The trip of patients with rare diseases and their families can be a long marked by erroneous diagnoses, so it is for those who have ultra -raised disorder with the abbreviated name PMM2 CDG. This enzymatic deficiency leads to muscle problems and development delays that are often confused with other diseases, said Steven Axon, CEO of the Startup Glycomine.
PMM2-CDG is genetic, but it is currently not part of the detection of newborns. The disease can be diagnosed with a genetic test, but a doctor needs to know for the test. If a patient does not see a doctor familiar with PMM2-CDG, the trip to a diagnosis can be one year or more. The most common malgiosis is cerebral palsy.
“If they were born before 1995, they can still believe they have cerebral palsy because that is when the PMM2 protein was identified as the culprit of this disorder,” Axon said. “But for other patients, they will have all kinds of challenges from the beginning, so they will have challenges with their liver, they raised liver enzymes, they will have this failure to prosper.”
The deficiency of the homonymous enzyme of the disease leads to problems through the body. The most common cause of death is organic insufficiency. In addition to support care, PMM2-CDG has no pharmacological treatments. Glycomine is developing a medication that adopts a novel approach to enzymatic deficiency. On Wednesday, Biotech, based in San Carlos, California, announced $ 115 million in new financing for clinical tests of the middle stage.
PMM2-CDG It is the abbreviation of phosphomannomutase 2 conferncial disorder or glucosylation. PMM2 enzyme voice deficiency of the PMM2 gene mutations that interrupt glucosilation, the process in which sugar chains bind to proteins. A PMM2 enzyme is needed to convert a certain chemical compound to Mantease-1-phosphate, a compound that is essential for this process.
Glucoproteins formed by glucosylation are key to the function of tissues and organic varosses through the human body. Humans have about 10,000 glucosylated proteins, all of which can be affected by PMM2-CDG, Axon said. Ataxia, the loss of muscle coordination, is the most common presentation of PMM2 CDG. Seizures, delays in development and cognitive challenges are common in the disease, which glucomin estimates affect between 10,000 and 15,000 people in the United States and Europe.
For many rare enzymatic deficiencies, treatment is typically enzymatic replacement therapy. But Glycomine is not trying to replace the PMM2 enzyme. The company’s drug candidate, with GLM101 code, is a replacement for the Hand-1-phosphate. The reason for this approach is the nature of the disease, Axon said. Enzymatic replacement is typically used for lysosomal storage disorders, diseases where enzyme is needed to eliminate something toxic. That is not the case with PMM2 CDG. Therefore, it is much easier to provide Hand-1-phosphate than to provide poor enzyme.
The challenge is to deliver Hand-1-phosphate in the body. Without protection, the body breaks down the molecule in approximately five minutes, there is not enough time to get where it takes to be helpful, Axon said. The glycomin encapsulates Handsa-1-phosphate in a lipid nanoparticle, extending the circulating half-life of its drug to approximately 80 hours. It is administered weekly through an intravenous infusion that takes about three hours, although the company is making changes that could be dosing time.
“We deliver that weekly because many of the proteins in which they interest us, give themselves in days,” said Axon. “We have this extended half -life, but by the time I reach the end of the week of the medicine, we are below the level of exposure in which we want to be and, therefore, we need to rest that.”
The Science Beind GLM101 was developed within Glycomine, a startup formed by scientists from the Bay area in 2014 and supported friends, family and seeds, Axon said, a veteran of the biopharmaceutical industry issued by the company in 2016. Precilinic development candidate along with $ 12 million in the financing of the series a directed by the sanding companies. Five years later, Glycomine closed its B series B series of $ 68 million to advance to the clinic.
Until now, Glycomina has tried GLM101 in 10 patients in a phase 2 study of open label. To date, data from four adults and five adolescents at six months show a significant statistically significant and clinical improvement in ataxia according to the qualification scale used to evaluate this symptom. In addition, the drug seems to be safe and well tolerated.
With early encouraging results, Glycomine is processed to a six -month phase test controlled with placebo designed to register between 40 and 50 participants of 4 years or more. Like the open study, evaluating ataxia will also be the objective of the clinical test controlled with placebo. But after six months, those who received placebo will cross a treatment arm and all patients will be followed in a long -term extension study. Axon hopes that the registration of phase 2B will begin at the middle of this year; Preliminary data could reach mid -2016. He added that the study is designed to potentially support a regulatory presentation, but that the determination still needs the FDA signature.
Axon said that GLM101 could be used to treat other glycosylation disorders, but those diseases, even rarely than the PMM2 CDG, affect patients’ handfuls, which makes development difficult. Glycomina has counted those indications. But the focus of using a lipid nanoparticle to deliver a payload with a wide distribution through the body could be applied to other diseases. Glycomine is exploring such applications, but the objectives of the disease remain without revealing.
Glycomine is not the only company that develops a PMM2-CDG treatment. This rare disease is one of the objectives for the main drug candidate for applied therapy, Govorestat. But that biotechnology is focusing on the development of this medication for galactosemia, a strange different disease without treatment approved by FDA. The past fall, the FDA rejected the application of applied in search of a regulatory approach in this indication. In PMM2, the applied small molecule has been tested in a single patient in a clinical trial initiated by the researcher, according to the company’s regulatory presentations.
The financing of the Glycomine C series announced Wednesday was led by CTI Life Sciences Fund, Funds Managed Inc. and Advent Life Sciences. These investors joined the previous investors Sanderling, Novo Holdings, Sanofi Ventures, Abingworth, Rivervest Venture Partners, Chiesi Ventures, Remiges Ventures and Asahi Kasei Ventures.
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