CMV pp65

Study is the first randomized, controlled trial examining a vaccine’s effectiveness in controlling CMV in recipients of HSCT from vaccinated donors Encouraging pilot study results demonstrated the benefit of vaccinating donors with Triplex to convey protective CMV-specific T cell immunity to allogeneic HSCT recipients at risk for CMV reactivation Jan. 27, 2025 -- Fortress Biotech, Inc. (Nasdaq: FBIO) (“Fortress”), and its majority-owned subsidiary, Helocyte, Inc. (“Helocyte”), today announced that the first patient was dosed in a multicenter, placebo-controlled and randomized Phase 2 clinical trial to evaluate Triplex, a cytomegalovirus (“CMV”) vaccine, when administered to human leukocyte antigen (“HLA”) matched related stem cell donors to reduce CMV events in patients undergoing hematopoietic stem cell transplantation (“HSCT”). The Phase 2 clinical trial is funded by a grant from the National Cancer Institute (“NCI”). Triplex is anticipated to induce a CMV-specific immune response in the donor’s body who then conveys that virus-specific immunity to the intended recipient of the stem cell transplant through the concept of adoptive immunity. Vaccination of donors with Triplex prior to stem cell harvest and transplant is believed to introduce virus-specific immunity sooner, and in turn, reduce CMV events in patients undergoing stem cell transplantation. The objective of the trial is to determine whether Triplex is safe and effective in reducing CMV events in recipients of HSCT from vaccinated donors. CMV reactivation is one of the most common and life-threatening complications following allogeneic HSCT. The virus reactivates in an estimated 60-70% of CMV-seropositive recipients of HSCT with primary CMV infection occurring in 20-30% of CMV-seronegative recipients of HSCT from CMV-seropositive donors. “CMV frequently affects patients undergoing transplants, posing significant risks to their recovery and survival. In this Phase 2 clinical trial, we are testing a new treatment approach, offering promise for better CMV management in HSCT recipients. This approach transfers CMV immunity from donors to transplant recipients, thereby potentially reducing the need for antiviral medications that can delay reconstitution of virus-specific immunity,” said Don J. Diamond, Ph.D., Professor, Hematology & Hematopoietic Cell Transplantation, City of Hope’s Los Angeles campus and the grants’ principal investigator. Dr. Diamond and his team developed Triplex in cooperation with the NCI “NExT” program. Dr. Diamond also serves as a paid consultant to Helocyte and holds equity in the company. The initial Phase 2 clinical trial (NCT03560752) builds upon Phase 1 pilot trial data that evaluated the potential safety and immunological response of Triplex presented at the 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR and published in the American Journal of Hematology. The study is being conducted across three nationally recognized transplant centers in the United States (City of Hope in Duarte, California; Brigham & Women’s Hospital and the Dana-Farber Cancer Institute in Boston; and Northside Medical Center in suburban Atlanta). A second trial, also funded by the NCI award, will formally test the same concept and will include higher risk transplant recipients, who are only partially HLA-matched to their donors. A preliminary study of that transplant population was also recently completed (NCT04060277). Lindsay A. Rosenwald, M.D., Fortress’ Chairman and Chief Executive Officer and Executive Chairman of Helocyte, Inc., said, “This new vaccination paradigm carries the advantage of potentially conveying earlier and more robust CMV immunity to a stem cell transplant recipient, versus vaccinating a HSCT recipient after engraftment has occurred around four weeks following transplant. We are very pleased that this trial is underway and believe that this novel treatment approach could play a significant role in the prevention and treatment of CMV in the future. Triplex is the subject of multiple ongoing, planned clinical trials in the transplant setting and for HIV-1.” Triplex was originally developed by City of Hope, one of the largest and most advanced cancer research and treatment organizations in the United States, and exclusively licensed to Helocyte. Triplex is a universal (non-HLA-restricted) recombinant Modified Vaccinia Ankara viral vector vaccine engineered to