Fovea Reports Positive Results With Prednisporin(TM) In Persistent Allergic Conjunctivitis

Fovea Pharmaceuticals announced positive results from its clinical proof-of-concept trial to assess the therapeutic effect of Prednisporin(TM) (FOV1101) in patients with persistent allergic conjunctivitis.

Prednisporin(TM) had the same efficacy and a better safety profile (no increase in intra-ocular pressure) than PredForte(TM), a prescription drug with a 10 fold higher dose of prednisolone acetate, in patients treated for the signs and symptoms (itching and redness) of persistent ocular allergic inflammation. A one-week pre-treatment with Pataday(TM) (an anti-histamine) had negligible effect on these parameters in this patient population.

The prospective, multicenter, randomized, double masked, bilateral comparison study with 150 patients was conducted by Ora Inc., in the USA utilizing Ora’s Enviro-CAC(TM) clinical technology. The combination therapy of low doses cyclosporine A and prednisolone acetate was compared to PredForte(TM) alone or vehicle alone during a 2-week dosing period.

“We are extremely pleased with these results, and they are totally in line with our expectations,” said Bernard Gilly, Chairman and Chief Executive Officer of Fovea. “We believe that Prednisporin(TM) has the potential to provide safe and effective therapy to millions of patients suffering from chronic inflammatory conjunctivitis, a complex indication, that is not addressed by existing treatments.”

Prednisporin(TM) is the first combination therapy developed for the treatment of persistent allergic conjunctivitis. It is a proprietary topical formulation of lower than the usual therapeutic doses prednisolone acetate and cyclosporine A, to retain the efficacy of a very potent steroid with an improved safety profile. The concept was first discovered and patented by CombinatoRx (Nasdaq: CRXX) and Fovea holds an exclusive worldwide license to this intellectual property for ophthalmic indications.

“This study validates both a new clinical technology and new therapeutic approach,” said Mark B. Abelson, M.D., Chairman and Chief Scientific Officer of Ora, Inc. “Patients with a history of chronic ocular background inflammation make up a large segment of the ocular allergy market, and are also patients that tend to evolve towards dry eye, another significant ocular disorder. In this study, they have been treated effectively and safely by Prednisporin(TM).”

Allergic conjunctivitis is a frequent disorder. It occurs in up to 90% of patients suffering from allergies and in more than 20% of the global population. In the USA alone, 80 million people experience ocular surface allergy and inflammation. More than 50% of all forms of allergic conjunctivitis have a chronic inflammatory background (persistent allergic conjunctivitis). As current therapies do not address the underlying chronic inflammation, they fail to treat such a disease effectively. Significant opportunities exist for novel products in the ocular allergy market.

Fovea is now preparing pivotal trials for Prednisporin(TM) both in the USA and in Europe with the goal of filing NDA applications late 2010.

About Fovea Pharmaceuticals

Fovea Pharmaceuticals SA (Fovea) is a privately-held biopharmaceutical company specialized in development and commercialization of drugs for the treatment of ocular diseases, with a special focus on retinal pathologies. Founded in May 2005, Fovea has raised euro 50.5m ($69m) in two financing rounds from a strong international syndicate of investors.

Fovea has built a project portfolio including internal research programs on dry AMD, glaucoma (neuroprotection) and retinal dystrophies as well as clinical programs underway for such indications as allergic conjunctivitis, diabetic macular edema, retinal vein occlusion, and retinitis pigmentosa.

To advance the development and commercialization of its programs, Fovea is working both independently and through collaborations with industrial partners like Dyax, Novartis, Genzyme and CombinatoRx, as well as with academic teams, like the Inserm unit U968 (Vision Institute), the Rothschild Ophthalmological Foundation or the Johns Hopkins University.

About Ora

Ora is the world’s leading independent ophthalmic drug and device development firm, with more than 30 NDA approvals during its 30-year history. Ora provides technology-based, concept-to-market services and solutions that accelerate development timelines and improve the predictability of clinical research. Prednisporin(TM) trial was conducted using the Enviro-CAC(TM) which is an evolution of the standard clinical model for ocular allergy, Ora’s proprietary Conjunctival Allergen Challenge (CAC) which has been used for development and approval of 14 ocular allergy products.

