Centenary Institute

Two-year overall survival rate in patients with steroid-resistant acute GvHD was 60% MELBOURNE, Australia, May 22, 2024 /PRNewswire/ -- Cynata Therapeutics Limited (ASX: " CYP", "Cynata", or the "Company"), a clinical-stage biotechnology company specialising in cell therapeutics, is pleased to announce the publication of two-year follow-up data of CYP-001 in patients with steroid-resistant acute graft versus host disease (SR-aGvHD) in the prestigious peer-reviewed journal Nature Medicine. CYP-001 is Cynata's Cymerus™ off-the-shelf iPSC[1]-derived MSC[2] product for intravenous infusion, which is being investigated as a potential immune modulating treatment. Graft versus host disease (GvHD) is a potentially life-threatening complication in recipients of bone marrow transplantation or similar procedures. It arises when immune cells in the transplant (the graft) attack the recipient's tissues (the host) as "foreign". SR-aGvHD occurs when there is no response to corticosteroid treatment, which is the standard first-line treatment for aGvHD. The newly published paper reports sustained outcomes at the two-year follow-up in the Phase 1 clinical trial of CYP-001 in patients with SR-aGvHD. Key results include a two-year overall survival rate of 60% (9/15 patients), with no treatment-related serious adverse events or safety concerns identified. This survival rate compares very favourably to previously reported outcomes in SR-aGvHD. For example, in the Phase 3 study that supported approval of the drug ruxolitinib, the 18-month overall survival rates were only 38% in the ruxolitinib group and 36% in the "best available treatment" control group (survival at two years was not evaluable).[3] Historically the prognosis in patients with SR‑aGvHD has been very poor, with two-year overall survival rates below 20%.[4] The details of the paper are as follows: Kelly K, Bloor AJC, Griffin JE, Radia R, Yeung DT, and Rasko JEJ. Two-year safety outcomes of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease. Nat Med, 2024, The two-year follow-up results build on the highly encouraging primary evaluation results at Day 100, which included Complete Response and Overall Response rates of 53% and 87%, respectively. The original paper summarising the primary evaluation results was published in Nature Medicine in 2020.[5] Professor John Rasko, AO,[6] the international coordinating Principal Investigator for the trial, said: "The publication of a second paper on this trial in such a high-impact journal is a testament to the importance of this project to the wider field of cellular therapy. This was the first ever completed clinical trial worldwide involving iPSC-derived cells of any kind. The overall survival outcomes and safety data in this group of patients are very promising, and we look forward to the continued development of Cymerus MSCs, in particular the ongoing global Phase 2 trial in aGvHD. [7] More broadly, our demonstration of the safe clinical use of iPSC-derived cells anticipates their application in diverse human diseases and regenerative medicine." Authorised for release by Dr Kilian Kelly, CEO & Managing Director About Cynata Therapeutics (ASX: CYP) Cynata Therapeutics Limited (ASX: CYP) is an Australian clinical-stage stem cell and regenerative medicine company focused on the development of therapies based on Cymerus™, a proprietary therapeutic stem cell platform technology. Cymerus™ overcomes the challenges of other production methods by using induced pluripotent stem cells (iPSCs) and a precursor cell known as mesenchymoangioblast (MCA) to achieve economic manufacture of cell therapy products, including mesenchymal stem cells (MSCs), at commercial scale without the limitation of multiple donors. Cynata's lead product candidate CYP-001 met all clinical endpoints and demonstrated positive safety and efficacy data for the treatment of steroid-resistant acute graft-versus-host disease (GvHD) in a Phase 1 trial. A Phase 2 clinical trial in GvHD under a cleared US FDA IND, as well as trials of Cymerus products in osteoarthritis (Phase 3) and diabetic foot ulcers (DFU) are currently ongoing, while a trial in renal transplant is expected to commence in the near future. In addition, Cynata has also demonstrated utility of its Cymerus technology in preclinical models of numerous diseases, including critical limb ischaemia, idiopathic pulmonary fibrosis, asthma, heart attack, sepsis, acute respiratory distress syndrome (ARDS) and cytokine release syndrome. Cynata Therapeutics encourages all current investors to go paperless by registering their details with the designated registry service provider, Automic Group. [1] iPSC = induced pluripotent stem cell. [2] MSC = mesenchymal stem (or stromal) cell. [3] Zeiser R. et al. N Engl J Med. 2020;382(19):1800-1810. [4] Westin J.R. et al. Adv Hematol. 2011;2011:601953. [5] Bloor AJC, et al. Nat Med. 2020;26:1720–1725. [6] Prof Rasko is Head of Department, Cell & Molecular Therapies, Royal Prince Alfred Hospital, Sydney; Professor, Faculty of Medicine & Health, The University of Sydney; and Head, Gene and Stem Cell Therapy Program, Centenary Institute, Sydney. [7] SOURCE Cynata Therapeutics

