NASDAQ:TNXP
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Business Update
Mpox Declared a. Public Health Emergency of International Concern
On August 14, 2024, the World Health Organization (WHO) declared mpox a public health emergency of international concern. The current outbreak of mpox was caused by Clade 1 monkeypox virus, while the 2022 outbreak was caused by the Clade 2 monkeypox virus. According to the WHO, the number of mpox cases reported this year in the DRC has totaled more than 15,600 and resulted in 537 deaths (WHO).
Tonix Pharmaceutical Holdings Corp. (NASDAQ:TNXP) is developing TNX-801 as an mpox vaccine candidate. It is a live replicating, attenuated virus vaccine based on horsepox virus. For a full overview of the program, see this presentation. The company previously tested TNX-801 in non-human primates (NHPs) and showed that the vaccine was well tolerated and protected animals from the development of lesions and severe disease following a lethal challenge with monkeypox virus (Noyce et al., 2023). The study had four cohorts; a TNX-801 high dose, a TNX-801 low dose, a recombinant vaccinia virus (rVACV), or mock immunized. The following slide gives an overview of the study, in which NHPs were challenged 60 days following vaccination and then followed through Day 88.
Immunological analysis showed that 100% of TNX-801-immunized animals had a positive antibody response that was 2- to 16-fold higher than baseline by Day 28 and 4- to 8-fold higher by Day 56. In addition, 88% of TNX-801 animals had neutralizing antibody responses 8- to 50-fold higher than baseline by Day 56. Following challenge with mpox virus, the robust immunological response of TNX-801-immunized animals translated to minimal or no viral shedding, as shown in the following figure. In contrast, animals immunized with rVACV or mock immunized exhibited viral shedding. In addition, no TNX-801-immunized animals had observable lesions. The lack of viral shedding and no lesions is a good indication that TNX-801 may be able to reduce or eliminate forward transmission of the virus.
Lastly, the following figure shows that no animals immunized with TNX-801 or rVACV died and 50% of the mock immunized animals did not survive past Day 12 post infection.
In summary, TNX-801 has a number of positive characteristics that support its continued development as a mpox vaccine, including the fact it is a live replicating, attenuated virus that is >1,000-fold more attenuated than 20th century vaccinia (VACV) strains in immunocompromised mice, it only requires one dose for protection, it can be administered with a bifurcated needle, vaccinated individuals develop a “take” that is a biomarker of T cell immunity, and it does not require cold-chain storage.
On August 26, 2024, Tonix announced a collaboration with Bilthoven Biologicals (BBio) to advance TNX-801. BBio is a global vaccine company that produces both prophylactic and therapeutics vaccines. It was selected by the European Union for its pandemic preparedness program of ‘ever warm’ vaccine manufacturing companies. It also has a long track record of supplying vaccines to European markets and global health partners such as UNICEF, PAHO, and WHO/GAVI.
Tonmya™ NDA Filing on Track for 2H24 Submission
Tonix will be filing a new drug application (NDA) for TNX-102 SL (conditionally accepted trade name Tonmya™) for the treatment of fibromyalgia (FM) in the second half of 2024. In support of this, the company has completed two meetings with the FDA:
• On June 20, 2024, Tonix announced the receipt of the formal minutes from a pre-NDA Type B Chemistry, Manufacturing, and Controls (CMC) meeting in which the company believes it is in alignment with the FDA on key topics, including proposed drug substance and drug product commercial specifications, shelf life assignment, manufacturing, and commercial drug packaging.
• On July 8, 2024, Tonix announced the receipt of the formal minutes from a pre-NDA meeting regarding the proposed data package. At the meeting the company and the FDA agreed that the proposed data package is sufficient to support NDA submission.
First Patient Dosed in Phase 2 CATALYST Study of TNX-1300
On August 20, 2024, Tonix announced that the first patient has been dosed in the Phase 2, single blind, placebo controlled, proof-of-concept trial of TNX-1300 for the treatment of acute cocaine intoxication in the emergency department.
TNX-1300 is a recombinant enzyme derived from the cocE gene of a Rhodococcus species that utilizes cocaine as a sole source of carbon and nitrogen (Bresler et al., 2000). The CocE enzyme was tested in a rat model of cocaine toxicity to determine if it could protect the animals from cocaine-induced lethality (Cooper et al., 2006). Results showed that it required a 1000 mg/kg dose of cocaine to overcome the protective effects of 1 mg CocE (LD50 for IP dose is 70 mg/kg cocaine).
