Berliner Boersenzeitung - BioNxt Advances Sublingual Everolimus ODF for Organ Transplant Rejection with Initiation of Large-Animal Pharmacokinetic Study

Everolimus test materials have been prepared for shipment to a preclinical research facility in China for a planned pharmacokinetic ("PK") study comparing two proprietary sublingual Everolimus formulations with an orally administered 1 mg Everolimus reference product. The study represents an important transition from formulation development into comparative in-vivo study and is expected to generate data supporting formulation selection, dose optimization and subsequent development planning.

BioNxt's development objective is to improve how Everolimus is delivered. In transplantation medicine, maintaining appropriate systemic drug exposure is particularly important: insufficient exposure can contribute to inadequate immunosuppression, while excessive exposure can increase the risk of adverse effects. Conventional oral Everolimus is affected by gastrointestinal absorption, CYP3A4 metabolism, P-glycoprotein transport and food intake. By delivering Everolimus through a rapidly dissolving film placed under the tongue, BioNxt is evaluating whether oromucosal absorption can provide a more consistent and potentially more efficient delivery profile, reduce reliance on gastrointestinal absorption and food-related variability, and potentially achieve the required systemic exposure using an optimized dose. The ODF may additionally offer the convenience of a compact, swallow-free dosage form. These potential advantages have not yet been demonstrated by BioNxt and are the subject of the Company's ongoing preclinical and planned clinical development program. (Sources: Zortress® U.S. Prescribing Information; Certican® Summary of Product Characteristics; BioNxt Everolimus regulatory development assessment.)

BioNxt is initially positioning its Everolimus program toward transplantation medicine, where Everolimus is an established immunosuppressive medicine used to help prevent rejection following certain solid-organ transplants. The Company intends to evaluate additional Everolimus applications, including oncology, at later stages as part of its broader strategy to develop differentiated sublingual formulations of established pharmaceutical compounds.

A Growing Global Transplantation Market with Long-Term Treatment Needs

Solid-organ transplantation is a life-saving treatment for patients with end-stage organ failure, but successful transplantation does not end with surgery. Because the recipient's immune system can recognize the transplanted organ as foreign, patients generally require long-term, often lifelong, immunosuppressive treatment to protect the graft from rejection.

According to the Global Observatory on Donation and Transplantation, a collaboration between the World Health Organization ("WHO") and Spain's Organización Nacional de Trasplantes, 173,727 solid-organ transplants were performed worldwide in 2024, approximately 2% more than in 2023, including 110,467 kidney, 42,497 liver, 10,287 heart and 8,236 lung transplants. Despite record activity, the Observatory estimates that current transplantation volumes meet no more than approximately 10% of global need. (Source: Global Observatory on Donation and Transplantation, Global Report 2024.)

The pharmaceutical opportunity extends beyond annual procedure volumes because transplant recipients require sustained immunosuppression. Grand View Research estimates the global organ-transplant immunosuppressant drug market at approximately US$5.8 billion in 2025, with projected growth to approximately US$8.3 billion by 2033. Separately, Mordor Intelligence estimates the broader mTOR inhibitor market at approximately US$8.25 billion in 2025, with Everolimus representing approximately 35% of the market under its methodology and organ transplantation accounting for approximately 38% by indication. (Sources: Grand View Research, Organ Transplant Immunosuppressant Drugs Market, 2025; Mordor Intelligence, mTOR Inhibitors Market, 2025).

Everolimus: An Established Transplantation Medicine

Everolimus is a derivative of sirolimus, or rapamycin, and inhibits the mammalian target of rapamycin ("mTOR"), a central intracellular signaling pathway involved in cell growth, proliferation, metabolism and immune activity. By inhibiting mTOR signaling, Everolimus suppresses proliferation of activated immune cells involved in the rejection response.

In Europe, Everolimus is marketed as Certican® for the prophylaxis of organ rejection in certain adult kidney, heart and liver transplant recipients. Treatment requires careful therapeutic drug monitoring because Everolimus has a narrow therapeutic index and systemic exposure is closely linked to efficacy and safety. European product information reports lower rates of biopsy-proven acute rejection among renal, cardiac and hepatic transplant recipients achieving Everolimus trough concentrations of at least 3.0 ng/mL compared with patients below that threshold. (Source: Novartis Certican® Summary of Product Characteristics.)

