Navidea Biopharmaceuticals Ltd.

Findings to showcase the promise of company's 'Macrophage Conditioning' approach in reversing immunosuppression within acidic tumor microenvironment and driving anti-tumor activity OXFORD, UK, Nov. 3, 2022 /PRNewswire/ -- Pathios Therapeutics Limited ("Pathios"), a biotech company focused on the development of first-in-class therapies for cancer, today announced that new preclinical data highlighting the therapeutic potential of the company's novel GPR65 inhibition platform will be the focus of a poster presentation at the upcoming 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022). Presented results will showcase the company's unique approach to "macrophage conditioning" with novel GPR65 inhibitors as a means to reversing the immunosuppression that results from an acidic tumor microenvironment, and, in turn, driving anti-tumor activity. SITC 2022 is being held November 8-12, 2022, in Boston, Massachusetts. Details of the company's presentation at SITC 2022 are as follows: Poster Presentation #1324: Title: Inhibition of Acid Sensing by GPR65 Normalizes Gene Expression in Macrophages, Increases Immune Cell Infiltration in Tumors, and Restrains Subcutaneous MC38 Growth in Mice Presenting Author: Alastair Corbin, DPhil, senior scientist at Pathios Date/Time: Friday, November 11, 2022, 9:00 a.m. – 8:30 p.m. Eastern Time Location: Poster Hall C Additional information on the 37th Annual Meeting of SITC is available through the conference website at: About Acidity in the Tumor Microenvironment The acidic tumor microenvironment, inherent to many cancers, causes a profound immunosuppression of infiltrating immune cells. This environment disarms the anti-cancer immune response and negates the effectiveness of current immunotherapies. This is particularly evident in tumor associated macrophages (TAM), where acidity is sensed by the cell-surface receptor GPR65, leading to the widespread suppression of a host of pro-inflammatory mediators and anti-tumorigenic genes, as well as the upregulation of several tissue repair genes and angiogenic factors. About Pathios Therapeutics Launched in 2017, Pathios is a drug discovery and development company focused on translating innovative science into new medicines. Pathios was founded by a team of experienced biotech and pharmaceutical industry professionals, entrepreneurs, and clinicians. The company is focused on developing small-molecule inhibitors of the pH-sensing G protein-coupled receptor GPR65 to target immunosuppressive macrophages in advanced cancers. To date, Pathios has secured a total of US$33M in Series A funding from the leading venture capital firms, Canaan Partners, and Brandon Capital. Pathios is headquartered at the Innovation Centre on Milton Park, a key science precinct south of Oxford, UK. For more information, please visit . Contacts Pathios Therapeutics Stuart Hughes, Chief Executive Officer, +44 1865 292 039 [email protected] Tim Brons Vida Strategic Partners (media) 646-319-8981 [email protected] SOURCE Pathios Therapeutics

Currently used cisplatin-based combination treatments have limited efficacy against mesothelioma, which is one of the deadliest solid cancers Combining cisplatin with Allocetra™ led to a substantial and statistically significant survival benefit in a murine mesothelioma model, with a survival rate of 55% observed in the combination therapy group versus rates of 0% in untreated and cisplatin monotherapy groups, and 14.2% in the Allocetra™ monotherapy groupData highlight Allocetra’s™ broadly applicable immunotherapeutic effects and support an ongoing Phase I/II trial evaluating Allocetra™ combined with chemotherapy in patients with peritoneal metastases arising from solid cancer Nes-Ziona, Israel, Sept. 12, 2022 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced new preclinical data in a murine mesothelioma model showing a substantial and statistically significant survival benefit when Allocetra™ is combined with the chemotherapeutic agent, cisplatin. The data are featured in a poster being presented at the European Society for Medical Oncology (ESMO) Congress 2022, which is taking place both virtually and in-person at the Paris Expo Porte de Versailles in Paris, France from September 9, 2022 through September 13, 2022. Data featured in the ESMO poster are from preclinical studies in mice implanted with AB12 mesothelioma cells. Following implantation, mice were given vehicle (untreated group), intravenous (IV) cisplatin monotherapy, Allocetra™ monotherapy administered intraperitoneally (IP), or IV cisplatin in combination with IP Allocetra™. On day-57 post-implantation, the survival rate in the untreated group was 0%, and the mean survival duration was 31.7 ± 2.6 days. These were similar to the survival rate of 0% and slightly superior mean survival duration of 36.2 ± 5.0 days in the cisplatin monotherapy group. The survival