CMV pp65

[13-February-2024] Acquiring all intellectual properties relating to BRII-179 and eliminating future milestone and royalty payments to VBI, subject to achievement of certain activities Transferring manufacturing technologies of BRII-179 and PreHevbrio/PreHevbri to additional manufacturing sites and expanding footprint for global commercial supplies, subject to achievement of certain activities Acquisition of VBI-1901 APAC (minus Japan) rights, subject to achievement of certain activities, opens new opportunities in the Asia-Pacific region DURHAM, N.C. and BEIJING, Feb. 13, 2024 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio," "we," or the "Company", stock code: 2137.HK), a biotechnology company developing therapies to improve patient health and choice across diseases with high unmet needs, today announced that it has entered into agreements with VBI Vaccines, Inc. ("VBI", NASDAQ: VBIV), ensuring expansion and control of future clinical and commercial supplies of BRII-179, a late-stage clinical asset in Brii Bio's HBV functional cure portfolio. Under these agreements, Brii Bio will issue a $2.5 million promissory note to VBI initially. This will eliminate royalty and milestone payments for PreHevbri. Upon meeting specific conditions, the note will increase to $10 million, securing all of VBI's intellectual properties (IP) for BRII-179, with associated payments also eliminated. In addition, subject to certain approvals, Brii Bio and VBI will work together to transfer the manufacturing technologies of BRII-179 to a site designated by Brii Bio. Upon completion of essential activities relating to such technology transfer, subject to certain potential adjustments, Brii Bio will issue up to an additional $8 million promissory note to VBI. After satisfaction of certain conditions, Brii Bio will also take control of VBI's Rehovot-based manufacturing facilities for BRII-179 and PreHevbrio/PreHevbri for $10 million cash on or after June 30, 2024, when Brii Bio and VBI plan to enter into supply agreement under which Brii Bio will become VBI's commercial supplier for PreHevbrio and PreHevbri. Separately, subject to achievement of certain conditions by VBI, Brii Bio will secure an exclusive license to develop and commercialize VBI-1901, VBI's glioblastoma (GBM) immunotherapeutic candidate, in the Asia Pacific (APAC) region excluding Japan and issue a $5 million promissory note to VBI. VBI-1901 has received fast-track and orphan drug designations from the U.S. Food and Drug Administration (FDA) and a Phase 2b study is ongoing. "We are grateful to our VBI colleagues at the Rehovot site who despite significant challenges continued to provide uninterrupted supplies of BRII-179," said Dr. Zhi Hong, Ph.D., Chairman and Chief Executive Officer of Brii Bio. "As Brii transitions to late-stage development of HBV programs, a global manufacturing strategy becomes critically important. We look forward to working together with the biologics manufacturing experts at the Rehovot site and timely integration of our R&D and manufacturing capabilities." About BRII-179 BRII-179 (VBI-2601) is a novel recombinant protein-based HBV immunotherapeutic candidate that expresses the Pre-S1, Pre-S2, and S HBV surface antigens, and is designed to induce enhanced and broad B-cell and T-cell immunity. BRII-179 is currently being investigated in two Phase 2 clinical trials in combination with BRII-835 or PEG-IFNα as part of a potential functional cure regimen for the treatment of chronic HBV infection. Brii Bio licensed BRII-179 from VBI Vaccines, Inc. ("VBI") in December 2018, providing Brii Bio with commercial rights to BRII-179 in the licensed territories of China, Hong Kong, Macau, and Taiwan. The exclusive license for BRII-179 has been extended to worldwide markets since July 2023. In November 2023, the Center for Drug Evaluation (the "CDE") of the National Medical Products Administration (the "NMPA") granted BRII-179 Breakthrough Therapy Designation. About PreHevbri® PreHevbri® is the only 3-antigen hepatitis B vaccine, comprised of the three hepatitis B surface antigens of the hepatitis B virus – S, pre-S1, and pre-S2. It is approved for use in the United States, European Union/European Economic Area, United Kingdom, Canada, and Israel. The brand names for this vaccine are: PreHevbrio® (US/Canada), PreHevbri® (EU/EEA/UK), and Sci-B-Vac® (Israel). About VBI-1901 VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. The FDA has granted VBI-1901 Fast Track Designation and Orphan Drug Designation for the treatment of recurrent glioblastoma. These designations are intended to provide certain