Source: Fovea Pharmaceuticals

Use Of Amniotic Membrane May Cause Complications In Strabismus Surgery

Postoperative adhesions are a major complication in strabismus surgery. Amniotic membrane has been used in the hopes of preventing these adhesions by forming a biological barrier during healing. In an article in the December 2010 issue of the Journal of AAPOS, the Official Publication of the American Association of Pediatric Ophthalmology and Strabismus, a team of researchers from Cairo University have discovered that the new approach may also have the opposite effect.

Dr. Rehab Kassem and coauthors describe how they wrapped the extraocular muscles with lyophilized amniotic membrane in a patient undergoing a strabismus reoperation on both medial rectus muscles. However, the surgical result was not optimal, and the patient underwent a fourth procedure that included exploration of the medial rectus muscles. Instead of finding less scarring, the surgeons found extensive adhesions and inelastic, fibrotic muscles.

Amniotic membrane may be fresh or preserved. Preserved amniotic membrane may be either frozen, air-dried, or freeze-dried. Frozen amniotic membrane is expensive and it must be stored at -80°C, thus limiting its availability. Dried amniotic membrane is less expensive and does not require special storage conditions.

The authors of the article speculate that their results may have been due to the use of dried, rather than frozen, amniotic membrane. Writing in the article, Rehab Kassem, MD, states, “What caused the fibrosis in our case? Was it related to the use of amniotic membrane or was it coincidental, perhaps the result of excessive dissection to achieve a large recession? If the former, then was the fibrosis related to the nature (lyophilized vs. cryopreserved) of the amniotic membrane used or to its possibly having been placed toward the sclera rather than the muscle? In conclusion, although the cause of the fibrosis in our case is not clear, lyophilized amniotic membrane was ineffective in protecting against its development.”

“There are only a few reports of the use of amniotic membrane in extraocular muscle surgery, and the results of those studies are equivocal,” says David G. Hunter, MD, PhD, Editor-in-Chief of the Journal of AAPOS. “While this material may have been used successfully in other parts of the eye, strabismus surgeons should only consider using it around extraocular muscles in cases where there is already extreme scarring, and not as a preventive measure, as was done here.”

The article is “Severe fibrosis of extraocular muscles after the use of lyophilized amniotic membrane in strabismus surgery” by Rehab R. Kassem, MD, FRCS(Glasg), Ghada I. Gawdat, MD, and Rasha H. Zedan, MD. It appears in the Journal of AAPOS, Volume 14, Issue 6 (December 2010) published by Elsevier.



Acucela’s Novel Visual Cycle Modulator Demonstrates Promise As A Treatment For Dry Age-Related Macular Degeneration

Acucela, a clinical-stage biotechnology company focused on developing new treatments for blinding eye diseases, announced today that data on the company’s novel visual cycle modulator, ACU-4429, a potential oral treatment for dry age-related macular degeneration (AMD), will be featured at the Aegean Retina XI Meeting being held in Crete, Greece from July 3 to 5, 2009. Dry AMD is a leading cause of vision loss in people over the age of 50, yet there are no therapies currently approved to treat this condition.

“Over the next 20 years, the population of Americans over age 65 is expected to double. With this rapidly aging society, it is critical to address the significant unmet needs in treating blinding eye diseases associated with aging to ultimately prevent vision loss and blindness,” stated Ryo Kubota, M.D., Ph.D., president and chief executive officer of Acucela and discoverer of the gene that causes glaucoma. “Dry AMD is a particularly concerning disease related to aging, yet there are currently no approved therapies to treat dry AMD. We believe our approach to visual cycle modulation will offer new hope to patients suffering from this condition.”

AMD occurs in “dry” and “wet” forms, which together are estimated to affect more than 29 million people worldwide, according to a 2007 Visiongain report. This number is expected to double in the next 20 years due to the aging population. About 90 percent of AMD patients – or 26 million people – suffer from dry AMD, a degenerative disease that affects the part of the retina responsible for fine visual acuity and color vision.

