Biotech Strategy Blog

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

Posts tagged ‘Biotech Drug Development’

BIO-CEO-2012-New-York-CityThe 2012 BIO CEO & Investor conference starts today in New York.

The meeting from February 13-14 is being held at the landmark Waldorf-Astoria hotel.

I’m looking forward to seeing some of the iconic hotel features such as the 1893 lobby clock originally produced for the Chicago World Fair.

With Wall Street analysts and investors in mind, the main focus of the 14th annual conference is on publicly traded biotechnology companies.

I expect that a number of the corporate presentations will be webcast, but if you are unable to be in NYC, you can follow the #BIOCEO2012 twitter conversation below:


As always, part of the attraction of these events is the opportunity for networking.

Rodman & Renshaw are hosting a party at the Rockefeller Center’s sunken plaza restaurant.

I hope to see you there or at one of the BIO CEO 2012 receptions.


Update Waldorf-Astoria Hotel 8.13 am February 13, 2012
I was all set-up with my trusty Zi8 flip camera to record a few clips of Moncef Slaoui’s fireside chat to share with blog readers, but was publicly told off by BIO staff that I could not shoot any video, despite a media registration. The head of media relations for BIO was not readily available when I asked to speak with her about this.

I’m sorry BIO but you’ve lost the plot. There’s no unpublished scientific data at this meeting, no information that is not publicly available, being webcast or being tweeted. If I’m not welcome, I do have other things to do with my time than attend your meeting, write blog posts about, do a video report & tweet about it. #fail

Update Waldorf-Astoria Hotel 8.58 am  February 13, 2012

Waldorf-Astoria-Hotel-Lobby-ClockAfter 20 minutes I have given up waiting for a BIO media rep to talk to about the “no video” policy for this meeting.

If organizations have a specific photo/video policy for a conference they should take the trouble to communicate this beforehand, at registration or prior to a session starts. Nobody bothered to do that at BIO CEO 2012 today. That’s inept organization.

What BIO did communicate by email to those who registered for BIO CEO 2012 in advance was that:

“By registering for this meeting, attendees authorize BIO to use any photographs taken during the Conference, which may be included in promotion materials.” 

BIO could at the same time clearly have indicated any photography/video policy for media or attendees.  They didn’t.

In the absence of any specific instruction otherwise and the fact that all attendees had consented to be photographed, I had no reason to believe that video or photography was prohibited.

What’s more, I shot a video report at BIO 2011 that I am sure the folk at BIO were aware of. I received no complaints about it, and if I shot a video report before it would not be a leap of imagination to expect I might shoot another video report.

Nobody likes to be publicly humiliated or told they can’t do something in a public forum after a session has started.  I certainly didn’t enjoy that happening to me today.

As a result of my experiences at BIO CEO 2012, Biotech Strategy Blog will not be providing any publicity, promotion or coverage of any future BIO event.

I am sorry if this inconveniences any blog readers. However, on reflection, I don’t think it’s a great loss given that there’s no breaking science or clinical trial data presented at any BIO meeting and company presentations are usually webcast or otherwise publicly available.

Bone is a tissue in constant state of remodeling by osteoclasts (cells responsible for bone resorption) and osteoblasts (cells responsible for new bone formation).

Osteoporosis is a disease of progressive bone loss that is associated with increase risk of fractures.  Particularly debilitating are hip fractures in the elderly that are costly to treat and also lead to increased death and reduction in quality of life.  It’s estimated that osteoporosis affects 44 million people in the United States over the age of 50.

Most treatments for osteoporosis inhibit bone resorption e.g. bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid).  By inhibiting or reducing bone resorption, there is a lower amount of bone loss.

Recent research published in the November 2011 issue of the journal Nature Medicine has highlighted a new potential target for osteoporosis drug development that acts on osteoblasts and promotes bone formation.

In a series of elegant experiments, Takako Negishi-Koga and colleagues found that osteoclast-derived Semaphorin 4D (Sema4D) inhibits bone formation.

