Understanding the biology of colorectal cancer will lead to more rational drug development

Posted on January 31, 2012 by Daedalus

Cancer drug development is becoming more targeted and focused as a result of scientific advances. The understanding of ALK gene rearrangements in lung cancer led to the development of crizotinib (Xalkori) for the subset of patients who are ALK-positive.

Sally Church, Ph.D on Pharma Strategy Blog has reviewed some of the recent advances in our understanding of colororectal cancer (CRC).

Resistance to chemotherapy in colon cancer

The transcription factor AP-2 epsilon (TFAP2E-DKK4) appears to be responsible for some of the resistance to chemotherapy that occurs during colon cancer.

As Sally noted, “the presence of the TFAP2E-DKK4 mutation may explain why some patients with colorectal cancer do better with chemotherapy than others.”

Inflammation linked to the early development of colon cancer

Researchers from MD Anderson Cancer Center have identified the role of inflammation and silencing of tumor suppressor genes in early colorectal cancer.

Understanding the biology of the disease could lead to the ability to identify those at high risk of developing colon cancer. Chemopreventative drugs could then be given to this subset of high risk patients to delay the onset of cancer. An exciting prospect!

Understanding the role of CIMP in early colorectal cancer

CpG island methylator phenotype (CIMP) can occur in 30% of colorectal cancer patients and has been shown to be an independent predictor of survival with 5FU in early or adjuvant CRC. CIMP may play an important role in tumor development. Expect to hear more on the link between inflammation, DNA methylation and early development of CRC.

Identifying subsets of patients will support rational drug development

Researchers have now shown that BRAF(V600E) mutations occur in 8-10% of colon cancers. The ability to identify this subset of patients could allow therapeutic options to be specifically targeted at them, in the same way that ALK+ lung cancer patients now receive crizotinib. Previously though, we didn’t know why vemurafenib was showing lack of efficacy in this group. New research has now given us some pointers.

As Sally noted on Pharma Strategy Blog, “a combination of vemurafenib and and an EGFR inhibitor such as as erlotinib, cetuximab or gefitinib, might be a useful clinical approach to try therapeutically in patients with colon cancer harboring the BRAFV600E mutation.”

As we learn more about the biology and early development of colorectal cancer, the ability to undertake rational drug development will increase. This is good news both for patients and for biotechnology and pharmaceutical companies who want to successfully bring new products to market.

Pharma Conference Coverage Strategy

Posted on January 23, 2012 by Daedalus

We live in a world of data that threatens to overwhelm our work and personal lives. Part of the reason for this is the price of data storage continues to fall dramatically.

Today, an external hard drive offers a 1TB capacity; a few years ago the same product offered 100GB. A 10x increase in storage capacity for the same money in the space of a few years.

Data is now available from online posters, abstracts, webcasts and presentations. We also have Facebook, Twitter, Linkedin and other social media competing for our time.

ASCO 2011: “the never ending walk”

What this means is that if you plan to attend a major medical or scientific meeting such as the annual meeting of the American Society of Clinical Oncology (ASCO), which offers a lot of data, you need to have a conference coverage strategy.

Here are a few tips we suggest you consider:

Don’t go for a “Data Dump”

Too often we see a “fear of missing out” (FOMO) mentality drive a “we must capture everything” policy. All this results in is a mass of data that somebody has to analyze after the meeting. Too often a 300+ page data dump report (when it finally is produced) ends up sitting on the metaphorical shelf.

Focus on Key Questions

Prior to a major medical or scientific meeting it’s important to develop a list of the key questions that a brand, commercial or new products team need answered. The questions could be on competitor activity, developments in a pathway or impact of clinical data on the standard of care. Data collection can then be focusoned on answering those key questions.

Insights cost more

Recently, staff at a top 20 pharma company told us they were paying $X for a conference “data dump” but only had 10% of $X available for strategic insights. In Twitter speak, they had #LostThePlot as it should be the other way round since insights are more valuable than raw data.

As management consultants, we might produce a Powerpoint slide with a table or chart based on data from 20 posters. In order to select those 20 key posters, we could have reviewed perhaps 200 posters originally. Which would you rather have, one slide with insights and analysis or 200 Powerpoint slides with data? Our philosophy is “less is more.”

Insights cost more because it takes in-depth therapeutic area knowledge and expertise to condense data into a meaningful story and make strategic recommendations.

What is your conference coverage strategy for this year? Please contact us if you would like to learn more about our capabilities.

Bruton’s Tyrosine Kinase is a novel target for B-Cell Malignancies

Posted on January 5, 2012 by Daedalus

ASH 2011 Poster Session

Two Bruton’s Tyrosine Kinase (BTK) inhibitors in clinical development (PCI-32765 & AVL-292) generated a lot of interest at the recent American Society of Hematology (ASH) annual meeting in San Diego.

