Brii Biosciences Provides Corporate Update and Reports Full Year 2021 Financial Results

– Advancing key programs in HBV, CNS, and HIV –

– Received first BLA approval for COVID-19 Treatment in China and added to China's latest COVID-19 Diagnosis and Treatment Guidelines–

– Multiple clinical value drivers expected across the portfolio in 2022 and beyond –

– Cash, bank balances, and potential revenue to support operations through 2025–

– Brii Bio to host conference call today at 8:00 PM HKT / 8:00 AM ET –

DURHAM, N.C. and BEIJING, March 23, 2022 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio", "we" 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, today announced a corporate update and reported financial results for the full year ended December 31, 2021.

"2021 was a year of strong momentum for Brii Bio. We successfully completed our IPO in the Hong Kong Stock Exchange and became the first company in Greater China to introduce a monoclonal antibody combination treatment for COVID-19, marking our first BLA approval," said Zhi Hong, Ph.D., Chairman and CEO of Brii Bio. "Moving forward in 2022, we will continue to advance our key programs for a functional HBV cure, postpartum depression treatment and prevention, and long-acting HIV treatment while commercializing our COVID-19 antibody therapy. Each of our key programs has the potential to fundamentally change how patients will be cared for, accelerating our mission to tackle the world's biggest public health challenges."

"Our pipeline spanning all phases of clinical development includes more than 10 innovative product candidates that focus on significant infectious diseases and mental illnesses. To build further on this robust clinical pipeline, we plan to add additional therapeutic candidates in 2022 through internal discovery and partnerships."

2021 and Recent Pipeline Highlights and Upcoming Milestones

Hepatitis B Virus (HBV) Functional Cure Program

We are progressing multiple combination studies led by our team in China or our partner Vir Biotechnology.

BRII-179 (VBI-2601) and BRII-835 (VIR-2218) (therapeutic vaccine and siRNA) Combination

• The safety and antiviral activity findings of the Phase 2 BRII-835 (VIR-2218) monotherapy study conducted in mainland China will be presented during the 2022 Asian Pacific Association for the Study of the Liver (APASL) conference in March.
• Phase 2 BRII-179 (VBI-2601)/BRII-835 (VIR-2218) MRCT combination study is fully enrolled with interim topline clinical data expected by the end of 2022.
• If positive results are achieved for the combination study, we plan to submit an Investigational New Drug Application (IND) application to China Center for Drug Evaluation (CDE) to initiate a pivotal study in 2023.

BRII-179 (VBI-2601) and PEG-IFN-α Combination

• Data announced from completed Phase 1b/2a study demonstrated the ability of BRII-179 (VBI-2601) to induce both B cell (antibody) and T cell responses in chronically infected HBV patients, with a well-tolerated safety profile.
• A two-part Phase 2a/2b combination study with BRII-179 (VBI-2601) in HBV patients receiving pegylated interferon alfa ("PEG-IFN-α") and NRTI treatment is recruiting patients under an IND from the China National Medical Products Administration (NMPA).
• Patient enrollment for part 1 (Phase 2a of approximately 120 patients) of the study is expected to complete in the second half of 2022, with interim topline results expected in the first half of 2023.

VIR-2218 (BRII-835) and PEG-IFN-α Combination

• Refer to Vir's Annual Report on Form 10-K filed with the US Securities Exchange Commission on February 28, 2022: Vir presented new data evaluating the potential for VIR-2218 (BRII-835) in combination with PEG-IFN-α to achieve a functional cure for HBV in November 2021.
• Additional data from the Phase 2 trial of BRII-835 (VIR-2218) in combination with PEG-IFN-α are expected in the first half of 2022.

VIR-2218 (BRII-835) and VIR-3434 (siRNA and neutralizing monoclonal antibody) Combination

• Refer to Vir's Annual Report on Form 10-K filed with the US Securities Exchange Commission on February 28, 2022: Initial data from the first cohorts of Phase 2 MARCH (Monoclonal Antibody siRNA Combination against Hepatitis B) trial of VIR-2218 (BRII-835) in combination with VIR-3434, are expected in the first half of 2022. As some of the clinical trial sites are in Ukraine and Moldova, Vir is monitoring the situation to determine any impact resulting from the current conflict in this region.

