Study Offers Roadmap for Speeding Development of Monoclonal Antibodies for Other Diseases; Techniques have been applied to COVID-19 studies, in which Company has completed Phase 1 Trial
Tychan, a Singapore-based clinical-stage biotechnology company focused on developing life-saving treatments through disruptive technologies, announced today a publication in New England Journal of Medicine (NEJM) demonstrating the safety and efficacy for TY014, a novel monoclonal antibody candidate treatment for yellow fever (YF). The publication highlights the significant reduction of monoclonal antibody (mAb) development time through the use of Tychan’s proprietary rapid-response platform, developed by co-founders Prof. Ram Sasisekharan and Prof. Ooi Eng Eong, and offers a roadmap for research of therapeutics for other infectious diseases, including COVID-19.
"Speeding access to effective therapeutics is an imperative and a high priority as infectious disease outbreaks will happen with increasing frequency and with greater adverse impact on lives and livelihoods, societies and economies. The COVID-19 pandemic is a case in point," said Ram Sasisekharan, PhD, a founder of Tychan as well as professor in Biological Engineering and Health Sciences & Technology at MIT.
Studies enabling Investigational New Drug (IND) applications, including chemistry, manufacturing, and control (CMC), and the Phase 1 trials were completed in record timeframes. IND-enabling studies for the development of Tychan’s successful mAb for yellow fever took seven months from design to first-in-human infusion. Importantly, our accomplishments to date illustrate that this process can, not only be replicated but further shortened.
"Tychan was set up to more effectively battle infectious disease outbreaks. That has been our mission. We have therefore been confident in our innovative rapid response platform. Results from this NEJM study provide evidence that TY014 has the potential to offer a significant clinical advancement for the treatment of yellow fever, further boosting our confidence that our development will be able to contribute to the global efforts in eradicating the scourge of infectious diseases one day," said Teo Ming Kian, Chairman of the Board, Tychan.
TY014 for Yellow Fever
Data published in the New England Journal of Medicine demonstrate that TY014 was not only safe and well tolerated at the highest doses tested, but also completely eradicated the yellow fever virus in the bloodstream of all participants within 48 hours of infusion. The results of this study set the stage for a phase 2 trial in geographies endemic for yellow fever, to assess the efficacy of TY014 as the first treatment for yellow fever.
"Much thought has been given to the design of the trial. The strategy is to accelerate the study of TY014 for yellow fever as the disease has a mortality rate of 20 – 50%. There is no treatment specifically indicated for yellow fever, and the currently available vaccine is contraindicated for the most vulnerable populations, including infants, pregnant women, the elderly and the immunocompromised," said Prof. Ooi Eng Eong, Co-founder of Tychan and Deputy Director, Emerging Infectious Diseases Programme, Duke-National University of Singapore Medical School.
Phase 1A of the TY014 study evaluated safety, tolerability and pharmacokinetics of this monoclonal antibody in healthy volunteers and consisted of five randomized cohorts with a double-blind design for first dose cohort (0.5 mg/kg), and an open-label design for the remaining four dose cohorts (2, 5, 10 and 20 mg/kg); 22 volunteers received TY014 and five received placebo. This phase of the study met safety and efficacy endpoints with 100% of subjects testing negative for viremia within 48 hours after infusion. Phase 1B evaluated safety, tolerability and efficacy of TY014, and was a time lagged, parallel-group, randomized, placebo-controlled, double-blinded, single-ascending-dose study of TY014. Volunteers in phase 1B received a weakened version of live yellow fever vaccine before treatment with TY014 (n=5) or placebo (n=5); only 10 subjects (from dose cohort 1) were recruited because of the success in phase 1A of the study. At 48 hours post treatment, none of the volunteers in the phase 1B study who received the starting 2 mg/kg TY014 dose had detectable yellow fever virus in the bloodstream.
The trial was administered by SingHealth Investigational Medicine Unit, led by Associate Professor Jenny Low, senior consultant, Department of Infectious Diseases, Singapore General Hospital and co-director, Viral Research and Experimental Medicine Centre (ViREMiCS).
TY014 is the first monoclonal antibody designed and engineered to treat yellow fever virus infected patients to enter the clinic. TY014 is directed against the envelope (E) protein on the surface of the virus, and prevents viral replication by limiting viral fusion to host cells.
Application to COVID-19
The same platform was used to develop TY027, the first novel mAb that specifically targets SARS-CoV-2, the virus that causes COVID-19.
There has been good progress with the development of TY027. In less than four months, first in human infusion was done in a Phase 1 study approved by the Health Sciences Authority of Singapore (HSA). Dosing of healthy volunteers up to a maximum dose of 20 mg/kg has been completed with good safety outcome. Tychan is finalizing plans for Phase 3 trial of TY027 in patients with COVID-19, expected to be initiated within the next few weeks upon approval by regulatory and ethics authorities.
About Tychan Pte. Ltd.
Tychan, a Singapore based clinical-stage biotechnology company, is focused on bringing life-saving treatments for emerging infections to those in need through disruptive technologies. In a coordinated effort with regulatory authorities, the company is accelerating the translation from non-clinical studies to clinical trials for emerging pathogens. Founded by Professor Ram Sasisekharan of Massachusetts Institute of Technology (MIT)/Singapore MIT Alliance for Research and Technology (SMART) and Professor Ooi Eng Eong of Duke-National University of Singapore (Duke-NUS) Medical School, whose expertise spans the fields of biologics development and biology of acute viral infections. Temasek Holdings is the founding investor of Tychan. For more information on Tychan Pte. Ltd, please visit: www.tychan.com.