Investing in Arda Therapeutics

Cells are the functional unit of life. And yet, they are also the functional units of disease. All human diseases are ultimately caused by dysfunctional cellular function in some fashion—whether by excessive cell growth, hyper- or hypo-activity, altered cell-cell interactions, or changes in the biomolecules a cell produces. And yet, the vast majority of therapeutics approved or in development today act via modulating the activity of individual proteins or other biomolecules within or expressed by the cell. In many cases, this can be an effective strategy. However, given the complexity of cellular function and evolved redundancies in regulatory networks, the modulation of individual protein targets or pathways (rather than cells) may leave significant potency on the table. Perturbing pathways might win battles, but triumph in the war on disease may sometimes require eliminating the true enemy: bad cells.

In oncology, our most potent cancer medicines—including chemotherapy—work by eliminating cells. Indeed, the entire field of oncology therapeutics has been focused on tumor cell clearance as a mechanism of action for decades. Several exciting recent additions to our cancer drug arsenal—CAR-T cells, antibody drug conjugates, T cell engagers, and radiopharmaceuticals—fundamentally depend on our ability to identify pathogenic (bad actor) cell populations and then target them precisely for killing. And the current wave of targeted cell clearance modalities in oncology has been further buoyed by advances in single cell profiling (allowing better differentiation between tumor versus healthy cells), and novel engineering approaches (enabling us to design drugs that can even more selectively kill those tumor cells).

If these modalities have proven to be so effective (in some cases, even curative) against cancer, is there a role for them outside oncology, in the treatment of chronic diseases that might also be driven by a population of bad-actor cells?

Arda Therapeutics is building upon exactly this bold hypothesis: that selective cell killing can be a highly effective and safe therapeutic strategy in many diseases beyond cancer where excessive cell proliferation or activity is the primary driver of pathogenesis. Or, in other words, rather than tinkering with individual proteins or signaling pathways, why not remove the root problem: the entire cell?

Arda has built a sophisticated single-cell discovery platform, leveraging single-cell RNA sequencing and single cell proteomics, to identify disease-causing pathogenic cells, along with their unique surface markers. These cell surface markers then act as “cellular handles” for antibody-based biologics to specifically recognize and trigger selective elimination of only harmful pathogenic cells, preserving nearby healthy tissue. This strategy could have broad applicability across a wide range of disorders from fibrosis to autoimmune disease, and leverages many of the modality engineering principles worked out over the past decade in oncology. To use the language of Sun Tzu, by knowing precisely who the enemy cells are in each disease and by building the best warrior to attack them, Arda is betting that our drugs can fight chronic disease safely, avoiding the “disaster” of toxicity.

At a16z, we love product focused biotech companies with a repeatable, data-informed platform where continual learning enables rapid iteration and efficiency. Arda has been a model company proving that this is possible. When we first invested in Arda at the Seed, the company was little more than a big idea and a motivated, scrappy founding CEO, Adam Freund. Alongside Arda’s co-founder and CTO Rémi Laberge, Adam has now turned the team into a fully integrated therapeutic development organization, marching towards the clinic with multiple programs that have demonstrated impressive preclinical efficacy and safety. It was this excellence in execution combined with a paradigm-shifting vision that got us excited to lead Arda’s Series A.

Becky has known Adam for almost 20 years; they first met at UC Berkeley orientation, where both were starting graduate studies in Molecular and Cellular Biology. Adam has always been a mold-breaker, unafraid to do things differently and tackle the biggest of problems. When he arrived at Cal, he was the only student in the class who had never before picked up a pipette, having come from a background in materials science and engineering, not biology. Unlike most students, he came in laser focused with a clear vision of what he wanted to do: tackle the biggest disease of all—aging. After earning his early drug development chops as part of the founding scientific team at Calico Life Sciences, Adam decided it was time to make the jump and turn his big idea into a reality.

We were thrilled when Scott Turner decided to make the jump as well, and joined Arda as CSO earlier this year. Scott came to Arda from Pliant Therapeutics, where he also served as CSO and led development of Pliant’s fibrosis discovery platform, resulting in a successful Phase 2a study for the anti-fibrotic therapy Bexotegrast. Scott brings uniquely well-suited R&D experience to Arda, which will be invaluable as we rapidly advance towards becoming a clinical stage company.

It has been a distinct pleasure to have worked with the Arda Therapeutics founding team since inception. If our mission to “target cells—not pathways” excites you, join us!