6 minute read
calendaR of events
december 2012/ January 2013
December 15-19
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ASCB 52nd Annual Meeting Venue: San Francisco, CA Tel: 301-347-9300 Fax: 301-347-9310 Email: ascbinfo@ascb.org Web: www.ascb.org
JAnUARY 2013
January 7-9
Biotech Showcase™ 2013 Venue: San Francisco, CA Tel: +1 760 930 0500 Email: jgriego@ebdgroup.com Web: www.ebdgroup.com/bts/index.php
January 12-16
SLAS 2013 Venue: Orlando, FL Tel: 630-256-7527 Fax: 630-741-7527 Email: slas@slas.org Web: www.slas2013.org
January 20-24
11th Winter Conference on Medicinal & Bioorganic Chemistry Venue: Steamboat Springs, CO Tel: +44-1435-873062 Email: claire@scientificupdate.co.uk Web: www.mbcfconference.com/events/ wmbcf-next-event-2013.html
January 26-29
2013 Annual Meeting of the ORS Venue: San Antonio, TX Tel: 847-823-5770 Fax: 847-823-5772 Email: ors@ors.org Web: www.ors.org/
FEBRUARY 2013
February 11-12
BIO CEO & Investor Conference Venue: New York, NY Email: bd_registration@bio.org Web: www.bio.org/events/conferences/ bio-ceo-investor-conference
February 22-24
2013 BIOTECanada Whistler Meeting on the Mountain and CEO Summit Venue: Whistler, BC Email: kira.pejemsky@biotech.ca Web: www.biotech.ca/en/ what-we-do/2012events.aspx
February 24-26
11th Annual BioPartnering North America Venue: Vancouver, BC Tel: 604.601.8372 Fax: 604.689.4486 Email: contact@techvision.com Web: www.techvision.com/bpn/
MARch 2013
March 11-13
BIO-Europe Spring Venue: Barcelona, Spain Tel: 760-930-0500 Email: chundschell@ebdgroup.com Web: www.ebdgroup.com/bes/index.php
March 17-22
PITTCON Venue: Philadelphia, PA Tel: 412-825-3220 Fax: 412-825-3224 Email: info@pittcon.org Web: www.pittcon.org
ApRiL 2013
April 22-25
Bio International Convention Venue: Chicago, IL Email: reg2013@bio.org Web: www.convention.bio.org
Company & advertiser index
coMpAnY pAgE WEBsiTE
AlbertatBay..............................................................................................................25 ..........................................................................................www.albertatbay.com Allon Therapeutics Inc. ................................................................................ 6........................................................................www.allontherapeutics.com Andor Technology plc................................................................................. 27......................................................................................... www.andor.com AstraZeneca Canada .................................................................................... 8.................................................................................... www.astrazeneca.ca Beckman Coulter Life Sciences ................................................................... 26.........................................................................www.beckmancoulter.com Belart .......................................................................................................... 26......................................................................................... www.belart.com Best Western Victoria Park Suites........................................................................25 .........................................................................................www.victoriapark.com Bioniche Life Sciences Inc. ........................................................................... 6......................................................................................www.bioniche.com Biopartnering North America ..............................................................................13 .................................................................................www.techvision.com/bpn/ Canadian Government Executive ........................................................................3 ............................................................................www.cgeleadershipsummit.ca Children’s Miracel Network ...................................................................................9 ......................................................................www.ChildrensMiracleNetwork.ca Eppendorf................................................................................................................32 ........................................................................... www.eppendorcomplete.com GE Healthcare ............................................................................................. 26............................................................................ www.gelifesciences.com Mitomics Inc. .............................................................................................. 10...............................................................................www.mitomicsinc.com NEOMED Institute ........................................................................................ 8..........................................................................................www.neomed.ca Pfizer Canada............................................................................................... 8.............................................................................................. www.pfizer.ca POI .............................................................................................................................31 ............................................................................................................. www.poi.ca Sheldon Manufacturing Inc......................................................................... 26....................................................................................... www.shellab.com Tekmira Pharmaceuticals Corp. .................................................................. 10............................................................................www.tekmirapharm.com Thermo Fisher Scientific Inc........................................................................ 26.........................................................................www.thermoscientific.com VWR............................................................................................................................2 ..............................................................................................https://ca.vwr.com/ Warner Instruments.................................................................................... 26............................................................................. www.warneronline.com
By Robert Foldes
Improving Investor Confi dence Amidst CLINICAL FAILURES:
Robert Foldes is Managing Partner of Cognovie Inc. and can be contacted at Robert@cognovie. com
IS IT TIME TO RETHINK OUR APPROACH TO DRUG DISCOVERY?
“For every problem there is a solution which is simple, clean and wrong.”
