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We are delighted to announce that we have been selected for an oral presentation at the 37th European Immunogenetics and Histocompatibility (EFI) Conference! The presentation has been made May 21th by Séverine Planel. Title of the talk was: Humoral response in lung cancer patients treated with a plasmacytoid dendritic allogeneic cell line-based cancer vaccine. Using an antibody-mediated complement-dependent cytotoxicity (CDC) assay in flow cytometry using healthy donor’s or patient’s sera, we have shown that PDC*line cells were resistant to the complement dependent killing mediated by patient’s anti-HLA Ab despite the functionality of the patient’s complement system. Interestingly, we have shown that PDC*line cells express high level of membrane-bound complement regulatory proteins (mCRPs: CD46, CD55, and CD59) render them resistant to Ab-mediated CDC as shown by experiments using blocking Ab. Altogether, these results show the innocuity and the absence of deleterious effect of anti-HLA Ab on PDC*line cells used as a cancer vaccine platform. Abstract of the presentation is available through this link: /sites/default/files/images/ABSTRACT%20EFI%202024_vFinal.pdf About the event: The conference is the annual event of the European Federation of Immunogenetics (EFI). It has been held in Geneva, Switzerland from 20 - 23 May 2024. hashtag

SEOUL, South Korea, April 22, 2024 /PRNewswire/ -- OSR Holdings, a global healthcare holding company, announced that it has signed a memorandum of understanding (MOU) with SillaJen, a Kosdaq-listed biotech firm with a pipeline of immuno-oncology drug candidates, to share technology and clinical development resources and launch a strategic collaboration between the two companies. Through the MOU, the two companies will explore various ways to collaborate to create synergies between current platform technologies and new drug candidates. OSR Holdings was established in 2019 in South Korea as a "hub-and-spoke" business model, which has become more visible in the biopharma space over the past decade. The "hub-and-spoke" model, exemplified by companies like Roivant Sciences, PureTech Health and BridgeBio Pharma, enables centralized management of drug development strategies, clinical plans, and resource allocation by the holding company. The model allows the holding companies' subsidiaries to concentrate on the advancement of new drug assets and technological innovations. The model's scalability and resource efficiency are notably enhanced, especially as clinical phases of drug development progresses. OSR Holdings' current portfolio includes Vaximm AG, a Swiss entity developing immuno-oncology therapeutics; Darnatein, a South Korean drug developer of osteoarthritis therapeutics; and RMC, a distributor of specialized medical devices. Vaximm AG, a venture spun out from Merck KGaA, has completed Phase 2a clinical trials for glioblastoma. Darnatein, established by Dr. Seung-Hyun Choi, a former researcher at one of the leading research institutes in the U.S., Salk Institute for Biological Studies, boasts a robust platform for cartilage and bone regeneration and is developing new drugs for other diverse disease indications based on this foundational technology. SillaJen boasts a diverse pipeline of new drugs, including the SJ-600 series and BAL0891, and is leading the way in developing anti-cancer viruses based on its GEEV® platform. Known for its immune-evasion capabilities, GEEV® enables anti-cancer viruses to efficiently target affected areas. The SJ-600 series is an anti-cancer pipeline based on SillaJen's GEEV® platform. BAL0891, a mitotic checkpoint inhibitor, has advanced to Phase 1 clinical trials targeting solid tumors and will be conducted in the United States. Sung Jae "Alex" Yu, COO of OSR Holdings, stated, "the signing of this MOU marks the two companies transitioning into strategic partners for the development of innovative drug technologies in the global immuno-oncology market. We eagerly anticipate exploring a variety of opportunities to further our relationship and collaborations with SillaJen, particularly in the U.S., the largest pharmaceutical market in the world." A representative of SillaJen stated, "We can anticipate synergies by collaborating between a company that possesses original anti-cancer drug development technology and a company with global business expertise," and added, "Aside from our cooperation with existing partners, we will have the opportunity to present SillaJen's exceptional pipeline in the U.S. market." About OSR Holdings OSR Holdings, headquartered in Korea, is a global healthcare holding company with biopharma and medical device subsidiaries in areas with high unmet medical needs such as certain cancer indications. The biopharma subsidiaries are developing novel drug candidates based on differentiated technologies. The medical device subsidiary operates as an exclusive distributor of neuro-intervention devices to nationwide hospitals in Korea. In November 2023, OSR Holdings announced a business combination with Bellevue Life Sciences Acquisition Corp (Nasdaq: BLAC), a SPAC that completed a $69M IPO in February 2023. About SillaJen SillaJen, Inc. (KOSDAQ: 215600) is a publicly held biotech company developing anti-cancer therapies, with its clinical-stage products, Pexa-Vec, an oncolytic viral immunotherapy, and BAL0891, a mitotic checkpoint inhibitor. The company is also developing a unique CD-55 expressing vaccinia virus platform, GEEV®, which can be delivered to tumors via intravenous injection while evading the complement system and neutralizing antibodies against oncolytic viruses. Additional information about SillaJen is available at . Disclaimer Language: This press release contains certain forward-looking statements regarding, among other things, statements relating to goals, plans and projections regarding the Company's financial position, results of operations, market position, product development and business strategy. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and OSR Holdings undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law. SOURCE OSR Holdings

