St. Vincent's Institute of Medical Research

Enrollment of Patients with Autoimmune Disease in Phase 1b Study has Begun SEATTLE, March 17, 2025 /PRNewswire/ -- Mozart Therapeutics, the leading developer of CD8 Treg modulators for the treatment of autoimmune disease, today announce the successful completion of their Phase 1a study of MTX-101 in healthy adults. The randomized, blinded, placebo-controlled study evaluated MTX-101—a first-in-class autoimmune checkpoint inhibitor—as single and multiple doses in an ascending-dose design (NCT06324604). Data from the study in healthy adults show MTX-101 is well tolerated. Most adverse events were low-grade and there were no serious adverse events. Participants receiving MTX-101 experienced transient and self-limited decreases in lymphocytes, which the Company believes are consistent with the study drug's mechanism of action and indicative of target engagement. Data further demonstrate that MTX-101 has predictable, dose-dependent pharmacokinetics (PK) and receptor occupancy that are expected to enable a convenient and competitive dosing regimen. Pharmacodynamic data support proof of mechanism and show that MTX-101 is highly selective for regulatory CD8 T cells, and that engagement with MTX-101 results in CD8 Treg activation. Mozart plans to present full data from the Phase 1a study at upcoming medical symposia. "We are thrilled that the initial MTX-101 Phase 1 data in healthy adults confirm the mechanistic and safety findings from our pre- and nonclinical studies. This represents not only an important milestone for Mozart, but also a significant achievement as we work to advance a class of CD8 Treg modulators to restore durable immune homeostasis in autoimmune disease," said Katie Fanning, President and Chief Executive Officer of Mozart Therapeutics. "Our observations from the healthy adults hold great promise for patients with autoimmune disease," echoed Jason Chien, M.D., M.S., Mozart's Chief Medical Officer. "The well-tolerated safety profile, antibody-like PK, and clear evidence of target engagement and activation represent an exciting novel class of therapeutics that has the potential to deliver substantial clinical benefit. With these data, we are quickly advancing MTX-101 in patients with type 1 diabetes and celiac disease." The first patients with type 1 diabetes and celiac disease have been enrolled in Part B of the study, which is being conducted at multiple clinical sites in Australia. "MTX–101 has a novel mechanism of action that has great potential to improve the lives of people living with autoimmune disease," said Professor John Wentworth, M.D.; Endocrinologist, The Royal Melbourne Hospital Department of Medicine; Senior Clinical Research Fellow, St Vincent's Institute of Medical Research; Director, ANZ Type 1 Diabetes TrialNet. "This is why our type 1 diabetes community is so excited to participate in the MTX-101 development program and help determine its ability to decrease dependance on insulin injections." About MTX-101 MTX-101 is an antigen-agnostic bispecific antibody targeting inhibitory KIR and CD8 expressed on regulatory CD8 T cells. This autoimmune checkpoint inhibitor aims to restore the intrinsic functions of CD8 Treg, acting early in the autoimmune disease process to suppress and eliminate pathogenic T cells, halt downstream inflammation, and prevent tissue destruction. About Mozart Therapeutics Mozart Therapeutics is focused on developing first-in-class disease-modifying therapies for autoimmune diseases, utilizing a novel approach to restoring immune system function by targeting the CD8 T regulatory network. The company is headquartered in Seattle, WA. For more information, visit and follow the company on LinkedIn @Mozart–tx.com. SOURCE Mozart Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Researchers have shown that targeting a gene regulated by two cancer-fuelling proteins can kill cancerous cells and halt their growth in laboratory models of B-cell acute lymphoblastic leukemia (ALL). Researchers have found a new way to potentially treat one of the most common forms of acute lymphoblastic leukaemia. The study, led by WEHI and the Peter MacCallum Cancer Centre, was able to kill leukaemia cells in the lab and stop cancer cells from growing, after identifying two new proteins critical for the development of the aggressive disease. The findings could lead to enhanced treatment options in the future, with plans underway to develop a clinical trial based on the research. Around 5200 people are diagnosed with a form of leukaemia in Australia each year. An estimated 1500 of these cases are acute -- meaning the blood cancer appears suddenly and grows quickly. Blood cancers like leukaemia are notoriously difficult to treat in adults, with 50% of Australian patients relapsing after the first round of chemotherapy and subsequently becoming