ACU-4429 utilizes Acucela’s proprietary visual cycle modulation (VCM) technology, and is designed to prevent or inhibit the generation of naturally toxic by-products of the visual cycle that can lead to degenerative eye conditions like dry AMD. In preclinical studies ACU-4429 has demonstrated the ability to selectively target the human eye’s rod system (responsible for night vision ability) while leaving the cone system (responsible for day vision ability) unaffected. In doing so, ACU-4429 is able to successfully reduce the activity of the rod system – even when not being used for night vision, rod cells are critical to human sight, sending essentially unused information to the brain and creating toxic by-products – and decrease the rate of toxic by-product accumulation. Importantly, ACU-4429 is administered to patients as an oral, daily pill rather than by injection into the eye, which is typical of many current eye therapeutics.

Dr. Kubota will provide initial data from Acucela’s Phase 1 clinical trial to assess safety, tolerability and effectiveness of ACU-4429 for the treatment of dry AMD. The data being presented at the Aegean Retina meeting were also featured at the Association for Research in Vision and Ophthalmology (ARVO) 2009 Annual Meeting and demonstrate the safety and tolerability of ACU-4429 in healthy volunteers aged 55-80. In addition, the data demonstrate a dose-dependent modulation of the visual cycle using electroretinography (ERG), an established eye test in the evaluation of response and recovery of the retina that is used to help diagnose disease.

“During the ERG test, the cells of the retina (the rods and cones) produce tiny amounts of electricity in response to brief flashes of light. The ERG test enables us to track those retinal cells’ response and recovery from these flashes of light to determine exactly how the rod and cone cells are functioning as part of the visual cycle,” stated Dr. Kubota. “The ERG results achieved in this study suggest that ACU-4429 may effectively slow the rod visual cycle and therefore may have potential for treating a broad range of degenerative eye conditions. These data are exciting as they confirm what we’ve seen in our preclinical studies and mark the first time that a non-retinoid therapeutic in a convenient pill form has effectively targeted the visual cycle in a dose-dependent manner.”

Enrollment in the Phase 1 trial of ACU-4429 was completed in June 2009 and complete data from this trial are expected in the fourth quarter of this year. Based on the promising results obtained in the Phase 1 trial, Acucela plans to enter into a Phase 1b and then a Phase 2 trial of ACU-4429 later this year.

About the Aegean Retina Meeting XI

After its foundation almost 20 years ago by Evangelos Gragoudas, M.D., of the Massachusetts Eye and Ear Infirmary, Harvard Medical School, and Ioannis Pallikaris, M.D., Ph.D., Professor of Ophthalmology at the University of Crete, Greece, the Aegean Retina Meeting continues its tradition of exciting clinical and research presentations combined with lively discussion. Noteworthy presentations have included one of the first presentations on PDT therapy, as well as one the first presentations concerning anti-VEGF therapy for wet AMD. This year’s 11th biannual meeting is being held in Chania, Crete and features topics such as Advances in Vitreoretinal Diseases, Diagnostics, Pharmacotherapy, Surgical Instrumentation and Basic Research. For more information about the conference, visit

About ACU-4429

ACU-4429 utilizes Acucela’s proprietary visual cycle modulation (VCM) technology, and is designed to prevent or inhibit the generation of toxic by-products of the visual cycle that can lead to degenerative eye conditions like dry AMD. Preclinical data indicate that ACU-4429 slows the rod visual cycle, resulting in decreased accumulation of a toxic by-product that is the precursor of lipofuscin, which are deposits of toxic substances. The chronic accumulation of lipofuscin has been implicated in degenerative retinal diseases. ACU-4429 is administered to patients as an oral, daily pill rather than by injection into the eye, which is typical of many current eye therapeutics.

Acucela Inc.

Key Gene Controlling Eye Lens Development Identified

Investigators at St. Jude
Children’s Research Hospital have discovered in mouse models that a gene
called Six3 is one of the earliest critical regulators that control
development of the eye lens in the mammalian embryo.

