Biotech vet Phil Greenberg on his new cancer-fighting startup and immunotherapy’s next phase

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Fred Hutch investigator and Affini-T co-founder Philip Greenberg. (Fred Hutch Photo)

Philip Greenberg has been trying to stop cancer for decades. With Affini-T Therapeutics, the Fred Hutchinson Cancer Research Center investigator may finally have his chance.

The company announced $175 million in funding last week to move cell therapies developed by Greenberg and his colleagues into the clinic.

Greenberg, based in Seattle, has co-founded biotech companies before. But none have advanced the anti-cancer technology he helped develop through clinical trials. He’s learned some lessons along the way, and he co-founded Affin-T Therapeutics with the aim of finally seeing clinical success.

“I’m a little late in my career now. And I wanted to see this through,” he told GeekWire in an interview.

The approach involves removing a patient’s T cells and engineering them to make a molecule that recognizes cancer cells, a T cell receptor (TCR). The cells are infused back into the patient where they bind to cancer cells and kill them.

In the early 1990s Greenberg co-founded Targeted Genetics. But it was “too early” for the technology to succeed, said Greenberg, and the company folded in 2009.  

In 2013, Greenberg co-founded Juno Therapeutics with other immunotherapy researchers. The Seattle company became a juggernaut, selling to Celgene five years later for more than $9 billion. But Juno ultimately developed a different type of therapy, T cells engineered with a chimeric antigen receptor (CAR).

CAR T cells can yield dramatic rates of remission in patients with certain blood cancers. And several are now on the market, including Breyanzi, Juno’s lead product. Many scientists, including Greenberg, view CAR T cells as a key example of the promise of immunotherapy.

The next frontier is solid tumors like breast and colon cancer. And that is where his approach has advantages, Greenberg said. CARs only work against a few targets on the surface of cancer cells. But TCRs can recognize proteins found inside cancer cells, including key “driver” targets that propel cancer forward.

More than 200 clinical trials are testing TCR therapies at multiple institutions worldwide, including at Fred Hutch. But Greenberg and his scientific co-founders Thomas Schmitt and Aude Chapuis at the Hutch are aiming beyond their institution.

Two T cells (red) attacking a cancer cell (white). (Baylor College of Medicine Image / Rita Elena Serda)

“You need a commercial partner in order to actually be able to treat any more than just a handful of patients,” said Greenberg. Cell therapy is labor intensive, and costly to develop and manufacture.

Enter Affini-T Therapeutics. Since launching last spring, the company has grown to 57 employees at its headquarters near Boston and labs in Seattle. Physician Jak Knowles left his position as a VP at Leaps by Bayer, which co-led the funding round, to become CEO and a co-founder of Affini-T.

Greenberg also receives research funding from the company. “They are giving us the latitude to get back into the lab and continue to make it better.”

Greenberg is hopeful that they’ve landed on the right research approach to bring the therapy to market. “I’m almost certain it’ll have anti-tumor activity,” said Greenberg. “What we’d like to see is tumor eradication. That’s really the goal.”

We spoke with Greenberg to learn about the new company and his approach to working with industry. The interview was edited for clarity and brevity.  

GeekWire: Tell us about the origins of Affini-T Therapeutics.

Greenberg: Originally when Juno was formed, it was part of the large picture of a company with a large bandwidth for bringing T cell therapies to patients. And the reality is that it wound up getting acquired by Celgene and then Bristol Myers Squibb. What was very surprising to me was the bandwidth shrunk rather than expanded. With all the extra resources, they focused on the development of reagents that were essentially already proven in the clinic. That was essentially two CAR T cell trials. They really lost momentum for going forward with any of the rest of the work. Ultimately, we got back most of our IP, which was still evolving, for T cell therapies.

GW: How did the company come together?

Greenberg: We weren’t necessarily looking for a company. We were looking to see if we could find somebody we could license this to and give us the resources so we can develop it. Jak Knowles was one of the investors we were talking to and he suggested that we should really do this as an independent company. It took off from there.

GW: Have you been involved in helping structure the company in way to help move your ideas and the therapy forward?

Greenberg: We wanted this to be something that would allow us to realize what has been our dream — to make this a therapy for patients. Our lab is good at discovery science, at asking questions, trying to solve problems, and then starting to move those forward. What we needed was a partner who would support our lab, and support the discovery science without essentially everything being a deliverable — to say, “go do some science, discover things,” and give us some bandwidth to ask adventuresome questions and hopefully uncover things that will be very useful. But then to take the things we have already validated and move them forward. Affini-T has been great at both of those things.

We already know immunotherapy unequivocally can work and have a real impact in cancer. The question is, where’s the bar? Where’s the upper limit? And we don’t know that yet. But we know it’s much higher than it is right now. And that’s really what the goal is.

Cell therapy companies use different approaches to engineer their cells. This is Affini-T’s secret sauce.

GW: What did you learn from your Juno experience and how is it affecting your work with Affini-T?

Greenberg: There comes this point with companies, at least from our prior experiences, where they become very focused and internal. As Juno expanded its internal programs, we knew less and less about what was actually happening there. It stopped being very collaborative.

So we’ve really tried to make clear from the beginning, and in the relationships as they’re evolving, that this has to be collaborative. There are some things that we as an academic lab will almost certainly do better than a company in terms of discovery. And there are some things that a company can do that just are totally impractical in an academic lab. Making something that little bit better is essential for an optimal product, but it’s not what drives the science.

There shouldn’t be a silo between the founders’ labs and the company. That just slows productivity and output, and so we’ve really tried to be open about this. We’re willing to share credits but it has to be collaborative. So far that’s working beautifully.

Philip Greenberg (center front) and members of his lab at Fred Hutch. (Fred Hutch Photo)

GW: Have you set up new structures to facilitate collaboration?

Greenberg: We are meeting much more regularly. We are making sure that when we present data that there’s data presentation by both groups, it can’t be just us describing what we’ve done. We need to understand what they’ve done, and we need to be able to critique it. We need to say: “that’s great” or “that’s disappointing,” and “why is that going so slowly” or “why did you go off on a tangent?” And they can say the same thing to us.

GW: Were you involved in building the company and finding the right partner and CEO?

Greenberg: Absolutely. As we were shopping, we didn’t have a CEO. And we met Jak and we interacted with him for two or three months before it came up that he might be interested in leaving Leaps by Bayer and becoming CEO. While he was helping us trying to form a company, he was providing enough intellectual insight that made it clear for us that that he would be a good CEO. And he of course had the business background as well. And then we’ve been part of the interview process for all the senior positions.

GW: What are you excited about for the future?

Greenberg: The field of immunotherapy has exploded in the last decade or more. For those of us who have been studying cancer immunology, to finally see it having an impact is extraordinarily gratifying. Now with synthetic biology, we can start not just improving on the immune responses to cancer but creating new immune responses. And the wonderment of science is that you can do all that now. We have no doubt that this is the end of the beginning, and we are moving into the next phase.



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