Few people outside the scientific community will have heard of Harvard Professor Douglas Melton.
Yet he is one of the godfathers of modern biotechnology and was twice listed in the Time Magazine’s 100 Most Influential People in the World
The founder of what is today Gilead Sciences, a US$65bn American colossus, he was also pivotal in the development of messenger RNA as a drug.
For those with a passing acquaintance with vaccine development, mRNA drives the immune response triggered by the Pfizer/BioNTech and Moderna Covid jabs.
So, when Melton speaks, opines, or writes on any subject matter, the wider scientific world tends to stop what it’s doing and takes note.
His current fascination is midkine, a heparin-binding growth factor, which, when over-expressed, is linked with a whole host of nasty ailments including cancer, inflammation, and autoimmune diseases.
Japan leads field
While Japan has led the field, midkine, or midkine inhibition, has gained little traction with researchers outside the country.
Well, until recently. Midkine and its potential were validated in 2020 in the highly regarded scientific journal, Nature Medicine.
And the arrival of Melton on the scene, together with other top research groups in the US and Europe, has provided significant validation of the work being carried out by a growing corps of academics, medical scientists and companies.
Among them is LYRAMID, a research and development biotech company spun out from Australian anti-ageing group Cellmid, and recently acquired by UK-listed Roquefort Therapeutics PLC (LSE:ROQ).
In all, around A$40mln has been invested in intellectual property held by LYRAMID.
The aim is to use this expertise in midkine research to develop first-of-their-kind drugs targeting midkine for Covid, cancer, chronic inflammation, and autoimmune disorders.
Pivot
Most of the midkine R&D up to now has focused on monoclonal antibodies, which enlist your body's germ-fighting immune system to battle diseases such as cancer.
However, Lyramid has pivoted, to focus on gene silencing technologies in its bid to inhibit or suppress the over-expression of midkine.
That’s a leap of faith, but one that the company’s chief scientific officer, Graham Robertson, believes is justified.
He feels the path to the clinic using gene silencing techniques will be a lot more predictable, while scaled manufacturing will also be easier and cheaper than it might be producing an antibody-based drug.
Lyramid is basing its R&D activities around oligonucleotide technologies designed to create very targeted RNA therapeutics
“Antisense oligonucleotides and siRNA have been used to block midkine successfully, and so we thought that a similar gene silencing approach may overcome some of the limitations of the antibodies,” says Robertson.
Early stages
Despite 10 years of research, the company is still at the pre-clinical stage of its journey.
That said, with a £1.5mln investment from Roquefort, the pace should pick up.
The initial focus will be cancer and Covid. On the oncology programme, Robertson explains: “We're getting good results in terms of molecular outcomes, changing the midkine expression in tumour cells.
“The next step, which will happen over the next couple of months, will be to actually test whether blocking midkine using gene silencing approaches will alter human cancer cell behaviour.
“That's not necessarily just cancer cell proliferation, which is where cancer treatments were 20 years ago.
“It's actually far more sophisticated in terms of altering the tumour immune microenvironment required for successful cancer immunotherapies.
“Targeting midkine to overcome resistance to the blockbuster immune checkpoint drugs will be of immense benefit for many cancer patients.”
Robertson says the company is on course to take its cancer programme into phase I clinical trials in late 2023. This will likely take place locally in Australia before it launches studies in the US and Europe.
Investors familiar with the biotechnology sector will recognise the successful conclusion to phase II clinical trials as the value inflexion point for aspiring drug developers.
Risk vs reward
It strikes the balance between risk and reward.
However, we are seeing deals, substantial transactions, being struck very much earlier in the cycle, sometimes even during late pre-clinical development.
Robertson says there has already been interest from within the industry in the company’s pioneering new approach to midkine inhibition; however, what’s required is a clinical proof-of-concept.
“We need to have completed the critical de-risking step,” he explains. “That’s an early clinical trial, just because midkine based drugs will be first-in-class.”
For Roquefort, LYRAMID is likely to be its sole investment focus for the foreseeable future.
Multiple shots on goal
It has multiple shots on goal in different therapeutic areas, boasting a completely new approach to disease, and is likely to be the primary investment in the sector – so plenty to keep the team busy.
“We think we can create significant value in the next two years, even with the limited funds we raised,” says Stephen West, Roquefort’s chairman.
“We've earmarked a million pounds and put in another half a million pounds of contingency.
“We think we can deliver a lot of value from that just working through the midkine programme that Graham set out.
“So, we were incredibly excited about this and amazed we were able to pick it [the business] up for such a reasonable price.
“At this stage, we're not actually looking for any other acquisitions, because we just think there's so much unrealised value in here and we're totally focused on that.”