benefits to drug developers, including more frequent meetings with the FDA, and Accelerated Approval and Priority Review, if relevant criteria are met, among other benefits. About Brii Bio Brii Biosciences Limited ("Brii Bio", stock code: 2137.HK) is a commercial stage biotechnology company developing therapies to address major public health challenges where patients experience high unmet medical needs, limited choice and significant social stigmas. With a focus on infectious and central nervous system diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs against hepatitis B viral infection (HBV), postpartum depression (PPD), and major depressive disorder (MDD). The Company is led by a visionary and experienced leadership team and has operations in key biotech hubs, including Raleigh-Durham, the San Francisco Bay Area, Beijing and Shanghai. For more information, visit . Company Codes: HongKong:2137, OTC-PINK:BRIBY

Multi-center, randomized, controlled, open-label study to enroll up to 60 patients with first recurrent GBM FDA has granted both Fast Track Designation and Orphan Drug Designation to VBI-1901 in the recurrent setting, following encouraging Phase 1/2a study results Interim data analysis expected mid-year 2024, subject to speed of enrollment CAMBRIDGE, Mass.--(BUSINESS WIRE)--VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, today announced the first patients have been dosed in the randomized, controlled Phase 2b study of VBI’s cancer vaccine immunotherapeutic candidate, VBI-1901, in patients with first recurrent glioblastoma (rGBM). The study will assess the safety, tolerability, tumor response rates, and survival following treatment with VBI-1901, as a monotherapy, at 10 leading neuro-oncology centers across the United States. Andrew B. Lassman, M.D., Chief of Neuro-Oncology at Columbia University Vagelos College of Physicians and Surgeons, Associate Director for Clinical Trials at the NCI-designated Herbert Irving Comprehensive Cancer Center, and principal investigator of the study, commented, “Based on the pre-clinical and clinical data seen in earlier stages of this study, I look forward to demonstrating the potential value of VBI-1901, relative to current standard of care, in my patients in this next phase of clinical development, with the hope to provide meaningful benefit against a brain tumor that is notoriously aggressive with a high mortality rate.” Francisco Diaz-Mitoma, M.D., Ph.D., VBI’s Chief Medical Officer, commented, “Median overall survival in the recurrent GBM setting is just eight months, making any advancement in patient care critical. As we work to offer new hope to the patients, family members, and caretakers who are battling this devastating and historically treatment-resistant brain tumor, we are excited to kick-off this next phase of development for VBI-1901.” In the Phase 1/2a study of VBI-1901 in the rGBM setting, extensive biomarker panels suggested normal baseline CD4+/CD8+ T-cell ratios, which is a measure of immunological fitness, along with boosting of cytomegalovirus (CMV) gB specific antibody responses were correlated with tumor and clinical responses. These learnings have been incorporated into patient enrollment eligibility criteria for the Phase 2b study to help identify patient populations that may be more likely to respond to treatment with VBI-1901. Phase 1/2a Study Data Highlights – VBI-1901 10µg + GM-CSF Study Arms (n=16) 44% disease control rate achieved (n=7/16) – disease control rate is defined as stable disease (SD) + partial tumor response (PR) + complete tumor response (CR) 2 partial responses (PR) were observed – 1 patient was on treatment for more than 28 months (2.33 years), surviving at least 40 months (3.33 years) as of August 1, 2023, with a maximum tumor reduction of 93% relative to baseline 5 additional patients demonstrated stable disease (SD) for a sustained period of time All patients with a tumor response (PR or SD) (n=7/16) reached a minimum survival of 12 months Median overall survival (mOS) was 12.9 months, comparing favorably to 8-month mOS for monotherapy standard-of-care2 Phase 2b Study Design Multi-center, randomized, controlled, open-label study in up to 60 patients with first recurrent GBM Patients will be randomized in a 1:1 ratio across two study arms: Intradermal VBI-1901 + GM-CSF: 10 µg dose every 4 weeks until clinical disease progression Monotherapy standard-of-care: either intravenous carmustine or oral lomustine, every 6 weeks until disease progression or intolerable toxicity Endpoints include: Safety and tolerability Overall survival (OS) – median and overall Tumor