CHICAGO - Fast Forward has awarded a small New Zealand biotech called Innate Therapeutics $550,000 to help fund Phase IIa testing of its novel immunomodulator MIS416 in patients with progressive forms of multiple sclerosis, the pair announced May 5.

With validation from Fast Forward, the venture philanthropy arm of the National Multiple Sclerosis Society, Innate will collect another NZD600,000 (about $430,000) toward the study from the New Zealand government. "The fact that we had the support of Fast Forward played a large part in unlocking that grant," Innate CEO Simon Wilkinson said in an interview at the Biotechnology Industry Organization meeting.

Innate, an unlisted public company, now has funds on hand or committed funds from existing shareholders to take care of the balance of the funding for the study, Wilkinson said.

As a condition of the financing, Fast Forward takes an equity stake in Innate, and EMD Serono, the charity's collaborator in the grant-making program, gains an exclusive option to in-license the therapy at the end of the study. The funding will be provided over 15 months.

The grant to Innate is one of the first given in Fast Forward's Accelerating Commercial Development category.

"We think the MS Society and Fast Forward have really done something quite innovative and creative in their approach," said Wilkinson. "From a New Zealand perspective, where there's very little available by way of grant money ... we're not used to getting free money [and] we're very happy to be providing an equity return when we're getting cash coming in the front door."

And "for a small drug company that knows he's going to have to partner at some point," the relationship opening with EMD Serono is a good start, he said.

Fast Forward and EMD Serono struck up the collaboration, which added $19 million to the effort's coffers, in 2009 (Also see "EMD Serono Buys $19M Seat At MS Society’s Research Table" - Pink Sheet, 20 March, 2009.).

MS Funding Tipped The Balance On Indication Choice

For a start-up, the challenge is picking the indication for the clinical program, Wilkinson said. Innate's choice of progressive MS "was really happenstance."

Innate was "reasonably down the oncology and anti-infective pathway" with preclinical development of its immunomodulator technology when it was approached about 18 months ago by a progressive MS patient and a doctor requesting a supply of its lead candidate under New Zealand's compassionate use program, the CEO said.

Under that law, doctors with patient consent, and normally at patient request, can ask for a supply of a non-approved experimental medicine with the provision that it is produced under GMP conditions, which MIS416 is. "That experience gives you preclinical experience in humans," Wilkinson noted. The preview of human reaction led Innate to refocus its development efforts.

"We could see a certain justification for the approach [to treat MS] based on what we knew our agent was doing with the regulatory side of the immune system ... but I think it really came as a very pleasant surprise to our patient and to ourselves that that very first patient ... responded very quickly and very significantly to the drug." That success led to a word-of-mouth situation, recounted Wilkinson. Ultimately the company had seven progressive MS patients on the drug, who experienced varying degrees of improvement in symptoms or at least saw their condition stabilize.

Innate was on the spot. "We had very, very good conventional animal model data supporting the oncology and anti-infective pathway, but on the other hand we had this human data in an indication that was quite different," Wilkinson said.

Commercially, he said, the MS space was compelling because progressive MS is "really a complete unmet medical need," and there are few players in the market. And, "there appeared to be some quite significant funding potentially available through the likes of the MS society. So that tipped the balance."

A Bacteria Shell As A Delivery Mechanism

Innate's technology is designed to stimulate a broad (it targets no specific immune system cell) and entirely normal, but much lustier, response from the regulatory aspects of the body's "innate" immune system, Wilkinson explained.

To do that, Innate has created a sort of "therapeutic bacteria" that is recognized by the immune system as a familiar microparticle to ingest and break down, releasing the NOD2 and TLR9 ligands it carries. Those ligands then interact with receptors inside the cell and set up immune responses that trigger the NOD2 and TLR9 pathways.

The bacteria, which Innate calls it's "microparticle technology," has been fermented, then put through a series of extraction and purification steps that leave essentially the bacterial wall. That wall is rich in muramyl dipeptide (MDP), an activator of the NOD2 immune pathway that was once studied as a drug candidate but abandoned because of toxicity in its soluble state. Innate found a way to "nonsolubleize" MDP and incorporate it into the particulate structure of that bacterial cell wall, along with a natural TLR9 ligand that comes from the remnants of the bacteria itself.

In the patient, the immunomodulating agent performs a dual function, Wilkinson explained. First, it boosts the regulatory cytokines, the parts of the immune system that control and down-regulate the inflammatory aspects of the autoimmune disease. Second, it up-regulates production of the immune cells responsible for clearing away the myelin debris from the site of recent demyelinization around nerves. Research by others has shown that recently demyelinized nerves can remyelinate, he said.

"If you have been able to clear away the debris from the site of damage, if you can down-regulate the inflammation that's going on, you're allowing the body's own repair mechanisms to function," he said. The goal of treatment is to stop progression, and a plus is "we might be able to halt progression and have a limited reversal of some of the more recent signs and symptoms associated with more recent damage."

Treating Progressive MS Is A High-Risk Endeavour

While the more common relapsing and remitting MS is characterized by periods of neurological worsening followed by periods of spontaneous remission, progressive MS is an unremitting form of the disease that is characterized by gradually increasing degrees of handicap without recovery periods. Unlike relapsing/remitting MS, no therapies are approved for progressive MS.

Currently approved drugs aim at cutting down on the relapses in RRMS. Generally perceived as first-line are Biogen Idec's Avonex (interferon beta-1a), Merck Serono's Rebif (interferon beta-1a), Teva's Copaxone (glatiramer), followed by Biogen's Tysabri (natalizumab). Novartis' oral drug fingolimod (FTY720), branded Gilenia , is pending at FDA (Also see "Novartis' Gilenia Extension Trial Data Support Efficacy Of Low-Dose Version" - Pink Sheet, 13 April, 2010.), and others are working on oral therapies (Also see "Side Effects Dampen Neurologists' Enthusiasm For Novel MS Drugs" - Pink Sheet, 25 February, 2009.).

But the road to a therapy for progressive MS is strewn with failures, and according to Elsevier's Inteleos drug development database there is only tentative activity in the field, where pharmas mostly test their RRMS candidates in progressive patients as a secondary effort. Studies with Copaxone and Rebif have failed, as did Biogen/Roche's Rituxan (rituximab).

One other company working in the space is the Swiss specialty pharma Santhera Pharmaceuticals. Santhera is developing its synthetic coenzyme Q10 idebenone for progressive MS with the help of NIH's National Institute of Neurological Disorders and Stroke. A three-year Phase I/II adaptive design study being conducted by NINDS launched in July 2009, and results are expected in 2015.

Idebenone is approved in Canada as Catena for treatment of Friedreich's Ataxia, an inherited disease that causes progressive damage to the nerves that control muscles, and it is being investigated in Duchenne Muscular dystrophy.

-Shirley Haley (s.haley@elsevier.com)

Innate Therapeutics Wins $550K From Fast Forward For Therapy Aimed At Progressive MS

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