MELAS

Precision BioSciences Announces Publication in Nature Metabolism Supporting ARCUS® In Vivo Gene Editing as a Potentially Curative Treatment for Mitochondrial Diseases

Retrieved on: 
Monday, December 4, 2023

For mitochondrial diseases, what makes ARCUS such an elegant and simple tool is that it is a single protein that both recognizes and eliminates the mutant mitochondrial DNA,” said Jeff Smith, Ph.D., Chief Research Officer of Precision BioSciences.

Key Points: 
  • For mitochondrial diseases, what makes ARCUS such an elegant and simple tool is that it is a single protein that both recognizes and eliminates the mutant mitochondrial DNA,” said Jeff Smith, Ph.D., Chief Research Officer of Precision BioSciences.
  • “Today’s publication further validates the ability of ARCUS to overcome the limitations of CRISPR-based gene editing technologies for treating mitochondrial disease and eliminating mutated mitochondrial DNA with high specificity to improve overall mitochondrial function.
  • By eliminating the mutant mitochondrial DNA and allowing the wild-type mitochondrial DNA to repopulate, mitoARCUS drives a shift toward healthy mitochondrial DNA, a process known as shifting heteroplasmy.
  • “To date, there are no curative treatments for mitochondrial diseases, so a gene editing approach is a novel way to offer hope to the patients suffering from mitochondrial myopathy.

Khondrion announces grant of patents in the US and Europe for its lead candidate sonlicromanol, covering the anti-inflammatory effect on mPGES-1

Retrieved on: 
Wednesday, November 1, 2023

Sonlicromanol works in three distinct ways by modulating oxidative and reductive distress, along with anti-inflammatory properties.

Key Points: 
  • Sonlicromanol works in three distinct ways by modulating oxidative and reductive distress, along with anti-inflammatory properties.
  • The compound is currently under investigation for its effectiveness in treating adult patients diagnosed with primary mitochondrial disease due to the m.3243A>G mutation in their mitochondrial DNA.
  • This mutation is linked to various conditions such as classical MELAS and MIDD syndromes, CPEO, and mixed phenotypes.
  • These findings suggest a wider range of potential applications for sonlicromanol beyond its initial focus on primary mitochondrial diseases.

Khondrion announces grant of patents in the US and Europe for its lead candidate sonlicromanol, covering the anti-inflammatory effect on mPGES-1

Retrieved on: 
Wednesday, November 1, 2023

Sonlicromanol works in three distinct ways by modulating oxidative and reductive distress, along with anti-inflammatory properties.

Key Points: 
  • Sonlicromanol works in three distinct ways by modulating oxidative and reductive distress, along with anti-inflammatory properties.
  • The compound is currently under investigation for its effectiveness in treating adult patients diagnosed with primary mitochondrial disease due to the m.3243A>G mutation in their mitochondrial DNA.
  • This mutation is linked to various conditions such as classical MELAS and MIDD syndromes, CPEO, and mixed phenotypes.
  • These findings suggest a wider range of potential applications for sonlicromanol beyond its initial focus on primary mitochondrial diseases.

Tisento Therapeutics Initiates Interview Study with Individuals with MELAS to Elucidate the Symptoms and Impact of Disease and Inform the Zagociguat Clinical Development Program

Retrieved on: 
Wednesday, October 25, 2023

CAMBRIDGE, Mass., Oct. 25, 2023 (GLOBE NEWSWIRE) -- Tisento Therapeutics, a privately held, clinical-stage biotechnology company developing novel medicines for diseases with significant unmet medical needs, today announced the initiation of a patient interview study to identify and describe the signs, symptoms, and health-related quality-of-life impacts of MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes) that are most burdensome to adults and adolescents living with this rare mitochondrial disease. The interviews will inform the selection of clinical outcomes assessments and endpoint strategy for the company’s planned Phase 2b study of its investigational medicine, zagociguat, in MELAS. 