Modern transplantation medicine therefore requires a careful balance: sufficient immunosuppression to protect the transplanted organ while limiting the adverse effects associated with long-term treatment. This is particularly relevant to calcineurin inhibitors ("CNIs") such as Tacrolimus and Cyclosporine. CNIs are highly effective immunosuppressants, but prolonged exposure can adversely affect renal function. In appropriately selected regimens, Everolimus provides a complementary mechanism that can enable reduced CNI exposure while maintaining effective immunosuppression.

Clinical Evidence Supports Everolimus-Based CNI Reduction

Large randomized studies support this treatment strategy. In the H2304 liver-transplant study, Everolimus combined with reduced-exposure Tacrolimus was noninferior to standard-exposure Tacrolimus for the composite endpoint of treated biopsy-proven acute rejection, graft loss or death at 12 months, at 6.7% versus 9.7%. Treated biopsy-proven acute rejection occurred in 2.9% versus 7.0%, while adjusted renal function was superior by approximately 8.5 mL/min/1.73 m² in the Everolimus plus reduced-Tacrolimus group. (Source: De Simone et al., American Journal of Transplantation, 2012; H2304 randomized liver-transplant study.)

A 2025 systematic review and meta-analysis encompassing seven randomized studies and 1,853 liver-transplant recipients similarly reported a 33% lower relative risk of treated biopsy-proven acute rejection with Everolimus plus reduced Tacrolimus compared with standard Tacrolimus, together with significantly better renal function. The analysis also identified higher rates of certain adverse events, underscoring the importance of careful dosing, monitoring and patient selection. Evidence extends to kidney transplantation: the large TRANSFORM trial involving 2,037 kidney-transplant recipients demonstrated noninferiority of Everolimus with reduced CNI exposure compared with mycophenolate and standard CNI exposure for its primary 24-month efficacy endpoint. (Sources: 2025 systematic review and meta-analysis of randomized Everolimus/Tacrolimus studies in liver transplantation; TRANSFORM randomized kidney-transplant study, 24-month results.)

Together, these findings illustrate why Everolimus has an established role in modern transplantation medicine: it can provide effective immunosuppression while enabling reduced CNI exposure in appropriately selected treatment regimens.

Why Drug Delivery Matters

Maintaining appropriate Everolimus exposure is particularly important in transplantation, which provides the scientific rationale for BioNxt's drug-delivery approach. Conventional oral Everolimus is a substrate of CYP3A4 and P-glycoprotein ("P-gp"), both of which influence its absorption and metabolism. Food can also materially affect exposure. Current Zortress® prescribing information reports that a high-fat meal reduced Everolimus Cmax by approximately 60% and AUC by approximately 16%, while delaying Tmax by approximately 1.3 hours compared with fasting administration. Conventional oral Everolimus is therefore recommended to be administered consistently either with or without food to reduce variability in exposure.

(Sources: Zortress® U.S. Prescribing Information; Certican® Summary of Product Characteristics.)

BioNxt's upcoming comparative study is designed to determine how its proprietary sublingual formulations perform against conventional oral Everolimus and whether the anticipated advantages of sublingual delivery are supported by comparative in-vivo data.

Comparative Large-Animal Pharmacokinetic Study

The planned study will use six beagle dogs in a three-period crossover design. Each animal is planned to receive two proprietary sublingual Everolimus formulations and a 1 mg oral Everolimus reference treatment during separate study periods, with seven-day washouts between dosing periods.

Blood samples will be collected before dosing and at multiple intervals through 48 hours following administration and analyzed using liquid chromatography-tandem mass spectrometry ("LC/MS-MS"). Predefined pharmacokinetic parameters include maximum concentration ("Cmax"), time to maximum concentration ("Tmax") and exposure through 48 hours ("AUC48"), with terminal half-life and total systemic exposure also calculated where supported by the data. The protocol additionally provides for local tolerability assessments following sublingual administration.

