Vividion Therapeutics: Small molecule drug company targeting transcription factors applies for IPO

Vividion Therapeutics submitted a preliminary prospectus of US$100 million, and the institutions holding >5% of the shares before the IPO are as follows:

In the $135 million round C financing completed in February, Logos Capital and Boxer Capital jointly led the investment. Other investors include SoftBank, Avoro Capital, BlackRock, RA Capital, T. Rowe Price Associates, and Surveyor Capital (a Citadel company) , Woodline Partners LP, Acuta Capital and Driehaus Capital. Existing investors ARCH Venture, BVF, Casdin Capital, Mubadala Capital, Nextech Invest and Versant Ventures also participated in this round of financing.

Company technology platform and pipeline

Vividion Therapeutics is a biopharmaceutical company focused on precision therapy, focusing on the development of targets that were previously considered non-medicinal. Its proprietary chemical proteomics (chemoproteomic) platform technology discovers undiscovered functional pockets on the surface of proteins and binds them with small molecules in the proprietary library. So far, the company has screened more than 75,000 cysteine residues on about 12,500 proteins, clarified more than 800 new binding pockets for 250 validated targets, and developed a number of covalently binding small molecules with 80 targets. More than 100 unique binding pockets are combined.

At present, the research pipeline mainly targets two key transcription factors, NRF2 and STAT3, and the DNA oxidative damage repair gene WRN. The structure of transcription factors is complex and disordered and lacks small molecule binding pockets. Traditionally, it is believed that targeting transcription factors through small molecule ligands is not druggable. Vividion's STAT3 project was developed in cooperation with BMS (Bristol-Myers Squibb), and WRN was developed in cooperation with Roche. At present, all pipelines are still in pre-clinical research, and it is expected to nominate the first drug candidate and submit an IND to the FDA in 2022.

1. Chemical proteomics (chemoproteomic) platform technology

The platform is based on the research of the company's co-founders Benjamin F. Cravatt, Phillip Baran and Jin-Quan Yu at Scripps Research Institute. Dr. Cravatt's laboratory uses spectrometry-based proteome profiling to monitor the binding of cysteine-reactive small molecules to specific sites on thousands of proteins. The chemical methods developed by Drs. Baran and Dr. Yu enabled them to explore three-dimensional chemistry and protein space, and constructed chemical scaffolds and cysteine group libraries.

Chemoproteomic screening technology uses high-resolution mass spectrometry and chemical probes to detect the interaction between small molecules and proteins (regardless of the functional level). After finding the specific cysteine binding sites in the protein, use the small molecules in the library to test Combine effectiveness. The following figure is the output of the test, the row (Target) is the cysteine binding site on the target protein, which is listed as the compound:

With the expansion of the library of small molecules, the discovery of druggable pockets of disease-related proteins has also increased:

This test method allows the company to discover a variety of different types of compounds, including allosteric activators/inhibitors, protein stabilizers, PPI (protein-protein interaction) inhibitors, and protein degradation agents.

2. Pipeline

1、KEAP-NRF2

The company develops compounds that can inhibit or activate NFR2 to treat different diseases. In tumors, abnormal activation of NRF2 acquired by mutation or treatment can be a key adaptation of cancer cells to achieve a highly malignant and therapeutic resistance state.

Almost all mutations in NRF2 exist in two regions, called "DLG" and "ETGE" sequence subunits. Mutations in these regions hinder the recognition of NRF2 by KEAP1, prevent the proteasome degradation of NRF2, and increase the level of NRF2. The NRF2 inhibitors developed by the company focus on squamous cancers with NRF2 "DLG" mutations, and are indicated for NRF2 mutation tumors, such as NSCLC, ESCC and HNSCC. The company estimates that more than 10,000 people in the United States are diagnosed with this type of mutation each year, and more than 50% are NSCLC squamous cell carcinomas. This type of population is not sensitive to chemotherapy and PD-1/PD-L1.

In addition, the NRF2 activator corresponds to the up-regulation of NRF2 activity and activates the anti-inflammatory response. The indication is inflammatory diseases such as IBD. Companies that develop the KEAP1-NRF2 pathway also include Reata Pharmaceuticals and yTy Therapeutics, which are developing NRF2 activators, which are in the clinical stage.

2、STAT3

Another project targeting STAT3 cooperated with BMS. In March 2018, Vividion and BMS reached a research and development cooperation to develop small molecule drugs for the targets specified by BMS. The advance payment was US$95 million. The subsequent fees received will be determined by BMS exercise. Certainly.

The currently established STAT3 target is an oral STAT3 allosteric inhibitor, which binds to another pocket that is not the DNA binding domain, thereby inducing a conformational change that negatively affects the function of the DNA binding domain and preventing STAT3 from binding to DNA. . Indications are inflammatory diseases and tumors. Tvardi Therapeutics is also developing STAT3 inhibitors, which is in the clinical stage; Kymera Therapeutics and Roivant Sciences are developing STAT3 protein degradation, which is in the preclinical stage.

The currently approved therapies mainly target upstream activation signals, and STAT3 inhibitors theoretically have the potential for combined use.

3、WRN

Vividion reached a cooperation with Roche in April 2020. Vividion develops small molecule drugs based on a series of targets (Low twenties) selected by it. Roche paid a one-time prepayment of US$135 million in cash, and subsequent fees received will be determined by Roche's exercise of the rights. .

WRN is the first target selected in the collaboration (May 2021). The WRN inhibitor developed selectively inhibits the helicase activity of WRN in the MSI-H (microsatellite highly unstable) cell line.

Also developing targeting WRN are the WRN project of IDEAYA Biosciences and GSK, preclinical; the WRN project of Nimbus Therapeutics, preclinical; and the WRN inhibitor of Beactica Therapeutics, preclinical.

2020 and 2021 Q1 financial performance

Cash and cash equivalents: 333M (As of March 31, 2021)

Reprinted from: Weizhi U.S. Stocks Biomedicine https://mp.weixin.qq.com/s/P_BqF6ZQiNk2-Qh9cWTivA