one of the key messages of Tak Wah Mak (Princess Margaret Hospital, Toronto) in his plenary presentation at the recent ESMO/ECCO multidisciplinary cancer congress in Stockholm.

An examples of this is the PI3-Kinase RAS axis that also inhibits glycolysis.

Sally Church in today’s post on Pharma Strategy Blog picks up on this, and how “understanding the process of tumorigenesis, ie tumour formation and growth, is critical to figuring out how to stop it.”

She discusses recent research from MD Anderson Cancer Center on Pyruvate Kinase M2 (PKM2) that is highly expressed in human cancer.

PKM2 plays an important role in glycolysis (Warburg effect) but also has a non-metabolic effect on tumor formation and growth.

The MD Anderson researchers showed how epidermal growth factor (EGFR) activation led to translocation of PKM2, but not PKM1.

You can read more on Pharma Strategy Blog about the significance of these findings and how this might lead to new biomarkers and treatment approaches.

Targeting Tumor Metabolism is one of the plenary sessions at the forthcoming AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Congress in San Francisco.

Recent advances in Cancer Imaging

Posted on November 8, 2011 by Daedalus

Richard Steinman from the University of Pittsburgh School of Medicine in “The Oncologist” (the journal of the Society of Translational Oncology), comments on the importance of the noncancerous cells in tumors (the stroma):

“The stroma, including fibroblasts, adipocytes, endothelial cells, and immune cells, had been demonstrated to provide critical metabolites to cancer cells and engages in tumor-promoting crosstalk with cancer cells.”

hi NIDA61733716 300x231 Recent advances in Cancer Imaging

PET scan of enzyme MAO-B Image Source: NIH

Recent research has shown the ability to image metabolic markers of tumor activity. On Biotech Strategy Blog, Pieter Droppert writes about a metabolic marker of malignant glioma cells, 5-ALA (5-Amino-Levulinic-Acid) and how this may help glioblastoma surgery.

Meanwhile on Pharma Strategy Blog, Sally Church discusses the use of folate receptor alpha fluorescence imaging in ovarian cancer.

Imaging of metabolic markers may assist in the identification and targeting of critical mediators of cancer-stromal crosstalk. This is an interesting area to watch.

The forthcoming AACR-NCI-EORTC conference on Molecular Targets and Cancer Therapeutics has a plenary session on “Targeting the Tumor Stroma Interaction.“

PI3-Kinase pathway molecular targets

Posted on November 1, 2011 by Daedalus

The phosophoinositide-3-kinase (PI3K) pathway is a hot area in cancer new product development and is currently attracting a lot of interest in drug development.

Infinity Pharmaceuticals yesterday announced they would begin two Phase 1 trials of their small molecule (IPI-145), previously licensed from Intellikine, that inhibits PI3K delta and PI3K gamma.

A review by Sally Church of the top posts of the past year on Pharma Strategy Blog, showed that the most popular post was, you guessed it on:

PI3K: A hot topic in cancer research

Amongst the 640,000 reads of Pharma Strategy Blog this past year and a choice of over 900 posts, that is certainly quite an achievement. Incidentally, No 9 in the list of top 10 posts for the year, was Sally’s Update on PI3K from ASCO.

The PI3-kinase or PI3K pathway is one of Sally’s favorites, and as she notes it “has been shown to play a major role in proliferation and survival in a wide variety of human cancers, thus making it a potential target for therapeutic intervention.”

In addition to Infinity, an number of biotech and pharma companies are actively involved in clinical research that targets this pathway.