Spark Therapeutics Announces Acquisition of Genable Technologies

Spark Adds New Program for One of the Leading Causes of Inherited Retinal Disease, Broadening Its Pipeline of Potential Treatments for Rare Blinding Conditions

PHILADELPHIA -- Spark Therapeutics (NASDAQ:ONCE) today announced that it has acquired Dublin, Ireland-based Genable Technologies, a private gene therapy innovator with which Spark has collaborated since 2014 in the development of Genable's therapeutic program targeting one of the most prevalent forms of inherited retinal disease (IRD).

With the acquisition, Spark acquires RhoNova™, a potential treatment targeting rhodopsin-linked autosomal dominant retinitis pigmentosa (RHO-adRP), an IRD that routinely leads to visual impairment and in the most severe cases to blindness. Using an adeno-associated virus (AAV) vector developed and manufactured at Spark, RhoNova™ is designed to both suppress the expression of a faulty gene and deliver normal copies of the RHO gene to restore normal expression. RhoNova™ has been granted Orphan Drug Designation in both the U.S. and Europe in addition to the Advanced Therapy Medicinal Product designation from the European Medicines Agency. There is currently no approved pharmacologic treatment for RHO-adRP, which affects an estimated 12,000 patients in the United States and the five major European markets (EU5).

“This transaction advances our strategy of leveraging Spark’s best-in-class gene therapy platform through a combination of internal innovation, acquisition and collaboration,” said Jeffrey D. Marrazzo, Spark co-founder and chief executive officer. “Genable’s technology and promising RhoNova™ development program further strengthens our portfolio of treatments for IRDs, which is led by our Phase 3 program for RPE65-mediated blindness which recently reported overwhelmingly positive pivotal stage data.”

“Genable has provided convincing data in animals to support their innovative scientific approach for the treatment of autosomal dominant diseases, where it is critical to both suppress faulty genes and replace them with a functional copy in order to have a meaningful therapeutic effect,” said Katherine A. High, MD, co-founder, president and chief scientific officer of Spark. “We look forward to using our validated gene therapy development platform and expertise to accelerate the clinical development of RHoNova, while examining other potential applications for the Genable suppression/augmentation approach outside of this initial indication.”

The consideration paid to Genable shareholders consisted of $6 million in cash and 265,000 shares of Spark common stock. Additional financial terms were not disclosed.

About Spark Therapeutics

Spark is a gene therapy leader seeking to transform the lives of patients with debilitating genetic diseases by developing one-time, life-altering treatments. Spark’s initial focus is on treating rare diseases where no, or only palliative, therapies exist. Spark’s most advanced product candidate, SPK-RPE65 (voretigene neparvovec), which has received both breakthrough therapy and orphan product designation, recently reported positive top-line results from a pivotal Phase 3 clinical trial for the treatment of rare blinding conditions. Spark’s validated gene therapy platform is being applied to a range of clinical and preclinical programs addressing serious genetic diseases, including inherited retinal dystrophies, hematologic disorders and neurodegenerative diseases. Spark builds on two decades of research, development and manufacturing at The Children’s Hospital of Philadelphia, including human trials conducted across diverse therapeutic areas and routes of administration. To learn more, please visit www.sparktx.com.

About Genable Technologies

Genable Technologies Ltd. is a privately held, venture-capital-backed, Dublin (Ireland)- based gene therapy company. Genable is developing new gene therapies to treat "dominant" genetic diseases. Genable has received significant support and investment form Fountain Healthcare Partners, Delta Partners, Fighting Blindness Ireland, Foundation Fighting Blindness Clinical Research Institute (U.S.), Trinity College Dublin and Enterprise Ireland. To learn more please visit www.genable.net.

Genable Technologies Ltd Moving GT038 Into Full Development

Dublin - The Genable team recently attended a Pre-IND meeting with the Food and Drug Administration (FDA) in Washington USA, to discuss the development of GT038 for the treatment of Rhodopsin linked autosomal dominant retinitis pigmentosa (Rho-AdRP). It was a very informative meeting during which the FDA provided feedback and advice on the preclinical and clinical development plans for GT038.

Dr Jason Loveridge Genable CEO commented “ Following a very informative and useful meeting with the US medicines regulatory authority, the FDA, we are delighted to confirm that GT038 has now moved from research to development. The FDA’s input taken together with advice from our Medical Advisory Board and most importantly Genable’s close links with patient groups increases the probability that we can progress GT038 into the clinic and subsequently provide benefit for RP patients.

