Collaboration combines more than 9,000 KetaMist® patient treatments with PharmaTher's prior FDA-approved ketamine experience

Pursuing an efficient FDA development pathway toward approval for treatment-resistant depression and other potential indications, leveraging KetaMist's real-world treatment foundation

KetaMist represents a differentiated, patient-controlled ketamine platform with the potential to build a multi-indication ketamine franchise

Toronto, Ontario--(Newsfile Corp. - July 21, 2026) - PharmaTher Holdings Ltd. (CSE: PHRM) (OTCQB: PHRRF) ("PharmaTher" or the "Company"), a specialty pharmaceutical company focused on personalized medicines for peptides and psychedelics, today announced a collaboration with Curtis W. Cassidy, M.D., the inventor and developer of KetaMist® (ketamist.com), a needle-free ketamine treatment platform, to pursue U.S. Food and Drug Administration ("FDA") approval for treatment-resistant depression (TRD) and other neuropsychiatric and medical conditions where ketamine has demonstrated therapeutic benefit.

KetaMist is a proprietary, patient-controlled and needle-free ketamine treatment platform developed by Dr. Cassidy for patients with treatment-resistant depression and other conditions. According to Dr. Cassidy, KetaMist has been used in more than 9,000 patient treatments, creating a meaningful body of real-world clinical experience that PharmaTher believes may support an efficient and potentially expedited FDA development strategy.

Targeting the Large and Growing TRD Market While Building a Ketamine Franchise

Treatment-resistant depression represents a significant unmet medical need, affecting millions of patients in the United States who do not respond adequately to standard antidepressant therapies. The current FDA-approved ketamine-based therapy for TRD, Spravato® (esketamine nasal spray), has demonstrated strong commercial traction, generating approximately $1.7 billion in worldwide sales in 2025, with trailing twelve-month sales through June 30, 2026 of approximately $2.0 billion.¹ Analysts have reportedly projected that Spravato could generate approximately $3 billion in annual sales by 2027 and up to $5 billion in peak annual sales, highlighting the significant commercial opportunity for differentiated ketamine-based treatments.²

PharmaTher believes KetaMist has the potential to compete in this large and growing market by offering a differentiated treatment approach that may address certain limitations associated with existing therapies.

KetaMist is designed as a patient-controlled and needle-free delivery system, which may offer several potential advantages, subject to FDA approval:

• Personalized dosing and administration, allowing physicians to tailor treatment to individual patient response;
• Simplified delivery method, potentially improving patient comfort and accessibility;
• Potential for broader clinical adoption, depending on regulatory requirements and labeling; and
• Use of racemic ketamine, which may provide a differentiated pharmacological profile compared to esketamine.

Beyond TRD, PharmaTher views KetaMist as a franchise platform with the potential to be developed across multiple indications where ketamine has already demonstrated clinical utility, including but not limited to depression, anxiety disorders, post-traumatic stress disorder (PTSD), chronic pain, and other neuropsychiatric and neurological conditions. While many of these uses are currently off-label, the Company believes KetaMist's flexible and personalized delivery approach may support expansion into additional therapeutic areas over time, subject to regulatory approval.

A Potentially Expedited Path Toward FDA Approval

PharmaTher and Dr. Cassidy plan to work with the FDA to find an efficient path to approval for KetaMist.

Because ketamine is already an FDA-approved drug, the Company may be able to build on existing knowledge. KetaMist has already been used in more than 9,000 patient treatments, providing real-world experience on how the therapy is administered, how patients respond, and overall safety. PharmaTher will prepare regulatory documents to help guide discussions with the FDA toward a potentially expedited approval pathway.

Leveraging PharmaTher's FDA-Approved Ketamine Foundation

PharmaTher previously obtained FDA approval for Ketamine Hydrochloride Injection USP under ANDA #217858, demonstrating the Company's ability to complete the regulatory, manufacturing, analytical and quality requirements necessary to secure an FDA ketamine approval.

Although PharmaTher completed its sale of its ANDA in December 2025, the Company retained its rights to pursue non-generic ketamine opportunities, including new formulations, delivery technologies and therapeutic indications. PharmaTher also retained significant regulatory and product-development experience generated through the successful ANDA program.

