K-Bios face string of clinical failures in H1

Raises red flag for technology exports

Genexine and BridgeBio fail to prove efficacy in Phase II clinical trials

Orum discontinues clinical trials due to safety concerns….also faces challenges in the course of stem cell therapy development

A series of clinical trial failures for new drug candidates under development by Korean biotech companies in the first half of the year have raised concerns about the feasibility of future technology exports.

 

Orum Therapeutics halted a clinical trial due to safety concerns, while Genexine and Bridge Biotherapeutics both failed to demonstrate statistical significance in their respective Phase II trials for glioblastoma and idiopathic pulmonary fibrosis.

 

Stem cell therapy developers such as Anterogen and SCM LifeScience are also struggling to prove efficacy in clinical settings.

 

According to industry sources on the 19th, Orum Therapeutics recently suspended its Phase 1 trial of ORM-5029.

 

ORM-5029 was the company’s only pipeline in clinical trials targeting human epidermal growth factor receptor 2 (HER2), a major biomarker for solid tumors.

 

The company received IND approval for ORM-5029 from the U.S.

 

FDA in 2022.

 

However, a severe adverse event (sAE) occurred during the trial, upon which the company reported it to the FDA.

 

Due to toxicity issues, administration had to be halted even at low doses.

 

ORM-5029 is a Degrader Antibody Conjugate (DAC) candidate.

 

DACs combine Targeted Protein Degradation (TPD) mechanisms with Antibody Drug Conjugates (ADCs) and are expected to offer higher safety due to the use of TPD, which are small-molecule degraders.

 

Orum emphasized that the sAE was limited to only the ORM-5029 substance and that there were no issues with the company's technology or platform itself.

 

Orum plans to focus its resources on its blood cancer candidate ORM-1153, which also utilizes the company’s DAC platform.

 

The company explained that it has shown strong GSPT1 degradation and robust anti-proliferative effects in blood cancer cell lines.

 

Genexine and Bridge Biotherapeutics fail Phase II trials Genexine and Bridge Biotherapeutics both faced setbacks in Phase II trials.

 

In March, Genexine's GX-I7 (Interleukin-7), an immune-oncology drug candidate, failed to demonstrate efficacy in glioblastoma mulifrome (GBM) patients.

 

GX-I7 is a new drug candidate that maximizes immune anticancer effects by inducing T-cell amplification in the body.

 

GBM is a type of glioma, a malignant tumor that originates in the brain.

 

Despite surgery and chemotherapy, the five-year survival rate for GBM is only 5%, with an average survival time of about a year.

 

The Phase II trial for GX-I7 enrolled 20 patients with recurrent or progressive glioblastoma, and evaluated a combination of the GX-I7 and bevacizumab (Avastin), a VEGF inhibitor used as a targeted therapy.

 

Bevacizumab inhibits angiogenesis to prevent tumor growth, and its combination with existing anticancer drugs was expected to enhance therapeutic efficacy.

 

However, no significant improvement was observed in the primary endpoints of progression-free survival (PFS) and overall survival (OS).

 

Meanwhile, Bridge Biotherapeutics announced in April that its top-line data analysis results showed that its idiopathic pulmonary fibrosis (IPF) candidate BBT-877 failed to demonstrate a statistically significant improvement in the primary endpoint of forced vital capacity (FVC) change at 24 weeks.

 

BBT-877 is an innovative novel drug candidate that selectively inhibits the novel target protein autotaxin.

 

Autotaxin is a protein known to bind to intracellular receptors and be involved in pathological mechanisms such as fibrosis and tumorigenesis.

 

BridgeBio previously secured global exclusive rights to BBT-877 from LegoChem Bio (now LigaChem Bio) in 2017.

 

In May, BridgeBio received a recommendation from the IDMC to continue the clinical trial.

 

The Phase 2 clinical trial of BBT-877 was conducted in 5 countries - South Korea, the United States, Australia, Poland, and Israel - to evaluate the efficacy, safety, and tolerability of the drug in patients with idiopathic pulmonary fibrosis (IPF).

 

A total of 129 patients participated, and the study results showed that changes in FVC were observed in both the drug group and the placebo group; however, there was no statistically significant difference between the two groups.

 

Bridge Biotherapeutics licensed out BBT-877 to Boehringer Ingelheim in 2019 in a deal worth up to KRW 1.5 trillion.

 

Upon transferring BBT-877, which was in Phase 1 clinical trials, the company received approximately KRW 600 billion in upfront and milestone payments (short-term milestones).

 

In late 2019, following the completion of Phase I clinical trials for BBT-877, BridgeBio paid approximately KRW 50 billion to LigaChem Bio as milestone revenue sharing.

 

However, in 2020, Boehringer Ingelheim returned the rights to BBT-877 due to potential toxicity issues.

 

BridgeBio determined that the toxicity issues were caused by high-dose drug administration in additional experiments and decided to develop the candidate on its own, but failed to demonstrate its efficacy in trials.

 

stem cell therapy developers also struggling with commercialization

Stem cell therapy developers are also facing commercialization hurdles.

 

SCM LifeScience failed to achieve statistical significance in Phase 2 clinical trials of its stem cell therapy candidate SCM-CGH.

 

This is the company's second failed attempt at commercialization following the failure of its acute pancreatitis clinical trial in 2022.

 

The trial, which targeted patients with steroid-resistant or steroid-dependent chronic graft-versus-host disease, was conducted from 2017 to 2024 at 11 hospitals in South Korea, including Seoul St.

 

Mary's Hospital.

 

The results of the Phase II clinical trial of SCM-CGH showed no statistically significant difference in the primary efficacy endpoint, the overall response rate (ORR) at 12 weeks.

 

Upon closer examination, the ORR at 12 weeks was higher in the placebo group than in the SCM-CGH group, and the results were not statistically significant.

 

Anterogen failed to demonstrate the efficacy of its stem cell therapy ALLO-ASC-DFU in the U.S.

 

Phase III clinical trial.

 

In the trial, ALLO-ASC-DFU recorded a complete wound closure rate of 46%, which was lower than the 60% in the control group that was treated with hydrogel sheets.

 

The therapy had garnered attention as a treatment for diabetic foot ulcers (DFU), but its failure to meet the key primary endpoint has significantly reduced the likelihood of its FDA approval.

 

Anterogen is conducting further analyses to revise its development strategy.