Twiggy's Invex Therapeutics | The Imminent Coin Flip

Welcome to the Invex Therapeutics thread to end all other threads, a collation of many years following the Invex story, one certainly worth telling as we lead into the Phase III results. Enjoy, and as always DYOR!

The Condition: Imagine waking up one day with a headache like your head is in a vice, then 2 weeks later losing vision, and the weeks following being completely blind due to fluid build up within your skull. That is not abnormal in severe IIH cases, with no drug on the market pertaining to treating IIH presenting an urgent need for these patients or endure CSF shunts to relieve the pressure and regain sight.

Idiopathic Intracranial Hypertension (IIH) is a disorder characterized by an excessive production of cerebrospinal fluid (CSF) in the brain, leading to increased pressure inside the skull that affects the optic nerve and results in vision loss, persistent migraines, and nausea. The term "Idiopathic" in the name of the condition implies that it occurs spontaneously and without a known cause. Many individuals with IIH exhibit symptoms similar to those of brain tumors, but these are excluded through magnetic resonance imaging (MRI) and a series of other tests, which reveal no alternative explanations for the symptoms.

Notably, there are currently no approved medications for IIH, a condition with an incidence rate of 4.7 per 100,000 people and an annual total addressable market (TAM) of $1.6 billion. The relatively low incidence rate prompted the FDA to grant Invex Therapeutics an Orphan Designation for Presendin, ensuring seven years of US patent protection and ten years of EU patent protection. Given that IXC's Chief Scientific Officer, Alex Sinclair, is the author of IIH treatment guidelines, the introduction of an effective medication to the market would likely lead to a rapid integration of Presendin into treatment protocols. Consequently, this would result in faster market penetration and an accelerated timeline to peak sales.

While the cause of IIH remains unknown, it is observed that 90% of affected individuals are overweight women of reproductive age, and the number of patients is increasing at a rate of 3.4% annually, corresponding to the rise in obesity rates. Invex Therapeutics estimates that the financial burden of IIH on the healthcare system in England alone amounts to £400 million per year. Additionally, 40% of patients experience multiple hospitalizations, necessitating invasive lumbar punctures to alleviate intracranial pressure and prevent blindness. This highlights an urgent need for pharmaceutical intervention, as well as the potential for significant pricing power for treatments such as Presendin (IXC's drug candidate).

The Drug:

IXC's Chief Scientific Officer, Alex Sinclair, the leading expert in IIH globally and co-author of IIH treatment guidelines, found that Presendin (Repurposed diabetes drug; Exenatide) reduced cerebrospinal fluid production in rats with elevated intracranial pressure during preclinical research at Birmingham University, suggesting a potential mechanism of action (MOA). Following encouraging preclinical results, the intellectual property was transferred from Birmingham University to Invex Therapeutics and subsequently listed on the ASX as IXC in 2019 to support funding for the Phase II clinical program.

After completing the Phase II trials in 2020, the data reinforced the earlier MOA findings, showing an average reduction in intracranial pressure of 18-21% in human subjects, a 37.7% decrease in headache days, and a one-line improvement in vision. Intriguingly, the results also led to the unauthorized use of Exenatide for off-label purposes within the IIH community. Numerous anecdotal accounts in IIH Facebook support groups reported successful symptom relief with the drug, highlighting the severity of symptoms, patients' willingness to try off-label treatments after exhausting other options, and the evident unmet medical need for an effective medication in the IIH market.

Andrew "Twiggy" Forrest:

After the Phase II trial results in 2020, IXC secured $26 million in funding to complete its Phase III study. Major shareholder Tattarang, an investment management firm owned by iron-ore billionaire Andrew "Twiggy" Forrest, contributed an additional $5 million, along with other cornerstone investors. A vote of confidence.

The Imminent Coin Flip | The Phase III Trial:

The current Phase III trial aims to obtain market access for the EU/UK and AU regions, representing a potential $1 billion total addressable market (TAM). The data from this Phase III trial will facilitate discussions with the FDA in 2025 for a smaller, secondary Phase III trial to gain entry into the US market (an additional $600 million TAM), anticipated to begin in 2026 and conclude in 2029 (Personal estimation). This secondary trial is estimated to cost 35% of the first Phase III trial (Personal estimation). The necessity for two separate Phase III trials stems from the FDA's refusal to align with the EU/UK/AU regulators regarding the primary endpoint of CSF reduction, preferring a clinically meaningful endpoint related to vision or headache days instead. The company opted for this strategy as the least risky path to market, following the example of Clinuvel Pharmaceuticals Limited (ASX:CUV), which successfully obtained EU/UK/AU approval before using the data to advance discussions with the FDA and ultimately gain access to the US market three years later.

The "coinflip" represents the Neurology peer phase III success rate of 47.8%. A coin flip to gain access to an unencumbered $1.6B TAM!

Manufacturing Deal:

In September 2021, Invex announced an Exclusive Collaboration, Manufacturing and Supply agreement with Peptron, Inc based in Daejeon, South Korea (KOSDAQ: KS:087010) for a sustained release (SR) formulation of Presendin™ in a biodegradable poly(lactic-co-glycolic acid) microsphere (PLGA). This 1x per week, sub cutaneous formulation has undergone numerous pre-clinical and clinical studies. The agreement is anticipated to save Invex $3M and 12 months of planned lead-in activities (tolerability, human pharmacokinetic studies) ahead of a Phase III trial. Invex can utilise Peptron’s extensive preclinical and clinical data package for its own global regulatory submissions.

Peptron will provide Presendin™ at a fixed cost per dose for clinical and commercial supply to Invex for IIH. No royalties are payable. The deal offers significant revenue potential for both Invex and Peptron upon regulatory approvals and numerous benefits to patients, including more convenient dosing and handling.