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PubMed | Center for Gene Therapy, Beckman Research Institute and Clinical Trial Office.
Type: Journal Article | Journal: Blood | Year: 2016

Attenuated poxvirus modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding 3 immunodominant cytomegalovirus (CMV) antigens, which stimulates a host antiviral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination). Three escalating dose levels (DL) were administered IM in 8 subjects/DL, with an identical booster injection 28 days later and 1-year follow-up. Vaccinations at all DL were safe with no dose-limiting toxicities. No vaccine-related serious adverse events were documented. Local and systemic reactogenicity was transient and self-limiting. Robust, functional, and durable Triplex-driven expansions of CMV-specific T cells were detected by measuring T-cell surface levels of 4-1BB (CD137), binding to CMV-specific HLA multimers, and interferon- production. Marked and durable CMV-specific T-cell responses were also detected in Triplex-vaccinated CMV-seronegatives, and in DryVax-vaccinated subjects. Long-lived memory effector phenotype, associated with viral control during CMV primary infection, was predominantly found on the membrane of CMV-specific and functional T cells, whereas off-target vaccine responses activating memory T cells from the related herpesvirus Epstein-Barr virus remained undetectable. Combined safety and immunogenicity results of MVA in allogeneic hematopoietic stem cell transplant (HCT) recipients and Triplex in healthy adults motivated the initiation of a placebo-controlled multicenter trial of Triplex in HCT patients. This trial was registered at www.clinicaltrials.gov as #NCT02506933.


NEW YORK and CLEVELAND, Feb. 17, 2017 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq:ABEO): Abeona Therapeutics Inc. (NASDAQ:ABEO), a leading clinical-stage biopharmaceutical company focused on developing therapies for life-threatening rare genetic diseases, announced updated data from the ongoing gene therapy clinical trial for Sanfilippo syndrome Type A (MPS IIIA), at the 13th Annual WORLDSymposium™ 2017 lysosomal storage disorders conference in San Diego, CA. The ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH) is a first-in-man clinical trial utilizing a single intravenous injection of AAV gene therapy for subjects with MPS IIIA, a rare autosomal recessive disease affecting every cell and organ in the body, which results in neurocognitive decline, speech loss, loss of mobility, and premature death in children. “We remain encouraged by continued signs of tolerability and biopotency in the low-dose cohort, and enrollment of the high-dose cohort is underway,” stated Kevin M. Flanigan, M.D., principal investigator with the Center for Gene Therapy at Nationwide Children’s Hospital and Professor of Pediatrics and Neurology at The Ohio State University College of Medicine. “Additionally, we are pleased to see further decreases in CSF GAG measurements, as well as preliminary evidence for stabilization or improvement of some cognitive functions, at six months post-dosing.” Per the design of the clinical trial, subjects received a single, intravenous injection of ABO-102 to deliver the AAV viral vector systematically throughout the body to introduce a corrective copy of the gene that underlies the cause of the MPS IIIA disease. Subjects are evaluated at multiple time points post-injection for safety assessments and initial signals of biopotency and clinical activity, which suggest that ABO-102 successfully reached target tissues throughout the body, including the central nervous system. Observations reported at the WORLDSymposium™ conference included: “The data demonstrate an early and robust systemic delivery of ABO-102, and the increased reductions in CNS HS GAG support our approach for intravenous ABO-102 delivery for subjects with Sanfilippo syndromes,” stated Timothy J. Miller, Ph.D., President and CEO of Abeona Therapeutics. “We are excited about continued biomarker signals in this trial, as well as early positive signals in the neurocognitive assessments. While we are still very early in the trial, we are extremely encouraged by these early results and look forward to expanding enrollment in this clinical trial with enrollments accelerating at two additional international clinical sites.” Abeona’s MPS IIIA program, ABO-102, has been granted Orphan Product Designation in the USA and in the European Union, has received the Rare Pediatric Disease Designation in the US, and recently received Fast Track designation by the US FDA. Sanfilippo syndromes (or mucopolysaccharidosis (MPS) type III): a group of four inherited genetic diseases each caused by a single gene defect, described as type A, B, C or D, which cause enzyme deficiencies that result in the abnormal accumulation of glycosaminoglycans (GAGs, or sugars) in body tissues. MPS III is a lysosomal storage disease, a group of rare inborn errors of metabolism resulting from deficiency in normal lysosomal function. The incidence of MPS III (all four types combined) is estimated to be 1 in 70,000 births. Mucopolysaccharides are long chains of sugar molecule used in the building of connective tissues in the body. There is a continuous process in the body of replacing used materials and breaking them down for disposal. Children with MPS III are missing an enzyme which is essential in breaking down the used mucopolysaccharides called heparan sulfate. The partially broken down mucopolysaccharides remain stored in cells in the body causing progressive damage. In MPS III, the predominant symptoms occur due to accumulation within the central nervous system (CNS), including the brain and spinal cord, resulting in cognitive decline, motor dysfunction, and eventual death. Importantly, there is no cure for MPS III and treatments are largely supportive care. About Abeona: Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene therapies for life-threatening rare genetic diseases. Abeona's lead programs include ABO-102 (AAV-SGSH) and ABO-101 (AAV-NAGLU), adeno-associated virus (AAV) based gene therapies for Sanfilippo syndrome (MPS IIIA and IIIB, respectively). Abeona is also developing EB-101 (gene-corrected skin grafts) for recessive dystrophic epidermolysis bullosa (RDEB), EB-201 for epidermolysis bullosa (EB), ABO-201 (AAV-CLN3) gene therapy for juvenile Batten disease (JNCL), ABO-202 (AAV-CLN1) gene therapy for treatment of infantile Batten disease (INCL), and ABO-301 (AAV-FANCC) for Fanconi anemia (FA) disorder and ABO-302 using a novel CRISPR/Cas9-based gene editing approach to gene therapy for rare blood diseases. In addition, Abeona has a plasma-based protein therapy pipeline, including SDF Alpha™ (alpha-1 protease inhibitor) for inherited COPD, using its proprietary SDF™ (Salt Diafiltration) ethanol-free process. For more information, visit www.abeonatherapeutics.com. This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, and that involve risks and uncertainties. These statements are subject to numerous risks and uncertainties, including but not limited to continued interest in our rare disease portfolio, our ability to enroll patients in clinical trials, the impact of competition; the ability to develop our products and technologies; the ability to achieve or obtain necessary regulatory approvals; the impact of changes in the financial markets and global economic conditions; our belief that initial signals of biopotency and clinical activity, which suggest that ABO-102 successfully reached target tissues throughout the body, including the central nervous system; our belief that the data demonstrate an early and robust systemic delivery of ABO-102, and the increased reductions in CNS GAG support our approach for intravenous delivery for subjects with Sanfilippo syndromes, and other risks as may be detailed from time to time in the Company's Annual Reports on Form 10-K and other reports filed by the Company with the Securities and Exchange Commission. The Company undertakes no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise.


