Post-Traumatic Stress Disorder in Focus

Psychiatry drug development is historically a challenging space to navigate, but Seth Lederman, CEO of Tonix Pharmaceuticals, is unwavering in his mission to develop the next therapy for post-traumatic stress disorder (PTSD). Dr. Lederman shares key learning for Tonix’s recent clinical trials and how they are using their expertise to provide relief to unmet patient populations. Finally, Dr. Lederman shares his insights into how his unique background as an academic and scientist, places him in an optimal position to lead Tonix to success.

Moe Alsumidaie: What unmet need is Tonix addressing?

Seth Lederman: At Tonix, we are developing a product called TNX-102 SL or “Tonmya®,” as a treatment for PTSD. We've completed two large studies in military-related PTSD patients, a subset of the PTSD patient population that is distinguished by trauma occurring during military service. The development of therapies for this subpopulation is an unmet need because the two currently FDA-approved drugs for PTSD, selective serotonin reuptake inhibitors (SSRIs) Paxil and Zoloft, have not shown efficacy in military-related PTSD. We believe that

Seth Lederman

our veterans and active military who suffer from PTSD from military trauma deserve the best chance to heal and that TNX-102 SL can help. Our product Tonmya is a new sublingual formulation of cyclobenzaprine, a tricyclic with no recognized abuse potential. The treatment regimen is bedtime administration, nightly for twelve weeks and the mechanism of therapy is to improve sleep quality. Sleep is an essential process necessary to health that becomes disrupted in PTSD.

MA: Tonmya was recently evaluated in a Phase 3 clinical study? Tell me about its results and what you have learned from them.

SL: The HONOR study was a Phase 3 study focusing on Tonmya in military-related PTSD. It was designed to enroll 550 participants, but we conducted a pre-planned interim analysis of the first 275 enrolled patients. The results led us to discontinue the study because the interim data did not meet a pre-specified continuation threshold. While we were surprised and disappointed that the study did not meet the endpoint, we were also glad that we had planned the interim analysis, because it saved us time and money and provided us a valuable opportunity to learn from the study and to design a better one. Our upcoming Phase 3 RECOVERY study was designed to reflect these lessons. For example, based on our analysis of the HONOR study, in the RECOVERY phase 3 trial we are going to limit patient enrollment to those who have experienced their trauma within nine years of the trial. We learned in the HONOR study that PTSD from trauma experienced beyond nine years appears to be either less responsive to TNX-102 SL treatment or are harder to study.

MA: What other differences and adjustments have you made between the initial Phase 3 HONOR study and the imminent RECOVERY study?

SL: Another difference between the new RECOVERY study and the finished HONOR study, is that in the RECOVERY study we are going to enroll both PTSD patients who experienced either civilian or military-related trauma. The HONOR study was restricted to just PTSD from military-related trauma.  We are including civilian-related trauma in RECOVERY because we want to model the U.S. PTSD patient population better and that a positive study will provide data to regulators and payers that our potential therapy is effective at treating the entirety of the intended market. Approximately 75% of the U.S. adult PTSD patient population is composed of civilians who have experienced non-military trauma-ranging from rape and assault to natural disasters to terrorist events and mass shootings. As previously mentioned, there are two drugs FDA-approved for treating PTSD. Neither of the approved drugs has shown efficacy in PTSD from military trauma. While the two approved drugs have demonstrated efficacy in PTSD from civilian trauma, many patients are still suffering. We believe that civilian PTSD is an important potential market for TNX-102 SL that deserves attention.

MA: What other companies are in the clinical stage of PTSD drug development and what are the advantages of Tonix in terms of your drug development strategy?

SL: Our biggest competitor right now is not a company, but a group called the Multi-disciplinary Association of Psychedelic Studies (MAPS). MAPS is a nonprofit that was founded to promote the medical benefits of certain drugs with psychedelic properties. In PTSD drug development, MAPS is in Phase 3 development of MDMA for drug-assisted psychotherapy. Another competitor with exciting Phase 2 data is Otsuka and Lundbeck, who recently announced significant results for their atypical antipsychotic Brexpiprazole in combination with Sertraline. However, we do not view these PTSD therapeutic developments as competition-at Tonix, we are rooting for everyone and hope that together we can provide relief to those with PTSD.

MA: What struggles have you encountered during clinical trial recruitment and retention?

SL: While PTSD is ubiquitous, approximately 12 million adults in the U.S., it's surprisingly challenging to enroll participants in a clinical study. Why is that? Well, one of the core symptoms of PTSD is called, “avoidance.” Avoidance is a group of behavioral patterns by which PTSD sufferers avoid triggers in the environment that would remind them of the traumatic experience. Unfortunately, testing new drugs in PTSD necessarily involves numerous interactions with healthcare professionals in which the study participants with PTSD are required to discuss their traumatic experiences and related symptoms. Given how unpleasant these interactions can be and how these interviews challenge their avoidance symptoms, we anticipate there will be continued challenges in identifying PTSD patients for clinical trials.

MA: You are both a scientist and CEO; how are these roles similar and make you uniquely qualified to head a challenging clinical program?

SL: Psychiatry drug development is not a straight line. The chances of success in any given trial are similar to the probability of success in getting “hits” in baseball.  A successful hitter might only get a hit one out of three times at bat. In both academia and psychiatry drug development, you must be prepared to have some unsuccessful bats. You anticipate these unsuccessful experiences, which allow you to hone your study design, dosing, and other detailed aspects of the study. Most importantly, you need to persevere. I think the most important message is that Tonix has acquired a great deal of experience studying TNX-102 SL and PTSD.  We now know so much more about TNX-102 SL and PTSD, that, in my opinion, the program has never been more valuable or closer to success.

Moe Alsumidaie, MBA, MSF is Chief Data Scientist at Annex Clinical.