Among them is Dr. Tadashi Kimura, a scientist who has been conducting research on bioactive peptides contained in venomous animals such as tarantulas to create therapeutic disulfide-rich peptides (DRPs) targeting transmembrane proteins, ion channels, transporters, and G protein-coupled receptors (GPCRs), which are considered difficult to discover drugs.
DRPs—which are bioactive peptides with high activity and selectivity—have excellent properties as drug modality. Dr. Kimura has developed a proprietary drug discovery system, ‘Veneno Suite,’ to accelerate DRP drug discovery. Through his startup venture, Veneno Technologies, Dr. Kimura is focusing on DRPs to promote new drug discovery innovations. “We are the first in the world to build a comprehensive platform that consists of three innovative technologies: DRP Space, PERISS, and Super Secrete. The Veneno Suite is an integrated DRP drug discovery system that includes everything from library creation to screening and production,” says Dr. Kimura, founder, CSO, CTO, and director, Veneno Technologies.
Addressing the Major R&D Hurdles in DRP Drug Discovery
With the motto ‘From toxins to medicines,’ Veneno Technologies pays homage to the wisdom of nature and creates new medicines and functional peptides using the most advanced technology. To demonstrate the efficacy of their drug discovery platform, the firm is creating novel peptide drugs targeting membrane proteins. In particular, their strategy is to advance drug discovery for ion channels, which are generally considered to be highly challenging due to extremely low structural stability, limited epitopes on the membrane surface, and the fact that it is a dynamic molecule with multiple conformations. “Many pharmaceutical companies have attempted to develop ion channel drugs using small molecules but failed due to factors such as insufficient selectivity for target molecules, which makes it difficult to create antibodies,” explains Dr. Kimura. DRPs, on the other hand, are excellent natural ion channel modulators; these peptides have unique molecular characteristics and mechanisms of action that are not found in antibodies or small molecules, such as high permeability to cell membranes.
Veneno Technologies: Accelerating Therapeutic Drp Drug Discovery
Compared to conventional screening methods, PERISS dramatically increases the probability of obtaining highly active DRPs
A One-Stop Solution for DRP Drug Development
Veneno Suite’s DRP Space, a gene-based library, uses natural DRP as templates and artificially adds random mutations to their DNA sequences using a proprietary algorithm to construct a massive library of the order of billion (ten to the power of nine). Its proprietary algorithms include an accelerated evolutionary approach similar to that used by venomous animals to evolve peptide toxins and in silico methods such as molecular surface charge and hydrophobicity based on 3D structural information, enabling the design and construction of diverse libraries.
At the core of the Veneno Suite is the company’s novel DRP high-throughput screening technology, PERISS—Intra Periplasm Secretion and Selection. It uses the periplasmic space between the inner and outer membranes of E. coli and employs periplasmic display technology based on molecular evolutionary engineering to enable rapid screening from a huge DRP library with one billion amino acid sequences produced by DRP Space. “Compared to conventional screening methods, PERISS dramatically increases the probability of obtaining highly active DRPs. In addition, it takes only about 12 months from the start of screening to the acquisition of hit DRP peptide sequences, which enables much more efficient and rapid screening than existing rapid electrophysiological methods,” mentions Dr. Kimura. Besides, the PERISS method can also be used to search for fragment antibodies such as nanobody (VHH antibody), Fab antibodies, as well as IgG antibodies.
In order to produce DRPs in large quantities at a low cost, Veneno Technologies is using E. coli that can correctly fold DRPs using periplasmic space. The team is developing a proprietary technology (IP patented), Super Secrete, to produce DRPs into the culture medium outside E. coli in collaboration with a Japanese chemical company. Super Secrete will significantly reduce the contamination of impurities and simplify the purification process. “At present, small-scale production at the laboratory level (cultivation and purification using a small jar-fermenter) has been established. In the future, we expect the Super Secrete technology to be applied to continuous cultivation methods and GMP production, making it an engine for realistically promoting DRP drug discovery,” affirms Dr. Kimura.
Paving the Way for a Better Future
Even though Veneno Technologies is only a year old, the firm has already succeeded in finding numerous new DRPs with inhibitory and facilitative effects on several ion channels using its innovative technology. For example, the firm recently demonstrated— electrophysiologically—how a newly discovered DRP molecule against a potassium channel with no known ligand acts on the target channel and completely inhibits its activation.
In addition to the pharmaceutical business, the company also focuses on the R&D of green agricultural chemicals with low environmental impact. “In concrete, we have started joint research with a chemical company to create new bioactive peptides as new biostimulants and peptide-based drug-resistant insecticides. We are in charge of screening and conducting research to support sustainable agriculture in response to the recent climate change and population growth problems,” states Dr. Kimura.
Veneno Technologies’ plan for the future is to invest in constant R&D and continuously improve existing technologies and develop new ones. Alongside, the company is looking to introduce robotics and AI in the library design and screening processes in order to maintain and strengthen its competitive advantage in the marketplace. “We are also actively seeking alliances with other organizations for related technologies and value the strategic investment and concentration of capital,” wraps up Dr. Kimura.