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Start-up company A-Alpha Bio sets out to solve major protein problems faced by large pharmaceutical companies


Pharmaceutical and biotech companies that are looking for new drugs conduct tests in the process to understand how proteins interact. David Younger, co-founder and CEO of A-Alpha Bio, said that analyzing protein-protein interactions can reveal how cells communicate, how genes are regulated, and how the immune system recognizes and attacks diseases. This is a necessary process, but it is a time-consuming process. For companies large and small, this usually means testing one protein interaction at a time.

A-Alpha Bio’s technology can simultaneously test millions of protein interactions. The Seattle-based startup already has a handful of partners in the biotechnology industry. It now has $20 million to expand its technical capabilities and develop its business. The Series A financing announced on Wednesday was led by Madrona Venture Group; Perceptive Xontogeny Venture Fund and Lux ​​Capital also invested.

A-Alpha Bio is part of a growing team in proteomics (large-scale protein research). This field has become a hot spot for investment. Nautilus Biotechnology recently went public in a merger transaction, injecting $350 million into it. The Seattle company’s technology generates protein landscape maps that can provide insight into disease pathways and disease progression.Headquartered in Redwood City, California Seer raised $55 million Supported the development of its protein analysis platform last year. Although these companies detect the proteins in the samples, Younger said that A-Alpha Bio is dedicated to different areas of proteomics to find out which proteins bind to each other.

The startup’s approach started with yeast, which is the yeast used to bake bread and brew beer. Yeast cells are often used in scientific experiments because they have some similarities with human cells and they have a high degree of engineering ability. A-Alpha Bio’s technology, called AlphaSeq, is a laboratory method developed by the company to simultaneously test millions of protein interactions using genetically engineered yeast cells.

Younger said that traditional methods used to test protein interactions require a trade-off between quantity and quality. In order to obtain high-quality results, the scientists tested two proteins in an experiment. This method has no scale. If the quantity is the goal, the technology platforms of companies such as Adimab and Distributed Bio can analyze a large number of proteins. But every measurement is of low quality, Younger said.

AlphaSeq aims to provide quality and quantity in the same test. The company focuses its research on two areas: the discovery of antibodies and the targeting of molecular glues, which are key components of an emerging treatment called targeted protein degradation. A-Alpha Bio works with pharmaceutical companies to help them discover these goals. Publicly disclosed partners include Twist Biopharma (a division of Twist Bioscience headquartered in South San Francisco) and Seattle-based Lumen Bioscience.

Younger did not set out to make better antibodies or molecular glues. The origin of A-Alpha Bio can be traced back to nearly ten years when he was a graduate student at the Institute of Protein Design and Center for Synthetic Biology at the University of Washington. At the time, he was trying to solve the problems faced by him and many of his peers. Using computers, it is common for students to design up to a thousand proteins in a week or even a day.

“Due to the maturity of computational protein design, it has come a long way,” said Younger. “But you still need to test them. This is the bottleneck. It is impossible to test all these proteins.”

Younger’s graduate work involves developing a platform that will become AlphaSeq. As the research progresses, he faces the question of how to maximize its influence. Publishing a paper will enable others to conduct research. He is also considering licensing the research to a company. He chose the third option: starting a company.

A-Alpha Bio was established in 2017. The following year, the startup received the first small business innovation research grant. First stage reward For the development of a drug analysis platform using yeast cells. The company’s focus on antibodies and molecular glue stems from the client discovery part of the grant preparation. Younger said that he and his team were forced to go out and talk to as many pharmaceutical industry experts as possible to determine market needs. In the field of antibodies, the problem Younger has repeatedly heard is that a company may have thousands of drug candidates, but their tools can only screen one at a time.​​​ Therefore, there may be only 10 or fewer antibodies that need to be fully tested because it is impossible to test all antibodies.

Molecular glue is a new research area in this industry, because targeted protein degradation is still a new research area. The technology involves marking a disease-causing protein, which is processed by the cell’s built-in machinery to remove old or damaged proteins. The challenge is that not all proteins have the affinity to adhere to the molecular tags that mark the protein to be processed. This is where molecular glue comes in. A-Alpha Bio received Second phase funding The molecular glue discovery technology was developed last year.

Currently, A-Alpha Bio’s technology supports the drug research of larger partners. The startup received an advance payment under the agreement, which also promised milestone payments and received royalties from the sale after the treatment was commercialized. Looking ahead, Younger believes that A-Alpha Bio will eventually use its technology to build an internal drug pipeline. In the near future, A-Alpha Bio’s research may help the development of Covid-19 drugs. The startup is looking for antibodies that can bind to SARS-CoV-2, and this research is supported by Lumen. Grant From the Bill and Melinda Gates Foundation.A year ago, A-Alpha Bio was awarded SBIR funding for the first phase Develop an antibody generation platform for coronavirus variants.

The ability to test millions of protein interactions means that AlphaSeq generates a lot of data. Younger said that the next step for A-Alpha Bio includes building the ability to analyze this data. The company aims to use machine learning technology to predict how proteins interact. In the next 18 to 24 months, Younger predicts that the number of employees at this startup may increase from 13 to 50, many of whom will join the machine learning and data science team, which is led by Adaptive Biotechnologies veteran Ryan Emerson leadership.

“Over time, we will accumulate the largest library of protein interactions,” Younger said. “When we build that database, we can use tools such as machine learning to start turning engineered protein interactions into a computational problem rather than an experimental problem.”

Photos of Flickr users Roger W Through knowledge sharing license



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