What changed in this filing

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Item 1. Business

2024-03-28 compared with 2023-03-31 · 89 added, 81 removed, 179 unchanged (49% of the section changed)

ITEM 1—BUSINESS

Tenax Therapeutics was originally formed as a New Jersey corporation in 1967 under the name Rudmer, David & Associates, Inc., and subsequently changed its name to Synthetic Blood International, Inc.

The Company was originally formed as a New Jersey corporation in 1967 under the name Rudmer, David & Associates, Inc., and subsequently changed its name to Synthetic Blood International, Inc.

Effective June 30, 2008, we changed the domiciliary state of the corporation to Delaware and changed the Company name to Oxygen Biotherapeutics, Inc.

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On November 13, 2013, we acquired a license granting Life Newco, our wholly-owned subsidiary, an exclusive, sublicensable right to develop and commercialize pharmaceutical products containing levosimendan, 2.5 mg/ml concentrate for solution for infusion / 5ml vial in the United States and Canada.

On October 9, 2020 and January 25, 2022, we entered into an amendment to the license to include two new oral products containing levosimendan, in capsule and solid dosage form, and a subcutaneously administered product containing levosimendan, subject to specified limitations.

On January 15, 2021, we acquired 100% of the equity of PHPrecisionMed Inc., a Delaware corporation, or PHPM, with PHPM surviving as our wholly-owned subsidiary.

As a result of the merger, we are developing and plan to commercialize pharmaceutical products containing imatinib for the treatment of pulmonary arterial hypertension, or PAH.

In October 2020 and January 2022, we entered into an amendment to the license agreement between the Company and Orion to include in the scope of the license two new oral product formulations containing levosimendan, in capsule and solid dosage form (TNX-103), and a subcutaneously administered dosage form (TNX-102), subject to specified limitations.

In February 2024, we entered into an additional amendment to the license, providing global rights to oral and subcutaneous formulations of levosimendan used in the treatment of PH-HFpEF, revising the royalty structure, lowering the royalty rates, modifying milestones associated with certain regulatory and commercial achievements, and excluding from our right of first negotiation the right to commercialize new applications of levosimendan for neurological diseases and disorders developed by Orion.

On January 15, 2021, we acquired 100% of the equity of PHPrecisionMed Inc., a Delaware corporation(“PHPM”), with PHPM surviving as our wholly-owned subsidiary.

As a result of the merger, pending the outcome of our strategic process, we plan to commercialize pharmaceutical products containing imatinib for the treatment of pulmonary arterial hypertension (“PAH”).

Business Strategy

Having carefully considered alternatives within the ongoing strategic process announced in September 2022, and having raised capital to fund the Company through to the first quarter of 2024, the Company has recently elected to prioritize the Phase 3 testing of levosimendan, ahead of imatinib, with plans to commence a levosimendan Phase 3 study in 2023.

Supporting this strategic decision is a U.S.

Patent issued in March 2023, covering the use of IV levosimendan in patients with PH-HFpEF.

This patent is the second levosimendan patent granted to Tenax since the start of 2022, and Tenax believes it provides strong precedent for the ongoing review of a third patent which might be granted in 2023 or 2024.

This prioritization of the Phase 3 testing of levosimendan places the start of a Phase 3 imatinib trial likely outside the 2023 timeframe, pending fundraising to support that trial, as well as other strategic considerations.

The Company took steps to reduce its monthly operating expenses and conserve cash, as it commenced exploring strategic alternatives.

The Company has cancelled substantially all of its non-essential operating expenses such as consulting, its office lease, and dues and subscriptions and office supplies associated with that leased office.

Prior to announcing the strategic process, our principal business objective has been to identify, develop, and commercialize late-stage pharmaceutical therapeutic products for serious cardiovascular and pulmonary diseases with high unmet medical need.

The Company has been developing TNX-103 (oral levosimendan) for the treatment of Pulmonary Hypertension with Heart Failure with Preserved Ejection Fraction (PH-HFpEF) and TNX-201 (modified release imatinib) for the treatment of pulmonary arterial hypertension (PAH).

Both TNX-103 and TNX-201 are Phase 3-ready assets, each with the potential to meaningfully impact the quality and longevity of patient lives.

Pending the outcome of our strategic process, the key elements of our long-term business strategy are outlined below.