They found that the transmembrane protein Sema4D is expressed by osteoclasts and inhibits osteoblastic bone formation. In other words, Sema4D is a critical mediator of osteclast-osteoblast communication. 

They reported that:

In osteoblastic cells, Sema4D stimulation decreased the expression of cadherin-11 at the cell-cell contact region suggesting that Sema4D stimulates cell motility through an impairment of cell-cell adhesion, which in turn results in the reduction in bone-forming activity.

Osteoclast-derived Sema4D inhibits bone formation: 

The binding of Sema4D to its receptor Plexin-B1 on osteoblasts resulted in the activation of the small GTPase RhoA, which inhibits bone formation by suppressing insulin-like growth factor-1 (IGF-1) signaling and by modulating osteoblast motility. 

The implication of these findings is that blocking Sema4D could promote osteoblastic bone formation without affecting osteoclastic bone resorption.  The researchers successfully tested this hypothesis using an antibody to Sema4D.

They concluded that:

These results suggest that the blocking Sema4D–Plexin-B1 interaction is a new and potentially effective strategy for increasing bone formation in humans.

This preclinical work using an animal model is highly promising and suggests that as we learn more about the bone microenvironment, new therapeutic and molecular targets for drug development may emerge.

ResearchBlogging.orgNegishi-Koga, T., Shinohara, M., Komatsu, N., Bito, H., Kodama, T., Friedel, R., & Takayanagi, H. (2011). Suppression of bone formation by osteoclastic expression of semaphorin 4D Nature Medicine, 17 (11), 1473-1480 DOI: 10.1038/nm.2489

Everybody who has sat too long in the sun knows how painful sunburn can be, and how ineffective current treatments such as topical creams can be.

Research by John Dawes and colleagues at King’s College London & University College London has shed new light on how sunburn causes pain.

They investigated the inflammatory response associated with ultraviolet B radiation of the skin and found that the chemokine CXCL5 (also known as epithelial-derived neutrophil-activating peptide-78) mediates UVB irradiation-induced pain in the skin of rats.

The results, published in Science Translational Medicine (STM), suggest that CXCL5 mediates UVB irradiation-induced pain and may be a target for the development of new analgesics or pain killers.

The elegant series of experiments done by Dawes and colleagues attempted to overcome one of the main challenges of pain research – the results from animal models don’t always predict pain relief in humans.

They designed custom-made Taqman array cards to determine the expression of inflammatory mediators in UVB treated rat and human skin, and found chemokine CXCL5 expression to be up-regulated in both rat and humans 40 hours after UVB treatment.

They then tested the hypothesis that CXCL5 was the cause of the pain, and that neutralization of this reduced mechanical hypersensitivity in rats and decreased the number of infiltrating cells. The STM paper is well worth reading for the series of experiments they performed.

Inflammation and inflammatory mediators are poorly understood in many diseases such as osteoarthritis (OA), so generating a better understanding of the underlying biology and mediators of inflammation is key to drug development.

It is too early to tell whether CXCL5 will turn out to be a druggable target, but the work by Dawes and colleagues is a good example of translational medical research worth exploring further.

ResearchBlogging.orgDawes, J., Calvo, M., Perkins, J., Paterson, K., Kiesewetter, H., Hobbs, C., Kaan, T., Orengo, C., Bennett, D., & McMahon, S. (2011). CXCL5 Mediates UVB Irradiation-Induced Pain Science Translational Medicine, 3 (90), 90-90 DOI: 10.1126/scitranslmed.3002193

The patient advocacy session at the recent 16th Congress of the European Hematology Association in London focused on adherence to cancer treatments, and was filled to capacity, with the many attendees having to watch it from an overflow area.

Dr David Marin, Reader in Onco-Haematology at Imperial College, London presented research published last year in the Journal of Clinical Oncology that dramatically demonstrated how adherence to chronic myeloid leukemia (CML) therapy is the critical factor for achieving molecular responses.

