HK-001 | ALS Treatment

HK-001 Soft Capsules

ALS Treatment

Curing Rare Diseases

Rare Diseases affect so few people that trying to cure them makes little economic sense without public incentives and special regulatory benefits.
Our mission is to develop orphan drugs to treat rare diseases chosen for their low probability of survival due to the lack of effective treatments, the presence of few competitors offering objectively inferior products based on key medical metrics, and the possibility of rapidly gaining market share via licensing agreements with global pharma partners.

Amyotrophic lateral sclerosis (ALS)

The age of onset for amyotrophic lateral sclerosis (ALS) is 40 to 70 years, with a mean age of 55 years. In the United States, about 5,000 to 6,000 new cases are diagnosed each year, while in Taiwan, there are 300 to 500 new cases per year.
Approximately 90% of ALS cases have no clear family history or genetic mutation as the cause. The remaining 5-10% of cases are called familial ALS (FALS), which are inherited from known mutated genes associated with ALS.
No effective treatment: Currently: there is no known cure for ALS, and the only available treatment options can only slow the progression of the disease and improve quality of life.
High mortality rate: According to the statistics from the ALS Association, patients typically survive for an average of 2 to 5 years after onset of symptoms, which may vary from person to person, and only 10% of patients can survive more than 10 years.

Our Innovative Approach

Use Small Molecules Drugs as Our Key Therapeutics

Given their relatively low molecular weight, simple chemical structures, more predictable pharmacokinetics and pharmacodynamics, small molecule drugs not only have superior safety profiles, but they can pass through cell membranes to reach intracellular targets and be formulated in many forms.

Harness the Power of the Human Immune System

We are actively identifying and developing active compounds that can enhance the body’s natural defense capabilities across multiple indicators. Our goal is to achieve therapeutic effects by inhibiting the overactive autophagy process through mTor target inhibition and other mechanisms.

Improving Efficacy with Targeted Drug Delivery

We use targeted drug delivery platforms to improve the efficacy of our products with options like slow-released local delivery system, systemic drug delivery system, dripping pill formulation, dermal application formulation and injectable formulation.

Product Profile

Product Name

HK-001 Soft Capsules

Disease

Amyotrophic lateral sclerosis (ALS)

Target Market

The seven major countries, including the United States, France, Germany, Italy, Spain, the United Kingdom, and Japan, are expected to increase to 37,000 patients by 2023.

Market Size

In the 7 major countries is estimated to reach approximately USD 1.2 billion annually by 2027.

Competition Size

There is currently no drug on the market that can truly cure ALS.

Objective Size

First-in-class in the market, aiming to secure a 15% market share through direct competition.

HK-001 Soft Capsules

The HK-001 soft capsule contains a small molecule active pharmaceutical ingredient EF-API-001 produced under PIC/S GMP standards. Through targeted inhibition of mTor and suppression of excessive autophagy, it aims to delay the progression of ALS in patients.

The HK-001 capsule is an oral dosage form, and two improvements were observed in animal testing results (ALS mice, SOD1^G93Amice):

- Delayed onset of ALS progression: Using a BBB scale (Basso, Beattie and Bresnahan scale) score of less than 15 as the disease onset threshold, it was observed that the onset time of ALS in mice orally administered with HK-001 was delayed compared to the control drug Riluzole.
- Prolonged survival in ALS: The survival of ALS mice orally administered with HK-001 was superior to the untreated group and also superior to the control drug Riluzole.

To Determine the Maximum Tolerated Dose (MTD) of HK-001 in Healthy Volunteers

ClinicalTrials.gov Identifier: NCT03651349

Phase I clinical Trial
- Initiated Phase I clinical trial in April 2021.

The Advantages of HK-001 in the Treatment of ALS are as follows:

Delayed Onset of ALS Progression

The number of Days with BBB scale < 15

Untreated

Riluzole

HK-001 (low dose)

HK-001 (middle dose)

HK-001 (high dose) - 188 days

Using a BBB scale score of less than 15 as the disease onset threshold, it was observed that the onset time of ALS in mice orally administered with HK-001 was delayed compared to the control drug Riluzole.

Prolonged Survival in ALS

Survival

Untreated

Riluzole

HK-001 (low dose)

HK-001 (middle dose)

HK-001 (high dose) - 240 days

The survival of ALS mice orally administered with HK-001 was superior to the untreated group and also superior to the control drug Riluzole.

The Mechanism of Action of HK-001: Involves the Inhibition of Excessive Autophagy

The accumulation of LC3-II is closely related to the role of autophagy, and abnormal accumulation of the LC3-II protein is also considered one of the main causes of ALS deterioration.
In NSC-34-SOD1^G93Acell line experiments, it was found that HK-001 can stimulate the activation of mTOR signaling in SOD1^G93A mutant cell lines, thereby reducing the accumulation of LC3-II.
Results in animal experiments showed that the accumulation of LC3-II in the spinal nerves of SOD1^G93A mice was higher than that in the normal group, and after HK-001 treatment, the mice had higher mTOR activity than the treatment group, and the accumulation of LC3-II was reduced to levels close to the wild type group.
Using specific antibodies for staining motor neurons, it was observed that the number of motor neurons in the HK-001 treatment group was much higher than that in the untreated group, and the number of motor neurons was correlated with BBB scale results. Confirmation was also obtained using LC3-II-GFP transgenic mice, where a decrease in fluorescence intensity was observed in mice treated with HK-001.
These findings confirmed that HK-001 prolongs the lifespan of SOD1^G93A mice mainly by regulating the accumulation of LC3-II and downstream autophagy through the phosphorylation/activation of mTOR to achieve the effect of prolonging the lifespan of SOD1^G93A mice.

About Riluzole

An orally-administered benzothiazole medication that works by blocking glutamatergic neurotransmission in the CNS. Glutamate itself is an excitatory amino acid that is believed to be associated with the excitotoxicity that causes neurodegeneration in ALS, though the true disease mechanism of ALS is not fully understood, and this is one possible hypothesis.
The drug is not effective in improving survival time or delaying the use of mechanical ventilation for end-stage ALS patients, as indicated on the monograph.
Clinical trial results have shown a median survival of 17.7 months in the treatment group, which is higher than the 14.9 months in the placebo group.
There may be some side effects, such as weakness, nausea, and abnormal liver function indices. About 14% of the subjects discontinued the trial due to these side effects during the clinical trial of this medication.

The neuroprotective mechanism of HK-001

The neuroprotective effect of HK-001 (including the active ingredient EF-API-001) targets calpain and autophagy, both of which are associated with the protein degradation pathway. Inhibition of calpain results in a reduction of abnormal protein degradation. Regulation of autophagy accelerates the clearance of toxic proteins, which is associated with mutant SOD1 accumulation and related neuron degeneration.