resistant to further treatments. Associate Professor Ashley Ng, a corresponding author on the paper, said this presented a unique treatment challenge for these blood cancers and highlighted the urgent need for new therapeutics. "About 135,000 people live with a blood cancer or blood disorder in Australia, with 16 people dying every day from the disease," Assoc Prof Ng, a WEHI researcher and clinical haematologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, said. "Despite the medical advancements made in the cancer field over the years, the incidence of blood cancer has grown by 47% in the past decade. "The best way to enhance treatment options for patients is to continually improve our understanding of how leukaemia cancers behave and what drives their growth. "Our new research has identified two proteins that are critical for the development of B-cell acute lymphoblastic leukaemia, expanding our knowledge into how these cancers can form. "By uncovering this new vulnerability in leukaemia formation, we hope to exploit the findings for therapeutic benefit and also apply them to other forms of the disease." The research is published in the journal Science Advances. Master regulators Assoc Prof Ng has spent over a decade researching a protein that regulates gene activity in the cell nucleus, known as ERG. Imbalances in this protein can lead to blood cancers, like acute lymphoblastic leukaemia. His previous research uncovered the protein's critical role in Down syndrome associated blood disease and normal blood cell function, including how B cells -- which are essential for producing antibodies to fight against infections -- develop. First author Dr Kira Behrens said the research team wanted to understand what other types of proteins ERG works with to fuel leukaemia development. "We looked at the proteins that control how specific genes switch 'on' or 'off' to analyse how normal B-cells -- and critically -- B-cell acute lymphoblastic leukaemia -- can develop," Dr Behrens said. "After analysing the genes regulated by ERG and another protein, c-MYC, we discovered that these proteins were actually the master regulators of several important pathways and processes within the leukaemia cell." Researchers then narrowed the list down to focus on one pathway essential for making proteins, known as ribosome biogenesis. This led the team to focus on targeting a key gene essential to this pathway, POL I, which is also controlled by these master regulator proteins. The gene helps direct an important cell growth and division process that can lead to the development of cancer if it goes awry. Dr Behrens said: "By targeting POL I with inhibitors, we were able to kill leukaemia cells and stop their growth in our pre-clinical and human tissue models." "This was a surprising, yet remarkable discovery, as we were able to unravel a new pathway and potential drug target that can hopefully be used in the fight against leukaemia in the future." The study also involved a collaboration with Associate Professor Elaine Sanij (St. Vincent's Institute of Medical Research) whose work focuses on targeting POL I and ribosome biogenesis in cancer therapy. "The findings show that a subset of aggressive acute lymphoblastic leukaemia exhibit a form of addiction to producing of ribosomes, the protein making molecular machinery," Assoc Prof Sanij said. "They render this aggressive leukaemia sensitive to POL I inhibitors which target ribosome production. "Altogether, our work highlights the importance of developing this new approach to cancer therapy to treat oncogene-driven cancers." Collaborative power One of the drugs used in the study to target POL I was an agent developed by the Peter MacCallum Cancer Centre. Professor Rick Pearson, former Associate Director of Laboratory Research at Peter Mac, said the team hopes to mimic the study in a future clinical trial to help patients with acute lymphoblastic leukaemia. "We worked with WEHI researchers to confirm our agent is effective in targeting POL I activity and demonstrated its potency in impeding the leukaemia cell growth and division. "These findings highlight the power of collaboration and the remarkable results that can be achieved when bringing together experts from across various areas. "We hope this research will translate into successful clinical trials and potentially offer doctors a new treatment option for patients with acute lymphoblastic leukaemia," Professor Pearson said. This research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft), the National Health and Medical Research Council (NHMRC), Cancer Council Victoria, National Stem Cell Foundation of Australia, the Leukaemia Foundation and Victorian Cancer Agency. The study, "ERG and c-MYC Regulate a Critical Gene Network in BCR::ABL1-Driven B-cell Acute Lymphoblastic Leukaemia," is published in Science Advances.

