Dyskeratosis Congenita

BALTIMORE, MD, USA I December 12, 2022 I Elixirgen Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery, development and commercialization of therapies using its controllable self-replicating RNA (c-srRNA) platform, today announced new data from a Phase 1/2 trial ( NCT04211714 ) showing successful ex vivo telomere elongation with lead asset, EXG-34217 (autologous CD34+ hematopoietic stem cells that have been treated ex vivo with EXG-001), in a patient with dyskeratosis congenita, a telomere biology disorder (TBD) that can lead to bone marrow failure. In addition, the telomere flow-FISH study suggests the potential emergence of a cell population with longer telomeres in vivo . The data were presented in an oral presentation at the 64th American Society of Hematology (ASH) Annual Meeting, taking place December 10-13, 2022 in New Orleans, Louisiana. “The encouraging data in this study represent the first time that ex vivo telomere elongation of CD34+ cells has been demonstrated in a patient with TBD. Dyskeratosis congenita has historically been characterized by a triad of abnormalities in the skin, nails and oral mucosa but can also include pulmonary and liver disease,” said Kasiani C. Myers, M.D., associate professor, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, and principal investigator in the study. “In addition, due to the shortened telomeres, most patients develop bone marrow failure, which requires the need for hematopoietic stem cell transplantation (HSCT), a procedure that is accompanied with potentially life-threatening complications. The data presented here provide promising early signs of the potential of EXG-34217 to provide an alternative treatment option for bone marrow failure in these patients and their families.” Presentation Title: Successful ex vivo telomere elongation with EXG-001 in a patient with a dyskeratosis congenita Session Name: Gene Therapies: Advances in Clinical Gene Therapy for Hematological Disorders Publication Number: 781 Presenter: Kasiani C. Myers, M.D., Associate Professor, Department of Pediatrics, Cincinnati Children's Hospital Medical Center Key Findings: Akihiro Ko, chief executive officer of Elixirgen Therapeutics, added, “We’re pleased to share these early positive data from our lead indication at a prestigious conference like ASH. This is a critical milestone in a process that started with the identification of ZSCAN4 by our Chief Scientific Officer, Dr. Minoru Ko, at the NIH. Our nuanced understanding of this protein has allowed us to create a novel potential treatment approach for TBD that is genotype and mutation independent. In addition, the absence of a conditioning regimen or immunosuppression is of significant importance in this radiation and chemotherapy sensitive population. We look forward to sharing additional data as we continue to enroll patients with our partners at Cincinnati Children's Hospital Medical Center.” About Elixirgen Therapeutics, Inc. Elixirgen Therapeutics, Inc. is a clinical-stage biotechnology company focused on the discovery, development and commercialization of therapies using its controllable self-replicating RNA (c-srRNA) platform. The company has two products in Phase 1/2 clinical trials ( NCT04211714 and NCT04863131 ). For more information, visit ElixirgenTherapeutics.com. SOURCE: Elixirgen Therapeutics

Treatment with EXG-34217 increased the telomere length of CD34+ cells by 1.24-fold ex vivo Telomere flow-FISH study suggests the potential emergence of a cell population with longer telomeres in vivo No acute or long-term adverse effects were observed for 9 months BALTIMORE, Dec. 12, 2022 (GLOBE NEWSWIRE) -- Elixirgen Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery, development and commercialization of therapies using its controllable self-replicating RNA (c-srRNA) platform, today announced new data from a Phase 1/2 trial (NCT04211714) showing successful ex vivo telomere elongation with lead asset, EXG-34217 (autologous CD34+ hematopoietic stem cells that have been treated ex vivo with EXG-001), in a patient with dyskeratosis congenita, a telomere biology disorder (TBD) that can lead to bone marrow failure. In addition, the telomere flow-FISH study suggests the potential emergence of a cell population with longer telomeres in vivo. The data were presented in an oral presentation at the 64th American Society of Hematology (ASH) Annual Meeting, taking place December 10-13, 2022 in New Orleans, Louisiana. “The encouraging data in this study represent the first time that ex vivo telomere elongation of CD34+ cells has been demonstrated in a patient with TBD. Dyskeratosis congenita has historically been characterized by a triad of abnormalities in the skin, nails and oral mucosa but can also include pulmonary and liver disease,” said Kasiani C. Myers, M.D., associate professor, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, and principal investigator in the study. “In addition, due to the shortened telomeres, most patients develop bone marrow failure, which requires the need for hematopoietic stem cell transplantation (HSCT), a procedure that is accompanied with potentially life-threatening complications. The data presented here provide promising early signs of the potential of EXG-34217 to provide an alternative treatment option for bone marrow failure in these patients and their families.” Presentation Title: Successful ex vivo telomere elongation with EXG-001 in a patient with a dyskeratosis congenita Session Name: Gene Therapies: Advances