Mutations in human Six3 have been identified in patients with
holoprosencephaly, a disease that can cause the part of the brain called
the cerebrum to fail to divide normally into two lobes.

Previously, the St. Jude team demonstrated that Six3 activity is
critical for the normal development of the forebrain in mice. The
researchers have now extended these results by showing in the developing
eye that Six3 normally exerts its effect by directly activating Pax6, a
gene considered the “master regulator of eye development.” A report on this
work appears in the prepublication online issue of The EMBO Journal.

“This information might one day contribute to strategies for preventing
or treating diseases caused by disruption of Six3 function,” said Guillermo
Oliver, Ph.D., a member of the St. Jude Genetics and Tumor Cell Biology
department and senior author of the paper.

“Our work gives us important insights into the interplay of genes
during this crucial time,” said Wei Liu, Ph.D., a postdoctoral fellow in
Oliver’s laboratory and first author of the paper.

Other authors of this study include Oleg V. Lagutin (St. Jude); and
Michael Mende and Andrea Streit, King’s College, London.

This work was supported in part by the National Institutes of Health, a
Cancer Center Support Grant, the Biotechnology and Biological Sciences
Research Council and ALSAC.

St. Jude Children’s Research Hospital

St. Jude Children’s Research Hospital is internationally recognized for
its pioneering work in finding cures and saving children with cancer and
other catastrophic diseases. Founded by late entertainer Danny Thomas and
based in Memphis, Tenn., St. Jude freely shares its discoveries with
scientific and medical communities around the world. No family ever pays
for treatments not covered by insurance, and families without insurance are
never asked to pay. St. Jude is financially supported by ALSAC, its
fund-raising organization. For more information, please visit

St. Jude Children’s Research Hospital

‘Devastating’ Eye Injuries Can Be Caused By Paintballs

Paintballs can cause severe and ‘visually devastating’ eye injuries, especially when used in unsupervised settings without proper eye protection, reports a study in the February issue of the American Journal of Ophthalmology (AJO), published by Elsevier.

“Eye injuries secondary to high-velocity paintballs can cause tremendous damage to vital ocular structures often requiring extensive surgical intervention,” comments Dr. Kyle J. Alliman of Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. “Unfortunately, visual loss is often permanent.”

Dr. Alliman and colleagues analyzed the characteristics and outcomes of 36 patients treated for paintball injuries to the eye at Bascom Palmer Eye Institute between 1998 and 2005. The patients were mainly young men, average age 21 years.

The injuries were often quite severe, including rupture of the eyeball in 28 percent of patients and detached retina in 19 percent. Surgery was required in 81 percent of patients – including eventual removal of the eye (enucleation) in 22 percent. Even when the eye was saved, many patients had permanent visual loss. Overall, near-normal vision (20/40 or better) was restored in only 36 percent of eyes.

All of the patients were injured when using paintballs in a “non-recreational, uncontrolled setting,” according to Dr. Alliman. None of the injuries occurred in formal, sponsored event. In all but one of the 36 cases, the patient was not wearing any type of eye protection when the injury occurred.

Paintball has become a popular recreational activity, with an estimated 10 million participants in the United States alone. The risk of paintball-related eye injuries has long been recognized. Organizers of formal paintball games require eye protection and education, which has significantly reduced the risk of severe eye injuries.

The researchers hope their study will draw attention to the alarming frequency of serious eye injuries related to paintballs, including the potential for permanent visual loss. “Awareness of the severe nature of paintball-related eye injury is paramount,” says Dr. Alliman.

The new analysis suggests that severe paintball-related eye injuries are most likely to occur when paintballs are used in informal, uncontrolled settings. “Both the consumer and distributor alike must realize the seriousness of injury caused by the improper use of paintballs in order to implement effective precautionary strategies,” Dr. Alliman adds. “Eye protection can prevent over 97 percent of injuries.”

About the American Journal of Ophthalmology

The American Journal of Ophthalmology is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and visual science specialists describing clinical investigations, clinical observations, and clinically relevant laboratory investigations. Published monthly since 1884, the full text of the American Journal of Ophthalmology and supplementary material are also presented on the Internet at AJO

About Elsevier

Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier’s 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (sciencedirect/), MD Consult (mdconsult/), Scopus (info.scopus/), bibliographic databases, and online reference works.