rate and mean duration in the Allocetra™ monotherapy group were 14.2%, and 40.4 ± 10.9 days, respectively. When Allocetra™ was combined with cisplatin, a synergistic anti-cancer effect was observed, as the survival rate and mean duration in the combination therapy group were 55% and 49.3 ± 10.6 days, respectively. Notably, the increase in survival duration observed in the combination therapy group was statistically significant compared to the untreated group (p=0.0033, log rank), cisplatin monotherapy group ( p=0.0035, log rank), and Allocetra™ monotherapy (p=0.0413, log rank) group. Also featured in the ESMO poster are preclinical mesothelioma data showing a substantial survival benefit when Allocetra™ is combined with an anti-PD1 checkpoint inhibitor, and previously presented preclinical data in mesothelioma showing a substantial survival benefit when Allocetra™ is combined with a commercially approved anti-CTLA4 checkpoint inhibitor. “Our latest data add to an extensive body of preclinical evidence demonstrating Allocetra’s™ potential to address unmet needs in a variety of difficult-to-treat solid cancers,” said Prof. Dror Mevorach, M.D., Chief Scientific Officer of Enlivex and co-author of the poster. “The disproportionate presence of pro-tumor macrophages in tumor microenvironments severely limits the efficacy of many drug classes, including both immuno- and chemotherapies. With Allocetra™, we believe we can reprogram resident macrophages back to their homeostatic state, thereby enhancing the efficacy of complementary anti-cancer agents and avoiding the accumulation of pro-tumor macrophages. The data being presented at ESMO provide additional support for this hypothesis, as they highlight the potential benefits of combining Allocetra™ with cisplatin or immune checkpoint inhibitors such as anti-PD1 or anti-CTLA4. We look forward to discussing our findings with the medical community at this year’s congress.” Oren Hershkovitz, Ph.D., Chief Executive Officer of Enlivex, commented, “We are very pleased with the results of these preclinical studies, which support our ongoing Phase I/II trial evaluating Allocetra™ plus chemotherapy in patients with peritoneal metastases. This trial has been carefully designed to clinically demonstrate Allocetra’s™ novel mechanism of action and further our understanding of its safety profile and anti-cancer activity. Successfully achieving these goals would represent a key milestone, as it would bring us substantially closer to providing cancer patients with a novel and highly scalable next-generation cell therapy.” Mesothelioma, Treatment Landscape, and Macrophage-Solid Tumor Dynamics Mesothelioma is one of the deadliest solid cancers, with the few available treatment options having limited efficacy. These include checkpoint inhibitors targeting CTLA4 and PD1, as well as cisplatin-based combinations. People most at risk for mesothelioma generally have had long-term exposure to asbestos (e.g., construction workers, pipe fitters, and shipyard workers). In mesothelioma and other solid cancers, the efficacy of many anti-cancer agents is limited by tumor mechanisms that facilitate the recruitment of macrophages that become "pro-tumor" tumor associated macrophages (TAMs) rather than "anti-tumor" macrophages. The TAMs typically form a physical layer on top of the solid tumor and promote tumor growth and metastasis, thereby contributing to poor clinical outcomes and response to therapy. Allocetra™ is a cell therapy in development that targets these TAMs. Allocetra’s ™ proposed mechanism of action is to change the balance of macrophage populations so that they skew towards anti-tumor macrophages and away from pro-tumor macrophages. The ESMO poster (#479P) is titled, “Synergistic anti-tumor effect of Allocetra-OTS in combination with immune checkpoint inhibitors (ICI)/chemotherapy/CAR-T, through in-vivo reprogramming of macrophages.” It is currently available for viewing on ESMO’s virtual platform and will also be presented by Prof. Mevorach, during Poster Session 13 of the ESMO Congress. ABOUT ESMO ESMO is a leading professional organization for medical oncology. Its core missions are to: (1) improve the quality of cancer care, from prevention and diagnosis all the way to palliative care and patient follow-up; (2) educate – doctors, cancer patients and the general public – on the best practices and latest advances in oncology; and (3) promote equal access to optimal cancer care for all patients. ABOUT ALLOCETRA™ Allocetra™ is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra™ has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents. ABOUT ENLIVEX Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening conditions. For more information, visit https://enlivex.com/. Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “would”, “could,” “intends,” “estimates,” “suggests,” “has the potential to” and other words of similar meaning, including statements regarding expected cash balances, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRATM programs. All such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivex’s business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRATM product line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivex’s filings with the Securities and Exchange Commission, including in the Company’s most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law. ENLIVEX CONTACT Shachar Shlosberger, CFO Enlivex Therapeutics, Ltd. shachar@enlivexpharm.com INVESTOR RELATIONS CONTACTEric RibnerLifeSci Advisorseric@lifesciadvisors.com

