video: Seattle Children's Therapeutics is developing next-generation cell and gene therapies for kids like Greta with cancer and other childhood disease. view more
Credit: Seattle Children's Music: Think Different By: Adi Goldstein Courtesy of Music Vine Limited
As Dr. Michael Jensen looks out over South Lake Union from his lab on the 10th floor of Seattle Children's Building Cure, he sees a future of possibilities.
A future where children facing cancer and other life-threatening and debilitating diseases have the medicines they need to lead healthy lives and to achieve their full potential. Where it's no longer about beating the odds but changing them for generations to come. Here, Seattle's biotech corridor is home to a burgeoning pediatric life sciences hub and leading the way, under Jensen's direction, is the recently launched Seattle Children's Therapeutics.
"While the biotech industry develops life-saving medicines for many diseases they must make decisions on which opportunities to pursue based, in part, on financial returns and all too often, that deprioritizes kids because those medicines don't have sufficient return on investment," said Jensen, Seattle Children's chief therapeutics officer. "By building a non-profit therapeutics development enterprise within Seattle Children's, we can take the reins and develop the medicines that kids need."
Scale, speed and efficiency
Seattle Children's Therapeutics offers a new approach to developing and testing next-generation cell and gene therapies for a variety of pediatric conditions that can be ameliorated or cured through this emerging class of therapeutics.
Jensen likens Seattle Children's Therapeutics to a vertically-integrated biotech with all the gears needed to move a promising new therapy from the Research and Development lab to a first-in-human clinical trial and beyond: research and development, therapeutics manufacturing, FDA regulatory affairs compliance and clinical trials management and research subject analytics.
He says many other academic pediatric research enterprises may have some or all these components in disparate parts of their organizations, but he is unaware of any place where they are organized in a way that they come together as a well-oiled machine with all the gears working in sync. By taking a page from industry's playbook and structuring itself to look more like a biotech than an academic research program, Jensen believes Seattle Children's Therapeutics can accelerate and scale the discovery, development and deployment of new therapies that meet the unique needs of the pediatric population.
"To take a promising new therapeutic through the drug development "Valley of Death" - from the last mouse to the first human - requires concentrated, robust resources and expertise all working towards the same goal," Jensen said.
It's a model that emphasizes scale, speed and efficiency, and robust philanthropic support while keeping Seattle Children's mission of helping every child live the healthiest, most fulfilling life possible at the forefront.
"We can have the best children's hospital on the planet, but if we don't continue striving to find better therapies, we will either continue to lose children whose disease cannot be cured by current therapies or leave them with long-lasting and debilitating side effects from today's therapies," Jensen said.
Building on progress in childhood cancer
While Seattle Children's Therapeutics launched earlier this year as a unit in the Research Division within Seattle Children's, it expands on a successful cancer immunotherapy research program that opened its first clinical trial for childhood cancer in 2012.
The program has since designed, manufactured and launched a robust portfolio of chimeric antigen receptor (CAR) T-cell immunotherapy FDA-authorized clinical trials in the areas of pediatric and young adult leukemia, lymphoma, brain tumors and solid tumors. In the process of becoming one of the largest pediatric cancer immunotherapy research programs in the country, Seattle Children's amassed the expertise and infrastructure needed to support a venture such as Seattle Children's Therapeutics.
Many components of Seattle Children's Therapeutics were already in place when Jensen and other Seattle Children's leaders started discussing the possibility of expanding their impact in cell and gene therapies to a variety of childhood diseases and conditions beyond cancer. This included a new state-of-the-art research Good Manufacturing Practices (GMP) therapeutic cell manufacturing facility, the Cure Factory, which is one of the largest pediatric-focused facilities in the U.S. potentially capable of producing upward of 1,000 cell therapy products for clinical trials every year.
Together, with their experience partnering with clinical research teams at Seattle Children's to safely and swiftly translate advances made in the lab to care at the patient's bedside and the CureWorks collaborative that makes it possible for patients to access Seattle Children's immunotherapy clinical trials at member hospitals across the U.S. and Canada, Jensen felt they had a winning combination.
"Immunotherapy for childhood cancer is teaching us as we go and there are kids that are alive today because of our early phase clinical trials," Jensen said. "Those trials taught us how to build this infrastructure and how to make it work at scale, now with over a dozen trials actively enrolling children. Our accomplishments over the last eight years sets the stage for expanding into other areas of unmet pediatric medical needs."
Today, Jensen leads a team of 130 team members, who encompass and integrate the current cancer immunotherapy program, GMP cell product manufacturing, and clinical trials and regulatory affairs management. He anticipates that in as little as five years they will move into designing and developing cell and gene therapies for other life-threatening and debilitating diseases that afflict children.
