CD68

Study Met Primary Endpoint for Safety and Tolerability First-in-Human, Single-Agent Study Demonstrated Immune Activity Across Multiple Biomarkers Company to Seek Publication of Complete Data Analysis in 2023 TEL AVIV, Israel, Dec. 20, 2022 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial-stage biopharmaceutical company focused on oncology, today announced results from the Phase 1/2a study of intratumoral cancer vaccine candidate, AGI-134, designed to evaluate the safety and biological activity of AGI-134 in patients with unresectable metastatic solid tumors. The study met its primary endpoint of AGI-134's safety and tolerability. In this first-in-human trial, a total of 38 patients were treated with AGI-134: 5 patients in part 1, the accelerated dose-escalation part of the study; and 33 patients in part 2, the dose expansion part of the study. Part 1 demonstrated that AGI-134 was safe and well tolerated, with no dose-limiting toxicities reported. The maximum tolerated dose was not reached and the recommended dose for part 2 of the study (RP2D) was determined to be up to 200mg. In the dose expansion part 2 of the study, AGI-134 was generally well-tolerated, with treatment-related adverse events being transient and mostly mild to moderate. Generation of an immune response and markers of clinical efficacy were assessed as secondary endpoints. Most patients analyzed showed an increase in Alpha-Gal antibodies, indicating increased overall immune activity. Additionally, increases in antigen presenting cells (APCs) were observed in most tissue samples analyzed, and T cell and macrophage tumor infiltration was seen in approximately one-third of evaluable patients' injected tumors, and in approximately half of evaluable patients' un-injected lesions. Radiological assessments found that 29 percent of patients in the trial achieved best overall response of stable disease. Seven of the 11 patients who achieved stable disease had previously failed checkpoint-inhibitor therapy. "In this first-in-human, single-agent trial, we were encouraged with AGI-134's safety profile and the observed initiation of immune activity in patients," said Philip Serlin, Chief Executive Officer of BioLineRx. "We plan to seek publication of our data at a medical congress in 2023, and in consultation with our scientific advisory board, we will determine the next steps for the program in the first half of next year. We want to thank the patients who participated in this important trial, their caregivers, and our physician collaborators." The Phase 1/2a clinical trial was a multicenter, open-label study, which recruited a total of 38 patients in the UK, Spain and Israel. The study had two parts: part one was an accelerated dose-escalation study in five patients to determine the maximum tolerated dose and the recommended dose for part 2 of the study; part two was a dose expansion study at the recommended dose in 33 patients, designed to evaluate the safety and tolerability of AGI-134, and to validate AGI-134's mechanism of action using a wide array of biomarkers. For more information on this Phase 1/2a study, see NCT03593226. PATIENT CHARACTERISTICS Total enrollment: 38 patients Gender: 21 Male, 17 Female Solid Tumor Cancer Type: Melanoma (21), Colon (5), Breast (4), Squamous Cell (3). Sarcoma (2), Cervical Node (1), Endometrial (1), Synovial (1) ECOG score: 0 to 1 with life expectancy not less than 3 months SAFETY AGI-134 was generally well-tolerated, and adverse events (AEs) were mostly transient, mild to moderate in severity CLINICAL RESPONSE Best overall response of stable disease (SD) was observed in 29 percent (11/38) of patients according to RECIST1.1 criteria 7 of the 11 patients who achieved stable disease had failed prior checkpoint inhibitor therapy IMMUNE RESPONSE BIOMARKERS Increase in Alpha-Gal antibodies Most patients analyzed showed an increase in Alpha-Gal antibodies as measured by IgG and IgM titers Tumor infiltration following treatment with AGI-134 59 percent (10/17) of evaluable patients showed an increase in conventional dendritic cells (CD11c+ HLADR+) within or outside of the tumor 29 percent (5/17) of evaluable patients showed an increase in T helper cells (CD3+CD4+) in injected lesions and 47 percent (8/17) in un-injected lesions, 35 percent (6/17) of evaluable patients showed an increase in Cytotoxic T cells (CD3+CD8+) in injected lesions, and 47 percent (8/17) in un-injected lesions 24 percent (4/17) of evaluable patients showed an increase in macrophages (CD68+) in injected lesions and 47 percent (5/17) in un-injected lesions About AGI-134 AGI-134 is a synthetic alpha-Gal glycolipid in development for solid tumors that is highly differentiated from other cancer immunotherapies. AGI-134 is designed to label cancer cells with alpha-Gal via intra-tumoral administration, thereby targeting the body's pre-existing, highly abundant anti-alpha-Gal (anti-Gal) antibodies and redirecting them to treated tumors. Binding of anti-Gal antibodies to the treated tumors results in activation of the complement