Day One Biopharmaceuticals aims to provide a business solution to a moral problem: the inequity in pediatric oncology drug development.
Day One Bio CEO Jeremy Bender and co-founders Julie Grant and Dr. Samuel Blackman/courtesy of Day One Biopharmaceuticals
Sporting a team of 100 dedicated employees - including five trained pediatric oncologists and several pediatric nurses – Day One Biopharmaceuticals aims to provide a business solution to a moral problem: the inequity in pediatric oncology drug development.
September is Childhood Cancer Awareness Month, a time to recognize the approximately 16,000 American children who are diagnosed with cancer each year. Globally, this number is around 300,000. Unfortunately, the monetary return on investment for this field of research is low, which has stalled innovation.
The Mission
“A lot of the drugs that kids are getting have been around for twenty or thirty years,” Kelli Wright, associate director of patient advocacy at Day One, told BioSpace. “The innovation isn’t there for the pediatric oncology community. It’s not always a priority for companies.”
In the United States, while the Pediatric Research Equity Act (PREA) was passed in 2003, giving the FDA the authority to require pediatric studies for certain drugs and biological products, there is still a limited number of clinical trials in children’s cancers. Currently, on ClinicalTrials.gov, there are 1,534 pediatric cancer trials listed in the U.S. - a fraction of the 41,833 trials in cancer overall.
“Big companies rarely develop drugs all the way through approval for childhood cancer, and when they do drug development work for pediatric oncology, those efforts are invariably tied to whether or not that drug succeeds or doesn’t succeed for adult indications,” Dr. Samuel Blackman, M.D., Ph.D., co-founder and chief medical officer at Day One, told BioSpace.
It’s also not as simple as prescribing adult cancer drugs for children, as kids are not just miniature adults.
“While there is overlapping biology between pediatric cancer and adult cancer, there are a lot of pediatric cancers that are driven by molecular alterations that aren’t really a major driver for adult cancers,” Blackman said. Thus, not all adult drugs will necessarily work against children’s cancers.
Of course, what appears to be an obvious proposition almost never is. In this case, there are economic realities. In order to continue researching and developing drugs that will ultimately save the lives of children, parents and grandparents, companies need to be able to turn profits into R&D funding. This is where Day One’s unique business model comes in: leveraging the return on investment from an “all patients” approach to intentionally develop effective cancer therapies for kids.
“The company was really founded to bridge the gap between pediatric and adult patients in terms of therapeutic options,” Jeremy Bender, Ph.D., CEO of Day One told BioSpace.
As co-founder and board chair Julie Grant said, “We have created an economic solution to a moral problem.”
Celebrating 100 Employees
Upon its founding in 2018, Day One was a two-person operation consisting of Blackman and Grant. Realizing they needed more than just an altruistic mission, the partners reached out to senior biotech executives in their pediatric oncology network, which Blackman called a “small world”.
“Our mission was sort of a clarion call for some incredibly talented people in the biopharmaceutical industry who have been just as frustrated as we are about the slow pace of drug development for children,” he said, adding that it was easy to recruit these individuals because “everybody’s been waiting for a company like this to be built.”
Currently, more than 100 people have answered that call. The majority of this growth has come during the COVID-19 pandemic, with 50 percent of it occurring this year alone.
The timing of the expansion is a triumph over adversity in itself. It’s also an advantage. “We’ve hired the best people that we can find, independent of geography,” Blackman said.
“Being a company that was built during the pandemic, our hybrid workforce model is not a new normal for us. It’s normal for us,” Ryan Sanders, head of talent acquisition at Day One, shared. “We have team members all over the country.”
Day One is also adamant about “protecting the culture”, continuously connecting and seeking feedback, Sanders said. In addition to monthly all-company meetings, the company hosts two in-person all-hands meetings per year, including an upcoming October gathering in San Diego, where Sanders anticipates the headcount could be at 120.
When it comes to further recruitment, Sanders said that alignment to the mission is paramount.
“As we continue to grow, we’re looking for top rank folks who have the necessary skills for the roles, and even more importantly, folks who are aligned to our mission, the culture and the team that we’ve assembled to date. We are fortunate to have attracted the best possible talent with the brightest minds and the biggest hearts,” he shared.
A Promising Pipeline
Day One will need every one of these mission-driven employees as it shepherds its first drug to the market. Tovorafenib, a type II Pan-RAF inhibitor, is being developed to treat pediatric low-grade glioma (pLGG), the most common type of childhood brain cancer. In June, the company announced positive early data from the first 22 evaluable patients in the Phase II FIREFLY-1 trial. Tovorafenib led to a 64% overall response rate (ORR) and a 91% clinical benefit rate, with 14 partial responses. The drug was generally well-tolerated with the majority of adverse effects being grade 1 or 2. Overall, the data sent the company’s stock into the stratosphere.
Following these results, Day One is now preparing for the next phase of its evolution.
“We’re evolving from a clinical-stage company in drug development to a commercial-stage company with a product on the market. As such, we have a spike in commercial opportunities right now,” Sanders said. Simultaneously, he noted, “we continue to grow across the enterprise in all departments as we look to expand our pipeline and advance our current programs. There is a lot of very important work happening every day here at Day One. It’s an honor to be on this journey with this incredible team.”
Given the mission and so-far positive data, Day One is a natural landing spot for talent in the oncology space.
“There is a gravitational pull toward what’s happening at Day One,” Sanders said. “People are excited about our lead product because of its promise and the patients who are urgently awaiting new treatment options.”
With more than 60 patients now enrolled in FIREFLY-1, Blackman said the full dataset, expected early in 2023, should be sufficient to serve as the basis for a new drug application.
Later in 2022, Day One will open a Phase III study evaluating tovorafenib as a frontline therapy for pLGG. This trial, called FIREFLY-2, is now open for enrollment. The primary endpoint will be ORR, with progression-free survival being a key secondary endpoint.
“Most children will require some type of systemic therapy. For many, many years that has been intravenous chemotherapy… and both the short- and long-term toxicity of chemotherapy is well known,” Blackman said. “Moving targeted therapy into the frontline has the real potential to transform this disease.”
Day One takes its name from the first meeting pediatric oncologists are trained to lead with patients’ families when a child is diagnosed with cancer. During a lengthy conversation with tissues on-hand, the oncologist will go through the diagnosis, treatment plan, potential side effects and what the family can expect in the months and years to come. At Dana-Farber Cancer Institute, where Blackman did his fellowship, this was called the “Day One talk.”
“I wanted to have a company that’s going to make new drugs for us to have at the Day One talk. Instead of talking about the same chemotherapy drugs from 50 years ago, we’re going to talk about something new,” he said.
The Next Days
Day One is also exploring the potential of tovorafenib in more genetically complicated adult cancers, Blackman revealed. To that end, the company is studying the drug in combination with a second asset, pimasertib, which is an inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK) within the MAPK signaling pathway. Preclinical studies indicate the combination may have synergistic anti-tumor activity.
“We will continue to grow our pipeline and look for other drugs like tovorafenib that meet the unmet needs of children that we can develop intentionally for pediatric cancers,” Blackman stated.
Bender’s long-term vision for Day One is to build a growing and sustainable business.
“It’s my goal that in 5-plus years, Day One will have multiple commercial products and a growing portfolio of programs that are, or have the potential, to become new medicines for patients of all ages living with life-threatening diseases,” he said.
There are two big experiments playing out at Day One. “One is with tovorafenib, and the other is the business model itself, proving that you can address the needs of children with severe and life-threatening diseases using a biotech business model,” Blackman said. “That’s a big deal.”
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