Mission-centric incubator for pediatric therapies
An entrepreneurial physician-scientist who has co-founded several biotech companies, Jensen also recognizes collaboration with industry is key to accelerating the vision of Seattle Children's Therapeutics and bringing it to a global scale.
There is one requirement for any collaboration under the Seattle Children's Therapeutics' umbrella:
"It must have an upside for kids," Jensen said. "We will collaborate with external partners who share our vision to develop new therapies for children."
The Seattle Children's Therapeutics' team has already secured one such industry partnership with Bluebird Bio and they expect to finalize more licensing and sponsored research agreements in the coming months.
In addition to working with existing companies, Seattle Children's Therapeutics also sees opportunity to support the development efforts of new biotech companies by serving as an incubator hub. The incubator hub will provide organizations developing promising new therapies for children access to Seattle Children's research infrastructure and clinical product manufacturing.
"If there is not the appetite in biotech or big pharma to move the needle for kids with conditions that need better therapies, maybe we can support the launch of companies that will take the next game-changing drug forward for children," Jensen said.
Investing in the future
To make the model sustainable, future revenue generated as part of intellectual property licensing, sponsored research and clinical research agreements will be reinvested into Seattle Children's Therapeutics to improve and expand capabilities. This, in turn, will expedite the development of cell and gene therapies for a greater number of pediatric diseases.
The team is also adding in-house capabilities such as a lentiviral vector manufacturing facility called VectorWorks that will allow them to produce this critical component of many cell and gene therapy products, such as CAR T cells, in a more time and cost efficient manner than is otherwise possible by outsourcing this critical reagent. While making vectors for Seattle Children's clinical trials will be prioritized, Seattle Children's Therapeutics will also contract its vector manufacturing services to external partners, ideally partners with a pediatric impact focus. With a strong and growing demand for viral vectors in the U.S., Seattle Children's Therapeutics is positioned to benefit from another potential revenue-generating source.
Still, Jensen notes the progress in childhood cancer and the opportunity to build Seattle Children's Therapeutics, would not be possible without the generous support of the philanthropic community. He hopes Seattle Children's Therapeutics inspires donors to embrace this ambitious vision to change the world for good.
"This emerging generation of philanthropists want to change the world," he said. "We can be their change agents. Together with our spirit of innovation, support from our community and collaboration with pioneering organizations, we can realize our vision much faster than if we were working on our own siloed away in an ivory tower."
Seattle Children's and Jensen remain steadfast in their commitment to this vision. Even with the significant impact of COVID-19, they believe there's no better time than now to aim high for kids.
"What we have built is close to once in a lifetime opportunity in that the stars have aligned for us at Seattle Children's to do this," Jensen said. "There's a window of opportunity and by doing this now we hope to emerge in a place that is unlike any other pediatric hospital research enterprise in the country. If we're successful, Seattle Children's will create a legacy in pediatric health that will continue for decades to come."
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[Sidebar]
The Need for New Therapies for Childhood Diseases
All too frequently childhood diseases don't have medicines to heal and cure them or that are developed with the unique physiology of a child's body accounted for. Big pharma and the biotechnology industry have limited financial incentive to develop drugs specifically for children, as small numbers of patients can limit return on investment. Therapies developed exclusively for children for some of the most devastating conditions remain a critical unmet need. Take for example:
- Most drugs prescribed to children have never been tested in children. Up until recently, only about 20% of drugs approved by the FDA were labeled for pediatric use
- Many pediatric diseases and all pediatric cancers are considered rare diseases because they affect fewer than 200,000 Americans. More than 90% of rare diseases are still without an FDA-approved treatment.
- Pediatric research received less than 10% of the $41.7 billion federal funding provided by the National Institutes of Health. Even when competitive federal grants are secured, the cost of getting a new drug into a phase 1 clinical trial far exceeds the average grant amount by tens of millions of dollars.
Sources:
Center for Drug Evaluation and Research. "Drug Research and Children." U.S. Food and Drug Administration. FDA, May 6, 2016.
https://www.fda.gov/drugs/drug-information-consumers/drug-research-and-children;
NORD Rare Insights Orphan Drug Fact Sheet. "What is the Orphan Drug Act?" National Organization for Rare Diseases. NORD, October 2019,
https://rarediseases.org/wp-content/uploads/2019/10/NRD-1159-RI_WhatIsTheODA_2019_FNL-1.pdf;
National Institute of Child Health and Human Development (NICHD). "NIH Pediatric Research Consortium (N-PeRC)," December 17, 2019.
https://www.nichd.nih.gov/research/supported/nperc;
Wouters, Olivier J., Martin Mckee, and Jeroen Luyten. "Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018." Jama 323, no. 9 (2020): 844.
https://doi.org/10.1001/jama.2020.1166.