cascade, which destroys the tumor cells and creates a pro-inflammatory tumor microenvironment that also induces a systemic, specific anti-tumor (vaccine) response to the patient's own tumor neo-antigens. AGI-134 has been evaluated in numerous pre-clinical studies. In a mouse melanoma model, treatment with AGI-134 led to regression of established primary tumors and suppression of secondary tumor (metastases) development. Synergy has also been demonstrated in additional pre-clinical studies when combined with an anti-PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies, and improve the rate and duration of responses in multiple cancer types. AGI-134 was obtained by BioLineRx through the acquisition of Agalimmune Ltd. About BioLineRx BioLineRx Ltd. (NASDAQ/TASE: BLRX) is a pre-commercial-stage biopharmaceutical company focused on oncology. The Company's lead development program, motixafortide, a novel selective inhibitor of the CXCR4 chemokine receptor, may support diverse therapeutic approaches in oncology and other diseases. APHEXDA® (motixafortide) was successfully evaluated in a Phase 3 study in stem cell mobilization for autologous transplantation in multiple myeloma patients, has reported positive results from a pre-planned pharmacoeconomic study in the U.S., and has had its NDA submission accepted by the FDA with a PDUFA date of September 9, 2023. Motixafortide was also successfully evaluated in a Phase 2a study for the treatment of pancreatic cancer (PDAC) in combination with KEYTRUDA® and chemotherapy and is currently being studied in combination with LIBTAYO® and chemotherapy as a first-line PDAC therapy. A randomized phase 2b study with 200 patients in combination with an anti-PD1 and chemotherapy as a first-line PDAC therapy will initiate in 2023. BioLineRx is also developing a second oncology program, AGI-134, an immunotherapy treatment for multiple solid tumors that is currently being investigated in a Phase 1/2a study. For additional information on BioLineRx, please visit the Company's website at , where you can review the Company's SEC filings, press releases, announcements, and events. Forward Looking Statement Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "anticipates," "believes," "could," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," and "would," and describe opinions about future events. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of BioLineRx's therapeutic candidates; BioLineRx's ability to establish and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for and ability to access sufficient additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; statements as to the impact of the political and security situation in Israel on BioLineRx's business; and the impact of the COVID-19 pandemic and the Russian invasion of Ukraine, which may exacerbate the magnitude of the factors discussed above. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 16, 2022. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law. Contacts: United States John Lacey BioLineRx +1-781-392-5514 [email protected] Israel Moran Meir LifeSci Advisors, LLC +972-54-476-4945 [email protected] SOURCE BioLineRx Ltd.

– Data demonstrated [18F]OP-801 is a promising tracer for imaging activated macrophages/microglia with high sensitivity in the lumbar spine of a murine model of multiple sclerosis (MS) – – Treatment of MS model mice with a hydroxyl dendrimer CSF1R inhibitor demonstrated selective killing of reactive microglia and lower uptake of the investigative PET tracer compared to untreated mice – – Showed a reliable, high-yielding synthetic route to producing [18F]OP-801 enabling its use in humans – REDWOOD CITY, Calif., Sept. 29, 2022 (GLOBE NEWSWIRE) -- Ashvattha Therapeutics (“Ashvattha”), a clinical-stage company developing novel hydroxyl dendrimer therapeutics, today announced preclinical data presented by collaborators from Stanford University demonstrating that its hydroxyl dendrimer (HD)-based PET tracer, [18F]OP-801, can detect activated macrophages and microglia with high sensitivity and specificity in an experimental autoimmune encephalomyelitis (EAE) murine model of multiple sclerosis (MS), in addition to being reproducibly synthesized and suitable for human use. The data were presented at the World Molecular Imaging Congress being held September 28th – October 1st, 2022, at the Miami Beach Convention Center in Miami, FL. “Even though there are several immunomodulatory therapies available to treat MS, selection and monitoring of interventions has been hindered by a lack of specific in vivo imaging biomarkers,” stated Michelle James, PhD, an assistant professor of radiology and neurology at Stanford University. “We are encouraged by the promising data demonstrating Ashvattha’s hydroxyl dendrimer-based PET tracer’s ability to detect aberrant immune activation in an animal model of disease with high sensitivity and specificity and look forward to further investigating which cell subtypes take up this tracer in different neuroinflammatory models.” The presentation entitled “Specific detection of pathogenic myeloid cells in a mouse model of multiple sclerosis using [18F]OP-801 before and after treatment with a CSF1R inhibitor,” was based on a study evaluating [18F]OP-801 for its ability to detect pathogenic myeloid cells in an EAE murine model of MS at both pre-symptomatic and symptomatic disease stages. Key highlights from the presentation include: Quantification of PET images revealed a significantly higher signal in spinal cord of diseased mice, even prior to symptom development, compared to healthy mice.