Spark Therapeutics Announces Updated Data from First Cohort in Hemophilia B Phase 1/2 Trial Demonstrating Consistent, Sustained Therapeutic Levels of Factor IX Activity

All four subjects received one-time administration of SPK-9001 at initial low dose for a cumulative 58-weeks of follow-up without the need for immunosuppression 

           Lead investigational candidate, SPK-8011, selected for hemophilia A, with initial clinical data expected in first half of 2017

Investor conference call today, Monday, June 13, at 8:30 am ET

PHILADELPHIA, June 13, 2016 (GLOBE NEWSWIRE) -- Spark Therapeutics ONCE announced today updated results of the first cohort from the ongoing Phase 1/2 clinical trial of SPK-9001, the lead investigational candidate in its SPK-FIX program, which is being studied for the treatment of hemophilia B.  The company also provided an update on preclinical data in its SPK-FVIII program for the treatment of hemophilia A.

"Spark's validated platform has now successfully delivered gene therapies with proof of concept data in both the eye and the liver. We have made strong, tangible progress throughout our entire hemophilia franchise," said Jeffrey D. Marrazzo, co-founder and chief executive officer of Spark.  "The clinical data emerging from our hemophilia B program, which is partnered with Pfizer, and the strong parallels to the preclinical data from our rapidly progressing program in hemophilia A, give us early confidence in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with these diseases through a potentially one-time, intravenous administration of highly optimized gene therapies."

Hemophilia B Data Overview

SPK-9001, a novel bio-engineered adeno-associated virus (AAV) capsid expressing a codon-optimized, high-activity human factor IX variant, was developed using Spark's proprietary technology platform for selecting, designing, manufacturing and formulating highly optimized gene therapies.  SPK-9001 is being developed in collaboration with Pfizer Inc. PFE.  Data from the Phase 1/2 clinical trial of SPK-9001 were presented on June 11 at the 21^st Congress European Hematology Association (EHA) by Dr. Spencer Sullivan, an Assistant Professor of Pediatrics and Medicine at the University of Mississippi Medical Center and a trial investigator, and were an extension of the data released on May 19^th in the initial EHA abstract.

Data presented today show that the low dose cohort of four subjects enrolled in the study experienced consistent and sustained factor IX activity levels following a single administration of SPK-9001 at the initial dose level (5 x 10¹¹ vg/kg) studied in the trial. Factor IX activity in the first two subjects, which had no history of liver disease, rose consistently and have stabilized at 28% of normal through the first approximately twenty-six weeks post-administration in the first subject, and at 41% of normal at fifteen weeks post-administration in the second. Factor IX activity level in the third subject, with a history of liver disease, also rose consistently and was at 26% of normal at approximately ten weeks post-administration. The fourth subject, also with a history of liver disease and not included in the previously disclosed data, saw a clinical response similar to the earlier subjects and was at 33% of normal through approximately seven weeks.

To date, over a combined 58 weeks of observation, none of the first four subjects received regular infusions of factor IX concentrates to prevent bleeding events. One precautionary infusion took place due to a suspected ankle bleed in subject number three two days after administration.  Based on their pre-enrollment histories, it is estimated that the four subjects followed to date would have received more than 100 infusions of recombinant factor IX over the period of the study to prevent or treat bleeds as part of their normal care.

Across the cohort, we saw no sustained elevation in liver enzyme levels and no drop in factor IX levels.  To date, SPK-9001 has been well-tolerated and no subjects have needed, or received, immunosuppression.

Hemophilia A Program

Spark today highlighted preclinical results from SPK-8011, the lead investigational candidate in its SPK-FVIII program for hemophilia A.  SPK-8011 was developed using Spark's proprietary technology platform and uses Spark200, a novel bio-engineered adeno-associated virus (AAV) capsid optimized for more efficient transduction of human hepatocytes, and contains an optimized B-domain deleted FVIII expression cassette. Spark retains global commercialization rights to its SPK-FVIII program for hemophilia A.

Data presented at the meeting of the American Society of Gene and Cell Therapy in May demonstrated strong preclinical data, specifically FVIII expression in the 15% to 35% range in preclinical models at clinically relevant doses of 2 x 10¹² vg/kg.

Today, the company released additional preclinical data, utilizing an in vitro assay, of the Spark200 capsid demonstrated higher efficiency in transducing human hepatocytes compared to Spark100, the capsid used in SPK-9001.

