Terremoto Biosciences will receive $ 75 million to develop covalent drugs  BioSpace

Terremoto Biosciences will receive $ 75 million to develop covalent drugs BioSpace


Terremoto Biosciences is headquartered in San Francisco launched with $ 75 million in A-line funding for the development of highly targeted small molecule drugs.

Funding was co-managed OrbiMed and Third Rock Ventures. With funding, Terremoto plans to expand its lysine-focused covalence platform and create therapies for previously incurable diseases.

“Terremoto redefines what was once considered scientifically impossible with our well-defined approach to the platform and unrivaled team,” said Peter Thompson, MD, co-founder, CEO and board member of Terremoto Biosciences and general partner of OrbiMed. “With Series A funding, we will continue to build on the fundamental advances in our lysine-based covalence technology to dramatically expand the universe of target drugs and also significantly improve existing drugs for the patients who need them most. “

Although some of the first drugs were based on covalent bonds –such as aspirin and penicillin– Researchers were reluctant to produce them due to possible side effects. Non-covalent drugs can slip in and out of disease-associated proteins, but covalent drugs bind to proteins and deactivate them. Covalent drugs could potentially form bonds with proteins in the body that they shouldn’t, and cause off-target damage. Researchers also fear that the body may see covalent bonds as an intruder and attack them with the immune system.

However, the potential of covalent medicine still contained several benefits. Although covalent drugs may have bound to proteins they did not have until the body resynthesizes them, they also last longer in the body. If covalent drugs are properly developed, they can be given in lower amounts and less often. Covalent therapy also offers improved inhibition profiles that can inactivate mutated proteins for extended periods of time without increased toxicity.

As technology progressed, covalent drugs began to rise in popularity. According to RSC Med. Chem, number of publications related to covalent drugs doubled from 2001 to 2019. And from 2021 Life Chemicals states that approximately 30% of medicines on the market are covalent inhibitors, a type of drug that forms a covalent bond with a specific target protein.

Historically, covalent drugs have relied on binding to cysteine, an amino acid. However, cysteine ​​is unusual in proteins, so the number of drugs that can be developed is limited. The Terremoto team now plans to improve the way the industry makes covalent drugs. Terremoto develops drugs that covalently bind to lysines, an amino acid that is of interest in almost every protein.

“Lysine-focused covalent chemistry can be considered a game of dynamic Tetris, given the level of chemical and biological mastery required to covalently bind to this amino acid in a selective and targeted manner,” Thompson said.

To develop lysine-focused covalent drugs, Terremoto will use Series A funding to help develop its drug discovery platform. The platform can identify structure-based drug designs, perform cryo-electron microscopy, perform X-ray crystallography, and develop a library of electrophilic warheads along with its computational search engine.

“Terremoto’s lysine-focused covalent approach builds on these advances and is ready to expand the set of opportunities where covalent chemistry can be used, ultimately ushering in a new era in small molecule drug discovery,” said Reid Huber, Ph.D., board member. . of Terremoto a partner at Third Rock Ventures.

Terremoto’s leadership team is uniquely qualified to develop lysine-targeted covalent drugs. Matt Jacobson, Ph.D., professor and chair of the Department of Pharmaceutical Chemistry at UCSF, is a co-founder of Terremoto. He developed the only currently approved drug that binds to the amine on the hemoglobin molecule. Another co-founder is Jack Taunton, Ph.D., professor of cellular molecular pharmacology at the University of San Francisco and co-founder of Principia Biopharma, Cedilla Therapeutics, Kezar Life Sciences and Global Blood Therapeutics. T

erremoto also has a scientific advisory committee made up of renowned chemists and entrepreneurs in the field of serial life sciences, which helps make lysine-based covalent drugs available for a wide range of new diseases.

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