Last update 01 Nov 2024

BGA-002

Last update 01 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

asPNA

Synonyms

16 base single stranded peptide nucleic acid oligonucleotide ¿ 7 aminoacids peptide, 16-base single-stranded peptide nucleic acid oligonucleotide linked to 7-amino acid peptide

+ [1]

Target

N-Myc

Mechanism

N-Myc inhibitors(MYCN proto-oncogene, bHLH transcription factor inhibitors), Genetic transcription inhibitors

Therapeutic Areas

NeoplasmsRespiratory DiseasesOther Diseases

Active Indication

NeuroblastomaSoft Tissue SarcomaSmall Cell Lung Cancer

Inactive Indication-

Originator Organization

Biogenera SpA

Active Organization

Biogenera SpA

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (EU)

100 Clinical Results associated with BGA-002

100 Translational Medicine associated with BGA-002

100 Patents (Medical) associated with BGA-002

Literatures (Medical) associated with BGA-002

01 Aug 2024·Nucleic Acid Therapeutics

Preclinical Pharmacokinetics in Tumors and Normal Tissues of the Antigene PNA Oligonucleotide MYCN-Inhibitor BGA002

Article

Author: Tonelli, Roberto ; Nieddu, Giammario ; Della Pasqua, Oscar ; Bortolotti, Sonia ; Cerisoli, Lucia ; Angelucci, Silvia ; Bartolucci, Damiano ; Montemurro, Luca ; Amadesi, Camilla ; Scardovi, Anna Lisa ; Hrelia, Patrizia ; Oosterholt, Sean

Although MYCN has been considered an undruggable target, MYCN alterations confer poor prognosis in many pediatric and adult cancers. The novel MYCN-speciﬁc inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay. BGA002 concentrations in plasma showed linear PK, with dose proportional increase across the tested dose levels and similar exposure between male and female and between intravenous and subcutaneous route of administration. Repeated dosing resulted in no accumulation in plasma. Biodistribution up to 7 days after single subcutaneous administration of [¹⁴C]-radiolabeled BGA002 showed broad tissues and organ distribution (suggesting a potential capability to reach primary tumor and metastasis in several body sites), with high concentrations in kidney, liver, spleen, lymph nodes, adrenals, and bone marrow. Remarkably, we demonstrated that BGA002 concentrates in tumors after repeated systemic administrations in three mouse models with MYCN amplification (neuroblastoma, rhabdomyosarcoma, and small-cell lung cancer), leading to a significant reduction in tumor weight. Taking into account the available safety profile of BGA002, these data support further evaluation of BGA002 in patients with MYCN-positive tumors.

01 Dec 2022·Journal of Experimental & Clinical Cancer Research

The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma

Article

Author: Bartolucci, Damiano ; Fischer, Matthias ; Pession, Andrea ; Scardovi, Anna Lisa ; Bortolotti, Sonia ; Cerisoli, Lucia ; Amadesi, Camilla ; Hrelia, Patrizia ; Martelli, Alberto Maria ; Raieli, Salvatore ; Valente, Sabrina ; Nieddu, Giammario ; Paganelli, Francesca ; Lampis, Silvia ; Angelucci, Silvia ; Montemurro, Luca ; Pasquinelli, Gianandrea ; Tonelli, Roberto

