PERTH, Australia – Melbourne, Australia-based Dimerix Ltd. saw its shares gain 66% on the news that its lead candidate, DMX-200, has been chosen to enter the global REMAP-CAP platform trial as a potential treatment for COVID-19-related acute respiratory distress syndrome (ARDS).
The Randomized, Embedded, Multifactorial Adaptive Platform trial for Community-Acquired Pneumonia (REMAP-CAP) program – as well as companion platform REMAP-COVID – is an international adaptive platform trial run by a network of leading experts, institutions and research groups collaborating to answer crucial questions during a declared pandemic.
DMX-200, which is currently being studied in chronic kidney disease, reduces inflammation damage that promotes the progression of chronic kidney disease. It does that by blocking the signaling process by which inflammatory cells damage the kidney, said Dimerix CEO Nina Webster during a conference call June 4.
One of the hallmarks of severe cases of COVID-19 is ARDS caused by rapid, widespread inflammation of the lungs that can lead to respiratory failure and death.
The recent discovery that the virus may cause an imbalance in the angiotensin system that normally controls blood pressure and inflammation was a development that caught Dimerix’s attention.
“It was found that the virus is using one of the proteins of the renin-angiotensin system to enter the lung, and a lot of the studies globally are looking at angiotensin blockers to block that process,” Webster told BioWorld in a follow-up interview.
“When you look at where we fit into that, DMX-200 involves the inhibition of CCR2. That key protein allows immune cells to move to areas of inflammation with high concentrations of the chemokine MCP-1,” she said. “The damaged organs produce high levels of MCP-1 chemokine, and what we have shown is that blocking the CCR2 receptor at the same time as using an angiotensin receptor blocker reduces the movement of immune cells to the damaged organs.
“There is a lot of growing evidence that there are high concentrations of MCP-1 in the lungs of patients with ARDS, and the resulting movement of immune cells into the lung may be one of the factors of the cytokine storm in the lung,” Webster added. “For this reason, there is strong scientific evidence that DMX-200 on its own or in combination with an angiotensin receptor blocker may have the unique potential to reduce the COVID-related lung damage.”
Dimerix’s core patents claim the utility of CCR2 antagonists (DMX-200) given concurrently with angiotensin II receptor blockers (ARBs) in various chronic inflammatory conditions, including in the lung and the kidney. “We thought there was no reason that DMX-200 wouldn’t interrupt that cytokine storm and dial down that immune response.”
Webster reached out to several experts who suggested she speak with the REMAP-CAP group, which subsequently asked Dimerix to join the trial.
The study will examine whether DMX-200 could benefit ARDS patients with COVID-19 by reducing the inflammatory response in the lungs, thus reducing inflammation and subsequent scarring, she said.
The REMAP-CAP study has several existing domains, including a COVID-19 antiviral domain, a COVID-19 immune modulation domain and a COVID-19 immunoglobulin domain. A COVID-19 inflammatory treatment arm is being established and will include DMX-200 with an ARB.
Dimerix R&D Director Robert Shepherd said the REMAP-CAP study protocol enrolls patients globally wherever the pandemic moves. It allows multiple therapies to be tested, and because it’s an adaptive trial, it allows for additional arms without having to wait for the study to complete.
The REMAP-CAP pandemic special study designation ensures that results of any clinical trial are communicated directly with policymakers and public health officials around the world for rapid implementation into clinical practice, Webster said.
The overall REMAP-CAP study plans to include more than 7,000 patients from more than 200 study sites across Asia-Pacific, Europe and North America. REMAP-CAP is now working with Dimerix to prepare a new treatment group to include DMX-200, and to get the necessary regulatory clearances to begin trials.
This global study is supported by several funding agencies worldwide, with Dimerix responsible for providing the study drug to the trial sites.
Renal programs about to complete
Dimerix has two phase II programs underway: DMX-200 for focal segmental glomerulosclerosis (FSGS), which has orphan drug designation in both the U.S. and in Europe; the other trial is in diabetic kidney disease.
The two kidney studies are being conducted at sites across Australia and remain on budget and on track, with data readout expected mid-2020. The new COVID-19 opportunity has no impact on the status or development plans for the renal program, Webster said.
The FSGS study will dose the last patient this month, and the diabetic kidney trial will dose the last patient in July, so data from both trials will likely be reported in the next few months, she said.
An earlier phase IIa dose-escalation trial in chronic kidney disease met the primary endpoints of safety and tolerability. It also met secondary efficacy endpoints, with 25% of patients achieving a greater than 50% reduction in proteinuria, which is over and above the standard of care.
Excess protein in the urine, or proteinuria, is the most common symptom of kidney disease and is indicative of decreased kidney function.
Dimerix is in discussions with pharma companies to go into phase III trials. Even so, the FSGS trial will be a single phase III trial with a surrogate endpoint of protein in the urine, so the company could potentially run that trial on its own, the CEO said.
The company has AU$3.5 million (US$2.4 million) in cash, which will get it through the ARDS trial and its two phase II programs, she added.
Dimerix shares on Australia’s Securities Exchange (ASX:DXB) were up 66%, trading at AU45 cents per share at the end of trading June 4. The company has a market cap of roughly AU$49 million.