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)

Advanced ROS1-positive NSCLC

Completing two Phase 2 pivotal studies (TRUST-I & TRUST-II)

Additional TRUST-I data presented at ASCO in 2024;
Additional TRUST-II data to be presented later in 2024;
China NDAs under priority review by China’s NMPA5

Safusidenib2
(mIDH1)

Diffuse
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

ASCO: American Society of Clinical Oncology; BET: Bromodomain and Extra-Terminal motif; mIDH1: mutant isocitrate dehydrogenase 1; ROS1: c-ros oncogene 1. 1. Taletrectinib has been granted Breakthrough Therapy Designations by both the U.S. FDA and China’s NMPA for the treatment of patients with 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 cancer, triple-negative breast cancer (TNBC), advanced pancreatic cancer, 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. Based on results of the TRUST-I clinical study, under priority review for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who either have or have not previously been treated with ROS1 tyrosine kinase inhibitors (TKIs).

ROS1

Taletrectinib is an oral, potent, central nervous system-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 the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I in China, and TRUST-II, a global study. Taletrectinib has been granted Breakthrough Therapy Designations by both the U.S. Food and Drug Administration (FDA) and China’s NMPA for the treatment of patients with advanced or metastatic ROS1-positive NSCLC. Based on results of the TRUST-I clinical study, 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 who either have or 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 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment. While people with other types of lung cancer have seen great advances, there has been limited progress for people with ROS1-positive NSCLC who remain in need of new options.

mIDH1

Safusidenib is a novel, oral, potent, brain penetrant, targeted inhibitor of mutant IDH1 (mIDH1) being evaluated in a global Phase 2 study for the treatment of patients with diffuse 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 study. 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 is a BD2-selective, oral, small molecule bromodomain and extra-terminal (BET) inhibitor that 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. NUV-868 is currently being evaluated in a Phase 1b dose escalation study in combination with olaparib for the treatment of 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 for the treatment of patients with mCRPC.

DDC

NUV-1511, our first clinical-stage drug-drug conjugate (DDC), 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 treated the first patient in 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. FDA labeling, human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer, mCRPC, advanced pancreatic cancer, and platinum-resistant ovarian cancer (PROC).