Health/Life Sciences

Juno’s lasting legacy: How the cell remedy juggernaut influenced biotech in Seattle and past

Juno’s scientific co-founders, from left: Michel Sadelain, Michael Jensen, Isabelle Rivière, Philip Greenberg, Stanley Riddell, and Renier Brentjens. (Juno Therapeutics Photo)

When Juno Therapeutics launched in 2013, cell therapy was a nascent field. Early clinical studies were showing dramatic rates of remissions in leukemia patients treated with their own immune cells, rewired to attack tumors. The data was exciting, but the technology was young and later-stage clinical trials were still in the future.

Juno’s founders and investors saw a new way to treat cancer, and they ran with it. The Seattle company raised more than $300 million and went public within a year of its launch, ultimately selling for more than $9 billion in 2018 to Celgene.

ARCH Managing Director Robert Nelsen. (ARCH Photo)

Juno’s success reverberated throughout biotech in Seattle and beyond, fueling interest in cell and gene therapy and providing a blueprint for the next generation of startups founded in its wake.

“It provided huge capital influx to the region and to budding scientists and entrepreneurs,” said Robert Nelsen, managing director and co-founder of ARCH Venture Partners, an early investor in Juno and new biotech companies built in its mold.

In some ways, Juno resembles a Seattle version of PayPal, which had its “mafia” of executives and early employees who later launched other successful companies like Yelp, YouTube, and Tesla.

Juno veterans went on to start or fill leadership positions at Sana Biotechnology, Lyell Immunopharma, Umoja Biopharma, Shape Therapeutics, GentiBio, Eliem Therapeutics, Genemod, Century Therapeutics, Silverback Therapeutics, Tune Therapeutics, Affini-T Therapeutics, and others. All these companies are based in the Seattle region or have operations there.

Sana CEO Steve Harr. (Sana Photo)

“It validated Seattle as a hub for both cellular and gene therapies, as well as around immuno-oncology,” said former Juno CFO and Sana CEO Steve Harr. Juno catalyzed “a group of highly talented individuals around an exciting technology that really accelerated Seattle’s competitiveness,” added Harr, who is also a Sana co-founder.

Sana’s roster is peppered with Juno veterans, including Juno co-founder and CEO Hans Bishop, who co-founded Sana and went on to be CEO of Menlo Park, Calif., company GRAIL, prior to its acquisition for $8 billion.

Bishop and other Juno employees once worked at early cell therapy company Dendreon, co-founded by early Seattle biotech icon Christopher Henney. Henney left a position at Fred Hutch in 1980 to co-found Immunex and Icos, two of Seattle’s earliest biotech companies.

Spawning new companies

Former employees at Juno went on to start or join a flurry of biotech companies.

Five years ago, the Seattle biotech scene was still recovering from the loss of anchor biopharma company Amgen. But the industry soon soared.

The building of Juno “allowed companies like Sana and Lyell and GRAIL and others to flower based on the relationships built,” said Nelsen, who was also a member of Juno’s board of directors.

Life science companies in the Seattle area raised a whopping $1.11 billion in venture capital 2021, more than twice the amount in 2019, according to real estate firm CBRE. Life sciences employment has also climbed.

Washington Research Foundation/WRF Capital Managing Director William Canestaro. (Photo courtesy of William Canestaro)

Some of Seattle’s success can be attributed to a global biotech boom, and to other biotech stars like Adaptive Biotechnologies and Seagen. But the region was well prepared to prosper.

“Juno was transformative for the Puget Sound biotech community,” said William Canestaro, managing director of early Juno investor Washington Research Foundation/WRF Capital, in an email.

“First, it brought great executive talent like Steve Harr to the area. Second, it brought real expertise on cell therapy manufacturing,” said Canestaro. “Because Juno was one of the first clinical stage cell therapy companies, it had to quickly recruit talent up and down the organization. These people became the experts in regulatory, manufacturing, and clinical operations for cell therapy.”

Juno spun out of Fred Hutchinson Cancer Research Center; Seattle Children’s; and Memorial Sloan Kettering Research Institute, building up their leadership in cell therapy development. Fred Hutch owned 4.6% of Juno at its IPO, and the institution’s research budget fattened with the company’s success.