Triplex Demonstrated Favorable Safety and Immunogenicity at Multiple Dose Levels in Healthy Volunteers Data Published in Blood Support Ongoing Phase 2 Trial of Triplex in Allogeneic Hematopoietic Stem Cell Transplant Recipients DUARTE, Calif., and NEW YORK, Oct. 28, 2016 (GLOBE NEWSWIRE) -- City of Hope, a world-renowned independent research and cancer treatment center, and Helocyte, Inc., a majority-owned subsidiary of Fortress Biotech, Inc. (NASDAQ:FBIO), announced today that data from the Phase 1 trial of Helocyte’s Triplex vaccine were published online this month in Blood, the journal of the American Society of Hematology. The vaccine is initially being developed for control of cytomegalovirus (CMV) in allogeneic hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. In the Phase 1 study, Triplex was found to be safe, well-tolerated and highly immunogenic when administered to healthy volunteers at multiple dose levels. These data supported the initiation of an ongoing Phase 2 trial evaluating Triplex in patients undergoing allogeneic HSCT. In the Phase 1 trial, City of Hope researchers studied the response to the vaccine in 24 healthy volunteers. They found that Triplex generated robust and durable virus-specific immunity in those previously infected with CMV (addressing patients at greatest risk of viral complications following allogeneic HSCT) as well as in those with no prior CMV infection (addressing patients at greatest risk of viral complications following SOT). CMV can impede the recovery of patients undergoing HSCT for the treatment for certain blood or bone marrow cancers. The virus can be transmitted to seronegative transplant recipients through infected donor grafts, or reactivated in seropositive transplant recipients (particularly those with low baseline immunity) as a result of their immuno-suppressed condition. In either instance, CMV can cause severe and life-threatening complications, including pneumonia, gastroenteritis and retinitis. Triplex has the potential to benefit patients in numerous clinical settings since the immune response generated by most individuals to CMV is far greater than the response associated with any other virus or condition. “After years of work, it is very gratifying that we are making advancements in helping people worldwide achieve better health outcomes after a transplant procedure,” said Don J. Diamond, Ph.D., Chair of the Department of Experimental Therapeutics at City of Hope who led the team that developed Triplex. “Furthermore, Triplex’s favorable safety and immunogenicity may make the vaccine an ideal therapeutic platform to combat significant complications in many disease areas, like solid organ transplant and glioblastoma,” Diamond said. “We are pleased to announce the publication of these important data in Blood. CMV is a ubiquitous virus that causes life-threatening disease in those with weakened immune systems,” said Frank Taffy, Co-Founder, President, CEO and Board Member of Helocyte. “We look forward to a continued collaboration with City of Hope as we advance our ongoing Phase 2 in HSCT, and initiate studies of Triplex across multiple other indications,” said Mr. Taffy. John A. Zaia, M.D., Director of City of Hope’s Center for Gene Therapy and the Aaron D. Miller and Edith Miller Chair in Gene Therapy, served as the Phase 1 trial’s principal investigator. Research reported in the aforementioned Blood publication was supported by the National Cancer Institute of the National Institutes of Health under grant numbers: R01CA077544, R01CA181045 and P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About Triplex 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 a Phase 1 study, Triplex was found to be safe, well-tolerated and highly immunogenic when administered to healthy volunteers at multiple dose levels (ClinicalTrials.gov Identifier: NCT01941056).  The vaccine is currently being investigated in a randomized, multicenter, double-blind, placebo-controlled Phase 2 study in seropositive recipients of allogeneic HSCT (ClinicalTrials.gov Identifier:  NCT02506933). About City of Hope City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 47 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram. About Helocyte Helocyte is a clinical-stage company developing novel immunotherapies for the prevention and treatment of cancer and infectious disease (and in particular, cytomegalovirus or “CMV”). The Centers for Disease Control estimate that 50 to 80 percent of Americans are infected 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. Helocyte’s PepVax and Triplex vaccines are engineered to induce a robust and durable virus-specific T cell response to control CMV in transplant recipients. Helocyte’s Pentamer vaccine is designed to induce a neutralizing antibody response to prevent the transmission of CMV from mother to fetus, the most common congenital infection. There is no approved therapy for the prevention or treatment of congenital CMV. 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 can educate the body’s innate immune system to fight CMV. For more information, please visit www.helocyte.com. About Fortress Biotech Fortress Biotech, Inc. (“Fortress”) is a biopharmaceutical company dedicated to acquiring, developing and commercializing novel pharmaceutical and biotechnology products. Fortress develops and commercializes products both within Fortress and through subsidiary companies, also known as Fortress Companies. In addition to its internal development programs, Fortress leverages its biopharmaceutical business expertise and drug development capabilities and provides funding and management services to help the Fortress Companies achieve their goals.  Fortress and the Fortress Companies may seek licensing, acquisitions, partnerships, joint ventures and/or public and private financings to accelerate and provide additional funding to support their research and development programs. For more information, visit www.fortressbiotech.com. Forward-Looking Statements This press release may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated include: risks related to our growth strategy; risks relating to the results of research and development activities; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; uncertainties relating to preclinical and clinical testing; our dependence on third party suppliers; our ability to attract, integrate, and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law.


