PMM2

Glycomine, a biotechnology startup working on a treatment for a rare genetic disorder, has raised a $115 million Series C round to push its lead program deeper into clinical testing.The funding announced Wednesday for the San Carlos, California-based company will support development of its therapy GLM101, which is designed to treat phosphomannomutase 2-congenital disorder of glycosylation, or PMM2-CDG.PMM2-CDG is the most common among a family of inherited disorders that cause errors in glycosylation, the biological process by which sugar chains called glycans are added to proteins. This type of malfunction can affect the structure and function of cellular proteins throughout the body, leading to an array of symptoms, developmental delays and impaired motor function. There are no approved treatments for the roughly 15,000 people who are estimated to have the condition in the U.S. and Europe, though a few programs are in clinical testing.That need is extremely high, said Steven Axon, Glycomines CEO. There's no other therapies for these patients. There's only supportive care.Glycomine aims to change that by delivering into the body a component used in glycosylation mannose-1-phosphate thats deficient in people with PMM2-CDG.The companys approach is somewhat akin to the enzyme replacement therapies used to treat lysosomal storage disorders like Fabry or Pompe disease. Glycomines therapy is replacing a missing sugar molecule rather than an enzyme, however, and corrects a defective chemical process instead of clearing an accumulating toxin.Last year, Glycomine released Phase 2 data showing the drug appeared to impact ataxia, a common symptom of PMM2-CDG, in a small group of patients. The Series C round will carry the company through a more rigorous, randomized and placebo-controlled Phase 2b study that should start in the middle of this year and enroll between 40 to 50 participants, Axon said.The company hopes to report data in 2026 that will really tell us whether the effect we were seeing in the earlier clinical program has been confirmed, he said.If those results are positive, Axon said the company may explore a partnership with a pharmaceutical company.Having this randomized controlled data and really knowing that the drug works and its path to approval would be highly derisking for a pharma partner, he said.Though Glycomine has not disclosed specifics about the rest of its pipeline, its developing drug candidates for other rare diseases outside of PMM2-CDG, according to Axon.The companys Series C funding was led by CTI Life Sciences Fund, funds managed by Abrdn, and Advent Life Sciences. Other backers include Novo Holdings, Sanofi Ventures and Abingworth. Glycomine previously raised $80 million across Series A and B rounds. '

Art 3d banner collage of business people dollar roll cooperation success payment capital profit transaction money corruption. iStock, Deagreez The raise will go toward trialing the company’s lead drug for phosphomannomutase-2 congenital disorder of glycosylation, a rare disease that affects the entire body and produces a wide range of symptoms. California-based biopharma Glycomine announced a $115 million Series C raise Wednesday to push its lead rare disease molecule into Phase IIb trials. “We’re working on glycosylation disorders, putting sugar chains on proteins. There are hundreds of those,” CEO Steve Axon told BioSpace in an interview. The disorder that Glycomine is targeting is, according to Axon, the largest of that group: phosphomannomutase-2 congenital disorder of glycosylation, or PMM2-CDG, for which there is no FDA-approved treatment. “We think it’s maybe up to 15- 20 thousand patients in [the] U.S. and Europe, which is a relatively large population for a rare disease,” Axon said, likening the demographic size to Pompe disease. Glycomine is using the new funds to push its lead molecule, GLM101, into a randomized, placebo-controlled Phase IIb trial. In early 2024, the company announced “encouraging” data for a Phase II trial for the drug, showing improvements for nine adult and adolescent patients in ataxia, neurological symptoms characterized by loss of muscle control. Improving ataxia is the clinical endpoint for GLM101’s efficacy studies. The Phase IIb study, comprising 40 to 50 patients from two years to adults, is set to start by the middle of this year, with data expected sometime in mid-2026. Then, Glycomine will approach the FDA about filings. The FDA could also ask for more trials, but as there aren’t any other treatments for the disorder, “we’re hopeful for productive regulatory discussions,” Axon said. “We think we’re in good shape with the FDA.” PMM2-CDG is a genetic disease often diagnosed in infancy. It involves a range of mutations that all affect one protein, phosphomannomutase 2, which is involved in the glycosylation process. Symptoms and severity can vary and most patients experience some sort of neurological dysfunction, as well as language and motor issues from childhood. Ataxia, seizures, immune dysfunction and coagulation issues are also common with PMM2-CDG. “PMM2 has a 20% mortality rate within the first five years of life, from organ failure and failure to thrive,” Axon said. “And glycosylation is at the core of all of [those clinical signs].” GLM101 is a lipid nanoparticle–delivered mannose-1-phosphate (M1P) replacement therapy. Because of the phosphomannomutase 2 mutation, patients are critically short of M1P. The lipid nanoparticle delivery vehicle is critical, Axon said, because it extends M1P’s half life in the bloodstream from a few minutes to upwards of 80 hours. Glycomine is also investigating mRNA treatments to produce enzyme replacements for PMM2-CDG, but so far the company is sticking with simply replacing the missing molecule, an approach Axon called simple and elegant. “What we’ve settled on is something that has really wide biodistribution,” he said. The company has gone through multiple raises of increasing sizes on its journey to the clinic. A $12 million Series A in 2016 started things off, followed by two successive Series B raises of $33 million in 2019 and $68 million in 2021 .

