Brii Bio Presents Positive Phase 3 Data on BRII-196/BRII-198, the Company's SARS-CoV-2 Monoclonal Neutralizing Antibody Combination Therapy, in an Oral Late-Breaker Presentation at IDWeek 2021

Data demonstrated a 78% reduction in the risk of hospitalization or death in patients receiving single dose treatment of BRII-196/BRII-198 with zero deaths, versus eight compared to placebo, through the 28-day primary endpoint

Results show significant benefits in non-hospitalized, high risk COVID-19 patients who received treatment early or late following symptom onset, extending a potential therapeutic option to patients with challenges to access care timely

An improved safety outcome in Grade 3/4 adverse events was observed with patients on BRII-196/BRII-198 versus placebo, including no drug related serious adverse events or infusion reactions

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Brii Biosciences Limited

Oct 03, 2021, 20:00 ET

DURHAM, N.C.and BEIJING, Oct. 3, 2021 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio" or the "Company", stock code: 2137.HK) a multi-national company developing innovative therapies for diseases with significant unmet medical needs and large public health burdens, presented at IDWeek 2021 interim results from Phase 3 of the ACTIV-2 trial, which showed that BRII-196/BRII-198 ("combination BRII-196/BRII-198"), the Company's neutralizing monoclonal antibody (mAb) combination therapy for SARS-CoV-2 (virus that causes COVID-19), achieved a similar reduction in hospitalization or death among patients who initiated treatment early (within five days) versus late (six to 10 days) following symptom onset. These initial results suggest that combination BRII-196/BRII-198 may remain effective in a majority of patients who are late to treatment, potentially extending its clinical benefit in a real-world setting, where rapid access to care can be a challenge.

Overall, BRII-196/BRII-198 reduced the risk of hospitalization and death over placebo by 78% in 837 outpatients at high risk of clinical progression. Through the 28-day primary endpoint, zero (n=418) deaths were observed on BRII-196/BRII-198 versus eight (n=419) deaths on the placebo arm. Of those subjects who received treatment with BRII-196/BRII-198 within five days of symptom onset, 2% (4/196) progressed to hospitalization or death, compared with 11% (21/197) in the placebo arm. Similarly, 2% (5/222) of subjects who received treatment with BRII-196/BRII-198 at six to 10 days following symptom onset progressed to hospitalization or death, compared with 11% (24/222) of those receiving placebo. Grade 3 or higher adverse events (AEs) were less common in the BRII-196/BRII-198 treatment arm versus placebo, 3.8% (16/418) versus 13.4% (56/419), with no drug related severe adverse events (SAEs) or infusion reactions observed.

"We're very encouraged by the significant reduction of hospitalizations or death among COVID-19 outpatients at high risk of clinical progression, with these interim Phase 3 results demonstrating that BRII-196/BRII-198 may have clinical utility in patients presenting as late as 10 days after symptom onset, providing another solution to healthcare providers and institutions that continue to deal with increasing hospital admission rates and an overburdened system," said Teresa H. Evering, M.D., M.S., Weill Cornell Medicine, co-lead investigator of BRII-196/BRII-198 in ACTIV-2 and study presenter of the Phase 3 data at IDWeek. "We look forward to continuing to evaluate the full data set from this global trial, including the potential effects of BRII-196/BRII-198 on circulating COVID-19 variants that are driving new cases of COVID-19 around the world."

These findings were presented in an oral late-breaker presentation at the IDWeek 2021 annual meeting on September 30, 2021. The Company previously announced interim top-line results from Phase 3 of the ACTIV-2 trial on August 25, 2021.

"As we continue to grapple with the global effects of this pandemic, including increased incidence of disease based on current and newly-emerging variants, it is imperative that we prioritize and progress the development of safe and effective therapies for the prevention of severe disease," said Eric S. Daar, M.D., Lundquist Institute at Harbor-UCLA Medical Center, co-lead investigator of BRII-196/BRII-198 in ACTIV-2.

"This growing suite of positive data for combination BRII-196/BRII-198, including the consistently high risk reduction and improved safety profile across an expansive set of patients with varying disease progression, provides further validation of its potential to provide a novel therapeutic option for COVID-19 patients," said David Margolis, M.D., MPH, Vice President and Head of Infectious Diseases Therapy at Brii Bio. "We are pleased with the improved safety profile of BRII—196/BRII-198 combination. Safety is critically important in addressing such a global public health crisis."

