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HiFiBio Bets on Single-Cell Methods to Boost Drug Discovery

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This story has been updated to clarify the sample types used in HiFiBio's Nature Genetics study. 

NEW YORK – Pharmaceutical companies have demonstrated a swell of interest in omics-based profiling, including single-cell methods. From transcriptomics and epigenomic profiling technologies like chromatin immunoprecipitation sequencing, to single-cell versions and other droplet-based methods, these molecular methods are getting a try out at firms both large and small.

As one of the small ones, Cambridge, Massachusetts-based HiFiBio is taking a two-pronged approach, using single-cell technologies to help find better indicators of why existing drugs work and to find new antibodies that could be developed as treatments.

The firm has engineered single-cell technologies licensed from Harvard University and other leading academic institutions for both discovery, in its CelliGo technology, and clinical development, in its Drug Intelligent Science (DIS) applications. The firm has also developed its own intellectual property. 

Together, these methods are helping researchers sketch a new picture of drug discovery, where molecules are not just targets, but indicators of relevant phenotypes. Whether that helps match patients to existing drugs or reveal new biology that can be translated into treatment, the early studies are making their way into the literature.

In May, researchers from HiFiBio published a paper in Nature Genetics based on a study done in collaboration with researchers from France's ESPCI Paris and Institut Curie. The team used HiFiBio's DIS to profile cells resistant to breast cancer therapy. Using single-cell ChIP-seq and single-cell RNA-seq with HiFiBio's droplet microfluidics platform, the researchers found a common chromatin signature in resistant cells.

Surprisingly, they also found that some untreated cells had similar signatures. The cells were patient-derived xenografts used with a mouse model.

"If we have the right science to guide us, we can identify patients on deeper cell biology," HiFiBio Cofounder, CEO, and President Liang Schweizer said. The study, she said, was a "small-scale demo of that concept in a scientific research setting."

Further down the road, the best drug targets may even come from studying patient samples using these methods, she said.

Pharma giants have taken notice and placed bets with firms like HiFiBio, which has partnered with Takeda on antibody discovery and Gilead Science's immunotherapy subsidiary Kite Pharma in a deal for single T cell profiling worth $10 million up front, with the possibility for milestone payments.  The partnership and pipeline approach is similar to the strategy being pursued by another company focusing on single-cell technologies, Celsius Therapeutics, which was cofounded by Broad Institute researchers. Celsius recently partnered with Johnson & Johnson's Janssen, to use single-cell sequencing to identify biomarkers that predict response to treatment in a Phase II study of a combo of Janssen's guselkumab (Tremfya) and golimumab (Simponi) for ulcerative colitis.

HiFiBio and Celsius are also similar in that they can both trace their genesis to single-cell methods developed in academia.

For HiFiBio, that's the droplet technology developed by Harvard University's David Weitz and Allon Klein, which also powers 1CellBio's inDrop platform for single-cell labelling. HiFiBio has raised tens of millions, including a $37.5 million May 2018 Series B round, and has about 70 people at its Cambridge headquarters and two other sites, in Paris and Shanghai.

While the recent paper showed the firm's profiling capabilities, Schweizer said she's not interested in becoming a service provider. The firm is open to partnerships to help advance its technology, but ultimately it wants to develop its own drugs, using its droplet technology to discover candidates for antibody-based therapeutics.

While the Kite deal, signed in 2018, focused on T cell receptors, HiFiBio got its start looking at B cell-secreted antibodies in a droplet, Schweizer said. "From that we can identify which B cells produced antibodies of interest and sequence individual cells to determine the native pairing of heavy and light chain," she said. The ability to study single cells presents a great improvement over previous methods of B cell screening, which involved fusing B cells with transformed malignant cells to create immortal clones. Screening for all the possible antibodies created by B cells wasn't possible "because it is limited by the hybridoma fusion rate," Schweizer said. "You know you're only looking at a small fraction of antibody-producing cells. And CelliGo can do this screening quickly. "In one second we can screen 5,000 droplets," Schweizer said. "Antibody screening from the entire B cell repertoire from an immunized mouse and capture can be done within a day."

For now, HiFiBio is looking for strategic partners, both among pharma companies and with academic researchers, especially those that can provide access to clinical samples. If the firm can get patient samples running through its profiling processes, it might find new targets.

"We will announce some partnerships in the next half year before the end of 2019," Schweizer said. "One thing I firmly believe in is that making a drug is a team sport."

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