As part of the KetaMist collaboration, PharmaTher intends to apply its ketamine regulatory, analytical and chemistry, manufacturing and controls experience to the KetaMist development program and seek FDA feedback on the most efficient pathway toward approval.

Positioned at the Intersection of Ketamine, Personalized Medicine and Regulatory Momentum

The collaboration follows PharmaTher's recently announced strategy to advance personalized medicines for peptides and psychedelics through differentiated products, enabling technologies and regulatory pathways.

KetaMist is aligned with that strategy because its patient-controlled delivery approach is intended to allow treatment to be adjusted to individual patient response rather than relying solely on a standardized administration model.

Importantly, PharmaTher believes KetaMist's design supports its development as a multi-indication ketamine franchise, leveraging the well-established pharmacology of ketamine and its broad therapeutic potential across numerous conditions.

The program also arrives during a period of increased U.S. regulatory attention toward ketamine and innovative mental-health treatments.

PharmaTher believes that recent regulatory precedents demonstrate increasing openness to development strategies that incorporate real-world data and leverage existing clinical experience to support more efficient pathways to approval. While each program is evaluated independently by the FDA, these precedents may provide a framework for engaging with regulators on potential expedited development approaches.

"KetaMist fits our strategy perfectly-a doctor-developed ketamine treatment with over 9,000 patient uses and a path to FDA approval. While we are initially focused on treatment-resistant depression, we believe KetaMist represents a broader franchise opportunity across multiple indications where ketamine has already shown clinical benefit. By combining this real-world experience with our prior FDA-approved ketamine work, we believe we can move faster and more efficiently than traditional drug development and unlock meaningful value across several large markets," said Fabio Chianelli, Chief Executive Officer of PharmaTher.

Dr. Curtis W. Cassidy commented: "I developed KetaMist to give physicians and patients a more personalized and accessible approach to ketamine treatment. After more than 9,000 patient treatments, we have gained substantial practical experience regarding how patients respond and how treatment may be individualized across a range of conditions. PharmaTher shares that focus on personalized medicine and has the pharmaceutical-development and FDA experience needed to take the next important step toward broader access and potential regulatory approval."

Near-Term Development Priorities

The collaboration activities will include preparing an FDA meeting package to obtain guidance for a potentially accelerated path toward FDA approval.

Near-term milestones are expected to include regulatory engagement with the FDA, definition of the clinical and data requirements for a potential NDA submission, and evaluation of how existing real-world data may support the development program.

The collaboration agreement provides PharmaTher with a one-year evaluation period to assess KetaMist for potential development and commercial testing. During this period, the parties may negotiate and enter into one or more additional agreements (each a "Possible Transaction") relating to the further development and commercialization of KetaMist, subject to mutually acceptable terms.

KetaMist is not currently approved by the FDA, and its existing clinical use is considered off-label. There can be no assurance that the FDA will accept the proposed regulatory pathway, that the existing treatment information will be suitable for regulatory use, or that KetaMist will receive FDA approval.

About KetaMist®

KetaMist® is a proprietary, patient-controlled and needle-free ketamine treatment platform developed to provide a more personalized approach for patients with treatment-resistant depression and other neuropsychiatric and medical conditions. The system is designed to allow physicians to tailor dosing and administration based on individual patient response, offering flexibility compared to traditional ketamine delivery methods.

KetaMist has been used in more than 9,000 patient treatments, generating meaningful real-world clinical experience related to dosing, administration, safety observations and patient outcomes. For more information, visit Ketamist.com.

About PharmaTher

PharmaTher Holdings Ltd. (CSE: PHRM) (OTCQB: PHRRF) is a specialty pharmaceutical company focused on developing, acquiring and commercializing personalized medicines and enabling technologies, with an emphasis on peptides and psychedelics. For more information, visit PharmaTher.com.

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

Cautionary and Forward-Looking Statements

This news release contains "forward-looking information" and "forward-looking statements" within the meaning of applicable Canadian securities laws, collectively referred to as "forward-looking information." Forward-looking information is often identified by words such as "believe," "expect," "plan," "intend," "may," "could," "would," "should," "anticipate," "potential," "proposed," "target," "seek," "estimate," "forecast," "position," "develop," "advance," "expedite," "accelerate," "commercialize" and similar expressions, or statements that certain events or conditions "will," "may" or "could" occur.

