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There are currently no approved therapies that can reverse or slow down the course of HD. Friedreich ataxia (FA) is a devastating monogenic, autosomal recessive progressive disease caused by low levels of endogenous Frataxin (FXN) due to abnormally expanded GAA triplet repeat expansions in the first intron of the FXN gene. The disease is characterized by spinocerebellar ataxia, dysarthria, pyramidal weakness, deep sensory loss, hypertrophic cardiomyopathy, skeletal abnormalities and diabetes mellitus. Clinical onset occurs most often around puberty, leading to severe disability by early adulthood, with substantial functional loss, wheelchair dependence and loss of quality of life.
Towards SINEUP-based therapeutics: Design of an in vitro synthesized SINEUP RNA - ScienceDirect.com
Towards SINEUP-based therapeutics: Design of an in vitro synthesized SINEUP RNA.
Posted: Wed, 02 Feb 2022 03:19:45 GMT [source]
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He became involved in Auspex as an investor in 2007 and served as its chairperson until he took over as its chief executive officer in 2013, after which he took the company public and oversaw its growth until its acquisition by Teva Pharmaceuticals for $3.5 billion in 2015. Before that, Dr. Shah was a partner in the healthcare venture capital firm Thomas, McNerney & Partners for nearly a decade, and prior to that, he co-founded two biotechnology companies and was also a consultant at McKinsey & Company in San Francisco. Dr. Shah obtained his Ph.D. in biochemistry and molecular biology as well as his MBA in finance from the University of Chicago. Individuals with nucleotide repeat expansion diseases are born with abnormally expanded stretches of specific nucleotide sequences, often with hundreds to thousands of repeats present in the mutant gene.
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Low FXN expression results in mitochondrial and cellular dysfunction and leads to all FA disease manifestations. DT-216 is a GeneTAC™ small molecule designed to specifically target the GAA repeat expansion mutation, unblock the transcriptional machinery, and restore the production of functional, natural FXN mRNA. Our HD program is based on GeneTAC™ molecules consisting of a DNA-targeting moiety designed to target to the CAG repeats in the Exon 1 region of the HTT gene, linked to a ligand moiety that is designed to dial down the transcription of the mutant allele without disrupting the normal HTT expression.
BML Capital Management LLC Invests $2.73 Million in Design Therapeutics, Inc. (NASDAQ:DSGN)
Dr. Xu joined Roche from McKinsey US and worked in biotech R&D earlier in her career. Dr. Xu currently serves on the boards of Walking Fish Therapeutics, Zidan Medical, HBM Healthcare Investments AG and Therorna Inc. She was also previously a board member of ARMO BioSciences (ARMO), NextCure (NXTC), Centrexion Therapeutics and Tempest Therapeutics. We are advancing a pipeline of novel candidates with an initial focus on monogenic repeat expansion disorders with urgent medical need, including Friedreich ataxia, Fuchs endothelial corneal dystrophy, Huntington’s disease and myotonic dystrophy. We are a biopharmaceutical company advancing novel, small molecule therapeutic candidates designed to bring functional cures to serious genetic diseases with long-standing unmet need.
Data to be Presented during the 2021 Virtual Myotonic Dystrophy Foundation Annual Conference
Our novel small molecule therapeutic candidates are GeneTAC™ (Gene Targeted Chimera) molecules that target the underlying cause of inherited genetic diseases. Observational Biomarker Study in Friedreich AtaxiaIn parallel to the Phase 1 MAD study, Design conducted an observational study to evaluate FA biomarker assays in blood and skeletal muscle from individuals with FA, FA carriers and normal healthy volunteer controls for use in DT-216 interventional studies. The company developed procedures and methods to measure both FXN mRNA and FXN protein in muscle. Initial data from the observational study is based upon a data cutoff of August 7, 2023. Skeletal muscle biopsies were obtained from study participants at two visits several days apart to measure FXN mRNA and protein levels and characterize inter-and intra-individual variability.
