What is Dementia?

Dementia broadly refers to a state of various cognitive dysfunctions such as memory, caused by brain damage. The patient’s everyday life is impacted as the disease progresses.
Dementia is often classified into Alzheimer’s disease (60%), vascular dementia (20%), lewy body dementia, (15%) and fronto temporal dementia (5%), etc.

The Cause of Alzheimer’s Disease

The biggest causes of Alzheimer’s disease are known to be amyloid beta and hyper phosphorylated tau protein.

Both amyloid beta and hyper phosphorylated tau protein are known to be neurotoxic. Hyper phosphorylated tau protein is recently identified as the direct cause of degeneration in cognitive functions and memories.

Also, the theory that excessive generation of amyloid beta and hyper phosphorylated tau protein synergize to fasten the disease is gaining more ground.

New Dementia Treatment Target: VDT2

Closely Related to Alzheimer’s Disease
Recent study proved that VDT2 is linked to both generation of amyloid beta and tau protein phosphorylation, two known causes of Alzheimer’s disease. VDT2 was found to stimulate generation of amyloid beta, by phosphorylating amyloid beta precursor protein, and phosphorylated tau protein, by directly phosphorylating tau protein. Also, it’s been reported that both mRNA and protein volume of VDT2 in the brain of Alzheimer’s disease patients were significantly larger compared to healthy brains.

Therapy Development Status

Targeted therapy
Voronoi discovered a targeted therapy candidate that suppresses VDT2 activity and is currently pursuing clinical development. Preclinical toxicity study is ongoing, and overseas clinical investigation will begin in 2019.

Efficacy of Combined MoA Confirmed
We commissioned Dr. Huh Hyangsook and her team at the Korea Brain Research Institute to study the efficacy of our compound in treating the Alzheimer’s disease. Our compound was administered on 5xFAD mice, typical mice with Alzheimer’s. It was confirmed to 1) decrease amyloid beta plaque, 2) decrease tau protein phosphorylation and 3) suppress brain inflammation. This led to improved memory and cognitive function of the mice. Unlike amyloid beta single targeting antibody therapies repeating failures in recent clinical investigations, Voronoi’s compound has a combination of modes of action, indicating better efficacy.

Potential Expansion to Various Indications

Voronoi focuses on its candidate’s ability to suppress brain inflammation, and expands indications to include various inflammatory diseases. Indications also include metabolic diseases and degenerative diseases, often seen in Down’s syndrome patients in their 20’s to 30’s.

Source: 
Bloom, George S. “Amyloid-β and tau: the trigger and bullet in
Alzheimer disease pathogenesis.” JAMA neurology 71.4 (2014): 505-508.

What is Drug Repositioning?

Drug repositioning refers to investigating new therapeutic purposes of existing drugs, which are already in the market or whose clinical development has stopped due to reasons other than safety.

Benefits and Limitations of Drug Repositioning

Drug repositioning saves substantial amount of development cost and time, as early discovery, nonclinical trials and some early clinical phases can be skipped.
However, if the marketed drug product is priced low, drug repositioning may be difficult due to low economical value.

Benefits of VDT5 Target Therapies

Expensive Drug for Rare Diseases
Existing VDT5 target therapies are sold at high prices for rare diseases. Therefore, they can be easily stretched to treat chronic diseases like Alzheimer’s disease, for which drug prices are lower. Since the raw materials for these drugs are relatively inexpensive, developing them as Alzheimer’s disease drug can also secure sufficient profitability.

Combined Efficacy for Alzheimer’s Disease
VDT5 target therapies have already been confirmed to have high blood-brain-barrier penetration rate inside the body. They are also known to have strong anti-inflammatory effect on brain inflammation. In particular, in the 5xFAD mice model, they increased the amount of IDE (Insulin degrading enzyme), suppressing the generation of amyloid beta, and simultaneously suppressing hyper phosphorylation of tau protein caused by CDK5 and GSK3-beta. Such combined pharmacological actions are expected to show excellent clinical efficacy for treating Alzheimer’s disease.

Development Strategy

Clinical Investigation to Start in 2019
As a number of mandatory steps for clinical trial entry are exempt, development will progress with the goal of beginning clinical trials in 2019.

Patents Applied for Alzheimer’s Disease Therapy and Formulation
Voronoi possesses the right to exclusively develop the VDT5 targeted therapy for Alzheimer’s disease.
We are also developing drugs with improved bioavailability. Though this, we can pursue clinical investigation on an Alzheimer’s disease therapy with less API, to be priced separately.

Market Potential

As the original developer, we can enter the vast Alzheimer’s disease market with this program. Also, since this drug will be priced separately, it can be developed without cannibalizing the existing rare disease drugs.

Hur Hyangsook, PhD/Senior Researcher, Korea Brain Research Institute

Developing cure for Alzheimer’s disease is an arduous journey. Numerous pharmaceutical and venture companies have gone as far as late clinical trial stages, but have yet to see a medicine that can fundamentally cure the disease. The causes of breakout and progress of the disease are known to be amyloid beta and hyper phosphorylated tau protein.