Fred Hutch continues to foster new companies, most recently Affini-T Therapeutics, co-founded by Fred Hutch researcher and Juno co-founder Philip Greenberg. Lyell’s co-founders include Juno co-founder Stanley Riddell, a Fred Hutch researcher.

Cell therapy spinouts from Seattle Children’s include Umoja, co-founded by Children’s investigator and Juno co-founder Michael Jensen, and GentiBio, which aims to expand cell therapy’s reach to type 1 diabetes and other autoimmune conditions.

Juno’s influence has also expanded to companies beyond Seattle and the U.S.

Juno helped globalize its cell therapies with JW Therapeutics, a Chinese company it co-founded in 2016. The co-founders of Paris-based Mnemo Therapeutics include Juno co-founders Michel Sadelain and Isabelle Rivière, both investigators at Memorial Sloan Kettering.

“CAR T” cell therapies developed by Juno and its competitors are now approved for a variety of blood cancers, and the treatment is offered at an expanding number of centers worldwide.

Former Juno CEO Hans Bishop (left) speaking to Juno VP of Research and Receptor Discovery Francois Vigneault inside his lab. Vigneault is now CEO of Shape Therapeutics. (GeekWire Photo / Kurt Schlosser)

New deals, new backers

Juno’s outsized financial deals and fresh investors shifted the mindset of the biotech industry, said Nelsen, who has been called “the biggest dreamer in biotech investing” by Forbes.

Juno’s Series A round of $176 million was close to a record at the time. It brought in the Alaska Permanent Fund, owned by the state of Alaska, through a chance airport encounter between a fund manager and Juno co-founder and Fred Hutch investigator Larry Corey. Alaska’s involvement was an early example of increasing investment by government sovereign funds and other non-traditional funders in biotech.

Fred Hutch researcher and Juno co-founder Larry Corey. (Fred Hutch Photo)

The Series A round was followed rapidly by a $134 million Series B round.

“We did the deal when people thought you can’t make real returns in biotech,” said Nelsen. “It broke the mold of financings, bringing in sovereign wealth funds like Alaska into the A and investors with huge assets into the B, where they had waited for IPOs previously.”

Juno’s example, said Nelsen, “paved the way for a sea-change in how biotech companies were financed and a permanent change in the level of funding biotech could access, allowing biotech to be more independent from pharma.”

ARCH pulled in about $922 million with Juno’s acquisition, according to an analysis of SEC filings by Endpoints News. And the firm has plowed a chunk of that back into its investments in companies like Sana, Lyell and Seattle-based immunotherapy companies Mozart Therapeutics and OncoResponse.

Juno’s $264 million IPO was the biggest on record for biotech, according to Renaissance Capital. Juno’s outsized financial deals were later surpassed, as large raises and early IPOs became more common.

Rick Klausner, co-founder of Juno, Lyell, and GRAIL, and chief scientist of Altos Labs. (Lyell Photo)

Sana pulled in $700 million in venture funding and last year had a $587 million IPO, the largest ever for a preclinical biotech company. Lyell raised close to $500 million and went public in a $425 million IPO last summer; the company announced its first clinical trial in December. And Umoja recently raised more than $260 million in Series A and B funding.

Harr said it simply takes a lot of money to build a cell and gene therapy company.

“Juno recognized the importance of capital in building a successful, fully integrated company. And it realized that cell and gene therapy, because of the complexities of manufacturing, is just more expensive than traditional drug development.” said Harr. “You can not rely upon external parties to help you move forward.”

Juno’s CAR T therapy involves removing immune cells from a patient, engineering them to attack their tumors, and infusing them back into the patient. Cell therapy is labor-intensive, and costly to develop, manufacture, and deploy.

“We had to raise more money because it was a necessity,” said Harr of Juno.  

Meanwhile, Nelsen and Juno alums are dreaming up something even bigger. Boston and California-based Altos labs launched this January with $3 billion in financing and a mission to “rejuvenate” cells. Bishop is Altos’ president and Richard Klausner, a co-founder of Juno, GRAIL and Lyell, is its chief scientist. ARCH’s Altos investment is its biggest to date, Nelsen told STAT News.

