이 기사는 2022년 04월 05일 08:05 thebell 에 표출된 기사입니다.

South Korean biotech startups are increasingly wary of making big bets after U.S biopharmaceutical company Nektar Therapeutics and its partner Bristol Myers Squibb (BMS) disclosed disappointing results from a Phase 3 trial of an experimental cancer immunotherapy they're developing.

Nektar and BMS announced last month an update following the first analysis of the Phase 3 PIVOT IO-001 study evaluating the doublet therapy of bempegaldesleukin in combination with Opdivo (nivolumab) compared to Opdivo monotherapy as a first-line treatment for previously untreated unresectable or metastatic melanoma.

Following a review of the study for efficacy and safety by an independent Data Monitoring Committee, BMS and Nektar were informed that the study did not meet the primary endpoints of progression-free survival and objective response rate as assessed by Blinded Independent Central Review.

Opdivo was the key driver for BMS’s alliance with Nektar. BMS committed up to $3.6 billion to Nektar in early 2018 for the drug, which was the largest licensing deal in biotech history at the time.

Given the results, the companies have decided to unblind the trial and to perform no additional analyses for the OS endpoint. Additionally, based on the results from PIVOT IO-001, the companies have also made the decision to discontinue enrollment and unblind the ongoing PIVOT-12 study in adjuvant melanoma, which is evaluating the doublet therapy of bempegaldesleukin in combination with Opdivo compared to Opdivo monotherapy in patients at high risk for recurrence after complete resection of melanoma.

Bempegaldesleukin is a form of interleukin-2 (IL-2) that is designed to quickly activate the proliferation of cancer-killing T cells and natural killer cells without over-stimulating the immune system.

Korean drug companies that are developing IL-2 related immunotherapy include NeoImmuneTech, GI Innovation, Autotelic Bio, Selecxine and CT Cells. Market insiders are paying extra attention to Autotelic Bio, Selecxine and CT Cells as they recently completed their fundraisings.

Autotelic Bio is in a Phase 1b clinical trial to confirm the safety and effectiveness of OT-101/IL-2 in solid cancer patients in cooperation with U.K.-based pharmaceutical company Clinigen Group. Selecxine is currently developing the therapeutic agents capable of activating desired function of IL-2 selectively through the conjugation of IL-2 and antibody.

“Although Nektar released disappointing news, Alkermes, which also studies IL-2, has showed positive results,” said investors in the companies.

Last year, Alkermes presented new data from the ongoing phase 1/2 ARTISTRY-1 clinical trial for nemvaleukin alfa (nemvaleukin), the company's novel, investigational, engineered IL-2 variant immunotherapy. There were two complete response (CR) in the trial, better than Nektar’s Phase 1/2 study.

“Nektar's PEGylation technology has been understood to have weakness in chemistry, manufacturing and controls (CMC),” an investor said. “The IL-2 cytokine itself is difficult for CMC,” said another investor. "There seems to be a limitation on a concept of enhancing cell therapy activity by regulating IL-2.”

Companies that have included Nektar's licensing deal in their IR data will have to prove their own strengths through future clinical data.

NeoImmuneTech reportedly plans to present new preclinical data for the company’s lead asset NT-I7 (efineptakin alfa) during poster sessions at the American Association for Cancer Research annual meeting, to be held in New Orleans on April 8-13, 2022.

GI Innovation licensed out GI-101, a bispecific fusion protein for treating solid tumors, to China-based Simcere for 900 billion won ($739 million) in 2019. The company started a Phase 1/2 global clinical trial for GI-101 in July 2021. (Reporting by Jeong-yeo Lim)