University of Hong Kong

SOUTH SAN FRANCISCO, Calif., March 27, 2024 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Nasdaq: ALGS, “Aligos”), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in liver and viral diseases, today announced three oral presentations and one poster presentation at the 33rd Annual Meeting of the Asian Pacific Association for the Study of the Liver (APASL) 2024, being held March 27-31, 2024 in Kyoto, Japan. The poster presentation highlights ALG-055009 Phase 1 data that showed multiple-ascending doses (MAD) over 14 days in hyperlipidemic subjects produced favorable, dose-dependent pharmacodynamic effects on atherogenic lipids and sex hormone binding globulin (SHBG), an indicator of target engagement in the liver. The three oral presentations provide interim data from Parts 3 and 4 of Aligos’ ALG-000184 Phase 1 extended dosing study showing consistent, potent antiviral activity across different cohorts of untreated CHB patients receiving once daily doses of ALG-000184 as monotherapy or in combination with entecavir (ETV). “We are pleased to present these additional Phase 1 data for ALG-055009 and ALG-000184 at APASL 2024. After the recent initiation of our Phase 2a HERALD study of ALG-055009 in MASH subjects, we remain encouraged by the data presented showing a favorable safety profile and strong evidence of target engagement, as shown by induction of sex hormone binding globulin and lowering of atherogenic lipids. We continue to believe our molecule has the potential to be best-in-class,” said Lawrence Blatt, Ph.D., MBA, Chairman, President, and Chief Executive Officer at Aligos Therapeutics. “In addition, the three ALG-000184 oral presentations demonstrate a consistent effect in the reduction of key viral markers. These promising results affirm our belief that this compound will play an essential role in the future treatment of hepatitis B.” Details of the presentations are as follows: ALG-055009: Potential best-in-class small molecule THR-β agonist for metabolic dysfunction-associated steatohepatitis (MASH) Poster Presentation Title: Pharmacodynamics of Multiple Ascending Oral Doses of ALG-055009, a THR-β Agonist, in Hyperlipidemic Subjects Presented by Megan Fitzgerald, Ph.D.March 28, 2024 at 5:10pm GMT+9 ALG-000184: Potential best-in-class small molecule CAM-E for chronic hepatitis B (CHB) Oral Presentation Title: ALG-000184 (300mg) ± Entecavir Results in Substantial HBV Antigen Declines in Untreated HBeAg-Positive Subjects with CHB Presented by Professor Man-Fung Yuen, MBBS, MD, PhD, DSc, Chair and Chief of the Division of Gastroenterology and Hepatology, University of Hong KongMarch 28, 2024 at 9:30am GMT+9 Oral Presentation Title: ALG-000184 (100 mg) + ETV Leads to Stronger Antiviral Effects Compared to ETV Alone in HBeAg-Positive CHB Presented by Professor Jinlin Hou, MD, Director and Professor of the Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical UniversityMarch 28, 2024 at 9:48am GMT+9 Oral Presentation Title: ALG-000184 Has Favorable Antiviral Effect & Safety in Untreated Asian/Non-Asian HBeAg-Negative CHB Subjects Presented by Professor Man-Fung Yuen, MBBS, MD, PhD, DSc, Chair and Chief of the Division of Gastroenterology and Hepatology, University of Hong KongMarch 28, 2024 at 9:57am GMT+9 The presentations can be found on the Scientific Presentations & Conferences section of the Aligos website (www.aligos.com) after the live event. About AligosAligos Therapeutics, Inc. is a clinical stage biopharmaceutical company that was founded in 2018 with the mission to become a world leader in the treatment of liver and viral diseases. Aligos’ strategy is to harness the deep expertise and decades of drug development experience its team has in liver and viral diseases to discover and develop potentially best-in-class therapeutics for metabolic dysfunction-associated steatohepatitis (MASH) and viruses with high unmet medical need such as chronic hepatitis B (CHB) and coronaviruses. Forward-Looking Statement This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered “forward-looking statements,” including without limitation, with respect to ALG-055009, statements that the company remains encouraged by the data presented showing a favorable safety profile and strong evidence of target engagement and continues to believe the molecule has the potential to be best-in-class; and with respect to ALG-000184, statements around the promising results contained in the three oral presentations demonstrating consistent effect in the reduction of key viral models, which results affirm the company’s belief that this compound will play an essential role in the future treatment of hepatitis B. Forward-looking statements are typically, but not always, identified by the use of words such as “may”, “will”, “would”, “believe”, “intend”, “plan”, “anticipate”, “estimate”, “expect”, and other similar terminology indicating future results. Such forward looking statements are subject to substantial risks and uncertainties that could cause our development programs, future results, performance, or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties inherent in the drug development process, including Aligos’ clinical-stage of development, the process of designing and conducting clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, Aligos’ ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of Aligos’ capital resources to fund operations, reliance on third parties for manufacturing and development efforts, and the impact of global events and other macroeconomic conditions on the Aligos business. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Aligos in general, see Aligos’ Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 12, 2024 and its future periodic reports to be filed or submitted with the Securities and Exchange Commission. Except as required by law, Aligos undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events. Contacts CompanyJordyn TaraziVice President, Investor Relations & Corporate Communications(650) 910-0427jtarazi@Aligos.com MediaMichael Fitzhugh LifeSci Communications (628) 234-3889mfitzhugh@lifescicomms.com