Australian researchers have found an existing blood cancer drug can kill 'silent' HIV cells and delay reinfections -- a significant pre-clinical discovery that could lead to a future cure for the disease. An existing blood cancer drug has shown promise in killing 'silent' HIV cells and delaying reinfections -- a significant pre-clinical discovery that could lead to a future cure for the disease. Hidden HIV cells, known as latent infection, are responsible for the virus permanently remaining in the body and cannot be treated by current therapy options. These hibernating, infected cells are the reason why people living with HIV require life-long treatment to suppress the virus. Led by WEHI and The Peter Doherty Institute for Infection and Immunity (Doherty Institute) -- leading medical research institutes in Melbourne, Australia -- the landmark study is being translated into a new clinical trial to assess whether the blood cancer treatment can be repurposed to offer a pathway towards an HIV cure. At a glance An estimated 39 million people worldwide are living with HIV, including more than 29,400 Australians. Antiretroviral therapy (ART) is the standard of care treatment given to people living with HIV and is highly effective. But the medication cannot target hibernating HIV-infected cells, meaning it can only suppress the virus -- not cure it. ART for people living with HIV is life-long: if a person stops taking this medication, hibernating HIV-infected cells will reactivate within a very short timeframe, leading to a resurgence of the virus. An estimated 98% of Australians living with HIV currently have undetectable levels of the virus, as it is completely suppressed by their ongoing ART treatment. In the new study, WEHI researchers used the cancer drug venetoclax on enhanced pre-clinical models of HIV and found it delayed the virus from rebounding by two weeks, even without ART. Co-first author, Dr Philip Arandjelovic from WEHI, said the discovery is an exciting step towards developing treatment options for the tens of millions of people currently living with HIV globally. "In attacking dormant HIV cells and delaying viral rebound, venetoclax has shown promise beyond that of currently approved treatments," he said. "Every achievement in delaying this virus from returning brings us closer to preventing the disease from re-emerging in people living with HIV. Our findings are hopefully a step towards this goal." The study marks the first time venetoclax has been used on its own to assess HIV persistence in pre-clinical models. However, researchers also found the cancer treatment can be combined with another drug that acts on the same pathway and is currently in clinical trials, to achieve a longer delay in viral rebound, with a shorter duration of venetoclax treatment. "It has long been understood that one drug may not be enough to completely eliminate HIV. This finding has supported that theory, while uncovering venetoclax's powerful potential as a weapon against HIV," Dr Arandjelovic said. Lifelong memory game HIV primarily targets CD4+ T cells, a type of white blood cell crucial for the immune system to properly function. It is within these cells that HIV can lie dormant, ready to reactivate if the virus is not effectively eliminated. Using human CD4+ T cells donated by people living with HIV who are on suppressive ART, scientists at the Doherty Institute found venetoclax was also able to reduce the amount of HIV DNA in these white blood cells. Co-first author, The University of Melbourne's Dr Youry Kim and a Postdoctoral researcher at the Doherty Institute, said venetoclax potently reduced the amount of intact viral DNA in patient cells when studied in the laboratory. "This indicates that venetoclax is selectively killing the infected cells, which rely on key proteins to survive. Venetoclax has the ability to antagonise one of the key survival proteins," said Dr Kim. Milestone trial Venetoclax, marketed as VENCLEXTA, is based on a landmark discovery by Professor David Vaux AO in 1988. The drug is the result of a research collaboration between WEHI and companies Roche, Genentech (a member of the Roche Group) and AbbVie. It was developed by Roche, Genentech and AbbVie and co-developed and trialled in Australia. The Phase I/IIb clinical trial using venetoclax to treat HIV will start at the end of the year in Denmark, with plans to expand the study to Melbourne in 2024. It will be led by Professor Sharon Lewin (Director of the Doherty Institute), Professor Marc Pellegrini (Executive Director at the Centenary Institute) and Dr Thomas Rasmussen (clinician scientist at Denmark's Aarhus University). Prof Marc Pellegrini, a joint corresponding author and WEHI Honorary Fellow, said the trial will replicate the pre-clinical study conducted using WEHI's state-of-the-art technology and facilities. "The trial will assess the safety and tolerability of venetoclax in people living with HIV who are on suppressive antiretroviral therapy," said Prof Pellegrini, a former Head of WEHI's Infectious Diseases and Immune Defence Division. Melbourne Laureate Professor Sharon Lewin, a joint corresponding author, concluded: "It's exciting to see venetoclax, which has already helped thousands of blood cancer patients, now being repurposed as a treatment that could also help change the lives of people living with HIV and put an end to the requirement for life-long medication." The research was supported by the National Health and Medical Research Council (NHMRC), The Sylvia & Charles Viertel Senior Medical Research Fellowship, Australian Centre for HIV and Hepatitis Virology Research, the Victorian Government and Australian Government.