[18F]OP-801 accurately detected treatment response in EAE mice given daily HD-CSF1R inhibitor, used to deplete microglia and macrophages. Notably, there was significantly lower uptake in spinal cord PET images of successfully treated EAE mice compared to untreated EAE mice by post-hoc analysis.PET imaging data was corroborated by autoradiography images, showing significantly higher signal in the lumbar spinal cord of untreated compared to treated EAE mice.Importantly, [18F]OP-801 signal in treated mice corresponded with a dramatic reduction in CD68 immunostaining of spinal cord tissue compared to untreated mice.Taken together, there was no significant difference in [18F]OP-801 binding in peripheral tissues in diseased mice, further confirming the specificity of [18F]OP-801 for activated microglia/macrophages. The presentation entitled “Streamlined Production of [18F]OP-801 and Radiation Dosimetry to Enable Clinical Translation for Imaging Neuroinflammation,” describes the automated, high-yield radiosynthesis and quality control (QC) analyses of [18F]OP-801 for routine clinical production, in addition to analysis of its stability in human plasma, and human dosimetry estimates. Key highlights from the presentation include: [18F]OP-801 was reproducibly synthesized in suitable yield and greater than 99% radiochemical purity.Standard quality control tests confirmed that [18F]OP-801 is suitable for injection and human use.[18F]OP-801 was shown to be stable in vitro in formulation and human plasma, with >99% tracer intact after 90 minutes.Human dosimetry estimates based on mouse imaging data are conducive to translation and clinical imaging of [18F]OP-801. Chronic activation of macrophages and microglia play a major role in the onset and progression of many neurological diseases, such as ALS, Alzheimer’s disease and MS. While PET imaging has the potential to detect activated cells in the aforementioned diseases, most current PET tracers for imaging neuroinflammation are not entirely specific for macrophages/microglia. To address this need, Ashvattha is developing a Hydroxyl dendrimer-based PET tracer, [18F]OP-801, as a companion biomarker to pair with its HD therapeutics to treat neuroinflammation. Jeffrey Cleland, Ph.D., Chairman & CEO of Ashvattha Therapeutics, added, “This data builds on previous studies demonstrating our HD-based PET tracer’s potential to be an effective imaging agent that could play a critical role in the selection and monitoring of interventions in patients with neurodegenerative diseases characterized by neuroinflammation. We are conducting a Phase 1/2 clinical trial of [18F]OP-801 in healthy volunteers and ALS patients and anticipate sharing preliminary data in the first half of 2023.” About [18F]OP-801[18F]OP-801 is a hydroxyl dendrimer (HD) imaging agent that provides information on uptake of HDs across tissue barriers including the blood-brain barrier. [18F]-OP-801 selectively targets by reactive microglia in regions of neuroinflammation in neurodegenerative diseases. [18F]OP-801 has been shown to be selectively (>95%) taken up by reactive macrophages/microglia.1 [18F]OP-801 shows promise for visualizing the progression of neuroinflammation with high specificity and sensitivity, warranting clinical investigation. A Phase 1/2 clinical trial of [18F]OP-801 is currently underway in healthy volunteers and ALS patients. About Ashvattha Therapeutics Ashvattha Therapeutics is a clinical-stage biotech company developing novel hydroxyl dendrimer therapeutics (HDTs) targeting unmet medical needs in ophthalmology, neurology, inflammation and neuro-oncology. Hydroxyl dendrimers (HDs) are a targeted nanomedicine technology exclusively licensed from our founders, Kannan Rangaramanujam and Sujatha Kannan at Johns Hopkins University. HDs chemically conjugated to disease-modifying drugs create novel proprietary HDTs selectively targeting reactive inflammatory cells in disease tissue with localized sustained effects. Ashvattha has initiated multiple programs with HDTs focused on neurology, ocular neovascular disease including neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME), and hyperinflammation in diseases. For more information, visit: www.avttx.com. Media Contact Sky StriarLifeSci Communications 617-797-6672sstriar@lifescicomms.com _________________________________________1 Henningfield, C.M., Cleland, J.L., Sharma, R., Green, K.N.Selective targeting of plaque-associated microglia through systemic dendrimer administration in an Alzheimer’s disease model. Alzheimer's & Dementia. 2020; Volume 16. Issue S2. https://doi-org.libproxy1.nus.edu.sg/10.1002/alz.040661