induce a robust and durable virus-specific T cell response to three immuno-dominant proteins [UL83 (pp65), UL123 (IE1), UL122 (IE2)] linked to CMV complications in the post-transplant setting. In completed Phase 1 (see NCT01941056) and Phase 2 (see NCT02506933, NCT03383055) studies, Triplex was found to be well-tolerated and highly immunogenic. Triplex is currently the subject of multiple ongoing clinical trials, including: a Phase 2 evaluation for CMV control in recipients of liver transplant (see NCT06075745); a Phase 1/2 trial for CMV control in pediatric recipients of HSCT (see NCT03354728); a Phase 2 trial for safety and immunogenicity in adults living with HIV and CMV (see NCT05099965); a Phase 2 trial for CMV control in recipients of stem cell transplant in which the stem cell donor is vaccinated with Triplex (see NCT06059391) and a Phase 1 trial of Triplex in combination with a bi-specific CMV/CD19 Chimeric Antigen Receptor (CAR) T cell for the treatment of non-Hodgkin lymphoma (see NCT05432635). Triplex is also the subject of several planned studies, including a Phase 2 trial for CMV control in recipients of kidney transplants. Helocyte additionally entered into an option agreement with City of Hope for exclusive worldwide rights to a novel bispecific CMV/HIV CAR T cell therapy (optionally for use in combination with Triplex), which is currently the subject of a Phase 1 trial in adults living with HIV-1 (see NCT06252402). Helocyte is a clinical-stage company developing novel immunotherapies for the prevention and treatment of cancer and infectious diseases, including cytomegalovirus (“CMV”) and human immunodeficiency virus (“HIV”). The Centers for Disease Control estimate that 50 to 80 percent of Americans are living with CMV by the age of 40. While the virus is asymptomatic in healthy individuals, it can cause severe and life-threatening disease in those with weakened or uneducated immune systems. Patients undergoing allogeneic stem cell and solid organ transplantation are at particularly high risk of experiencing complications associated with CMV. According to the Center for International Blood and Marrow Transplant Research, there were approximately 9,000 allogeneic (unrelated and related) bone marrow and cord blood transplants performed in the United States in 2023. According to preliminary data from the Organ Procurement and Transplantation Network, there were over 46,000 organ transplants performed in the United States in 2023, comprised primarily of kidney and liver transplant procedures. Helocyte’s Triplex vaccine is engineered to induce a robust and durable virus-specific T cell response to control CMV in transplant recipients. While current antiviral therapies have reduced the rate of CMV disease-related mortality in transplant recipients, such treatments have been linked to increased toxicity, delayed immune reconstitution and late onset of CMV. The Helocyte vaccines may also educate the body’s innate immune system to fight CMV. For more information, please visit www.helocyte.com. Fortress Biotech, Inc. (“Fortress”) is an innovative biopharmaceutical company focused on acquiring and advancing assets to enhance long-term value for shareholders through product revenue, equity holdings and dividend and royalty revenue. The company has seven marketed prescription pharmaceutical products and over 20 programs in development at Fortress, at its majority-owned and majority-controlled partners and subsidiaries and at partners and subsidiaries it founded and in which it holds significant minority ownership positions. Such product candidates span six large-market areas, including oncology, rare diseases and gene therapy, which allow it to create value for shareholders. Fortress advances its diversified pipeline through a streamlined operating structure that fosters efficient drug development. The Fortress model is focused on leveraging its significant biopharmaceutical industry expertise and network to further expand the company’s portfolio of product opportunities. Fortress has established partnerships with some of the world’s leading academic research institutions and biopharmaceutical companies to maximize each opportunity to its full potential, including AstraZeneca, City of Hope, Fred Hutchinson Cancer Center, Nationwide Children’s Hospital and Sentynl. The content above comes from the network. if any infringement, please contact us to modify.