In a study of 87 CML patients taking imatinib (Glivec®/Gleevec®) for a median period of 91 days, Dr Marin showed that no major molecular response (MMR) was observed when adherence was ≤ 80% and no complete molecular responses (CMR) were observed when adherence was ≤ 90%.  The graphical figure that he presented from his paper, dramatically shows how missing only a few doses of drug can have a major impact on outcome:

Source: Marin D, et al.  J Clin Oncol 2010; 28(14):2381-2388

Although the work by Marin and colleagues at the Hammersmith Hospital was undertaken with CML patients taking imatinib, the paper notes that adherence problems

“may apply equally to patients receiving second-generation tyrosine kinase inhibitors.”

Imatinib is the only TKI approved in the UK, thus that’s the only one available for studies there to date.

What made this data so compelling was the study rationale that used an electronic pill container, the medical event monitoring system (MEMS™) from the Aardex Group. This product contains a microchip that records the date and time it is opened.

Dr Marin’s study showed that “lack of adherence is underestimated by conventional methods.”  Self-reporting of adherence and pill counts are inaccurate compared to electronic data capture using MEMS (study subjects were unaware of the micro-chip in the pill bottle).

When psychologists at the Hammersmith Hospital subsequently interviewed patients who missed doses of drug, they found intentional and non-intentional adherence reasons.

A few excepts of  patient quotes from Dr Marin’s presentation:

Intentional non-adherence:

“Oh I can’t be bothered tonight, it’s not going to kill me [to miss a dose]”

“I thought there was no way I was going [on holiday] and being tired.”

Unintentional non-adherence:

“And sometimes you just forget”

“[the pharmacy] had no medication for me, so I went for nearly a week with no medication.”

Other speakers in the excellent patient advocacy session chaired by Jana Pelouchová (European Cancer Patient Coalition, Czech Republic) and Jan Geissler (CML Advocates Network, Germany) included Giora Sharf (Israeli CML patient’s Organization and CML Advocates Network, Israel) and Professor Rudolf Schoberberger (Medical University of Vienna, Austria).

Professor Schoberberger focused on the impact of drug packaging on compliance, particularly in elderly patients, and presented compelling research on how “child-proof” equals “age-proof.”  Sally Church in her video blog from EHA also discusses the patient advocacy session and how pharma/biotech companies could improve drug packaging.

The issue of adherence is a personal choice that every patient taking a chronic therapy makes. However, as Sally notes on Pharma Strategy Blog more patient and physician education is needed so that patients know there may be dramatic consequences from missing only a few doses per month.

Not only may adherence have a major impact on patient outcome, but as one questioner from France pointed out at the end of the EHA patient advocacy session, “for a statistician it is a nightmare.” Poor adherence in clinical trials “means that the true effect of a drug is not well known. Efficacy may be under-estimated if adherence is low.”

More monitoring of adherence in clinical trials through the use of MEMS technology may, therefore, be necessary to ensure that clinical trial data shows the true efficacy and adverse event profile of a drug.

I hope that the European Hematology Association (EHA) will make a webcast of this informative patient advocacy session publicly available online as it raised issues of considerable importance to patients, physicians and biotech/pharma companies alike.

ResearchBlogging.orgMarin, D., Bazeos, A., Mahon, F., Eliasson, L., Milojkovic, D., Bua, M., Apperley, J., Szydlo, R., Desai, R., Kozlowski, K., Paliompeis, C., Latham, V., Foroni, L., Molimard, M., Reid, A., Rezvani, K., de Lavallade, H., Guallar, C., Goldman, J., & Khorashad, J. (2010). Adherence Is the Critical Factor for Achieving Molecular Responses in Patients With Chronic Myeloid Leukemia Who Achieve Complete Cytogenetic Responses on Imatinib Journal of Clinical Oncology, 28 (14), 2381-2388 DOI: 10.1200/JCO.2009.26.3087

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