Gam-COVID-Vac

SHANGHAI, March 30, 2023 /PRNewswire/ -- Everest Medicines (HKEX 1952.HK, "Everest", or the "Company"), a biopharmaceutical company focused on developing, manufacturing and commercializing transformative pharmaceutical products and vaccines, today announced its financial results for the full year ended December 31, 2022, along with a corporate update. "Despite a challenging external capital environment in 2022, we made solid advancements in our key therapeutic areas toward becoming a fully integrated biopharmaceutical company," said Rogers Yongqing Luo, CEO of Everest Medicines. "We received NDA approval for Xerava in China this month and successfully filed for New Drug Application for Nefecon in mainland China with Breakthrough Therapy Designation and Priority Review status, while also receiving fast-track review designations in other Asian territories for Nefecon. We reported positive topline results from multiple clinical studies and achieved the first pre-clinical proof-of-concept milestone from our self-discovery programs. Moreover, our state-of-the-art mRNA vaccine manufacturing facility began production and successfully completed trial runs. The company's loss in 2022 was reduced by RMB 760 million compared with the previous year. We head into 2023 with a strong balance sheet of US$432 million, along with a clear new strategy for the future." "2023 is set to be an exciting year for Everest, as the commercialization of our first product will propel the Company from a clinical-stage biotech to a commercial-stage biopharmaceutical company. We will establish a highly efficient commercial team to bring important novel treatments such as Xerava and Nefecon to Chinese patients as soon as possible. We also strive to make significant progress in clinical and regulatory development, internal R&D and business development across our key therapeutic areas of renal diseases and infectious diseases, as well as to our mRNA platform. We anticipate at least three more drug candidates to receive NDA approval in China over the next two years, which will bring very promising commercial prospects," said Luo. Recent Product Highlights and Anticipated Milestones INFECTIOUS DISEASE PORTFOLIO Xerava (Eravacycline), is a novel, fully synthetic fluorocycline intravenous antibiotic for the treatment of infections caused by susceptible gram-positive, gram-negative and anaerobic pathogens including those multidrug resistant ("MDR") isolates. 2022: ⎯ In August, the Company announced that the Taiwan Food and Drug Administration had accepted its submission of an NDA for Xerava (eravacycline) for the treatment of complicated intra-abdominal infections (cIAI). In addition, the Company entered into an exclusive partnership agreement with TTY for the commercialization of Xerava in Taiwan. ⎯ In October, the Company announced that the Department of Health of the Hong Kong Special Administrative Region, China, approved an NDA for Xerava for the treatment of cIAI in adult patients in Hong Kong. 2023: ⎯ In March, the Company announced that NMPA of China approved its NDA for Xerava for the treatment of cIAI in adult patients. ⎯ We expect NDA approval of eravacycline for the treatment of cIAI in Taiwan region in 2023. Taniborbactam, is a beta-lactamase inhibitor ("BLI") that, in combination with cefepime, may offer a potential treatment option for patients with serious bacterial infections caused by difficult-to-treat resistant gram-negative bacteria, most notably carbapenem- resistant Enterobacterales ("CRE") and carbapenem-resistant Pseudomonas aeruginosa ("CRPA"), particularly for those resistance caused by metallo beta-Lactamases. - In March 2022, our licensing partner, Venatorx Pharmaceuticals ("Venatorx"), reported positive results from its pivotal phase 3 study, CERTAIN-1 (Cefepime Rescue with taniborbactam in cUTI), evaluating cefepime-taniborbactam, an investigational new drug, versus meropenem as a potential treatment for hospitalized adult patients with complicated urinary tract infections (cUTI), including acute pyelonephritis. - We expect to file NDA for taniborbactam for the treatment of cUTI in China in 2023. EVER206 (also known as SPR206) is a potentially best-in-class, novel polymyxin derivative designed to reduce toxicity, especially nephrotoxicity, compared to the levels observed clinically with polymyxin B and colistin. ⎯ In January 2023, the Company announced topline results from a China phase 1 study on healthy subjects demonstrating that EVER206 is well-tolerated