By David Bautz, PhD
READ THE FULL TNXP RESEARCH REPORT
Enterprise Replace
Mpox Declared a. Public Well being Emergency of Worldwide Concern
On August 14, 2024, the World Well being Group (WHO) declared mpox a public well being emergency of worldwide concern. The present outbreak of mpox was brought on by Clade 1 monkeypox virus, whereas the 2022 outbreak was brought on by the Clade 2 monkeypox virus. Based on the WHO, the variety of mpox instances reported this 12 months within the DRC has totaled greater than 15,600 and resulted in 537 deaths (WHO).
Tonix Pharmaceutical Holdings Corp. (NASDAQ:TNXP) is growing TNX-801 as an mpox vaccine candidate. It’s a stay replicating, attenuated virus vaccine primarily based on horsepox virus. For a full overview of this system, see this presentation. The corporate beforehand examined TNX-801 in non-human primates (NHPs) and confirmed that the vaccine was effectively tolerated and guarded animals from the event of lesions and extreme illness following a deadly problem with monkeypox virus (Noyce et al., 2023). The research had 4 cohorts; a TNX-801 excessive dose, a TNX-801 low dose, a recombinant vaccinia virus (rVACV), or mock immunized. The next slide provides an outline of the research, through which NHPs have been challenged 60 days following vaccination after which adopted by way of Day 88.
Immunological evaluation confirmed that 100% of TNX-801-immunized animals had a optimistic antibody response that was 2- to 16-fold increased than baseline by Day 28 and 4- to 8-fold increased by Day 56. As well as, 88% of TNX-801 animals had neutralizing antibody responses 8- to 50-fold increased than baseline by Day 56. Following problem with mpox virus, the strong immunological response of TNX-801-immunized animals translated to minimal or no viral shedding, as proven within the following determine. In distinction, animals immunized with rVACV or mock immunized exhibited viral shedding. As well as, no TNX-801-immunized animals had observable lesions. The shortage of viral shedding and no lesions is an effective indication that TNX-801 might be able to scale back or remove ahead transmission of the virus.
Lastly, the next determine exhibits that no animals immunized with TNX-801 or rVACV died and 50% of the mock immunized animals didn’t survive previous Day 12 submit an infection.
In abstract, TNX-801 has a variety of optimistic traits that help its continued improvement as a mpox vaccine, together with the actual fact it’s a stay replicating, attenuated virus that’s >1,000-fold extra attenuated than twentieth century vaccinia (VACV) strains in immunocompromised mice, it solely requires one dose for cover, it may be administered with a bifurcated needle, vaccinated people develop a “take” that may be a biomarker of T cell immunity, and it doesn’t require cold-chain storage.
On August 26, 2024, Tonix introduced a collaboration with Bilthoven Biologicals (BBio) to advance TNX-801. BBio is a world vaccine firm that produces each prophylactic and therapeutics vaccines. It was chosen by the European Union for its pandemic preparedness program of ‘ever heat’ vaccine manufacturing corporations. It additionally has an extended observe file of supplying vaccines to European markets and international well being companions akin to UNICEF, PAHO, and WHO/GAVI.
Tonmya NDA Submitting on Monitor for 2H24 Submission
Tonix will likely be submitting a brand new drug utility (NDA) for TNX-102 SL (conditionally accepted commerce title Tonmya) for the remedy of fibromyalgia (FM) within the second half of 2024. In help of this, the corporate has accomplished two conferences with the FDA:
• On June 20, 2024, Tonix introduced the receipt of the formal minutes from a pre-NDA Kind B Chemistry, Manufacturing, and Controls (CMC) assembly through which the corporate believes it’s in alignment with the FDA on key subjects, together with proposed drug substance and drug product business specs, shelf life task, manufacturing, and business drug packaging.
• On July 8, 2024, Tonix introduced the receipt of the formal minutes from a pre-NDA assembly concerning the proposed information bundle. On the assembly the corporate and the FDA agreed that the proposed information bundle is adequate to help NDA submission.
First Affected person Dosed in Section 2 CATALYST Research of TNX-1300
On August 20, 2024, Tonix introduced that the primary affected person has been dosed within the Section 2, single blind, placebo managed, proof-of-concept trial of TNX-1300 for the remedy of acute cocaine intoxication within the emergency division.
TNX-1300 is a recombinant enzyme derived from the cocE gene of a Rhodococcus species that makes use of cocaine as a sole supply of carbon and nitrogen (Bresler et al., 2000). The CocE enzyme was examined in a rat mannequin of cocaine toxicity to find out if it might defend the animals from cocaine-induced lethality (Cooper et al., 2006). Outcomes confirmed that it required a 1000 mg/kg dose of cocaine to beat the protecting results of 1 mg CocE (LD50 for IP dose is 70 mg/kg cocaine).
