PIPELINE
Nuvation Bio is focused on treating patients with the most difficult-to-treat cancers for which conventional therapies have failed. We are advancing multiple clinical-stage candidates, including a ROS1 inhibitor, a mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor, a bromodomain and extra-terminal (BET) inhibitor, and a drug-drug conjugate (DDC).
Program
Potential Indication(s)
Current Stage of Development
Preclinical
Phase 1
Phase 2
Pivotal
Anticipated Milestones & Recent Updates
Taletrectinib1
(ROS1)
ROS1-positive NSCLC
China NDAs under priority review by China’s NMPA5;
Interim Phase 2 (TRUST-II) data presented at ESMO 2023
Safusidenib2
(mIDH1)
Grades 2 and 3
IDH1-mutant glioma
Phase 2 study ongoing
Advanced solid
tumors
Monotherapy
Maximum tolerated dose determined
NUV-868
(BET)
Advanced solid
tumors3
NUV-868 +
olaparib
Phase 1b dose escalation study ongoing
mCRPC
NUV-868 +
enzalutamide
Phase 1b dose escalation study ongoing
NUV-1511
(DDC)
Advanced solid tumors4
Phase 1 dose escalation study ongoing
ESMO: European Society for Medical Oncology; NDA: New Drug Application; NMPA: National Medical Products Administration; NSCLC: Non-small cell lung cancer; 1. Taletrectinib has been granted Breakthrough Therapy Designations from the U.S. FDA and China’s NMPA for the treatment of advanced or metastatic ROS1-positive NSCLC; worldwide development and commercial rights in-licensed from Daiichi Sankyo; Rights to taletrectinib have been out-licensed in China, Japan, and Korea. 2. Worldwide development and commercial rights in-licensed from Daiichi Sankyo, excluding Japan where Daiichi Sankyo retains development and commercial rights. 3. Includes patients with ovarian, triple-negative breast, pancreatic, and metastatic castration resistant prostate cancer (mCRPC). 4. Includes patients with advanced solid tumors who previously received and progressed on or after treatment with Enhertu® and/or Trodelvy® per approved U.S. FDA labeling, human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, mCRPC, advanced pancreatic cancer, and platinum-resistant ovarian cancer. 5. Under priority review for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC that have and have not previously been treated with ROS1 tyrosine kinase inhibitors.
ROS1
Taletrectinib is an oral, potent, CNS-active, selective, next-generation ROS1 inhibitor specifically designed for the potential treatment of ROS1-positive non-small cell lung cancer (NSCLC).
Taletrectinib is being evaluated for ROS1-positive NSCLC in two Phase 2 single-arm pivotal trials: TRUST-I in China, and TRUST-II, a global trial. Taletrectinib has been granted Breakthrough Therapy Designations by both the U.S. FDA and China’s NMPA for the treatment of advanced or metastatic ROS1-positive NSCLC. China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC that have and have not previously been treated with ROS1 tyrosine kinase inhibitors (TKIs). Worldwide development and commercial rights to taletrectinib have been in-licensed from Daiichi Sankyo. Rights to taletrectinib have been out-licensed in China, Japan, and Korea.
More than one million people globally are diagnosed with NSCLC annually, the most common form of lung cancer. It is estimated that approximately 1-3% of people with NSCLC are ROS1-positive. Up to one-third of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain. Approved ROS1 TKIs have provided significant benefits to ROS1-positive NSCLC patients, however, patients are still in need of tolerable therapies that provide sustained and durable disease control.
mIDH1
Safusidenib is a novel, oral, potent, targeted inhibitor of mutant IDH1 (mIDH1) being evaluated in a global Phase 2 trial in patients with grades 2 and 3 IDH1-mutant glioma.
Safusidenib has shown high blood-brain barrier penetration in both pre-clinical and clinical studies and demonstrated anti-tumor activity and tolerability in a Phase 1 clinical trial. Worldwide development and commercial rights to safusidenib have been in-licensed from Daiichi Sankyo, excluding in Japan.
Glioma is the most common type of adult brain cancer, and IDH1 mutations are present in the majority of low-grade diffuse gliomas. There are currently no targeted treatments approved for IDH-mutant glioma; current options include surgery, radiation, and chemotherapy.
BET
NUV-868, a BD2-selective oral small molecule bromodomain and extra-terminal (BET) inhibitor, inhibits BRD4. BRD4 is a key member of the BET family, which epigenetically regulates proteins that control tumor growth and differentiation.
NUV-868 is almost 1,500 times more selective for BD2 than BD1 and is designed to alleviate the therapeutic limiting toxicities observed by other non-BD2 selective BET inhibitors. NUV-868 in combination with androgen-receptor directed therapies may help to overcome resistance in prostate cancer. In addition, NUV-868 in combination with PARP inhibitors may act synergistically to increase efficacy across multiple solid tumors.
We have completed a Phase 1 monotherapy dose escalation study of NUV-868 and determined a Maximum Tolerated Dose in patients with advanced solid tumors. We are also conducting a Phase 1b dose escalation study of NUV-868 in combination with olaparib in patients with ovarian cancer, pancreatic cancer, metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer, and other solid tumors, and in combination with enzalutamide in patients with mCRPC. Treatment remains ongoing in the Phase 1b combination study.
DDC
NUV-1511, our first drug-drug conjugate (DDC) clinical candidate, is a derivative of a widely used chemotherapy agent.
Our proprietary, small molecule DDC’s leverage a novel therapeutic approach within the drug-conjugate class of anti-cancer therapies. The platform is designed to selectively deliver potent anti-cancer therapeutics to cancer cells to exert greater toxicity against these target tumor cells than against healthy non-target tissues. Utilizing this technology, we are able to design potent oncology-focused chimeric small molecules which combine tumor-targeting specificity with anti-cancer activity of known oncology agents. We believe our DDC technology will be broadly applicable and can be replicated across many existing therapies to transform the standard-of-care in multiple oncology indications.
In March 2024, we initiated a Phase 1/2 study of NUV-1511. The dose escalation portion of the study employs a flexible design that allows for the potential to explore two dosing schedules for NUV-1511 with the goal of establishing the recommended Phase 2 dose. The study will initially evaluate safety and tolerability, pharmacokinetic profile, and assess for signs of clinical activity in patients with advanced solid tumors who previously received and progressed on or after treatment with Enhertu® and/or Trodelvy® per approved U.S. Food and Drug Administration (FDA) labeling, human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, metastatic castration-resistant prostate cancer (mCRPC), advanced pancreatic cancer, and platinum-resistant ovarian cancer (PROC).