with no evidence of acute kidney injury and no new safety signals on healthy subjects with dose ranges applied in the study. The pharmacokinetics of healthy subjects in China were comparable to the results of the overseas phase I study (SPR206-101) and the safety profile was also similar to the results from the overseas Phase I trial, supporting Everest's plans to initiate next-phase clinical development in China soon. ⎯ We expect to initiate the phase 3 trial of EVER206 in 2023. RENAL PORTFOLIO Nefecon, our anchor drug candidate in the renal therapeutic area, is a novel oral formulation of budesonide in development for the treatment of primary IgAN. 2022: ⎯ In April, the Company announced the findings of reduction in proteinuria and stabilization of estimated glomerular filtration rate ("eGFR") in a Chinese subpopulation after nine months of treatment with Nefecon are in line with topline results from Part A of the pivotal global phase 3 clinical trial NefIgArd, which were reported in November 2020 by Calliditas. ⎯ In July, our partner Calliditas was granted conditional marketing authorization for Kinpeygo® (brand name of Nefecon in Europe) by the European Commission for the treatment of primary IgAN in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio (UPCR) ≥ 1.5 g/gram. ⎯ In November, the Company received an acceptance from the China NMPA for its NDA of Nefecon for the treatment of primary IgAN in adults at risk of rapid disease progression. ⎯ In November, the Company announced the Taiwan Food and Drug Administration granted Accelerated Approval Designation to Nefecon and the MFDS in South Korea granted Orphan Drug Designation to Nefecon. 2023: ⎯ In Jan., CDE of the China NMPA granted Priority Review for the NDA of Nefecon. ⎯ In February, South Korea's MFDS granted Global Innovative product on Fast Track ("GIFT") designation to Nefecon for the treatment of primary IgAN. Nefecon is the second product and the first non-oncology product included in MFDS's GIFT program. Inclusion of the GIFT program is expected to accelerate regulatory review time by 25% and allow for rolling review. ⎯ In March, our partner Calliditas reported positive topline results from Phase 3 NefIgArd Trial evaluating Nefecon in IgAN. The trial met its primary endpoint with Nefecon demonstrating a highly statistically significant benefit over placebo (p value <0.0001) in eGFR over the two-year period of 9-months of treatment with Nefecon or placebo and 15-months of follow-up off drug. ⎯ We expect to receive NDA approval for Nefecon for the treatment of primary IgAN in mainland China and Singapore in 2023. ⎯ We expect to file NDA of Nefecon for the treatment of IgAN in South Korea, Hong Kong and Taiwan region in 2023. EVER001 is the next-generation covalent reversible Bruton's tyrosine kinase (BTK) inhibitor in development globally for the treatment of renal diseases. ⎯ In September 2022, the Company announced that the CDE has approved the IND application for a phase 1b study of EVER001, in development for the treatment of glomerular diseases. mRNA PLATFORM PTX-COVID19-B, a potentially best-in-class lipid nanoparticle-formulated mRNA COVID-19 vaccine with strong immunogenicity and benign tolerability profiles. ⎯ In October 2022, our partner Providence reported positive topline data from a phase 2 study evaluating the safety, tolerability and immunogenicity of its mRNA COVID-19 vaccine candidate, PTX-COVID19-B. PTX- COVID19-B demonstrated non-inferiority compared to Comirnaty®, Pfizer's and BioNTech's U.S. Food and Drug Administration ("FDA") - approved mRNA vaccine, with respect to the geometric mean titer ratio of neutralizing antibodies observed two weeks after the second of two intramuscular injections. Additionally, PTX-COVID19-B was generally well-tolerated, with a safety and tolerability profile similar to Comirnaty®. This phase 2 study provides important clinical validation of our mRNA technology platform. EVER-COVID19-M1, is an Omicron-targeting bivalent COVID-19 booster vaccine candidate. ⎯ The Company is working on an Omicron-containing bivalent booster candidate — EVER-COVID19-M1, and initiated rolling submission of IND applications for phase 1 and 2 study which may enable potential emergency use authorization application. mRNA rabies vaccine ⎯ In December 2022, the Company announced it had achieved the pre-clinical proof-of-concept milestones for the mRNA rabies vaccine program. The rabies program is the first non-COVID 19 vaccine developed with our clinically- validated mRNA