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Exo Therapeutics, Inc. , a pre-clinical company developing a pipeline of drug candidates that target exosites, unique small-molecule binding pockets that are distinct from traditional active and allosteric sites, to reprogram target enzyme activity for precise and robust therapeutic effects, today presented a late-breaking poster on its preclinical program targeting the TBK1/STING interaction of the cGAS-STING pathway at the American College of Rheumatology’s Convergence Conference (ACR) in Washington, D.C. Aberrant activation of the cGAS/TBK1-/STING pathway has been shown to be linked to autoimmune diseases like SLE, CLE, SSc and Sjögren’s. Historically, inhibiting this pathway has proven to be difficult for active-site inhibitors due to their inadequate selectivity, which can lead to off-target effects and narrow therapeutic indices. Exo’s approach seeks to overcome these challenges with its novel exosite inhibitors that disrupt STING-mediated TBK1 activation while avoiding the beneficial functions of the kinase on viral suppression and maintenance of autophagy. Data presented show that EXO-TBKis, novel TBK1 inhibitors that selectively and potently inhibit the TBK1/STING pathway, demonstrated efficacy in multiple cellular and mouse models as well as patient-derived samples. These findings support the company’s nomination of a lead development candidate for the treatment of autoimmune diseases such as Systemic and Cutaneous Lupus (SLE and CLE), Systemic Sclerosis (scleroderma, SSc) and Sjögren’s Syndrome. “Exo’s TBK1 selective exosite inhibitors have demonstrated their ability to potently and selectively inhibit pathogenic effects of TBK1/STING, while sparing beneficial antiviral and cellular functions,” said Dr. Jörg Distler, University of Erlangen. “This approach has the potential to deliver therapeutic benefit to individuals living with autoimmune diseases like SSc and I’m looking forward to the nomination of their lead development candidate based on these promising data.” Data show that an EXO-TBK1i displayed exceptional exosite binding affinity on the target (IC50 -9nM), that translates into double-digit nanomolar potencies in human monocytes, THP1 cells, monocytes and mouse macrophages. EXO-TBK1i were also shown to demonstrate enhanced selectivity when compared to a TBK1 active-site, cGAS and STING inhibitors. Additionally, EXO-TBK1is were shown to preserve autophagy, while sparing RIG-I activity with 100-fold selectivity, two activities that are linked to effective immune responses to infection. Dose dependent suppression of p-TBK1, p-STING and inflammatory cytokines were observed in a STING activated DMXAA mouse model. In a disease model, TREX-1 null mouse, EXO-TBK1i was shown to suppress heart inflammation with a dramatic reduction of proinflammatory cytokines including IFNβ, CXCL-10, CXCL-9 and IFIT1. The TBK1i also displayed dose-dependent inhibition of p-TBK1, p-STING, p-IRF3 and p-P65 in the TREX-1 model. Most notably, EXO-TBK1i demonstrated robust effects in SLE and SSc patient samples. When assessed for activity in SLE patient-derived human whole blood and PBMC, EXO-TBK1i robustly suppressed pathway activation. Similarly, EXO-TBK1i significantly suppressed pathway activation and expression of SMA and stress fibers in SSc patient-derived fibroblasts. Details of the poster presentations are as follows: Abstract Title: Targeted Exosite Inhibition of STING Activation of TBK1 Selectively Blocks Type I Interferon and NFκB Responses for Treatment of Autoimmune Diseases Presenting Author: Bhavatarini Vangamudi, Ph.D. Presentation Type: Poster Session: Late-Breaking Posters (L01 - L14) Date: Monday, November 18 Presentation Time: 10:30 AM - 12:30 PM Abstract ID: 1943848 Final Number: L01 About Exo Therapeutics Exo Therapeutics is a small molecule drug discovery and development company co-founded by Professors David R. Liu, Alan Saghatelian and Juan Pablo Maianti with a pioneering technology to address intractable pharmaceutical targets. By leveraging the company’s ExoSight TM platform, Exo is developing a deep pipeline of potent drug candidates that bind exosites, distal and unique binding pockets that have the potential to reprogram enzyme activity for precise and robust therapeutic effect. Through this specific and selective approach to challenging targets, the company's team of world-class researchers is unlocking breakthrough therapeutics in inflammation, oncology and a broad range of other diseases. For more information, visit www.exo-therapeutics.com .