Having carefully considered alternatives within the ongoing strategic process announced in September 2022, and having raised capital expected to fund the Company through 2024, the Company has elected to prioritize its LEVEL trial (Phase 3 testing of oral levosimendan), ahead of imatinib.

Activity to initiate the LEVEL trial continued in the fourth quarter of 2023, and site qualification, selection, and initiation processes are ongoing, the Company having received U.S.

Food and Drug Administration (“FDA”) input into the oral levosimendan protocol and clinical development program in the third quarter of 2023.

The Company began initiating sites in the fourth quarter of 2023 and commenced enrolling patients early in 2024.

Additional funding will be needed to complete the LEVEL trial, which includes an open label extension phase following the completion of the randomized phase.

The Company will complete efficacy and safety analyses of levosimendan versus placebo at the end of the randomized treatment phase, but many patients will continue to be treated under the protocol on open label levosimendan, beyond the completion of these analyses.

Supporting this strategic decision to prioritize levosimendan development and commence Phase 3 trial work were two U.S.

Patents issued in March and July 2023, covering the use of IV and oral levosimendan in patients with PH-HFpEF.

These patents are the second and third levosimendan patents granted to us since the start of 2022.

An additional new patent to be issued in early 2024 provides protections covering all therapeutic doses of all three formulations of the product in patients with PH-HFpEF.

Given our prioritization of the Phase 3 testing of levosimendan, we have suspended plans to launch an imatinib Phase 3 trial.

The Company took steps to reduce its monthly operating expenses and conserve cash, as it commenced exploring strategic alternatives in late 2022.

The Company at that time cancelled many non-essential operating expenses such as consulting, its office lease, and dues and subscriptions and office supplies associated with that leased office.

During the third quarter of 2023, the Company and its contracted CRO increased outreach to North American clinical trial sites, Institutional Review Boards, and other partners who will support the LEVEL trial, and in the fourth quarter of 2023 commenced site initiations.

Pending the outcome of our ongoing strategic process, the key elements of our business strategy are outlined below.

Efficiently conduct clinical development to establish clinical proof of principle in new indications, refine formulation, and commence Phase 3 testing of our current product candidates .

Levosimendan and imatinib have been approved and prescribed around the world for more than 20 years, but we believe their mechanisms of action have not been fully exploited, despite promising evidence they may significantly improve the lives of patients with pulmonary hypertension.

We are conducting clinical development with the intent to establish proof of beneficial activity in cardiopulmonary diseases in which these therapeutics would be expected to have benefit for patients with diseases for which either no pharmaceutical therapies are approved at all, or in the case of PAH, where numerous expensive therapies generally offer a modest reduction of symptoms.

Levosimendan and imatinib have been approved and prescribed in countries around the world for more than 20 years, but we believe their mechanisms of action have not been fully exploited, despite promising evidence they may significantly improve the lives of patients with pulmonary hypertension.

We are conducting clinical development with the intent to establish proof of beneficial activity in cardiopulmonary diseases in which these therapeutics would be expected to have benefit for patients with diseases for which either no pharmaceutical therapies are approved at all, or in the case of pulmonary arterial hypertension (“PAH”), where numerous, expensive therapies generally offer a modest reduction of symptoms.

Our focus is primarily on designing and executing formulation improvements, protecting these innovations with patents and other forms of exclusivity, and employing innovative clinical trial science to establish a robust foundation for subsequent development, product approval, and commercialization.

We intend to submit marketing authorization applications following either one or two Phase 3 trials of levosimendan and, when appropriate, a single Phase 3 trial of imatinib.

We intend to submit marketing authorization applications following two Phase 3 trials of levosimendan and, when appropriate, a single Phase 3 trial of imatinib.

Our trials are designed to incorporate and reflect advanced clinical trial design science and the regulatory and advisory experience of our team.

We intend to continue partnering with innovative companies, renowned biostatisticians and trialists, medical leaders, formulation and regulatory experts, and premier clinical testing organizations to help expedite development, and continue expanding into complementary areas when opportunities arise through our development, research, and discoveries.

We also intend to continue outsourcing when designing and executing our research.

We also intend to continue outsourcing to CROs, and seeking and acting upon the advice of preeminent scientists focused on cardiovascular and pulmonary drug development, when designing and executing our research.

