Suzhou Abogen Biosciences Co., Ltd.

SUZHOU, China, Aug. 23, 2024 /PRNewswire/ -- Abogen Biosciences ("Abogen" or the "Company") announced a publication titled "Efficient circularization of protein-encoding RNAs via a novel cis-splicing system " in Nucleic Acids Research. In the article, Abogen has revealed a highly efficient RNA circularization cis-splicing system (referred to as the "Cis-System") which enables the production of circular RNA ("circRNA") with significantly extended protein expression, reduced innate immune activation, and flexible splice site design that offers substantial market potential. Continue Reading Screenshot of published paper (PRNewsfoto/艾博生物) The precursor RNA undergoes cis-splicing reaction to remove ribozyme intron segments, enabling circularization of the gene of interest (GOI) without sequence addition (PRNewsfoto/艾博生物) In recent years, circular RNA technology has gained significant attention from the biopharmaceutical industry, several circular RNA start-up companies raised a total of over 1 billion dollars in financing. Among the most notable are Flagship-incubated Sail Biomedicines (formed through the merger of Laronde and Senda Biosciences), which has raised nearly $800 million, and Orna Therapeutics, founded by MIT Professor Daniel Anderson, secured over $300 million in funding and recently acquired ReNAgade Therapeutics to accelerate its clinical development. Abogen's Cis-System-based circRNA not only has global IP, but also improves over PIE System The conventional technology for circRNA synthesis is the PIE method (Permuted Introns and Exons), patented by Orna and other companies. However, the Cis-System not only circumvents the patent restrictions by the PIE system, but also simplifies the circularization process and makes it more suitable for industrial production. As described in the publication, the Cis-System embeds a ribozyme core structure at one end of the precursor RNA, rendering the need for additional spacer elements between the ribozyme and the target gene. This invention significantly enhances the circularization efficiency thus offers a "scarless" and highly efficient translation process with less process-related impurities. The Cis-System-based circRNA shows promising prospects for the future The Cis-System reported in this study can achieve high circularization efficiency with essentially unrestricted base and sequence composition at the ends of RNA molecules, enabling truly efficient and scarless circularization. Furthermore, the Cis-System is designed to be more flexible, allowing customization based on specific therapeutic needs and compatibility with RNA molecule of different lengths. All these technological advances will lead to more sustained protein expression, reduced innate immune stimulation, and potential tissue-specific expression, which potentially bring more hopes in chronic disease treatment and immunotherapies where repeated dosing may be required. Dr. Shaojun Qi, Senior Scientist in mRNA Innovation department at Abogen commented: "I deeply appreciated the innovative culture at Abogen which is crucial for our success in overcoming the key bottlenecks in circular RNA technology. " Dr. Peng Gao, Vice President of Abogen (corresponding author of the publication), commented: "After over two years of commitment and continuous efforts, our team has finally overcome the critical technical hurdle presented in circRNA technology. Preliminary results from further studies have reinforced the great value and application potential of this technology. We hope to rapidly translate this achievement into clinical solutions to address the unmet medical needs." Link for the Original Paper Shaojun Qi, Huiming Wang, Guopeng Liu, Qianshan Qin, Peng Gao, Bo Ying, Efficient Circularization of Protein-Encoding RNAs via a Novel Cis-Splicing System, *Nucleic Acids Research*, 2024;, gkae711, []() About Abogen Biosciences Abogen Biosciences（"Abogen") is an innovative biopharmaceutical company focused on messenger RNA (mRNA) drug development. The company has established its own industry-leading proprietary mRNA platform and nanoparticle delivery system and is one of the few mRNA drug R&D enterprises in China with complete capabilities across mRNA value chain, covering all aspects from mRNA design, formulation development to large-scale manufacturing. The company has established a diversified product pipeline, with products ranging from infectious disease prevention and control, tumor immunology, to protein replacement therapies. SOURCE Abogen Biosciences