Key Points: 
  • The interviews will inform the selection of clinical outcomes assessments and endpoint strategy for the company’s planned Phase 2b study of its investigational medicine, zagociguat, in MELAS.
  • This interview study is one way we will thoughtfully and intentionally listen to individuals with MELAS and take action in response,” said Peter Hecht, Ph.D., chief executive officer of Tisento.
  • “The first step in improving quality of life for this community is to better understand what individuals with MELAS face on a daily basis.
  • Tisento plans to use the findings from the interviews to identify clinical outcomes assessments that may be used as clinical study endpoints to evaluate the efficacy of zagociguat for the treatment of MELAS.

Precision BioSciences Receives U.S. Patent Allowance Covering PBGENE-PMM for m.3243-Associated Mitochondrial Diseases

Retrieved on: 
Wednesday, September 27, 2023

18/161,560, titled “Engineered Meganucleases That Target Human Mitochondrial Genomes.” Once issued, the patent arising from this application will have a standard expiration date in April 2042.

Key Points: 
  • 18/161,560, titled “Engineered Meganucleases That Target Human Mitochondrial Genomes.” Once issued, the patent arising from this application will have a standard expiration date in April 2042.
  • The allowed composition of matter claims in this U.S. application encompass a mitochondria-targeted ARCUS nuclease (mitoARCUS) that is designed to specifically target, cleave, and eliminate mutant mitochondrial DNA comprising an m.3243A>G mutation.
  • Precision recently announced PBGENE-PMM, the Company’s clinical candidate targeting mutant mitochondrial DNA, as a potentially first-in-class opportunity for treatment of m.3243 associated primary mitochondrial myopathy.
  • Utilizing the claimed mitoARCUS nuclease, PBGENE-PMM is designed to target and eliminate mutant mitochondrial DNA, allowing for repopulation by wild-type mitochondrial DNA and restoration of mitochondrial function.

Tisento Launches with $81 Million From Top-Tier Investor Syndicate and Promising Cyclerion Assets

Retrieved on: 
Monday, July 31, 2023

CAMBRIDGE, Mass., July 31, 2023 (GLOBE NEWSWIRE) -- Cyclerion Therapeutics, Inc. (Nasdaq: CYCN) and Tisento Therapeutics, Inc. today announced the closing of the previously disclosed asset purchase agreement. Tisento is launching with an $81 million Series A financing to support its development of the Phase 2 soluble guanylate cyclase (sGC) stimulator zagociguat in MELAS and other genetic mitochondrial diseases, as well as the company’s advancement of additional assets for serious diseases with unmet need.

Key Points: 
  • Phase 2a clinical data, generated by Cyclerion, showed rapid improvements in disease-associated biomarkers in patients with MELAS who received zagociguat for 28 days.
  • Cyclerion received 10 percent equity ownership in Tisento with anti-dilution protection through $100 million in post-money valuation, as well as the right to purchase additional Tisento equity in the future.
  • The Tisento equity ownership provides Cyclerion shareholders with the opportunity to benefit from future Tisento value creation without further financial or operational obligations for the Tisento assets.
  • The launch of Tisento supports the optimal advancement of zagociguat and CY3018 while providing Cyclerion with near-term capital and potential future value for our shareholders.

GeneDx to Present New Data on Urine Mitochondrial DNA Testing at the 2023 United Mitochondrial Disease Foundation’s Mitochondrial Medicine Symposium

Retrieved on: 
Wednesday, June 28, 2023

STAMFORD, Conn., June 28, 2023 (GLOBE NEWSWIRE) -- GeneDx (Nasdaq: WGS), a leader in delivering improved health outcomes through genomic and clinical insights, today announced it will present new data on urine mitochondrial DNA testing at the 2023 United Mitochondrial Disease Foundation’s (UMDF) Mitochondrial Medicine Symposium in Charlotte, North Carolina, June 28 - July 1, 2023.

