Yungjin Pharm. Co., Ltd. (CEO & President Chae J. Lee) announced on May 24, 2021 that Abliva AB, a clinical-stage biopharmaceutical Swedish company (previously NeuroVive), reported positive clinical phase 1a/b results for KL1333 including safety and pharmacokinetic data as well as signals of efficacy in patients with rare and severe primary mitochondrial diseases (PMD). In addition, there were no serious adverse events in the study.

Out-licensing agreement with Abliva for KL1333 in 2017 could generate up to 57 USD million for Yungjin. The clinical phase 1 trial in the UK was approved in October 2018 and planned to complete in 2020, but it was delayed due to the COVID-19 pandemic.

The primary aim of this double-blind, randomized, placebo-controlled phase 1a/b study was to assess the safety and pharmacokinetics of KL1333 both in healthy volunteers and in patients. Data from the study confirms single ascending dose (SAD) data from a prior phase 1 study, and showed, for the first time, multiple-ascending dose (MAD) data from healthy volunteers and multiple day dosing in patients. The study included an analysis on the food effect and split dosing of KL1333 in healthy volunteers as well as a full characterization of pharmacokinetic parameters in both healthy volunteers and patients with primary mitochondrial diseases. “There were no serious adverse events in the study and further review of the safety data confirms no safety signals and reinforces the strong safety profile of KL1333 after dosing over 100 healthy volunteers and patients throughout development. KL1333 was generally well tolerated across patients and healthy volunteers,” said Magnus Hansson, Abliva’s CMO.

In a cohort of eight patients with primary mitochondrial diseases (six dosed with KL1333, two with placebo), there were signs of efficacy across well-established, relevant clinical endpoints including two different patient-reported fatigue endpoints and a functional endpoint, 30-Second Sit to Stand. Although the study was not primarily designed to evaluate efficacy and the duration of dosing was only 10 days, the mean of change was numerically greater in the patients dosed with KL1333 compared to the placebo group for all three endpoints. In addition, there was an association between levels of KL1333 in the patients and efficacy.

Abliva's intention is to apply for market approval during 2024 after successful completion of a pivotal clinical phase 2/3 study of KL1333 with the recommendation that Abliva received from FDA this year.

KL1333 has been demonstrated in preclinical models to increase mitochondrial energy output, have long-term beneficial effects on energy metabolism, strengthen muscle function and improve biomarkers of mitochondrial disease. Based on the preclinical data, Abliva plans to initiate a pivotal phase 2/3 study for KL1333 in patients with PMD such as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Kearns-Sayre syndrome (KSS), and chronic progressive external ophthalmoplegia (CPEO) through global CROs, Covance and ICON.

“This data package increases our confidence in our upcoming phase 2/3 study as we have confirmed the safety of KL1333, seen early signals of efficacy from relevant clinical outcomes, and identified a good dosing regimen,” said Ellen Donnelly, Abliva’s CEO. “The company will now review the totality of the data and work to finalize our clinical protocol as we move towards IND submission later this year.”

Yungjin will be able to expect profits based on successful achievement of development milestone. "We are pleased with the successful completion of the clinical phase 1 trial of KL1333, and we will continue our close collaboration with the team at Abliva and actively help to proceed and complete the global phase 2/3 study", said Chae J. Lee, Yungjin's CEO.

KL1333 is granted orphan drug designation by the US and the EU. It is estimated that nuclear mutations were responsible for clinically overt adult mitochondrial disease in 2.9 per 100,000 adults (ANN NEUROL 2015;77:753-759).