Staking a claim

Since the adventof stem cell research, Big Pharma has shown an interest in leveraging its powerfor their research and development efforts—although the world's top pharmashave shown reluctance to take on the inherent risks involved with technologyand knowledge that is still relatively young.

According tomarket research firm Frost & Sullivan, Big Pharma has been cautious inapproaching stem cell research, but companies have accelerated their researchpresence and investment in stem cells since President Barack Obama liftedrestrictions on government funding of human embryonic stem cell (hESC) projects.Since that time, there has been an increase in Big Pharma's efforts in thisarea, primarily in the way of drug screening and toxicity testing, says Frost& Sullivan.

"Big Pharmaadopted a cautious role by engaging in strategic alliances to develop andcommercialize stem cell-based products," says Frost & Sullivan analystSandhya Kamath. "Autologous stem cells, screening drugs with stem cells,induced pluripotent stem cells and stem cell lines are some areas where pharmais concentrating their efforts and submitting several patents."

Corporateventure funds of pharma companies have been supporting stem cell efforts fromresearch institutes and companies, which could be with a strategic interest inusing startup companies they fund for research collaboration or future mergersand acquisitions, adds Kamath.

While ourcoverage of companies involved in the stem cell market is by no meansconclusive (and the companies are listed in no particular order), we areshining a light on some of the leaders in this field, as identified by Frost& Sullivan.

Company: NovartisAG

Location: Basel, Switzerland

Focus: Neuromuscular disorders

The NovartisInstitutes for BioMedical Research (NIBR), the global pharmaceutical researchorganization for Novartis, says it is "committed to discovering innovativemedicines that treat disease and improve human health." Much of the NIBR's workhas focused on "pioneering a scientific approach that focuses on discoveringand developing medicines for diseases with significant unmet medical needs forwhich the underlying mechanism of disease is known."

Much of theNIBR's work with stem cells has focused on the use of hESCs, whileacknowledging that "our understanding of these cells is at an early stage; yet,they hold immense potential for combating diseases such as Parkinson's,Alzheimer's and diabetes."

With theseconcerns in mind, Novartis in 2002 established an ethics committee to assesspreclinical research projects involving human embryos and hESCs in order toensure compliance with the company's internal ethical guidelines. The committeeis comprised of external, independent specialists to oversee the company'sresearch efforts in the field of stem cell research and to advise Novartis'executive committee on all bioethical issues of relevance for the company.

"Novartisacknowledges that human embryonic stem cell research is an evolving field andone characterized by ethical complexities," the company says on its website."The role of our ethics committee is to help us establish criteria andprocedures which strike the right balance between freedom of research and thelegitimate demands of society."

In November,Novartis announced that it will invest $1 billion over the next five years inits R&D efforts in China, including a "significant expansion" of its NIBRfacilities in Shanghai.

The NIBR hasongoing research partnerships with academic centers, such as the Harvard StemCell Institute, and is focused on finding small molecules that affectneuromuscular disorders. Additionally, the institute is collaborating with anetwork of researchers, foundations and clinicians around spinal muscularatrophy (SMA) using SMA patient-derived stem cells.

"Inducedpluripotent stem cells and motor neurons derived from those cells providecellular models to study disease etiology and help to identify and validate newtherapies," says Tewis Bouwmeester, executive director of developmental andmolecular pathways at the NIBR.

Bouwmeesterexplains that SMA is caused by a single gene defect in the SMN1 gene, whichproduces the SMN protein, a lack of which leads to splicing errors. Somepatients experience progressive paralysis caused by the loss of motor neuronsin the spinal cord.

"Basic researchtells us that motor neurons are dying because they lack SMN protein, a targetthat scientists might be able to drug, making the disease potentiallytreatable," says Bouwmeester. "There are various distinctive ways to possiblyincrease SMN levels, including prevention of protein degradation or changingthe DNA sequence. Our approach is to search for molecules that increasefunctional SMN protein.

"Such newresearch insights could potentially lead to better understanding of otherneurodegenerative diseases, such as Alzheimer's disease," Bouwmeester notes.

Company: Roche

Location: Basel, Switzerland

Focus: Toxicology and drug development

Although stemcell research represents a small part of Roche's global R&D efforts, thecompany has several collaborations underway with outside partners involvingtoxicological and safety tests and screening in various human stem cell lines.

Kyle Kolaja,director and global head of predictive toxicology screens and investigativetoxicology screens for Roche in the United States, says Roche's goal is to"improve drug development while reducing animal testing and potential seriousadverse events in human trials."

"We provideexternal partners with compounds from our drug library for testing on hESCs,"Kolaja says. "We think it is very meaningful to help identify compounds thatwill have a better safety profile and a lower-stage attrition. If we canidentify and weed out bad-acting compounds and poor patient response, we canscreen them out early."

For example,Roche recently entered into a partnership with Cellular Dynamics InternationalInc. to test whether potential new drugs damage heart tissue using stem cells.

"We are lookingfor a better model of cardiotoxicity," Kolaja says. "If you look at what'savailable even in a stem cell-derived model of the heart, they are eitherrodent-based or don't beat. A lot of them will undergo cell division. Thatdoesn't happen in a normal heart. This slows it down to near or noproliferation rate. We can already see that this cell is behaving verydifferently. If you look at stem cell-derived cardiomyocytes, they beat atabout 40 beats per minute and don't proliferate. That's a very high level."