Combining the power of spatial biology and AI, Propath and Nucleai push the boundaries of pathology tissue analytics to develop a novel, high multiplexed immunofluorescence (IF) panel and associated AI-powered algorithm for biomarker discovery and development HEREFORD, United Kingdom & TEL AVIV, Israel--(BUSINESS WIRE)-- Propath UK, Europe’s leading CRO for spatial biology, and Nucleai, a leader in AI-powered spatial biology transforming precision medicine by unlocking spatial biology insights from pathology data, announce their collaboration to develop and validate a 30-plex immunofluorescence (IF) panel focused on protein targets relevant to immuno-oncology. For our pharmaceutical and biotechnology partners, this groundbreaking panel, in conjunction with Nucleai's validated AI assay, can be used to unlock insights from immunotherapy trials and inform the development of novel biomarkers and companion diagnostics (CDx). This press release features multimedia. View the full release here: Extract from a 10-plex immunofluorescence stain on human tonsil tissue, performed by Propath UK using the Lunaphore COMET. Blue – DNA (DAPI), Green - CD4, Orange – CD8, Teal – FoxP3, Red CD68, White – PD-1, Magenta - PanCK (Photo: Business Wire) “Our strategic partnership with Propath has far-reaching implications in biomarker discovery,” said Avi Viedman, CEO of Nucleai. “The collaboration allows us to develop and deploy AI-based multi-modal models to identify unique sets of previously unavailable biomarkers and drug targets. Together, we are pushing the boundaries of pathology tissue analytics.” Applying its expertise in multiomic spatial biology and high-plex immunofluorescence, Propath will develop a novel protocol using the innovative Lunaphore COMET™ platform for analysis of 30 high-value protein targets from a single tissue section. The COMET™ enables rapid development of highly multiplexed panels, with robust and reproducible staining. Propath UK will use experience gained across a range of spatial proteomic and transcriptomic projects completed on its in-house multiomic platforms. “Spatial biology is transforming biopharma research by enabling deeper analysis of cell phenotypes with full spatial context in the tissue microenvironment,” commented Dr Krish Soni, Chief Executive of Propath UK. “We are delighted to collaborate with Nucleai on this ambitious project which will empower researchers to unlock the potential of spatial biology, with relevance to programs from discovery through to translational and clinical research.” Nucleai’s collaboration with Propath comes on the heels of the recent news announcement that it made with Lunaphore, announcing their partnership to provide AI-powered spatial biology analysis to accelerate drug discovery. This three-way synergy between Propath, Lunaphore and Nucleai brings new capabilities to pharma companies. The partnership utilizes Lunaphore’s flagship COMET™ platform for hyperplex staining and imaging with Nucleai’s cutting-edge AI spatial models to derive new insights from tissue biopsies, including novel drug targets, mechanisms of action, and biomarkers to advance the field of precision medicine. Demonstrating the utility of the technology, Propath provides high-plex tissue analytics using the Lunaphore COMET™ as a fully managed service. Nucleai’s proprietary AI-powered, pathology-based biomarker discovery platform combined with Propath’s multiomic spatial biology and high-plex immunofluorescence will accelerate the pharmaceutical industry’s drug development and research programs. A fundamental aspect of precision oncology is predicting drug response for a patient cohort. The combined expertise will allow computational analysis of the tumor microenvironment, feature selections to predict disease prognosis and drug response including cancer sub-type determination, to stratify patients and support early detection and prognosis. About Propath UK Propath UK is a specialist CRO providing research services in molecular pathology, spatial biology and histopathology for the global biopharmaceutical sector. The company offers a range of technologies for spatial proteomic and transcriptomic tissue analysis, including the NanoString GeoMx and CosMx, the Lunaphore COMET™ and the Akoya PhenoCycler-Fusion™. Propath’s reputation has been gained across 35 years by providing a consistent and responsive service across thousands of pre-clinical and clinical studies. To learn more, please visit . About Nucleai Nucleai is an AI-powered spatial biology company with a mission to transform drug development and clinical treatment decisions by unlocking and analyzing the valuable information in the pathology data. Nucleai provides pharmaceutical companies, contract research organizations, and diagnostics laboratories with a state-of-the-art AI platform to improve clinical trials and clinical decision-making. For more information, please visit .