Skip to main content
Premium Trial:

Request an Annual Quote

Seattle Children's Spinout BrainChild Bio Bets on Four CAR T-Cell Targets in One

Brain cancer treatment

NEW YORK – BrainChild Bio spun out of Seattle Children's Hospital earlier this month with a clear directive from its founders: get a cell therapy to market that will save as many children with diffuse intrinsic pontine glioma (DIPG) as possible — and do it quickly.

"Patients are waiting," said BrainChild CSO Michael Jensen. "There's no curative therapy, and sadly when doctors tell parents about the diagnosis, they have to tell them their child will live somewhere between nine and 14 months."

But the biotech startup has far more expansive cell therapy ambitions in the long run. Ultimately, the firm wants to not only treat children with DIPG with a multiplex-targeted CAR T-cell therapy but also eventually market such a therapy for both children and adults with any type of solid tumor that metastasizes to the brain or central nervous system.

"Our vision is to create therapeutics based on cellular immunotherapies utilizing chimeric antigen receptors and other synthetic technologies to improve potency and specificity and to apply it to … eventually the 30 percent of all cancer patients who get a diagnosis of CNS mets," Jensen said. "That's 200,000 patients in the US each year … and that's usually a diagnosis that comes with chemotherapy and brain radiation, which are extremely toxic."

The firm may have an easier path to achieving its long-term goals of going after any CNS metastasis if BrainChild first paves the way by getting an autologous CAR T-cell therapy to the market for DIPG patients, then for children with other brain cancer subtypes and then adults with brain cancer.

"Now is the time to industrialize this," said BrainChild CEO Steven Brugger.

Four targets in one

Most of the autologous CAR T-cell therapies in clinical development are designed to target one or two tumor targets, and all of the marketed autologous CAR T-cell therapies go after only one target, such as CD19 or the B-cell maturation antigen (BCMA). BrainChild, however, has reason to believe it can design a therapy that homes in on four targets.

The firm has already validated the safety of cell therapies that individually inhibit the four targets of interest — B7-H3, EGFR806, HER2, and IL13-zetakine — in Phase I clinical trials.

Going after "each of these targets by itself was highly safe," Jensen said. "We went to the [US Food and Drug Administration] with a product that had those four targets that had been previously tested, and the FDA was quite agreeable with our thesis that if you have four safe targets and you put them into a single product, it's unlikely that you're going to have some de novo toxicity from the combination of the four."

The advantage of targeting four tumor antigens, according to Jensen and Brugger, is that the approach, which they call multiplex targeting, may get around the challenge of T-cell exhaustion. "We can create a network of targeting or a web of targeting that basically ensnares every tumor cell, so that escaping all four targets simultaneously is biologically a very unlikely event."

Accordingly, BrainChild has begun a Phase I study, dubbed BrainChild-04, to test the four-target CAR T-cell therapy as a treatment for children and young adults with recurrent or refractory CNS tumors, including DIPG. In the trial, BrainChild hopes to confirm the safety of this CAR T-cell therapy, which the firm calls SC-CAR4BRAIN, and to identify its best dose and the feasibility of manufacturing and administering the treatment. The company plans to enroll 72 patients, who will have their cells harvested, engineered, and infused back into their bodies at a Seattle Children's facility.

Although the firm's primary focus in the trial is to establish SC-CAR4BRAIN's safety and dosing, Jensen said investigators will look at biomarkers of tumor response and T-cell activation. They will also analyze cell-free DNA for mutations that can characterize DIPG patients' tumor burden and response.

BrainChild has already begun treating patients with SC-CAR4BRAIN in the trial, and while it's still early days, Jensen said the product looks "just as safe as the single-target CARs." In fact, he said that patients in the trial are receiving their infusions in the outpatient setting, and very few have been admitted to the hospital for side effects or complications. "We don't have cytokine storms, we don't have the neurotoxicity that you see in leukemia and lymphoma patients, and we don't have to give patients lymphodepleting chemotherapy," Jensen said. Unlike CAR T-cell therapies for blood cancers, which are often given as a one-time infusion, he added that SC-CAR4BRAIN is administered on a weekly basis using fresh cells that come out of the freezer "ready to go."

"That's another strategy to overcome this problem of T-cell exhaustion," he said.

Going forward, the firm believes that their multiplex targeting approach will be the key to moving the CAR T-cell therapy to indications beyond DIPG, and then beyond pediatric brain cancer.

"If you look at those [same] targets, for instance, on breast tumor metastases, it's a complete overlay," Jensen said. "We then have the ability to kind of mix and match to make combinations of targets that are best suited for a particular diagnostic class. … That's the general theme of how we're going to apply multiplex targeting to be able to go after multiple indications with a single target."

According to Jensen and Brugger, the fact that the engineered T cells are directly infused into the brain is also a safety advantage. "We use the blood-brain barrier as our ally because we're doing intracranial infusions [and] we don't find our cells in the bloodstream subsequent to dosing," Jensen said.

Logistics and funding

At the moment, BrainChild Bio sees its inextricable ties with Seattle Children's — both logistically and financially — as an advantage. The therapy has already been in development for over a decade through Seattle Children's Therapeutics. "They've built this unit to distribute therapeutics where they do everything from filing INDs to running Phase I clinical trials to obtaining the safety and efficacy data," Brugger said. "It's almost a turnkey startup where we've got Seattle Children's Therapeutics right there … so we will contract back for everything from the facilities to the clinical group to the Phase I center, the analytical group, the GMP manufacturing unit they have … [and] we can hit the ground running."

Thanks in part to this ready-to-go, all-in-one resource, the therapy can be harvested, made, and infused within a week, Jensen said.

At the moment, Seattle Children's Hospital is the firm's sole funder, according to Brugger. But looking ahead, especially if and when the firm expands beyond pediatric indications, BrainChild will seek more funding and facilities. "When the time comes, we can explore tech transferring out to larger [contract manufacturing organizations] for a commercial launch," Brugger said.

For now, BrainChild will stay based out of Seattle Children's and focus on completing the BrainChild-04 trial.

"We've got compelling data, and we believe we have opportunities to engage with the [FDA] sooner rather than later," Brugger said. "We will be exploring with the FDA different approaches as to how quickly we can go from initial Phase I safety [studies] into a Phase II registrational trial to at least get conditional approval and begin to move forward."

Although Brugger hesitated to predict a timeline for when BrainChild expects data readouts and regulatory filings, he said his team is optimistic that given the unique nature of the therapy with its individually validated targets and the unmet need in DIPG, BrainChild Bio will see a "fairly accelerated path and [have] ongoing dialogue with the agency."