in Clinical Gene Therapy for Hematological Disorders Publication Number: 781 Presenter: Kasiani C. Myers, M.D., Associate Professor, Department of Pediatrics, Cincinnati Children's Hospital Medical Center Key Findings: Zinc finger and SCAN domain containing protein 4 (ZSCAN4) is a protein that regulates telomere elongation and enhances genome stability. EXG-001 is a temperature-sensitive Sendai virus vector encoding for human ZSCAN4, which is non-integrating and non-transmissible. EXG-34217 is a dose of autologous CD34+ hematopoietic stem cells (HSCs) that have been treated ex vivo with EXG-001. In this Phase 1/2 trial, 2.8x106 CD34/kg were collected and treated with EXG-001 ex vivo in a functionally closed tubing system using the CliniMACS Prodigy (Miltenyi Biotec). Treatment increased the telomere length of the CD34+ cells by 1.24-fold, bringing them into the healthy control range. 0.85x106 CD34/kg autologous treated HSC (EXG-34217) were reinfused into the subject in February 2022 without a conditioning regimen. The telomere flow-FISH study suggests the potential emergence of a cell population with longer telomeres in vivo. No acute or long-term adverse effects were observed up to 9 months, and the differentiation potential of the CD34+ cells did not change after treatment. Akihiro Ko, chief executive officer of Elixirgen Therapeutics, added, “We’re pleased to share these early positive data from our lead indication at a prestigious conference like ASH. This is a critical milestone in a process that started with the identification of ZSCAN4 by our Chief Scientific Officer, Dr. Minoru Ko, at the NIH. Our nuanced understanding of this protein has allowed us to create a novel potential treatment approach for TBD that is genotype and mutation independent. In addition, the absence of a conditioning regimen or immunosuppression is of significant importance in this radiation and chemotherapy sensitive population. We look forward to sharing additional data as we continue to enroll patients with our partners at Cincinnati Children's Hospital Medical Center.” About Elixirgen Therapeutics, Inc. Elixirgen Therapeutics, Inc. is a clinical-stage biotechnology company focused on the discovery, development and commercialization of therapies using its controllable self-replicating RNA (c-srRNA) platform. The company has two products in Phase 1/2 clinical trials (NCT04211714 and NCT04863131). For more information, visit ElixirgenTherapeutics.com. Forward-Looking Statements This press release may contain "forward-looking" statements. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in pharmaceutical research and development. Any forward-looking statements in this press release speak only as of the date of this press release, and Elixirgen Therapeutics undertakes no obligation to update or revise the statements in the future, even if new information becomes available. Contact Media Relations: Slavena Salve Nissan, M.D. LifeSci Communications snissan@lifescicomms.com 718-483-4440

Courtesy of Getty Images When the 64th American Society of Hematology (ASH) annual meeting kicks off Saturday in New Orleans, established hematology leaders like AstraZeneca, Janssen and Merck will showcase new data, and new players like Vega Therapeutics will launch new programs. Janssen J&J’s Janssen will take a leading role at this year’s conference with more than 70 presentations on the schedule. Janssen will provide efficacy and safety data for Tecvayli (teclistamab) in addition to Darzelx Faspro and lenalidomide in patients who have received one to three prior lines of therapy. The FDA approved Tecvayli in this indication in October. The company will also reveal longer follow-up data from the MajesTEC-1 trial – which formed the basis of the approval - for Tecvayli as a monotherapy. In mantle cell lymphoma (MCL), Janssen will present data from the Phase III TRIANGE study of Imbruvica (ibrutinib) combination therapy in transplant-eligible younger adults with untreated disease. These results will be reported during the Sunday plenary session. In a real-world study, eight years of observational analysis showed Janssen’s oral Factor Xa inhibitor Xareleto was equally effective in treating cancer-associated thromboembolism (CAT) as Factor Xa inhibitor apixaban, an anticoagulant medication. This held true across a broad range of patients with varying cancers. Patients with CAT are at greater risk of venous thromboembolism. It is the second leading cause of death for people with cancer. Janssen and development partner Bayer will present the results on Dec. 11. Affimed Germany-based Affimed comes to ASH ready to provide a review of data and development update for its lead candidate AFM13, a CD30/CD16A bispecific Innate Cell Engager (ICE). In a Phase I study, the therapy showed an 88% overall response rate and 46% complete response rate when combined with Merck’s Keytruda in relapsed/refractory Hodgkin lymphoma. AFM13 is also being evaluated as a monotherapy in a registration-directed trial for peripheral T cell lymphoma. In a Phase I/II trial, a combination of AFM13 with allogeneic cord blood-derived NK cells yielded an ORR of 100% and a CR of 71% in 24 patients with CD30+ R/R Hodgkin and non-Hodgkin lymphomas treated at the highest dose level. Affimed is developing innate cell engagers that link natural killer cells to tumor cells. Other programs include AFM24 and AFM24 + adoptive NK cells. These therapies, both in Phase I, target EGFR-positive solid tumors. At the developmental stage, AFM28 targets