Key Highlights: Medical Research Future Fund (MRFF) has awarded St Vincent's Institute of Medical Research, Melbourne (SVIMR) a ~$1m grant to investigate Cynata’s mesenchymal stem cells (MSCs) in ischaemic heart disease (IHD) IHD is the leading cause of heart failure and death worldwide: there is an urgent need for new therapeutic strategies Cynata to partner with multiple leading research institutions on this project, which will be led by SVIMR Cynata’s Cymerus™ MSCs have been shown to have multiple positive effects in a preclinical model of IHD/heart attacks This project will focus on an innovative and minimally invasive method to harness the effects of MSCs in a sustained manner, to provide long-term cardiac reparative effects Melbourne, Australia; 26 September 2022: Cynata Therapeutics Limited (ASX: “CYP” or “Cynata”), a clinical-stage biotechnology company specialising in cell therapeutics, is delighted to announce that the Australian Government National Health and Medical Research Council (NHMRC) has awarded a grant of approximately $1 million under the NHMRC 2021 MRFF Cardiovascular Health Mission, to fund a major preclinical research project to investigate Cynata’s Cymerus™ MSCs as a treatment for IHD. The project will be led by Dr Shiang (Max) Lim (Head, Cardiac Regeneration Laboratory, St Vincent's Institute of Medical Research, Melbourne). It will also involve a number of other leading institutions, including the University of Adelaide, Baker Heart and Diabetes Institute, the University of South Australia, Duke-National University of Singapore Medical School, the University of Arizona, Monash University, Westmead Institute for Medical Research, and hearts4heart. Cynata will supply Cymerus MSCs at its cost to facilitate the study. The project is expected to run for a period of two years. It will involve encapsulating Cymerus MSCs in a clinical grade device which can be implanted below the skin (subcutaneously) to allow sustained delivery of the bioactive molecules released by the MSCs. Aims of the project include optimisation of the encapsulation approach, and demonstration of long-term cardiac repair in rat and sheep models of acute myocardial infarction, i.e. heart attack. If successful, it is anticipated that these studies would support progression to human clinical trials. Dr Lim said: “There is an urgent need for novel therapies to prevent the onset of heart failure and improve survival in patients with IHD. We firmly believe that MSC therapy has great potential to address this unmet need. Unlike conventional stem cell production methods, which are associated with scale up and consistency challenges, the Cymerus iPSC-based approach can provide an effectively unlimited source of consistent MSCs. This project aims to accelerate the development of a new, safe and minimally invasive method to deliver the beneficial secretions of Cymerus MSCs to patients, using a retrievable encapsulation device that protects the cells, to allow long-term treatment for effective cardiac repair.” Dr Kilian Kelly, Cynata’s Chief Operating Officer, said: “IHD is the leading cause of death worldwide, and accounts for about 12% of all deaths in Australia. Our previous research has established that Cymerus MSCs show great promise as a treatment for cardiovascular disorders, including IHD. This new project aims to enable clinical translation of a novel approach to achieve sustained delivery of Cymerus MSCs in this patient population. We are very pleased that the MRFF has seen fit to provide a substantial amount of funding to progress this, and we look forward to working with Dr Lim and the highly credentialled team that he has assembled to execute this important project.” -ENDS- Authorised for release by Dr Ross Macdonald, Managing Director & CEO CONTACTS: Dr Ross Macdonald, CEO, Cynata Therapeutics, +61 (0)412 119 343, ross.macdonald@cynata.com Lauren Nowak, Media Contact, +61 (0)400 434 299, laurenmaree@live.com.au 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. Planning for a Phase 2 clinical trial in GvHD under a cleared US FDA IND is presently underway. Clinical trials of Cymerus products in osteoarthritis (Phase 3) and diabetic foot ulcers (DFU) are currently ongoing. In addition, Cynata has demonstrated utility of its Cymerus technology in preclinical models of numerous diseases, including the clinical targets mentioned above, as well as 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.