‘Kid-first’ startup BrainChild wants to shift the paradigm on pediatric cancer drugs

The lab of Michael Jensen, M.D. at Seattle Children’s Hospital’s drug development arm, Seattle Children’s Therapeutics, has spent the past 13 years developing chimeric antigen receptor T cell (CAR-T) therapies to treat childhood cancer. Sixteen have made it into FDA-approved clinical trials. Jensen was also a co-founder of Juno Therapeutics; his Seattle Children’s team created the product that became Juno’s CAR-T drug Breyanzi—now owned by Bristol Myers Squibb. 

But despite being designed for a pediatric population, none of those therapies—including Breyanzi—have been commercialized for use in kids.

“The history of ‘trickle-down’ therapeutics development—the idea that something is approved for adults and eventually is licensed for pediatric indications—hasn’t really borne enough fruit to be viable,” Jensen told Fierce Biotech in an interview. “We think we just have to switch the paradigm on its head.”

That’s the idea behind BrainChild Bio, a newly-launched spinout of Seattle Children’s Hospital focused on childhood central nervous system cancers. Rather than starting with regulatory approval for its drugs in adults, the company will aim for a greenlight for peds patients first. Its inaugural program centers on a new CAR-T platform developed by Jensen’s lab, which is already being tested in children with different types of brain cancers, including the universally-fatal brain cancer diffuse intrinsic pontine glioma, or DIPG—through the BrainChild clinical trials.

“We can prove and pursue registration for these technologies in children, and only then step into adult glioblastoma and brain mets with those same technologies in the same CAR-T products,” Steve Brugger, CEO of BrainChild, said in an interview. “Quite frankly, it’s a very sound business strategy to prove out the technologies before you start stepping into larger indications.”

A ‘turnkey’ spinout

In the U.S., drug trials in kids lag behind adults by about 6.5 years. Between 2007 and 2017, less than 1% of trials were for children only. But that’s not because the FDA doesn’t prioritize pediatrics, Jensen said—insentive programs like Priority Review Vouchers, which shorten the FDA review time from 10 months to six for some indications, including life-threatening childhood diseases, are proof of that.

Instead, “the real friction occurs, maybe, in the boardrooms with investors,” Jensen said.“If the company has the resources to get one shot on goal, typically they’ll choose the adult indication because the market cap and return on investment are bigger,” he explained.

That tension isn’t a problem for BrainChild because its funding comes from a source with the same goals: Seattle Children’s. The founders decided to keep the institution as its sole investor, at least for now, so the focus can remain exclusively on pediatric brain cancer. The two-year agreement with Seattle Children’s provides enough money to hire 20 full-time staff members, advance BrainChild’s CAR-T platform and make progress in clinical trials.

“It’s completely aligned with Seattle Children’s perspective,” Jensen said. “So we’re all in a boat that’s rowing in the same direction.”

The pairing also has practical perks that make it easy to “hit the ground running,” Brugger added. Jensen himself is joining as founder and chief scientific officer. The R&D staff includes members of his lab who have been developing the company’s technology and running the ongoing BrainChild trials. And the startup won’t need to look for somewhere else to manufacture its CAR-T therapies—it will simply contract back with Seattle Children’s to use its GMP cell therapy manufacturing facilities.

“It’s almost like a turnkey startup,” Brugger said. “It’s not like we’re running around looking for space, looking for a team, looking for equipment—we can very quickly turn the corner and begin to move these things forward.”

BrainChild’s CAR-T platform is distinct from others in several ways. It doesn’t require lympho-depletion with chemotherapy and is delivered directly into the tumor in the brain. New cells are delivered on a weekly basis, a tactic that combats T cell exhaustion. And the strategy leverages the blood-brain barrier to keep the cells from migrating elsewhere and having off-target effects. So far, it’s been well-tolerated, Jensen said.

“We think that paradigm is very robust,” he said. “Our preclinical data and clinical data really show that we have the safety signals and maximum tolerated dose signals that are exactly what we predicted.”

But that’s not all: BrainChild’s CAR-T platform is also “multiplex,” or designed to target multiple antigens at once. The initial BrainChild clinical trials, which are now headed into phase 2, assessed whether it’s safe to go after each target separately. As of April 2023, Jensen’s team is studying all of them at the same time: BrainChild-04 assesses the feasibility of targeting B7-H7, EGFR806, HER2 and IL13-zetakine in a single drug, a first in the CAR-T space.

“[The earlier BrainChild clinical trials] set a foundation where we’ve proven that it’s safe to use these individual targets and an individual CAR in these pediatric tumors,” Brugger explained. “Now we’re looking at all four targets in pediatric brain tumors.”

The new spinout will test out other upgrades to the tech too, modifications to the platform that Jensen calls “stacking technologies”. These include tweaks to improve potency and regulation of the platform.

“We’ve got this great dataset in front of us now, almost like prototypes,” Brugger said. “Then we’ll add to those.”The company expects to present data from BrainChild-04 in 2024.