Researchers have identified a suite of genes explaining the disconnect between diagnosis and symptom. Treatment for rheumatoid arthritis (RA) has come a long way in recent years. In many cases, a battery of medications can now successfully stymy the inflammatory cells that cause swelling and pain when they infiltrate tissues around the joints. Yet for some reason, about 20% of patients with painful, visibly swollen joints consistently get no relief from multiple rounds of even the strongest of these anti-inflammatory drugs. Surgical interventions intended to remove inflamed tissue have revealed why: "In some cases, their joints aren't actually inflamed," says co-senior author Dana Orange, an associate professor of clinical investigation in Rockefeller's Laboratory of Molecular Neuro-oncology. "With these patients, if you press on the joint, it feels mushy and thick to the touch, but it's not caused by the infiltrating immune cells. They have excessive tissue growth, but without inflammation. So why are they experiencing pain?" In a new paper in Science Translational Medicine, she and her colleagues suggest an explanation. These patients have a suite of 815 genes that activate abnormal growth of sensory neurons in tissues that cushion the affected joints. "These 815 genes are rewiring the sensory nerves, which explains why anti-inflammatory drugs don't work to alleviate pain for these patients," says Orange. The findings may lead to new treatments for these outliers. A puzzling disconnection Rheumatoid arthritis is a tricky chronic disease. Its symptoms -- stiffness, tenderness, swelling, limited motion, and pain -- slowly emerge in the hands, wrists, feet, and other joints. It occurs symmetrically (not just in one hand but in both, for instance) and sporadically, with irregular flare-ups. Extreme fatigue and depression are also common. Most cases of RA are caused by products of immune cells such as cytokines, bradykinins, or prostanoids invading the synovium -- a soft tissue lining the joints -- where they bind to damage-sensing pain receptors. Drugs that target immune mediators have made RA a far more tolerable condition for most, but those suffering from the disconnection between inflammation and ache haven't benefitted. Doctors often prescribe these patients drug after anti-inflammatory drug in an ultimately fruitless attempt to give relief. As a result, "we are subjecting some patients to a lot of medications that cause immunosuppression and yet have little chance of making their symptoms better," Orange says. She and her colleagues sought answers in the genes expressed in the joint tissue samples of these patients. Genetic culprits The researchers looked at tissue samples and self-reported pain reports from 39 patients with RA who had pain but little inflammation. They also developed a machine-learning analysis that they coined graph-based gene expression module identification (GbGMI). GbGMI tests every possible combination of genes in a dataset to determine the optimal set of genes that together associate with a targeted clinical feature -- in this case, pain. Using RNA sequencing, the researchers found that of the 15,000 genes expressed in the tissue samples, about 2,200 had increased expression in the 39 patients. Using GbGMI, they identified 815 genes that together associated with patient reports of pain. "This is a challenging problem, because we have a large number of genes but a limited number of patients," says co-senior author Fei Wang, professor of population health sciences and founding director of the Institute of Artificial Intelligence for Digital Health at Weill Cornell Medicine. "The graph-based approach we used effectively explored the collective associations between a gene set and patient-reported pain." Single cell sequencing analysis found that of the four types of fibroblasts in synovial tissue, CD55+ fibroblasts exhibited the highest expression of pain-associated genes. Located in the outer synovial lining, CD55+ cells secrete synovial fluid, allowing for frictionless joint movement. They also expressed the NTN4 gene, which codes for a protein called Netrin-4. Proteins in the netrin family guide axon growth paths and promote new vascular growth. Surprising pain pathways These genes, it turned out, were enriched in pathways that are important for neuron axon growth, the researchers discovered. The keys to sensation, sensory neurons receive and transmit information to the central nervous system. Axons are the tendrils that branch out from them into tissues. "That led us to hypothesize that perhaps the fibroblasts are producing things that alter the growth of sensory nerves," Orange says. But what role was the protein playing in the sensation of pain? To find out, they grew neurons in vitro and then doused them with Netrin-4, which sparked the sprouting and branching of CGRP+ (gene-related peptide) pain receptors. It's the first time that Netrin-4 has been shown to alter the growth of pain-sensitive neurons, she notes. Imaging of RA synovial tissue also revealed an overabundance of blood vessels, which feed and nurture new cells. These vessels were encased by CGRP+ sensory nerve fibers and were growing towards the lining fibroblasts in areas of excessive tissue growth, or hyperplasia. This process likely leads to the squishy swelling that many rheumatologists and surgeons have mistaken for inflammation. Better drugs In the future, the researchers aim to home in on other products that fibroblasts may be producing that can affect the growth of pain-sensitive neurons. They'll also delve into the other types of sensory nerves that might be affected. "We studied one type, but there are about a dozen. We don't know if all nerves are affected equally. And we don't want to block all sensation. Sensory nerves are important for knowing that you should avoid certain movements and the position of your joint in space, for instance," Orange says. "We want to drill down on those details so that hopefully we can come up with other treatments for patients who don't have a lot of inflammation. Right now, they're taking medications that can cost $70,000 a year but have no chance of working. We must do a better job of getting the right drug to the right patient."