platform, highlighting the in-house discovery capabilities of the Company. OTHER CLINICAL-STAGE ASSETS ⎯ In May 2022, our licensing partner Pfizer Inc. presented detailed results from two pivotal studies that make up the ELEVATE UC phase 3 registrational program evaluating etrasimod, a once-daily, oral, selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately-to-severely active ulcerative colitis ("UC"). Both Phase 3, multi-center, randomized, placebo-controlled trials achieved all primary and key secondary endpoints, with etrasimod demonstrating a safety profile consistent with previous studies. ⎯ In December 2022, our licensing partner Pfizer received acceptance from the U.S. FDA for the review of an NDA for etrasimod for individuals living with moderately-to-severely active UC. The FDA's decision is expected in the second half of 2023. This anticipated U.S. FDA approval will be the first approval of etrasimod globally. In addition, the European Medicines Agency accepted the Marketing Authorization Application for etrasimod in the same patient population, with the decision anticipated in the first half of 2024. ⎯ We are conducting a phase 3 study in Asia for etrasimod for the treatment of moderate-severe UC, which is expected to complete enrollment in 2023. Business Development Updates ⎯ In March 2022, the Company entered into a license agreement with Calliditas to develop and commercialize Nefecon for the treatment of primary IgAN in South Korea, expanding its license in addition to rights held in Greater China and Singapore. ⎯ In August 2022, the Company announced that it entered into an agreement with Immunomedics, Inc. ("Immunomedics"), a wholly-owned subsidiary of Gilead, whereby Immunomedics will obtain exclusive rights to develop and commercialize Trodelvy® (sacituzumab govitecan) in Greater China, South Korea, Singapore, Indonesia, Philippines, Vietnam, Thailand, Malaysia and Mongolia (the "Agreement"). Under the terms of the Agreement, the Company will receive up to US$455 million in total considerations with US$280 million in upfront payments payable subject to, among other things, certain regulatory approvals and up to US$175 million in potential future milestone payments. In addition, the Company will be released from payment obligations for up to US$710 million in remaining milestone payments. Drug Discovery Our discovery team is focused on precision disease-modifying mechanisms in key pathogenic pathways in kidney diseases and promising mRNA vaccines such as prophylactic vaccines for infectious disease and therapeutic cancer vaccines against solid tumors. Our mRNA rabies vaccine program achieved pre-clinical proof-of-concept in December 2022 as the first of several non-COVID-19 mRNA vaccine/therapeutics candidates that have demonstrated our discovery capabilities. Manufacturing facility The company's state-of-the-art mRNA manufacturing facility in Jiashan, Zhejiang Province initiated operation and successfully carried out trial production runs in December 2022. The first phase of the project, covering an area of 58,000 square meters, has a set of advanced production facilities built to meet global and China GMP standards, and designed with an annual production capacity of 700 million doses of mRNA vaccines. Commercialization The regulatory approval of Xerava in Singapore was the first product approval wholly applied by and granted to Everest, and Xerava is our first marketed product. As the company transforms to a fully-integrated biopharma, we are building out a highly efficient and industry-leading commercial team, focusing on the therapeutic areas of internal medicines and infectious diseases. We expect to commercially launch Xerava in mainland China in Q3 2023 and the commercial team will be further expanded when approaching the expected approval of Nefecon in mainland China. In addition, under the supporting policies of the Boao Lecheng International Medical Tourism Pilot Zone, our commercial team is working on an early access program of Nefecon to bring benefits to patients sooner. Financial Highlights IFRS Numbers: Total assets of RMB 6.61 billion and net assets of RMB 5.65 billion for the year ended December 31, 2022. Revenue increased by RMB12.7 million to RMB12.8 million for the year ended 31 December 2022, from RMB54,000 for the year ended 31 December 2021, primarily due to the sales of eravacyline and Trodelvy in Singapore. Research and development (the "R&D") expenses increased by RMB196.3 million to RMB809.7 million for the year