HONG KONG – South Korea biotech venture Spark Biopharma Inc., based in Seoul, has secured KRW25 billion (US$21 million) in series B funding for new drug pipeline R&D. The company will accelerate small-molecule compound-based immuno-oncology therapeutics and treatments for nonalcoholic fatty liver disease (NAFLD).

The funding was led by venture capital companies based in Korea, including KB Investment Co. Ltd., KTB Network Co. Ltd., Partners Investment Co. Ltd., IMM Investment Corp., E&Venture Partners Inc. and Company K Partners Ltd. The company received KRW4.5 billion in a series A round in 2018 led by KB Investment and Solidus Investment Co. Ltd., which has driven the biopharma's core platform technology development.

"We plan to develop our main four areas – immuno-oncology, central nervous system [CNS], metabolic disease, and cardiovascular [CVD] therapeutics. Then we will carry out the preclinical trial of an inflamed tumor treatment late this year or early next year," a spokesman at Spark told BioWorld.

Founded in 2016, the firm is led by professor Seung Bum Park at the Chemistry Department of Seoul National University, based in the Creative Research Initiative (CRI) Center for Chemical Proteomics. Spark focuses on developing first-in-class small-molecule therapeutics by integrating biology, chemistry, proteomics and informatics. It has three original platform technologies and six candidates.

Spark is developing three programs in cancer treatment and one each in CNS, metabolic disease and CVD. The cancer candidates are targeting inflamed tumors, non-inflamed tumors and refractory tumors. The CNS treatment candidate targets Alzheimer's and Parkinson's diseases. The metabolic disease candidate aims to treat NAFLD and nonalcoholic steatohepatitis (NASH), while the CVD drug targets calcific aortic valve stenosis. All the programs are in discovery stage, except for the inflamed tumor therapy candidate, which will move to preclinical stages soon.

The company's platform technologies are designed to generate novel bioactive small molecules capable of modulating the biological systems related to the diseases. To do that, Spark shifts the common frame of drug discovery. The traditional drug discovery procedure is focused on the target-based approach; Spark's approach is to focus first on bioactive drugs and then try to discover the target protein, which has been previously undruggable.

Its core platform technology consists of three steps. The first step is molecular diversity improvement using its in-house technology, Privileged substructure-based Diversity Oriented Synthesis (pDOS). The technique generates collections of drug-like small molecules with high molecular diversity and biological relevancy that then assist in the discovery of novel therapeutic agents. During the process, privileged structures function as chemical navigators for the efficient construction of relevant small-molecule libraries with various structural features.

The second step is Seoul-Fluor (SF), a system to present a series of fluorescent small molecules and monitor various biological events. It shows tunable and predictable emission colors covering a full visible-color range, so that the company can tune the color of the molecules to their research goals.

The SF system has controllable brightness through a photo-induced electron transfer phenomenon, which is connected to the development of biological sensors or diagnostic molecules. Also, the system has environment-sensitive properties, and their fluorescent color or brightness can be changed according to the surroundings. That helps to enhance screening bioactive compounds in the small molecules.

The last step, Fluorescence difference In Two-dimensional Gel Electrophoresis (FITGE), identifies the target of the drug candidate. The technique attaches functional handles to original bioactive molecules, and the handles enable the molecule to bind to the target protein. The bind can be monitored in the whole cell without disturbing the plasma membrane, thus leaving the cellular signaling network undamaged.

The company uses another handle to visualize the drug-target complex, with fluorescence having high sensitivity. Then each protein is separated and analyzed by two-dimensional gel electrophoresis. Based on that process, the company identifies target proteins for its cancer agents, antibacterial agents and anti-inflammatory agents.

When attaching functional handles to an original drug fails due to an innate property of the drug, the company uses a modified version of FITGE, called TS-FITGE (Thermal stability Shift-FITGE). When the target protein is thermally stabilized upon drug binding, the company uses TS-FITGE to differentiate the stabilized or destabilized target protein from other proteins. Using the technique, the firm covers the target identification of natural products that have complex or minimal structures.

Its investors said the biotech firm and its technology could create huge corporate value.

"There are few biotech companies worldwide having multiple platforms like Spark Biopharma, and that is why we highly value the venture's technologies to discover and develop new drug candidates.," Jiwoong Chun, health care investment director at KTB Network, told BioWorld. "We believe in the firm's potential."

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