Beltrami-Moreira M.,Federal University of Rio Grande do Sul | Qi L.,Harvard University | Maestri M.K.,Federal University of Rio Grande do Sul | Fuchs F.D.,Federal University of Rio Grande do Sul | And 9 more authors.
Journal of the American Society of Hypertension | Year: 2015

Circulating adiponectin has been related to vascular diseases, but few studies examined the relationship between plasma adiponectin and microvascular abnormalities among hypertensive individuals. We tested the association between plasma adiponectin level and retinal vessel calibers in patients with hypertension.This study included 172 patients with confirmed hypertension, aged 18-80 years. Subjects with recent cardiovascular events, advanced heart failure and end-stage renal disease were excluded. Arteriolar and venular calibers were measured in retinographies using a microdensitometric image-processing method. Blood pressure was measured using a validated oscillometric device. We observed a statistically significant inverse association between plasma adiponectin and arteriolar caliber among participants aged 60 years or older after controlling for confounders (Adjusted β = -0.42; P = .001). In the final model, HbA1C and low-density lipoprotein also remained independently associated with arteriolar caliber. There was no association of adiponectin with venular caliber and retinal vessel calibers in participants <60 years old.Adiponectin is inversely associated with retinal arteriolar caliber in elderly hypertensive participants, suggesting that plasma adiponectin may be a marker of microvascular damage and of higher cardiovascular risk in this age stratum. © 2015 American Society of Hypertension.

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