(Source: Technical Service Contract and study protocol, "A Single Dose Everolimus Sublingual ODF in Dogs," dated August 17, 2026).

The crossover design is intended to provide direct comparative information on absorption and systemic exposure while limiting inter-animal variability. The resulting data are expected to guide formulation selection, dose optimization and subsequent preclinical and clinical development planning.

Hugh Rogers, CEO of BioNxt Solutions, commented: "Organ transplantation represents a compelling opportunity for our drug-delivery platform because successful transplantation requires not only a life-saving procedure, but effective long-term pharmacological management. Everolimus is an established immunosuppressive medicine for which maintaining appropriate systemic exposure is particularly important."

"Our objective is not simply to create another dosage form," Rogers continued. "We are evaluating whether sublingual delivery can make Everolimus exposure more consistent and potentially more efficient while maintaining the systemic drug levels required in transplantation medicine. The upcoming pharmacokinetic study is designed to provide the comparative data needed to evaluate that potential and guide the next stages of development."

Potential Regulatory Pathway and Manufacturing Development

BioNxt is evaluating a potential European hybrid development pathway under Article 10(3) of Directive 2001/83/EC. European Medicines Agency guidance provides for hybrid applications where, among other circumstances, a product differs from an established reference medicine in pharmaceutical form or route of administration and therefore requires additional preclinical or clinical data beyond a conventional generic application. The ultimate regulatory pathway and evidence requirements will depend on the final formulation, pharmacokinetic and clinical results, and regulatory guidance. (Source: European Medicines Agency guidance on generic and hybrid applications; Directive 2001/83/EC, Article 10(3)).

In parallel, BioNxt is developing customized manufacturing equipment designed for integration within an isolator environment to support the handling and production of potent compounds such as Everolimus and Cladribine under appropriate product and personnel protection conditions.

Expanding BioNxt's ODF Platform

The advancement of Everolimus represents another step in BioNxt's strategy to establish a diversified pharmaceutical pipeline around its proprietary sublingual drug-delivery capabilities. BioNxt's lead program, BNT23001, is a proprietary sublingual Cladribine ODF being developed for relapsing forms of multiple sclerosis ("MS") and has progressed through formulation development, animal pharmacokinetic and local tolerability studies, manufacturing development and regulatory preparation. BioNxt recently completed the Investigational Medicinal Product Dossier ("IMPD") for BNT23001 ahead of its planned first human bioequivalence study.

The Company is now applying the formulation expertise, pharmaceutical development capabilities and regulatory infrastructure established through Cladribine to additional compounds, including Everolimus and Semaglutide.

Rogers added: "Our Cladribine program has enabled BioNxt to build significant experience around the development of complex active pharmaceutical ingredients for sublingual delivery. Everolimus allows us to apply that experience to another established pharmaceutical with a clear drug-delivery rationale and significant existing therapeutic markets. Our objective is to progressively build BioNxt from a lead-product company into a multi-asset drug-delivery platform."

Additional Everolimus Development Opportunities

While BioNxt's initial Everolimus development strategy is focused on transplantation medicine, Everolimus has established therapeutic applications across several additional high-value indications. In oncology, Everolimus is used in certain advanced hormone receptor-positive, HER2-negative breast cancers, advanced renal-cell carcinoma and neuroendocrine tumors. Everolimus is also attracting interest in precision oncology for aggressive brain cancers. The international Phase II BIOMEDE trial evaluated Everolimus in children with diffuse intrinsic pontine glioma ("DIPG"), one of the most aggressive pediatric brain tumors, and found that tumors with mutations or activation of the mTOR pathway were associated with a better response to Everolimus. Four long-term survivors treated with an mTOR inhibitor remained alive and treatment-free more than six years after diagnosis, although the study did not demonstrate a statistically significant overall-survival benefit versus its historical control cohort. It is also established in the treatment of manifestations of tuberous sclerosis complex ("TSC"), including certain renal angiomyolipomas, subependymal giant-cell astrocytomas and TSC-associated seizures. These established and emerging areas may provide opportunities for BioNxt to evaluate additional dosage strengths and indication-specific sublingual Everolimus formulations following advancement of the transplantation program (Sources: U.S. National Cancer Institute Everolimus drug information; European Medicines Agency Votubia® product information; BIOMEDE randomized Phase II trial, Nature Medicine, 2026).