response rate (TRR) Progression-free survival (PFS) Immunologic responses Reduction in corticosteroid use relative to baseline Change in quality of life compared to baseline The U.S. Food and Drug Administration (FDA) has considered demonstration of a statistically significant improvement in overall survival relative to a randomized control arm to be clinically significant and has recognized this as criteria to support the approval of new oncology drugs.1 For more information about the Phase 2b study, visit clinicaltrials.gov and reference trial identifier: NCT03382977. About GBM and VBI-1901 Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 14,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and has a high mortality. VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI’s enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. The FDA has granted VBI-1901 Fast Track Designation and Orphan Drug Designation for the treatment of recurrent glioblastoma. These designations are intended to provide certain benefits to drug developers, including more frequent meetings with the FDA, and Accelerated Approval and Priority Review, if relevant criteria are met, among other benefits. About VBI Vaccines Inc. VBI Vaccines Inc. (“VBI”) is a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease. Through its innovative approach to virus-like particles (“VLPs”), including a proprietary enveloped VLP (“eVLP”) platform technology, VBI develops vaccine candidates that mimic the natural presentation of viruses, designed to elicit the innate power of the human immune system. VBI is committed to targeting and overcoming significant infectious diseases, including hepatitis B, coronaviruses, and cytomegalovirus (CMV), as well as aggressive cancers including glioblastoma (GBM). VBI is headquartered in Cambridge, Massachusetts, with research operations in Ottawa, Canada, and a research and manufacturing site in Rehovot, Israel. Website Home: News and Resources: Investors: References Oncology Center of Excellence, Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration. Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics; Guidance for Industry. FDA.gov. December, 2018 Taal W, Oosterkamp HM, Walenkamp AME, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomized controlled phase 2 trial. Lancet Oncol. 2014; 15: 943-953 Cautionary Statement on Forward-looking Information Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). The Company cautions that such forward-looking statements involve risks and uncertainties that may materially affect the Company’s results of operations. Such forward-looking statements are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including but not limited to, the impact of general economic, industry or political conditions in the United States or internationally; the impact of the COVID-19 pandemic and the continuing effects of the COVID-19 pandemic on our clinical studies, manufacturing, business plan, and the global economy; the ability to successfully manufacture and commercialize PreHevbrio/PreHevbri; the ability to establish that potential products are efficacious or safe in preclinical or clinical trials; the ability to establish or maintain collaborations on the development of pipeline candidates and the commercialization of PreHevbrio/PreHevbri; the ability to obtain appropriate or necessary regulatory approvals to market potential products; the ability to obtain future funding for developmental products and working capital and to obtain such funding on commercially reasonable terms; the Company’s ability to manufacture product candidates on a commercial scale or in collaborations with third parties; changes in the size and nature of competitors; the ability to retain key executives and scientists; and the ability to secure and enforce legal rights related to the Company’s products. A discussion of these and other factors, including risks and uncertainties with respect to the Company, is set forth in the Company’s filings with the SEC and the Canadian securities authorities, including its Annual Report on Form 10-K filed with the SEC on March 13, 2023, and filed with the Canadian security authorities at sedar.com on March 13, 2023, as may be supplemented or amended by the Company’s Quarterly Reports on Form 10-Q. Given these risks, uncertainties and factors, you are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement. All such forward-looking statements made herein are based on our current expectations and we undertake no duty or obligation to update or revise any forward-looking statements for any reason, except as required by law.