Embracing academia

Juno also approached its academic collaborations with a fresh approach, said Harr.

Academic researchers traditionally hand off their technology to biopharma and head back to the lab. The technology is licensed and sometimes disappears into a black box.

“We tried to reset the model to one where the innovators were a big part of the scientific strategy and execution going forward,” said Harr.

Juno’s launched with a powerhouse lineup of scientific co-founders, and the company collaborated with academic researchers in an “ongoing technology transfer,” said Harr.

“Instead of license and move on, it was license and really work together to push the field forward,” said Harr, who added that the model is more common and increasingly sought after by academics who are passionate about seeing their ideas succeed in the clinic.

How CAR T cell therapy works. Researchers engineer T cells to make “CAR” molecules that recognize tumors. (Bristol Myers Squibb Image)

Making something new

In 2017, the U.S. Food and Drug Administration approved the first CAR T cell therapies, but they were not from Juno. The company was beaten to market by Novartis and Kite Pharma, shortly after its acquisition by Gilead for $11.9 billion.

Juno’s scientific momentum had stalled a year earlier, after a series of deaths in its clinical trials. The company’s therapy ultimately met the bar of the FDA, after a pivot to a different CAR T cell program.

The basis of CAR T cell therapy: a human T cell. (U.S. NIAID Photo)

Juno’s CAR T cell product, Breyanzi, was approved by the FDA last year under the stewardship of Bristol Myers Squibb, which inherited Juno’s operations after buying Celgene. Clinicians have also learned how to better manage side effects of the novel therapies.

“This [therapy] and others in the field have provided important proof of principle that we can take human cells, gene modify and re-arm them safely, and have a really important clinical effect,” said Harr. “It’s really stimulated a whole field, both in oncology and beyond. And that’s true in Seattle and it’s true more broadly.”

Breyanzi’s approval was supported in part by a clinical trial led by Seattle Children’s that showed initial remission in 93% of lymphoblastic leukemia patients who had relapsed or failed to respond to standard treatment. After one year, half were still in remission.

Last week, cell therapy pioneer Carl June and his colleagues at University of Pennsylvania, a partner of Novartis, reported that two of the first patients to ever receive CAR T cells were disease-free after ten years. U. Penn research has fostered a parallel biotech ecosystem in Philadelphia, known as “Cellicon Valley.”

CAR T cell therapies are now approved for various types of leukemia, lymphoma, and myeloma, including some cleared for children. Worldwide biotech funding for cell-, gene-, and tissue-based therapies reached a record $23 billion last year, with about half going to cell-based immunotherapies, according to the Alliance for Regenerative Medicine.

There is a lot more to do. Preventing relapse is an ongoing challenge and the patient pool is limited. Breyanzi, for instance, is only approved for adults with certain B cell lymphomas who do not respond to conventional therapy or are resistant to it. And CAR T cell therapy typically costs hundreds of thousands of dollars.

BMS inherited Juno’s headquarters in Seattle’s South Lake Union neighborhood. (BMS Photo)

The next frontier

Bristol Myers Squibb is building the next generation of cell therapies in the Seattle region, where it employs more than 1,240 people.

“Our presence here is strong,” said BMS Seattle head Teresa Foy in a previous interview with GeekWire. “We’re hiring and we’re growing.”

The pharma giant and its biotech competitors take different research approaches, but they all have the same aim: to reach more patients with cell therapies.

Lyell chief medical officer and head of development Tina Albertson. (Lyell Photo)

“We really realized there were barriers to these cells working in all patients,” said pediatric oncologist Tina Albertson, former VP of global drug development at Juno.

“This has led a lot of us to move on to try to move into companies and groups that are trying to overcome these barriers,” added Albertson, who is now chief medical officer and head of development at Lyell.

Scientists are working on new ways to engineer therapeutic cells to better seek out and kill tumor cells. They are trying out different cell types, and adding new genes and taking out others. Many researchers are also testing “off the shelf” therapies from donor cells or stem cells, with the aim of making cell therapies cheaper and easier to make.

Solid tumors, like breast and lung cancer, are the next frontier.

Because of the complexity of cell therapy, “it’s incredibly valuable to hire someone who has been in the field,” said Albertson.“All of these new companies that those of us in the field for a long time are now joining are going to be learning alongside us, as we approach the next challenges in cell therapy.”