AbstractBackgroundNeuroblastoma is a deadly childhood cancer, and MYCN-amplified neuroblastoma (MNA-NB) patients have the worst prognoses and are therapy-resistant. While retinoic acid (RA) is beneficial for some neuroblastoma patients, the cause of RA resistance is unknown. Thus, there remains a need for new therapies to treat neuroblastoma. Here we explored the possibility of combining a MYCN-specific antigene oligonucleotide BGA002 and RA as therapeutic approach to restore sensitivity to RA in NB.MethodsBy molecular and cellular biology techniques, we assessed the combined effect of the two compounds in NB cell lines and in a xenograft mouse model MNA-NB.ResultsWe found that MYCN-specific inhibition by BGA002 in combination with RA (BGA002-RA) act synergistically and overcame resistance in NB cell lines. BGA002-RA also reactivated neuron differentiation (or led to apoptosis) and inhibited invasiveness capacity in MNA-NB. Moreover, we found that neuroblastoma had the highest level of mRNA expression of mTOR pathway genes, and that BGA002 led to mTOR pathway inhibition followed by autophagy reactivation in MNA-NB cells, which was strengthened by BGA002-RA. BGA002-RA in vivo treatment also eliminated tumor vascularization in a MNA-NB mouse model and significantly increased survival.ConclusionTaken together, MYCN modulation mediates the therapeutic efficacy of RA and the development of RA resistance in MNA-NB. Furthermore, by targeting MYCN, a cancer-specific mTOR pathway inhibition occurs only in MNA-NB, thus avoiding the side effects of targeting mTOR in normal cells. These findings warrant clinical testing of BGA002-RA as a strategy for overcoming RA resistance in MNA-NB.

15 Dec 2019·Cancer ResearchQ1 · MEDICINE

A Novel MYCN-Specific Antigene Oligonucleotide Deregulates Mitochondria and Inhibits Tumor Growth in MYCN-Amplified Neuroblastoma

Q1 · MEDICINE

Article

Author: Angelucci, Silvia ; Tonelli, Roberto ; Amadesi, Camilla ; Bartolucci, Damiano ; Venturelli, Leonardo ; Teti, Gabriella ; Montemurro, Luca ; Hrelia, Patrizia ; Raieli, Salvatore ; Cerisoli, Lucia ; Falconi, Mirella ; Scardovi, Anna Lisa ; Fischer, Matthias ; Lampis, Silvia ; Nieddu, Giammario ; Pession, Andrea

AbstractApproximately half of high-risk neuroblastoma is characterized by MYCN amplification. N-Myc promotes tumor progression by inducing cell growth and inhibiting differentiation. MYCN has also been shown to play an active role in mitochondrial metabolism, but this relationship is not well understood. Although N-Myc is a known driver of the disease, it remains a target for which no therapeutic drug exists. Here, we evaluated a novel MYCN-specific antigene PNA oligonucleotide (BGA002) in MYCN-amplified (MNA) or MYCN-expressing neuroblastoma and investigated the mechanism of its antitumor activity. MYCN mRNA and cell viability were reduced in a broad set of neuroblastoma cell lines following BGA002 treatment. Furthermore, BGA002 decreased N-Myc protein levels and apoptosis in MNA neuroblastoma. Analysis of gene expression data from patients with neuroblastoma revealed that MYCN was associated with increased reactive oxygen species (ROS), downregulated mitophagy, and poor prognosis. Inhibition of MYCN caused profound mitochondrial damage in MNA neuroblastoma cells through downregulation of the mitochondrial molecular chaperone TRAP1, which subsequently increased ROS. Correspondingly, inhibition of MYCN reactivated mitophagy. Systemic administration of BGA002 downregulated N-Myc and TRAP1, with a concomitant decrease in MNA neuroblastoma xenograft tumor weight. In conclusion, this study highlights the role of N-Myc in blocking mitophagy in neuroblastoma and in conferring protection to ROS in mitochondria through upregulation of TRAP1. BGA002 is a potently improved MYCN-specific antigene oligonucleotide that reverts N-Myc–dysregulated mitochondrial pathways, leading to loss of the protective effect of N-Myc against mitochondrial ROS.Significance:A second generation antigene peptide oligonucleotide targeting MYCN induces mitochondrial damage and inhibits growth of MYCN-amplified neuroblastoma cells.

100 Deals associated with BGA-002

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neuroblastoma	Preclinical	IT	Biogenera SpA	30 Apr 2022
Soft Tissue Sarcoma	Preclinical	IT	Biogenera SpA	30 Apr 2022
Small Cell Lung Cancer	Preclinical	IT	Biogenera SpA	-

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