SEOUL, South Korea, July 18, 2022 /PRNewswire/ — OliPass Corporation, a South Korea based biotech specialized in the development of RNA therapeutics, announced to move forward to the second stage of the Phase 2a trial in Australia in osteoarthritis (OA) patients for pain killer OLP-1002, an SCN9A antisense PNA selectively inhibiting the expression of Nav1.7 sodium ion channel.
The Phase 2a study consists of two stages. The first stage is an open label study to identify an optimum dose range meeting the target efficacy and therapeutic duration, in which patients receive a single subcutaneous injection of 1, 3, 10, 25, 50 or 80 mcg (microgram) OLP-1002. Low doses and high doses have been simulated to inhibit Nav1.7 expression mostly in peripheral nerves and the spinal cord, respectively. The second stage shall be a placebo-controlled double blind study to evaluate two doses of OLP-1002 selected based on the efficacy findings from the first stage.
The company briefed on the clinical readouts from the ongoing open label study as follows: Pain reductions on a daily basis were marked and persisted at least a month in all the 5 patients received 1 mcg OLP-1002. The average daily pain reductions by VAS were robust and ranged from 60% to 85% over the period of 30 days post dose. The maximum was observed around a week post dose. Interestingly the onset time was shorter than several hours. Pain reductions by WOMAC were comparable to those by VAS. Although the dosing and pharmacodynamic evaluation of 80 mcg OLP-1002 have yet to be completed, 50 mcg OLP-1002 appears to be the dose picking up pain reduction by CNS target engagement.
“Given that most of pain types are peripheral by nature, the efficacy profiles observed with 1 mcg OLP-1002 are very encouraging. The efficacy appears much stronger and persists far longer than known with conventional pain killers such as NSAIDs, COX-2 inhibitors, opioid analgesics, and so on. Furthermore, the observed onset time of several hours would be very attractive for managing acute pain including post-operative pain. OLP-1002 shall hopefully replace opioid pain killers. Thus, we are very much thrilled to recommend 1 mcg OLP-1002 and 2 mcg OLP-1002 for the second stage of the Phase 2a study in OA patients,” noted Dr. Shin Chung, CEO of OliPass Corporation.
“The global market of pain killers is estimated to be as large as 100 billion USD per year. Considering the market is currently prevailed with cheap generic pain killers with moderate efficacy or compromised safety, however, the market potential is certainly far larger. Lack of safe and effective pain killers triggered the outbreak of opioid crisis. There are huge unmet medical needs for pain killers with strong efficacy and good safety. If a pain killer covers 10% of patients with refractory pain in developed countries at an annual drug cost of 1,000 to 2,000 USD, the pain killer is estimated to generate an annual sales of 30 to 60 billion USD,” said Dr. Chung. “Endowed with strong efficacy, good safety and long therapeutic duration, OLP-1002 is envisaged to become a first line therapy for refractory chronic pain and neuropathic pain. The forthcoming placebo-controlled double blind study shall define the market potential of OLP-1002,” added Dr. Chung.
People with a loss-of-function mutation of the SCN9A gene (i.e., SCN9A channelopathy) were found insensitive to pain but with other sensory functions undisturbed. Since the SCN9A gene encodes Nav1.7 sodium ion channel subtype, selective inhibitors of Nav1.7 have been implicated to effectively and safely treat pain. Unfortunately, there are ca 10 sodium ion channels structurally indistinguishable with small molecule inhibitors. Although small molecule inhibitors of Nav1.7 have been avidly evaluated, none have manifested strong analgesic efficacy and good safety.
OLP-1002 is an SCN9A antisense peptide nucleic acid (PNA) and selectively inhibits the expression of Nav1.7 sodium channel, and therefore expected to replicate much of the phenotype of people with SCN9A channelopathy. In most of rodent pain model studies, OLP-1002 showed therapeutic activity by target engagement in the CNS. In the meantime, clinical readouts to date suggest that peripheral target engagement by OLP-1002 should be more than sufficient for pain management in human patients. Thus, animal pharmacodynamic data should be translated with discretion.
About OliPass Corporation
OliPass Corporation is a public biotech company listed in KOSDAQ in South Korea (ticker: KQ244460). The company is developing RNA therapeutics based on its proprietary oligonucleotide platform called OPNA (OliPass Peptide Nucleic Acid). OPNA was derived from PNA by rational chemical modifications in order to improve the cell permeability and RNA affinity. For therapeutic intervention, OPNA potently binds to target pre-mRNA, induces exon skipping, and yields mRNA splice variant. Unlike other types of RNA therapeutics, OPNA does not require formulational aid for in vivo therapeutic activity.