CD123-positive acute myeloid leukemia (AML). The company plans to update investors on its development plans for AFM13 in hematologic malignancies on Saturday at 4 pm CT at the conference and via webcast. BioSpace will update this story accordingly. Merck With the industry’s largest immuno-oncology clinical research program, it’s no surprise that Merck’s drugs and therapies currently involved in clinical studies will be featured in nearly 40 abstracts. One of the most anticipated presentations includes new and updated data for Keytruda, the company’s IO centerpiece. Keytruda is an anti-programmed death receptor-1 (PD-1) therapy that helps the immune system fight tumor cells. It keeps PD-1 and its ligands from interacting, which then activates T lymphocytes, which affect both healthy cells and tumor cells. Keytruda is prolific as part of various combination treatments. It is currently being studied in over 1600 trials in myriad cancer varieties. Merck will also present data for several of its investigational therapies, including favezelimab, an anti-LAG-3 antibody, zilovertamab vedotin, an antibody-drug conjugate targeting receptor tyrosine kinase-like orphan receptor 1 [ROR1] and nemtabrutinib, a reversible, non-covalent Bruton’s tyrosine kinase [BTK] inhibitor. Indications include melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma and many more. AstraZeneca AstraZeneca will present 47 abstracts showcasing new data from trials in its hematology portfolio. Ahead of the annual meeting, the company stated it will feature eight approved and potential new medicines in over 10 rare diseases and blood cancers. These include chronic lymphocytic leukemia (CLL), follicular lymphoma, diffuse large B-cell lymphoma, MCL, paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome and amyloid light chain amyloidosis. One of the most anticipated presentations will include updated results from the Phase II study of acalabrutinib, venetoclax and obinutuzumab (AVO) as a treatment for patients with CLL enriched for high-risk disease. All patients in the trial have been previously untreated. AstraZeneca also plans to spotlight breaking data from its next-generation BTK-inhibitor Calquence (acalabrutinib). Among these updates, the drugmaker will discuss a post-hoc safety analysis from the ELEVATE-RR Phase III trial comparing Calquence versus ibrutinib in relapsed or refractory CLL, as well as final long-term follow-up results of Phase I/II trials involving the therapy. Elixirgen Therapeutics On Monday, Elixirgen and its research collaborators will present data from EXG-001, a non-integrating temperature-sensitive non-transmissible Sendai virus vector encoding for human zinc finger and SCAN Domain Containing 4 (ZSCAN4). EXG-001 is a first-in-human cell therapy that aims to extend telomere length in patients with telomere biology disorders. Elixirgen 's lead candidate, EXG-34217, is a therapeutic dose of autologous CD34+ hematopoietic stem cells (HSCs) that have been treated ex vivo with EXG-001. Diseases like the rare skin and bone marrow disorder, dyskeratosis congenita, are characterized by short telomeres, which are believed to cause premature cellular senescence and puts them at higher risk of bone marrow failure. While studies have supported the role of ZSCAN4 in telomere extension, researchers acknowledge the mechanism remains elusive. Elixirgen CEO Akihiro Ko explained that there are currently limited treatment options for TBDs including androgen therapy. Ultimately, many patients will need to undergo hematopoietic stem cell transplant, which comes with a preconditioning regiment that can cause toxicities. "EXG-34217 is an autologous therapy...and it is infused into a patient without preconditioning or systemic immunosuppression," Ko told BioSpace. In a first-in-human clinical trial, the gene therapy increased telomere length of autologous CD34+ hematopoietic stem cells in adult patients with dyskeratosis congenita, bringing them into a healthy normal control range. Aside from its work in TBDs, Ko said Elixirgen is "actively exploring" how the technologies can be used to design cancer immunotherapies including CAR-T cell therapies as well as potential solutions for aging-related disorders. Vega Therapeutics Exploding into the constellation of Star Therapeutics this week, Vega will debut its first-in-class monoclonal antibody therapy, VGA039, being developed for von Willebrand disease (VWD), a common and chronic blood disorder. In a podium presentation given Dec. 12 by Chief Scientific Officer Sandip Panicker, Ph.D., Vega will unveil preclinical data demonstrating the potential of VGA039 as a universal hemostatic therapy for bleeding disorders. In particular, the antibody will address a fundamental mechanism of clot formation in VWD, according to the Tuesday press release. VGA039 reportedly works by modulating Protein S, which it describes as a key cofactor involved in thrombin generation during both the initiation and propagation of coagulation. The new company has secured Austrian Competent Authority approval of a clinical trial application for a Phase I study in VWD. Vega CEO and Co-founder Adam Rosenthal, Ph.D. said drug innovation for VWD has lagged. “At Vega, we see a future where we can better meet the needs of patients by advancing VGA039 as the first purpose-built antibody therapy for VWD,” he said in a statement Tuesday. Vega is supported by $40 million in financing from Star and several other investors including Westlake Village BioPartners, OrbiMed and Redmile