Stand-alone therapy with PD1 checkpoint inhibitors has shown limited efficacy against ovarian cancer, with response rates in prior clincical trials ranging from 7-15%. This contributes to poor patient outcomes, as ovarian cancer is currently the fifth leading cause of cancer death among women.Murine ovarian cancer study results: Substantial survival effect of the combination therapy (AllocetraTM + anti-PD1 immune checkpoint inhibitor), with up to 50% survival probability vs. 0% in the untreated group, and a highly significant 83% increase in survival durationComparable and strong effect in survival duration with stand-alone anti-PD1 and stand-alone Allocetra™ treatments (42% and 58% increase, respectively), and no significant effect on survival probability. Study conducted in collaboration with Yale Cancer Center These results, together with prior preclinical data in mesothelioma cancer, demonstrate Allocetra’s broadly applicable immunotherapeutic effects and its potential to deliver survival benefits across multiple solid cancers when combined with various immune checkpoint inhibitors. Nes-Ziona, Israel, May 31, 2022 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the “Company”), a clinical-stage macrophage reprogramming immunotherapy company, today announced new preclinical data from an ovarian cancer study conducted in collaboration with Yale Cancer Center. The study showed substantial and statistically significant improvements in survival benefit, survival duration and tumor burden reduction when Allocetra™ was combined with an anti-PD1 checkpoint inhibitor. The data will be featured in an upcoming poster presentation at the ASCO Annual Meeting, which is taking place both virtually and in-person at the McCormick Place convention center in Chicago, Illinois (United States) from June 3 – 7, 2022. The upcoming ASCO poster will also highlight a prior preclinical study in mesothelioma cancer that showed a substantial survival benefit when Allocetra™ was combined with a commercially approved anti-CTLA4 checkpoint inhibitor. Previously reported preclinical data in peritoneal cancer that show a substantial survival benefit when Allocetra™ is combined with chimeric antigen receptor (CAR) T-cell therapy will also be presented. Marcus Bosenberg, MD, PhD, Professor of Dermatology, Pathology, and Immunobiology and Director of the Center for Precision Cancer Modeling at Yale Cancer Center, commented: “I am highly encouraged by these preclinical findings, which clearly demonstrate Allocetra’s potential to address a long-standing unmet need. The immunosuppressive microenvironments of ovarian tumors have limited the clinical benefits of checkpoint inhibition in this indication. Allocetra™ may reverse immunosuppressive tumor microenvironments and may ultimately improve patient outcomes by synergistically enhancing checkpoint inhibitor efficacy in clinical trials.” Prof. Dror Mevorach, MD, Chief Scientific Officer of Enlivex, added: “In these latest murine studies, we once again saw Allocetra™ synergistically combine with a checkpoint inhibitor to deliver a statistically significant survival benefit in a difficult-to-treat solid tumor model. We are now working to translate these promising findings to the clinic and expect to initiate two solid tumor trials evaluating Allocetra-based combinations by year-end. Through these studies, we aim to clinically demonstrate the broad applicability of Allocetra’s proposed mechanism of action to enable the expansion of its potential therapeutic impact.” Ovarian Cancer, Checkpoint Inhibitors, and Macrophage-Solid Tumor DynamicsOvarian cancer is currently the fifth leading cause of cancer death among women. Stand-alone therapy with PD1 checkpoint inhibitors, which are designed to treat cancer by activating immune cells that can identify and destroy tumors, has thus far shown limited efficacy in this indication. Prior clinical trials in ovarian cancer evaluating anti-PD1 monotherapy have shown response rates of only 7% – 15%. The limited response rates of checkpoint inhibitors in ovarian and other solid cancers is linked to tumor defense mechanisms that facilitate the recruitment of macrophages which become “pro-tumor” tumor associated macrophages (TAMs) rather