Innate Immunotherapeutics plans move across Tasman

Biopharmaceutical company Innate Immunotherapeutics will set up a new office in Sydney in a move to capitalise on the building interest around its lead drug MIS416.

Executive director and CEO Simon Wilkinson said the next major step for the company is a Phase IIb trial of its lead candidate, MIS416, which is showing promise in the treatment of patients with secondary progressive multiple sclerosis (SPMS).

“Our new corporate office will be based in Sydney,” said Wilkinson, who has been involved with the company since its inception in 2000. “This was driven by our newly appointed chairman-designate and intellectual property attorney being Sydney based, and is underway as we speak.”

The chairman designate, Michael Quinn, will be confirmed at the company’s annual meeting of shareholders in October. Quinn is also a director with ResMed and Sydney-based biotech QrXPharma, and founder of Australian venture capital firm Innovation Capital.

Andrew Sneddon, a former life science partner at Price Waterhouse Coopers and chair of a range of companies in the technology and life science space, will take up the position of independent director.

Wilkinson said the R&D tax rebate, as well as getting closer to patients and neurologists in Australia, were also big incentives for them to make the move.

“The R&D tax incentive will provide significant gains for us financially,” said Wilkinson. “And having access to neurologists with experience as principle investigators in clinical trials is important.

“Moving to Australia will also provide us with more options to raise finance for our Phase IIb study,” said Wilkinson, indicating that private investors as well as pharmaceutical companies were interested in the progress the company was making with MIS416.

The Phase IIb placebo-controlled efficacy study of MIS416 will be the focus of the next 18 months for Innate Immunotherapeutics, which Wilkinson estimates will require overall capital of $12 million. He expects that pharma will come on board once the study has been completed.

“There are six or seven pharmaceutical companies already active in the SPMS space,” he said, “and there is also a well-understood path to market.”

The production facility and R&D set-up will remain in Auckland, where the company has a small expert team and a licensed GMP manufacturing facility.

An area of unmet need

MS is an Anglo-Saxon disease. It affects 2.5 million people worldwide who primarily reside in the UK, Western Europe, Canada, the US, Australia and New Zealand.

Superimposed on this is a latitudinal gradient - that is, the closer people are to the North or South Pole the higher the incidence of MS. For example, the incidence is higher in Adelaide and Tasmania than it is in Darwin.

“There is a gender element as well,” said Wilkinson, “three times more women have MS than men.”

About 85% of patients with MS are diagnosed with the early-stage relapsing remitting MS (RRMS).

RRMS involves acute inflammatory attack of the myelin sheaths that insulate the nerve cells in the brain and spinal cord. The disease occurs in a cycle of degeneration and remission, where myelin is damaged by immune system attack and then patients enter a recovery period during which most of the damage is repaired.

RRMS has a 10- to 15-year course after which about two-thirds of patients develop SPMS. SPMS is characterised by a worsening of myelin damage and accompanying disability with no remission period.

“There are nine drugs approved by the FDA to treat RRMS,” said Wilkinson. “Unfortunately, these treatments do not stop the disease course, they lengthen the period between attacks but the disease continues.

“Once a patient develops SPMS there are no approved treatments available; short-term high-dose steroids may be given to deal with acute attacks.”

MIS416 provides a promising option for these patients. Phase Ib and IIa studies have been conducted at a single dedicated site in New Zealand with promising results.

Results from the Phase IIa trial showed that 80% of patients with SPMS had a 30% or greater improvement in at least one measure of MS-related symptoms. And of the 15 patients with SPMS who received six or more doses, 13 (87%) reported modest to significant improvement in their health-related quality of life.

People with SPMS experience accumulating disabilities and the impact of the disease on their quality of life is significant. They are unable to work and maintain their usual social activities, becoming house bound and wheelchair bound - changes that then lead to secondary health conditions.

“For the next Phase IIb study, we aim to recruit 90 to 100 patients across six or eight sites, so we need larger neurological facilities and experienced neurologists to participate in this, which Australia can provide,” Wilkinson added.

Wilkinson expects recruitment for the trial will not be a problem.

The macrophages of the brain

So why don’t the drugs for RRMS work for SPMS?

“Fundamentally, it’s about different parts of the immune system,” said Wilkinson.

RRMS involves acute bouts of inflammation. The processes that drive this inflammation start off in the adaptive wing of the immune system, which is called into action once the inflammation is present. This process takes place in the peripheral bloodstream, which is where existing drugs are active.

SPMS involves the innate immune system, the components of which are constantly present in the body (such as natural killer cells and phagocytic leukocytes) and is driven in the central nervous system (CNS).

“The unique thing about MIS416 is that it targets the innate cells and has an effect inside the CNS,” explained Wilkinson. “The drug moves through the circulation to the liver where it sets up an immune regulatory response that results in anti-inflammatory factors getting inside the CNS.”

MIS416 was developed using Innate Immunotherapeutics’ immune-modulating microparticle technology. The technology uses a bacterially derived therapeutic microparticle that incorporates naturally occurring non-immunogenic ligands.

When administered to patients, the MIS416 microparticle/ligand complexes are readily absorbed by immune cells, primarily monocytes, macrophages, natural killer cells and dendritic cells. Once inside the immune cells, MIS416 activates immune signalling pathways that down-regulate chronic inflammation, reduce autoimmune factors and help repair damaged tissue.

MIS416 also appears to have an effect on the glial cells - the macrophages of the brain - to initiate repair and also has anti-inflammatory action inside the brain.

“The effects we are seeing in animal models and that patients describe wouldn’t be explained by the drug just having an anti-inflammatory effect,” said Wilkinson. “What we think might be happening is myelin repair, and for this to happen requires cells to clear out the myelin debris at the site of degeneration so that nerves can remyelinate.”

The macrophages that pass through the blood brain barrier from the periphery can clean up the myelin debris, and resident glial cells can play this role as well. So the proposed mechanism of action is that the drug influences one or both of these cell types to clear away the debris so that myelin can be regenerated.

“It may only be a 5 or 10% change to cause this but it can result in an improvement,” said Wilkinson.

“We also know that the immune cascade MIS416 sets up in the liver drives the production of myeloid cells from the bone marrow and these mature into regulatory cells that downregulate inflammation, along with anti-inflammatory chemokines and cytokines,” said Wilkinson.