Nuvation Bio Announces Pivotal Global Phase 3 SIGMA Trial (G203) for Safusidenib in IDH1-Mutant Glioma

Protocol amendment to change SIGMA from a Phase 2 to a Phase 3 study now complete

The currently enrolling SIGMA trial will now include patients with grade 2 astrocytoma with high-risk features in the maintenance setting, in addition to previously eligible patients with high-grade astrocytoma

A new exploratory cohort has also been added for patients with grade 3 oligodendroglioma in the post-surgical setting

Broad patient population in SIGMA represents most forms of IDH1-mutant glioma that do not have an FDA-approved targeted treatment option

Nuvation Bio Inc. (NYSE:NUVB), a global oncology company focused on tackling some of the toughest challenges in cancer treatment, today announced finalization of a protocol amendment to the ongoing global SIGMA study (also known as G203; NCT05303519) of safusidenib that expands it to a Phase 3 trial. SIGMA is evaluating the efficacy and safety of safusidenib versus placebo for the maintenance treatment of patients with high-risk or high-grade IDH1-mutant astrocytoma following standard-of-care. Safusidenib is a novel, oral, potent, brain-penetrant targeted inhibitor of mutant IDH1.

The new protocol broadens patient eligibility in the registrational portion of the trial and includes those with grades 2 and 3 IDH1-mutant astrocytoma with high-risk features and grade 4 IDH1-mutant astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. The primary endpoint is progression-free survival as assessed by Blinded Independent Central Review (BICR) per Response Assessment in Neuro-Oncology (RANO) 2.0. To support regulatory submissions for patients with astrocytoma, the protocol amendment significantly increases trial enrollment from 100 to 300 patients in the U.S., Australia and China.

The trial will now also enroll a non-pivotal single-arm cohort to examine the efficacy and safety of safusidenib in chemotherapy- and radiotherapy-naïve patients with grade 3 IDH1-mutant oligodendroglioma. The primary endpoint for this arm is objective response rate. This cohort is expected to enroll approximately 40 patients.

"These SIGMA protocol updates reflect alignment with U.S. regulators to support the potential approval of safusidenib as swiftly as possible for a patient population that is in dire need of options," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "Following discussions with regulatory agencies, advocacy groups and physicians, we substantially expanded the study to include most patients with an IDH1-mutant glioma who currently have no approved targeted therapies available. We are encouraged by the promising results seen in the Phase 2 study, which included both astrocytoma and oligodendroglioma, and are eager to explore the potential of safusidenib across multiple settings through this registrational trial. We expect initial data for the separate oligodendroglioma cohort in 2027."

"Patients with IDH1-mutant gliomas face a lack of available therapies with proven ability to extend long-term survival while maintaining quality of life," said David Arons, President and Chief Executive Officer of the National Brain Tumor Society. "This is particularly true for patients with higher-risk or high-grade IDH1-mutant astrocytoma and oligodendroglioma, where available treatment options — including clinical trials specific to their tumor type — are historically few and far between. Including such patients in pivotal trials, we hope, could bring meaningful benefit for this area of high-unmet medical need."

About IDH1-Mutant Glioma

Gliomas are the most common type of brain cancer in adults worldwide. In the U.S., nearly 2,400 people are diagnosed with IDH1-mutant gliomas each year. Most patients are diagnosed in their 30s and 40s. While patients with IDH1 mutations generally have longer survival times than those with wild-type IDH1, gliomas are not currently curable and prognosis worsens for those with high grade tumors.

About Safusidenib

Safusidenib is a novel, oral, potent, brain-penetrant, targeted inhibitor of mutant IDH1. In Phase 1 and 2 clinical studies, safusidenib was well-tolerated and demonstrated anti-tumor activity and high blood-brain barrier penetration.

About Nuvation Bio

Nuvation Bio is a global oncology company focused on tackling some of the toughest challenges in cancer treatment with the goal of developing therapies that create a profound, positive impact on patients' lives. Our diverse pipeline includes taletrectinib (IBTROZI^®), a next-generation ROS1 inhibitor; safusidenib, a brain-penetrant IDH1 inhibitor; NUV-868, a BD2-selective BET inhibitor; and an innovative drug-drug conjugate (DDC) program.

Nuvation Bio was founded in 2018 by biopharma industry veteran David Hung, M.D., who previously founded Medivation, Inc., which brought patients one of the world's leading prostate cancer medicines. Nuvation Bio has offices in New York, San Francisco, Boston, and Shanghai. For more information, visit www.nuvationbio.com or follow the company on LinkedIn and X (@nuvationbioinc).

Forward-Looking Statements

Certain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as "believe," "may," "will," "estimate," "continue," "anticipate," "intend," "expect," "should," "would," "plan," "predict," "potential," "seem," "seek," "future," "outlook," and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the need for new therapeutic options in glioma and the therapeutic potential of safusidenib, our expectations that the SIGMA study may support approval of safusidenib for the maintenance treatment of high-risk or high-grade IDH1-mutant astrocytomas, our enrollment plans for the SIGMA study, and our plans for future data updates. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the management team of Nuvation Bio and are not predictions of actual performance. These forward-looking statements are subject to a number of risks and uncertainties that may cause actual results to differ from those anticipated by the forward-looking statements, including but not limited to the challenges associated with conducting drug discovery and initiating or conducting clinical studies due to, among other things, difficulties or delays in the regulatory process, enrolling subjects or manufacturing or acquiring necessary products; the emergence or worsening of adverse events or other undesirable side effects; risks associated with preliminary and interim data, which may not be representative of more mature data; and competitive developments. Risks and uncertainties facing Nuvation Bio are described more fully in its Form 10-Q filed with the SEC on November 3, 2025, under the heading "Risk Factors," and other documents that Nuvation Bio has filed or will file with the SEC. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Nuvation Bio disclaims any obligation or undertaking to update, supplement, or revise any forward-looking statements contained in this press release.

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