By Deborah Borfitz 

December 10, 2020 | Several years ago, Seattle Children’s Research Institute realized it would need to “think and act” more like a biotech company to ramp up the development of medicines for pediatric use to treat cancer and other typically orphan-status diseases of childhood. The market for pediatric drugs is relatively small, which is why the pharmaceutical industry has been reluctant to study medicines in kids, says Michael Jensen, M.D., chief therapeutics officer for Seattle Children’s Hospital as well as vice president of its nonprofit spinout, Seattle Children's Therapeutics, which launched earlier this year.  

From the standpoint of investors looking for a return on their dollar, the reluctance is understandable. Few drug candidates are ultimately approved by the U.S. Food and Drug Administration (FDA) and, when they are, the journey often takes 10 years and up to a billion dollars, Jensen says.    

From the perspective of sick children, their families, and the doctors who care for them, the shortage of treatments FDA-approved for pediatric use can be unnerving, he says. An overwhelming number of drugs being prescribed to children have only been labeled for use in adults, which increases the risk of adverse events and poor outcomes with far-reaching and potentially deadly consequences.   

Many pediatric diseases and all pediatric cancers are considered rare diseases, 90% of which have no FDA-approved treatment, says Jensen. Even when grants are secured from the National Institutes of Health, the amount generally falls short of what’s needed to get a new drug into a phase 1 clinical trial by tens of millions of dollars.    

The aim of Seattle Children’s Therapeutics is to create a new model of drug development where all the component parts—from basic research in the lab and therapeutics manufacturing to regulatory compliance and clinical trials management—are working in sync to accelerate and scale the availability of next-generation cell and gene therapies that meet the unique needs of the pediatric population, says Jensen.  

Established as a unit in the research division of Seattle Children’s, the new not-for-profit entity builds on one of the nation’s largest pediatric cancer immunotherapy programs focused on chimeric antigen receptor (CAR) T-cell immunotherapy for kids with leukemia, lymphoma, brain tumors, and solid tumors. Seattle Children’s Therapeutics currently has 12 pediatric oncology CAR T-cell clinical trials accruing patients around the country, Jensen says, with plans to expand to a variety of other childhood diseases amenable to cell and gene therapies such as juvenile diabetes and lupus.  

“Some institutions have some of the [same] parts, but they’re not organized in the same way,” he continues. Seattle Children Therapeutics has truly “broken the status quo” of what a pediatric research organization looks like and taking “a fairly global perspective on what kids need in terms of therapies … both today and in the future.” 

Jensen’s prior experience in the biotech world equipped him to lead the new nonprofit, he says. The lifelong academician has been affiliated with the University of Washington School of Medicine for the past decade, where he helped develop the CAR T-cell technology that launched Juno Therapeutics—subsequently sold to Celgene and, more recently, Bristol-Myers Squibb. “The product we pioneered for pediatric leukemia, and became Juno’s flagship product, is now on the cusp of receiving FDA approval … and being available to patients around the world.”    

Once approved, a portion of global sales proceeds will come back to Seattle Children’s to fuel more research, Jensen notes. As cofounder of Juno Therapeutics (and several other biotechs since then), he has personally benefitted from having “an insider’s view on how to form an organized, effective and impactful drug development enterprise and to get all the people and talent aligned on that mission.”  

Pillars Of Support 

An unusual set of “wonderful circumstances” over the past decade has made creation of Seattle Children’s Therapeutics possible, says Jensen, including a decision by leadership of the not-for-profit hospital to invest philanthropic funds in manufacturing facilities meeting the strict standards of the FDA. Last year, Seattle Children’s opened one of the largest therapeutic cell manufacturing facilities—called the Cure Factory—capable of producing upward of 1,000 cell therapy products for clinical trials every year.  

The Cure Factory occupies the top floor of the new, 540,000 square-foot “Building Cure” facility of Seattle Children’s Research Institute. Soon to open nearby is a second manufacturing facility, VectorWorks, where viral vectors (the genetic modification part of immunotherapy) will be made. “We need to manufacture that part of the therapeutic puzzle because right now there is not enough capacity to make those vectors in the U.S.,” Jensen says.  