Sally Church on Pharma Strategy Blog has been following BTK as a novel drug development target, and saw its potential in early data presented at ASH 2010 and ASCO 2011.

Bruton’s Tyrosine Kinase is a critical kinase for lymphoma cell survival and proliferation. It plays an important role in B-lymphocyte development, differentiation and signaling. As Sally noted on Pharma Strategy Blog:

“It is a critical part of the BCL pathway that leads to cell proliferation, so targeting it leads to cell death or apoptosis.”

Sally’s insightful blog post goes into more detail on the Bruton’s Tyrosine Kinase clinical data presented at ASH by Dr Susan O’Brien (MD Anderson Cancer Center).

A number of companies are now taking an interest in BTK inhibition. Johnson & Johnson announced a $1B licensing deal for PCI-32765 just prior to the meeting. Sally’s analysis of this was:

“Based on the data seen over the last two years, I thought they got a steal”

BTK inhibition looks to be a promising target for B-cell malignancies such as non-hodgkin’s lymphoma (NHL), mantle cell lymphoma (MCL) & chronic lymphocytic leukemia (CLL). This is good news for patients.

BTK inhibitors are a new class of targeted therapies that we can expect to hear more about in the future.

What will be hot at ASCO 2012 in Chicago?

Posted on January 4, 2012 by Daedalus

ASCO 2012 is in Chicago from June 1 – 5

While everyone is busy making predictions about what the New Year will bring, we are already thinking about what are going to be hot topics at the 2012 annual meeting of the American Society of Clinical Oncology (ASCO).

ASCO is the largest and most important meeting of the year for those involved in oncology new product development and marketing strategy.

Predicting what will be hot at a meeting and when new trial data will be presented is not easy. However, positive or negative data from a major clinical trial can have a huge impact on a market or in the case of new products in development, the market potential.

Prior to ASCO 2011, Sally Church produced the following preview video. It’s still worth watching if you missed it the first time round.

Sally has already started working on her list of what may be hot at ASCO 2012 in preparation for this year’s video.

On Pharma Strategy Blog yesterday, Sally discussed the recent results for the VEGF inhibitor tivozanib (AVEO/Astellas) in advanced renal cancer (RCC).

Tivozanib showed a greater progression free survival (PFS) compared to sorafenib, but “the sorafenib arm did better than expected,” noted Sally. You can read more analysis about what this means on Pharma Strategy Blog.

The tivozanib data has been submitted as an abstract for ASCO this year (abstract deadline is February 1st), leading Sally to conclude that:

“This year’s ASCO is going to be a most interesting meeting for renal cell cancer.”

Time perhaps to starting making your New Year predictions of what may be hot at ASCO in 2012?

SABCS San Antonio Breast Cancer Symposium Conference coverage #SABCS

Posted on December 10, 2011 by Daedalus

Deserted River Walk due to San Antonio cold weather

If you are interested in news from the San Antonio Breast Cancer Symposium (SABCS) then Sally Church, PhD has a number of reports on Pharma Strategy Blog that are worth reading.

SABCS Video Preview

In her preview of the SABCS meeting (that you can also watch below), Sally reviews some of the BOLERO-2, CLEOPATRA and NEOSPHERE clinical trials, and what impact positive data may have on breast cancer patients. It is well worth watching.

SABCS Twitter Coverage

Although there is no wifi in the meeting rooms at SABCS, a few scientists, patients advocates and physicians are tweeting from the meeting including @drsteventucker and @teamoncology. You can easily follow the twitter conversation and check-out what’s been said through the #SABCS aggregator on Pharma Strategy Blog. As Sally would say, “check it out!”

As an example of how effective social media can be to share information, Pieter Droppert (@3NT) used storify to share some of the insights posted on twitter during the SABCS plenary lecture he attended on potential of macrophages as breast cancer drug development targets.

Breast Cancer and the Environment

Pieter also commented on the recent Institute of Medicine (IOM) report on “Breast Cancer and the Environment” which was somewhat disappointing to those hoping that it would highlight causal links.

Hot news at SABCS

The Alamo San Antonio Texas 300x225 SABCS San Antonio Breast Cancer Symposium Conference coverage #SABCS This year the San Antonio Breast Cancer Symposium had a lot of exciting new data. Two papers on the BOLERO-2 and CLEOPATRA trial data was published during the meeting.

Some of the interesting early data presented at the meeting included work on Notch inhibition to reduce aromatase inhibitor resistance, HER2 mutants and targeting HER3. You can read more updates from Sally Church on Pharma Strategy Blog.

Overall, this was one of the most interesting SABCS meetings of recent years with a good balance of science and clinical data.

Hopefully next year, there will be more discussants to put the data in context, as this would have made it an even better meeting.

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.

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.

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.