Zacks Small Cap Research – TNXP: Positive Results for Phase 3 RESILIENT Trial Sets Up NDA Filing in 2H24… – Technologist

By David Bautz, PhD

NASDAQ:TNXP

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Business Update

Positive Results for Phase 3 RESILIENT Trial; NDA Filing Expected in 2H24

On December 20, 2023, Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) announced positive topline results for the Phase 3 RESILIENT trial of TNX-102 SL for the management of fibromyalgia (NCT05273749). The trial achieved the primary outcome of reducing daily pain compared to placebo (P=0.00005) and showed an analgesic effect size of 0.38. In addition, statistically significant and clinically meaningful results were also seen in all key secondary endpoints related to improving sleep quality, reducing fatigue, and improving overall fibromyalgia symptoms and function. An overview of the data can be found here.

The following graph shows the primary outcome measure of reduction in pain over the 14-weeks of the trial. TNX-102 SL showed a rapid onset of action and separated from placebo for each week of the study. It exhibited a robust effect size of 0.38. The Week 14 least square (LS) mean (SE) change from baseline for TNX-102 SL was -1.82 (0.12) and for placebo -1.16 (0.12), with a least square mean difference from placebo of -0.65 (0.16) (P=0.00005).

An additional means to examine efficacy is the 30% responder analysis, which is the percentage of patients that showed a ≥ 30% reduction in pain. The following graph shows that 45.9% of those treated with TNX-102 SL and 27.1% of those treated with placebo were 30% responders (P<0.001). The 50% responder analysis showed 22.5% of those treated with TNX-102 SL responded compared to 13.3% of placebo-treated subjects, further supporting the strong efficacy of TNX-102 SL.

As mentioned previously, all of the six key secondary endpoints for the RESILIENT study were positive. The following figure on the left shows the Patient Global Impression of Change (PGIC) responder analysis while the figure on the right shows the Fibromyalgia Impact Questionnaire – Revised (FIQ-R) Symptoms Domain. The PGIC showed a statistically significant difference between TNX-102 SL and placebo for each week examined during the study. At Week 14, 35.1% of TNX-102 SL treated subjects were responders compared to only 19.1% of placebo-treated subjects (P=0.00013). For the FIQ-R Symptoms Domain, treated subjects separated from placebo subjects as early as Week 2 and there was a statistically significant difference between the groups through the whole study. The Week 14 LS mean (SE) change from baseline for TNX-102 SL was -16.0 (1.17) compared to -8.4 (1.17) for placebo-treated subjects (P=0.000002).

The proposed mechanism of action for how TNX-102 SL exerts its effects in fibromyalgia is through improved sleep quality. In support of this, the following figure shows a statistically significant improvement in the weekly average of the daily diary of sleep quality with the change for TNX-102 SL-treated subjects of -1.8 (0.12) units compared to -1.2 (0.12) units for placebo-treated subjects (P=0.0007). The PROMIS Sleep Disturbance instrument also showed significantly greater improvement over placebo on T-scores, with a LS mean (SE) difference from placebo of -4.2 (0.79) units (P<0.001).

TNX-102 SL was well tolerated in the RESILIENT trial and no new safety signals were observed. Of those randomized into the trial, 81.0% and 79.2% of TNX-102 SL- and placebo-treated subjects finished the study, respectively. The following table lists the treatment-emergent adverse events (TEAEs) that were seen at a rate of ≥ 3% in either treatment group. Hypoaesthesia oral and paraesthesia oral (tongue and mouth numbness or tingling), product taste abnormal, and tongue discomfort were local effects that were nearly always related to dose administration and transient in nature (< 60 minutes) in most occurrences. In addition to the four oral adverse events, COVID-19, somnolence, and headache were the only other TEAEs that occurred at a rate of 3.0% or greater in either arm. AEs that resulted in premature study discontinuation were 6.1% and 3.5% for TNX-102 SL and placebo, respectively.

Financial Update

Shortly after announcing the positive results from the RESILIENT trial Tonix announced a registered direct offering of up to $144 million. The company sold an aggregate of 54,054,054 shares of common stock (or prepaid warrants) and two series of registered warrants (Series C and Series D) to purchase an aggregate of 162,162,162 for a purchase price of $0.555 per share and associated warrants. The Series C warrants to purchase up to 81,081,081 shares of common stock at an exercise price of $0.555 are exercisable until the earlier of two years from the initial exercisable date and 10 trading days following the U.S. FDA’s acceptance of Tonix’s new drug application (NDA) for TNX-102 SL in patients with fibromyalgia. The Series D warrants to purchase up to 81,081,081 shares of common stock at an exercise price of $0.85 are exercisable for five years from the initial exercisable date.

Conclusion

The topline results for the RESILIENT trial were a fantastic outcome for the company as the trial achieved the primary endpoint and all six key secondary endpoints. This puts the company into position to file an NDA in the second half of 2024, with a pre-NDA meeting with the FDA likely occurring in the first half of 2024. Tonix is now turning its full attention to getting the NDA assembled and filed in a timely manner. With two positive Phase 3 trials now in fibromyalgia, we have increased the probability of approval for TNX-102 SL to 90%. We have also taken into account the company’s financing, which while necessary in order to get the company’s finances secure in preparation for a commercial launch of TNX-102 SL was highly dilutive. These changes have resulted in a valuation of $1.50.

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