COVID-19 Program

• We completed the ACTIV-2 Phase 3 study in August 2021, presenting positive primary endpoint results that the novel amubarvimab/romlusevimab neutralizing antibody combination therapy has demonstrated a statistically significant 80% reduction of hospitalization and death through 28 days in the treatment arm (0) relative to placebo (9), and improved safety outcome over placebo in non-hospitalized COVID-19 patients at high risk of clinical progression to severe disease.
• Amubarvimab/romlusevimab combination therapy (formerly BRII-196 and BRII-198 combination therapy) was granted first BLA approval for the treatment of COVID-19 in China in December 2021. Our combination therapy is approved for treating adults and certain pediatric patients with mild- and normal-type COVID-19 who are at high risk of progression to severe disease. The indication of pediatric patients (age 12-17 weighing at least 40 kg) is under a conditional approval.
• In January 2022, data from in vitro pseudovirus demonstrated that our amubarvimab/romlusevimab combination therapy retained neutralizing activity against Omicron SARS-COV-2 variant, adding to its proved neutralizing activity against other variants of concern, such as Delta and Delta Plus.
• We believe that our antibody therapy remains active against the Omicron variant given our high dose and that IV dosing provides antibody exposure in much excess.
• In March 2022, the National Health Commission of China added the amubarvimab/romlusevimab combination to its COVID-19 Diagnosis and Treatment Guidelines (9th Edition) for the treatment of COVID-19.
• Our US Emergency Use Authorization (EUA) application remains under review by US FDA and is pending on satisfactory completion of FDA inspection of the manufacturing sites at our contract development and manufacturing company (CDMO). Given the unique nature and mechanism of EUA we cannot predict when and what decision US FDA will make but we are working closely with our CDMO to respond to any regulatory inquiry. We are in active discussion with various governments regarding stockpiling and commercialization of our antibody therapy.

HIV Program

BRII-778

• We completed the Phase 1 single ascending dose and multiple ascending dose (SAD/MAD) study for BRII-778 in the US and selected one of the formulations to progress into further clinical evaluation.
• Phase 1 SAD/MAD data will be published at a future scientific conference in the second half of 2022.

BRII-732

• Our Phase 1 SAD/MAD study for BRII-732 is completed and BRII-732 is well tolerated without any CD4 cell count decrease observed. Data will be presented at a future scientific conference in the second half of 2022.
• In December 2021, the US FDA placed a temporarily hold on all islatravir-based clinical trials sponsored by Merck & Co., Inc. due to a decline in CD4 cell count in some subjects.
• BRII-732 is a prodrug of islatravir and was also placed on clinical hold by the US FDA out of abundance of caution and pending additional safety evaluations. The last multiple ascending dose cohort had not yet been dosed and is no longer needed.
• Based on published data and information disclosed by Merck & Co., Inc. in December 2021, the safety finding of CD4 cell count decrease is both dose and time dependent. We believe a safe dose of BRII-732 may be selected based on our phase 1 study and will be efficacious for patients. We plan to meet with the US FDA to discuss our plan to further investigate and develop BRII-732. Our aim is to lift the clinical hold in the second half of 2022 and proceed with development of our once-weekly oral combination of BRII-732 and BRII-778.

MDR/XDR Gram-negative Infections Program

BRII-636 (OMNIvance^®)

• In early 2022, Qpex announced that BRII-636 (INN: xeruborbactam) received Qualified Infectious Disease Product (QIDP) designation by the US FDA.
• Pharmacokinetic results from the single dose studies of xeruborbactam will be presented at the ECCMID meeting in April 2022. The Phase 1 topline data of the BRII-636 Phase 1 clinical study is expected to be presented in the second half of 2022 at a scientific conference.
• We will submit an IND application to China's NMPA in due course, in line with the goal of participating in Qpex's global Phase 3 study.

BRII-672 (ORAvance™)

• In early 2022, Qpex announced that BRII-672 received QIDP designation by the US FDA.
• The Phase 1 topline data are expected to be presented at a scientific conference in the second half of 2023.
• We will submit an IND application with China's NMPA in due course, in line with the goal of participating in Qpex's global Phase 3 study.