Elsevier (elsevier/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (reedelsevier/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier’s ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Source: Maureen Hunter


Can Heart Disease Treatments Combat AMD?

Can treatments that reduce risks for cardiovascular disease (CVD) also help combat age-related macular degeneration (AMD) , an eye disease that affects millions of Americans? CVD and AMD share some risk factors such as smoking, high blood pressure, and inflammation and a recent study found that people who have early-stage AMD are more likely to develop heart disease. This month’s Ophthalmology, the journal of the American Academy of Ophthalmology, reports on how two heart disease treatments, low-dose aspirin and statin medications, may impact AMD risk and disease progression.

Low-dose Aspirin May Offer Mild Protection from AMD

Records for 39,421 women enrolled in the 10-year Women’s Health Study (WHS) were used to evaluate the impact of low-dose aspirin on AMD risk. None of the women had AMD at the study outset; they were randomly assigned to take low-dose aspirin (100 mg on alternate days) or a placebo. It is known that low-dose aspirin substantially reduces the risk of serious blood vessel blockage, so researchers reasoned it might affect blood vessels that may play a role in AMD. Aspirin’s anti-inflammatory and anti-oxidant effects were also considered potentially relevant. The research was supported by the National Eye Institute.

“Although our study found no large benefit from low-dose aspirin, the possible modest protective effect we did find warrants further study,” said lead researcher William G. Christen, ScD, of Brigham and Women’s Hospital, Boston, MA. “If future studies confirm our findings, it could be important to make the public aware of this benefit,” he added.

The risk of developing vision-impacting AMD was reduced by18 percent in women who took low-dose aspirin. During the 10 year study, 245 AMD cases developed, 111 in the aspirin group and 134 in the placebo group. “Vision impact” was defined as a reduction in visual acuity to 20/30 or worse due to AMD. Though not statistically significant, the WHS risk reduction is similar to the result of the only other large randomized trial on this question: the Physicians’ Health Study I, which followed 22,071 men who took low-dose aspirin or a placebo for five years.

The primary aim of the WHS was to learn whether Vitamin E and low-dose aspirin would help prevent heart disease and cancer. The AMD study also found that women who were not taking multivitamins appeared to benefit more from low-dose aspirin than vitamin users.

Statins Do Not Stop Advanced AMD

In the largest study of statin use by advanced AMD patients to date, researchers followed 744 patients enrolled in the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) for five or six years. Statin drugs are primarily used to lower cholesterol in CVD patients, but they also affect mechanisms thought to impact AMD, including reduction of the inflammatory marker C-reactive protein. Earlier studies on statins’ effects had been inconclusive. All patients from the CAPT cohort study were at risk for advanced AMD, but none had developed advanced “wet” or “dry” AMD at baseline. The study was supported by the National Eye Institute.

“The CAPT data did not support a large effect for statins in decreasing advanced AMD risk in patients who already had large drusen in both eyes,” said lead researcher Maureen G. Maguire, PhD, Department of Ophthalmology, University of Pennsylvania. Drusen are whitish deposits, common in the eyes of people older than 60, which may signal AMD. Statin users were at slightly higher risk than non-users for developing advanced AMD, she said.

Dr. Maguire said several factors may be masking a protective effect for statins, the most important being that most patients who take statins for CVD are also at high risk for AMD. Only a randomized controlled trial could reveal statins’ impact on AMD in the wider population, but since so many elderly people take statins it could be difficult to recruit a control group. It is also possible that statins may need to be taken for longer than the CAPT study’s timeframe to show a protective effect, she added.

American Academy of Ophthalmology

Blindness Caused By Glaucoma Successfully Treated In Rat Model

Iowa State University researchers have developed a new technique that successfully treated rats for blindness caused by glaucoma. Their experimental treatment will be used on canine patients in the next year. If successful, it is expected to move to human trials.

