HK2

Company licenses novel deep learning-based epigenetic models from CUHK enabling the detection of 5hmC, 5mC hemimethylation, and 6mA in standard sequencing runsMENLO PARK, Calif., April 28, 2025 (GLOBE NEWSWIRE) -- PacBio (Nasdaq: PACB), a leading provider of high-quality, highly accurate sequencing platforms, today announced it plans to improve on its already highly accurate methylation detection capabilities in HiFi chemistry through licensing advanced DNA methylation detection methods developed by Professor Dennis Lo and colleagues at the The Chinese University of Hong Kong (CUHK) and Centre for Novostics. The licensed technology is designed to enhance PacBio HiFi sequencing with improved detection of DNA base modifications—including 5-hydroxymethylcytosine (5hmC) and hemimethylated 5-methylcytosine (5mC)—in native DNA. PacBio plans to bring these capabilities to its Revio and Vega systems, building on its existing 5mC support to deliver even more comprehensive epigenomic insights as part of standard HiFi whole-genome sequencing workflows. “PacBio was the first to detect native epigenetic modifications alongside accurate DNA sequencing. With the integration of the CUHK deep learning models, our technology will be able to detect many additional and biologically meaningful methylation signatures, including 5hmC and strand-specific 5mC,” said Christian Henry, President and CEO of PacBio. "Our commitment to continually improving HiFi chemistry will enable our customers to gain even deeper insights into the human genome, powering new discoveries and clinical possibilities." The newly licensed technology includes an enhanced AI deep learning framework known as Holistic Kinetic Model 2 (HK2), which integrates convolutional and transformer layers to model local and long-range kinetic features with extraordinary precision. HK2 is designed to significantly improve the accuracy of 5mC and N6-methyladenine (6mA) detection and introduces native 5hmC calling in single molecules—a first for HiFi sequencing. HiFi sequencing, available on both the Revio and Vega platforms, provides a comprehensive and simultaneous readout of the genome and epigenome from native DNA without the need for chemical conversion, additional sample preparation, or parallel workflows. The new capabilities from the HK2 model will be delivered to existing customers through software updates, with no changes to sequencing protocols and no additional cost. “I am delighted to see this technology now being deployed more broadly through PacBio’s global customer base,” said Professor Dennis Lo, Scientific Director of Centre for Novostics, CUHK. “Accurate detection of DNA methylation—particularly 5mC and 5hmC—on native molecules is important for advancing research in cancer, human development, and beyond. With the improvements enabled by HK2, methylation calling with PacBio HiFi sequencing is poised to set a new standard for accuracy in the industry, surpassing other available technologies.” CUHK, together with Take2 Technologies Limited, a Hong Kong-based biotechnology company, pioneered robust 5mC detection in 2021 using the PacBio platform. PacBio introduced on-instrument 5mC detection in April 2022 and extended support to 6mA in December 2024 for Fiber-seq chromatin architecture studies. HK2 is designed to push detection performance to new levels of accuracy. Importantly, HK2 will also enable strand-specific 5mC analysis, which opens new opportunities to study hemimethylation—an emerging epigenetic signal. HiFi 5-base sequencing has already been adopted by pioneering institutions such as Children’s Mercy Kansas City, the first to use comprehensive genomic and epigenomic profiling in a clinical setting​. GeneDx is also leveraging this capability to investigate the diagnostic potential of epigenetic signals in neonatal care​. The ability to profile 5hmC—a dynamic and tissue-specific epigenetic mark implicated in brain development, cancer, and neurodegenerative diseases—opens new frontiers in liquid biopsy, cancer detection, and cell-free DNA analysis​. Unlike chemical-based methods such as bisulfite or TAPS sequencing, which degrade DNA and diminish phasing and structural context, PacBio’s native detection maintains DNA integrity and supports haplotype-resolved analysis in complex genomic regions​. The licensing of HK2 marks another milestone in PacBio’s continued leadership in long-read epigenomics. Combined with the high accuracy and long read lengths of HiFi sequencing, HK2 delivers a uniquely powerful tool for understanding the full landscape of genome function—across both sequence and modification. "By enabling high-resolution, native detection of 5mC, 6mA, and 5hmC, we’re empowering researchers to ask more sophisticated questions and uncover new biology," said Mark Van Oene, Chief Operating Officer at PacBio. "And because this capability is powered entirely by software and existing sequencing signals, customers can access it with no added cost or workflow changes." PacBio aims to deliver these capabilities to Revio and Vega through a future software update. For more information about HiFi chemistry, visit https://www.pacb.com/technology/hifi-sequencing/. About Pacific BiosciencesPacBio (NASDAQ: PACB) is a premier life science technology company that designs, develops, and manufactures advanced sequencing solutions to help scientists and clinical