BRII-693 (QPX-9003)

• In early 2022, Qpex announced that BRII-693 received QIDP designation by the US FDA.
• Pharmacokinetic results from the single dose studies of QPX9003 will be presented at the ECCMID meeting in April 2022. The Phase 1 topline data are expected to be presented at a scientific conference in the second half of 2022.
• We will submit an IND application with China's NMPA in due course, in line with the goal of participating in Qpex's global Phase 3 study.

MDR/XDR TB Mycobacteria (TB) and Non-tuberculosis Mycobacteria (NTM) Program

BRII-658 (Epetraborole)

• In February 2022, our partner AN2 Therapeutics (AN2) reported data from a Phase 1b dose-ranging study of oral epetraborole where it demonstrated a predictable PK profile that supports continued development of oral, once-daily dosing. AN2 is developing epetraborole as a once-daily, orally administered treatment for patients with chronic non-tuberculous mycobacterial (NTM) lung disease, with an initial focus on treatment-refractory Mycobacterium avium complex (MAC) lung disease.
• AN2 plans to initiate patient enrollment in a pivotal Phase 2/3 clinical trial of epetraborole in treatment-refractory MAC lung disease in the first half of 2022. The US FDA granted epetraborole Fast Track and QIDP designations for treatment-refractory MAC lung disease, and orphan drug designation for the treatment of infections caused by NTM.

Central Nervous System Disease (CNS) Program

BRII-296

• Our Phase 1 study for BRII-296 is ongoing in the US and plan to complete in the second half of 2022.
• Based on the initial human PK data, we are planning to discuss with the US FDA and investigate in patients with severe postpartum depression (PPD) or at high risk of developing PPD in 2022. Currently there is no approved therapy to prevent PPD, we believe BRII-296 has the potential to change the paradigm of PPD treatment and prevention.
• Phase 1 results will be shared at a scientific conference in the second half of 2022.

BRII-297

• BRII-297 is a new program targeting various depression disorders. We held a pre-IND meeting with the US FDA in 2021 and determined the regulatory strategy to bring it to first time in human study and beyond.
• We plan to submit an IND to US FDA in the second quarter of 2022.

Corporate Developments

• On July 13, 2021, we successfully completed our listing on the Main Board of the Stock Exchange of Hong Kong Limited. We issued 111,580,000 shares globally at a final offer price of HK$22.25 per share, raising approximately HK$2.788 billion (approximately RMB2.325 billion) in gross proceeds with a partial exercise of the over-allotment option in the amount of 13,753,000 shares.
• In the fourth quarter of 2021, we were added to the Hong Kong Stock Connect exchange and included in eight associated indices, significantly raising our profile and trading liquidity.
• We have been broadly recognized by industry, authorities, and corporate channels for our accomplishments in advancing therapeutics from discovery through clinical development to commercialization, as well as our achievements as a newly listed public company. In acknowledgment of our achievements in 2021, we were the proud recipients of over ten awards.
• As of December 31, 2021, we had 113 total employees globally with 72 employees in China and 41 employees in the US. More than half of our employees hold advanced degrees such as MDs or PhDs. Investing in our people and talented pool of R&D professionals will be one of our continued areas of focus in 2022, with a goal of recruiting additional key leaders as our business grows.

Full Year 2021 Financial Results

• Other income was RMB99.0 million for the year ended December 31, 2021, representing an increase of RMB14.4 million or 17.0%, compared with RMB84.6 million for the year ended December 31, 2020. The increase was mainly attributable to the increased income recognized from People's Republic of China government grants.
• Research and development expenses were RMB494.6 million for the year ended December 31, 2021, representing a decrease of RMB381.2 million or 43.5%, compared with RMB875.8 million for the year ended December 31, 2020. The decrease was primarily due to the decrease in third party contracting costs relating to COVID-19 programs.
• Administrative expenses were RMB208.4 million for the year ended December 31, 2021, representing an increase of RMB105.0 million or 101.6%, compared with RMB103.4 million for the year ended December 31, 2020. The increase was primarily attributable to the increase in employee headcount.
• Total comprehensive expense for the year ended December 31, 2021, was RMB4,249.0 million, representing an increase of RMB3,075.9 million or 262.2%, compared with RMB1,173.1 million for the year ended December 31, 2020. The increase was primarily attributable to the increase in fair value loss on financial liabilities at fair value through profit or loss.

