HONG KONG – Suwon-based Olix Pharmaceuticals Inc. is completing the final preclinical work before starting clinical trials for its as-yet-unnamed COVID-19 drug candidate, developed inside three months using RNA interference (RNAi) technology.

Olix CEO Dong-ki Lee told BioWorld, “We have only tested the candidate against a model system so far, so the next step was to test it against the actual COVID-19 virus. We are now awaiting results of the drug’s efficiency against the live virus, from tests currently being conducted in a Korean government research institute.” He declined to specify when the tests are expected to be completed.

“Once the drug enters the clinic, the company plans to enter into partnerships with global pharmaceutical companies before the end of phase IIa tests, or even earlier, to generate revenue in the drug’s early stages of development as well as to share the costs and risks,” Lee said.

Olix filed a provisional patent application to develop RNAi therapeutics against COVID-19 on Feb. 25. The company said that the patent covered more than 30 siRNA designs targeting the virus’ available genomes, thus limiting its ability to replicate. The designs could also enable candidates to treat other coronaviruses, such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS).

The number of new COVID-19 cases in Korea has seen a downward trend recently, with Korea reporting only 28 new cases on July 28. If this continues, the trend could pose a challenge for Olix in patient recruitment once it obtains the approvals for human clinical trials. “The trials must definitely take place in a country with a bigger patient pool, such as the U.S.” said Lee, though he added it was too early to unveil plans.

But with the global number of cases topping 16.4 million as of July 28, according to Johns Hopkins University, Olix stands to benefit by bringing the product to market as quickly as possible. The company is looking to do exactly that, with its RNAi technology allowing for the “quick mass production” once it is ready for commercialization, according to Lee.

The company currently has “sufficient funding to support the development of several key pipelines, but more funds will be needed as the number of candidates in the pipeline increases,” Lee said. Olix is considering raising these funds via the aforementioned partnerships with global pharmaceutical companies, as well as fundraising from financial investors.” For the COVID-19 drug in particular, applying for R&D grants announced by the Korean government is another financing avenue.

Olix developed its own RNAi technology called asymmetric siRNA (asiRNA), which works by changing the sequence of the DNA’s antisense strand in accordance with the target messenger RNA.

The process is able to produce a more targeted potential drug substance by eliminating non-specific effects in conventional siRNA processes, such as off-target gene silencing mediated by the sense strand.

Meanwhile, the Korean company is not the only company working on RNAi therapies targeting COVID-19. Vir Biotechnology Inc. and Alnylam Pharmaceuticals Inc. announced in March that they are developing RNAi therapies targeting SARS-CoV-2, building on an infectious disease collaboration launched three years ago.

Alnylam has currently designed and synthesised more than 350 small siRNAs targeting all currently available genomes for the SARS-CoV as well as SARS-CoV-2 genomes.

Humble beginnings

Olix was founded by Lee under the name Biomolecular Therapeutics Inc. in February 2010. The company changed its name to Olix in 2014 and listed on the Kosdaq in July 2018. The road to establishing its name in the RNAi space has not been a smooth one though, as a startup competing against more established names such as Alnylam and Silence Therapeutics plc. However, Lee said the FDA’s approval of Onpattro (patisiran) in August 2018, a first for a RNAi therapy and Givlaari (givosiran) in November 2019 “helped to answer the question of whether RNAi therapies work” and made the path a little less rocky.

The Olix team plans to submit an IND to the FDA in the third quarter to begin phase IIa trials for OLX-101A, its injectable drug reversing the formation of hypertrophic and keloid scar tissue formed during surgery or injury, by switching off the gene known to be involved in forming scar tissue.

With the global hypertrophic and keloid scar market estimated to maintain ongoing growth over the next several years, the treatment fills a growing need that alternatives, such as silicon sheets and surgery, cannot fully meet.

Olix completed a phase I trial for OLX-101A in November 2019. The trial, which took place in the U.K., saw 44 patients injected with between 1 mg and 20 mg of OLX-101A in randomized, partial double-blind single and multiple dose placebo-controlled trial. The study, funded by the Korea Drug Development Fund, went on to prove OLX-101’s safety and pharmacokinetics.

The company is currently conducting phase IIa trials for OLX-101A in Korea. The independent trial is using an evaluator-blind, dose-escalation, untreated-controlled, within-subject design to explore three different doses for the treatment of hypertrophic scars. It has been recruiting patients since December 2019, with 30 participants currently enrolled. But Lee said that with COVID-19 inevitably causing delays in the recruitment process, Olix is currently in discussions with its partners, Hugel Inc., on how to minimize the delays.

Another drug in Olix’s pipeline is OLX-301A, treating both dry and wet age-related macular degeneration (AMD). With no currently approved treatment available for dry AMD, and the global AMD drug market continuing to grow, OLX-301A could address another global need.

The company signed a license and collaboration agreement with Théa Open Innovation, an arm of French pharmaceutical company Laboratoires Théa S.A.S, in March 2019. Théa paid a total of €63 million (US$72.9949 million) for the dry AMD and wet AMD treatment, including an up-front payment of €2 million; €43.5 million upon hitting certain milestones; a €17.5 million milestone option; and royalties in the double digits. The French company also acquired the rights to OLX-301A in Europe, the Middle East, and Africa. Olix will retain the rights in Asia and the U.S.

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