This press release contains forward-looking statements regarding, among other matters, the collaboration with Dr. Cassidy, the evaluation and development of KetaMist, the proposed regulatory pathway, the potential use of real-world data, future FDA interactions, required studies, intellectual-property, development, and commercial opportunities, possible transaction, and the potential submission or approval of an NDA. Forward-looking statements are based on management's current expectations and assumptions and are subject to regulatory, clinical, manufacturing, intellectual-property, financing, competitive and other risks and uncertainties. There can be no assurance that the FDA will agree with the proposed development plan, that available data will be suitable for regulatory purposes, that required studies will be successful, that sufficient financing or partnerships will be obtained, or that KetaMist will receive regulatory approval or achieve commercialization.

Forward-looking information is based on management's current expectations, estimates, forecasts, beliefs and assumptions as of the date of this news release. Material assumptions include, without limitation, that: the collaboration will remain in effect and the parties will perform their respective obligations; information regarding prior KetaMist treatments is accurate, complete, accessible and capable of being reviewed or organized for regulatory purposes; the Company will be able to engage with the FDA within anticipated timelines; the FDA will provide guidance that permits a feasible development pathway; any required studies can be designed, funded and successfully completed; suitable manufacturing, analytical, clinical and supply-chain capabilities can be obtained; the Company will have access to sufficient capital, personnel and third-party expertise; intellectual-property and commercial rights can be maintained or secured; the Company will enter into one or more possible transactions; applicable laws and regulatory policies will not change in a materially adverse manner; and market-size information, commercial estimates and third-party analyst forecasts referenced in this news release are reasonably accurate. These assumptions may prove to be incorrect. Forward-looking information is subject to known and unknown risks, uncertainties and other factors that could cause actual results, events or achievements to differ materially from those expressed or implied. Such risks include, without limitation: the possibility that the FDA may not agree with the Company's proposed development or regulatory strategy; that KetaMist may not qualify for an expedited or accelerated pathway; that the FDA may require substantial additional non-clinical, clinical, manufacturing, human-factors or other studies; that real-world data or information from prior patient treatments may be incomplete, inconsistent, retrospective, unverifiable or unsuitable for regulatory reliance; that existing treatment experience may not demonstrate safety or efficacy to the FDA's satisfaction; that studies may be delayed, unsuccessful or more costly than expected; and that KetaMist may never receive regulatory approval.

Readers are cautioned not to place undue reliance on forward-looking information, which speaks only as of the date of this news release. Except as required by applicable law, PharmaTher undertakes no obligation to update or revise any forward-looking information, whether as a result of new information, future events or otherwise. Additional risk factors are described in the Company's continuous disclosure filings available under the Company's profile on SEDAR+. The forward-looking information contained in this news release is expressly qualified by this cautionary statement.

This news release does not constitute an offer to sell or the solicitation of an offer to buy securities in any jurisdiction in which such offer, solicitation, or sale would be unlawful.

Footnotes

1. Johnson & Johnson, "Johnson & Johnson Reports Q4 and Full-Year 2025 Results," January 21, 2026, reporting worldwide Spravato sales of $1.696 billion for the year ended December 31, 2025; and Johnson & Johnson, "Johnson & Johnson Reports Q2 2026 Results, Raises 2026 Outlook," July 15, 2026, reporting worldwide Spravato sales of $1.052 billion for the six months ended June 30, 2026, compared with $734 million for the corresponding six-month period in 2025. Trailing twelve-month sales through June 30, 2026 were calculated as follows: $1.696 billion less $734 million, plus $1.052 billion, equalling approximately $2.014 billion. Figures may not add precisely due to rounding.
2. "Johnson & Johnson's Spravato Sales Growth Signals Upside for Psychedelic Drug Opportunity: Jefferies," April 14, 2026. The report stated that Jefferies projected Spravato annual sales of approximately $3 billion by 2027, $3.5 billion by 2028 and potential peak annual sales of up to $5 billion. These projections are analyst estimates and are not guarantees of future performance.

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