IONIS-DNM2-2.5Rx

Dynacure has ended its Unite-CNM Phase I/II trial on DYN101, an investigational therapy for the treatment of myotubular and centronuclear myopathies (CNM). In a letter addressed to patients, the company said it is "unable to continue dosing at the low study dose or increase to a dose level at which we would expect to see clinical efficacy." Dynacure noted that while the first cohort of trial participants, who received a single dose of DYN101, tolerated the drug well, those from the second cohort, who received a higher quantity at the lowest level possible to determine efficacy, experienced elevated liver enzyme levels. The researchers tried to adjust the dose based on the patients' actual to ideal body weight, but all six patients still showed elevated liver enzymes. Five out of the six also reported having low platelet counts. After reviewing the study with an independent data monitoring committee, it was decided that dosing should be paused. The patients who had already taken the investigational drug continued with their follow-up visits and did not demonstrate any exposure to further risk. "This is not the news we ever wanted to share, as we know how great your needs are for safe and effective treatments. As a company and as individuals, we are overwhelmed with disappointment," Chris Freitag, M.D., the chief medical officer of Dynacure, said in the letter. "Like all clinical research efforts into CNM, the learnings from Unite-CNM are hard-earned by these study participants and investigators. They will add to the world's growing understanding of CNM. As we continue to review the findings of Unite-CNM, we will stay connected with study investigators, researchers, and patient advocacy organizations around the world. We will fulfill our obligation of making study results public," Freitag added. Dynacure had a promising journey prior to this unfortunate news. In June 2021, the U.S. Food and Drug Administration accepted its Investigational New Drug application for DYN101 due to positive initial results from its UNITE-CNM study. In January, the FDA granted it a Fast Track Designation. "Dynacure is continuing to investigate new approaches to address CNM, but it is too early to comment on any efforts. We remain very grateful for the heroic efforts of the patient who participated in this study, and their families and caregivers who supported these difficult endeavors," the letter concluded. CNMs are rare, life-threatening disorders that affect skeletal muscles from birth and affect around 4,000 to 5,000 patients in Australia, the European Union, Japan and the U.S. People diagnosed with CNM start experiencing muscle weakness from birth to early adulthood, and many patients die within the first 18 months of life. Those who survive longer usually require intense and uninterrupted medical assistance. Current interventions are merely supportive and not curative.

Biopharma companies are building momentum to carry them through the bulk of 2022. BioSpace takes a look at some of the recent announcements. Biopharma companies are building momentum to carry them through the bulk of 2022. Companies are providing pipeline updates and forecasts that will position them for potential success. BioSpace takes a look at some of the recent announcements. Dynacure Snags Fast Track Designation Pennsylvania-based Dynacure received Fast Track designation from the U.S. Food and Drug Administration (FDA) for lead candidate DYN101 , a potential treatment for Myotubular and Centronuclear Myopathies (CNM), a group of rare genetic diseases. A Fast Track designation provides expedited development and review of drugs for indications with significant unmet medical needs. CNM is driven by mutations in multiple genes, including MTM1, DNM2, and BIN. Dynacure said its researchers had discovered a link between an increase in DNM2 protein and the direct cause of the disease. Dynacure is currently assessing DYN101 in the Phase I/II UNITE-CNM study. DYN101 is being studied in that trial as a treatment for the two most common forms of CNM—X-linked myotubular myopathy (XLMTM) and autosomal dominant CNM (ADCNM). The company anticipates initial data from the ascending dose study in the second half of this year. Freeline Therapeutics Receives Greenlight for Gaucher Type 1 Gene Therapy Trial London-based Freeline Therapeutics is expected to initiate a Phase I study of experimental gene therapy to treat Gaucher disease Type 1. The FDA cleared the company’s Investigational New Drug (IND) application for FLT201, an AAV capsid (AAVS3) that contains an expression cassette, which encodes for a novel glucocerebrosidase variant (GCasevar85) under the control of a liver-specific promoter. Michael Parini, chief executive officer of Freeline, said FLT201 is the first AAV-mediated gene therapy for Gaucher disease Type 1 to enter the clinic. Prior to FDA approval of the IND, Freeline had also received clearance to begin a Phase I/II dose-finding study of FLT201 in Europe. Later this year, the first patients are expected to be dosed in that study. Initial safety and biomarker data from the first cohort is expected in the third quarter. Freeline’s preclinical proof-of-concept studies suggest that FLT201 has the potential to reach challenging to treat tissues that are not sufficiently addressed by current standard-of-care enzyme replacement therapy. The company believes that FLT201 can be a transformative product for Gaucher Type 1. Neurocrine to Focus on Expansion of Ingrezzia, Other Clinical Programs As San Diego-based Neurocrine looks ahead into 2022, the company said its priorities are squarely focused on Ingrezzia (valbenazine), which the FDA first approved in 2017 for the treatment of tardive dyskinesia (TD). The company assesses its asset in multiple indications, including Chorea in Huntington’s disease. Neurocrine anticipates a supplemental New Drug Application will be filed for this indication in the second half of 2022. Neurocrine CEO Kevin Gorman said the company is well-positioned to drive the growth of Ingrezzia in TD and other indications, which will then support the development of its 13 other clinical programs in mid-to-late stage studies. “We exited 2021 helping more patients with tardive dyskinesia than ever before. Furthermore, we now have 13 clinical programs in mid-to-late-stage studies which will generate important data readouts over the next two years,” Gorman said in a statement. Mersana Therapeutics Unveils Big Plans for 2022 Cambridge, Mass.-based Mersana is also looking forward to 2022. This morning, the company announced multiple goals and milestones for the coming 12 months. Chief among those priorities is its plan to build upifitamab rilsodotin (UpRi) as a foundational medicine to treat ovarian cancer. UpRi is a first-in-class dolaflexin ADC that targets NaPi2b. Mersana enrolls patients in the UPLIFT clinical study, a registrational trial in platinum-resistant ovarian cancer. Enrollment is expected to be completed by the third quarter of this year. Additionally, the company is conducting the Phase III UP-NEXT study with UpRi in platinum-sensitive recurrent ovarian cancer. It also is running UPGRADE, a Phase I/II combination study in platinum-sensitive ovarian cancer. Interim data is expected from this study in the second half of 2022. In addition to UpRi, Mersana also assesses other oncology drugs, including XMT-1592, a first Dolasynthen ADC that targets NaPi2b and XMT-1660, a first-in-class Dolasynthen ADC targeting B7-H4. The company also plans to announce more information about two development candidates, XMT-2068 and XMT-2175, later this year. Both are STING-agonist ADCs targeting tumor-associated antigens.