Seattle’s new biopharma companies compete for the region’s highly-trained workforce, and they also lure talent to the area. And while the effort to find workers can be intense, the result is a burgeoning biotech ecosystem and a host of new potential therapies, some starting to enter clinical trials.

Said Harr: “For Sana, I’d say the most important element in our success is people.”

Here are some of the biotech companies with a presence in the Pacific Northwest that have connections to Juno founders, executives and scientists.

Sana Biotechnology

Location: Headquarters in Seattle. Locations in South San Francisco, Calif. and Cambridge, Mass.

Co-founder connection: Three of Sana’s co-founders hail from Juno: Sana CEO Steve Harr (Juno CFO); Sana chief medical officer Sunil Agarwal (Juno R&D head); and Sana board chair Hans Bishop (Juno CEO, also former CEO of GRAIL).

Other Juno connections: LinkedIn shows a raft of Juno alums at Sana, from its controller to an executive assistant. Juno alums include Nate Hardy, chief financial officer; Christian Hordo, chief business officer; Robin Andruvelich, chief people officer; Farah Anwar, head of development operations and inclusion, diversity and equity; Paul Brunetta, head of clinical and translational science; and Jim MacDonald, general counsel. Patrick Yang is a former VP at Juno and is a board director at Sana and several other biotech companies, and he is a co-founder of cell therapy biotech Acepodia. Robert Nelsen, managing director at ARCH Venture Partners, a key Juno and Sana investor, is also a Sana director.

Read more about Sana.

Lyell Immunopharma

Location: Headquarters in South San Francisco, Calif., with locations in Seattle and Bothell, Wash.

Co-founder connection: Lyell co-founder and former CEO Rick Klausner was also a Juno co-founder. Klausner was also formerly head of the U.S. National Cancer Institute and head of global health at the Bill & Melinda Gates Foundation. Lyell scientific co-founder, Stan Riddell, a Fred Hutch investigator and UW professor, was also a Juno co-founder.

Other Juno connections: Lyell’s chief medical officer Tina Albertson was former VP of global drug development at Juno, and Lyell’s VP of process sciences Allison Bianchi was formerly a senior director at Juno and a postdoctoral scientist at early Seattle biotech company Immunex.

Umoja Biopharma

Location: Headquarters in Seattle, building manufacturing plant in Louisville, Colo.  

Co-founder connection: Umoja co-founder Michael Jensen was a Juno co-founder; he is also a UW professor and chief therapeutics officer at Seattle Children’s, where he leads a large cellular therapy  group. Umoja CTO and co-founder Ryan Crisman was former technical operations leader at Juno. 

Other Juno connections: Juno alums include Umoja’s Head of Immunology Ryan Larson and VP of clinical development and operations Jacob Garcia.

Read more about Umoja.

Shape Therapeutics

Location: Seattle

Co-founder connection: Shape co-founder and CEO Francois Vigneault was formerly VP of research at Juno. 

Other Juno connections: Juno alum at Shape include Adrian Briggs, VP and head of platform technologies; David Huss, head of research; Ken Prentice, VP and head of process and product development and Melissa Works, head of pipeline research, and others.

Read more about Shape Therapeutics.

Affini-T Therapeutics

Location: Headquarters in Boston, with a research lab in Seattle.

Co-founder connection: Affini-T Therapeutics scientific co-founder and Fred Hutch investigator Philip Greenberg was a Juno co-founder.

Read more about Affini-T.

Tune Therapeutics

Location: Based in Seattle and Durham, N.C.

Co-founder connection: Tune co-founder and CFO Akira Matsuno is a former program lead at Juno and former head of corporate development at Lyell.

Other Juno connections: Technical operations head Heidi Zhang was a Juno executive director, and research head Blythe Sather was an associate director at Juno and a senior director at Lyell.

Read more about Tune.

GentiBio

Location: Headquarters in Boston with operations in Seattle

Co-founder connection: GentiBio co-founder and CTO Andy Walker is a former senior VP of technical operations at Juno. He is also formerly CEO of Jewel Biotherapeutics.