researchers resolve genetically complex problems. Our products and technologies stem from two highly differentiated core technologies focused on accuracy, quality and completeness which include our HiFi long-read sequencing and our SBB® short-read sequencing technologies. Our products address solutions across a broad set of research applications including human germline sequencing, plant and animal sciences, infectious disease and microbiology, oncology, and other emerging applications. For more information, please visit www.pacb.com and follow @PacBio. PacBio products are provided for Research Use Only. Not for use in diagnostic procedures. About The Chinese University of Hong Kong (CUHK)Founded in 1963, CUHK is a leading comprehensive research university with a global reputation and world-leading rankings. Located in the heart of Asia, CUHK has a vision and a mission to combine tradition with modernity, and to bring together China and the West. The University is devoted in cutting edge research and translation of research outputs into useful products. CUHK is renowned for its leading role in molecular diagnostics research. The noninvasive prenatal diagnostic test for Down syndrome developed by Dennis Lo is widely adopted globally with more than 100 million tests performed since its inception. Centre for Novostics, an affiliate CUHK, is supported by the InnoHK initiative under the Innovation and Technology Commission of the Hong Kong Special Administrative Region Government dedicated to molecular diagnostic research. About Take2 Technology Limited (Take2)Founded in 2019, Take2 is a Hong Kong-based biotechnology company. Take2 focuses on the development of novel molecular diagnostic approaches, in particular in the area of epigenetic analysis and cancer screening. Forward Looking StatementsThis press release contains “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the U.S. Private Securities Litigation Reform Act of 1995. All statements other than statements of historical fact are forward-looking statements, including statements relating to the uses, advantages, quality or performance of, the benefits or expected benefits of using, PacBio products or technologies, including in connection with anticipated improvements to methylation detection with respect to 5hmC, 5mC, 6mA, and strand-specific 5mC, and related opportunities for customers to gain deeper insights, power new discoveries and enable clinical possibilities with no additional cost or change to sequencing protocols; setting new standards for accuracy, and other future events. You should not place undue reliance on forward-looking statements because they are subject to assumptions, risks, and uncertainties that could cause actual outcomes and results to differ materially from currently anticipated results. These risks include, but are not limited to, risks inherent in developing and commercializing new technologies; rapidly changing technologies and extensive competition in genomic sequencing; unanticipated increases in costs or expenses; interruptions or delays in the supply of components or materials for, or manufacturing of, PacBio products and products under development; third-party claims alleging infringement of patents and proprietary rights or seeking to invalidate PacBio's patents or proprietary rights; and other risks associated with general macroeconomic conditions and geopolitical instability. Additional factors that could materially affect actual results can be found in PacBio's most recent filings with the Securities and Exchange Commission, including PacBio's most recent reports on Forms 8-K, 10-K, and 10-Q, and include those listed under the caption “Risk Factors.” These forward-looking statements, including PacBio’s preliminary unaudited financial information and PacBio’s financial guidance, are based on current expectations and speak only as of the date hereof; except as required by law, PacBio disclaims any obligation to revise or update these forward-looking statements to reflect events or circumstances in the future, even if new information becomes available. Contacts Investors: Todd Friedmanir@pacificbiosciences.com Media:pr@pacificbiosciences.com

Actinic keratosis is a pre-cancerous area of thick, scaly, or crusty skin. Credit: Douglas Cliff via Shutterstock. Vidac Pharma has secured €600,000 ($645,651) in additional funding to support the clinical development of its two lead cancer candidates. The funding from existing investors, announced at the company’s recent shareholder meeting, will enable Vidac to initiate a new Phase IIb trial for its lead candidate VDA-1102 (tuvatexib) ointment. The hexokinase 2 inhibitor is being investigated in advanced cases of actinic keratosis, a skin condition that can progress to cutaneous squamous cell carcinoma (SCC). Alongside VDA-1102, the UK-based biotech continues preclinical studies of VDA-1275. Both candidates target the metabolic pathways of cancer cells by disrupting hexokinase 2 interactions with mitochondrial channels, aiming to reverse the high-energy demands of tumours and promote cancer cell death. VDA-1275 is being developed as a systemic drug for the treatment of solid tumours. Interim data from a Phase IIa study (NCT02844777) released in January 2023 showed a 56% objective response rate (ORR), with 22% complete responses (CR), observed between eight and 12 weeks. This compares