Most antibody projects that solely targeted amyloid beta failed at phase 3. On the other hand, Voronoi’s candidate was confirmed to suppress the phosphorylation of both amyloid beta and tau protein. It effectively suppresses the substances the cause the disease, and dramatically improves the cognitive function as proved in animal tests.

Kwon Jihye, PhD

Korea Brain Research Institute is the best research center in Korea when it comes to dementia and other degenerative brain diseases. Excellent resources, dozens of species of diseased animals and behavioral- and cognitive function measurement equipment are possible thanks to the government support. In particular, Neuro Degenerative Disease Lab is at the forefront within the Institute, by generating the most reliable data. The Lab is conducting joint research to develop Voronoi’s candidate compound.

Normal

Jaeyoung kim

(Korean) 나의 하루가 누군가의 더 나은 삶을 위해 쓰인다는 것

Pipeline

VRN02, DYRK1A, Autoimmune Disease

VRN02 program is under development for the treatment of autoimmune diseases, by inhibiting DYRK1A kinase activity. Series of animal experiments have suggested that VRN02 has efficacy for major autoimmune diseases such as rheumatoid arthritis, lupus, psoriasis, inflammatory bowel disease, and atopic dermatitis, and we are expanding into other indications. VRN02 is under development not only as oral pills, but also as topical formulation to apply on skin.

Pipeline

VRN04, RIPK1, Autoimmune diseases

VRN04 program is under development for the treatment of inflammatory diseases, by inhibiting RIPK1 kinase activity. Series of animal experiments have suggested that VRN04 has efficacy for major inflammatory diseases such as acute lung injury, rheumatoid arthritis, psoriasis, and inflammatory bowel disease, and we are expanding into other indications.

Pipeline

VRN08, TTK, Triple-negative Breast cancer

Voronoi’s VRN08 program aims to treat TNBC by targeting TTK. We plan to expand indication to other solid tumors like pancreatic cancer and brain cancer. As TNBC, pancreatic cancer, and brain cancer are areas where existing targeted therapeutics and immuno-oncology drugs have little efficacy, development of effective and safe therapeutics is urgently needed.

Pipeline

VRN02, DYRK1A, Autoimmune diseases

VRN02 program is under development for the treatment of autoimmune diseases, by inhibiting DYRK1A kinase activity. Series of animal experiments have suggested that VRN02 has efficacy for major autoimmune diseases such as rheumatoid arthritis, lupus, psoriasis, inflammatory bowel disease, and atopic dermatitis, and we are expanding into other indications. VRN02 is under development not only as oral pills, but also as topical formulation to apply on skin.

Pipeline

VRN01, LRRK2, Glioblastoma

VRN01 program is under development for the treatment of brain tumor, especially GBM (Glioblastoma multiforme) which is known to be the most malignant form of brain tumor, by inhibiting LRRK2 kinase activity.

Pipeline

Brain Tumor

We are developing a new therapy targeting brain tumor stem cells, a cause of brain tumor relapse. We are working to treat GBM, or Glioblastoma, the most malignant form of brain cancer.

Pipeline

Alzheimer’s Disease

We are developing a therapy that targets both amyloid beta and tau.
Animal tests have proven that Voronoi’s candidate significantly suppresses them and
substantially improves cognitive function.

Pipeline

Chronic Inflammatory Disease

TNF- α is well known as a core cause of inflammation, accompanied by autoimmune diseases. Voronoi has identified a candidate compound that blocks signal transduction of TNF- α. We are now developing therapies for rheumatoid arthritis, inflammatory bowel disease, systemic psoriasis, xerophthalmia, macular degeneration and degenerative brain disease.

Pipeline

Non-Small-Cell Lung Carcinoma

We identified a candidate that can overcome the EGFR (Epidermal growth factor receptor) resistance issues existing cancer drugs had. The candidate is being developed as therapy for lung cancer and various solid cancers.

Science

Pipeline

We focus on developing therapies for intractable and rare diseases.

Science

R&D Platform

We lead next-generation therapy development based on advanced technologies and platform.

Science

Collaboration

"Voronoi endeavors to open a new chapter in tumor treatment, giving patients new hope."

Meet the experts

Nathanael Gray, PhD

​Nathanael Gray is the Nancy-Lurie Marks Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Dana Farber Cancer Institute.

Company

Our work

Voronoi develops novel TPD (Target protein degraders) and kinase inhibitors with the aim to treat intractable and rare diseases. We are developing competitive therapies based on deep understanding of diseases and innovative technologies.

Company

About VORONOI

Voronoi Group consists of the parent company Voronoi and its subsidiaries Voronoi Bio and B2S Bio. Voronoi leads clinical development throughout the R&D journey. Voronoi Bio focuses on R&D of molecular modeling and kinase inhibitor, and B2S Bio focuses on TPD.

People

Meet the experts

Our experts and the management bring to the team years of experience and expertise in various fields.