Yuhan Corp., of Seoul, South Korea, has inked a ₩150 billion (US$108.6 million) deal with Korean biotech Ubix Therapeutics Inc. to gain exclusive global rights to UBX-103, Ubix’s oral small-molecule androgen receptor (AR) degrader for prostate cancer.

Yuhan also announced July 1 that it gained the U.S. FDA’s nod to start a phase I study of a Gaucher disease drug candidate called YH-35995.

For UBX-103, Seoul-based Ubix said it would out-license exclusive worldwide rights to the therapy candidate for ₩5 billion in an up-front payment and up to ₩145 billion in additional development, regulatory and commercial milestone payments, along with a high single-digit royalty payment based on net sales. 

Under the terms, Ubix is also eligible for profit-sharing, in case Yuhan chooses to sublicense the asset to a third party.

UBX-103 is a potential best-in-class, oral bioavailable AR degrader for metastatic castration-resistant prostate cancer developed with Ubix’s targeted protein degradation (TPD) platform technology coined the Degraducer.

AR is known to be a key driver of prostate cancer. While hormone deprivation therapy is the standard of care for patients with metastatic prostate cancer, the tumors often progress to castration-resistant metastatic disease due to the amplification of the AR gene or treatment-induced gain-of-function AR mutations, Ubix explained.

UBX-103 in preclinical studies showed potency with half-maximal degradation concentration (picomolar DC50) and efficacy against a broad spectrum of treatment-induced resistance mutations, the company said. Notably, UBX-103 effectively inhibited growth of tumors that are typically resistant to next-generation hormonal therapy in vivo preclinical models.

Along with UBX-103, Ubix’s TPD pipeline includes UBX-303-1, a Bruton's tyrosine kinase degrader for relapsed or refractory B-cell malignancies. Ubix’s Degraducer technology helps leverage the body’s own natural protein degradation machinery to eliminate diseased proteins and render near-complete inactivation of disease-causing pathways, the company explained.

Yuhan CEO Wook-Je Cho noted that the licensing deal would “enhance technology exchange and collaborative efforts to develop TPD-leveraging, next-generation therapies,” while Ubix CEO BK Seo signaled confidence in Yuhan to “enhance the development and potential commercialization of UBX-103” based on its global track record in R&D and commercialization.

Yuhan has been an active player in the immunotherapy and cancer drug space, including gaining approval of its oral third-generation tyrosine kinase inhibitor, Leclaza (lazertinib), for lung cancer and inking a recent $156 million deal for Cyrus Therapeutics Inc. and Kanaph Therapeutics Inc.’s SOS1 inhibitor, CYRS-1645, for various cancers.

Yuhan to start US study of YH-35995

On July 1, Yuhan separately announced that the U.S. FDA granted IND clearance on June 28 to start a phase I study of its Gaucher disease drug, YH-35995, which was co-developed with South Korea’s GC Biopharma Corp. since June 2018.

The U.S.-based first-in-human phase I study of YH-35995 will enroll healthy adult males to examine the safety, tolerability, pharmacokinetic and pharmacodynamic effects of orally administered YH-35995, Yuhan said.

Developed with then-Green Cross under an open innovation model, YH-35995 is an oral, small-molecule, glucosylceramide synthase inhibitor. As a substrate reduction therapy, YH-35995 works to reduce the production of glucosylceramide (GL-1), which is known to accumulate in cells and certain organs in patients with Gaucher disease.

Yuhan noted that YH-35995 showed superior efficacy and safety in preclinical studies, and the therapy demonstrated successful penetration of the blood-brain barrier in animal studies to produce a longer and greater inhibiting action of GL-1 levels in the brain compared to existing treatments.

“YH-35995 was able to successfully enter multiple stages of clinical development as a result of the Yuhan Research Institute investing years on lead asset discovery, optimization, and preclinical development,” Yuhan R&D president Kim Yeol-hong said. “[IND approval] is significant [considering YH-35995 is] the first rare disease therapy developed by Yuhan, with patient enrollment expected to begin soon.”

Gaucher disease is a rare hereditary disease caused by the deficiency of the glucosylceramidase enzyme, which impacts the whole body including the hematological, organ, and skeletal systems. Only around 6,500 patients are known worldwide to have Gaucher’s; Korea reported about 70 patients in 2018.

Among the three types of Gaucher disease, the most common form is type 1, which does not impact brain or spinal cord but affects the spleen, liver, blood and bones. Two treatment modalities, enzyme replacement therapy and substrate reduction therapy, are approved for Gaucher disease type 1.

Gaucher disease type 2 and 3 are more severe and include acute and chronic neurological symptoms such as convulsions (seizures), hypertonia, neurodegeneration (dementia), intellectual disability and ocular muscle apraxia. Type 2 and 3 patients are known to have limited treatment options. The rare genetic disorder is classified as a type of lysosomal storage disease.

Shares of Seoul-based Yuhan (KOSPI:000100) on the Korean stock exchange rose 3.58% to close July 1 at ₩83,800. Shares of GC Biopharma (KOSPI:006280) were also up 1.31% on the Korea exchange, closing at ₩115,800.