Other Juno Connections: Several fomer Juno employees work at GentiBio, including Mirna Mujacic, GeniBio’s senior director, head of process and analytical development; and Tom Crevier, senior director automation, informatics and IT, who is also a Microsoft alum.

Read more about GentiBio.

Eliem Therapeutics

Location: Redmond, Wash.

CEO connection: Eliem president and CEO Bob Azelby is a former Juno executive VP and chief commercial officer. Prior to leading Eliem, Azelby was CEO of Bothell, Wash.-based Alder BioPharmaceuticals, which was acquired by H. Lundbeck for $2.3 billion in 2019. He also previously worked at Amgen.

Read more about Eilem.

GeneMod

Location: Seattle

Co-founder connection: CEO and co-founder Jacob Lee is a former Juno engineer in technology strategy and innovation

Read more about GeneMod.

Century Therapeutics

Location: Based in Philadelphia with a Seattle “Innovation hub”

Key Juno Connections: Century’s president of R&D, Hy Levitsky, is a former Juno CSO. Nikolaus Trede, Century’s VP of early development, is a former Juno senior medical director.

Read more about Century.

Sonoma Biotherapeutics

Location: South San Francisco and Seattle

Key Juno connection: Michelle Blake, Sonoma VP of translational sciences, is a former principal scientist at Juno, and also a former senior director at Shape Therapeutics. 

Read more about Sonoma.

Silverback Therapeutics

Location: Seattle

Key Juno Connection:  Valerie Odegard, President and CSO at Silverback was a former Juno VP of research. Bob DuBose, Silverback’s executive director of research informatics is also a Juno alum.

Read more about Silverback.

Other companies based in the Pacific Northwest or with a Pacific Northwest presence that employ Juno alum:

Seattle-area:  2seventy bio (formerly Bluebird Bio), Zymeworks, Chinook, Orca Bio, Modulus Therapeutics, Seagen, Galera Therapeutics, Neoleukin Therapeutics, Just – Evotec Biologics. Vancouver, B.C.-area: STEMCELL Technologies, Zymeworks and Notch Therapeutics.

Some of the companies outside of Seattle with key Juno connections:

Mnemo Therapeutics: Juno co-founders Isabelle Rivière and Michel Sadelain co-founded this Paris-based biotech company. Both are also investigators at Memorial Sloan Kettering Cancer Center.

Vir Biotechnology: This San Francisco biotech was co-founded by Larry Corey, Juno co-founder and former president and director of Fred Hutch. Corey also co-founded South San Francisco-based CERo Therapeutics.

Altos Labs: This venture to “rejuvenate” cells launched with $3 billion in investment this January with Hans Bishop, Juno CEO and co-founder as president. Juno and Lyell co-founder Richard Klausner is its chief scientist.

Acepodia: Mark J. Gilbert, a former Juno chief medical officer, is VP of R&D at Alameda, Calif.-based Acepodia, co-founded by Juno alum Patrick Yang. Gilbert is also chief medical officer at the Chinese cell therapy biotech JW Therapeutics, formed as a joint venture with Juno and Chinese company WuXi AppTec. Gilbert is also a former employee of early Seattle biotech company Immunex.

Day One Biopharmaceuticals: Samuel Blackman, co-founder and chief medical officer of this South San Francisco-based biotech is a former Juno senior medical director.

Miltenyi Biomedicine: In 2017 this German cell therapy company acquired Living Pharma, co-founded by Ronald Dudek, former VP of commercial strategy at Juno. Dudek was a co-founder of cell therapy company Restoration Oncology, which had earlier licensed technology from Memorial Sloan Kettering, according to an essay by Atlas Venture partner Bruce Booth, “Two Really Big Fish that Got Away.”  Dudek was also previously marketing director at Seattle T cell therapy company Xcyte Therapies, where Christopher Henney served as board chair, and ARCH’s Robert Nelsen was an investor. Xcyte folded in 2005 after an FDA decision stymying a clinical trial, which Nelsen described at the time as “a .50-caliber shot in the heart.”

Editor’s note: Charlotte Schubert previously worked as a science editor and writer at Seattle Children’s Therapeutics (SCTx). Michael Jensen, Juno and Umoja co-founder, is vice president at SCTx.

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