There was a transient increase of FXN mRNA in peripheral blood mononuclear cells (PBMCs) 24 hours after dose, which is consistent with and confirms the results from the Phase 1 single ascending dose study. Based on current methods and procedures, the treatment effect of DT-216 on FXN protein was inconclusive due to high intra-individual variability, consistent with what was seen in the observational study. Study results showed that levels of endogenous FXN mRNA across individuals with FA, FA carriers and healthy individuals differed significantly. Additionally, levels in the interquartile range for FA patients did not overlap with FA carriers, which shows FXN mRNA levels between these two populations are distinct.
Shares of Design Therapeutics stock traded down $0.01 during trading on Wednesday, hitting $3.65. The stock had a trading volume of 192,880 shares, compared to its average volume of 262,557. The stock has a market cap of $206.19 million, a PE ratio of -3.04 and a beta of 1.82.
Updated: FDA approves Pfizer’s hemophilia B gene therapy, with $3.5M price tag
Xaira’s internal platforms incorporate leading technologies and personnel which were spun out into Xaira at inception from Illumina’s long-standing functional genomics R&D effort. The company has also integrated a leading proteomics group from Interline Therapeutics. Rodney Lappe, Ph.D., has had a distinguished career as a biopharmaceutical scientist and executive.
Exploring the Potential of Gene Therapies for Limb-girdle Muscular Dystrophies
Finally, Jump Financial LLC boosted its position in shares of Design Therapeutics by 284.7% during the third quarter. Jump Financial LLC now owns 46,700 shares of the company's stock worth $110,000 after acquiring an additional 34,561 shares during the last quarter. Pharmacokinetics Plasma PK data were available in participants at 100mg, 200mg, and 300mg DT-216 doses. The average DT-216 concentration in muscle was approximately 8-10nM two days after the third weekly dose and approximately 1nM seven days after the third weekly dose in both the 200mg and 300mg cohorts.
Nucleotide repeat expansions are pathologic when they either impair transcription of the mutated gene (e.g., in Friedreich ataxia) or lead to formation of a pathogenic mRNA or mutant protein (e.g., Fuchs endothelial corneal dystrophy or Huntington disease). A higher number of excess repeats can lead to more severe, and sometimes a more rapidly progressive, form of disease. Over 70% of FECD cases are caused by cytosine-thymine-guanine (CTG) nucleotide repeat expansions in the TCF4 gene, which is transcribed into pathogenic TCF4 RNA that forms nuclear foci and sequesters splicing proteins, leading to transcript mis-splicing (spliceopathy) and CEC death. CECs harbor the longest known TCF4 repeat expansions in the body, potentially explaining why the cornea is the only affected tissue.
DM1 is caused by a mutation in the DMPK gene and is estimated to have a genetic prevalence of 1 in 2,300–8,000 people, affecting more than 70,000 people in the United States and more than 90,000 people in Europe. Each of these programs has the potential to generate blockbuster products with first-in-class or best-in-class profiles. Our proprietary GeneTAC™ platform offers significant potential advantages over other modalities. When systemically administered, GeneTAC™ molecules can distribute widely to reach target cells, overcoming a central challenge for traditional genomic medicines.
In addition, Dr. Shah serves as chairperson of the board at ARS Pharmaceuticals. Until February of 2020, he served as chairperson of Synthorx, Inc., a biotechnology company developing innovative protein therapeutics for cancer and autoimmune disorders that was acquired by Sanofi for $2.5 billion. Before that, Dr. Shah was president and chief executive officer of Auspex Pharmaceuticals, a biopharmaceutical company focused on the development and commercialization of novel medicines for people with movement disorders, including AUSTEDO® (deutetrabenazine).
We have shown that GeneTAC™ small molecules can directly distribute into multiple tissues and can be formulated for different routes of administration. Similar to other small molecules, GeneTAC™ molecules can be tailored to achieve a desired effect without requiring cutting, editing or inserting exogenous genes, thereby avoiding the challenges and risks of developing a therapeutic that causes a permanent genetic change. Design is leveraging its proprietary GeneTAC (gene targeted chimera) platform to develop therapeutic candidates for inherited diseases driven by nucleotide repeat expansions, such as DM1. Transcription of the mutant DMPK gene forms pre-mRNAs with large CUG hairpin loops that trap splicing proteins in the nucleus. Specifically, the mutant DMPK pre-mRNAs trap a critical CUG-binding protein called muscle blind-like protein 1 (MBNL1), which leads to the formation of toxic nuclear foci.
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