"We believe that the key to the hemophilia B results was the optimization of SPK-9001, which allowed us to observe therapeutic levels of FIX activity utilizing a low dose.  The data emerging from our hemophilia A program show parallels to the preclinical data in hemophilia B," said Katherine A. High, MD, co-founder, president and chief scientific officer of Spark. "We remain on track to rapidly progress SPK-8011 for hemophilia A into a Phase 1/2 clinical trial in the second half of 2016, and to potentially see the first human data from this program in the first half of 2017."

Conference Call Information
Spark management will discuss these data in a conference call on Monday, June 13, 2016 at 8:30 a.m. ET.  A slide presentation will also be available on the Events page of the company's website, www.sparktx.com, to accompany the conference call.  The call can be accessed by dialing (855) 851-4526 (domestic) or (720) 634-2901 (international), and entering passcode 27643823.

About Hemophilia A and Hemophilia B
Hemophilia is a rare genetic bleeding disorder that causes the blood to take a long time to clot as a result of a deficiency in one of several blood clotting factors, and occurs almost exclusively in males. People with hemophilia face specific risks as they are not able to form blood clots efficiently and are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life threatening.  People with severe hemophilia often bleed spontaneously into their muscles or joints. Hemophilia A is more common than hemophilia B. The incidence of hemophilia A is one in 5,000 male births. People with hemophilia A have a deficiency in clotting factor VIII, a specific protein in the blood. Hemophilia A is also called congenital factor VIII deficiency or classic hemophilia. Current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant factor VIII to control and prevent bleeding episodes.   The incidence of hemophilia B is one in 25,000 male births.  People with hemophilia B have a deficiency in clotting factor IX, a specific protein in the blood. Hemophilia B is also called congenital factor IX deficiency or Christmas disease. Current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant factor IX to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with hemophilia.  

About the SPK-FIX and SPK-FVIII Programs
Spark's proprietary technology platform for selecting, designing, manufacturing and formulating highly optimized gene therapies was applied to developing compounds in the SPK-FIX and SPK-FVIII programs. The SPK-FIX and SPK-FVIII programs both leverage a long track record of hemophilia gene therapy research and clinical development conducted by Spark and its founding scientific team over nearly three decades.

SPK-9001 is a novel bio-engineered adeno-associated virus (AAV) capsid expressing a codon-optimized high-activity human factor IX variant enabling endogenous production of factor IX.  SPK-9001 is being developed under a collaboration with Pfizer. Spark and Pfizer entered into a collaboration in 2014 for the SPK-FIX program, including SPK-9001, under which Spark will be responsible for conducting all Phase 1/2 studies for any product candidates, while Pfizer will assume responsibility for pivotal studies, any regulatory activities and potential global commercialization of any products that may result from the collaboration. 

SPK-8011, the lead investigational candidate from our SPK-FVIII program in hemophilia A, is a novel bio-engineered adeno-associated virus (AAV) capsid optimized for more efficient transduction of human hepatocytes expressing a codon-optimized B-domain deleted factor VIII transgene enabling endogenous production of factor VIII.  Spark retains global commercialization rights to its SPK-FVIII program.

About Spark Therapeutics

Spark Therapeutics, a fully-integrated gene therapy company, is seeking to transform the lives of patients with debilitating genetic diseases by developing one-time, life-altering treatments. Spark's validated gene therapy platform is being applied to a range of clinical and preclinical programs addressing serious genetic diseases, including inherited retinal diseases, liver-associated diseases, such as hemophilia, and neurodegenerative diseases.  Spark's validated platform has successfully delivered gene therapies with proof-of-concept data in the eye and liver. Spark's most advanced product candidate, SPK-RPE65 (voretigene neparvovec), which has received both breakthrough therapy and orphan product designation, reported positive top-line results from a pivotal Phase 3 clinical trial for the treatment of rare blinding conditions. Spark's hemophilia franchise has two lead assets: SPK-9001 in a Phase 1/2 trial for hemophilia B and SPK-8011, a preclinical candidate, for hemophilia A.  To learn more, please visit www.sparktx.com.

Spark Cautionary Note on Forward-looking Statements

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the company's SPK-FIX program. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that: (i) our lead SPK-FIX product candidate, SPK-9001, may not produce sufficient data in our Phase 1/2 clinical trial to warrant further development; (ii) our overall collaboration with Pfizer may not be successful; and (iii) preclinical SPK-8011 data may not be predictive of clinical results, if any, seen in human clinical trials. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties and other important factors, in our Annual Report on Form 10-K, our Quarterly Reports on Form 10-Q and other filings we make with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Spark undertakes no duty to update this information unless required by law.