Key Points: 
  • STAMFORD, Conn., June 28, 2023 (GLOBE NEWSWIRE) -- GeneDx (Nasdaq: WGS), a leader in delivering improved health outcomes through genomic and clinical insights, today announced it will present new data on urine mitochondrial DNA testing at the 2023 United Mitochondrial Disease Foundation’s (UMDF) Mitochondrial Medicine Symposium in Charlotte, North Carolina, June 28 - July 1, 2023.
  • Poster: Is the m.3243A>G variant detected in urine diagnostic for the patient’s disease?
  • “Mitochondrial disease may be caused by genetic variants in DNA found in the nucleus of cells or by genetic variants in the body's mitochondrial DNA (mtDNA).
  • Data presented this week by GeneDx demonstrates how urine mitochondrial DNA testing can be a clinically impactful and non-invasive option for analysis of the m.3243A>G variant.”

Cyclerion Announces Definitive Agreement for Zagociguat and CY3018

Retrieved on: 
Thursday, May 11, 2023

CAMBRIDGE, Mass., May 11, 2023 (GLOBE NEWSWIRE) -- Cyclerion Therapeutics, Inc. (Nasdaq: CYCN) announced today that it has signed a definitive agreement with a new private company (“NewCo”) to sell two of its sGC stimulator assets in exchange for cash and equity ownership. Investors in NewCo have agreed to invest $81M to develop zagociguat (previously CY6463) to treat MELAS* and other diseases associated with mitochondrial dysfunction and advance CY3018.

Key Points: 
  • Investors in NewCo have agreed to invest $81M to develop zagociguat (previously CY6463) to treat MELAS* and other diseases associated with mitochondrial dysfunction and advance CY3018.
  • Each of the current Cyclerion investors who are participating in the NewCo capitalization have agreed to vote their Cyclerion shares in favor of the transaction.
  • Following the closing, NewCo will be solely responsible for all activities and expenses related to developing and commercializing zagociguat and CY3018.
  • Signing of the definitive agreement triggered the previously announced $5M equity investment by CEO Peter Hecht.

Cyclerion Therapeutics Receives U.S. FDA Orphan Drug Designation for Zagociguat for the Treatment of Mitochondrial Diseases

Retrieved on: 
Monday, March 27, 2023

CAMBRIDGE, Mass., March 27, 2023 (GLOBE NEWSWIRE) -- Cyclerion Therapeutics, Inc. (Nasdaq: CYCN), a clinical-stage biopharmaceutical company on a mission to develop treatments for serious diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to zagociguat (previously CY6463) for the treatment of mitochondrial diseases.

Key Points: 
  • CAMBRIDGE, Mass., March 27, 2023 (GLOBE NEWSWIRE) -- Cyclerion Therapeutics, Inc. (Nasdaq: CYCN), a clinical-stage biopharmaceutical company on a mission to develop treatments for serious diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to zagociguat (previously CY6463) for the treatment of mitochondrial diseases.
  • Zagociguat is the first CNS-penetrant sGC stimulator to be developed as a symptomatic and potentially disease-modifying therapy for serious diseases that involve the CNS.
  • “Orphan drug designation underscores the FDA’s recognition of zagociguat’s potential promise as a first-ever therapy for patients with MELAS, a rare, genetic mitochondrial disease,” said Peter Hecht, Ph.D., Chief Executive Officer of Cyclerion.
  • Orphan drug designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions, and seven-year marketing exclusivity upon FDA approval.

Cyclerion Reports Corporate Update and Full Year 2022 Financial Results

Retrieved on: 
Wednesday, March 22, 2023

More recently, Cyclerion filed a request with the FDA for Orphan Drug Designation and manufactured drug product to support the Phase 2b study.

Key Points: 
  • More recently, Cyclerion filed a request with the FDA for Orphan Drug Designation and manufactured drug product to support the Phase 2b study.
  • Cash, cash equivalents, and restricted cash balance on December 31, 2022 was approximately $13.4 million, as compared to approximately $20.4 million on September 30, 2022.
  • Research and development expenses were approximately $31.5 million for the full year 2022, as compared to approximately $37.6 million for the full year 2021.
  • Net Loss: Net loss was approximately $44.1 million for the full year 2022, as compared to $51.6 million for the full year 2021.