to the standard-of-care treatment mechlorethamine, which has a 13% CR and a longer median response time of 26 weeks. Final results are expected in Q4 2024. Vidac has also completed a Phase IIb clinical trial (NCT03538951) for VDA-1102 in actinic keratosis. In a post-hoc analysis, the therapy demonstrated a 40% complete clearance of lesions and an 80% overall reduction in lesion count. The study also indicated that patients with advanced actinic keratosis responded more favourably to the treatment than those with less severe forms. Based on these findings, the upcoming Phase IIb trial will focus specifically on patients with advanced actinic keratosis. Unlike conventional actinic keratosis treatments that directly destroy abnormal cells, through topical therapies, cryotherapy, or photodynamic therapy, VDA-1102 works by reprogramming cancer cell metabolism. This selective approach aims to spare healthy cells, and in the Phase IIa trial, resulted mostly in mild, localised side effects, with one moderate case. Standard actinic keratosis treatments, by contrast, can cause skin inflammation, scaling, or burning, and are often invasive. In the announcement accompanying the funding, Vidac’s CEO Max Herzberg said: “I want to thank our board, advisers, team and shareholders for their support for our entirely new approach in oncology, with drugs that reverse the supercharged metabolism of cancer cells.” In June 2024, Almirall ’s Klisyri (tirbanibulin) secured FDA-expanded approval to treat larger actinic keratosis areas to up to 100cm² from the previous maximum of 25cm². Klisyri works by blocking cell division and killing abnormal cells. The most common side effects are local skin reactions, including erythema (reddening of the skin), flaking/scaling, crusting, swelling and the formation of sores and ulcers. Innovations in the pharma and medical device landscape are looking to expedite the diagnosis of skin cancers. In July 2023, the National Cancer Institute (NCI), part of the US National Institutes of Health (NIH), awarded $2m in funding to Enspectra Health through the Small Business Innovation Research (SBIR) programme. The grant will fund the development of deep learning algorithms that can predict which actinic keratosis skin lesions are likely to turn into SCC.

An international research team has discovered a new way to effectively treat cancer, by using nutrients to reactivate suppressed metabolic pathways in cancer cells. An international research team has discovered a new way to effectively treat cancer, by using nutrients to reactivate suppressed metabolic pathways in cancer cells. The researchers used a common amino acid, tyrosine, packaged as a nanomedicine, to change the metabolism of melanoma, a deadly skin cancer, and prevent cancer growth. Australia has the highest rate of skin cancer in the world. This new approach could be combined with current therapies to better treat melanoma. The technique also has the potential to treat other types of cancer. The study, Nutrient-delivery and metabolism reactivation therapy for melanoma, was led by Professor Wenbo Bu from Fudan University and Professor Dayong Jin from the University of Technology Sydney, and recently published in the journal Nature Nanotechnology. Tyrosine has limited bioavailability in living organisms. However, the researchers used a new nanotechnology technique to package it into tiny particles called nanomicelles, which are attracted to cancer cell membranes, and break down easily, boosting absorption. The research team then tested the innovative treatment in mice and in human-derived melanoma cells in the lab and found that the tyrosine nanomicelles reactivated dormant metabolic pathways, triggered melanin synthesis, and inhibited tumour growth. "Uncontrolled rapid growth is a key feature that distinguishes cancer cells from normal cells. In cancer cells some metabolic pathways are over-activated, and others are suppressed, to create the environment necessary for rapid spread," said Professor Jin. "While a few metabolism-based drugs for cancer have been developed previously, such as aromatase inhibitors impeding estrogen synthesis in breast cancer and HK2 inhibitors targeting glycolysis in various cancers, these work by suppressing over-activate metabolic pathways," he said. "Our research shows for the first time that cancer can be stopped by reactivating metabolic pathways that are dormant. And this can be done using simple nutrients, such as amino acids, sugars, and vitamins, which are safe, readily available and well tolerated," said Professor Bu. Different types of cancer will respond to different nutrients. Melanoma cells develop from melanocytes -- skin cells that produce melanin. Tyrosine is needed to produce melanin and it can stimulate melanin production, hence its effectiveness with melanoma. The reactivation of melanin synthesis forces the melanoma cell to reduce glycolysis, the process of converting sugar to energy, which is believed to be the mechanism for its anti-cancer effect. Melanoma cells are also susceptible to heat stress. The researchers found that by combining tyrosine nanomicelle treatment with near-infrared laser treatment, they were able to eradicate melanoma in mice after six days and it did not reoccur during the study period. The findings suggest a promising a new frontier in the use of nanomedicine for cancer therapy.