One of the issues with the native CocE enzyme is that its half-life is only a few minutes at physiological temperature (37ºC) (Cooper et al., 2006). Thus, a study was performed to develop thermostable variants of CocE using a computational approach along with in vitro and in vivo studies (Gao et al., 2009). A variant was identified with two amino acid substitutions (T172R/G173Q) that resulted in increased stability at 37ºC.
The double mutant CocE enzyme (then called RBP-8000, now TNX-1300) was evaluated in a Phase 2 clinical trial conducted by Reckitt Benckiser Pharmaceuticals, the previous licensee to the product (NCT01846481). It was a double blind, placebo controlled, randomized, four-sequence, two-period cross-over study. Subjects were non-treatment seekers with a DSM-IV diagnosis of cocaine abuse. During the study period, subjects were given an IV infusion of 50 mg of cocaine over 10 minutes followed by TNX-1300 (100 mg or 200 mg) or matching placebo one minute after completion of the cocaine infusion. Outcomes included pharmacokinetics of both cocaine and TNX-1300 along with any effect by TNX-1300 on cocaine-induced physiological changes (Nasser et al., 2014).
A total of 29 subjects were randomized in the trial. Safety results showed that no anti-TNX-1300 antibodies were detected in any of the subjects at any time point. In addition, there were no clinically significant abnormalities in vital signs, clinical laboratory markers, or physical examinations. A total of seven subjects reported treatment-emergent adverse events that were considered related to treatment with any study drug, with most being assessed as mild in severity. Of note, vital signs of subjects treated with TNX-1300 returned to or below baseline earlier than subjects that received placebo.
Plasma cocaine rapidly decreased following administration of TNX-1300, with a 90% drop of peak plasma cocaine concentrations within two minutes and a 95% decline in plasma cocaine exposure. The 200 mg dose of TNX-1300 produced a longer-lasting effect on cocaine pharmacokinetics compared to the 100 mg dose. These preliminary results fully support the evaluation of TNX-1300 in the current Phase 2 study.
Financial Update
On August 19, 2024, Tonix announced financial results for the second quarter of 2024. Net product revenues for the second quarter of 2024 were approximately $2.2 million and the cost of sales was $3.4 million, which included a write-down related to Tosymra® and Zembrace® finished goods inventory of approximately $1.7 million based on an assessment of inventory on hand and projected sales prior to the respective expiration dates.
R&D expenses for the second quarter of 2024 were $9.7 million, compared to $22.0 million for the second quarter of 2023. The decrease was primarily due to decreased clinical, non-clinical, and manufacturing expenses aligned with the company’s capital efficient strategy. G&A expenses for the second quarter of 2024 were $7.5 million, compared to $7.0 million for the second quarter of 2023. The increase was primarily due to sales and marketing and the transition services expenses associated with the company’s recently acquired marketed products partially offset by a decrease in financial reporting expenses.
Net loss available to common shareholders for the second quarter of 2024 was $78.8 million, or $19.28 per share, compared to a net loss of $28.4 million, or $49.23 per share, for the same period in 2023. Included in the net loss for the three months ending June 30, 2024 are non-cash asset impairment charges totaling $58.9 million.
As of June 30, 2024, Tonix had approximately $4.2 million in cash and cash equivalents. On August 30, 2024, the company announced that during August 2024 it had sold approximately 82 million shares of stock for gross proceeds of approximately $34.9 million. As of August 31, 2024, the company had approximately 104.0 million shares outstanding and, when factoring in stock options and warrants, a fully diluted share count of approximately 110.6 million.
Conclusion
Now that the WHO has declared mpox a public health emergency of international concern, we look forward to the advancement of TNX-801 as a vaccine candidate for mpox and potentially see the opportunity for non-dilutive funding from government sources if mpox continues to spread. At the same time, the company is fully committed to getting the NDA for Tonmya filed with the FDA in the second half of 2024, and with Fast Track designation there is the potential for expedited review of the NDA. Following the stock sale in August, the company now has approximately $30 million in cash, which should be sufficient to fund operations past the NDA filing and its potential acceptance by the FDA. After incorporating the recent financing into our model our valuation now stands at $4.00 per share.
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