ended 31 December 2022, from RMB613.4 million for the year ended 31 December 2021, primarily due to i) additional clinical trials for our drug candidates; (ii) expansion of internal discovery team to build up in-house R&D capabilities; (iii) increased technical transfer related costs for our drug candidates. R&D expenses related to Trodelvy after August 1, 2022 would be reimbursed by Gilead. General and administrative expenses increased by RMB33.8 million to RMB276.5 million for the year ended 31 December 2022, from RMB242.7 million for the year ended 31 December 2021, primarily due to increased professional service expenses. Distribution and selling expenses increased by RMB128.5 million to RMB326.7 million for the year ended 31 December 2022, from RMB198.2 million for the year ended 31 December 2021, primarily due to increased employee benefit expenses and launch and pre-launch activities carried out for commercialization. Distribution and selling expenses related to Trodelvy after August 1, 2022 would be reimbursed by Gilead. Net loss for the year ended 31 December 2022 was RMB247.3 million, compared with RMB1,008.7 million for the year ended 31 December 2021, primarily due to the other gain of RMB1,322.3 million from Trodelvy transaction. Cash and cash equivalents and bank deposits amounted to RMB1,651.4 million as of 31 December 2022. Pro forma for the Trodelvy Agreement upfront considerations we received in early 2023, our Cash and cash equivalents and bank deposits amounted to USD432 million. Non-IFRS Measure: Adjusted loss for the year[1] was RMB17.4 million for the year ended 31 December 2022, representing a decrease of RMB759.9 million from RMB777.3 million for the year ended 31 December 2021, primarily due to other gain of RMB1,322.3 million from Trodelvy® transaction. Conference Call Information The English session of the conference call will be held at 9:00 AM on March 31, 2023 Beijing Time (9:00 PM U.S. Eastern Time on March 30, 2023), and the Mandarin session of the conference call will be held at 11:00 AM Beijing Time on the same day (11:00 PM U.S. Eastern Time on March 30, 2023). The conference calls can be accessed by the following links: For English Session: Time: 9:00 AM Beijing Time, Friday, March 31, 2023 Pre -Registration Link: Webcast Link: Alternatively, participants may dial in to the conference call using below dial-in information: For Mandarin Session: Time: 11:00 AM Beijing Time, Friday, March 31, 2023 Webcast Link: Alternatively, participants may dial into the conference call using below dial-in information: The replay of English session will be available shortly after the call and can be accessed by visiting the Company's website at . About Everest Medicines Everest Medicines is a biopharmaceutical company focused on developing, manufacturing and commercializing transformative pharmaceutical products and vaccines that address critical unmet medical needs for patients in Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record from both leading global pharmaceutical companies and local Chinese pharmaceutical companies in high-quality discovery, clinical development, regulatory affairs, CMC, business development, and operations. Everest Medicines has built a portfolio of potentially global first-in-class or best-in-class molecules in the company's core therapeutic areas of renal diseases, infectious diseases and autoimmune disorders. For more information, please visit its website at . Forward-Looking Statements: This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law. SOURCE Everest Medicines

The medicinal secrets of the Chilean soapbark tree have been laid bare, unlocking a future of more potent, affordable, and sustainably sought vaccines. Researchers have taken a major step forward in addressing this problem, by using a combination of genome mining and bioengineering techniques to produce saponin-based vaccine adjuvants in the laboratory without harvesting material directly from trees. The medicinal secrets of the Chilean soapbark tree have been laid bare, unlocking a future of more potent, affordable, and sustainably sought vaccines. The evergreen species, Quillaja saponaria has, for decades, been highly prized for producing molecules called QS saponins, which are used in the food and drinks industry as foaming agents. More recently an important new function has emerged with saponins obtained from the tree's bark used as potent adjuvants in the production of vaccines. Adjuvants play a critical role in some vaccines, working