Efficiently explore new high-potential therapeutic applications, in particular where expedited regulatory pathways are available, leveraging third-party research collaborations and our results from related areas.

Levosimendan has shown promise in multiple disease areas in the two decades following its approval.

Our own Phase 2 study and open-label extension has demonstrated that a formerly under-appreciated mechanism of action of levosimendan, its property of relaxing the venous circulation, brings about durable improvements in exercise capacity and quality of life, as well as other clinical assessments, in patients with heart failure with preserved ejection fraction and associated pulmonary hypertension (PH-HFpEF).

Levosimendan has shown promise in multiple disease areas in the more than two decades following its approval.

Our own Phase 2 study and open-label extension has demonstrated that its property of relaxing the venous circulation, a formerly under-appreciated mechanism of action of levosimendan, , brings durable improvements in exercise capacity and quality of life, as well as other clinical assessments, in patients with PH-HFpEF.

We believe this patient population today has no pharmaceutical therapies available and we are committed to exploring potential clinical indications where our therapies may achieve best-in-class profile, and where we can address significant unmet medical needs.

We believe these factors will support approval by the United States Food and Drug Administration (the “FDA”) of these product candidates based on positive Phase 3 data.

Through our agreement with our licensor, Orion Corporation (“Orion”), the originator of levosimendan for acute decompensated heart failure, we have access to a library of ongoing and completed trials and research projects, including certain documentation, which we believe, in combination with positive Phase 3 data we hope to generate in at least one indication, will support FDA approval of levosimendan.

Likewise, the regulatory pathway for approval of imatinib for the treatment of PAH, as formulated by Tenax Therapeutics at the dose shown to be effective in a prior Phase 3 trial conducted by Novartis, allows Tenax to build on the dossier of research results already reviewed by the FDA.

In order to achieve our objectives of developing these medicines for new groups of patients, we have established collaborative research relationships with investigators from leading research and clinical institutions, and our strategic partners.

We believe these factors will support approval by the FDA of these product candidates based on positive Phase 3 data.

Through our agreement with our licensor, Orion, the originator of levosimendan for acute decompensated heart failure, we have access to a library of ongoing and completed trials and research projects, including certain documentation, which we believe, in combination with positive Phase 3 data we hope to generate in at least one indication, will support FDA approval of levosimendan.

Likewise, the regulatory pathway for approval of imatinib for the treatment of PAH, as formulated by us at the dose shown to be effective in a prior Phase 3 trial conducted by Novartis, allows us to build on the dossier of research results already reviewed by the FDA.

In order to achieve our objective of developing these medicines for new groups of patients, we have established collaborative research relationships with investigators from leading research and clinical institutions, and our strategic partners.

These collaborative relationships have enabled us to explore where our product candidates may have therapeutic relevance, gain the advice and support of key opinion leaders in medicine and clinical trial science, and invest in development efforts to exploit opportunities to advance beyond current clinical care.

Additionally, we believe we will be able to leverage clinical safety data and preclinical results from some programs to support accelerated clinical development efforts in other areas, saving substantial development time and resources compared to traditional drug development.

Continue to expand our intellectual property portfolio .

Our intellectual property and the confidentiality of all our Company information is important to our business and we take significant steps to help protect its value.

Our research and development efforts, both through internal activities and through collaborative research activities with others, aim to develop new intellectual property and enable us to file patent applications that cover new applications of our existing technologies, alone or in combination with existing therapies, as well as other product candidates.

We received in 2022 a patent covering the subcutaneous administration of levosimendan (TNX-102) in humans for any medical condition, through 2039.

On March 21, 2023, we received our second patent for this product, covering the IV formulation of levosimendan (TENX-101) tested in the Phase II HELP trial in patients with PH-HFpEF.

At present, we have two patents pending, with additional decisions expected in 2023.

Our research and development efforts, both through internal activities and through collaborative research activities with others, aim to develop new intellectual property and enable us to file patent applications that cover new uses of our existing technologies, alone or in combination with existing therapies, as well as other product candidates.

Notice of Allowance and Patents.

On February 1, 2023, the Company announced it was granted a Notice of Allowance from the United States Patent and Trademark Office (“USPTO”) for its patent application with claims covering the use of IV levosimendan (TNX-101) in the treatment of PH-HFpEF.

This patent (U.S.