Background Information

Genable Technologies Ltd. is a privately held Irish bio-pharmaceutical company developing new gene medicines to treat autosomal dominant genetic diseases based on the pioneering work of Professor Jane Farrar, Dr Paul Kenna & Professor Peter Humphries at the Smurfit Institute for Genetics in Trinity College Dublin, Ireland. Genable has received significant financial backing to date from venture capital companies including, Fountain Healthcare Partners, Delta Partners and the patient-led research charities, Fighting Blindness Ireland and Foundation Fighting Blindness Clinical Research Institute.

Genable's approach is innovative and unique, utilising well-established, clinically safe & effective AAV vectors to obtain expression of RNA interference (RNAi) molecules, which suppress the expression of both copies of the disease gene, normal and faulty and a replacement gene which is genetically modified and is refractory to suppression but still encodes a normal wild-type protein. The combination of suppression and replacement overcomes the significant hurdle in dominant disease of mutation variability by eliminating the need to target specific mutations and is applicable to a wide range of disorders

Genable's lead product, GT038, is designed for the treatment of patients with rhodopsin linked autosomal dominant retinitis pigmentosa (Rho-adRP), a debilitating, progressive form of inherited blindness resulting from a diverse array of mutations in the RHO gene. Genable's technology is protected by a broad suite of granted patents and patent applications in the USA, EU and worldwide.

This sub-type of adRP affects approximately 1 in 30,000 people and represents an already identified and potentially treatable population of around 30,000 patients in the US and Europe. Genable will employ the same approach to develop other gene medicines for a number of other sub-types of adRP. The company has received Orphan Drug Designation for GT038 in both the EU and US.

Agreements were executed in 2014 with Spark Therapeutics for the supply of GLP & GMP grade GT038 for the completion of preclinical development as well as the clinical trial programme.

For further information please contact jloveridge@genable.net

Spark Therapeutics and Genable Technologies Announce Collaboration to Advance a Gene Therapy Treatment for a Rare Form of Retinitis Pigmentosa

PHILADELPHIA -  Spark Therapeutics and Genable Technologies announced today that they have entered into a collaboration agreement for Genable's lead therapeutic to treat rhodopsin-linked autosomal dominant retinitis pigmentosa (RHO adRP), GT038. Under the terms of the collaboration, Genable will license certain adeno-associated virus (AAV) vector manufacturing patents from Spark. The parties have entered into a broad agreement in which Spark will be the exclusive manufacturer of the product and provide development advice and expertise to Genable to help in the ongoing development of GT038. Spark will receive milestone payments and royalties on future sales of GT038, as well as near-term revenue from the manufacture and supply of product.

"We are excited to apply our deep expertise in AAV clinical development and manufacturing to augment Genable's great work, and expand the number of debilitating diseases of the eye that can be addressed through gene therapy," said Jeffrey D. Marrazzo, Spark Therapeutics co-founder, president and CEO.

Dr. Jason Loveridge, CEO of Genable Technologies commented, "We have chosen Spark as our partner to advise, lend their experience and manufacture GT038 based on their broad expertise in gene therapy. We see them as a world-class organization, and we are excited to be advancing our novel therapy GT038 into the clinic."

"The collaboration with Spark provides an exciting opportunity to greatly expedite development of Genable's novel therapy targeted towards RHO-adRP," said Professor Jane Farrar, founder and director, Genable Technologies; professor, Trinity College (Dublin).

GT038 is a potential treatment for rhodopsin (RHO)-linked autosomal dominant retinitis pigmentosa (adRP), an inherited retinal dystrophy that leads to blindness in most cases. There is currently no approved pharmacologic treatment for adRP, which affects an estimated 30,000 patients worldwide. GT038 utilizes AAV vectors with an established safety and efficacy profile to deliver RNA interference (RNAi) molecules to suppress the expression of faulty and normal copies of RHO and restore normal gene expression. GT038 has been granted Orphan Drug Designation in both the U.S. and Europe.

About Genable Technologies

Genable Technologies Ltd. is a privately held, venture-capital-backed, Dublin (Ireland)- based bio-pharmaceutical company. The company is developing new gene therapies to treat "dominant" genetic diseases. The company has received significant support and investment form Fountain Healthcare Partners, Delta Partners, Fighting Blindness Ireland, Foundation Fighting Blindness Clinical Research Institute (U.S.) and Enterprise Ireland. To learn more please visit www.genable.net

About Spark Therapeutics

Spark Therapeutics is developing potentially curative, one-time gene therapy products to transform the lives of patients and re-imagine the treatment of debilitating diseases. Spark's lead gene therapy candidate, for RPE65-related blindness, is currently in Phase 3 clinical trials with the potential to be the first approved gene therapy in the U.S., and the first treatment to address the significant unmet needs of patients living with blindness due to inherited retinal dystrophies.