An estimated 3 million people in the U. S. are affected by glaucoma, the second leading cause of blindness in the developed world and the number one cause of vision loss among blacks. People with elevated intraocular pressure are at greatest risk for developing glaucoma.

Iowa State researchers leading the six-year project are Dr. Sinisa Grozdanic, a veterinary ophthalmologist and assistant professor of veterinary clinical sciences; Donald Sakaguchi, neuroscientist and associate professor of genetics, development and cell biology; and Matt Harper, doctoral student in neuroscience. The team also included researchers from the University of Iowa, Yale University, Tulane University and the University of Miami. The work was presented at a recent meeting of the Association for Research in Vision and Ophthalmology Conference.

The researchers previously determined that animals with glaucoma increase production of proteins with neuron-protective capabilities (neurotrophins) in an attempt to shield against blindness. So, they imitated that process in the laboratory, modifying bone marrow-derived stem cells. Then they transplanted the cells into the eyes.

“Once we realized the nature of these self-protective mechanisms, we just tried to mimic the same thing exactly,” Grozdanic said. “We used bone-derived stem cells from the patient, modified them to produce the neurotrophin and injected these cells into glaucomatous eyes.”

A sophisticated computerized analysis of noninvasive measurements of optic nerve function and the retina’s electrical activity showed dramatic improvement in the rats’ visual functions after the procedure.

Four years earlier, the researchers had conducted experiments in which biodegradable polymers coated with neuroprotective substances were inserted into the eyes of rats. As the polymer degrades, the neuroprotective substance is released into the eye. The approach worked well, and the same procedure was successful in dogs with optic nerve damage. However, because polymer-based drug delivery generally lasts for only months and glaucoma destroys vision in humans over a period of decades, the scientists shifted their strategy to a longer-lasting approach. They genetically modified the bone marrow stem cells for transplantation so the delivery of the neuroprotective protein can be achieved for years.

“One of the really unique aspects of this approach is that we can isolate these stem cells from the same individual being treated,” Sakaguchi said. “It eliminates the ethical issues associated with embryonic stem cells, and the immunological problems of graft rejection.”

Grozdanic said the “results were phenomenal.” So, the Iowa State team intends to use the technique on dogs as soon as possible.

“Dogs suffer many of the same diseases people do and there’s a lot of physiological similarity in their eyes and ours,” Grozdanic said.

“Four years ago, I was very skeptical that this would work,” he said. “Now I see positive results. Hopefully in a few years, we’ll be able to say it’s working in humans.”

The cell biology work and the genetic modification were conducted by Sakaguchi and Harper, while Grozdanic developed techniques for evaluating the molecular changes in the animals. Researchers at the University of Miami provided genetic material for the modification while collaborators at Tulane assisted with culturing the bone marrow stem cells. A biodegradable polymer engineered with neuroprotective substances used in preliminary testing was developed by Erin Lavik at Yale University. Three faculty from the University of Iowa’s Department of Ophthalmology and Visual Sciences — Dr. Randy Kardon, Dr. Young Kwon and Dr. Markus Kuehn — helped develop models of elevated eye pressure and assessing visual function. They also compared data from tissue from the rats and dogs to data from human donor tissue to help the team better understand molecular changes caused by glaucoma.

Source: Donald Sakaguchi

Iowa State University

Rare Genetic Eye Disease Discovery Could Have Implications For More Common Medical Disorders

Halifax, July 2007: Schnyder crystalline corneal dystrophy (SCCD) is an inherited eye disease that can cause blindness. Although studies of SCCD
carried out by research groups in the United States were able to determine the general location of the Schnyder gene, its exact identity remained
frustratingly elusive. Until now.

As part of the Atlantic Medical Genetics and Genomics Initiative (AMGGI), a team of Dalhousie Medical School scientists working with clinicians from
the Queen Elizabeth II Health Sciences Centre and IWK Health Centres studied the DNA of a large Nova Scotia family affected with SCCD. The result:
AMGGI scientists have now pinpointed the gene responsible for the disease, a gene identified as UBIAD1 but not previously known to play a role in any
human genetic disorder.