11,607,412) was issued on March 21, 2023.

On July 19, 2023, the Company announced USPTO issuance of another patent, this one including claims covering the use of oral levosimendan (TNX-103) in patients with PH-HFpEF.

This issued patent (U.S.

11,701,355) provides exclusivity through December 2040.

On February 6, 2024, the Company announced it was granted a Notice of Allowance from USPTO for its patent application broadening IP protection for oral, I.V., and subcutaneous use of levosimendan and its active metabolites in PH-HFpEF, at all therapeutic doses and in combination with various cardiovascular drugs.

At present, the Company has other patent applications pending, with additional decisions expected in the future.

Patents pending in Europe may lead to intellectual property protections on the use of levosimendan in patients with PH-HFpEF in 2024.

Enter into licensing or product co-development arrangements .

In addition to our internal development efforts, an important part of our product development strategy is to work with collaborators and partners to accelerate product development, maintain our low development and business operations costs, and broaden our commercialization capabilities globally.

We believe this strategy will help us to develop a portfolio of high-quality product development opportunities, enhance our clinical development and commercialization capabilities, and increase our ability to generate value from our proprietary technologies.

We believe this strategy will help us develop a portfolio of high-quality product development opportunities, enhance our clinical development and commercialization capabilities, and increase our ability to generate value from our proprietary technologies.

As we focus on our strategic process, we also continue to position ourselves to execute upon licensing and other partnering opportunities.

To do so, we need to continue to maintain our strategic direction, manage and deploy our available cash efficiently, and strengthen our collaborative research development and partner relationships.

Historically, we have financed our operations principally through equity and debt offerings, including private placements and loans from our stockholders.

Based on our current operating plan, there is substantial doubt about our ability to continue as a going concern.

Management has implemented certain cost-cutting measures as described above and is actively exploring a diverse range of strategic options to help drive stockholder value including, among other things, capital raises, a sale of our Company, merger, one or more license agreements, a co-development agreement, a combination of these, or other strategic transactions; however, there is no assurance that these efforts will result in a transaction or other alternative or that any additional funding will be available.

Our ability to continue as a going concern depends on our ability to raise additional capital, through the sale of equity or debt securities and through collaboration and licensing agreements, to support our future operations.

If we are unable to complete a strategic transaction or secure additional capital, we may be required to curtail our research and development initiatives and take additional measures to reduce costs.

Our Current Programs

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Levosimendan was discovered and developed by Orion.

Levosimendan is a calcium sensitizer/K-ATP activator developed for intravenous use in hospitalized patients with acutely decompensated heart failure.

It is currently approved in over 60 countries for this indication but is not available in the United States or Canada.

Levosimendan, as marketed around the world today, is a calcium sensitizer/K-ATP activator developed for intravenous use in hospitalized patients with acutely decompensated heart failure.

It is currently approved in 58 countries for this indication but is not available in the United States or Canada.

It is estimated that to date over 1.9 million patients have been treated worldwide with levosimendan.

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Opening of potassium channels in the vasculature smooth muscle, resulting in a vasodilatory effect on all vascular beds.

Increased cardiac contractility by calcium sensitization of troponin C, resulting in a positive inotropic effect which is not associated with substantial increases in oxygen demand.

Increasing cardiac contractility by calcium sensitization of troponin C, resulting in a positive inotropic effect which is not associated with substantial increases in oxygen demand.

Opening of mitochondrial potassium channels in cardiomyocytes, resulting in a cardioprotective effect.

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In 2013, we acquired certain assets of Phyxius Pharma, Inc.

(“Phyxius”), including its North American rights to develop and commercialize intravenous levosimendan for any indication in the United States and Canada.

The license was subsequently amended in 2020 to include the rights to develop and commercialize oral and subcutaneous formulations of levosimendan.

(“Phyxius”), including its North American rights to a license agreement with Orion to develop and commercialize intravenous levosimendan for any indication in the United States and Canada.

On October 9, 2020 and January 25, 2022, we entered into an amendment to the license agreement to include in the scope of the license two new oral product formulations containing levosimendan, in capsule and solid dosage form (TNX-103), and a subcutaneously administered dosage form (TNX-102), subject to specified limitations.

In the countries where it is marketed, intravenous levosimendan is indicated for the short-term treatment of acutely decompensated heart failure in situations where conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate.