Spark's founding team includes scientists who led the movement to develop gene therapy as a new treatment paradigm, establishing clinical proof of concept in the eye and liver and contributing key insights to the field that have resulted in a resurgence of industry interest in gene-based medicines. In addition to the Phase 3 program in RPE65-related blindness, the company has a Phase 1/2 program in hemophilia B, and preclinical programs to address neurodegenerative diseases and other inherited retinal dystrophies and hematologic disorders. Spark has rights to a proprietary manufacturing platform that has an unparalleled track record of success in supporting clinical studies across diverse therapeutic areas and routes of administration. The company's expertise across research, clinical, regulatory and manufacturing builds on a legacy of innovation and excellence in gene therapy established by Spark's team while at The Children's Hospital of Philadelphia Center for Cellular and Molecular Therapeutics. To learn more visit www.sparktx.com.

Media Inquiries:

Jessica Rowlands, 202-729-4089, jessica.rowlands@fkhealth.com

Dr. Jason Loveridge + 33 674177812, jloveridge@genable.net

Leading International Blindness Charities Welcome Genable’s Enhanced Patent Portfolio

Genable Technologies Ltd., Dublin, Ireland, has recently expanded its intellectual property portfolio having obtained grants for two additional US patent applications on its novel suppression and replacement technology. The first of Genable’s recently granted US patents encompasses aspects of RNA interference (RNAi) mediated suppression and replacement (12/710343), while the second US patent (13/539,835) is focused on the generation of optimized replacement vectors for incorporation in innovative therapeutic strategies such as suppression and replacement therapies.

Avril Daly, CEO of Ireland’s Fighting Blindness commented “As a patient-led research charity the development of appropriate therapies for unmet medical needs is paramount therefore our organization was a founding investor in Genable Technologies. Having these newly granted patents improves the likelihood that the products will become viable therapies for patients with genetic blindness and we congratulate the inventors and the Company.”

Dr Stephen Rose, Chief Research Officer at US charity Foundation Fighting Blindness added “our key focus is to enable effective therapies get to patients and we recognize that securing IPR is a very important step on this journey. As such, we continue to support Genable as they bring their lead therapy GT038 to the clinic”.

Suppression and replacement technology represents a unique solution that enables treatment of dominantly inherited genetic disorders. The Company’s lead product, GT038, is focused on an ocular indication, Rhodopsin-linked autosomal dominant Retinitis Pigmentosa. GT038 has been granted orphan drug status and is currently in late preclinical development.

About Genable Technologies Ltd

Genable Technologies Ltd. is a privately held, venture capital backed Dublin (Ireland) based bio-pharmaceutical company and secured financing from Fountain Healthcare Partners and Delta Partners in 2011. The company is developing new gene therapies to treat "dominant" genetic diseases based on the pioneering work of Professor Jane Farrar, Dr Paul Kenna & Professor Peter Humphries of Trinity College Dublin. The background research has been supported by Fighting Blindness Ireland, Science Foundation Ireland, Foundation Fighting Blindness-National Neurovision Research Institute (USA), Enterprise Ireland & EVI-GenoRet (EU FP6-funded). www.genable.net

About Fighting Blindness

Irish research funded by Fighting Blindness has made a global impact in the search for therapies and cures for conditions causing sight loss. Since 1983, the patients who founded the organisation met regularly to help each other cope with the reality of degenerating vision. There was no treatment, nor was there real hope of one. Now not only do we understand how the conditions develop, but we also know what the treatments will look like. Since its founding, Fighting Blindness has invested over €10 million in Irish research, and our goal of cures and treatments is in sight. Our research is also contributing to international discoveries and developments and many clinical trials are being undertaken in both genetically inherited and age related conditions.

http://www.fightingblindness.ie

About Foundation Fighting Blindness

Foundation Fighting Blindness is a US-based non-profit organization driving the research that will lead to preventions, treatments and cures for retinitis pigmentosa, macular degeneration, Usher syndrome and the entire spectrum of retinal degenerative diseases that affects more than 10 million Americans. Since 1971, the Foundation has raised more than $550 million as the leading non-governmental funder of inherited retinal research. Breakthrough Foundation-funded studies using gene therapy have restored significant vision in children and young adults who were previously blind, paving the way for additional clinical trials to treat a variety of retinal degenerative diseases. With a coveted four-star rating from Charity Navigator, the Foundation also has nearly 50 chapters that provide support, information and resources to affected individuals and their families in communities across the country. http://www.fightblindness.org/