Next Steps

Everolimus test materials are being prepared for transfer to the China-based preclinical research facility. Under the current technical service agreement, the testing program is contemplated to be completed within approximately two months following receipt of the initial payment and sufficient test samples.

Following receipt and analysis of the study data, BioNxt expects the results to guide formulation selection, dose optimization and subsequent regulatory and clinical development planning. Subject to successful results and regulatory guidance, the Company intends to continue advancing its sublingual Everolimus program toward human pharmacokinetic and bioavailability study while assessing additional Everolimus indications and opportunities within its broader drug-delivery platform.

About BioNxt Solutions Inc.

BioNxt Solutions Inc. is a bioscience innovator focused on next-generation drug delivery platforms, diagnostic screening systems, and active pharmaceutical ingredient development. Its proprietary platforms include sublingual thin films, transdermal patches, oral tablets, and a new targeted chemotherapy platform designed to deliver cancer drugs more selectively to tumors with the goal of reducing systemic exposure.

With research and development operations in North America and Europe, BioNxt is advancing regulatory approvals and commercialization efforts, primarily focused on European markets. BioNxt is committed to improving healthcare by delivering precise, patient-centric solutions that enhance treatment outcomes worldwide.

BioNxt is listed on the Canadian Securities Exchange: BNXT, OTC Markets: BNXTF and trades in Germany under WKN: A3D1K3. To learn more about BioNxt, please visit www.bionxt.com.

Investor Relations & Media Contact

Email: [email protected]

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Co-Founder, CFO & Director
Phone: +49 151 25284192

Hugh Rogers
Co-Founder, CEO & Director
Phone: +1 604-250-6162

Web: www.bionxt.com
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Cautionary Statement Regarding "Forward-Looking" Information

This news release contains "forward-looking information" and "forward-looking statements" within the meaning of applicable Canadian securities laws (collectively, "forward-looking statements"). Forward-looking statements are based on management's current expectations, estimates, projections, beliefs and assumptions as of the date of this news release and are subject to known and unknown risks, uncertainties and other factors that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements.

Forward-looking statements in this news release include, but are not limited to, statements regarding the completion, review and planned submission of the Investigational Medicinal Product Dossier (IMPD); the planned submission of a Clinical Trial Application (CTA); the timing, design, initiation and completion of planned human bioequivalence studies; the continued development and advancement of BNT23001 and the Company's proprietary oral dissolvable film (ODF) platform; anticipated regulatory review processes and approvals; the Company's hybrid regulatory pathway in Europe; the therapeutic, commercial and strategic potential of its product candidates and drug delivery technologies; future development activities; intellectual property protection; commercialization, licensing and strategic partnering opportunities; and the achievement of future development, regulatory and commercial milestones.

Forward-looking statements involve significant risks, uncertainties and assumptions, many of which are beyond the Company's control. These include, without limitation, risks associated with pharmaceutical research and development; formulation development; manufacturing and scale-up; analytical method development; preclinical and clinical testing; regulatory review, approvals and inspections; preparation and acceptance of regulatory submissions; intellectual property protection and enforcement; reliance on third-party manufacturers, suppliers, contract research organizations and development partners; product performance; financing requirements; market acceptance; competitive technologies; and general economic, financial and capital market conditions.

There can be no assurance that the Company's planned regulatory submissions, clinical studies or development activities will proceed as currently anticipated or at all, that regulatory authorities will accept the Company's submissions or grant required approvals, that intellectual property protection will be obtained or maintained as expected, or that any product candidate will successfully complete clinical development or achieve commercialization. Readers are cautioned not to place undue reliance on these forward-looking statements.

Except as required by applicable securities laws, BioNxt Solutions Inc. undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Zortress^®, Certican^®, and Votubia^® are registered trademarks that are not owned by, affiliated with, sponsored by, or associated with BioNxt Solutions Inc.

SOURCE: BioNxt Solutions Inc.

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(Y.Yildiz--BBZ)