In acute decompensated heart failure patients, levosimendan has been shown to significantly improve patients’ symptoms as well as acute hemodynamic measurements such as increased cardiac output, reduced preload and reduced afterload.

In acute decompensated heart failure patients, levosimendan has been shown to significantly improve patient symptoms as well as acute hemodynamic measurements such as increased cardiac output, reduced preload and reduced afterload.

TNX-101 (IV), TNX-102 (subcutaneous) and TNX-103 (oral) (levosimendan) Development for Pulmonary Hypertension Patients

In 2020, we completed a Phase 2 clinical trial of intravenous levosimendan in North America for the treatment of patients with pulmonary hypertension associated with heart failure with PH-HFpEF, a disease defined hemodynamically by a mean pulmonary artery pressure (“mPAP”) of ≥25 mmHg, and a pulmonary capillary wedge pressure “(PCWP”) of >15 mmHg.

In 2020, we completed a Phase 2 clinical trial of intravenous levosimendan in North America for the treatment of patients with PH-HFpEF, a disease defined hemodynamically by a mean pulmonary artery pressure (“mPAP”) of ≥25 mmHg, and a pulmonary capillary wedge pressure (“PCWP”) of >15 mmHg.

Pulmonary hypertension in these patients is believed to arise from a passive backward transmission of elevated filling pressures from left-sided heart failure.

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Over time, these changes often lead to advanced pulmonary arterial and venous disease, increased right ventricle afterload, and right ventricle failure.

PH-HFpEF is the most common of five forms of pulmonary hypertension, with an estimated U.S.

Per the World Health Organization, PH-HFpEF is the most common of five forms of pulmonary hypertension, with an estimated U.S.

prevalence exceeding 1.5 million patients.

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Several published studies provide evidence that levosimendan may improve right ventricular dysfunction which is a common comorbidity in patients with pulmonary hypertension.

While none of these studies have focused specifically on PH-HFpEF patients, the general hemodynamic improvements in these published studies of various types of pulmonary hypertension provide a basis for further research into the potential beneficial impact of levosimendan in PH-HFpEF patients.

While none of these studies has focused specifically on PH-HFpEF patients, the general hemodynamic improvements in these published studies of various types of pulmonary hypertension provide a basis for further research into the potential beneficial impact of levosimendan in PH-HFpEF patients.

In March 2018, we met with the FDA to discuss development of levosimendan in these patients.

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We initiated the first of our HELP Study clinical sites in November 2018 and the first of 37 patients was enrolled in the HELP Study in March 2019.

Enrollment in the HELP Study was completed about one year later, in March 2020.

Enrollment in the HELP Study was completed in March 2020.

The primary endpoint of the HELP Study was based on the change in pulmonary capillary wedge pressure (“PCWP”) during exercise versus baseline compared to placebo.

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In the randomized double-blinded 6-week trial, levosimendan demonstrated a statistically significant reduction in PCWP compared to baseline (p=<0.0017) and placebo (p=<0.0475) when these three measurements were combined:

at rest, with legs up, and on exercise.

at rest, with legs up, and during exercise.

While there was no significant change in PCWP during exercise, patients receiving levosimendan had reductions from baseline at Week 6 in PCWP and PAP that were statistically significant when patients were “at rest” and/or with their “legs raised” (p<0.05).

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Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF:

Results of the Randomized Placebo-Controlled HELP Trial.

Results of the Randomized Placebo-Controlled HELP Study.

JACC Heart Fail.

2021 May;9(5):360-370.

On October 9, 2020, we entered into an Amendment to the License Agreement between the Company and Orion to include two new product formulations containing levosimendan, in a capsule solid oral dosage form (TNX-103) and a subcutaneously administered dosage form (TNX-102), to the scope of the license, subject to specified limitations.

On January 4, 2022, Tenax Therapeutics was issued US Pat.

On October 9, 2020 and January 25, 2022, we entered into amendments to the license agreement between the Company and Orion to include in the scope of the license two new oral product formulations containing levosimendan, in capsule and solid dosage form (TNX-103), and a subcutaneously administered dosage form (TNX-102), subject to specified limitations.

On January 4, 2022, we were issued US Pat.

11,213,524, entitled PHARMACEUTICAL COMPOSITIONS FOR SUBCUTANEOUS ADMINISTRATION OF LEVOSIMENDAN.