Around the same time AstraZeneca struck up a vaccine partnership with Oxford last April, the pharma giant also put together a game plan to develop treatments — both new and repurposed — for Covid-19. One of them has now ended in failure. The Phase III DARE-19 trial recruited 1,250 patients hospitalized with Covid-19 over the past year and gave half of them the diabetes drug Farxiga on top of standard of care therapy. When compared to those receiving placebo, the drug didn’t hit statistical significance in either of the primary endpoints: preventing measuring organ dysfunction and all cause mortality, or improving recovery (as measured by a change in clinical status) at 30 days. Focusing on the bright side, Mene Pangalos, EVP of biopharmaceuticals R&D, noted: “Prior to the DARE-19 Phase III trial, there was little data on the use of SGLT2 inhibitors in hospitalised patients with COVID-19 and we have now helped to fill this knowledge gap.” Mikhail Kosiborod, the principal investigator of the trial and the VP of research at AstraZeneca partner Saint Luke’s Mid America Heart Institute, echoed Pangalos and called the findings “very interesting and valuable.” Details are due to be released at the American College of Cardiology Scientific Sessions in May. While originally designed as a diabetes pill, Farxiga has been shown across large studies to have cardio and renal protective effects not just in that population but also for those with heart failure with reduced ejection fraction and chronic kidney disease (CKD). Coincidentally, scientists had observed that Covid-19 patients with “cardiac, renal and metabolic comorbidities” tended to have poor outcomes — leading AstraZeneca to test whether Farxiga may help in this setting as well. Like a slew of other commercial drugs that biopharma companies big and small tried to repurpose, it didn’t. AstraZeneca itself has already concluded that Calquence, the blockbuster BTK inhibitor approved for cancer, made little difference in mortality or saving Covid-19 patients from respiratory failure. While the pharma giant didn’t specify the next steps, it seems to imply that this will mark the end of the Farxiga program in Covid-19. Days after the US government and Eli Lilly agreed to halt all distribution of bamlanivimab as a monotherapy, the company said officials have officially revised the antibody supply deal. That means the purchase agreement for bamlanivimab will be terminated, the company said in a statement, canceling the planned delivery of 350,836 doses the original agreement had called for. Concerns of bamlanivimab’s diminished efficacy against certain coronavirus variants first led the US to stop direct ordering of bamlanivimab alone in three states , before extending that ban to the whole country. Instead, hospitals could order either bamlanivimab and etesevimab together or etesevimab alone to pair with any remaining doses of bamlanivimab on hand. The arrangement is now codified in the modified contract. First developed by AbCellera, bamlanivimab was the first monoclonal antibody to gain an emergency use authorization at the FDA. Lilly subsequently paired it with etesevimab, which originated from China’s Junshi, generating a solid slate of combo data that led to another EUA, also for mild to moderate Covid-19. Together, the two regimens were the subject of a $1.2 billion supply deal. As concerns grew that certain variants could evade antibody treatments, the FDA has directed both Lilly and Regeneron to monitor genomic database(s) for the emergence of global viral variants and track how well their drugs can tackle those variants. As Fosun Pharma prepares to push BioNTech’s Covid-19 vaccine toward an approval in China, a senior industry figure says homegrown mRNA players will also be ready to jump in the game soon. “We fully expect that there is a high possibility that a domestic mRNA vaccine will hit the market by this year,” Feng Duojia, president of the China Association of Vaccines, told the South China Morning Post. One candidate jointly developed by the Academy of Military Science, Walvax Biotechnology and Suzhou Abogen Biosciences has been through Phase II trials with “satisfactory” results, he said, with Phase III trials underway overseas. Another from Shanghai-based Stemirna went into the clinic last month. Fosun, meanwhile, is sorting through data from Phase II trials conducted in Jiangsu province, SCMP reported. The plan is to combine those with Phase III results from overseas in its regulatory filing. While Fosun started off as the developer and distributor of BioNTech’s vaccines — having started delivering doses made in Germany to Hong Kong and Macau — the company has inked a deal to produce locally. “The preparations at the production facility are ready,” Feng added. “After effective results are obtained through these trials, an application will be submitted to the relevant government agency immediately, with the hope to start domestic production of the foreign vaccine in China.” For a look at all Endpoints News coronavirus stories, check out our special news channel .