For more information please contact:

Dr. Jason Loveridge,
CEO Genable Technologies Ltd.
c/o Delta Partners
Media House South County Business Park
Leopardstown Dublin 18 Ireland
Ph. +33 674177812

www.genable.net

Genable Technologies Ltd appoints Annette Clancy as Chairman of the Board

DUBLIN, Ireland, 13th May 2013: Genable Technologies Ltd., a bio-pharmaceutical company developing new gene medicines to treat ‘dominant’ genetic diseases, today announced the appointment of Annette Clancy as Chairman of the Board. Annette graduated in Pharmacology from Bath University UK and also holds a series of American Management Diplomas. She has had a celebrated 30-year career in the pharmaceutical/biotechnology industry, predominantly at GlaxoSmithKline, where she has worked on a variety of R&D and commercial functions

Ms Clancy was Head of Transactions and Alliance Management at GlaxoSmithKline (GSK) where she was responsible for executing innovative deals ranging from early drug discovery partnerships, to global commercial alliances and Mergers and Acquisitions.

Since her retirement from GSK in 2008, Ms Clancy has been appointed as Non-Executive Board Director to Silence Therapies plc. (2008-2012) and Clavis Pharma in Norway (2008 ongoing). Ms Clancy also currently serves as Senior European Advisor to the biopharmaceutical team of Frazier Healthcare Ventures, for whom she provides strategic advice on both new and existing investments.

As a Non-Executive Board Member to Genable Technologies Ltd., Ms Clancy will also provide strategic consultancy advice to the company.

Ms Clancy said, “This is a very exciting time for the company and I am looking forward to working with the Genable Technologies team as they continue to make advances for suffers of genetic diseases.”

Welcoming Ms Clancy’s appointment, Genable’s outgoing Chairman Dr John Monahan said, “Annette has extensive and impressive experience in this industry and we are delighted that she will bring some of that experience to Genable Technologies as Chairman. We have seen significant advances in our products and research recently and we are certain that Annette’s proficiency and skill will enhance the expertise already within the company.” The company are also delighted to note Dr Monahan will remain on the Genable Board as a Non-Executive Director.

Genable Technologies Ltd gene therapy product, GT038, has recently been granted Orphan Drug Designation by the Federal Drug Administration (FDA) in the USA for the treatment of Retinitis Pigmentosa, complimenting the previous orphan drug designation granted by the European Commission. This is a significant milestone as it provides Genable Technologies with seven years market exclusivity once GT308 has secured regulatory approval.

GT038 is an adeno-associated viral vector containing DNA encoding an RNAi targeting rhodopsin in combination with an adeno-associated viral vector containing a rhodopsin gene for the treatment of rhodopsin-linked Retinitis Pigmentosa. The product is currently undergoing formal pre-clinical assessments prior to commencing clinical studies in patients.

About Genable Technologies Ltd

Genable Technologies Ltd. is a privately held, venture capital backed Dublin (Ireland) based bio-pharmaceutical company and secured financing from Fountain Healthcare Partners and Delta Partners in 2011. The company is developing new gene therapies to treat "dominant" genetic diseases based on the pioneering work of Professor Jane Farrar, Dr Paul Kenna & Professor Peter Humphries of Trinity College Dublin. The background research has been supported by Fighting Blindness Ireland, Science Foundation Ireland, Foundation Fighting Blindness-National Neurovision Research Institute (USA), Enterprise Ireland & EVI-GenoRet (EU FP6-funded). www.genable.ie

For additional information:

Eilish Joyce
FTI Consulting
Tel: +353 1 663 3609 / +353 87 791 4641
Email: eilish.joyce@fticonsulting.com

Ireland’s Genable Technologies Ltd secures Orphan Drug Designation by FDA for gene therapy product GT308

DUBLIN, Ireland, 12th April, 2013 - Genable Technologies Ltd gene therapy product, GT038, has been granted Orphan Drug Designation by the Federal Drug Administration (FDA) in the USA for the treatment of Retinitis Pigmentosa. This is a significant milestone as it provides Genable Technologies with seven years market exclusivity once GT308 has secured regulatory approval.

GT038 is an adeno-associated viral vector containing DNA encoding an RNAi targeting rhodopsin in combination with an adeno-associated viral vector containing a rhodopsin gene for the treatment of rhodopsin-linked Retinitis Pigmentosa. The product is currently undergoing formal pre-clinical assessments prior to commencing clinical studies in patients.