Following their completion of the randomized treatment phase of the HELP trial, patients were able to enter a study extension.

For over two years, Tenax and our HELP investigators continued studying the safety and efficacy of TNX-103 in all patients participating in the open-label extension of the HELP Study, all of whom previously received weekly infusions of intravenous levosimendan.

The 2022 and 2024 amendments to the license, which adjusted the timeframe for Phase 3 development and regulatory efforts and broaden the North American rights to be worldwide, as well as the additional patents issued by USPTO, furthered the Company’s justification for continuing and prioritizing the development of levosimendan.

Following patient completion of the randomized treatment phase of the HELP Study, patients were able to enter a study extension.

For over two years, the Company and our HELP investigators continued studying the safety and efficacy of TNX-103 in all patients participating in the open-label extension of the HELP Study, all of whom previously received weekly infusions of intravenous levosimendan.

These patients were safely transitioned from the intravenous to the oral formulation in late 2021, with positive signs of efficacy observed across all measured parameters during the transition study phase of the open-label extension study (“OLE”).

We expect the OLE to come to a conclusion in the first half of 2023.

The OLE concluded in the first half of 2023.

In October 2020, we met with the FDA for an End-of-Phase 2 Meeting to discuss the Phase 2 clinical data and further development of levosimendan in PH-HFpEF patients.

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The FDA also agreed to a plan to replace weekly intravenous levosimendan dosing with daily TNX-103 doses in a Phase 3 clinical study.

The FDA expressed that a safety database could be necessary and indicated that the need for a larger safety database could be dependent on the final design of the Phase 3 study.

The FDA expressed that a safety database could be necessary and indicated that the need for a larger safety database could depend on the final design of the Phase 3 study.

A proposed Phase 3 study design was provided in late 2021 for FDA review and comment on the safety database requirements at filing.

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We believe that the combination of the unique HELP Study patient population, innovative weekly 24-hour dosing, unique home-based site of administration, the transition from intravenous to oral therapy in a subset of these patients who continued in the OLE until the commencement of this transition sub study, and the novel findings of efficacy and safety in PH-HFpEF patients represent important discoveries and significant intellectual property.

These discoveries, among others from the HELP Study, form the basis for U.S.

patent applications we have filed.

We received two U.S.

Patents issued in March and July 2023, covering the use of IV and oral levosimendan in patients with PH-HFpEF.

On November 13, 2023, the Company announced that the FDA had reviewed and cleared the Company’s Investigational New Drug (IND) Application for TNX-103 (oral levosimendan) for the treatment of pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF), enabling Tenax to proceed with the first of two Phase 3 studies.

The LEVEL Study ( LEV osimendan to Improve E xercise L imitation in PH-HFpEF Patients) launched with site initiations in the fourth quarter of 2023.

TNX-201 (imatinib) Background

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Encouraged by the success of imatinib in treating CML patients, scientists explored its effect in other cancers, and it was found to produce a similar positive effect in malignancies where tyrosine kinases were overexpressed.

Tyrosine kinases are important mediators of the signaling cascade, determining key roles in diverse biological processes like growth, differentiation, metabolism, and apoptosis in response to external and internal stimuli.

Deregulation of protein kinase activity has been shown to play a central role in the pathogenesis of human cancers.

Imatinib, a 2-phenyl amino pyrimidine derivative, is a tyrosine kinase inhibitor with activity against ABL, BCR-ABL, PDGFRA and PDGFRB, and c-KIT.

Imatinib works by binding close to the ATP binding site, therefore inhibiting the enzyme activity of the protein.

Imatinib also inhibits the ABL protein of noncancer cells.

Imatinib is well absorbed after oral administration with a bioavailability exceeding 90%.

It is extensively metabolized, principally by cytochrome P450 (CYP)3A4 and CYP3A5 and can competitively inhibit the metabolism of drugs that are CYP3A4 or CYP3A5 substrates.

Imatinib is generally well tolerated in cancer patients.

Common side effects include fluid retention, headache, diarrhea, loss of appetite, weakness, nausea and vomiting, abdominal distention, edema, rash, dizziness, and muscle cramps.

Serious side effects may include myelosuppression, heart failure, and liver function abnormalities.

Novartis manufactures Gleevec.