Conference Call Information

A live conference call will be hosted on March 23, 2022, at 8:00 PM Hong Kong time (March 23, 2022 at 8:00 AM U.S. Eastern Time). Participants must register in advance of the conference call. Details are as follows:

Registration Link: http://apac.directeventreg.com/registration/event/2843869

All participants must use the link provided above to complete the online registration process in advance of the conference call. Upon registering, each participant will receive an email with important details for this call such as the call date and time, as well as a full list of participant dial-in numbers to join the call. Also included is a unique Registrant ID. This ID is to be kept confidential and not shared with other participants.

Additionally, a live and archived webcast of the conference call will be available shortly after the call and can be accessed by visiting the Company's website at www.briibio.com. at Investor Relations part.

About our Programs

HBV (licensed from VBI Vaccines Inc. and Vir Biotechnology, Inc.)

To treat HBV, we are currently developing BRII-179 (VBI-2601), an HBV-specific B cell and T cell immunotherapeutic vaccine candidate, and BRII-835 (VIR-2218), an investigational HBV-targeting siRNA, that has the potential to stimulate an effective immune response and have direct antiviral activity against HBV. We hold exclusive rights to develop and commercialize BRII-179 (VBI-2601) and BRII-835 (VIR-2218) in Greater China. As a potential HBV functional cure regimen, we are focusing on developing BRII-179 (VBI-2601) and BRII-835 (VIR-2218) as a combination therapy.

BRII-179 (VBI-2601) is a novel recombinant protein-based HBV immunotherapeutic candidate that builds upon the 3-antigen conformation of VBI's prophylactic HBV vaccine candidate, with a Th-1 enhancing adjuvant to induce both B-cell and T-cell immune responses.

BRII-835 (VIR-2218) is an investigational, subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and have direct antiviral activity against HBV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index.

COVID-19 (discovered in collaboration with Tsinghua University and Third People's Hospital of Shenzhen through our subsidiary, TSB Therapeutics Ltd (Beijing) Co. Limited) Amubarvimab and romlusevimab 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 and prolong the plasma half-lives for potentially more durable treatment effect.

Approved by the China's NMPA in December 2021, our amubarvimab/romlusevimab cocktail therapy is approved to be administered by intravenous infusion in two sequential doses for the treatment in adults and pediatric patients (age 12-17 weighing at least 40 kg) of mild- and normal-type COVID-19 at high risk for progression to severe disease, including hospitalization or death. The indication of pediatric patients (age 12-17 weighing at least 40 kg) is under a conditional approval. In March 2022, the National Health Commission of China included the amubarvimab/romlusevimab combination in its COVID-19 Diagnosis and Treatment Guidelines (9th Edition) for the treatment of COVID-19.

HIV (internally discovered)
We are developing BRII-778 and BRII-732 as a once-weekly single-tablet combination therapy that will offer a more discreet, convenient, and non-invasive maintenance therapy for HIV patients.

BRII-778 is an extended-release formulation of an FDA-approved NNRTI, Edurant (rilpivirine hydrochloride). Edurant, an instant-release formulation of rilpivirine, has exhibited antiviral activity against a broad panel of HIV's most common strains. BRII-778, like all NNRTIs, binds to the NNRTI binding site, a flexible allosteric pocket located at a site adjacent to the DNA polymerizing processing site, resulting in conformational changes, and altered function of reverse transcriptase.

BRII-732 is a new chemical entity (NCE) that is metabolized upon oral administration into EFdA or islatravir. EFdA functions not only as a potent chain-terminator like other NRTIs, but also as a potent HIV reverse transcriptase translocation inhibitor (NRTTI), with high binding affinity to the active site of RT, that inhibits HIV reverse transcriptase by blocking translocation of nascently synthesized strand[s] for the next nucleotide incorporation.

Postpartum Depression (PPD)/Major Depressive Disorder (MDD)/Other depressive disorders (internally discovered)
We are developing BRII-296 and BRII-297 to address the challenges associated with current treatments for PPD, MDD, and other depressive disorders. We are doing this by leveraging insight gained from, and applied drug formulation know-how utilized in developing long-acting therapies, where drug administration convenience and patient compliance are critical to potential treatment success.