Patients with rhodopsin-linked Retinitis Pigmentosa have a mutation in the rhodopsin gene which causes a patient's sight to worsen, eventually leading to blindness. Almost 300,000 people worldwide have Retinitis Pigmentosa (RP) and of these, approximately 30% will have rhodopsin- linked (RP). GT038 is a novel and unique therapy for rhodopsin-linked Retinitis Pigmentosa that utilizes AAV vectors to obtain expression of RNA interference molecules, which suppress the expression of the faulty gene, and replaces this with a gene encoding a functioning protein. This simple combination overcomes the significant hurdle in diseases such as rhodopsin-linked Retinitis Pigmentosa of mutation variability by eliminating the need to target specific mutations.

Professor Alan Boyd MD of Genable Technologies Ltd said, ‘‘Retinitis Pigmentosa is a serious condition that leads to blindness in young people. There are currently no approved treatments for this condition and having orphan designation for GT038 in the US as well as Europe, is fundamental to the future development of our product that could have a significant impact on patients’ lives.’’

This orphan drug designation for GT038 by the FDA compliments the previous orphan drug designation granted by the European Commission to Genable Technologies Ltd, (Orphan Designation EU/3/10/817) for the treatment of rhodopsin-linked retinitis pigmentosa.

About Genable Technologies Ltd

Genable Technologies Ltd. is a privately held, venture backed, Dublin (Ireland) based bio-pharmaceutical company developing new gene medicines to treat "dominant" genetic diseases based on the pioneering work of Professor Jane Farrar, Dr Paul Kenna & Professor Peter Humphries of Trinity College Dublin. The company has secured financing from Fountain Healthcare Partners and Delta Partners. The background research has been supported by Fighting Blindness Ireland, Science Foundation Ireland, Foundation Fighting Blindness-National Neurovision Research Institute (USA), Enterprise Ireland & EVI-GenoRet (EU FP6-funded). www.genable.ie/

For additional information:

Eilish Joyce
FTI Consulting
Tel: +353 1 663 3609 / +353 87 791 4641
Email: eilish.joyce@fticonsulting.com

Ireland’s Genable Technologies Completes €5M Series B Financing

DUBLIN, Ireland, 11th November, 2011 - Genable Technologies (Dublin, Ireland), today announced that is has successfully completed a new financing round for €5m led by new investors Fountain Healthcare Partners alongside existing investors Delta Partners.  This funding will support the on-going development of Genable’s suppression/replacement gene therapy technology and specifically progress Genable’s lead product GT038 for Retinitis Pigmentosa (RP) forward into clinical evaluation in man.

Patients with rhodopsin-linked Retinitis Pigmentosa have a mutation in the rhodopsin gene, which causes a patient’s sight to worsen over time, eventually leading to blindness.  There are currently no available therapies for Retinitis Pigmentosa.  GT038 is a pioneering and unique therapy to treat rhodopsin-linked Retinitis Pigmentosa that utilizes AAV vectors to obtain expression of RNA interference molecules, which suppress the expression of the faulty gene, and replaces this with a gene encoding a functioning protein. This simple combination represents a new paradigm in medicine with the potential to cure this debilitating disease and not just treat the symptoms. Genable Technologies Ltd, was granted orphan drug designation for GT038 by the European Medicines Agency in December 2010.

Commenting on the new funding Dr. Ena Prosser, Partner at Fountain Healthcare Partners said, “This renowned Trinity College-based team, along with the dedication and support of Irish families who carry genes which can lead to inheritable blindness, has pioneered research into this disease over several years. We believe that GT038 offers a significant technological breakthrough to address Retinitis Pigmentosa and we look forward to working closely with the Company to accelerate the development of GT038 and other products to the market.”

Genable Chairman Dr. Geoffrey Vernon commented, “We would like to welcome Fountain Healthcare Partners as an investor with extensive industry expertise onto the Board. We would also like to take the opportunity to thank Delta Partners, Fighting Blindness Ireland, Foundation Fighting Blindness-National Neurovision Research Institute (USA) and Enterprise Ireland for the support they have provided Genable to date and their on-going commitment to the Company and its development of novel therapies for serious ophthalmic diseases.”

Professor Jane Farrar of Trinity College Dublin and co-Founder of Genable Technologies Limited concluded, “We are extremely pleased to see GT038 raise the necessary finance to translate basic research performed at TCD into the clinic.  It will help raise awareness of Retinitis Pigmentosa as a serious disease and ultimately help more patients receive therapy for their disease”.