Previous Imatinib Development for Pulmonary Arterial Hypertension Patients

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Novartis sponsored a Phase 2 proof-of-concept trial to evaluate the safety, tolerability, and efficacy of imatinib as an adjunct to PAH-specific therapy in patients with PAH.

This was a 24-week randomized, double-blind, placebo-controlled study of PAH subjects who remained symptomatic on one or more PAH therapies in WHO Functional Class (FC) II-IV.

The Phase 2 trial of imatinib in PAH caused significant hemodynamic improvement in some patients but failed to meet the primary endpoint of an increase in 6-minute walk distance (22 meters, p=NS).

Novartis then sponsored a Phase 3 trial (IMPRES) which met its primary endpoint of significant increase in 6-minute walk (32 meters, p=0.002), an effect maintained in the extension study in patients remaining on imatinib.

However, the data were confounded by a high rate of dropouts in the patients randomized to imatinib attributed largely to gastric intolerance during the first eight weeks.

The sponsor proposed consideration of a surrogate endpoint under the subpart H provision as a basis for approval but was denied.

Consequently, Novartis chose to withdraw the Investigational New Drug application as the drug went off patent.

Current TNX-201 Development for Pulmonary Arterial Hypertension Patients

On May 30, 2019, PHPrecisionMed Inc., a Delaware corporation (“PHPM”), which was to be acquired by Tenax Therapeutics in January 2021, met with the FDA to discuss a proposal for a Phase 3 trial of imatinib for PAH.

On May 30, 2019, PHPrecisionMed Inc., a Delaware corporation (“PHPM”), which we acquired in January 2021, met with the FDA to discuss a proposal for a Phase 3 trial of imatinib for PAH.

At that meeting, PHPM discussed a single Phase 3 trial using change in 6-minute walk distance as the primary endpoint (p<0.05).

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In July 2020, PHPM received agreement from the FDA for the development of a modified release formulation that would require only a small comparative PK/bioavailability study.

We recruited 16 volunteers, who received a single dose of the modified release formulation and a single dose of the existing immediate release formulation.

This formulation was later optimized in preparation for a second Phase 1 study, completed in the second quarter of 2022.

A Phase 3 study of TNX-201, this optimized modified release formulation of imatinib, would be the next clinical trial to commence in Tenax’ development planning, pending the outcome of our strategic process and funding of the trial costs.

A Phase 3 study of TNX-201, this optimized modified release formulation of imatinib, would be the next clinical trial to commence in our development planning, pending the outcome of our strategic process and funding of the trial costs.

Manufacturing and Supply

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We do not own or operate any manufacturing facilities and we have no plans to build any owned clinical or commercial scale manufacturing capabilities.

We believe that the use of third-party manufacturers and contract manufacturing organizations (“CMOs”) eliminates the need to directly invest in manufacturing facilities, equipment and additional staff.

We believe that the use of third-party manufacturers and contract drug manufacturing organizations (“CMOs”) eliminates the need to directly invest in manufacturing facilities, equipment and additional staff.

Pursuant to the terms of our license for levosimendan, Orion is contractually our sole manufacturing source for TNX-103.

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We also require employees, consultants, and advisors whom we expect to work on our products to agree to disclose and assign to us all inventions conceived during the workday, developed using our property, or which relate to our business.

We have two granted patents, and two U.S.

patent applications pending, related to product candidates and proprietary process, method and technology.

As of the date of this filing, the Company has been granted three patents and has one U.S.

patent application pending, for which the Company has received a Notice of Allowance, all related to product candidates and proprietary process, method and technology.

Our issued levosimendan patents expire in 2039 and late 2040.

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Simdax License Agreement

On November 13, 2013, we acquired, through our wholly-owned subsidiary, a license agreement between Phyxius and Orion, which was later amended on October 9, 2020 and January 25, 2022 (as amended, the “License”).

The License grants us an exclusive, sublicenseable right to develop and commercialize pharmaceutical products containing levosimendan in the United States and Canada (the “Territory”) and, pursuant to the October 9, 2020 amendment to the License, also includes two product dose forms containing levosimendan, in capsule and solid dosage form, and a subcutaneously administered product containing levosimendan, subject to specified limitations (together, the “Product”).

On November 13, 2013, we acquired, through our wholly-owned subsidiary, a license agreement between Phyxius and Orion, which was later amended on October 9, 2020, January 25, 2022, and February 19, 2024 (as amended, the “License”).

