Biocurious: Noxopharm has the ‘burning fire’ of inflammation squarely in its sights

• After a strategy revamp, Noxopharm is targeting inflammatory diseases – lupus in particular
• Affecting five million people, lupus has proved a tricky disease to tackle
• The company is pondering a phase II trial, most likely in skin lupus

Noxopharm (ASX:NOX) CEO and managing director Dr Gisela Mautner describes inflammation as “like a burning fire in your body” – but a condition that is largely unappreciated.

“Inflammation kills millions of people globally, but why don’t we hear more about it,” she says.

“Inflammation is the underlying reason for many different diseases, such as heart and neurodegenerative diseases.

“Anything you can do to alleviate inflammation has a huge market potential.”

After three years of soul searching, Noxopharm is zeroing in on a particular manifestation of inflammation: the autoimmune disease lupus.

Or even more specifically: cutaneous lupus erythematosus (CLE).

Folk of a certain age will remember the ‘Cure Lupus’ stickers that adorned car bumpers in the 1970s.

Sadly, they haven’t.

On the CLE front, Noxopharm hopes to redress the situation with its drug candidate Sof-Skn, which has a different mechanism of action to the standard of care treatment.

The company cites autoimmune diseases as a US$163 billion market currently, forecast to rise to US$220 billion by 2035.

About 90% of autoimmune conditions have an inflammatory component.

Other ASX biotechs tackling inflammatory pathways include Syntara (ASX:SNT) (myelofibrosis), AdAlta (ASX:1AD) (idiopathic pulmonary fibrosis),  Paradigm Biopharmaceuticals (ASX:PAR) (knee osteoarthritis) and Dimerix (ASX:DXB) (kidney disease).

Meanwhile Argent Biopharma (ASX:RGT) tackles acute respiratory distress syndrome, the body’s inflammatory (over) response that caused so many Covid casualties.

Changing tack

Mautner has headed Noxopharm for three years, having been the company’s chief medical officer.

Previously, she held senior roles at MSD (Merck), Bayer and Amgen.

The well-credentialled Mautner holds a German Doctor of Medicine degree and a PhD, as well as a Master of Public Health from Harvard University and a Master of Business Administration from Northwestern University of Chicago.

“I’ve been in big pharma for too many years to count and have done more than 20 drug launches,” she says.

In April 2023, the company ditched an experimental cancer drug called Veyonda, partly because its suppository formulation was “not widely accepted by patients”.

In an entirely different rear-guard action, the company changed tack and decided to focus on Sofra.

“We have completely restructured the company,” Mautner says.

Based on a discovery at the Melbourne based Hudson Institute of Medical Research, the Sofra platform is based on short nucleic acid sequences (the building blocks of DNA or RNA).

Known as oligonucleotides, these sequences act on specific immune sensors to regulate inflammation at its source.

“In essence, the Sofra technology for autoimmune diseases replicates what is naturally occurring in the bodies of healthy people, but is either absent or too little in patients with autoimmune conditions,” the company says.

In effect, Sofra turns the bodily switches – immune sensors – on and off.

Noxopharm has a ‘library’ of more than 1000 of these assets (RNA sequences).

Targeting the root causes of lupus

Targeting autoimmune skin diseases, Sof-Skn is the first drug from the Sofra platform.

Lupus is caused when the immune system mistakenly attacks the body’s own healthy tissues and organs, causing inflammation and damage.

About five million people suffer some form of lupus, with celebrity sufferers including Selena Gomez, Lady Gaga, the musician Seal and the late Michael Jackson.

The disease is more common in females and typically appears between the ages of 20 and 40.

Lupus can affect the skin, joints, kidneys, brain, heart, and lungs.

Symptoms can include fever, achy joints, fatigue, rashes and hair loss.

CLE is a subset of the disease that affects the skin.

“Skin diseases can get very horrible, very nasty to look at and very debilitating,” Mautner says.

“But [CLE] can also become a systemic, lethal form of the disease.”

Sofra targets the immune sensor TLR-7/8, which is known to be implicated in lupus.

As a topical cream rather than a pill, Sof-Skn enables better drug absorption.

Noxopharm chief scientific officer John Wilkinson says drug developers always have struggled to penetrate the dermis, owing to the skin’s defensive mechanism against foreign material.

“It’s a very complicated organ.”

The labours of Heracles

Noxopharm’s showpiece clinical study, Heracles has completed its safety and dose ranging stage, enrolling 16 healthy volunteers across four cohorts.

This month the company reported the drug to be “safe and well tolerated” across the single ascending doses.

The trial is being conducted by Doherty Clinical Trials Ltd in Melbourne, an arm of the Peter Doherty Institute for Infection and Immunity.

The company promises an update “soon” on the next step for Heracles.

The Sofra platform could also be applied to rheumatoid arthritis, type I diabetes, inflammatory bowel disease and even dementia (which is linked to immune system dysregulation).

“We will see what patient mix we go into for a phase II trial, but lupus most likely is our lead indication,” Mautner says.

“It’s also a matter of balancing the unmet need, the biology and the market opportunity.”

Mautner says the company plans to meet with the FDA “at some point in time”, in view of an Investigational New Drug (IND) application.

An IND is permission to trial an unapproved agent.

“We’ll pursue it, but there’s no rush and it won’t impact our clinical program one way or the other.”

Making other drugs safer

As a side project Noxopharm also is working on Sof-vac. This involves offering Sofra-derived therapy candidates to other drug makers, to use with their therapies to avoid inflammation.

For instance, Covid vaccines could be safer – which surely would be music to the ears of RFK Junior.

“One of the biggest problems for RNA drugs is inflammation, which means they need to reduce their dosage,” Mautner says.

“The company is enabling other developers – both large and small – to test it out in the hope of licensing it.”

As of the end of June, Noxopharm had a slender $1.5 million in the bank.

Management is tight-lipped about its funding strategy, but clearly the company needs to do a raising or find a cornerstone investor.

Out of the cave and into the limelight

Noxopharm estimates the cutaneous lupus market at US$3.4 billion globally which, Mautner says, “is very large for such a specific indication”.

But where’s the competition?

The US Food & Drug Administration has approved only two drugs for CLE, a corticosteroid (Kenalog-10) and an antimalarial (Plaquenil).

(Inflammation results from the body’s response to malaria, but also causes symptoms such as fever.)

“They are not targeted drugs for lupus and have a lot of side effects,” Mautner says.

“Corticosteroids account for about half the market; the rest is filled by off label ‘whatever’.”

Mautner says four big pharma companies have TLR-7/8 antagonist drugs, in oral and intravenous form.

“Their main focus is systemic lupus; the CLE part is … not their main game.”

Mautner says the company’s CLE program could appeal to drug developers with an interest in rheumatology.

“There’s always a need to feed the beast and bring new drugs to market.”

While it’s still early days for Noxopharm, the $28 million market cap company looks to be at a pivotal stage as it considers its next trial.

“We have been living in a cave,” Mautner says.

“But now we are happy to come into limelight and show the world how we brought tech from the bench to the bed side.”