Rapid Response Initiative

Rapid Response effort is intended to reduce the time taken to develop therapeutics from many years to a matter of mere months. We have been able to condense the timeline by performing many of the steps necessary for drug development as parallel processes. Traditional drug development processes are rigidly linear, and span many years. To get a therapeutic to human consumers rapidly during a infectious disease outbreak (either epidemic or pandemic) the best-case scenario for testing in humans is a year to 18 months. To be able to develop a drug in six months or even less time, then several of the practical steps need to happen concomitantly.

We explore new approaches to compress this timeline by performing many of the necessary steps simultaneously, using analytical techniques to address regulatory risks associated with drug safety, manufacturing, and clinical study design. With advanced instrumentation support from Agilent Technologies, our approach is to use the regulatory framework as a design constraint.  In beginning  with this framework in mind and working with regulators each step along the way, we can more rapidly develop, produce, and evaluate antibody candidates for safety and efficacy in humans

Using such an approach,  a candidate Zika treatment was developed in 2017-2018 within nine months and Phase 1a clinical trials were completed. A similar approach was also deployed to develop a potential treatment for Yellow Fever. Yellow Fever, a mosquito-borne disease, tends to appear seasonally in tropical and subtropical regions of South America and Africa. A particularly severe outbreak began in Brazil in January 2018 and endured for several months.

Several innovative steps were performed for the development of the anti-Yellow Fever candidate TY014. These included production methods to create small, uniform batches that they could use to perform necessary testing phases at the same time. These tests include studying the drugs’ effectiveness in human cells, determining the most effective dosages, testing for potential toxicity, and analyzing how the drug behaves in animal models. Once deemed safe through these non-clinical studies, the first in-human clinical trials commenced in December 2018.

TY014 was clinically tested in parallel to address safety through dose escalation in healthy human volunteers. Once an appropriate dose was deemed safe, phase 1b trial was initiated, in which the antibody’s ability to clear the virus was evaluated. Although the 1b trial had begun, the 1a trial continued until a maximum safe dose in humans was identified. Because there is a vaccine available for Yellow Fever, we could perform a challenge study. Volunteers were first vaccinated and then 24 hours later, they received either the experimental antibody drug or a placebo. Two days after that, we measured whether the drug cleared the weakened viruses that make up the vaccine. Following treatment, we found that the virus was undetectable in blood samples from the volunteers who received TY014. The treatment also reduced inflammation following vaccination, compared to people who received the vaccine but not TY014. The phase 1b trial was completed in July 2019 and the study published in the New England Journal of Medicine.

The COVID-19 pandemic has brought much of the world to a halt. Phase 1 clinical trials to evaluate TY027, a monoclonal antibody that specifically targets SARS-CoV-2, the virus that causes COVID-19 was initiated in June 2020. The development of TY027, including discovery and laboratory and preclinical studies, took only four months. This four-month timeline is a further improvement from the earlier successful mAb efforts with Yellow Fever, which took seven months from design to first-in-human infusion, and Zika, which took nine months. TY027 is being developed in partnership with several Singaporean government agencies, including the Ministry of Defense, Ministry of Health, and the Economic Development Board. With the successful completion of Phase I, TY027 is now being evaluated in Phase 3 studies for the treatment of patients with COVID-19 to slow the progression of the disease and accelerate recovery, as well as for its potential to provide temporary protection against infection with SARS-CoV-2. 

The Sasisekharan Lab in Singapore (AMR-IRG, SMART) is collaborating with various groups in Singapore and the region to establish the Rapid Response Initiative. This includes the Princess Chulababhorn Research Institute, Bangkok, Thailand.