Bridging the Pediatric Innovation Gap: Day One Biopharmaceuticals' Differentiated Development Path

Person of the Week:Jeremy Bender, President and Chief Executive Officer of Day One Biopharmaceuticals

Company Focus:Day One Biopharmaceuticals was founded with the goal of "addressing the innovation gap between cancer treatments for children and adults," says Bender. But the company is not solely focused on pediatric drug development. What sets it apart is its commitment to "advancing early clinical trials in pediatric and adolescent patients," rather than waiting for a drug to be approved in adults first and then seeking a pediatric indication.

"We pursue this strategy in parallel with our adult trial efforts. This requires coordination with regulators, collaboration with trial sites, and sometimes dedicated investment in formulations and early toxicology studies," he says. "But fundamentally, our mission is to develop new medicines across patients of all ages. So we act early. It sounds simple, but it's quite different from what other companies do."

In September, Day One submitted a rolling New Drug Application to the U.S. Food and Drug Administration (FDA) for its lead candidate, tovorafenib, as a monotherapy for relapsed or progressive pediatric low-grade glioma. The company expects the FDA to make an acceptance decision by mid-November.

"Our mantra is: the right project, the right patient population, the right biology."

— Jeremy Bender, Chief Executive Officer of Day One Biopharmaceuticals

The pipeline also includes pimasertib, a small molecule inhibitor of mitogen-activated protein kinase 1 and 2. Additionally, Day One has entered into an exclusive worldwide license agreement and research collaboration with Sprint Bioscience for the VRK1 program, aiming to develop treatments for pediatric and adult cancers with high unmet need.

Why It Matters: The Pediatric Drug Innovation Gap

There is awell-known gapbetween the innovative medicines available to adult and pediatric patients. Often, drugs are approved for adults first and only much later for children. Day One aims to change that.

"Over the past few decades, we've seen many breakthrough drugs for adult cancers, but very few for children," says Bender. "On average, drugs are approved for children six to seven years later than for adults, and sometimes they are never approved at all."

Although researchhas shownsuccessful examples of adult-pediatric combined trials submitted to the FDA, this approach still faces multiple barriers.

"It's more difficult partly because of safety considerations and the regulatory process for clinical trial approval," says Bender.

For example, "regulators really require adult exposure data before a new drug can be used in children, to address any potential safety concerns associated with that new drug."

He also points to the lack of infrastructure and experience in academic institutions for conducting pediatric oncology trials, as well as the fact that the number of pediatric cancer patients is much smaller than that of adults, as significant factors.

Below, Bender further elaborates on Day One and its approach to drug development.

This interview has been edited for brevity and style.

PHARMAVOICE: Why do you describe Day One's process and commercial strategy as innovative?

JEREMY BENDER:In the case of Day One, our innovative approach stems from two components. One is pushing pediatric work as early as possible, which is unique and differentiating. The second is that we employ a process to look at indications and biology that may not have been focused on or deeply considered by competitors. This leads to our mantra: the right project, the right patient population, the right biology. If you combine these elements and have deep insights into each, you can develop new drugs faster and with a higher probability of success. Applying this approach—which is what we all strive for in this industry—is the reason for our success with tovorafenib so far, and we hope to apply it to other programs.

You mentioned wanting to be part of changing the lives of pediatric cancer patients. Do you think the company is doing that, and how?

That is absolutely our aspiration and it motivates every employee at the company. Our people joined Day One to make an impact on patients—especially pediatric patients. I hope we can achieve that, and I believe we are on the right path. The data from our lead program, tovorafenib, in relapsed or progressive pediatric low-grade glioma suggests we are headed in the right direction. The clinical trial for that patient population is called Firefly-1, and over the past 18 months we have released some results and are encouraged by the data we've seen.

I'd like to emphasize that in the approximately 76 patients in that trial, 80% to 90% had tumor stabilization or shrinkage, depending on how it's measured. That's an early strong signal of making a difference for these patients.

What does this mean for patients' lives? By stabilizing and often shrinking tumors in the brain, you can prevent any functional deficits that tumor growth might cause. In some cases, it can also improve function; and equally important, it avoids the use of subsequent therapies that may be more challenging, more toxic, or have greater long-term safety impacts—whereas we hypothesize tovorafenib has fewer of those.

Ultimately, this could translate into a truly better quality of life for these children in terms of visual, cognitive, or motor function. And of course, the families and caregivers of these children also benefit from this improvement.

What should other biotech and pharma executives understand about how you are advancing this work?

For our model to succeed, and frankly for the biotech and pharma industry (especially biotech) to thrive and make progress, it depends on several key elements. The first is ongoing and significant collaboration with regulators. Whether that dialogue is productive, clear, and supportive of innovative approaches—especially in pediatric patients—is critical to our model.

The second is our industry's reliance on capital formation and the ability to raise funds from investors, whether through venture capital or the public markets. These two elements—capital availability and the regulatory process (which are, of course, interconnected)—are essential for having the opportunity to continue building a sustainable business and achieving our goals.