Replies to post #247315 on Biotech Values

[Mufaso]

VKTX - Info on VK0214. As noted by rfj1862, X-ALD affects about 50,000 people in the US. Viking’s VK0214 is being studied to treat this disease. VK0214 is an oral TRß Agonist (like Viking’s VK2809 for NASH) and it was acquired from Ligand (also like VK2809).

For those of you not familiar with VK0214 in X-ALD, here is some info from Viking’s 1s q CC:

X-ALD is a rare and often fatal metabolic disorder. Patients with X-ALD have genetic mutations that impact the function of a peroxisomal transporter of very long chain fatty acids. When transporter function is impaired, patients are unable to efficiently metabolize very long chain fatty acids and the resulting accumulation of these compounds is believed to contribute to the onset and progression of X-ALD.

In a prior Phase 1 study in more than 100 healthy volunteers, VK0214 demonstrated dose-dependent exposures, no evidence of accumulation and a half-life consistent with anticipated once-daily dosing. Subjects who received VK0214 experienced reductions in LDL cholesterol, triglycerides, apolipoprotein B and lipoprotein a.
VK0214 also demonstrated an encouraging safety and tolerability profile with no serious adverse events reported and no treatment or dose-related signals observed for GI side effects, vital signs or cardiovascular measures.

Following these favorable results, Viking initiated the Phase 1b study of VK0214 in patients with the adrenomyeloneuropathy or AMN form of X-ALD. AMN is the most common form of X-ALD affecting approximately 50% of patients. The Phase 1b trial is a randomized, double-blind, placebo-controlled, multicenter study in adult male patients with AMN. The primary objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of VK0214 administered once daily orally for 28 days.

Data from in vivo studies have demonstrated that administration of VK0214 produces a significant reduction of very long chain fatty acids (VLCFAs) in both plasma and tissue, potentially leading to a therapeutic benefit. VK0214 has been granted orphan drug designation by the FDA for the treatment of X-ALD. Here is a slide from Viking’s corporate presentation suggesting VK0214 will work in both forms of X-ALD:



More detailed info on X-ALD as a disease at: https://www.childneurologyfoundation.org/disorder/adrenoleukodystrophy/
Some selected excerts from the above link appear below:

Description

X-linked Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the leukodystrophies that cause damage to the myelin sheath, an insulating membrane that surrounds nerve cells in the brain. Women have two X chromosomes and are the carriers of the disease, but since men only have one X chromosome and lack the protective effect of the extra X chromosome, they are more severely affected. People with X-ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex.

... While nearly all patients with X-ALD suffer from adrenal insufficiency, also known as Addison’s disease, the neurological symptoms can begin either in childhood or in adulthood. The childhood cerebral form is the most severe, with onset between ages 4 and 10.

... The milder adult-onset form is also known as adrenomyeloneuropathy (AMN), which typically begins between ages 21 and 35. Symptoms may include progressive stiffness, weakness or paralysis of the lower limbs, and ataxia. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function. Almost half the women who are carriers of X-ALS will develop a milder form of AMN; such carriers almost never develop symptoms that are seen in boys the X-ALD. X-ALD should not be confused with neonatal adrenoleukodsystrophy, which is a disease of newborns and young infants and belongs to the group of peroxisomal biogenesis disorders.

Treatment

Adrenal function must be tested periodically in all patients with ALD. Treatment with adrenal hormones can be lifesaving.
... Recent evidence suggests that a mixture of oleic acid and erucic acid, known as "Lorenzo's Oil," administered to boys with X-ALD prior to symptom onset can prevent or delay the appearance of the childhood cerebral form.

... Lorenzo's Oil has no beneficial effect in symptomatic boys with X-ALD. Bone marrow transplantations can provide long-term benefit to boys who have early evidence of the childhood cerebral form of X-ALD, but the procedure carries risk of mortality and morbidity and is not recommended for those whose symptoms are already severe or who have the adult-onset or neonatal forms.

Prognosis

Prognosis for patients with childhood cerebral X-ALD is generally poor due to progressive neurological deterioration unless bone marrow transplantation is performed early. Death usually occurs within 1 to 10 years after the onset of symptoms. Adult-onset AMN will progress over decades.

[rfj1862]

However I was expecting the results for the 1b trial in X-ALD more towards the end of the year (e.g. 4th q) rather than the next few months. I am thinking this because the 1b trial was still enrolling as of the 1st q cc which was 4-26. CEO Brian Lian in his prepared remarks then said:

Here's my thinking:

The study has been designed since 2021 and all study sites are on board. This is a rare disease with no good treatment options so enrollment of the 28 patients is going to be near immediate--I am sure they had patients waiting for study initiation. I would expect it is already fully enrolled; if last patient in was June 1, primary completion of all patients is in July and results in September. The endpoints are very simple and quick to assess.

CT.gov says primary completion Sept 30 but from experience those are always *extremely* conservative, sometimes they are months or even years off.

Here's the study design:

https://clinicaltrials.gov/ct2/show/NCT04973657?cond=VK0214&draw=2&rank=1#contacts