Biocurious: It’s a case of animal magnetism as Island eyes the FDA’s new rule on non-human testing

•  Having acquired a second anti-viral program, Island Pharmaceuticals hopes to avail of an FDA approval shortcut for one of the world’s nastiest diseases
• Island was so impressed with Galidesivir that it fast-tracked the acquisition process
• The company hopes both Galidesivir and its legacy program ISLA-101 will become eligible for potentially lucrative FDA priority review vouchers

The term ‘Animal Rule’ is redolent of George Orwell’s seven rules of Animal Farm.

Who could forget the perverse ‘all animals are equal’? Or how about the ‘kill the pig’ chant in Lord of the Flies as the stranded lads descend into animalistic savagery?

In drug development, Animal Rule now means something less foreboding – but just as far reaching.

Three years ago, the US Food & Drug Administration (FDA) devised the Animal Rule to enable approvals without the rigmarole of a human trial.

Conventional wisdom goes that drug makers must test out their candidates on human flesh and blood.

Trialling drugs on our nearest relative – primates – can only go so far.

But what if the disease is so awful and fatal that human testing would not be ethical or feasible?

In these cases, the FDA might approve treatments based on “adequate and well-controlled” animal efficacy studies.

These remedies must prevent “serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic chemical, biological, radiological, or nuclear” agents.

Tackling some of the world’s worst viruses

The Animal Rule concession is likely to be crucial for Island Pharmaceuticals (ASX:ILA), which this month acquired the rights to an antiviral compound, Galidesivir.

The vendor was the Nasdaq-listed Biocryst Pharma.

A broad spectrum anti-viral, Galidesivir is claimed to be effective against more than 20 viruses, including the hideous hemorrhagic Ebola and Marburg.

Biocryst tested healthy volunteers in phase 1 trials for some of the ‘lesser’ diseases, establishing safety.

Subsequent primate and hamster testing for yellow fever, Zika, Marburg and Ebola produced what Island CEO Dr David Foster dubs “phenomenal results”.

These include 100% survival, whereas the control animals were dead within days.

In particular, the Marburg primate results could provide the foundation for availing of the Animal Rule.

Foster says the program supplements Island’s existing program ISLA-101, to treat and prevent the mosquito-borne dengue fever.

The deets of the deal

The deal sees Island acquiring Galidesivir  from the Nasdaq-listed Biocryst Pharma for US$550,000.

The initial agreement was by way of a US$50,000 option fee.

“After considerable diligence we became very excited about the asset and elected not to (avail of option) and go straight to an acquisition,” Foster says.

Island also pays $US500,000 to Biocryst on phase II trial completion and a further US$500,000 on FDA approval.

Thus far, Biocryst has completed one acceptable animal study.

“We may be one successful animal study away from submitting a New Drug Application [to the FDA],” Foster says.

“This can happen very quickly and we are laying the groundwork for [a] primate study. We hope to have it completed 12 months from closing the acquisition.”

The obvious question is: if Galidesivir is so promising, why was Biocryst happy to dispose of it for not much more than a song?

Foster notes the program was funded almost entirely by US grants, which eventually dried up (see below).

Biocryst also shifted strategy in favour of becoming a rare diseases company.

With cash of $7.25 million as of June 30, Island is well funded for a second simian study.

America’s quiet war on (bio) terror

US authorities have been keenly interested in Galidesivir’s development, because of the potential for Ebola and Marburg to be “weaponised”.

Uncle Sam has poured at least US$70 million into developing the compound, as a counter bioterrorism strategy against such horrible hemorrhagic viruses.

Via the disaster preparation agency BARDA, the US has a long history of dealing in germ warfare – and it’s not monkeying around.

BARDA, for instance, has spent hundreds of millions of dollars on anthrax and smallpox vaccines.

Foster notes government contracts – such as those offered by BARDA – don’t entail hiring an army of salespeople.

“It’s a great commercial opportunity,” he says.

“We could select any number of viruses. Zika stands out, but we’re laser focused on Marburg.”

Let’s not put the moz on ISLA-101

Foster adds that Island has not lost is passion for its original program ISLA-101, targeting the mosquito-borne dengue fever.

Usually not fatal but most unpleasant, dengue fever is spreading, to the extent that half of the world’s populace is vulnerable.

Currently about 400 million people are infected annually.

Island has carried out a randomised, placebo-controlled, double-blinded phase 2a/b study, dubbed Protect.

The trial covers both treatment and prophylactic cohorts.

In the June quarter, Island released top-line results.

These showed a “considerable reduction” in viral load in the preventative cohort. The study also showed a “clear drug signal” in the treatment group.

The latter received a weakened form of the virus (or a placebo).

As a repurposed drug with a long-established safety profile, ISLA-101 should benefit from a truncated approval pathway.

Similarly, Galidesivir initially was intended to be used for hepatitis C.

This means the drugs could be commercialised much faster than traditional therapies, which might take more than a decade (and billions of dollars) to get to market.

Island saddles up for multiple PRVs

The potential Animal Rule shortcut aside, Island could be in line for a coveted FDA Priority Review Voucher (PRV), for both the Galidesivir and ISLA-101 programs.

Irreverent folk dub PRVs as ‘Willy Wonka’ vouchers, given their potential to create untold riches (without the choccie overload tummy aches).

The FDA might bestow a PRV on the maker of an approved therapy, the idea being that a second drug is subject to fast-track assent.

Most likely, the recipient sells the fungible paperwork to another party. As a result, PRVs have changed hands for US$100 million to US$150 million.

In the case of blockbuster drugs, getting to market three months earlier can mean billions more in sales.

In the case of  Galidesivir, Biocryst would take a 25% stake in any PRV spoils.

Island chairman Jason Carroll is unaware of any other ASX biotech with the ability to secure two PRVs.

Come to think of it, so are we …

Off to the races

Island is assembling a dossier to present to the FDA, in view of getting feedback on using the Animal Rule.

To date, no Australian company has availed of the concession … but there’s always a first.

“What people are calling a pony is going to win the Melbourne Cup,” Carroll says.

Island may be off to the races. But it still needs some luck on its side because infectious disease drug developers only get one-third of their therapies to market.

That’s a much better strike rate relative to the wider drug pantheon.

“We are in a fortunate position to have two phenomenal assets,” Foster says.

“We want to set up the next ISLA-101 trial, but  Galidesivir will lead the way because it is such a short path to approval.”

Ticking the boxes

A recent Island board appointee, Carroll heads psychedelic drug developer Tryptamine Therapeutics (ASX:TYP).

“When you look at a pharma company value there are a few things to ask,” Carroll says.

“Does it work? Is it safe and effective and how do you protect its value? Can you make it? How many trials [are required] and how does [the company] pay for commercialisation?”

Evidently, both Galidesivir  and ISLA-101 pass muster on these counts.

“This is a much bigger opportunity than what most people think,” Carroll says.

“… this is one of the most significant products any Australian biotech can get hold of.”