PERTH, Australia – Cellmid Ltd.'s lead anti-midkine antibody, CAB-102, reduced kidney injury and preserved renal function in a preclinical model of focal segmental glomerulosclerosis (FSGS), according to studies performed at the Westmead Institute in New South Wales.
The new data in the rare kidney disease will allow the Sydney-based company to submit orphan drug applications with the FDA and the EMA.
Cellmid CEO Maria Halasz told BioWorld that she expects the company's first antibodies to be in the clinic in 18 to 24 months.
The humanized antibody reduced the area of kidney injury threefold compared to control mice with FSGS (p < 0.05), while renal function was improved (p < 0.05), according to study results that were presented at the 54th annual meeting of the Australia and New Zealand Society of Nephrology.
"We believe there are some opportunities for orphan drug filings in one or potentially two indications for Cellmid's midkine antibodies," Halasz said, noting that the company is working with regulatory agencies to complete those filings.
The study confirmed previous findings that blocking midkine alleviates damage to the kidney and prevents ensuing defects in renal function. The results demonstrated that a humanized antibody targeting midkine is as effective as its murine precursor.
The technology originally came out of Japan. Professors Takashi Muramatsu and Kenji Kadomatsu discovered the midkine protein in 1988 at Nagoya University. They have both published more than 250 peer-reviewed publications on the function and properties of the novel target. Both scientists are listed as inventors on a number of Cellmid's patents and continue to actively contribute to the field of midkine research.
"Midkine is prevalent in most solid tumors, and a lot of the science behind midkine was around trying to detect it in the body. It's found in tissues including blood and secretions like tears, and a lot of the early publications about midkine focused on cancer diagnosis," Halasz said.
Midkine is a modulator of cell signaling, and it interacts with a variety of receptors under different inflammatory and disease settings, she said, adding that midkine expression is often evident early in disease outset, and as such it is an important early marker for diagnosing cancers and autoimmune diseases.
In 2007, there were about 350 publications on midkine from multiple groups, and in the last eight years, the number of publications has grown to about 870 peer-reviewed publications, she said.
When Halasz joined Cellmid in 2007, she did a complete overhaul of the company. Within 12 months, she restructured the capital, acquired the midkine portfolio and rebuilt the board.
The company's R&D model is focused on partnerships. As a small company, that was a necessity, she said, but "sometimes out of necessity you find some amazing partnerships that give you the opportunity to work with some incredible research organizations."
Not your typical drug development company
"We're not a typical drug development company where we have one drug and a well-defined clinical development path. We are an unusual company in that we have an entire target.
"When you look at our patent portfolio, we own this target for everything – all our antibodies come from composition of matter to matter of use in cancer, inflammatory disease, autoimmune diseases, adhesions and others. With such a broad intellectual property portfolio, it would be irresponsible for us not to fully understand where we deliver the most benefit to patients," she said.
"It takes time. Cells only grow so fast. Animals can only tell you so much. So we have to do the hard work."
In 2017, the company restructured itself into three separate wholly owned subsidiaries. The Lyramid portfolio focuses on the midkine antibodies for treatment of fibrosis, chronic kidney disease and associated conditions. The Kinera unit is developing midkine as a therapy for acute ischemic injury (MK-103).
Advangen focuses on Cellmid's FGF5 inhibitor hair growth products sold as over-the-counter products. Cellmid acquired the hair loss product in 2013, and because it was a consumer business, the company decided to split those units apart.
Cellmid's pipeline consists of a number of antibodies targeting midkine, including humanized monoclonal antibody (MAb) CAB-102 in solid tumors and CAB-101 in kidney injury and inflammatory diseases.
Cellmid has a number of preclinical programs studying the midkine target as well as a recombinant midkine protein program in cardiac ischemia. It also licenses a number of midkine diagnostics.
Cellmid recently completed a capital raise of more than A$10 million (US$7.1 million) that consisted of a A$9 million share placement to sophisticated and institutional investors. The placement consisted of 23.7 million shares priced at A38 cents in two tranches. An additional A$1 million was raised from an oversubscribed placement to existing shareholders on the same terms.
The funds raised will scale up distribution of Cellmid's evolis hair loss products in the U.S., China, Australia and Japan.
Halasz said the hair loss product started as a therapeutic product but the active ingredients are plant-based with extensive human use, so with its safety track record, Cellmid didn't need to conduct rigorous safety studies.
"However, we have conducted rigorous blinded efficacy studies to support the claims we are making," she said, noting that lately the company has focused more on its consumer portfolio, which she expects to become profitable this year.
Halasz said Cellmid has no real competitors with its midkine target. "In terms of the clinical indications, if you look at autoimmune myocarditis, it's an incredibly poorly served area.
"We feel we are in a space where there are not many therapies at all, and we have very nice preclinical data that show our antibodies could potentially be very helpful in that setting."
"We have a first-in-class drug," she added. "We own all the IP globally for this target, so that's our claim to fame. As soon as we get to the clinic, all the other data will begin to generate value."
Cellmid is listed on Australia's Securities Exchange (ASX:CDY), and has a market cap of A$24.5 million. Its shares were trading at A39 cents at market close on Thursday.