In addition to the late-breaker data, Brii Bio presented findings in a poster presentation at IDWeek from both preclinical and Phase 1 studies. The preclinical results showed that BRII-196/BRII-198 exhibited neutralizing activity against pseudo-virus variants that contained spike mutations of a panel of ten variants of concern or interest, including commonly identified variants B.1.1.7 (Alpha), B.1.351 (Beta), B.1.1.248/P.1 (Gamma), B.1.429 (Epsilon), B.1.617.2 (Delta), C.37 (Lambda) and B.1.621 (Mu). BRII-196/BRII-198 were evaluated via a microneutralization assay demonstrating that there was no change in the average fold reduction in susceptibility across the pseudo variants. Further, the Phase 1 data showed that combination BRII-196/BRII-198 was well-tolerated with no SAEs and no reported AEs that led to study discontinuation or death. The pharmacokinetic (PK) profiles of BRII-196 and BRII-198, when used in combination, were consistent with those observed as monotherapies, suggesting there are no interactions between the two mAbs.

Based on these findings and the growing body of evidence supporting the use of combination BRII-196/BRII-198, Brii Bio plans to submit an application for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration by the end of the year and will continue to pursue additional regulatory filings in both established and emerging global markets.

Phase 3 of the ACTIV-2 trial was conducted at clinical sites around the world, including the U.S., Brazil, South Africa, Mexico, Argentina and the Philippines, enrolling patients between January and July of 2021 – a period of rapid global emergence of novel SARS-CoV-2 variants. Study participants had the following baseline demographics: median age of 49 years-old, 51% female, 49% Hispanic/Latino ethnicity and 17% Black/African American. Data on the clinical efficacy of combination BRII-196/BRII-198 by variant type is also being evaluated as part of the study.

About BRII-196 and BRII-198
BRII-196 and BRII-198 are non-competing SARS-CoV-2 monoclonal neutralizing antibodies derived from convalesced COVID-19 patients. They have been specifically engineered to reduce the risk of antibody-dependent enhancement, enhance antibody penetration to the lung and prolong the plasma half-lives for potentially more durable treatment effect. Their non-overlapping epitope binding regions provide a high degree of neutralization activity against SARS-CoV-2.

Investigational New Drug (IND) applications have been submitted for the combination therapy to the U.S. Food and Drug Administration (FDA), the China National Medical Products Administration (NMPA) and the Department of Health in Hong Kong, China. The combination of BRII-196/BRII-198 was generally safe and well tolerated in Phase 1 studies, supporting evaluation in later stage studies. In addition to the collaboration with NIAID, Brii Bio is conducting additional studies in China, evaluating the pharmacokinetics and safety of combination BRII-196/BRII-198 as well as a Phase 2 efficacy study of combination BRII-196/BRII-198 for the treatment of COVID-19.

About ACTIV-2
The ACTIV-2 trial (NCT04518410) is sponsored by NIAID, one of the institutes of the NIH, and is led by the NIAID-funded AIDS Clinical Trials Group (ACTG). ACTIV-2 is part of NIH's Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a public-private partnership program to create a coordinated research strategy that prioritizes and speeds development of the most promising treatments and vaccines.

The ACTIV-2 master protocol evaluates the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with COVID-19 under a randomized, blinded, controlled adaptive platform. Participants identified as being at high risk for progression to more severe disease were eligible for enrollment onto combination BRII-196/BRII-198 or placebo. Phase 3 of the study was designed to determine if combination BRII-196/BRII-198 prevents the composite endpoint of either hospitalization or death through study day 28. The Phase 3 trial was a continuation of the Phase 2 trial in which combination BRII-196/BRII-198 met study-defined safety and efficacy criteria.

About Brii Bio
Brii Biosciences Limited ("Brii Bio", or the "Company", stock code: 2137.HK) is a biotechnology company based in China and the United States committed to advancing therapies for significant infectious diseases, such as hepatitis B, human immunodeficiency virus (HIV) infection, multi-drug resistant (MDR) or extensive drug resistant (XDR) gram-negative infections, and other illnesses, such as the central nervous system (CNS) diseases, which have significant public health burdens in China and worldwide. For more information, visit www.briibio.com.

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