Welcome to Talking Precision Medicine (TPM podcast) — the podcast in which we discuss the future of healthcare and health technology, and how advances in data and data science are fueling the next industrial revolution. 

What a pleasure to sit down with my long time colleague and friend, Art Krieg, to discuss his latest venture, Zola Therapeutics, and his adventures in the great outdoors. Art has launched and exited a number of innovative biotechs, each time delving deeper into mechanisms by which we can harness the immune system for therapeutic purposes. Join us as we discuss how — despite a well earned retirement — the siren song that led to Zola was strong enough to get Art back in the game.

Come on in and have a listen.

Links:

• Art Krieg on LinkedIn
• Timmerman Traverse
• Art Krieg and Genialis’ previous collaboration on Xerna™ TME Panel

 

Episode highlights:

 

Zola Therapeutics

• Zola Therapeutics is a biotech company focused on pioneering cancer immunotherapy through novel immune system activators.

“I thought that after Regeneron acquired Checkmate Pharmaceuticals [Art’s previous company], I was going to retire and that I was done. But I kept thinking about how the immune system works and what we were missing with the DNA. All along, I was thinking that this is a defense mechanism that we’re trying to harness. I started thinking more about what we are really trying to mimic. I realized that what we really want to do is trick the immune system into thinking there is a retroviral infection in our own cells, because a retrovirus copies its genome into our cells.”

Scientific Foundations and Innovations

• Zola Therapeutics is leveraging natural immune mechanisms, specifically focusing on nucleic acid immunity, which includes a new class of compounds for immune system activation.
• Art Krieg discusses the historical context of immune stimulatory mechanisms, starting from bacterial CRISPR systems and shares his journey from discovering immune stimulatory CpG DNA to developing a potent combination of RNA and DNA for cancer immunotherapy.
• Zola is developing RNA-DNA hybrids that mimic viral infections, which could trigger the strongest immune responses by simulating a retroviral infection within cells.
• They are currently scaling up their lead compound and preparing for preclinical trials in animals, with plans to initiate human trials in early 2026.

“I hypothesized that this RNA-DNA structure ought to be the strongest danger signal that the immune system could possibly detect as a sign of this infection. And so I had a contract lab synthesize some new designs of RNA-DNA hybrids that I thought would mimic this. And one of those was just extraordinarily active. It was more than 10 times more potent than the strongest activator that we’d ever seen before. Plus, it activates additional cell types that we had never stimulated with our previous compounds. And I just thought, you know, I have to start a new company and develop this.”

Unique Business Model

• The company aims to independently finance early stages of development to maintain strategic control without heavy reliance on venture capital.
• Unlike traditional biotechs that partner with a single pharma, Zola plans to license its diverse compounds to multiple pharmaceutical companies, ensuring broad utilization and development.
• This strategy is designed to produce a range of activators for different immune targets to maximize their therapeutic potential and reach.

The Future of Cancer Immunotherapy

• Art Krieg reflects on the evolution of cancer therapies, emphasizing the need for new strategies that integrate immune system activation with existing treatments.

“I think the cancer immunotherapeutic landscape will involve much less traditional chemotherapy. And I think that CAR T therapies will be replaced by these CD8 T cell inducers. Instead of growing large numbers of CD8 T-cells outside the body and giving them back to patients, we will be able to induce them endogenously.  […] I think essentially, every cancer patient will be treated with the cocktail of one or more checkpoint inhibitors and an innate immune activator.”

Art Krieg’s Sport and Charity Involvement

• Art Krieg enjoys trail running and hiking, activities that he finds stimulate subconscious problem-solving related to his professional work.
• He participates in the Timmerman Traverse, a three-day hiking event across the Presidential Range, raising funds for various charities and engaging biotech executives in outdoor challenges.

“The surgeon told me it would be six months until I could run again. And I remember telling him: ‘Oh, well, that’s okay. Because that means I can run the Boston Marathon.’ This was September five and the Boston Marathon was April 15. And he looked at me like I was joking. And then he realized I actually wasn’t joking.”

 

This has been Talking Precision Medicine. Please subscribe and share our podcast with your colleagues, leave a comment or review, and stay tuned for the next episode. Until then you can explore our TPM podcast archive and listen to interesting guests from our past conversations.