MELBOURNE, Australia, 28 April 2016 - Dimerix Limited (ASX: DXB), a clinical-stage biotechnology company committed to discovering and developing new therapeutic treatments identified using its proprietary screening assay, today announced that it has filed a request to the US Food and Drug Administration (FDA) for a pre Investigational New Drug (IND) application meeting in relation to the Development Plan for DMX-200 in Focal Segmental Glomerularsclerosis (FSGS). This event triggers conversion of 75,000,040 Class B Performance Shares to ordinary shares.
FSGS is a chronic kidney disease, for which Dimerix’s DMX-200 has received orphan drug designation.
The FDA encourages entities developing drugs for Orphan Indications, to obtain guidance on the data necessary to warrant IND submission, and seek early agreement with the FDA on critical questions which will define the data and the development plans ultimately used to register the drug in the US. Dimerix anticipates its discussion on DMX-200 will be scheduled in late June and this will enable receipt of critical planning information from the FDA in Q3 2016.
DMX-200 combines two existing drugs, a chemokine receptor CCR2 blocker (propagermanium) used for its anti-inflammatory properties, and an angiotensin II type I receptor blocker (irbesartan) which is registered in the USA for hypertension and treatment of diabetic nephropathy in certain patients.
Preclinical testing of DMX-200 in models relevant for kidney disease showed a significant reduction in proteinuria, strongly supporting the potential of DMX-200 to improve the same condition in patients.
Dimerix Executive Chairman Dr James Williams said, “Discussing DMX-200 with the FDA will provide us with valuable clarity around our US chronic kidney disease program and clinical trial designs, and the nonclinical package which the FDA will require for each development stage, including ultimate registration requirements of DMX-200 for FSGS. This information should place Dimerix in a strong position to map out the registration pathway and is a critical step towards realising the commercial value of our lead asset DMX-200.”
Filing the FDA pre-IND meeting application triggers Milestone B of the Class B Performance Shares which were issued to Dimerix Bioscience shareholder vendors on 3 July 2015. As such, 75,000,040 Class B Performance Shares convert to 75,000,040 ordinary shares. See the following Appendix 3B.
Dimerix Bioscience Limited
Dimerix Limited’s wholly owned subsidiary Dimerix Bioscience Limited is a clinical-stage pharmaceutical company committed to discovering and developing new therapeutic models identified using its proprietary screening assay, termed Receptor-Heteromer Investigation Technology (Receptor-HIT). This assay enables the identification of pairs of receptors that function in a joint manner (interact) when ligands, small molecule drugs, peptides or antibodies, bind to them. The Receptor-HIT technology was used to identify DMX-200 and an internal drug development program, initially for the treatment of a subset of patients with chronic kidney disease. In addition to its own therapeutic programs, the company also earns revenue by providing this technology to global pharmaceutical firms. For more information see www.dimerix.com
DMX-200 combines two existing drugs, irbesartan and propagermanium. Irbesartan is an off-patent angiotensin II type I receptor blocker indicated for the treatment of hypertension and nephropathy in Type II diabetic patients. Propagermanium (PPG) is a chemokine receptor (CCR2) blocker, which has been used for the treatment for Hepatitis B in Japan and is available in the USA for its anti-inflammatory properties. DMX-200 has been shown to improve the outcome of chronic kidney disease by reducing proteinuria by more than 50 per cent in animal models.
The DMX-200 Phase II Trial
The trial is a single arm, open label study in adult patients with chronic kidney disease (with proteinuria). The primary end points are the incidence and severity of adverse events and the clinically significant changes in the safety profile of participants. The secondary end points are obtained from statistical analysis of biomarker data at each time point including change from baseline, and the proportion of responders defined as those participants achieving normalisation of proteinuria (proteinuria within normal limits) or those participants achieving a 50 per cent reduction in proteinuria.
The trial has two parts, Part A is a dose escalation trial recruiting up to 30 patients. All patients recruited to the trial will be on stable irbesartan therapy, and will be treated with propagermanium dosed orally three times per day. Each patient will commence on 30mg PPG/day and the dose increased each 28 days to a maximum of 240mg/day, or until proteinuria is absent or reduced to a level the clinician considers acceptable.
The Company expects to carry out an interim analysis of the Part A data to confirm the safety of the therapy and observe any biomarker changes on up to 15 patients. It is expected interim data will be available during 2016.
Part B is an expansion study, in which up to 30 patients are recruited on the best dose identified from Part A. The company expects to review the design of Part B in consultation with the FDA and in light of all data available to the company, prior to commencement of Part B. These discussions will be in line with the company’s strategy of pursuing registration for an orphan indication in which the sufferers exhibit chronic kidney disease. The company has achieved orphan designation for Focal Segmental Glomerulosclerosis (FSGS) from the FDA. The trial has commenced at four sites in Melbourne, Australia, and may be expanded into other jurisdictions to meet recruitment targets and regulatory goals.
Chronic Kidney Disease
Chronic kidney disease can result from diabetes, high blood pressure and diseases that cause inflammation specifically in the kidneys. Proteinuria is the most common manifestation of the disease. As the disease progresses it can lead to end-stage renal disease (ESRD) where the kidneys fail. The only treatment for ESRD is a kidney transplant or regular blood-cleansing treatments called dialysis. More than 26 million people suffer from the disease in the United States.
(1) Functional interaction between angiotensin II receptor type 1 and chemokine (C-C motif) receptor 2 with implications for chronic kidney disease.
Ayoub MA, Zhang Y, Kelly RS, See HB, Johnstone EK, McCall EA, Williams JH, Kelly DJ, Pfleger KD. PLoS One. 2015 Mar 25;10(3):e0119803. doi: 10.1371/journal.pone.0119803. eCollection 2015.
Issued for and on behalf of Dimerix by Instinctif Partners.
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