Among the 7 patients on VBI-1901 treatment long enough to have 1+ MRI scan at the time of analysis, one partial tumor response (PR) and two stable disease (SD) observations have occurred as of May 15, 2024 The partial response, which demonstrated a 67% reduction in tumor size vs. baseline, was observed at week 6, after 2 doses of VBI-1901 The disease control rate (DCR) in the VBI-1901 study arm was 43% (n=3/7) compared to 0% in the control arm (n=0/6) – n=5/6 patients in the control arm have experienced a 2-8x increase in tumor size vs. baseline and have been taken off study protocol FDA has granted both Fast Track Designation and Orphan Drug Designation to VBI-1901 in recurrent GBM following previous Phase 1/2a study results Additional interim data expected Q4 2024, including additional tumor response data and initial survival data from early-enrolled participants, subject to speed of enrollment CAMBRIDGE, Mass.--(BUSINESS WIRE)-- VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, today announced new interim tumor response data from the ongoing randomized, controlled Phase 2b study of VBI-1901, the Company’s immunotherapeutic cancer vaccine candidate, in recurrent glioblastoma (rGBM) patients. These data will be presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting on Saturday, June 1, 2024. David E. Anderson, Ph.D., VBI’s Chief Scientific Officer, said: “The tumor responses we have seen to date are incredibly encouraging, and, like the tumor responses did in the Phase 1/2a study, I am excited to see how this translates to clinical and survival outcomes later this year. The approved treatments for recurrent GBM patients have limited to no efficacy, which is consistent with the data seen in the standard-of-care arm in this study. VBI-1901’s ability to stimulate an immune response capable of generating a disease control rate of 43% at this interim stage of the study, including a partial response, is hopefully an indication of the potential of this candidate to make a meaningful difference in the lives of patients, providers, and families.” Jeff Baxter, VBI’s President and CEO, said: “These data represent a considerable advancement in our effort to make a difference in the fight against GBM. Throughout the remainder of 2024, we expect to have additional tumor response data and initial survival data. Pending the strength of these clinical data, we believe we can start discussions with the FDA around what an accelerated development and approval pathway looks like, under our Fast Track and Orphan Drug Designations.” Phase 2b Data Poster Highlights As of May 15, 2024, 23 patients had been randomized 1:1 to either the active treatment arm, VBI-1901, or to the control treatment arm (standard-of-care). Active Study Arm: VBI-1901 + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 11 patients have been randomized – tumor response data was available for 7 of those patients as of May 15, 2024 One (1) PR and two (2) SD observations seen to date The patient with the PR saw a 67% tumor reduction compared to baseline at week 6, after receiving two monthly doses of VBI-1901 43% (n=3/7) disease control rate achieved in evaluable patients to date 2 additional patients appear to be experiencing stabilization of tumor growth after their second dose of VBI-1901, but do not yet meet the threshold to qualify as stable disease Control Study Arm: Standard-of-Care (SoC) Therapy – Carmustine or Lomustine 12 patients have been randomized – tumor response data was available for 6 of those patients as of May 15, 2024 No tumor responses have been observed in the SoC arm (n=0/6; 0% DCR) 5 evaluable patients have experienced tumor progression of 2-8x increase in tumor size and have been taken off study protocol Tumor response rates are an objective measure of treatment efficacy in oncology trials. In VBI’s previous Phase 1/2a study of VBI-1901 in rGBM, a 44% disease control rate was observed (n=7/16), which translated to clinical improvements in overall survival, with a median overall survival (mOS) of 12.9 months after treatment with VBI-1901 compared to the 8-month mOS historical benchmark for standard-of-care chemotherapy treatment. ASCO Poster Details Title: Randomized Phase 2b trial of a CMV vaccine immunotherapeutic candidate (VBI-1901) in recurrent glioblastomas Abstract Number: TPS2100 Date & Time: 9:00 AM – 12:00 PM CDT, Saturday, June 1, 2024 Poster Session: Central Nervous System Tumors VBI’s poster presentation will be made available on the Posters page of VBI’s website, under News and Resources, after the Central Nervous System Tumors poster session concludes on June 1, 2024. Phase 2b Patient Enrollment Update 26 patients have been randomized as of May 28, 2024 Patient enrollment rate continues to increase, with six (6) patients randomized in May VBI expects the study to be fully enrolled (n=60) by year-end 2024, subject to continued pace of enrollment Phase 2b Study Design Multi-center, randomized, controlled, open-label study in up to 60 patients with first recurrent GBM Patients will be randomized in a 1:1 ratio across two study arms: Intradermal VBI-1901 + GM-CSF: 10 µg dose every 4 weeks until clinical disease progression Monotherapy standard-of-care: either intravenous carmustine or oral lomustine, every 6 weeks until disease progression or intolerable toxicity Endpoints include: Safety and tolerability Overall survival (OS) – median and overall Tumor response rate (TRR) Progression-free survival (PFS) Immunologic responses Reduction in corticosteroid use relative to baseline Change in quality of life compared to baseline The randomized, controlled Phase 2b study is evaluating overall survival, tumor response rates, and safety and tolerability of VBI-1901 as a monotherapy treatment in rGBM patients. There are no effective, approved treatments available for patients with rGBM, and median overall survival