CYP-001 / Cynata Therap - LARVOL DELTA

A Study of CYP-001 in Combination with Corticosteroids in Adults with High-risk AGvHD (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cynata Therapeutics Limited | Trial completion date: Dec 2026 ➔ Jun 2027 | Trial primary completion date: Apr 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Two-year safety outcomes of iPS cell-derived mesenchymal stromal cells in acute steroid-resistant graft-versus-host disease. (PubMed, Nat Med) - P1 | "After intravenous infusion of mesenchymal stromal cells (CYP-001 derived from a clone of human iPS cells), we reported the safety, tolerability and efficacy within the primary evaluation period at day 100...In conclusion, systemic delivery of iPS cell-derived cells was safe and well tolerated over 2 years of follow-up, with sustained outcomes up to 2 years after the first infusion. ClinicalTrials.gov registration: NCT02923375 ."

Journal • Stroma • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Oncology • Transplantation

Further CYP-001 GvHD Clinical Data Published in Nature Medicine (PRNewswire) - P1 | N=16 | NCT02923375 | Sponsor: Cynata Therapeutics Limited | "Cynata Therapeutics Limited...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....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....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."

P1 data • Acute Graft versus Host Disease

First Patient Treated in Phase 2 GvHD Trial (PRNewswire) - "Cynata Therapeutics Limited...confirms that the first patient has been enrolled and treated in its Phase 2 clinical trial of CYP-001 in high-risk acute graft versus host disease (aGvHD)....This global Phase 2 trial aims to enrol approximately 60 patients with high-risk aGvHD, who will be randomised to receive either steroids plus CYP-001, or steroids plus placebo....The trial has been approved to commence in Australia, the USA and Turkey, and numerous clinical centres across those jurisdictions are now open for recruitment. The first patient was enrolled in the USA."

Trial status • Acute Graft versus Host Disease

Turkey Approves Cynata Therapeutics' Phase 2 Trial (Mirage News) - "Clinical-stage cell therapy company Cynata Therapeutics (ASX:CYP) has received regulatory and ethics approval to commence its Phase 2 clinical trial of CYP-001 in patients with High-Risk acute Graft versus Host Disease (HR-aGvHD) at clinical centres in Turkey....Cynata said it intends to open multiple clinical centres in Turkey, with the first site initiation visits anticipated within the next 1-2 months....Start-up activities for this trial continue to progress well, and we remain focussed on our goals of completing patient recruitment by the end of 2024, with primary results expected in the second half of 2025."

Enrollment status • New P2 trial • P2 data • Acute Graft versus Host Disease

MEND: The MEseNchymal coviD-19 Trial: MSCs in Adults With Respiratory Failure Due to COVID-19 or Another Underlying Cause (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Cynata Therapeutics Limited | Phase classification: P1/2 ➔ P1

Phase classification • Acute Respiratory Distress Syndrome • Critical care • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CRP

A Study of CYP-001 in Combination With Corticosteroids in Adults With High-risk aGvHD (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cynata Therapeutics Limited | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2026 ➔ Dec 2026 | Initiation date: May 2023 ➔ Aug 2023 | Trial primary completion date: Jun 2024 ➔ Apr 2025

Combination therapy • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Cynata Therapeutics (ASX: CYP) to present two-year clinical study data in SR-aGvHD at ISCT (Kalkine Media) - P1 | N=16 | NCT02923375 | Sponsor: Cynata Therapeutics Limited | "Cynata Therapeutics Limited...has announced a positive update concerning CYP-001, the company’s Cymerus™ mesenchymal stem cell (MSC) product candidate for acute graft versus host disease (aGvHD)....The long-term data follows highly promising results from the primary evaluation at Day 100 with Complete Response and Overall Response rates marked at 53% and 87%, respectively....The two-year follow-up demonstrates a sustained result with overall survival at 60% (9/15 patients), without any treatment-related serious adverse events or safety concerns detected. This survival rate compares very favourably to previously reported outcomes in SR-aGvHD, where longer term survival is typically less than 40%, says the company."

P1 data • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Cynata Receives Ethics Committee Approval for Proposed aGvHD Phase 2 Clinical Trial (BioMelbourne Network) - "Cynata Therapeutics Limited...has today announced that it has received approval from the Australian Human Research Ethics Committee (HREC) to commence the proposed Phase 2 clinical trial in acute graft-versus-host disease (aGvHD)....'We continue to make good progress towards commencing a Phase 2 clinical trial in aGvHD, with our expectations being to commence patient recruitment this quarter and to complete our primary evaluation of the trial data in 2024.'"

New P2 trial • Non-US regulatory • P2 data • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

A Phase I Trial of iPSC-Derived MSCs (CYP-001) in Steroid-Resistant Acute GvHD (ASH 2018) - P1; "Treatment response and overall survival rates are encouraging compared to previously published outcomes. The Cohort B primary evaluation period is expected to be completed by September 2018, and progression to a Phase II trial in this clinically challenging disease will then be considered."

P1 data • Biosimilar • Graft versus Host Disease • Hematological Disorders • Immunology • Neutropenia • Transplantation

A Study of CYP-001 in Combination With Corticosteroids in Adults With High-risk aGvHD (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Cynata Therapeutics Limited

Combination therapy • New P2 trial • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

MEND: The MEseNchymal coviD-19 Trial: MSCs in Adults With Respiratory Failure Due to COVID-19 or Another Underlying Cause (clinicaltrials.gov) - P1/2 | N=14 | Completed | Sponsor: Cynata Therapeutics Limited | Recruiting ➔ Completed | N=24 ➔ 14 | Trial completion date: Dec 2022 ➔ May 2022 | Trial primary completion date: Dec 2022 ➔ Apr 2022

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Critical care • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CRP

MEND: The MEseNchymal coviD-19 Trial: MSCs in Adults With Respiratory Failure Due to COVID-19 or Another Underlying Cause (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Cynata Therapeutics Limited | Trial completion date: Dec 2021 ➔ Dec 2022 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Critical care • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CRP

US FDA Clears IND for Cynata's Phase 2 Clinical Trial of CYP-001 in GvHD (PRNewswire) - "Cynata Therapeutics...is delighted to announce that the United States (US) Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for Cynata's Phase 2 clinical trial of CYP-001, Cynata's lead product, in patients with acute graft versus host disease (aGvHD)....The proposed Phase 2 clinical trial will seek to recruit approximately 60 patients with high risk aGvHD...The trial is expected to commence enrolment by later this year, with results of the primary evaluation expected in early 2024."

IND • New P2 trial • P2 data • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Cynata Enters into a New Strategic Partnership with Fujifilm (PRNewswire) - “Cynata has regained all development and commercialisation rights to CYP-001 for graft-versus-host disease with US$5m fee payable by Fujifilm to Cynata. Cynata to immediately pursue GvHD product development strategy in the US, building on the existing US Orphan Drug Designation for CYP-001. Cynata Therapeutics Limited…announced that it has entered into a new strategic partnership agreement (‘SPA’) with Fujifilm Corporation (‘Fujifilm’)….As part of the new partnership agreement, Fujifilm has agreed to a new voluntary escrow over the approximately 8.1 million shares it holds in Cynata….Cynata will now engage with the FDA on further clinical development of CYP-001 in the US via a Phase 2 clinical trial…A Phase 2 trial in GvHD will be an important late-stage addition to Cynata's active pipeline…”

Licensing / partnership • New P2 trial • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

First Patient Enrolled in Cynata’s MEND Clinical Trial (GlobeNewswire) - "...the first patient has been enrolled in its MEND (MEseNchymal coviD-19) clinical trial. Originally designed to recruit COVID-19 patients admitted to intensive care with respiratory distress the study was expanded in late March this year to include patients in intensive care with respiratory failure resulting from causes beyond COVID-19....First patient with respiratory failure enrolled in Cynata’s MEND clinical trial....Twelve patients will be randomised to receive Cymerus MSC infusions, in addition to standard of care, while 12 patients will be randomised to the control group and will receive current standard of care only."

Enrollment status • Infectious Disease • Novel Coronavirus Disease

MEND: The MEseNchymal coviD-19 Trial: MSCs in Adults With Respiratory Failure Due to COVID-19 or Another Underlying Cause (clinicaltrials.gov) - P1/2; N=24; Recruiting; Sponsor: Cynata Therapeutics Limited; Trial completion date: Mar 2021 ➔ Dec 2021; Trial primary completion date: Mar 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Critical care • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CRP

Cynata Expands MEND clinical trial in COVID-19 and Respiratory Failure (GlobeNewswire) - "Cynata Therapeutics Limited...is pleased to announce that it has received ethics committee approval to expand recruitment criteria in its active MEND (MEseNchymal coviD-19) clinical trial....Ethics committee approval received to expand the recruitment criteria of Cynata’s MEND clinical trial in patients in intensive care with respiratory failure, to include other causes beyond COVID-19 (such as influenza); The MEND trial will investigate early efficacy of Cymerus MSCs in patients with respiratory failure, who meet the well-established criteria for Acute Respiratory Distress Syndrome (ARDS); The trial expansion increases the pool of eligible patients, and is therefore expected to significantly accelerate recruitment."

Trial status • Novel Coronavirus Disease

New Preclinical Study to Investigate the High Potency of Cymerus MSCs (GlobeNewswire) - "Cynata Therapeutics Limited...announced the initiation of a new study to investigate in a pre-clinical model of lung disease the potential molecular mechanisms involved in the observed high potency of Cynata’s proprietary Cymerus™ mesenchymal stem cells (MSCs)....The observations are expected to provide very useful information relevant to the potential mechanisms of action of Cynata’s MSC products...Professor Samuel’s study is expected to commence shortly and conclude within 6 months."

Preclinical • Infectious Disease • Novel Coronavirus Disease

New Preclinical Study to Investigate the High Potency of Cymerus MSCs (GlobeNewswire) - "Cynata Therapeutics Limited...today announced the initiation of a new study to investigate in a pre-clinical model of lung disease the potential molecular mechanisms involved in the observed high potency of Cynata's proprietary Cymerus™ mesenchymal stem cells (MSCs). The data generated in this model, which mimics features of idiopathic pulmonary fibrosis (IPF)...The observations are expected to provide very useful information relevant to the potential mechanisms of action of Cynata’s MSC products and will be important in leveraging commercial and regulatory activities....Study is expected to commence shortly and conclude within 6 months."

Preclinical • Idiopathic Pulmonary Fibrosis

Cynata boosts coffers with $1.4m Government grant (The West Australian) - “Cynata Therapeutics’ recent run of successful capital raisings has been bolstered by a lazy A$1.39 million tax refund courtesy of the Federal Government’s Research & Development Tax Incentive grant scheme, or 'R&D' adding to its already burgeoning $24.9m pile of cash as at the end of December 2020….Plans are also afoot for further clinical trials of the fascinating Cymerus MSC products in 'Graft-versus-host' disease through licensee Fujifilm.”

Financing • Graft versus Host Disease

Cynata raises $15 million to fast-track stem cell therapies (The West Australian) - "Cynata Therapeutics has nailed down a $15 million placement to fund the expansion of its research and to develop a pipeline of stem cell therapies based upon the company’s revolutionary Cymerus technology. The most promising of the Cymerus therapies has been the development of the CYP-001 technology which is used to treat 'graft-versus-host' disease."

Financing • Graft versus Host Disease • Immunology

Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. (PubMed, Nat Med) - P1 | "CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process...OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases."

Clinical • Journal • Graft versus Host Disease • Immunology

MEND: The MEseNchymal coviD-19 Trial: a Pilot Study to Investigate Early Efficacy of MSCs in Adults With COVID-19 (clinicaltrials.gov) - P1/2; N=24; Recruiting; Sponsor: Cynata Therapeutics Limited

Clinical • New P1/2 trial • Acute Respiratory Distress Syndrome • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP

A Study of CYP-001 for the Treatment of Steroid-Resistant Acute Graft Versus Host Disease (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: Cynata Therapeutics Limited; Active, not recruiting ➔ Completed

Clinical • Trial completion • Graft versus Host Disease • Immunology