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Archive - Jan 5, 2020

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NIH Researchers Discover Rare Autoinflammatory Disease (CRIA Syndrome) and Determine Its Biological Cause: Mutations in the RIPK1 Gene; Immunosuppressive Drug (Tocilizumab) Is Effective Treatment in Some Cases

Over the last 20 years, three families have been unsuspectingly linked by an unknown illness. Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and other organizations have now identified the cause of the illness, a new disease called CRIA syndrome. The results were published online on December 11, 2019 in Nature. The article is titled “Mutations That Prevent Caspase Cleavage of RIPK1 Cause Autoinflammatory Disease.” NHGRI Scientific Director Daniel Kastner (photo), MD, PhD, a pioneer in the field of autoinflammatory diseases, and his team discovered CRIA, which has symptoms including fevers, swollen lymph nodes, severe abdominal pain, gastrointestinal problems, headaches, and, in some cases, abnormally enlarged spleen and liver. The disorder has characteristics typical of an autoinflammatory disease, where the immune system appears to be activated without any apparent trigger. Although the condition is not life-threatening, patients have persistent fever and swollen lymph nodes from childhood to old age, as well as other symptoms that can lead to lifelong pain and disability. When confronted by the symptoms of patients, who were first seen at the NIH Clinical Center, researchers looked for infections and cancer as the cause. After those were ruled out, they sought answers in the genome, a person’s complete set of DNA. Dr. Kastner and his team sequenced gene regions across the genome and discovered only one gene — RIPK1 — to be consistently different in all patients. The image here depicts the kinase domain of the RIPK1 protein. Researchers identified a specific type of variation in the patients: a single DNA letter at a specific location incorrectly changed. This change can alter the corresponding amino acid added to the encoded protein.

Wave Life Sciences Reports 12.4% Reduction in Mutant Huntingtin Protein Using Allele-Specific Stereopure Antisense Oligo Targeted at SNP2 in Mutant Huntingtin Transcript; Reports Topline Data from Ongoing Trial & Plans to Initiate Higher-Dose Cohort

On December 30, 2019, Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic medicines company committed to delivering life-changing treatments for people battling devastating diseases, today announced topline data from the ongoing Phase 1b/2a PRECISION-HD2 trial evaluating investigational therapy WVE-120102, designed to be the first allele-selective approach to treat Huntington’s disease (HD). In an analysis comparing all patients treated with multiple intrathecal doses of WVE-120102 to placebo, a statistically significant reduction of 12.4% (p<0.05) in mutant huntingtin (mHTT) protein was observed in cerebrospinal fluid (CSF). An analysis to assess a dose response across treatment groups (2, 4, 8, or 16 mg) suggested a statistically significant response in mHTT reduction at the highest doses tested (p=0.03). WVE-120102 was generally safe and well tolerated across all cohorts. These data support the addition of higher dose cohorts, and Wave expects to initiate a 32 mg cohort in January 2020. “This topline analysis has given us the opportunity to evaluate early data from our ongoing dose finding study. The data demonstrate a reduction in mutant HTT and a safety and tolerability profile that supports exploration of higher doses of WVE-120102, with the goal of maximizing mutant HTT reduction and avoiding a negative impact on the healthy huntingtin protein,” said Michael Panzara, MD, MPH, Chief Medical Officer of Wave Life Sciences. “We plan to initiate the 32 mg cohort imminently and look forward to sharing data in the second half of 2020.”

Roche Concludes Acquisition of Spark Therapeutics to Strengthen Presence In Gene Therapy

On December 17, 2019, Roche (SIX: RO, ROG; OTCQX: RHHBY) and Spark Therapeutics, Inc. (NASDAQ: ONCE) (“Spark”) announced the completion of the acquisition following the receipt of regulatory approval from all government authorities required by the merger agreement. Commenting on this important step forward, Severin Schwan, CEO of Roche, said, “We are excited about this important milestone because we believe that together, Roche and Spark will be able to significantly improve the lives of patients through innovative gene therapies. This acquisition supports our long-lasting commitment to bringing transformational therapies and innovative approaches to people around the world with serious diseases.” Spark Therapeutics, based in Philadelphia, Pennsylvania, is a fully integrated, commercial company committed to discovering, developing, and delivering gene therapies for genetic diseases, including blindness, hemophilia, lysosomal storage disorders, and neurodegenerative diseases. Spark Therapeutics will continue to operate as an independent company within the Roche Group. “Today ushers in a new and promising era in the development of genetic medicines for patients and families living with inherited diseases and beyond,” said Jeffrey D. Marrazzo, Co-Founder and CEO of Spark Therapeutics. “Spark and Roche share an ethos of imagining the unimaginable. Together, we have the potential to change the future of medicine and deliver the medicines of tomorrow today. We couldn’t be more thrilled about what’s next.” Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives.