ONC201 Receives FDA Approval

With the help of Cancer Commons and xCures, Oncoceutics officially opened the ONC201 EAP in early 2019. The intermediate-size Expanded Access Program gave options to patients who did not qualify for clinical trials. 
Cancer Commons EAP News

On May 17, 2019—DIPG Awareness Day—Kansas State student Jace Ward was diagnosed with DIPG. He quickly learned about a promising new treatment: ONC201. He did not qualify for existing clinical trials. Jace eventually gained access through the EAP thanks to the determination of his mother, Lisa, and support from the foundations funding the EAP. Jace bravely shared his treatment journey publicly, becoming one of the most visible advocates for ONC201 and helping elevate awareness of both the treatment and the urgent needs of DIPG patients.

On June 20, 2019, Jenny Mosier, then Executive Director of Michael Mosier Defeat DIPG Foundation, delivered emotional testimony before the FDA. She highlighted the dire prognosis of H3K27M-mutant gliomas and emphasized the promise of ONC201, reminding regulators that families had no time to wait.
Jenny Mosier Statement to the FDA

By late 2019, Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation began receiving research proposals specifically tied to ONC201. Recognizing the potential, the foundation (based on direction from its Scientific Advisory Council) awarded two New Investigator Grants—one to Dr. James Stafford (University of Vermont) and one to Dr. Matthew Dun (University of Newcastle). This marked the foundation’s first investment in scientific research focused on ONC201 and laid the groundwork for future discoveries.
Stafford New Investigator Grant
Dun New Investigator Grant

Although data from DMG-ACT did not inform the FDA’s approval of ONC201, the Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation played a pivotal role in launching this groundbreaking initiative—one that is now positioned to support future breakthroughs. Recognizing the urgent need for a more unified and innovative approach to clinical research, the foundations jointly invested in building the infrastructure for what would become DMG-ACT (Diffuse Midline Glioma – Adaptive Combinatorial Trial). Rather than a single trial, DMG-ACT is a collaborative clinical trial framework designed to accelerate the evaluation of promising treatments for DMG, including ONC201, through adaptive, multi-arm studies across multiple institutions. This early support positioned the foundation as a founding partner in a new model of research that breaks through traditional barriers in pediatric cancer and lays the groundwork for sustained progress.
Funding DMG-ACT
PNOC’s DMG ACT

In February 2020, Jace Ward delivered the closing remarks at the inaugural DIPG Advocacy Briefing to Congress in Washington, D.C. He shared his personal journey with ONC201 and urged lawmakers to act on behalf of children battling DIPG. His message—“I can’t die, I’m busy”—resonated deeply and helped bring national attention to the urgent need for research funding and access to promising therapies.
Jace Ward Remarks

Again working with Onoceutics, Michael Mosier Defeat DIPG Foundation, The ChadTough Foundation and Dragon Master Foundation committed $250,000 to support the opening of an additional Expanded Access Program for ONC201 in response to growing demand. Dozens of children gained access who otherwise had no treatment options.
Additional Round of Expanded Access
Chimerix Expanded Access

Michael Mosier Defeat DIPG Foundation and The ChadTough Foundation officially merged to form the ChadTough Defeat DIPG Foundation, combining leadership, networks, and strategic vision to strengthen their collective impact. The merger unlocked new levels of influence and fundraising capacity, enabling deeper, more coordinated investments in high-impact research—particularly around ONC201. Just as importantly, it marked a philosophical shift: an open invitation for other families to join the movement. The merged foundation embraced the idea that defeating this disease would take a united community, welcoming Family, Research & Navigator Partners into the fold. This inclusive model continues to grow, accelerating progress through collaboration, shared resources, and a steadfast commitment to change.

Oncoceutics—the small biotech company that had led the early development of ONC201—was acquired by Chimerix, Inc., a publicly traded biopharmaceutical company. This acquisition was a major turning point for the drug. Chimerix brought expanded infrastructure, regulatory expertise, and financial stability that strengthened the path toward FDA approval. The transition to a larger company meant that ONC201 could progress more rapidly through the later stages of development, gain broader access to regulatory engagement, and prepare for commercial scale. The acquisition helped ensure that the promise of ONC201 would not stall, but continue moving forward toward patients.
Chimerix Acquires Oncoceutics – Press Release

The infrastructure developed through the DMG-ACT initiative led to the launch of its first clinical trial: PNOC022. This innovative, multi-arm study was designed to evaluate ONC201 in combination with other promising agents in children and young adults with H3 K27M-mutant diffuse midline gliomas, including DIPG. The trial opened to enrollment in November 2021, marking a critical milestone for the collaborative model established by DMG-ACT. It represented the first tangible realization of the foundation-supported effort to transform the clinical research landscape for DMG, moving from fragmented, single-agent studies toward a coordinated, adaptive framework capable of accelerating progress.
 PNOC022 Launch