A research team has recently made a significant breakthrough in understanding how the DNA copying machine helps pass on epigenetic information to maintain gene traits at each cell division. Understanding how this coupled mechanism could lead to new treatments for cancer and other epigenetic diseases by targeting specific changes in gene activity. A research team led by Professor Yuanliang ZHAI at the School of Biological Sciences, The University of Hong Kong (HKU) collaborating with Professor Ning GAO and Professor Qing LI from Peking University (PKU), as well as Professor Bik-Kwoon TYE from Cornell University, has recently made a significant breakthrough in understanding how the DNA copying machine helps pass on epigenetic information to maintain gene traits at each cell division. Understanding how this coupled mechanism could lead to new treatments for cancer and other epigenetic diseases by targeting specific changes in gene activity. Their findings have recently been published in Nature. Background of the Research Our bodies are composed of many differentiated cell types. Genetic information is stored within our DNA which serves as a blueprint guiding the functions and development of our cells. However, not all parts of our DNA are active at all times. In fact, every cell type in our body contains the same DNA, but only specific portions are active, leading to distinct cellular functions. For example, identical twins share nearly identical genetic material but exhibit variations in physical characteristics, behaviours and disease susceptibility due to the influence of epigenetics. Epigenetics functions as a set of molecular switches that can turn genes on or off without altering the DNA sequence. These switches are influenced by various environmental factors, such as nutrition, stress, lifestyle, and environmental exposures. In our cells, DNA is organised into chromatin. The nucleosome forms a fundamental repeating unit of chromatin. Each nucleosome consists of approximately 147 base pairs of DNA wrapped around a histone octamer which is composed of two H2A-H2B dimers and one H3-H4 tetramer. During DNA replication, parental nucleosomes carrying the epigenetic tags, also known as histone modifications, are dismantled and recycled, ensuring the accurate transfer of epigenetic information to new cells during cell division. Errors in this process can alter the epigenetic landscape, gene expression and cell identity, with potential implications for cancer and ageing. Despite extensive research, the molecular mechanism by which epigenetic information is passed down through the DNA copying machine, called the replisome, remains unclear. This knowledge gap is primarily due to the absence of detailed structures that capture the replisome in action when transferring parental histones with epigenetic tags. Studying the process is challenging because of the fast-paced nature of chromatin replication, as it involves rapid disruption and restoration of nucleosomes to keep up with the swift DNA synthesis. In previous studies, the research team made significant progress in understanding the DNA copying mechanism, including determining the structures of various replication complexes. These findings laid a solid foundation for the current research on the dynamic process of chromatin duplication. Summary of Research Findings This time, the team achieved another breakthrough by successfully capturing a key snapshot of parental histone transfer at the replication fork. They purified endogenous replisome complexes from early-S-phase yeast cells on a large scale and utilised cryo-electron microscopy (cryo-EM) for visualisation. They found that a chaperone complex FACT (consisting of Spt16 and Pob3) interacts with parental histones at the front of the replisome during the replication process. Notably, they observed that Spt16, a component of FACT, captures the histones that have been completely stripped off the duplex DNA from the parental nucleosome. The evicted histones are preserved as a hexamer, with one H2A-H2B dimer missing. Another protein that involved in DNA replication, Mcm2, takes the place of the missing H2A-H2B dimer on the vacant site of the parental histones, placing the FACT-histone complex onto the front bumper of the replisome engine, called Tof1. This strategic positioning of histone hexamer on Tof1 by Mcm2 facilitates the subsequent transfer of parental histones to the newly synthesised DNA strands. These findings provide crucial insights into the mechanism that regulates parental histone recycling by the replisome to ensure the faithful