-Top-Line Data Expected in the Second Quarter of 2025- ROCKVILLE, Md.--(BUSINESS WIRE)-- Immunomic Therapeutics Inc., a privately held, clinical-stage biotechnology company pioneering the study of nucleic acid immunotherapy platforms, today announced dosing of the first patient in its Phase 1 clinical trial evaluating ITI-1001, a plasmid DNA (pDNA) vaccine, for the treatment of Glioblastoma Multiforme (GBM), a rare but aggressive form of brain cancer. The study is being conducted at the Dana-Farber Cancer Institute in Boston, Massachusetts and is being led by Dr. David Reardon, Clinical Director, Center for Neuro-Oncology. "Dosing of the first patient in the Phase 1 clinical trial of ITI-1001 in patients with GBM is a significant clinical development milestone for Immunomic, representing the first time this pDNA vaccine is being administered in humans,” stated Dr. Teri Heiland, Chief Scientific Officer of Immunomic Therapeutics. "We are eager to evaluate the safety and preliminary efficacy in this patient population, who have only limited treatment options for this devastating disease and expect to read out top-line data in the second quarter of 2025.” The single-center, open label, First-In-Human Phase 1 clinical trial is designed to evaluate the safety, tolerability, immunogenicity and preliminary efficacy of 8 mg of ITI-1001 in newly diagnosed GBM patients having unmethylated MGMT promoter mutations. For more information on the Phase 1 trial of ITI-1001 in GBM, please visit , NCT05698199 About ITI-1001 ITI-1001 is an investigational plasmid DNA vaccine therapy that leverages Immunomic’s proprietary UNITE® platform to treat patients with newly diagnosed GBM. ITI-1001 is designed to target the pp65, IE-1 and gB viral antigens of Cytomegalovirus (CMV) which are expressed in GBM, but not in normal brain cells. About UNITE® ITI’s UNITE platform leverages the ability to engineer chimeric proteins, directing antigen presenting cells to present antigens to the immune system through a targeted pathway and driving a robust immune response. UNITE vaccines are distinct in that they combine two components: nucleic acid constructs that encode a specific antigen and an endogenous Lysosomal Associated Membrane Protein (LAMP-1) sequence. The UNITE platform harnesses LAMP-1 as a means of presenting the vaccine target to the immune system, resulting in antibody production, inflammatory cytokine release, and establishing critical immunological memory, something that other vaccine approaches commonly lack. This approach could put UNITE technology at the crossroads of immunotherapies in multiple indications, including cancer, human allergy, animal health, and infectious disease. Preclinical data is currently being developed to explore whether LAMP-1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses in tumor types that otherwise do not provoke an immune response. About Immunomic Therapeutics, Inc. Immunomic Therapeutics, Inc. (ITI) is a privately-held, clinical-stage biotechnology company pioneering the development of vaccines through its proprietary technology platform UNITE®, which is designed to utilize the body’s natural biochemistry to develop vaccines that generate broad immune responses. ITI is primarily focused on applying the UNITE platform to oncology indications, where it could potentially have broad applications, including development of antigen-derived antibodies as biologics in a number of cancers. The company has built a pipeline leveraging UNITE with programs in oncology, animal health, infectious disease, and allergy. ITI maintains its headquarters in Rockville, Maryland. For more information, please visit . Forward-Looking Statements This press release includes statements relating to the current progress of the ITI-1001 program for Glioblastoma Multiforme (GBM) and ITI’s technology platform and development efforts. These statements and other statements regarding our future plans and goals constitute "forward-looking statements" and are intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties that are often difficult to predict, are beyond our control and which may cause results to differ materially from expectations, including, without limitation, whether we are able to capitalize on the ITI-1001 program, achieve positive results in our clinical trials to develop an immunotherapy that is successful in treating GBM, and be able to advance the utilization of our UNITE® platform. You are cautioned not to place undue reliance on these forward-looking statements, which are based on our expectations as of the date of this press release and speak only as of the origination date of this press release. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.