to boost the potency of a vaccine by enhancing the host immune response. Molecules extracted from soapbark tree are used as adjuvants in vaccines protecting people against COVID-19, shingles, and malaria. QS saponins are sourced directly from the tree and although this is at a much smaller scale than the food and drink industry, vaccine manufacturers are actively working to reduce the environmental impact and improve sustainability of sourcing these important resources. Researchers at the John Innes Centre have taken a major step forward in addressing this problem, by using a combination of genome mining and bioengineering techniques to produce saponin-based vaccine adjuvants in the laboratory without harvesting material directly from trees. Dr James Reed, first author of the study and postdoctoral researcher at the John Innes Centre says: "These are complex molecules that have thwarted attempts to synthesize them at scale using chemistry in the lab. After many twists and turns, we have now discovered the core set of genes responsible for the biosynthesis of QS saponins." In research which appears in Science, the Osbourn group at the John Innes Centre first sequenced the genome of Quillaja saponaria. Then they used powerful computational gene-mining tools to predict which among the ~30,000 genes that make up its genome were responsible for saponin biosynthesis. This led to the identification of a biosynthetic pathway of 16 genes which together produce the enzymes which are nature's building blocks for saponin production. Together these newly discovered genes and enzymes act as an instruction manual for future adjuvant bioengineering, say the team. Identification of a further three enzymes resulted in a complete biosynthetic pathway to the saponin QS-7, a saponin that is included in a vaccine adjuvant with proven clinical efficacy, but that is notoriously difficult to purify from soapbark tree. The pathway to these molecules was reconstructed in a plant called Nicotiana benthamiana, using a rapid and powerful technique called transient combinatorial expression. This dwarf wild relative of tobacco is well known as an amenable host for the bioproduction of therapeutic proteins and pharmaceuticals. The team is already using this instruction manual to attempt to produce other valuable saponins including QS-21, a potent adjuvant and key component in human vaccines. The levels of saponins produced in this study equate to amounts normally obtained from the leaves of the soapbark tree rather than its bark. The team have partnered with Plant Bioscience Limited (PBL, Norwich UK), who are leading on the commercialisation of the research and are now looking to work with commercial and academic partners to scale up these quantities further. Professor Anne Osbourn, the lead of the study, and a group leader at the John Innes Centre said: "The COVID-19 pandemic has demonstrated the huge demand for lifesaving vaccines. By assembling the genome sequence of Quillaja saponaria we now have the instruction manual which has enabled us to decode how the tree makes these potent medicinal molecules. This opens the possibility of producing known and new-to-nature saponin-based vaccine adjuvants optimized for immunostimulant activity and suitable for human applications in our rapid transient plant expression system." Elucidation of the pathway for biosynthesis of saponin adjuvants from the soapbark tree appears in Science. Vaccine Adjuvants -- a brief timeline Described as hidden helpers, vaccine adjuvants are immunostimulatory substances that are added to some vaccines to boost the immune response, doing so by inducing strong antibody and T-cell responses. Until recently the only adjuvants in clinical use were insoluble aluminium salts or oil in water emulsions containing squalene, an organic compound obtained from shark liver. As natural surfactants, saponins have been used in veterinary medicine for a century. But these adjuvants have been unsuitable for human use due to poor tolerability. A vaccine containing a saponin-based adjuvant has been approved for use in humans. QS-7 and QS-21 are included in a complex mix of saponins formulated as Matrix-M adjuvant in the Novavax COVID 19 vaccine. Approval of this vaccine in countries worldwide is increasing the interest for saponin-based adjuvants and alternative methods of production. Knowledge of the biosynthetic pathway will enable researchers to develop bespoke saponin-based adjuvants with a diverse spectrum of immune-stimulating properties.