BRII-296 is our novel and single treatment option for the treatment and prevention of PPD. It acts as a gamma-aminobutyric acid A (GABAa) receptor positive allosteric modulator. BRII-296 is in clinical Phase 1 study.

BRII-297 is a new chemical entity discovered internally. BRII-297 is under development for treatment of various depression disorders.

Multidrug- and Extensively Drug-Resistant (MDR/XDR) Gram-negative Infections (licensed from Qpex):
We are developing our MDR/XDR therapies in collaboration with our partner Qpex as part of their global development plan. We retain responsibility for the development and regulatory activities in Greater China, while Qpex is responsible for all development and regulatory activities outside Greater China. Qpex is progressing BRII-636, BRII-672, and BRII-693 in parallel with a goal of moving each to global Phase 3 studies when Brii is expected to join with China as part of the global studies. All BRII-636, BRII-672, and BRII-693 candidates obtained QIDP designation from the US FDA, which may receive incentives in the future. We are collaborating with Qpex to progress OMNIvance^® (BRII-636, a broad spectrum BLI, in combination with an IV β-lactam antibiotic), ORAvance^® (BRII-672, a broad spectrum oral BLI in combination with an oral β -lactam antibiotic) as an oral β-lactam antibiotic, respectively, and BRII-693 (a next generation IV polymyxin antibiotic) for the treatment of bacterial infections for which there are critical needs for new antibiotics.

BRII-636 (BLI of OMNIvance^®) is a novel cyclic boronic acid derived broad-spectrum inhibitor designed to cover all major SBLs and MBLs to restore the bacterial activity of multiple carbapenems and cephalosporins. It is administered by IV to deliver BRII-636 into the bloodstream.

BRII-672 (BLI of ORAvance^®) BRII-672 is a prodrug of BRII-636 that can be administered orally to deliver BRII-636 into the bloodstream. These agents were discovered by our partner Qpex as part of their expertise in BLIs, using the boron atom as a part of pharmacophore.

BRII-693 (QPX-9003) is a next generation, synthetic polymyxin, which has emerged as a development candidate based on a combination of increased in vitro and in vivo potency, and an improved safety profile. BRII-693 has the potential to represent a significant advancement in the polymyxin class of hospital (IV) antibiotics.

MDR/XDR Tuberculosis Mycobacteria (TB) and Non-Tuberculosis Mycobacteria (NTM) Program (licensed from AN2)
We are developing TB and NTM Program with AN2 Therapeutics. Epetraborole (BRII-658) is a novel antibiotic for MDR/XDR TB and NTM that has potent and broad-spectrum activity against mycobacteria and other bacterial pathogens. AN2 is initiating global Phase 2/3 clinical trials of epetraborole (BRII-658) for treating NTM, with an initial focus on treatment-refractory Mycobacterium avium complex (MAC) lung disease. We obtain a license to develop, manufacture, and commercialize epetraborole (BRII-658) in Greater China.

BRII-658 (Epetraborole) is a novel mechanism of action antibiotic. It is a boron-containing, orally available, small molecule inhibitor of mycobacterial leucyl-tRNA synthetase, or LeuRS, an enzyme that catalyzes the attachment of leucine to transfer RNA, or tRNA, molecules, an essential step in protein synthesis.

This press release contains references to third-party information. Such information is not deemed to be incorporated by reference in this press release. Brii disclaims responsibility for such third-party information.

About Brii Bio

Brii Biosciences Limited ("Brii Bio," or the "Company," stock code: 2137.HK) is a biotechnology company based in China and the U.S. and is committed to advancing therapies for significant infectious diseases, such as hepatitis B, COVID-19, 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.

FORWARD LOOKING STATEMENT

The information communicated in this press release contains certain statements that are or may be forward looking. These statements typically contain words such as "will", "expects", "believes", "plans" and "anticipates" and words of similar import. By their nature, forward looking statements involve risk and uncertainty because they relate to events and depend on circumstances that will occur in the future. There may be additional material risks that are currently not considered to be material or of which the Company are unaware. These forward-looking statements are not a guarantee of future performance. Against the background of these uncertainties, readers should not rely on these forward-looking statements. The Company assumes no responsibility to update forward-looking statements or to adapt them to future events or developments.