Highlights

• Two FDA designation applications submitted for creatine monohydrate in guanidinoacetate methyltransferase (GAMT) deficiency: Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD).

• First-in-class product opportunity. No FDA-approved treatment exists for GAMT deficiency. Families measure and mix high-dose creatine powder by hand, several times a day, for life.

• 3D printing for children. Weight-banded, taste-masked, 3D-printed dissolvable tablets give each child a precise dose that can change as they grow.

• Voucher potential. If approved, the program could earn a rare pediatric disease priority review voucher (PRV). Recent vouchers have sold for US$150-200 million.

• Upcoming milestones. FDA decisions on both designations and a pre-IND meeting with the FDA are expected in Q1 2027.

Toronto, Ontario--(Newsfile Corp. - October 28, 2026) - PharmaTher Holdings Ltd. (CSE: PHRM) (OTCQB: PHRRF) ("PharmaTher" or the "Company"), a specialty pharmaceutical company advancing 3D-printed medicines, today announced that it 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. PharmaTher is developing the product as 3D-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 three. Birth prevalence is estimated at 0.5 to 2 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 400-800 mg per kilogram of body weight per day, split into 3 to 6 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.

Why creatine monohydrate

Creatine monohydrate directly replaces what the body cannot make and has been the cornerstone of GAMT treatment since 1996, giving PharmaTher published clinical experience to build on. Because the FDA has never approved creatine monohydrate as a drug, it qualifies as a new active ingredient, a requirement for a priority review voucher.

The FDA has approved other supplement ingredients as prescription drugs, including Carnitor (levocarnitine) for primary systemic carnitine deficiency, Endari (L-glutamine) for sickle cell disease and Lovaza, a prescription fish oil, for severe hypertriglyceridemia.

Why 3D Printing for GAMT, and Beyond

• A precise dose for every weight band. One validated formulation can print many strengths, so a dose change is a file change, not a new production run.

• Child-friendly formats. Taste-masked dissolvable tablets are designed to replace hand-mixed powders.

• Dose accuracy and traceability. Each printed dose comes with a digital batch record.

• Room for combination products. 3D printing can combine creatine with other GAMT medicines, such as ornithine, in a single unit.

The same approach can serve other medicines children take by body weight, and each program adds formulations, data and regulatory know-how for the next.

Why 3D Printing for Rare Diseases

About 95% of the roughly 10,000 known rare diseases have no FDA-approved treatment, according to the U.S. National Institutes of Health. Many need only a few thousand doses a year, too few for a production line. With 3D printing, a formulation validated once as a digital recipe can be printed in small batches at qualified sites in PharmaTher's planned M3DICINES™ network, closer to patients.

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.

Rare Pediatric Disease Designation, for serious rare diseases that primarily affect children, can earn a transferable priority review voucher on approval of a never-approved active ingredient, cutting FDA review of another drug from about 10 months to about six.

Jazz Pharmaceuticals sold a voucher for US$200 million in January 2026, and Abeona Therapeutics sold one for US$155 million in June 2025. The program runs through September 30, 2029. There is no assurance that PharmaTher will receive a voucher, that a voucher could be sold, or what price it would bring if sold.

Next steps. PharmaTher expects FDA decisions on both designation requests, and a pre-IND meeting with the FDA, in Q1 2027.

Why a Widely Available Ingredient Can Become an FDA-Approved Drug

Under U.S. law, a product's regulatory status depends on its intended use, not its molecule. A dietary supplement cannot claim to treat a disease, so a creatine product for GAMT deficiency needs FDA approval as a drug. Approval brings FDA-reviewed quality and pediatric dosing, a prescription product insurers can cover, and seven years of orphan exclusivity against other approved creatine products for GAMT deficiency.

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 PharmaTher. "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 3D printing in pediatrics and rare diseases, where patients need precise doses in small batches that conventional manufacturing cannot economically provide."

About PharmaTher Holdings Ltd.

PharmaTher Holdings Ltd. (CSE: PHRM) (OTCQB: PHRRF) is a specialty pharmaceutical company advancing 3D-printed medicines. Through its M3DICINES™ platform and its exclusive North American distribution of Craft Health's CraftMake™ system, PharmaTher develops proprietary personalized medicines, including peptides, treatments for rare and pediatric diseases, and medical countermeasures. The Company also provides product development and small-batch production services to healthcare companies, and partners with pharmacies and government organizations. Learn more at PharmaTher.com.

Neither the Canadian Securities Exchange nor its Regulation Services Provider accepts responsibility for the adequacy or accuracy of this release.

Cautionary Note Regarding Forward-Looking Information

This news release contains forward-looking information within the meaning of applicable Canadian securities laws, including statements about: the FDA's review of, and decisions on, the Company's Orphan Drug and Rare Pediatric Disease Designation applications; the development, clinical testing and potential approval of 3D-printed creatine monohydrate for GAMT deficiency; the timing of a pre-IND meeting; potential orphan exclusivity, tax credits and fee waivers; and potential eligibility for, award of and sale value of a priority review voucher. Such statements are based on management's current expectations and are subject to risks and uncertainties that could cause actual results to differ materially, including that: the FDA may not grant either designation; clinical development may not succeed or may take longer or cost more than expected; the FDA may require more evidence than anticipated; regulatory approval may not be obtained; a priority review voucher may not be awarded, including because the rare pediatric disease priority review voucher program is currently authorized only through September 30, 2029, or may not be sold on attractive terms; the Company may not obtain financing on acceptable terms; and the Company depends on Craft Health and other third parties. Additional risks are described in the Company's continuous disclosure filings on SEDAR+ at www.sedarplus.ca. The Company's product candidates are investigational and have not been approved by the FDA, Health Canada or any other regulator. Voucher sale prices are taken from public disclosures by the companies involved and have not been independently verified. Readers should not place undue reliance on forward-looking information, which speaks only as of the date of this release. Except as required by law, PharmaTher undertakes no obligation to update it. CraftMake™ is a trademark of Craft Health Pte. Ltd. All other trademarks are the property of their respective owners. This news release does not constitute an offer to sell or a solicitation of an offer to buy any securities.

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/321351