Building on the success of PNOC022, the DMG‑ACT infrastructure enabled the initiation of PNOC023, an open-label Phase 1 and target validation study evaluating ONC206 in children and young adults with newly diagnosed or recurrent diffuse midline glioma (DMG), along with other recurrent malignant CNS tumors. The trial opened for enrollment in September 2022 at the University Children’s Hospital Zurich—becoming the first ONC206-based study launched under the DMG‑ACT model.
 PNOC023 Launch

That same year, ChadTough Defeat DIPG Foundation awarded a Game Changer Grant to Dr. Richard Lu, whose lab focused on uncovering epigenetic mechanisms behind therapy resistance and sensitivity in DMG. His work offered vital insights into the molecular landscape that determines ONC201 response, supporting smarter trial design and biomarker development.
2022 Game Changer Grant – Dr. Richard Lu

ChadTough Defeat DIPG Foundation doubled down on its commitment to empowering the next generation of researchers. It awarded three research fellowships to Drs. Erik Peterson, Ryan Duchatel, and Akash Deogharkar—each focused on exploring how ONC201 works and why resistance may develop. Their investigations ranged from tumor heterogeneity to therapeutic sequencing and mitochondrial stress response.
Erik Peterson – 2023 Predoctoral Fellowship
Ryan Duchatel – 2023 Postdoctoral Fellowship
Akash Deogharkar – 2023 Postdoctoral Fellowship

Meanwhile, the DMG-ACT clinical trial platform continued to expand its global reach and impact. By 2023, more than 40 trial sites worldwide were participating in studies launched under the DMG-ACT infrastructure. The flagship trial, PNOC022, added new treatment arms to evaluate ONC201 in combination with additional investigational agents, furthering its adaptive approach to testing promising therapies for children and young adults with diffuse midline glioma. In parallel, PNOC023, launched under the same umbrella, advanced early-phase evaluation of ONC206, a next-generation imipridone. The continued growth of DMG-ACT reflects the strength of the collaborative model it was built on—bringing together researchers, institutions, and foundations to drive smarter, faster clinical progress against one of the most devastating pediatric brain cancers.

Critical to the eventual FDA approval, a landmark paper led by Drs. Carl Koschmann and Sriram Venneti (Cancer Discovery, Aug 2023) reported significant survival benefit in ONC201–treated children with H3 K27M DMG (median overall survival of ~22 months vs ~12 months historically). The study linked clinical outcomes to metabolic and epigenetic activity—including restored H3K27me3 and altered TCA cycle metabolites—strengthening both the scientific rationale and regulatory momentum for ONC201. It also uncovered EGFR/FOXG1-driven resistance mechanisms, guiding future combination strategies.
  Koschmann et al., Cancer Discovery (2023)

By 2024, DMG-ACT had grown into a global research engine, driving progress across dozens of institutions and rapidly generating data that informed treatment decisions in real time. The PNOC022 trial, supported under the DMG-ACT umbrella, had more than 32 active sites, with multiple ONC201 arms enrolling patients at all stages of the disease—from newly diagnosed to recurrent. This adaptive model not only produced critical clinical insights, but also dramatically expanded access to ONC201 for families facing DIPG who had previously struggled to obtain the drug.

Recognizing the importance of this infrastructure, the ChadTough Defeat DIPG Foundation continued to provide core operating support for DMG-ACT while playing a leading role in regulatory engagement, scientific advocacy, and patient access efforts. The foundation worked closely with researchers, regulators, and company leadership to ensure that families could benefit from emerging science as quickly—and equitably—as possible.

Throughout the year, real-world data from trials like PNOC022 and expanded use programs added weight to the growing body of evidence supporting ONC201. These efforts helped bridge the gap between early-phase trial results and the FDA’s threshold for accelerated approval. In December 2024, Chimerix submitted its New Drug Application (NDA) for ONC201 in recurrent H3 K27M-mutant diffuse midline glioma, marking a pivotal step forward in what had long been considered an untreatable disease.

In February 2025, the FDA accepted Chimerix’s New Drug Application (NDA) seeking accelerated approval for ONC201 (dordaviprone) to treat patients with recurrent H3 K27M-mutant diffuse midline glioma. The application was granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 18, 2025. ONC201 had previously received Orphan Drug, Fast Track, and Rare Pediatric Disease designations, reinforcing the urgency and promise of the therapy.
FDA Acceptance & Priority Review

In March, it was announced that Jazz Pharmaceuticals would acquire Chimerix, signaling a major milestone in the drug’s commercial trajectory. The acquisition brought the resources and global infrastructure needed to support ONC201’s broad clinical adoption and future development.
Jazz Acquires Chimerix

Then, on August 6, 2025, the long-awaited moment arrived: The FDA granted accelerated approval of ONC201 (now known as Modeyso™) for patients with recurrent H3 K27M-mutant diffuse midline glioma—making it the first-ever FDA-approved treatment for DMG/DIPG. The decision marked a historic turning point in pediatric neuro-oncology, validating years of research, collaboration, advocacy, and philanthropic investment.
FDA Approval Announcement