Lyell spinout Outpace leverages de novo proteins to control cell and gene therapies

BY KAREN TKACH TUZMAN, SENIOR EDITOR

Outpace is taking cell and gene control technology originally in-licensed by Lyell out of that company’s toolbox and into a broad partnering model it thinks could transform the field.

Outpace Bio Inc. launched in March with a $30 million series A round led by Artis Ventures and Lyell Immunopharma Inc., with participation by Abstract Ventures, Civilization Ventures, Mubadala Capital, Playground Global, Sahsen Ventures and WRF Capital.

The company’s leadership and scientific teams include inventors of de novo protein design technology developed at University of Washington’s Institute for Protein Design (IPD), many of whom joined Lyell when their inventions were brought under the well-funded cancer cell therapy company’s roof. That IP is now assigned to Outpace.

“The reason we’re spinning out from Lyell is that even massively capitalized companies can’t chew on all the hypotheses we want to address while moving at full speed on internal clinical development,” said Outpace co-founder and CEO Marc Lajoie. “We have a lot to offer the field, and Lyell will benefit from that.”

Outpace is developing “a whole platform of control modalities” to program cell and gene therapies for greater potency and safety, said Lajoie.

That includes synthetic biology strategies using “AND” or “NOT” Boolean logic gates to recruit or exclude signaling molecules to specific subcellular locations, control protein turnover, or require a specific combination of signals to unlock a desired function.

By designing fit-for-purpose proteins that don’t exist in nature, the company can go beyond standard strategies that manipulate expression of individual genes.

“First-generation approaches have been mainly focused on over-expressing this gene, or knocking out that gene,” which can face limitations when a gene is integral to cell function in one setting but hampers it in another, said Lajoie. In contrast, he said, working at the protein level gives Outpace the ability to introduce desired changes in more context-specific ways.

Rather than develop its own pipeline, which would require investing in clinical development, the company is partnering with others to develop products via milestone- and royalty-driven deals. “The opportunity here is to create a step change in the field, and to be able to do that, we needed to focus our efforts on early development,” Lajoie said.

In some cases, Outpace and the partner company will jointly design the program from the bottom-up, while in others, the partner will come to Outpace and use the company’s existing technology to solve a specific problem in an ongoing program, said co-founder and CSO Scott Boyken.

While the products developed through collaborations will belong to the partner companies, the underlying control technologies developed through the process belong to Outpace. “We can leverage our progress on the products we’re working on to increase our efficiency for other projects in the future,” Lajoie said.

Outpace’s most advanced program is a collaboration with Lyell to develop cell therapies with controlled expression of an undisclosed cytokine. Other programs in development include a CAR cell therapy resistant to exhaustion, and a strategy for drug-induced gene regulation; the partnering status of these programs is undisclosed.

Lajoie said that while Outpace’s technology can be applied to any cell or gene therapy, the company’s “sweet spot” is T cell therapies for cancer.

Lajoie and Boyken co-authored a 2020 Science study with Fred Hutchinson Cancer Research Center professor Stanley Riddell showing the Co-LOCKR (Colocalization-dependent Latching Orthogonal Cage/Key pRoteins) technology they developed, part of Outpace’s IP portfolio, directed T cells to kill target cells expressing precise combinations of cell surface antigens, opening the door to more selective tumor targeting.

“There’s no single antigen that really distinguishes cancer cells from healthy cells, but there are aberrant combinations of antigens. That’s the unique handle we really wanted to pursue in that collaboration,” said Lajoie.

He believes the series A round will give the company approximately three years of runway.

At least two other companies have been founded to develop synthetic biology control mechanisms for partners’ cell therapies.

Cell Design Labs Inc. was acquired by Gilead Sciences Inc. (NASDAQ:GILD) for $175 million up front and $322 million in total milestones after Gilead’s 2017 acquisition of Cell Design Labs’ partner, Kite Pharma Inc. The University of California San Francisco spinout, which raised $34.4 million in venture funds, developed technology to control CAR T cell function; its UCSF founders published two Science Translational Medicine studies on the technology last month.

Senti Biosciences Inc., which raised a $105 million series B round in January and a $53 million A round in 2018, has both a pipeline strategy and a partnering model.

The company is developing its own allogeneic CAR NK cell  therapies, and in April announced a collaboration with the Spark Therapeutics unit of Roche (SIX:ROG; OTCQX:RHHBY) to develop cell type- and disease specific-synthetic promoters for gene therapies directed at the central nervous system, eye or liver. Senti received an undisclosed upfront payment and is eligible for additional payments and royalties, with a total potential deal value exceeding $645 million.

COMPANY PROFILE
Outpace Bio Inc.
Seattle, Wash.
Technology: Control technologies for cell and gene therapies based on synthetic biology techniques including de novo protein design
Origin of technology: University of Washington and Lyell Immunopharma Inc.
Disease focus: N/A
Clinical status: N/A
Founded: 2020 by Marc Lajoie and Scott Boyken
Academic collaborators: University of Washington
Corporate partners: Lyell Immunopharma Inc.
Number of employees: 19
Funds raised: $30 million
Investors: Artis Ventures, Lyell Immunopharma Inc., Abstract Ventures, Civilization Ventures, Mubadala Capital, Playground Global, Sahsen Ventures, WRF Capital
CEO: Marc Lajoie
Patents: 6 issued covering protein design, protein assemblies, and control technologies

‍

‍