than “anti-tumor” macrophages. Pro-tumor TAMs typically form a physical layer on top of solid tumors and induce an immunosuppressive tumor microenvironment (TME). This in-turn promotes tumor growth and metastasis and makes it very difficult for immune cells or any anti-cancer drug to efficiently attack cancerous cells. Allocetra™ is a cell therapy in development that is targeted towards TAMs. Its proposed mechanism of action is to change the balance of macrophage populations so that they skew towards anti-tumor macrophages and away from pro-tumor macrophages. This is expected to enhance the efficacy of checkpoint inhibitors and other immunotherapeutic agents. The Ovarian Cancer ModelTo expand upon its previous preclinical findings in mesothelioma and test the potential effects of cell-therapy-induced macrophage reprogramming in a second difficult-to-treat solid tumor model, Enlivex collaborated with the Yale Cancer Center to run preclinical studies in which groups of mice were implanted with ID8 ovarian cancer cells. The difference between the groups was the treatment given, which started on day 7 after the cancer’s initial growth period. Results from the preclinical ovarian cancer study further support Allocetra’s potential to significantly improve survival outcomes by facilitating macrophage reprogramming in the solid tumor microenvironment. Twelve weeks after the initial treatment, untreated mice (vehicle) showed a survival rate of 0%, and a median survival duration of 6 weeks. Survival duration was increased with stand-alone treatment with either an anti-PD1 inhibitor or Allocetra™. The magnitude of the increases were similar between these two monotherapy groups (42% and 58% increase, respectively), with no significant effect on overall survival probability observed between the monotherapy groups. Notably, combining Allocetra™ with anti-PD1 therapy led to a synergistic anti-cancer effect, with survival rates of up to 50% (5/10) and an 83% increase in median survival duration observed in the combination therapy groups. The attached figure shows the Kaplan-Meier survival probability curve for each group of the study, and the table below provides the treatment data. No treatmentAnti PD-1 (1.25 mg/kg) monotherapyAllocetra 20M monotherapyCombination AllocetraL 20M + Anti PD-1 (1.25 mg/kg)Median survival duration (weeks)68.59.511% Survival duration increase vs untreated--42%58%83%Overall survival percent0%10%(not statistically significant)0%50%(statistically significant) As previously reported, Enlivex plans to initiate a Phase Ib trial evaluating Allocetra™ in combination with chemotherapy in solid peritoneal tumors in Q3 2022, and a Phase I/II trial evaluating Allocetra™ in combination with an immune checkpoint inhibitor in late 2022. The title of the upcoming ASCO poster is “In-vivo reprogramming macrophages and dendritic cells with Allocetra-OTS: Successful mono- and combination-antitumor therapy.” The poster will be presented during the ASCO Annual Meeting’s “Developmental Therapeutics – Immunotherapy” poster session, which is taking place on June 5, 2022, from 8:00 AM - 11:00 AM CDT (9:00 AM - 12:00 PM ET). A copy of the poster’s corresponding abstract is currently available on the ASCO Annual Meeting Website. ABOUT THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY Founded in 1964, the American Society of Clinical Oncology is the world's leading professional organization for physicians and oncology professionals caring for people with cancer. ABOUT ALLOCETRA™ Allocetra™ is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra™ has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents. ABOUT ENLIVEX Enlivex is a clinical-stage macrophage reprogramming immunotherapy company developing Allocetra™, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening conditions. For more information, visit http://www.enlivex.com.Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as “expects,” “plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,” “would”, “could,” “intends,” “estimates,” “suggests,” “has the potential to” and other words of similar meaning, including statements regarding expected cash balances, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRATM programs. All such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivex’s business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRATM product line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivex’s filings with the Securities and Exchange Commission, including in the Company’s most recent Annual Report on Form 20-F filed with the Securities and Exchange Commission. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law. ENLIVEX CONTACT Shachar Shlosberger, CFO Enlivex Therapeutics, Ltd. shachar@enlivexpharm.com INVESTOR RELATIONS CONTACTEric RibnerLifeSci Advisorseric@lifesciadvisors.com Attachment Ovarian Cancer ID8 Study – Survival Probability