Data from Orphan Technologies' Prospective Natural History Study in Classical Homocystinuria Demonstrates That Current Treatments Do Not Prevent Severe Disease Outcomes

Orphan Technologies, a Company dedicated to developing novel therapies to dramatically improve the lives of patients suffering from homocystinuria and related diseases, today described data from the first-ever prospective Natural History Study of patients with classical homocystinuria. Three posters were presented at the Society for the Study of Inborn Errors of Metabolism Conference 2019 (SSIEM 2019), demonstrating that the current standard of care for homocystinuria is unable to prevent serious manifestations of the disorder. HCU is a rare genetic metabolic disorder that causes debilitating cardiovascular, neurologic and ophthalmic complications. The natural history study has enrolled 58 patients to date in 3 countries and is prospectively measuring baseline and longitudinal characteristics, including demographics, medical and family histories, medications, dietary information, cognitive, skeletal and ophthalmologic assessments, multiple biomarkers, as well as plasma total Hcy (tHcy) and related metabolites.

"This Natural History study is quantifying, for the first time, the significant unmet need that patients with homocystinuria face and the dramatic need for new therapies to treat this devastating disease," commented J. Frank Glavin, CEO of Orphan Technologies. "Orphan Technologies is developing OT-58, a novel enzyme therapy in classical homocystinuria with the hope that we can bring an effective therapeutic to patients suffering from the devastating cardiovascular, neurologic, skeletal, and ophthalmic complications associated with this disease."

Characteristics of Patients Participating in a Study of Homocystinuria Due to Cystathionine Beta-synthase Deficiency by Sellos-Moura, et al, demonstrates that, despite being seen at centers of excellence and being prescribed a natural protein-restricted diet and supplements, many patients have plasma tHcy values 5 to 40 times the upper limit of normal for tHcy, as well as ocular deficits, signs of inflammation, metabolic and liver dysfunction. These data indicate that current diet and therapeutic interventions are suboptimal and/or that most patients are not able to remain compliant, leading to high tHcy levels.

Homocysteine is negatively correlated with Cognition in Homocystinuria Due to Cystathionine Beta-synthase Deficiency by Goodlet BD, et al, highlights the severe cognitive impairment in many diagnosed and treated HCU patients. The overall cognitive function of HCU patients was severely affected. The median Total Cognition Composite for all patients was in the 20^th percentile (21^st percentile for adult and 14^th percentile for pediatric patients). Patients with lower plasma tHcy levels performed better on measures of executive functioning, extending prior studies showing that controlling tHcy levels is essential for maintaining intellectual functioning. Cognition was measured using the NIH Toolbox, a validated clinical outcome assessment instrument with demonstrated value for assessing cognitive functioning over time. The results of this study have practical implications for the management of HCU. For children with HCU, support similar to those for children with other executive functioning problems may be appropriate.

Skeletal Fragility in a Natural History Study of Homocystinuria Due to Cystathionine Beta-synthase Patients by Sellos-Moura, et al, demonstrates that most HCU patients have skeletal fragility, as measured by DXA, despite a relatively young median age of 21. Forty six percent of adults and 53% of pediatric patients had bone densities below the 15^th percentile (Z-scores ?-1) in at least one location. The data suggest that by chronically restricting their total protein intake to control their tHcy levels, patients may be increasing their skeletal fragility. Compliance with the mainstay of treatment, the protein restricted diet, may negatively impact bone health.

The Natural History Study posters are available on the Orphan Technologies website.

About Homocystinuria

Classical homocystinuria is a rare genetic metabolic disorder caused by a deficiency in the enzyme cystathionine beta synthase (CBS). CBS is a pivotal enzyme in the conversion of the amino acid methionine to homocysteine and then to cysteine. Classical homocystinuria leads to significantly elevated levels of the amino acid homocysteine that can result in debilitating comorbidities in patients including severe cardiovascular, skeletal, neurologic and ophthalmologic complications. The current treatment for patients with classical homocystinuria is a severely protein restricted diet and compliance with these dietary restrictions is extremely difficult, regularly resulting in inadequate metabolic control and lack of disease control.

About OT-58

OT-58 is a modified recombinant enzyme therapy in development for patients suffering from the rare disease classical homocystinuria. OT-58 is designed to help patients reduce their homocysteine levels and restore a normal lifestyle.

About Orphan Technologies

Orphan Technologies is dedicated to developing novel therapies to dramatically improve the lives of patients suffering from the rare disorder, classical homocystinuria and related diseases. OT-58, our lead drug development candidate, has been optimized as an enzyme therapy for classical homocystinuria, a genetic disease characterized by debilitating cardiovascular, skeletal, neurologic, and ophthalmologic complications. OT-58 is designed to reduce homocysteine levels via a targeted mechanism of action and may have therapeutic applications in other diseases. For more information, please visit www.orphantechnologies.com.