In June, Rocheannounced an agreement to provide the latest-generation microarray systems,high-throughput screening instruments, genetic expression profilers and exomesequencing technologies to cancer researchers at UCLA. Roche also serves on thesteering body of the U.K. consortium Stem Cells for Safer Medicines (SC4SM),and has ongoing collaborations with Harvard University, Massachusetts GeneralHospital and the Institute for Stem cell Therapy and Exploration of MonogenicDiseases (I-STEM) in Paris.

In addition tothese external partnerships, Roche has commenced stem cell research in-house,including use of hESCs both as a discovery tool and as a potential therapeuticmodality, with the goal to develop treatment strategies for incurable orinadequately treated severe disease such as central nervous system disorders.Roche has already started research and preclinical feasibility projects on theuse of adult stem cells in other devastating diseases like lung fibrosis, andevaluates similar indications with high unmet medical need like renal failureor type 1 diabetes.

All of theseefforts will lead Roche down a path to realizing the promise of personalizedmedicine—which has become a buzzword in the pharma realm in recent years, saysKolaja.

"To me,personalized medicine means getting the right dose of the right drug to theright patient at the right time," he says. "In doing so, this will link all ofthe arms of the Roche group together, from our diagnostic arm, to our appliedscience arm and to our pharma division."

Company: GlaxoSmithKlinePLC (GSK)

Location: London

Focus: Therapeutic agents; regenerative medicine

For U.K.-basedGSK, stem cells are viewed as complementary to many of the pharma's drugdiscovery platforms. This means the industry could be able to test compounds inhuman cells instead of non-human cells, thereby improving the prediction ofpreclinical screens for efficacy and safety, a spokesman tells ddn.

"They have thenotable advantage that potentially they can be used to produce multiple maturehuman cell types that previously were either impossible or difficult to obtain,such as neurons or cardiomyocytes," GSK says. "We are also excited about the manipulationof the naturally occurring stem cells within the body to increase theirabilities to repair tissues, although this is a longer-term project."

Prioritizationof this research depends on the goals of the R&D organization, GSK says.

"Stem cells providenovel opportunities that didn't previously exist—they could ultimately bebeneficial to drug discovery in many ways, including as tools and targets fordrug discovery and as new therapeutic agents," GSK's spokesman says. "In thegeneration of tools, stem cells can be induced to generate specific human celltypes for research and compound screening. It may also become possible togenerate human cells of relevance to diseases, thereby improving the relevanceof cell models to human diseases. As therapeutic targets, adult stem cellsresiding in multiple organs of the body could be modulated by therapeuticreagents to induce regeneration. For instance, in Alzheimer's disease, if adrug could be found that is able to induce the production of new neurons fromneural stem cells, there is the potential of returning lost function. Finally,stem cells have the potential to be used as therapeutic agents. Stem cells andtheir progenies grown and manipulated outside the body might be introduced intothe body for therapeutic purposes."

One of thepharma's most advanced clinical development programs, one being developed byGSK's Rare Diseases unit, is a stem cell gene therapy for severe combinedimmune deficiency (ADA-SCID), a rare and life-threatening immune deficiencydisorder. Results from these clinical studies were published in 2009 in the New England Journal of Medicine.

GSK has alliedwith the Harvard Stem Cell Institute to develop new medicines, and with theFondazione Telethon and Fondazione San Raffaele to research and develop noveltreatments to address rare genetic disorders, using gene therapy carried out onstem cells taken from the patient's bone marrow. GSK is also a founding memberof the Stem Cells for Safer Medicine (SC4SM) initiative in the United Kingdom,which brings together pharmaceutical companies and public-sector organizations.

Company: Pfizer Inc.

Location: New York

Focus: Drug screening

When peoplethink of human embryonic stem cells, they don't often imagine the power ofthese cells in drug discovery, but Pfizer says it has been using animal oradult stem cells in its laboratories for more than a decade to help screen newcompounds and identify safer and more effective medicines.

In 2009, Pfizerannounced that it will invest $100 million into its international stem celldevelopment program.

"Pfizer hasbegun to explore accessing drug development technology from leading academic,biotechnology or pharmaceutical partners around the world, who also haveexperience with currently available, human embryonic stem cell lines that meetthe highest ethical standards set by leading scientific authorities," thecompany says on its website.

In April, Pfizerestablished a new biotech unit in Cambridge, the United Kingdom, that willcombine research in pain, sensory disorders and regenerative medicine. TakingPfizer's expertise in the field of sodium ion channels, Neusentis scientistswill apply this knowledge to deliver new medicines across all forms of paininfluenced by this mechanism, as well as a regenerative medicine portfolio.Neusentis is developing a cell-based therapy for age-related maculardegeneration constituted by retinal-pigmented epithelium made in vitro from a continuously growinghuman pluripotent stem cell line. Pfizer and Neusentis initiated their firststem cell clinical study for patients with ulcerative colitis this year.

Some of Pfizer'sexternal partners include the University College of London and the Universityof Wisconsin's Alumni Research Foundation.