Congenital Disorder of Glycosylation Type 1A

A small California biotech hopes to get its rare disease drug candidate to the FDA’s doorstep next year with the help of a $115 million Series C. The funding for Glycomine, disclosed Wednesday morning, comes four years after a Series B extension . The new money will take the startup into a Phase 2b trial and help it collect primary data from the test around the middle of next year, CEO Steven Axon told Endpoints News . Glycomine is developing a mannose-1-phosphate replacement therapy called GLM101 for patients with phosphomannomutase-2 congenital disorder of glycosylation. It estimates there are about 10,000 to 15,000 people in the US and Europe with the genetic disorder, also called PMM2-CDG, for which there are no approved therapies. Despite many investors and large pharma companies gravitating toward drug development opportunities in broader patient populations, like immunology and obesity, Glycomine was able to drum up interest in its Series C over the course of about six months, Axon said. “Rare diseases are probably not the hottest area of investment,” Axon said. “But when you have a later-stage drug, when you have relatively compelling clinical data, a pretty simple story, this is a 15-person company, people that looked at the program felt that this really could be a drug.” Investors in the decade-old startup include CTI Life Sciences Fund, Aberdeen, Advent Life  Sciences, Novo Holdings, Sanofi Ventures, Abingworth and others. PMM2-CDG is one of several hundred disorders of glycosylation, which involves the processing of sugar on protein surfaces. PMM2-CDG represents about 60% of all genetic glycosylation disorder patients, Axon said. The disease can impact any one of roughly 10,000 glycosylated proteins, Axon said. To make its mannose-1-phosphate replacement therapy effective, Glycomine encapsulates the phosphate in a lipid nanoparticle that extends its half-life from about five minutes to 80 hours, the CEO said. That LNP delivery also helps get the substrate directly into the cell, he said, noting mannose-1 “a charged molecule and has no transporter access into cells.” Glycomine is investigating GLM101 in adults and children as young as 2 years old in a Phase 2a study. It expects to start the Phase 2b trial in the middle of this year, and plans to include about 40 to 50 people in the placebo-controlled trial, Axon said. The trial will test whether a high dose of GLM101, at 30 mg/kg, is better than placebo on an evaluation known as the International Cooperative Ataxia Rating Scale (ICARS) at six months. After the initial six months, patients on placebo will switch over to Glycomine’s drug and continue to be followed. “It could be a pivotal study but it will require regulatory discussions to determine if there’s any additional data that’s required before we file,” Axon said. Glycomine is using about 10 to 14 sites in the US and Europe for the trial. Axon said those sites helped Glycomine do a 140-patient natural history study. The Series C gets Glycomine “well beyond the Phase 2b readout” but not enough to launch the drug, should it get approval, Axon said. The company could consider pharma partnerships, an IPO or other routes to become a commercial drugmaker. “We’re cognizant of the financial markets and the ability to go public, which would be a reasonable next step in good markets,” Axon said. “Fingers crossed on the markets turning a little bit in the right direction for us.” The biotech’s board has pharma dealmaking know-how. Glycomine added Joshua Grass as its chair in the fall of 2024. Grass was CEO of Escient Pharmaceuticals when Incyte bought the biotech startup for $750 million last year, and before that was CEO of Modis Therapeutics when Zogenix bought the early-stage drug developer for $250 million upfront .

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. '

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.