TENX: Notice of Allowance Increases Confidence
NASDAQ:TENX
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Additional Support for Oral Levosimendan
Tenax Therapeutics, Inc. (NASDAQ:TENX) announced that the US Patent and Trademark Office (USPTO) has granted a Notice of Allowance for its patent covering the use of oral levosimendan in pulmonary hypertension in patients with heart failure and preserved ejection fraction (PH-HFpEF). The Notice of Allowance is a precursor to patent issuance and declares that the invention meets the requirements for patentability. A fee is required prior to grant of the patent, which is the next anticipated step for Tenax prior to the grant of the patent.
A patent for oral levosimendan in PH-HFpEF is significant as it extends protection for this use until the end of 2040. Patent extension and potentially other mechanisms could extend this even further. A patent grant would lengthen what would otherwise be available, which is five years of exclusivity as a New Chemical Entity (NCE). NCE exclusivity is available to drugs that contain an active moiety that has not been previously approved by the FDA in any other drug.
Based on the confidence inspired by the recent USPTO successes with levosimendan in PH-HFpEF, Tenax plans to pursue a Phase III study of oral levosimendan in these patients. The US Patent Office set a precedent by recognizing PH-HFpEF as a condition separate from heart failure. This provides support for later approval of a patent for an oral version of levosimendan in a follow-on patent application that is being reviewed by the agency. With the recent $15.6 million raise, Tenax is in a position to start its Phase III levosimendan trial.
Imatinib Program
With its near-term development focus on PH-HFpEF, Tenax will soon begin its oral levosimendan trial. The company’s second program with imatinib for pulmonary arterial hypertension (PAH) will take a back seat due to financial considerations. While not active, there are events in motion that may orient investor interest towards Tenax’s imatinib program. This could complement any good news that emerges from the levosimendan trial next year. Tenax is not the only company pursuing a disease modifying therapy for PAH, as others including Aerovate Therapeutics (AVTE), Gossamer Bio (GOSS) and Acceleron/Merck (MRK) are all traveling along this route. We provide a review of the other programs and also identify some of the hurdles that Aerovate faces with using an inhaled form of imatinib. If Aerovate is not able to achieve favorable results with its inhaled imatinib, the focus may turn to Tenax which offers a modified formulation that sidesteps the gastrointestinal (GI) side effects that plagued the oral form of imatinib used in the IMPRES study.
Inhaled Imatinib
Imatinib is the subject of a trial by Aerovate Therapeutics that is investigating a dry powder formulation of imatinib for PAH. The sponsor is running a Phase III clinical trial designated IMPAHCT and a long term extension of this trial called IMPAHCT-FUL. The primary endpoint for the Phase III will be the placebo-corrected change in the six-minute walk distance after 24 weeks of treatment. There will be ~460 participants in the randomized trial. As of mid-May, Aerovate expects to report topline data in 2Q:24.
Imatinib is a tyrosine kinase inhibitor (TKI) and was shown to improve a PAH subject’s six-minute walk test in the IMPRES study. Another TKI, seralutinib, was effective in animal models using an inhaled route of administration but had limited effect in humans. Due to its mechanism, the inhaled route of administration may have limitations in humans that are not fully represented in the animal model.
While the inhalation route is attractive on many fronts, including avoiding GI related side effects and direct delivery to the organ of interest, clinical efficacy using this route may not be feasible. Precise dosing and delivery to the alveolar-capillary region is difficult. Furthermore, drug delivered via the peripheral airways has a shorter effect than drug delivered via other routes as it is absorbed quickly.2
Seralutinib
Gossamer conducted a Phase 2 study of seralutinib in patients with pulmonary arterial hypertension (PAH). Seralutinib is a tyrosine kinase inhibitor (TKI) that targets PDGFRα/β, CSF1R, and c-KIT. It is specifically designed to be delivered via dry powder inhaler for the treatment of PAH. The company reported topline data in December 2022. While the primary endpoint of pulmonary vascular resistance (PVR) improved by 14.3% (p value = 0.031), the magnitude was lower than expected. The secondary endpoint was improvement in six-minute walk distance. Active arm results were better than placebo for this endpoint; however, they were not significant. Gossamer is expected to move forward with a Phase III, but lacks investor confidence as indicated by a market cap below cash holdings.
Sotatercept
Acceleron/Merck are developing sotatercept, which is a is a first-in-class therapeutic fusion protein that targets an imbalance in activin–growth differentiation factor and BMP pathway signaling. Sotatercept is the subject of clinical trials investigating PAH. In a Phase III study designated STELLAR, Merck reported a clinically meaningful improvement in the six minute walk distance after 24 weeks in October 2022. An improvement in NT-proBNP level was also achieved in the study. Further analysis was provided in a New England Journal of Medicine article Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension.
Selection of explanatory research for the levosimendan and imatinib programs:
➢ June 3, 2020 – Results from Phase II levosimendan study
o TENX: Target Up on Solid HELP Results
➢ April 9, 2021 – Background on imatinib
o TENX: HELP Results & New Asset to Boot
➢ June 2023 – Corporate Presentation
o Tenax Therapeutics Corporate Presentation
Patents
Patent Application Granted Notice of Allowance
On February 1st, Tenax announced it had received a notice of allowance from the US Patent and Trademark Office (USPTO) for patent number 11,607,412 entitled Levosimendan for Treating Pulmonary Hypertension with Heart Failure and Preserved Ejection Fraction (PH-HFpEF). A notice of allowance is issued when an examiner determines that a patent application satisfies the requirements for patentability. On March 22nd, Tenax reported that the patent was issued. The patent is expected to provide protection until December 2040 and addresses the subcutaneous use of levosimendan. Intravenous levosimendan has been available generically for many years in Europe as the patent expired in 2015; however, the drug was not approved in the US in any form. With the additional protection that is expected to be provided by this patent, the value of levosimendan in PH-HFpEF has improved.
Tenax was granted a Notice of Allowance for oral levosimendan in PH-HFpEF as memorialized in a May 31 press release. Several administrative requirements must be completed, including the payment of the issue fee before the patent is issued. This process took approximately two months for the intravenous levosimendan patent in PH-HFpEF during the first quarter, and we expect a similar time frame for the oral patent.
Summary
With the issue of a Notice of Allowance for oral levosimendan in PH-HFpEF, Tenax can enjoy intellectual property protection for a related product until at least the end of 2040. With sufficient capital in the bank, we expect Tenax to begin its Phase III trial soon with potential interim data reported next year. While imatinib for PAH is on hold, it may move into the spotlight next year if peer Aerovate fails to show beneficial effect for inhaled imatinib in PAH patients. This could stimulate investor interest in Tenax’s imatinib program and attract capital to run a Phase III in a second indication.
We see therapeutic potential for Tenax’s two candidates that may provide a material improvement in multiple PAH groups. With existing cash on hand, Tenax has sufficient capital to advance its levosimendan program in PH-HFpEF. Based on the financial opportunity and the low entry price, the opportunity for investors with sufficient funds to see the programs to conclusion appears to be substantial.
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1. Tenax Therapeutics June 2023 Corporate Presentation
2. Agnihotri, V., et al. An Update on Advancements and Challenges in Inhalational Drug Delivery for Pulmonary Arterial Hypertension. Molecules, May 2022.
3. Tenax Therapeutics June 2023 Corporate Presentation