This quote attributed to H.L. Mencken, the American journalist known as the “Sage of Baltimore,” dominated much of my thinking since I fi rst stumbled upon it in graduate school. I would draw on this concept in every seminar and hallway conversation to challenge my colleagues and fellow scientists to gain new perspectives to analyze their research endeavors. In those days of reductionism, it was all too easy for molecular biologists and biochemists to focus on genes or proteins of interest and lose sight of the immense complexity (and redundancy) inherent in all biological systems. Of course, scientifi c research has evolved tremendously over these past 20 to 30 years. “Systems biology” has now developed into an interdisciplinary fi eld of study that focuses on complex interactions within biological systems using a more holistic approach. Researchers are currently using these approaches to model properties of cells, tissues and organisms.
One might argue that the pharmaceutical industry is still trapped in the traditional paradigms of reductionism. Very few (if any) drug candidates are externally sourced,
or internally developed, without demonstrating a high affi nity and “specifi c” interaction with a well characterized protein target. This focus involves optimizing for nanomolar potency against the target, even though this potency does not predict biological effi cacy. An increasing volume of evidence suggests that many drugs derive their therapeutic benefi t from interactions with multiple “The pharmaceutical industry is still trapped in the traditional paradigms of reductionism” proteins rather than a single target. Notwithstanding rational drug design, every drug will interact in varying degrees with unknown or unintended biological targets. And despite scientifi c advances, there are no models in current use that can accurately predict safety and effi cacy in humans of a new chemical entity or biological entity with a novel mechanism of action, no matter how well it has been characterized in cell-based or animal models. This is the chief failing of reductionist approaches to drug discovery that are likely largely accountable for the continuing slide in clinical trial success
rates. It is now estimated that 30 preclinical programs are needed to produce a single new drug.
A favourite approach of the industry to increase clinical success has involved reformulation or repurposing of marketed drugs. Another approach has been to focus on chemistries and mechanisms that have already yielded market-validated drugs (this would also include “biosimilars”). However, regulators and payers continue to raise the bar on so-called “me-too” drugs, limiting the long-term viability of these strategies.
As Matt Ridley wrote in the Wall Street Journal last year, “…the goal of most pharmaceutical research – identifying a “target” for drug action – is misconceived” since “biochemical networks are designed to work around the loss of any one node.” He suggests that “drugs must be designed to nudge whole networks rather than single
targets” meaning “hitting multiple targets simultaneously.” These targets can be informed by network analysis or systems biology. And certainly in agreement with H.L. Mencken, effective cures must be tailored to reflect the complexity of the disease.
The oncology field has realized for some time that there are powerful synergies through multiple interventions within a complex biological network. These are manifested in combination chemotherapeutic regimens involving “single-target” drugs. These regimens may arise through serendipity or “trial-and-error” approaches. However, the high-level of toxicity usually associated with individual cancer drugs introduces many challenges in designing tolerable combination regimens. Hopkins et al. (Current Opinion in Structural Biology 16: 127-136, 2006) discuss how it might be possible to rationally design promiscuous drugs by combining advances in chemoinformatics and structural biology. Another approach may involve reexamining chemical compounds shown to be associated with beneficial health outcomes or biological activities but not previously developed into drugs due to lack of target specificity. Natural products derived from plants provide a rich resource of such chemical knowledge.
One example of a promiscuous compound that displays polypharmacology is epigallocatechin-3-gallate (EGCG) an abundant component of green tea. As many of us know, green tea consumption has been associated with reduced risk of developing certain cancers. A large volume of scientific literature has demonstrated the anti-tumour properties of EGCG in animal models in the absence of significant toxicities. EGCG has been shown to directly inhibit chymotrypsin-like proteasome activity (at submicromolar concentrations) while also affecting (but likely at lower affinities) important other cancer targets such as mTOR, PI3Kα, AMPK and others. The attraction of EGCG as a drug candidate has been limited by its relatively low bioavailability and lack of composition of matter patent protection. However, analogs and derivatives of EGCG have been designed that address these issues and furthermore provide enhanced biological potency. In this case, the risk of failure due to safety issues would be relatively low. Similar to any other drug candidate, selecting the optimal dosing regimen and patient population is critical, although in this case one would be informed by many years of human experience with green tea consumption. Compounds like EGCG that affect multiple pathways of importance for disease intervention while maintaining a good safety profile provide new approaches to reduce clinical risk and hope to ultimately restore investor confidence in the sector.
After writing this article, I became aware of an excellent paper by Scannell et al. (nature reviews drug discovery 11, 191-200, 2012) that reinforces and expands on several points I raise above. I welcome your comments and feedback.
To see this story online visit http://biotechnologyfocus.ca/?p=3045
