Late on the front of coronavirus vaccine development and procurement, South Korea is pinning hopes on one particular company to provide the much-needed relief in this dark, pandemic winter -- Celltrion.

The company is expected to announce in coming days results of its global clinical phase 2 trial of an anti-COVID-19 monoclonal antibody treatment candidate, CT-P59.

Celltrion’s media-friendly founder and chairman Seo Jung-jin has said plenty of times that its drug, if approved, would “put an end” to the country’s struggles with the deadly virus.

In apparent show of confidence, the company has already produced 100,000 doses of the antibody agent for immediate distribution upon approval from local authorities.

There are many doubts about these claims. But if they become reality, a whole new chapter of growth will open for Celltrion, which began life in 2002 as a miniscule venture startup.

It will also be the perfect legacy for Seo, as the 63-year-old founder is set to retire at the end of 2020.


Imminent unveiling


Celltrion’s monoclonal antibody agent has finished a phase 2 trial involving 327 people on Nov. 25. The firm has now spent roughly a month analyzing the data from the tests, in order to apply for conditional use approval with Korea’s Ministry of Food and Drug Safety.

Monoclonal antibodies play an important role in suppressing the deadliness of the coronavirus. The CT-P59 (regdanvimab) is known to prevent mild COVID-19 from progressing to a seriously ill stage.

Spearheading the pursuit for COVID-19 antibody treatment so far are US firms Eli Lilly and Regeneron. Eli Lilly’s bamlanivimab monoclonal antibody received an emergency use authorization from the US’ Food and Drug Administration on Nov. 9.

Regeneron’s casirivimab-imdevimab antibody cocktail REGEN-COV2 also gained the EUA, shortly after, on Nov. 21. US President Donald Trump was treated with REGEN-COV2 when he was infected in the beginning of October.

The International AIDS Vaccine Initiative estimates there are some 70 antibody treatments being pursued across the globe to combat coronavirus pandemic. However, as antibody treatments are more expensive and difficult to make than small-molecule drugs, many of these treatments fail to reach patients in low- and middle-income nations, according to the non-profit International AIDS Vaccine Initiative.

The median price for antibody therapies in the US is somewhere between $15,000 and $200,000 per year of treatment, according to the IAVI–Wellcome report.

This is why every step of the progress of Celltrion’s CT-P59 is being closely watched here: It’s a reliable yet domestic option to fall back on, more so because Seo has pledged to prioritize Koreans, and provide the drug at no margin.


Timeline of Celltrion’s COVID-19 R&D

What enabled Celltrion’s COVID-19 antibody treatment research was its previous experience researching for a Middle East Respiratory Syndrome treatment, as well as the unstoppable work culture and its capacity to single-handedly mass-produce biologic drugs. Chairperson Seo’s relentless drive bound the three elements together and drove Celltrion on a whirring-speed development.

The company’s researchers worked around the clock on a 24-hour rotation shift to derive 300 antibodies from a recovered COVID-19 patients’ blood in just three weeks of procuring the said blood, Celltrion announced March 23.

Normally this process requires three to six months.

It then took Celltrion two more weeks to narrow down the most efficient antibody candidate to work with. Of the 300 antibodies picked up, the company was able to sift out 106 that bound better to the SARS-CoV-2 antigen. Of the 106, a total of 38 antibodies showed neutralizing powers and 14 among them showed strong neutralizing features. Celltrion confirmed the neutralizing qualities of its antibody candidates on April 13.

“We are bringing our full resources and expertise to overcome this global health crisis and are glad to have identified these antibodies sooner than previously expected,“ Kwon Ki-Sung, Head of R&D Unit at Celltrion had said, ”These antibodies can recognize multiple epitopes, increasing the probability of nonspecific antigen binding.”

CT-P59 goes on to prove neutralizing powers in preclinical trials with ferrets by June 1, and further display strong efficacy by eradicating SARS CoV-2 virus from mildly affected patients within five days of the drug administration, in a clinical phase 1 trial targeting 18 mildly affected people, which result was announced Nov. 6.

Celltrion is now preparing to apply for a conditional use approval from the Drug Ministry in Korea. This is not identical, but similar, to the US FDA’s emergency use authorization, in that both allow preliminary use of the drug prior to full approval.

Having started mass-production of the pipeline from September, Celltrion already has enough stock of the CT-P59 for 100,000 people, for immediate distribution upon approval.

As of Tuesday, Korea had 14,810 people under quarantine for testing positive to COVID-19.

“Antibody treatments can be reliably administered if there is 18-months inventory of the drug. Due to the specifics of the distribution process, there always needs to be a minimum of 9 months’ stock,” Seo had said.

Should there be greater need for the drug, Celltrion would consider placing an order with a contract manufacturing organization, so that the urgency of the COVID-19 treatment does not impede Celltrion’s biosimilar sales, according to the chairman.

“We must retain the output of our existing product lines while we produce COVID-19 treatment. We are considering to work with CMOs if necessary.”

At the time of this writing, Celltrion had no updates regarding CMO deals.

The first batch of the Celltrion treatment was manufactured from the company’s 100,000-liter capacity Plant 1, which comprises eight 12,500-liter bioreactors.

The company’s production capacity includes the 90,000-liter capacity Plant 2, comprising six 15,000-liter bioreactors. Another plant in Cheongju, North Chungcheong Province, can produce 5 billion tablets of chemical drugs a year.

From November, Celltrion has begun building a 600,000-liter capacity Plant 3, with a projected date of operation start from June 2024.


Praise and doubts


Established in 2002 by a group of five ex-Daewoo employees led by Seo, Celltrion has risen to the global stage with its antibody biosimilars.

Biosimilars are biologics drugs that are “similar” to the original drugs. Unlike chemical drugs, which are relatively easy to copy, biologic drugs are much tougher to imitate because they are made through biological processes. Even the original biologics drugs can differ in quality every time a batch is manufactured.

When Celltrion first set out to create biosimilars, the industry had reacted with distrust and cynicism for the vast uncertainty of the business.

Celltrion has since risen to be a leading biotech firm here and is challenging, with its biosimilars, global biopharmaceutical companies like Johnson & Johnson, Roche and Pfizer, which are all more than 100 years older than Celltrion.

Skepticism still persists about the firm. Some foreign analysts warn of media hype and overvaluations. In its latest comment, JP Morgan called for “caution” on investing in Celltrion stocks, citing their “overstretched” valuations.

With or without a COVID-19 cure, the year 2021 will be the beginning of a new era for Celltrion.

Seo is entrusting the future of Celltrion in the hands of his left and right arms, Kee Woo-sung and Kim Hyung-ki, who have played instrumental roles in bringing Celltrion thus far. Kee is currently the CEO of Celltrion and Kim the CEO of Celltrion Healthcare.

Seo’s two sons, who each work as Celltrion’s executive vice-president and member of the board of directors, will remain in post.

Celltrion’s core strength comes from the fact that it is young and quick to respond to the changing times, analyzes a newly published, and the first book on Celltrion, “Celltrionism.”

By Lim Jeong-yeo (kaylalim@heraldcorp.com)