Although Schnyder Dystrophy itself is a rare disorder, this discovery could have exciting implications for the treatment of more common disorders,
like heart attack, stroke and cancer. “We anticipate that this gene plays a role in other biological processes,” says AMGGI scientist Dr. Mark
Samuels. “Its structure, combined with the results of other non-genetic studies, suggests potential links to cholesterol metabolism and/or
cancer”. Other genetic disorders involving errors in cholesterol metabolism lead to a similar clinical picture, consistent with such a role for
UBIAD1. In follow-up studies, the team will be looking in more detail at the function of this gene and its role in various physiological processes.”

“The AMGGI project is unique in that it looks at many diseases simultaneously and requires the collaboration of both basic and clinical scientists
working throughout the Atlantic Provinces” says Dr. Steven Armstrong, President and CEO, Genome Atlantic. “It is an example of how governments,
universities, hospitals, research foundations and other not-for-profit organizations can work together in order to make important discoveries that
improve not only the health of Atlantic Canadians, but can also enable positive socio-economic impact .”

Project sponsors see this as a major milestone. “This is one in a series of original discoveries made by our genetics group which has the potential
to cure disease and alleviate suffering” says Dr Alan Cruess, head of Ophthalmology and Visual Sciences at Dalhousie Medical School and Capital
Health. “We have a brilliant group of clinicians and scientists all collaborating in a most productive way – putting Dalhousie and our teaching
hospitals on the world map of genetic discovery” Dr. Jonathan B. Kronick, Head, Department of Pediatrics, IWK agrees. “I am delighted about yet
another gene discovery by the scientists and physicians working in the Faculty of Medicine, the Department of Pediatrics Medical Genetics Division and
the IWK Health Centre. The collaborative efforts of the members of the AMGGI illustrate the power of working together to improve the health of the
people of Atlantic Canada. I expect more good news coming from the AMGGI in the near future.”

AMGGI is a unique initiative to systematically identify genes and genetic mutations underlying familial, monogenic disorders arising in populations
and communities throughout the Atlantic Provinces. The research program links human genetic research efforts in Newfoundland, based at Memorial
University, with activities encompassing the three Maritime Provinces centred at Dalhousie University. This Genome Atlantic managed project was made
possible through funding by: Genome Canada, the Nova Scotia Health Research Foundation, Dalhousie University, Nova Scotia Research Innovation Trust,
IWK Health Centre, Capital District Health Authority, Glaucoma Research Foundation, Memorial University Faculty of Medicine, National Institutes of
Health (USA), Marshfield Clinic, Janeway Childrens Hospital Foundation, Newfoundland and Labrador Centre for Applied Health Research, Department of
Health and Community Services, St. Jude Medical, Canadian Helicopters, Industrial Research and Innovation Fund NL, Memorial University Faculty of
Medicine (ORGS) and Memorial University VP. More information on this project can be found on the AMGGI website: AMGGI.

With over $40 million committed to projects to date, Genome Atlantic invests in and supports the management of outstanding genomics research with
commercial potential.

Orr A, Dub?� M-P, Marcadier J, Jiang H, Federico A, et al (2007)
Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy.
PLoS ONE 2(8): e685. doi:10.1371/journal.pone.0000685
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Promedior Announces Initiation Of Phase 2a Of Anti-Fibrotic Therapeutic, PRM-151, In The Prevention Of Post-Surgical Scarring In Glaucoma Patients

Promedior, Inc., a clinical stage biotechnology company developing novel therapies to treat fibrotic and inflammatory diseases, announced that it has initiated a Phase 2a clinical study of PRM-151 to evaluate the efficacy, safety, and tolerability of PRM-151 in preventing post-surgical scarring in glaucoma patients following glaucoma filtration surgery. There currently are no approved drugs for preventing post-surgical scarring in glaucoma, and there are no approved anti-fibrotic drug therapies in the U.S. or Europe for any fibrotic disease.

