Mr. Fabio Chianelli reports

PHARMMATHER SUBMITS ORPHAN DRUG AND RARE PEDIATRIC DISEASE DESIGNATION APPLICATIONS TO FDA FOR 3D-PRINTED CREATINE MONOHYDRATE IN GAMT DEFICIENCY

Pharmmather Holdings Ltd. has submitted applications to the U.S. Food and Drug Administration (FDA) for orphan drug designation and rare pediatric disease designation for creatine monohydrate to treat GAMT deficiency. Pharmmather is developing the product as 3-D-printed, orally dissolvable mini-tablets or pellets on its M3Dicines platform.

GAMT deficiency: a treatable disease without an approved treatment

GAMT deficiency is an inherited disorder in which the body cannot make creatine, which brain and muscle cells need for energy, while its precursor, guanidinoacetate (GAA), builds up to toxic levels.

Untreated children develop intellectual disability, limited speech, seizures, low muscle tone, and movement and behavioural problems by age 3. Birth prevalence is estimated at 0.5 to two per million live births.

The unmet need

No FDA-approved therapy. Patients take lifelong supplement-grade or compounded creatine monohydrate, often with ornithine, sodium benzoate and a restricted diet.

A heavy daily burden. Dosing is 400 milligrams to 800 mg per kilogram of body weight per day, split into three to six doses that caregivers weigh and mix by hand.

More children are being found earlier. GAMT deficiency joined the U.S. Recommended Uniform Screening Panel in January, 2023, so more infants are diagnosed at birth.

Early treatment works. Treatment started before symptoms appear substantially improves outcomes.

What the designations could mean

Orphan drug designation, for diseases affecting fewer than 200,000 people in the U.S., brings seven years of U.S. market exclusivity on approval, a tax credit for clinical trial costs and a waiver of the FDA application fee.

Next steps

Pharmmather expects FDA decisions on both designation requests, and a pre-IND meeting with the FDA, in the first quarter of 2027.

Management commentary

"There is still no FDA-approved medicine for children with GAMT deficiency, and families measure and mix creatine powder by hand several times a day," said Fabio Chianelli, chief executive officer of Pharmmather. "These applications are our first step toward a precisely dosed, approved medicine that changes as they grow. We believe this program opens up many opportunities for 3-D printing in pediatrics and rare diseases, where patients need precise doses in small batches that conventional manufacturing cannot economically provide."

About Pharmmather Holdings Ltd.

Pharmmather Holdings is a specialty pharmaceutical company advancing 3-D-printed medicines. Through its M3Dicines platform and its exclusive North American distribution of Craft Health's CraftMake system, Pharmmather develops proprietary personalized medicines, including peptides, treatments for rare and pediatric diseases, and medical countermeasures.

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