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 compounds that have resulted from our drug discovery and development programs, which include a cyclin-dependent kinase (CDK) inhibitor program, a bromodomain and extra-terminal (BET) inhibitor program, and a drug-drug conjugate (DDC) platform that to date has yielded investigational compounds targeting solid tumors.
Program
potential indication(s)
Current Stage
preclinical
phase 1
Phase 2
Phase 3
ANTICIPATED MILESTONES &
RECENT UPDATES
rGBM
NUV-422
Phase 1 Dose Escalation Data by Year End 2022;
Pre-surgical Study Initiation Mid-2022;
Phase 2 Initiation by Year End 2022
aBC
NUV-422
Phase 2 Initiation by Year End 2022
aBC
Brain Mets
NUV-422
Phase 2 Initiation by Year End 2022
NUV-422
(CDK 2/4/6)
aBC
NUV-422 +
Fulvestrant
Phase 1b Initiation by Year End 2022
NUV-422
Phase 2 Initiation by Year End 2022
mCRPC
NUV-422 +
Enzalutamide
Phase 1b Initiation by Year End 2022
Advanced
Solid Tumors
NUV-868
First Patient Dosed in Phase 1 Dose Escalation in Q1 2022
NUV-868
(BET)
Ovarian, TNBC,
Pancreatic & mCRPC
NUV-868 +
Olaparib
Phase 1b Initiation by Year End 2022
mCRPC
NUV-868 +
Enzalutamide
Phase 1b Initiation by Year End 2022
Drug-Drug Conjugate
Platform
Solid Tumors
Clinical Candidate Selection by Year End 2022
aBC: Advanced Breast Cancer; BET: Bromodomain and Extra-Terminal Motif Proteins; CDK: Cyclin-Dependent Kinase; rGBM: Recurrent Glioblastoma Multiforme;
mCRPC: Metastatic Castration-Resistant Prostate Cancer; TNBC: Triple-Negative Breast Cancer
CDK 2/4/6
NUV-422, our lead product candidate, is a selective small molecule cyclin-dependent kinase (CDK) 2/4/6 inhibitor.
CDK4/6 inhibitors are known clinical entities with proven efficacy, but cancer cells can evade these treatments by increasing signaling through CDK2. Inhibition of CDK2 in addition to CDK4/6 cuts off the tumor’s natural escape route. NUV-422 is a potent inhibitor of CDK 2, 4 and 6. Preclinical studies have shown that NUV-422 has favorable blood-brain barrier penetration. NUV-422 is also designed to limit CDK1 inhibition, a potential cause of toxicity in other second-generation inhibitors. NUV-422 is being studied in multiple advanced solid tumors, including recurrent/refractory glioblastoma, hormone receptor-positive advanced breast cancer (HR+ aBC) with and without brain metastases, and metastatic castration-resistant prostate cancer (mCRPC).
NUV-422 has been granted the U.S. Food and Drug Administration (FDA) Orphan Drug Designation for the treatment of patients with malignant gliomas and Fast Track Designation for the treatment of high-grade gliomas.
NUV-422 is currently being studied in three clinical trials:
- Phase 1/2 Monotherapy Study (NUV-422-02): We are currently enrolling patients in the dose escalation portion of the Phase 1 study. After the determination of the recommended Phase 2 dose, the Phase 2 portion will enroll recurrent GB, HR+/HER2- aBC, and mCRPC patients. This study is designed to evaluate safety and efficacy of NUV-422 as a monotherapy in these advanced solid tumors.
- Phase 1b/2 aBC Study of NUV-422 in combination with fulvestrant (NUV-422-03): We plan to initiate a Phase 1b/2 study in patients with HR+/HER2- aBC who have received prior hormonal therapy combined with an approved CDK 4/6 inhibitor. This study will begin with a Phase 1b dose escalation portion designed to evaluate safety and tolerability of the NUV-422 plus fulvestrant combination and to determine a recommended Phase 2 combination dose of NUV-422. The Phase 2 portion is a randomized, non-comparative study designed to evaluate the safety and efficacy of NUV-422 in combination with fulvestrant relative to NUV-422 monotherapy and fulvestrant monotherapy.
- Phase 1b/2 mCRPC study of NUV-422 in combination with enzalutamide (NUV-422-04): We plan to initiate a Phase 1b/2 study in patients with mCRPC who have received prior treatment with abiraterone acetate. This study will begin with a Phase 1b dose escalation portion designed to evaluate safety and tolerability of NUV-422 plus enzalutamide combination and to determine a recommended Phase 2 combination dose of NUV-422. The Phase 2 portion will be an open-label, single-arm study designed to evaluate safety and efficacy of NUV-422 in combination with enzalutamide in previously treated mCRPC patients who can have measurable or nonmeasurable disease.
BET
NUV-868, a BD2-selective oral small molecule bromodomain and extra-terminal (BET) inhibitor, inhibits BRD4, a key member of the BET family that 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 have synergistic activity to increase efficacy across multiple solid tumors.
We dosed the first patient in a Phase 1 dose escalation study of NUV-868 for the treatment of patients with advanced solid tumors in the first quarter of 2022. This Phase 1 study is designed to determine the safety and dose of NUV-868 to be used as a monotherapy and in combination with olaparib or enzalutamide for the Phase 2 and 2b portions of the study.
WEE1
NUV-569 is a differentiated oral small molecule selective inhibitor of Wee1 kinase, an important regulator of DNA damage repair. Wee1 inhibitors increase the efficacy of DNA-damaging therapies by forcing cancers to replicate before they can repair their damaged DNA.
NUV-569 is a highly potent Wee1 kinase inhibitor that synergizes with DNA-damaging agents to enhance cancer cell death. NUV-569 is designed to avoid off-target effects by improving its kinase selectivity. NUV-569 has low inhibition of PLK1, which may improve tolerability including reduction of bone marrow and GI toxicity.
We intend to submit an IND for NUV-569 by year end 2022 and initiate Phase 1 trials in patients with advanced solid tumors following IND clearance.
A2A
Our adenosine receptor inhibitors are designed to have high affinity for the A2A adenosine receptor, which plays multiple critical roles in human physiology and pathophysiology including anti-cancer immunity.
We also designed our adenosine receptor inhibitors to have a reduced affinity for the adenosine A1 receptor, which may potentially improve tolerability.
We intend to nominate a clinical development candidate by year end 2022.
DDC
Our proprietary Drug-Drug Conjugate (DDC) platform leverages a novel therapeutic approach within the DDC class of anti-cancer therapies designed to selectively deliver potent targeted therapeutics to cancer cells to exert greater toxicity against these target cells than against healthy non-target tissues.
Utilizing this platform, we are able to conjugate tissue-selective targeted small molecules with anti-tumor agents to create unique therapeutic candidates.
We plan to select the first clinical candidate for the DDC program by the end of 2022.
