inixaciclib (NUV-422) / Nuvation Bio - LARVOL DELTA

Discovery of macrocyclic CDK2/4/6 inhibitors with improved potency and DMPK properties through a highly efficient macrocyclic drug design platform. (PubMed, Bioorg Chem) - "Using dihedral angle scan and structure-based, computer-aided drug design to select an optimal ring-closing site and linker length for the macrocycle, we identified compound 8 as a potent new CDK2/4/6 inhibitor with optimized cellular potency and safety profile compared to NUV422. Our platform leverages both experimentally-solved as well as generative chemistry-derived macrocyclic structures and can be deployed to streamline the design of macrocyclic new drugs from acyclic starting compounds, yielding macrocyclic compounds with enhanced potency and improved drug-like properties."

Journal • Oncology

Phase 1/2 dose escalation study of NUV-422, a potent inhibitor of cyclin-dependent kinases 2, 4, and 6, in recurrent or refractory (r/r) high-grade gliomas (HGG) and solid tumors. (ASCO 2022) - P1/2 | "Enrollment was initiated in December 2020, and dose escalation is ongoing. The NUV-422 program will also be expanded in 2022 to include additional studies in mBC and mCRPC in combination with standard of care treatments."

P1/2 data • Brain Cancer • Breast Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • HER2 Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • CDK1 • HER-2

Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors (clinicaltrials.gov) - P1/2 | N=72 | Terminated | Sponsor: Nuvation Bio Inc. | N=269 ➔ 72 | Trial completion date: Dec 2023 ➔ Aug 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2023 ➔ Aug 2022; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Brain Cancer • Breast Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Glioma • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • CAST • HER-2

Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Nuvation Bio Inc. | N=236 ➔ 0 | Suspended ➔ Withdrawn

Combination therapy • Enrollment change • Trial withdrawal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Study of NUV-422 in Combination With Enzalutamide in Patients With mCRPC (clinicaltrials.gov) - P1b/2 | N=0 | Withdrawn | Sponsor: Nuvation Bio Inc. | N=76 ➔ 0 | Suspended ➔ Withdrawn

Combination therapy • Enrollment change • Trial withdrawal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Nuvation Bio Announces Discontinuation of NUV-422 Clinical Development Program (Businesswire) - "Nuvation Bio Inc...announced that it will prioritize NUV-868 and development of its novel small molecule DDC platform and discontinue clinical development of NUV-422. The decision to discontinue clinical development of NUV-422 is the result of an internal risk-benefit analysis factoring in feedback received from the U.S. Food and Drug Administration (FDA) in a partial clinical hold letter for the Company’s monotherapy Phase 1/2 study (Protocol NUV-422-02) and clinical hold letters for its combination Phase 1b/2 studies (Protocols NUV-422-03 and NUV-422-04)....Enrollment is ongoing in the Phase 1 monotherapy study of NUV-868, and the Company has planned Phase 1b studies of NUV-868 in combination with olaparib or enzalutamide to enhance the potential value of this program across multiple tumor types."

Discontinued • Trial status • Oncology • Solid Tumor

Study of NUV-422 in Combination With Enzalutamide in Patients With mCRPC (clinicaltrials.gov) - P1b/2 | N=76 | Suspended | Sponsor: Nuvation Bio Inc. | Initiation date: Apr 2022 ➔ Sep 2022 | Recruiting ➔ Suspended

Combination therapy • Trial initiation date • Trial suspension • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC (clinicaltrials.gov) - P1/2 | N=236 | Suspended | Sponsor: Nuvation Bio Inc. | Initiation date: Apr 2022 ➔ Sep 2022 | Recruiting ➔ Suspended

Combination therapy • Trial initiation date • Trial suspension • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors (clinicaltrials.gov) - P1/2 | N=269 | Active, not recruiting | Sponsor: Nuvation Bio Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Breast Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2

Nuvation Bio Announces FDA Partial Clinical Hold for Phase 1 Study of NUV-422 in Solid Tumors (Businesswire) - "Nuvation Bio Inc...announced the Food and Drug Administration (FDA) has placed a partial clinical hold on the Company’s Phase 1 dose escalation study of NUV-422 in solid tumors, including high grade glioma, HR+/HER2- advanced breast cancer and metastatic castration resistant prostate cancer...While the partial hold is in place, no new patients will be enrolled in the NUV-422 program, although current study participants may continue to be treated in the Phase 1 study....The Company will provide updates on the direction of the NUV-422 program after it has completed its internal risk-benefit analysis which will factor in feedback from FDA."

FDA event • Breast Cancer • Genito-urinary Cancer • Glioma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Prostate Cancer

Study of NUV-422 in Combination With Enzalutamide in Patients With mCRPC (clinicaltrials.gov) - P1b/2 | N=76 | Recruiting | Sponsor: Nuvation Bio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC (clinicaltrials.gov) - P1/2 | N=236 | Recruiting | Sponsor: Nuvation Bio Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Nuvation Bio Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Business Update (Businesswire) - "The Company will initiate a Phase 1 monotherapy dose escalation study of NUV-868 in mid-2022....The Company began a monotherapy Phase 1/2 study of NUV-422 in December 2020 in high grade gliomas and later amended the protocol in the second quarter of 2021 to include HR+/HER2- advanced breast cancer (with and without brain metastases) and mCRPC. The Company is continuing to enroll patients in the monotherapy Phase 1 dose escalation portion of the study, with safety data expected in 2022."

New P1 trial • P1 data • Brain Cancer • Breast Cancer • Glioma • Oncology • Prostate Cancer • Solid Tumor

Study of NUV-422 in Combination With Fulvestrant in Patients With HR+HER2- aBC (clinicaltrials.gov) - P1/2; N=236; Not yet recruiting; Sponsor: Nuvation Bio Inc.