The funding will be used to advance GLM101 into a Phase IIb trial: Credit: Malte Mueller via Getty Images. Glycomine has raised $115m in Series C financing to advance its lead investigational therapy, GLM101, into a Phase IIb clinical trial for an ultra-rare disorder. GLM101 is being developed as a treatment for phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG), a rare and life-threatening genetic disorder with no approved treatments. Glycomine is currently conducting an open-label Phase II clinical trial (NCT06657859) at sites in Europe and the US, with 20 patients enrolled to date. The company recently initiated dosing in paediatric patients. Interim results from nine adult and adolescent patients showed an average 11.9-point improvement over 24 weeks on the international cooperative ataxia rating scale, indicating potential clinical benefit in one of the most debilitating features of the disease. The candidate is a mannose-1-phosphate replacement therapy aimed at correcting the metabolic deficiency caused by mutations in the PMM2 gene. These mutations impair the synthesis of N-linked glycans, which are critical for the normal function of proteins and lipids in the body. The resulting condition manifests with a wide range of symptoms, like ataxia (poor muscle control), developmental delays, vision loss, and multi-organ involvement. Current management is limited to supportive care such as physiotherapy, assistive equipment, and symptom-targeting interventions. The latest investment builds on the company’s previous $35m raise in June 2021, which supported its Phase I programme for GLM101. In the 16 April announcement, Glycomine’s CEO Steve Axon said: “This financing will enable us to advance GLM101 into a randomised, placebo-controlled trial later this year – an important step toward bringing the first disease-modifying therapeutic to patients with PMM2-CDG.” CTI Life Sciences Fund and Advent Life Sciences co-led the funding round, with participation from Novo Holdings, Sanofi Ventures, Abingworth, RiverVest Venture Partners, Sanderling Ventures, Chiesi Ventures, Remiges Ventures, and Asahi Kasei Ventures. In parallel to Glycomine’s programme, a separate effort is underway to assess the potential of a repurposed therapy for PMM2-CDG. Maggie’s Pearl – a joint venture between the rare disease biotech Perlara, the non-profit organisation Maggie’s Cure, and Mayo Clinic – is sponsoring a Phase III trial of oral epalrestat (NCT04925960) in 40 paediatric patients. The US Food and Drug Administration (FDA) cleared the Phase III study in December 2021, and the study is now fully enrolled and expected to complete by YE. Epalrestat is an aldose reductase inhibitor approved in Japan for the treatment of diabetic neuropathy. This recent update comes amid growing uncertainty around the future of incentives for rare disease drug development in the US. In particular, the potential discontinuation of the FDA’s paediatric priority review voucher (PRV) programme is raising concerns across the sector.