NMS-293 / Nerviano Medical Sciences - LARVOL DELTA

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1/2 | N=150 | Active, not recruiting | Sponsor: Nerviano Medical Sciences | Trial completion date: Nov 2025 ➔ Sep 2027 | Trial primary completion date: Jun 2025 ➔ May 2027

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • EGFR • IDH1 • IDH2 • MGMT • TERT

Study of NMS-03305293 in Adult Patient With Relapsed Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Nerviano Medical Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Study of NMS-03305293 in Adult Patients With Relapsed Ovarian Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Nerviano Medical Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor

Study of NMS-03305293 in Adult Patients With Relapsed Ovarian Cancer (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Nerviano Medical Sciences | Trial completion date: Mar 2027 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ May 2027

Platinum resistant • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor

Study of NMS-03305293 in Adult Patient With Relapsed Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Nerviano Medical Sciences | Trial completion date: Nov 2026 ➔ Feb 2027

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Study of NMS-03305293 in Adult Patients With Relapsed Ovarian Cancer (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Nerviano Medical Sciences

New P1 trial • Oncology • Ovarian Cancer • Solid Tumor

Study of NMS-03305293 in Adult Patient With Relapsed Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Nerviano Medical Sciences

New P1 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1/2 | N=150 | Active, not recruiting | Sponsor: Nerviano Medical Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • EGFR • IDH1 • IDH2 • MGMT • TERT

Study of NMS-03305293 in Pts with Selected Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=52 | Terminated | Sponsor: Nerviano Medical Sciences | N=150 ➔ 52 | Trial completion date: Dec 2024 ➔ May 2024 | Active, not recruiting ➔ Terminated; The study closure is related to sponsor decision to shift towards the clinical development of NMS-03305293 in combination in a broader range of indication and not based on emerging safety or efficacy concerns.

Enrollment change • Metastases • Trial completion date • Trial termination • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HER-2

Study of NMS-03305293 in Pts With Selected Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Active, not recruiting | Sponsor: Nerviano Medical Sciences | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Dec 2024

Enrollment closed • Metastases • Trial completion date • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HER-2

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Nerviano Medical Sciences | N=75 ➔ 150

Enrollment change • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • EGFR • IDH1 • IDH2 • MGMT • TERT

Nerviano Medical Sciences Presents Preliminary, Encouraging Clinical Phase 1 Data for PARP-1 Selective Inhibitor at the 35th AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - P1 | N=150 | NCT04182516 | "In PARPA-293-001...NMS-293 has been administered orally in dose escalation as a single agent, in adult patients with selected advanced/metastatic, relapsed/refractory solid tumors who have exhausted standard treatment options. An MTD has been identified at 100 mg BID for 28 days on 28-day cycle, a dose providing exposure in a meaningful, active range relative to preclinical predictions....The most frequent (≥10%) any-grade treatment related adverse events (TRAEs) in PARPA-293-001 were reversible QTcF prolongation, nausea, asthenia, decreased appetite and vomiting, mainly mild/moderate."

P1 data • Oncology • Solid Tumor

Nerviano Medical Sciences Presents Preliminary, Encouraging Clinical Phase 1 Data for PARP-1 Selective Inhibitor at the 35th AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - "As an oral, brain penetrant PARP-1 selective inhibitor, NMS-293 has shown strong antitumor activity and complete tumor regression in BRCA mutated preclinical models as a single agent. NMS-293 shows remarkable selectivity towards PARP-1 and efficiently inhibits cellular PARP activity resulting in selective antiproliferative responses on BRCA mutated cell lines. Furthermore, NMS-293 is synergistic and well tolerated in combination with temozolomide (TMZ) in both MGMT methylated and MGMT unmethylated glioblastoma mouse models."

Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Nerviano Medical Sciences Presents Preliminary, Encouraging Clinical Phase 1 Data for PARP-1 Selective Inhibitor at the 35th AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - P1/2 | N=75 | NCT04910022 | Sponsor: Nerviano Medical Sciences | "The initial clinical data presented in glioma is the first demonstration of our therapeutic hypothesis that a PARP-1 inhibitor can be combined with chemotherapy such as TMZ paving the way for indications outside of BRCA mutant tumors...To date, no DLTs in PARPA-293-002 have been characterized, and overall, NMS-293 was well tolerated with no trends of myelosuppression.... In PARPA-293-002, no TRAEs above grade 3 were reported and the most frequent (≥10%) any-grade TRAEs were: nausea, fatigue, vomiting, decreased appetite, and decreased platelet count, mainly grade 1 adverse events."