The License grants us an exclusive, sublicenseable right to develop and commercialize pharmaceutical products containing levosimendan worldwide (the “Territory”) and, pursuant to the October 9, 2020 amendment to the License, also includes two product dose forms containing levosimendan, in capsule and solid dosage form, and a subcutaneously administered product containing levosimendan, subject to specified limitations (together, the “Product”).

Pursuant to the License, Tenax and Orion will agree to a new trademark when commercializing levosimendan in either of these forms.

Pursuant to the License, we have a right of first refusal to commercialize new developments of levosimendan, including developments as to the formulation, presentation, means of delivery, route of administration, dosage or indication (i.e., line extension products).

Pursuant to the License, we have a right of first negotiation to commercialize new developments of levosimendan, including developments as to the formulation, presentation, means of delivery, route of administration, dosage or indication (i.e., line extension products).

Neurological diseases and disorders are excluded from this right of first negotiation.

Orion’s ongoing role under the License includes sublicense approval, serving as the sole source of manufacture of oral formulations of levosimendan, holding a first right to enforce intellectual property rights in the United States and Canada, and certain regulatory participation rights.

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In the event that no regulatory approval for levosimendan has been granted in the United States on or before September 20, 2030, however, either party will have the right to terminate the License with immediate effect.

As consideration for the License, we agreed to pay Orion (i) a one-time up-front payment in the amount of $1.0 million, (ii) development milestones consisting of (a) $2.0 million upon the grant of FDA approval and (b) $1.0 million upon the grant of regulatory approval for the Product in Canada, (iii) commercialization milestones aggregating to up to $13.0 million, upon achievement of certain cumulative net sales amounts in the United States and Canada, and (iv) royalties based on net sales of the Product in the United States and Canada.

As consideration for the License, we agreed to pay Orion (i) a one-time up-front payment in the amount of $1.0 million, (ii) development milestones consisting of (a) $10.0 million upon the grant of FDA approval and (b) $1.0 million upon the grant of regulatory approval for the Product in Canada, (c) $5.0 million due upon the grant of regulatory approval for a levosimendan-based product in Japan, (iii) commercialization milestones aggregating to up to $45.0 million, upon achievement of certain cumulative net sales amounts in the United States and Canada, and (iv) royalties based on net sales of the Product in the Territory.

After the end of the License term, the Company must pay Orion a royalty based on net sales of the Product in the Territory for as long as the Company sells the Product in the Territory.

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Novartis developed imatinib for PAH and conducted a Phase 3 trial that in 2013 succeeded in meeting its primary endpoint.

However, the high number of dropouts of patients randomized to imatinib led the FDA and EMA to request another trial before they would approve the product in PAH.

To address this, we are developing a modified-release oral formulation designed to reduce the stomach’s exposure to imatinib, and the nausea and vomiting commonly observed in patients receiving imatinib.

However, the high number of dropouts of patients randomized to imatinib led the FDA and the European Medicines Agency (“EMA”) to request another trial before they would approve the product in PAH.

To address this, we are developing a modified-release oral formulation designed to reduce the stomach’s exposure to imatinib, thereby lessening the nausea and vomiting commonly observed in patients receiving imatinib.

Other companies are developing an inhaled route of administration as their strategy to mitigate gastric intolerance.

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After FDA approval for its initial indications, further clinical trials may be necessary to gain approval for the use of a product for additional indications.

The FDA may also require post-marketing testing, which can involve significant expense, to monitor for adverse effects.

The FDA may also require post-marketing testing to monitor for adverse effects, which can involve significant expense.

The effects of government regulations on our business are discussed under the heading “Risk Factors - Risks Relating to Regulatory Matters” included elsewhere in this Annual Report on Form 10-K.

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We have assembled a high-quality team of clinical development managers and executives with significant experience in the biotechnology and pharmaceutical industries.

As of December 31, 2022, we had seven full-time employees and one part-time employee.

As of December 31, 2023, we had five full-time employees and one part-time employee.

In addition to our employees, we also rely on the service and support of outside consultants and advisors.

None of our employees are represented by a union, and we believe relationships with our employees are good.

None of our employees is represented by a union, and we believe relationships with our employees are good.

Available Information

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business