Pharmather talks ketamine as Parkinson's treatment

Mr. Fabio Chianelli reports PHARMATHER PROVIDES UPDATE ON KETAMINE PROGRAM FOR LID-PARKINSON'S DISEASE Pharmather Holdings Ltd. has provided an update regarding its initiative to develop ketamine as a treatment for levodopa-induced dyskinesia (LID-PD) in patients with Parkinson's disease. Phase 3 program targeting a potential $2.2-billion (U.S.) United States market opportunity; 505(b)(2) regulatory path leveraging prior human data to reduce risk, cost and time; Food and Drug Administration-reviewed CMC package validated through prior ANDA approval; Patent coverage to 2036 for ketamine in Parkinson's and related motor disorders; Active pharmaceutical partnering discussions; Upcoming catalysts (Q4 2025 to Q2 2026): FDA meeting, pivotal study readiness, pharma partnership. Pharmather's objective is to continue the development of its ketamine program for LID-PD via the 505(b)(2) regulatory pathway, leveraging existing scientific and clinical evidence together with the company's FDA-reviewed chemistry, manufacturing and controls (CMC) foundation to reduce development risk, cost and timelines. The company is preparing for a phase 3, well-controlled clinical study designed to evaluate efficacy and safety in support of a potential new drug application (NDA), subject to FDA feedback. Four-pillar strategy Regulatory alignment. Pharmather intends to request a prephase 3 meeting with the FDA to obtain clarity on a phase 3 -- enabling path and confirm key components of a registrational plan for LID-PD. Clinical plan. The company plans to pursue FDA acceptance for a single, well-controlled phase 3 study to support NDA submission. The protocol will include safety monitoring aligned with the ketamine class and will assess pain and depression as exploratory secondary outcomes, alongside dyskinesia-focused primary end points. CMC leverage. Pharmather will utilize the work completed for its FDA-reviewed Ketamine ANDA to streamline analytical methods, specifications and stability programs for intended clinical and commercial presentations under 505(b)(2). Partnering and capital efficiency. The company is engaged in active discussions with prospective pharmaceutical partners that could acquire or licence the program, supporting a capital-efficient advancement to and through pivotal development. Ketamine's value proposition in LID-PD Mechanistic rationale. Excessive glutamatergic/NMDA signaling is implicated in dyskinesia. The only FDA-approved LID therapy (amantadine ER) is NMDA-based, validating the target class. Ketamine, a non-competitive NMDA receptor antagonist with additional receptor-level actions, therefore has a strong biological rationale for evaluation in LID-PD. Clinical evidence. In a previously reported phase I/II study, ketamine was safe and well tolerated. All treated subjects experienced reductions in dyskinesias, as measured by the Unified Dyskinesia Rating Scale (UDysRS): 51 per cent from baseline during infusion 2 (p equals 0.003), 49 per cent at three weeks (p equals 0.006) and 41 per cent at three months (p equals 0.011). No adverse events were reported postinfusion. Time and cost advantages. Leveraging Pharmather's FDA-validated CMC platform from the ANDA program is expected to compress development timelines and costs for the NDA submission by streamlining manufacturing, quality and regulatory activities. Patent coverage. Pharmather has exclusive rights to U.S. patent No: 11,426,366 (expires May, 2036), titled "Compositions and Methods for Treating Motor Disorders," which includes claims intended to cover ketamine in the potential treatment of Parkinson's disease and motor disorders that cause involuntary or uncontrollable movement or actions of the body. Market opportunity Approximately 1.1 million individuals in the United States are currently living with Parkinson's disease, with an estimated 90,000 new diagnoses occurring annually. Projections indicate that the prevalence of PD will reach approximately 1.2 million by the year 2030 in the U.S. Globally, it is estimated that the number of Parkinson's cases will grow to more than 25 million by 2050. Published literature indicates that approximately 30 to 40 per cent of patients receiving levodopa treatment develop dyskinesia within four to six years. This prevalence tends to increase, reaching approximately 50 to 60 per cent or higher, with prolonged exposure to the medication. There could be a significant market opportunity for a ketamine-based treatment in LID-Parkinson's disease, with an implied treated market estimated between $750-million and $2.2-billion (U.S.). This is based on approximately 1.1 million Parkinson's disease patients, 30 to 40 per cent of whom develop clinically meaningful LID (330,000 to 440,000), 15 to 25 per cent of these patients are treated (50,000 to 110,000), at a net price of $15,000 to $20,000 per treated patient annually. Strategic significance Pharmather's LID-PD program represents a high-value clinical and commercial opportunity in a validated treatment category with proven reimbursement viability. With proprietary clinical data, patent protection to 2036 and an FDA-reviewed CMC foundation, the company is positioned to advance a capital-efficient, late-stage program with potential for strategic licensing or acquisition. Pharmather believes that its progress in LID-PD, together with its broader ketamine franchise, offers multiple near-term catalysts to unlock shareholder value -- including FDA feedback on the phase 3 pathway, potential partnership developments, and expansion opportunities in other neurological and motor disorders. "This program not only addresses a major unmet need in Parkinson's disease but also highlights the scalability of our 505(b)(2) regulatory strategy," said Fabio Chianelli, chief executive officer of Pharmather. "Each milestone we reach with ketamine for LID brings us closer to unlocking broader value in our ketamine platform across multiple indications." Anticipated near-term milestones Q4 2025 to Q1 2026: submit prephase 3 FDA meeting request and briefing package; hold meeting and receive minutes (timing subject to agency scheduling); Q1 to Q2 2026: finalize pivotal protocol (end points, inclusion/exclusion, statistical plan) based on FDA feedback; H1 2026 and onward: initiate late-stage study, contingent on FDA alignment and financing/partnering; provide periodic updates on enrolment, safety and business development activities. Fabio Chianelli, chief executive officer of Pharmather, concluded: "The phase 3-ready ketamine program for LID-Parkinson's positions Pharmather at an inflection point. With a derisked regulatory path, a validated manufacturing foundation and a multibillion-dollar addressable market, this program represents one of the most promising late-stage ketamine opportunities in neurology today. Our goal is to create meaningful value for both patients and shareholders as we advance toward FDA alignment, pivotal initiation and strategic partnership in 2026." About Pharmather Holdings Ltd. Pharmather Holdings is focused on unlocking the pharmaceutical potential of ketamine for mental health, pain and neurological disorders. We seek Safe Harbor.