propagation of epigenetic information at each cell division. This study, led by Professor Zhai, involved a collaborative effort that spanned nearly eight years, starting at HKUST and concluding at HKU. He expressed his excitement about the findings, 'It only took us less than four months from submission to Nature magazine to the acceptance of our manuscript. The results are incredibly beautiful. Our cryo-EM structures offer the first visual glimpse into how the DNA copying machine and FACT collaborate to transfer parental histone at the replication fork during DNA replication. This knowledge is crucial for elucidating how epigenetic information is faithfully maintained and passed on to subsequent generations. But, there is still much to learn. As we venture into uncharted territory, each new development in this field will represent a big step forward for the study of epigenetic inheritance.' The implications of this research extend beyond understanding epigenetic inheritance. Scientists can now explore gene expression regulation, development, and disease with greater depth. Moreover, this breakthrough opens up possibilities for targeted therapeutic interventions and innovative strategies to modulate epigenetic modifications for cancer treatment. As the scientific community delves deeper into the world of epigenetics, this study represents a major step towards unravelling the complexities of replication-coupled histone recycling.

A collaborative project has made a breakthrough in enhancing the speed and resolution of wide-field quantum sensing, leading to new opportunities in scientific research and practical applications. A collaborative project led by Professor Zhiqin Chu, Professor Can Li and Professor Ngai Wong, at the Department of Electrical and Electronic Engineering of the University of Hong Kong (HKU) has made a breakthrough in enhancing the speed and resolution of widefield quantum sensing, leading to new opportunities in scientific research and practical applications. By collaborating with scientists from Mainland China and Germany, the team has successfully developed a groundbreaking quantum sensing technology using a neuromorphic vision sensor, which is designed to mimic the human vision system. This sensor is capable of encoding changes in fluorescence intensity into spikes during optically detected magnetic resonance (ODMR) measurements. The key advantage of this approach is that it results in highly compressed data volumes and reduced latency, making the system more efficient than traditional methods. This breakthrough in quantum sensing holds potential for various applications in fields such as monitoring dynamic processes in biological systems. The research paper has been published in the journal Advanced Science titled "Widefield Diamond Quantum Sensing with Neuromorphic Vision Sensors." "Researchers worldwide have spent much effort looking into ways to improve the measurement accuracy and spatiotemporal resolution of camera sensors. But a fundamental challenge remains: handling the massive amount of data in the form of image frames that need to be transferred from the camera sensors for further processing. This data transfer can significantly limit the temporal resolution, which is typically no more than 100 fps due to the use of frame-based image sensors. What we did was trying to overcome the bottleneck," said Zhiyuan Du, the first author of the paper and PhD candidate at the Department of Electrical and Electronic Engineering Du said his professor's focus on quantum sensing had inspired him and other team members to break new ground in the area. He is also driven by a passion for integrating sensing and computing. "The latest development provides new insights for high-precision and low-latency widefield quantum sensing, with possibilities for integration with emerging memory devices to realise more intelligent quantum sensors," he added. The team's experiment with an off-the-shelf event camera demonstrated a 13× improvement in temporal resolution, with comparable precision in detecting ODMR resonance frequencies with the state-of-the-art highly specialized frame-based approach. The new technology was successfully deployed in monitoring dynamically modulated laser heating of gold nanoparticles coated on a diamond surface. "It would be difficult to perform the same task using existing approaches," Du said. Unlike traditional sensors that record the light intensity levels, neuromorphic vision sensors process the light intensity change into "spikes" similar to biological vision systems, leading to improved temporal resolution (≈µs) and dynamic range (>120 dB). This approach is particularly effective in scenarios where image changes are infrequent, such as object tracking and autonomous vehicles, as it eliminates redundant static background signals. "We anticipate that our successful demonstration of the proposed method will revolutionise widefield quantum sensing, significantly improving performance at an affordable cost," said Professor Zhiqin Chu. "This also brings closer the realisation of near-sensor processing with emerging memory-based electronic synapse devices," said Professor Can Li. "The technology's potential for industrial use should be explored further, such as studying dynamic changes in currents in materials and identifying defects in microchips," said Professor Ngai Wong.