Variant Emerges With $16M to Find “Outlier Humans” to Reveal New Drugs

Xconomy Seattle — 

Human DNA holds secrets that, once uncovered, have led scientists to develop a number of treatments for disease. A slew of biopharmas and biotechs—not to mention national health systems—have hoovered up genetic data from millions of people in hopes of leveraging the information contained within to drive their R&D.

Variant Bio, which debuted Thursday with $16 million in Series A financing, is betting that its narrower strategy of identifying small groups of “outlier humans” with variations in DNA that affect disease risk will prove both quicker and cheaper.

Founded in New York, the 10-person startup will—once restrictions imposed by the pandemic loosen—take root in Seattle under the oversight of Bill & Melinda Gates Foundation alum Andrew Farnum. The Variant CEO most recently led the Gates Foundation’s Strategic Investment Fund; prior, at the Children’s Investment Fund Foundation, he developed private sector projects in Africa and India.

Over the past year Variant has partnered with groups on four continents based on research that indicates that those populations’ genetics could provide clues that may one day lead to drug discovery work in metabolic, autoimmune, and neurodegenerative disorders. One such agreement, signed in New Zealand, is with a group that Variant believes could lead to discoveries related to kidney disease and metabolic disease.

When it comes to drug discovery and development, Farnum described Variant as agnostic to types of therapies.

“The modalities that can come out of this are potentially broad—small molecule, biologics, theoretically gene therapy—depending on the targets we find,” he said.

In some ways the company’s aims aren’t dissimilar from bigger players doing similar work, such as Thousand Oaks, CA-based Amgen (NASDAQ: AMGN), with its genomics research subsidiary, deCODE, and GlaxoSmithKline (NYSE: GSK), which invested $300 million in 23andMe in July 2018 as part of a four-year deal to develop drugs based on the company’s genetic insights.

Genomic insights from deCODE have prompted Amgen to develop drugs intended to mimic the impact of a genetic variant, and to shutter other programs. In January GlaxoSmithKline’s CEO Emma Walmsley told the Financial Times it aims to move a drug discovered as part of the 23andme partnership into the clinic by year’s end.

Learnings from population subgroups have already led to broadly applicable therapies. For example, studies of people with very high cholesterol levels and people with very low levels of cholesterol led to the discovery of the gene PCSK9, which plays a key role in the metabolism of this type of fat. Drug makers have since used those findings to develop biologic drugs that lower cholesterol by inhibiting PCSK9.

“They’re all following a basic strategy of, we need to get our hands on as many data points as possible,” Farnum said. “We believe strongly in the overall approach, but we think we have a better way to find these knockouts and rare variants, which is, instead of sequencing everyone who walks through the door of a hospital or university or wherever the partnership might be and sequencing them … we purposefully, from the beginning, do research and see where are we more likely to find these rare variants or these human knockouts that will be valuable for drug discovery and development.” (Human “knockouts” refers to people who are born missing a gene or genes of interest.)

Variant believes it will have better luck than its larger counterparts because nature has already done some of the screening for the startup. Populations in which the the company believes it is likely to find promising targets are those that have gone through what is known as a population bottleneck, or sudden reduction in size that reduces genetic variation; live in an environment that results in variants that provide an advantage there via a process known as selective pressure; and those with high rates of consanguinity, or reproductive relationships between people who are closely related.

In other ways, though, Variant is unlike typical drug discovery outfits. For instance, in addition to geneticists, molecular biologists, and anthropologists, Variant has a four-person ethics advisory board.

Farnum says the company is determined to ensure that the groups with which it works benefit from sharing their genomic data. Unlike, say, patient advocacy groups that team up with drug developers in the hopes that their support will lead to a new drug, some of the groups studied may be, uniquely, not in need of any therapy that emerges. (Others, though, may, if what Variant learns indications a genetic predisposition toward a deleterious condition.)

Given the groups’ disparate needs, talks intended to identify what each outlier group may desire in exchange for their contributions are happening on a case-by-case basis, he says.

The money Variant raised will go toward the project in New Zealand and others, in Nepal, Pakistan, and the Faroe Islands, an archipelago situated between Iceland, Norway, and Scotland. The startup also plans to spend some cash kicking off more projects, in places across South America, Africa, and Asia.

Lux Capital led Variant’s Series A round. As part of the deal Lux’s Josh Wolfe and Adam Goulburn and Biomatics Capital’s Julie Sunderland join the Variant Bio board.