P1/2 data • Brain Cancer • Glioma • Oncology • Solid Tumor

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1/2 | N=75 | Recruiting | Sponsor: Nerviano Medical Sciences | N=125 ➔ 75

Enrollment change • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • EGFR • IDH1 • IDH2 • MGMT • TERT

Nerviano Medical Sciences to Present Preliminary Phase 1 PARP1 selective inhibitor data at the 35th AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - "Nerviano Medical Sciences...announced today it will present initial data from the PARP1 inhibitor Phase 1 studies at the upcoming AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, being held October 11-15 in Boston, MA. The PARPA Phase 1 studies, PARPA-293-001 and PARPA-293-002 are evaluating NMS-03305293 (NMS-293), an oral, brain-penetrant PARP-1 selective inhibitor as single agent or in combination with temozolomide, in relapsed/refractory selected solid tumor types (PARPA-293-001) or patients with High-grade gliomas (PARPA-293-002, including glioblastoma). On September 14, 2022, NMS Group entered into a worldwide option agreement with Merck KGaA, Darmstadt, Germany for the development and commercialization of NMS-293."

Licensing / partnership • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Initial Results from 2 Phase I Studies of NMS-03305293, a Selective PARP1 Inhibitor (AACR-NCI-EORTC 2023) - No abstract available

Late-breaking abstract • P1 data • Oncology

Merck KGaA, Darmstadt, Germany Enters Collaboration and Option to License Agreement with Nerviano Medical Sciences to Develop Next-Generation PARP1 Selective Inhibitor (Businesswire) - "Merck KGaA, Darmstadt...announced a collaboration agreement with licensing option with Nerviano Medical Sciences S.r.l. (NMS) for the next-generation highly selective and brain-penetrant PARP1 (poly (ADP-ribose) polymerase) inhibitor, NMS-293....NMS-293 is in early clinical development for the treatment of patients with BRCA-mutated tumors as a single agent and in combination with temozolomide in recurrent glioblastoma....Under the current agreement, Merck KGaA, Darmstadt, Germany will make early payments (up-front and option exercise fees) of up to $65 million to NMS. Furthermore, NMS will receive payments for the achievement of certain development, regulatory and commercial milestones and tiered royalties on net sales by Merck KGaA, Darmstadt, Germany. Upon exercise of the option, NMS will grant to Merck KGaA, Darmstadt, Germany the exclusive rights to research, develop, manufacture, and commercialize NMS-293."

Licensing / partnership • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1/2 | N=125 | Recruiting | Sponsor: Nerviano Medical Sciences | Not yet recruiting ➔ Recruiting | Trial completion date: May 2025 ➔ Nov 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Enrollment open • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

Study of NMS-03305293 in Pts With Selected Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Nerviano Medical Sciences | N=100 ➔ 150 | Trial completion date: Apr 2023 ➔ Dec 2023 | Trial primary completion date: Nov 2021 ➔ Jul 2023

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HER-2

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1/2; N=125; Not yet recruiting; Sponsor: Nerviano Medical Sciences; Initiation date: May 2021 ➔ Sep 2021

Clinical • Trial initiation date • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT • MRI

Ph I/II Study of NMS-03305293+TMZ in Adult Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1/2; N=125; Not yet recruiting; Sponsor: Nerviano Medical Sciences

Clinical • New P1/2 trial • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

Study of NMS-03305293 in Pts With Selected Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=100; Recruiting; Sponsor: Nerviano Medical Sciences; Trial completion date: Jun 2022 ➔ Apr 2023; Trial primary completion date: Apr 2021 ➔ Nov 2021

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HER-2

NMS-P293, a PARP-1 selective inhibitor with no trapping activity and high CNS penetration, possesses potent in vivo efficacy and represents a novel therapeutic option for brain localized metastases and glioblastoma (AACR 2018) - "In agreement with these PD effects, NMS-P293, orally administered as single agent, induced potent dose-related growth inhibition of BRCA mutated tumor model, with cured animals. Furthermore, NMS-P293 also possesses potent synergistic efficacy and tolerability in combination with temozolomide (TMZ) in glioblastoma (GBM) tumor models, including TMZ resistant MGMT hypomethylated GBMs.The unique preclinical features of NMS-P293, which includes a highly permissive profile in GLP drug safety studies, render this compound an appealing candidate for clinical development, both as a single agent and in drug combination therapy regimes."

BRCA Biomarker • PARP Biomarker • Preclinical • Breast Cancer