Promedior’s lead product, PRM-151, is a recombinant form of a naturally circulating human protein, Pentraxin-2 (PTX-2, also called human SAP), that regulates a fundamental mechanism of the innate immune system and activates the body’s natural ability to resolve tissue damage in disease processes that cause fibrosis and inflammation. PRM-151 has shown broad anti-fibrotic and anti-inflammatory activity in multiple preclinical models of fibrotic disease and inflammation, including glaucoma, pulmonary fibrosis, and acute and chronic nephropathy. Promedior successfully completed a Phase 1 clinical study of PRM-151 earlier in 2010.

“The initiation of this clinical trial represents important progress for Promedior as we believe that PRM-151 represents a novel and powerful first-in-class agent to prevent and treat fibrotic diseases,” said Dominick Colangelo, President and Chief Executive Officer of Promedior. “This study is designed to clearly demonstrate the anti-fibrotic activity of PRM-151 which we believe, based upon a common cellular immune mechanism across tissues and organs, may translate into potential therapeutic utility of PRM-151 in other ophthalmic surgical procedures and chronic eye diseases involving fibrosis, as well as other chronic systemic diseases such as pulmonary fibrosis and kidney fibrosis.”

This multicenter, multinational, randomized, double-masked, placebo-controlled Phase 2 study is expected to enroll approximately 130 patients. The primary efficacy endpoints of the study will be improvement and maintenance of intraocular pressure and reduction in post-surgical scarring as assessed by optical coherence tomography (OCT) and a clinical assessment scale. PRM-151 will be administered as a subconjunctival injection at the end of surgery and at additional designated timepoints following surgery.

PRM-151 was granted Orphan Medicinal Product Designation by the European Commission in September 2009 for use in the prevention of scarring post glaucoma filtration surgery. Beyond the current Phase 2a glaucoma surgery study, Promedior anticipates initiating a Phase 1b multiple-dose study in patients with idiopathic pulmonary fibrosis (IPF) and a Phase 1b study in a second ophthalmic indication within the next year.

About Glaucoma Filtration Surgery

Glaucoma, one of the leading causes of blindness in the world, is a disease that affects the optic nerve and leads to progressive loss of vision. Glaucoma filtration surgery generally is used to treat patients with advanced glaucoma and persistently elevated intraocular pressure (IOP) that are at high risk for visual loss. Post-surgical scarring due to fibrotic disease processes is a serious complication that diminishes the effectiveness of glaucoma filtration surgery, resulting in the loss of IOP control and risk of progression to visual loss or blindness.



Pentraxin Therapeutics

Can-Fite BioPharma To Initiate Phase II Clinical Trial With CF101 For The Treatment Of Glaucoma

Can-Fite BioPharma (TASE:CFBI), a biotechnology company traded on the Tel Aviv Stock Exchange, announced on December 13 the initiation of the regulatory process for a Glaucoma Phase II clinical study in Israel. Leading Medical Centers in Israel will enroll 44 patients with Ocular Hypertension or Glaucoma for the first segment of the trial, who will be treated for 16 weeks with CF101 or placebo. The study will be expanded by up to an additional 88 patients upon successful conclusion of an interim analysis of the first segment. The study protocol was developed with the assistance of Dr. Paul Kaufman, a noted glaucoma researcher at the University of Wisconsin. The study will investigate the efficacy of CF101, as manifest by a decrease in intraocular pressure, as well as the safety of CF101 in this population.

The rationale for the conduct of this study is based on unexpected positive findings from the recently concluded Phase II study in Dry Eye, demonstrating a decrease in the intraocular pressure in patients who were treated with CF101.

Glaucoma is one of the leading causes for blindness and currently about 90 million patients worldwide are affected by the disease. The main treatments today consist of eye drops, which are not easy for patients to use regularly and thus raise compliance challenges. Therefore, there is a market need for a systemic, orally administered drug such as CF101. The market size today is $5.5 Billion and is estimated to grow to around $8.4 Billion in 2012.

Can-Fite announced recently that it retained Plexus Ventures, a global pharmaceutical business development consultancy, to assist with the identification of a partner with the necessary expertise and the appropriate organization to support the clinical development and commercialization of CF101 in the United States, Europe and other markets. CF101 is already licensed out in Japan and South Korea.

Can-Fite BioPharma