One of many points with the native CocE enzyme is that its half-life is just a few minutes at physiological temperature (37ºC) (Cooper et al., 2006). Thus, a research was carried out to develop thermostable variants of CocE utilizing a computational method together with in vitro and in vivo research (Gao et al., 2009). A variant was recognized with two amino acid substitutions (T172R/G173Q) that resulted in elevated stability at 37ºC.
The double mutant CocE enzyme (then referred to as RBP-8000, now TNX-1300) was evaluated in a Section 2 medical trial carried out by Reckitt Benckiser Prescribed drugs, the earlier licensee to the product (NCT01846481). It was a double blind, placebo managed, randomized, four-sequence, two-period cross-over research. Topics have been non-treatment seekers with a DSM-IV prognosis of cocaine abuse. In the course of the research interval, topics got an IV infusion of fifty mg of cocaine over 10 minutes adopted by TNX-1300 (100 mg or 200 mg) or matching placebo one minute after completion of the cocaine infusion. Outcomes included pharmacokinetics of each cocaine and TNX-1300 together with any impact by TNX-1300 on cocaine-induced physiological modifications (Nasser et al., 2014).
A complete of 29 topics have been randomized within the trial. Security outcomes confirmed that no anti-TNX-1300 antibodies have been detected in any of the themes at any time level. As well as, there have been no clinically vital abnormalities in important indicators, medical laboratory markers, or bodily examinations. A complete of seven topics reported treatment-emergent opposed occasions that have been thought-about associated to remedy with any research drug, with most being assessed as delicate in severity. Of word, important indicators of topics handled with TNX-1300 returned to or under baseline sooner than topics that obtained placebo.
Plasma cocaine quickly decreased following administration of TNX-1300, with a 90% drop of peak plasma cocaine concentrations inside two minutes and a 95% decline in plasma cocaine publicity. The 200 mg dose of TNX-1300 produced a longer-lasting impact on cocaine pharmacokinetics in comparison with the 100 mg dose. These preliminary outcomes totally help the analysis of TNX-1300 within the present Section 2 research.
Monetary Replace
On August 19, 2024, Tonix introduced monetary outcomes for the second quarter of 2024. Internet product revenues for the second quarter of 2024 have been roughly $2.2 million and the price of gross sales was $3.4 million, which included a write-down associated to Tosymra® and Zembrace® completed items stock of roughly $1.7 million primarily based on an evaluation of stock readily available and projected gross sales previous to the respective expiration dates.
R&D bills for the second quarter of 2024 have been $9.7 million, in comparison with $22.0 million for the second quarter of 2023. The lower was primarily resulting from decreased medical, non-clinical, and manufacturing bills aligned with the corporate’s capital environment friendly technique. G&A bills for the second quarter of 2024 have been $7.5 million, in comparison with $7.0 million for the second quarter of 2023. The rise was primarily resulting from gross sales and advertising and marketing and the transition providers bills related to the corporate’s not too long ago acquired marketed merchandise partially offset by a lower in monetary reporting bills.
Internet loss out there to widespread shareholders for the second quarter of 2024 was $78.8 million, or $19.28 per share, in comparison with a web lack of $28.4 million, or $49.23 per share, for a similar interval in 2023. Included within the web loss for the three months ending June 30, 2024 are non-cash asset impairment fees totaling $58.9 million.
As of June 30, 2024, Tonix had roughly $4.2 million in money and money equivalents. On August 30, 2024, the corporate introduced that in August 2024 it had bought roughly 82 million shares of inventory for gross proceeds of roughly $34.9 million. As of August 31, 2024, the corporate had roughly 104.0 million shares excellent and, when factoring in inventory choices and warrants, a totally diluted share rely of roughly 110.6 million.
Conclusion
Now that the WHO has declared mpox a public well being emergency of worldwide concern, we sit up for the development of TNX-801 as a vaccine candidate for mpox and probably see the chance for non-dilutive funding from authorities sources if mpox continues to unfold. On the similar time, the corporate is totally dedicated to getting the NDA for Tonmya filed with the FDA within the second half of 2024, and with Quick Monitor designation there’s the potential for expedited overview of the NDA. Following the inventory sale in August, the corporate now has roughly $30 million in money, which needs to be adequate to fund operations previous the NDA submitting and its potential acceptance by the FDA. After incorporating the latest financing into our mannequin our valuation now stands at $4.00 per share.
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