It is exorbitantly expensive to manufacture vectors, which can hold up the start of clinical trials with CAR T-cells for years, he notes. VectorWorks could potentially serve as a contract manufacturer of vectors for other academic institutions and young biotech companies in the future. 

Seattle Children’s Research Institute—founded 14 years ago and now comprising one million square feet of clinical, laboratory and office space—had already built out all the necessary infrastructure “to go from the last mouse experiment to the first child being treated at Seattle Children’s Hospital,” continues Jensen. In fact, Seattle Children’s Therapeutics partners with over 30 pediatric oncologists with the institute’s Cancer and Blood Disorders Center to provide clinical research support for the open phase 1 and phase 2 CAR T-cell trials.   

As an academic entity, the research institute wasn’t vertically integrated in the way envisioned by Seattle Children’s Therapeutics “where every part of the enterprise knows what the other part is doing and everyone is working in synchrony,” says Jensen, explaining the genesis for the spinout. But financing drug development is a constant challenge for both organizations.   

“Drug development costs a lot of money and we don’t have stock options and IPOs, and we don’t do rounds of Series A investment, so we have to fund [efforts] in a much more multifaceted way,” Jensen says. Among the sources of charitable dollars specific to the pediatric cancer immunotherapy work being done by Seattle Children’s Therapeutics are CELLEBRATION, an annual fundraising event held virtually this year that raised $1.3 million from supporters around the world. 

The national grocery chain, Safeway Albertson’s, has raised more than $6 million over the last five years for immunotherapy research at Seattle Children’s, he adds. Families of patients can also start a “guild” as a way of contributing to this specific area of research. One called ImmunoMomentum! is currently endeavoring to raise $1 million. 

Profit-generating activities, including royalties generated by patent licenses, are expected to be major sources of revenue for Seattle Children’s Therapeutics over the long term, says Jensen.   

Collaborative Approach 

Among the near-term plans of Seattle Children’s Therapeutics is to establish more sponsored research agreements mirrored after its first partnership with Bluebird Bio, which will soon yield a clinical trial for children with acute myeloid leukemia (AML), says Jensen. While predominantly a cancer that strikes adults, AML also occurs in about 500 children in the U.S. each year—frequently as a second cancer among children treated for other cancers. 

Seattle Children’s Therapeutics will also serve as an incubation hub to support biotech development efforts that “pay particular attention to applications in children,” he adds, citing the sponsored spinout of Umoja Biopharma as an example. Umoja is focused on developing a new approach to cancer therapy that retools a patient’s immune system in vivo, and the intellectual property originated with Seattle Children’s Research Institute and Purdue University. Jensen is a cofounder of Umoja and sits on the company’s advisory board.  

CureWorks, a collaborative allowing kids at member hospitals across the U.S. and Canada to access Seattle Children's phase 1 and 2 immunotherapy clinical trials, will also be expanding, Jensen says. “More kids need therapy than we can possibly get into the rooms we have at Seattle Children’s Hospital,” he explains, plus many of them couldn’t easily get to Seattle for study participation.   

The research partners currently include Children’s National (Washington, D.C.), Riley Children’s Health (Indianapolis), Children’s Hospital Los Angeles, and BC Children’s Hospital (Vancouver, British Columbia). But hospitals across North America and Europe—and, more recently, Australia and Asia—have expressed interest in joining the effort, says Jensen. “We’re starting with trials from Seattle Children’s, but we hope in the end all of the hospitals will be sharing their best trials amongst one another.” The leadership team for CureWorks will likewise expand to include representatives from all participating hospitals.   

Jensen currently leads a 130-member team, but the roster is growing rapidly since Seattle Children’s Therapeutics is a full-sized enterprise endeavoring to develop dozens of new therapies over the next decade, he says. The organization is open to collaboration not only with the ready-to-tap brain trust represented by the Seattle Children’s Research Institute, but any group of scientists who has a promising therapy in need of clinical testing and FDA-grade manufacturing, he quickly adds.