remains low at approximately eight (8) months. The U.S. Food and Drug Administration (FDA) has considered demonstration of a statistically significant improvement in overall survival relative to a randomized control arm to be clinically significant and has recognized this as criteria to support the approval of new oncology drugs.1 For more information about the Phase 2b study, visit clinicaltrials.gov and reference trial identifier: NCT03382977. Phase 1/2a Study Data Highlights – VBI-1901 10µg + GM-CSF Study Arms (n=16) 44% disease control rate achieved (n=7/16) – disease control rate is defined as stable disease (SD) + partial tumor response (PR) + complete tumor response (CR) 2 partial responses (PR) were observed – 1 patient was on treatment for more than 28 months (2.33 years), surviving at least 40 months (3.33 years) as of August 1, 2023, with a maximum tumor reduction of 93% relative to baseline 5 additional patients demonstrated stable disease (SD) for a sustained period of time All patients with a tumor response (PR or SD) (n=7/16) reached a minimum survival of 12 months Median overall survival (mOS) was 12.9 months, comparing favorably to 8-month mOS for monotherapy standard-of-care2 About GBM and VBI-1901 Scientific literature suggests CMV infection is prevalent in multiple solid tumors, including glioblastoma (GBM). GBM is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and has a high mortality. VBI-1901 is a novel cancer vaccine immunotherapeutic candidate developed using VBI’s enveloped virus-like particle (eVLP) technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. The FDA has granted VBI-1901 Fast Track Designation and Orphan Drug Designation for the treatment of recurrent glioblastoma. These designations are intended to provide certain benefits to drug developers, including more frequent meetings with the FDA, and Accelerated Approval and Priority Review, if relevant criteria are met, among other benefits. About VBI Vaccines Inc. VBI Vaccines Inc. (“VBI”) is a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease. Through its innovative approach to virus-like particles (“VLPs”), including a proprietary enveloped VLP (“eVLP”) platform technology and a proprietary mRNA-launched eVLP (“MLE”) platform technology, VBI develops vaccine candidates that mimic the natural presentation of viruses, designed to elicit the innate power of the human immune system. VBI is committed to targeting and overcoming significant infectious diseases, including hepatitis B, coronaviruses, and cytomegalovirus (CMV), as well as aggressive cancers including glioblastoma (GBM). VBI is headquartered in Cambridge, Massachusetts, with research operations in Ottawa, Canada, and a research and manufacturing site in Rehovot, Israel. Website Home: News and Resources: Investors: References Oncology Center of Excellence, Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration. Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics; Guidance for Industry. FDA.gov. December, 2018 Taal W, Oosterkamp HM, Walenkamp AME, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomized controlled phase 2 trial. Lancet Oncol. 2014; 15: 943-953 Cautionary Statement on Forward-looking Information Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are forward-looking information within the meaning of Canadian securities laws (collectively, “forward-looking statements”). The Company cautions that such forward-looking statements involve risks and uncertainties that may materially affect the Company’s results of operations. Such forward-looking statements are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including but not limited to, the Company’s ability to regain and maintain compliance with the listing standards of the Nasdaq Capital Market, the Company’s ability to satisfy all of the conditions to the consummation of the transactions with Brii Biosciences, the Company’s ability to comply with its obligations under its loan agreement with K2 HealthVentures, the impact of general economic, industry or political conditions in the United States or internationally; the impact and continuing effects of the COVID-19 epidemic on our clinical studies, manufacturing, business plan, and the global economy; the ability to successfully manufacture and commercialize PreHevbrio/PreHevbri; the ability to establish that potential products are efficacious or safe in preclinical or clinical trials; the ability to establish or maintain collaborations on the development of pipeline candidates and the commercialization of PreHevbrio/PreHevbri; the ability to obtain appropriate or necessary regulatory approvals to market potential products; the ability to obtain future funding for developmental products and working capital and to obtain such funding on commercially reasonable terms; the Company’s ability to manufacture product candidates on a commercial scale or in collaborations with third parties; changes in the size and nature of competitors; the ability to retain key executives and scientists; and the ability to secure and enforce legal rights related to the Company’s products. A discussion of these and other factors, including risks and uncertainties with respect to the Company, is set forth in the Company’s filings with the SEC and the Canadian securities authorities, including its Annual Report on Form 10-K filed with the SEC on April 16, 2024, and filed with the Canadian security authorities at sedarplus.ca on April 16, 2024, as may be supplemented or amended by the Company’s Quarterly Reports on Form 10-Q. Given these risks, uncertainties and factors, you are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement. All such forward-looking statements made herein are based on our current expectations and we undertake no duty or obligation to update or revise any forward-looking statements for any reason, except as required by law.