Alamar Biosciences Supercharges Proteomics to Detect Disease and Boost Research

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December 2021 – Genomic sequencing provides tremendous insights into biology and disease, but it’s only a partial picture. To really understand what’s happening in the body, scientists and clinicians need to measure proteins.

That’s the guiding vision behind Fremont, California-based Alamar Biosciences, which is leveraging a novel proteomics platform to develop hyper-sensitive liquid biopsies and boost fundamental discovery research.

Signal and Noise

Yuling Luo, Ph.D., is the Founder, Chairman and CEO of Alamar. At his previous company, Advanced Cell Diagnostics (ACD), Dr. Luo developed a breakthrough technology called RNAscope, which is still the industry standard for ultra-sensitive, single-molecule RNA detection. After selling ACD to Bio-Techne, Dr. Luo was determined to develop a similarly powerful platform to detect protein biomarkers.

RNAscope overcame one of the most significant challenges for any molecular detection platform – increasing signal without also increasing noise. “We came up with a unique probe design strategy that works together with a robust signal amplification system to boost signal without also boosting background noise,” said Luo.

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Fast-forward a few years, and Alamar has adapted this concept to protein detection. Luo believes these capabilities will provide stronger proteomic signatures and detect molecules that may be invisible to other technologies.

“There are more than 10,000 proteins in plasma,” said Luo, “but only about 3,500 are detectible and quantifiable with current technologies. Many of the currently undetectable molecules could be valuable as early disease biomarkers.”

Liquid Biopsy

For Luo and the Alamar team, one of the most critical high-sensitivity proteomics applications is cancer detection. This is a classic needle-in-a-haystack problem, particularly in early-stage cancers: Detect a small number of cancer markers in a sea of normal molecules. However, Alamar’s proteomics strategy has a distinct advantage over ctDNA platforms.

“All cells, including cancer cells, have only two DNA copies,” said Luo. “But proteins have hundreds of thousands, if not millions, of copies, providing natural amplification you don't have with DNA.”

Alamar is bringing two unique technologies into the mix. NULISA, the company’s nucleic acid-linked immunoassay, provides high sensitivity, wide dynamic range and scalability. Attobody is a bioengineering platform that produces high-affinity antibodies.

These approaches can be combined into a unique platform that can help researchers find the most informative but rare biomarkers. Their inspiration is heart-specific troponin, a protein that only appears in the blood following a heart attack. The group is hunting for cancer protein markers that provide similar, tissue-specific information long before symptoms appear. They believe their unique platform will be a critical tool for researchers to explore a wide range of diseases.

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“These proteins would normally not appear in the blood, but when you have increased apoptosis and necrosis from aggressive cancer, they get released,” said Luo.

“While most liquid biopsy efforts focus on circulating tumor DNA (ctDNA), Alamar is taking a different path, looking for circulating cancer-associated protein biomarkers,” said Nick Naclerio, Ph.D., Founding Partner of Illumina Ventures. “This is mostly undiscovered territory and could ultimately lead to highly sensitive diagnostics that find cancer and other diseases early when they are most treatable.”

Multiple Applications

Cancer detection is Alamar’s first liquid biopsy focus, but it won’t be their last. Many other diseases, including Alzheimer’s and Parkinson’s, may shed disease biomarkers into the blood, making them amenable to high-sensitivity proteomic analyses.

“These platforms will have applications far beyond cancer detection,” said Alamar Chief Technology Officer, Xiao-Jun Ma, Ph.D. “Plasma is the ultimate diagnostic material, with great promise to detect and interrogate many conditions.”

The company is moving full speed ahead: developing its early cancer detection platform and commercializing its proteomics technology to help scientists pursue a wide range of discovery research. In October 2021, Alamar successfully concluded a $90 million Series B with support from Illumina Ventures and a broad syndicate of investors.

“We are gratified by the support we are receiving from Illumina Ventures and others,” said Luo. “This funding will help us identify and validate candidate biomarkers a