Clinical • Combination therapy • New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Nuvation Bio Provides Corporate Update and Highlights Key 2022 Milestones (PRNewswire) - "In 2022, Nuvation Bio seeks to achieve the following milestones across its broad pipeline of potential product candidates: NUV-422...Identify a recommended Phase 2 dose and initiate Phase 2 monotherapy dose expansion cohorts for NUV-422 in glioblastoma multiforme, advanced breast cancer (aBC), and metastatic castration-resistant prostate cancer (mCRPC), Initiate Phase 1b combination studies for NUV-422 in aBC and mCRPC, Present safety data from NUV-422 Phase 1 dose escalation study."

Enrollment status • P1 data • Breast Cancer • Glioblastoma • Oncology • Prostate Cancer • Solid Tumor

Nuvation Bio Receives FDA Fast Track Designation for NUV-422 for the Treatment of High-Grade Gliomas, Including Glioblastoma Multiforme (PRNewswire) - "Nuvation Bio Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to NUV-422, a cyclin-dependent kinase (CDK) 2/4/6 inhibitor, for the treatment of patients with high-grade gliomas, including glioblastoma multiforme...'We look forward to continuing to work closely with the FDA to expedite the development of NUV-422 with data from the Phase 1 portion of the study, which is on track for 2022.'"

Fast track designation • New P1 trial • Glioblastoma • Glioma • Oncology

Nuvation Bio Announces FDA Clearance of Investigational New Drug Application for NUV-422 for the Treatment of Prostate Cancer (PRNewswire) - "Nuvation Bio Inc...announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application to evaluate NUV-422, a cyclin-dependent kinase (CDK) 2/4/6 inhibitor, for the treatment of prostate cancer....With the clearance of this IND in prostate cancer, Nuvation Bio will be initiating a Phase 1b/2 study in patients with mCRPC who have received prior treatment with abiraterone acetate."

IND • Genito-urinary Cancer • Oncology • Prostate Cancer

Nuvation Bio Announces FDA Clearance of Investigational New Drug Application for NUV-422 for the Treatment of Advanced Breast Cancer (PRNewswire) - "Nuvation Bio Inc...announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application to evaluate NUV-422, a cyclin-dependent kinase (CDK) 2/4/6 inhibitor, for the treatment of advanced breast cancer...'We look forward to sharing data from the Phase 1 dose escalation portion in the second half of 2022.'"

IND • Breast Cancer • Oncology

Nuvation Bio Reports Third Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "Enrollment ongoing in Phase 1/2 multiple expansion cohort study of NUV-422....Enrollment is ongoing and data from the Phase 1 portion of the study is expected in 2022."

P1 data • Brain Cancer • CNS Tumor • Glioma • Oncology

Nuvation Bio Reports Second Quarter 2021 Financial Results and Provides Business Update (PRNewswire) - "Enrollment ongoing in Phase 1/2 multiple expansion cohort study of NUV-422....Enrollment is ongoing and data from the Phase 1 portion of the study is expected in 2022."

Enrollment status • P1 data • Brain Cancer • CNS Tumor • Glioma • Oncology

Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors (clinicaltrials.gov) - P1/2; N=218; Recruiting; Sponsor: Nuvation Bio Inc.; N=80 ➔ 218

Clinical • Enrollment change • Brain Cancer • Breast Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2

Nuvation Bio Granted Orphan Drug Designation for NUV-422 for the Treatment of Patients with Malignant Gliomas (PRNewswire) - “Nuvation Bio Inc…announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to NUV-422, a cyclin-dependent kinase (CDK) 2/4/6 inhibitor, for the treatment of patients with malignant gliomas…Patient enrollment and dosing is ongoing in the Phase 1/2 study of NUV-422 in adult patients with recurrent or refractory high-grade gliomas, including glioblastoma multiforme (GBM)….The Phase 2 dose expansion part of the study is expected to initially focus on patients with high-grade gliomas and is designed to evaluate overall response rate, duration of response and survival. Data from the Phase 1 portion of this study is expected in 2022.”

Orphan drug • P1/2 data • Glioma • Oncology

Nuvation Bio Closes Transaction with Panacea, Debuts as Publicly Traded Oncology Company - "Nuvation Bio Inc...announced the completion of its business combination with Panacea Acquisition Corp...trading its shares on the New York Stock Exchange (NYSE) under the ticker symbol 'NUVB' on February 11, 2021....Nuvation Bio will have a total cash position of approximately $830 million...Nuvation Bio anticipates submitting up to five additional Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA) by 2026 for therapies targeting some of the most difficult-to-treat solid and hematologic cancers."

IND • M&A • Brain Cancer • Glioma • Hematological Malignancies • Oncology • Solid Tumor

Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas (clinicaltrials.gov) - P1/2; N=80; Recruiting; Sponsor: Nuvation Bio, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Brain Cancer • Glioma • Oncology • Solid Tumor

Nuvation Bio Announces FDA Acceptance of Investigational New Drug (IND) Application for NUV-422 for Treatment of Patients with High-grade Gliomas (PRNewswire) - "Nuvation Bio, Inc...today announced that the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for NUV-422, an investigational CDK2/4/6 inhibitor. The company plans to initiate enrollment in a Phase 1/2 study of NUV-422 in patients with high-grade gliomas by the first quarter of 2021...The company anticipates reporting top-line data from that part of the study in 2022."

Enrollment status • IND • P1/2 data • Brain Cancer • Glioma • Oncology