AsiDNA (etidaligide) / Valerio Therap - LARVOL DELTA

REVOCAN: Safety and Efficacy of AsiDNATM, a DNA Repair Inhibitor, Administered Intravenously in Addition to PARP Inhibitors in Patients With Relapsed Platinum Sensitive Ovarian Cancer Already Treated With PARP Inhibitors Since at Least 6 Months (clinicaltrials.gov) - P1/2 | N=13 | Terminated | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris | N=26 ➔ 13 | Trial completion date: Oct 2023 ➔ Apr 2024 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2023 ➔ Apr 2024; Treatment availability issue: The manufacturer of AsiDNA™ decided to cease production to develop an improved version, and the contract ensuring access to this molecule has expired.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Ovarian Cancer • Solid Tumor • BRCA • MUC16

Valerio Therapeutics Reports its Half-Year 2024 Financial Results and Provides an Update on its Activities (Businesswire) - "AsiDNA specifically targets tumor cells and has a very favorable safety profile in humans observed in four Phase 1/1b clinical studies...Given the limited efficacy observed during phase 1 clinical trials especially as a monotherapy, it was not considered beneficial for patients to further pursue clinical development of AsiDNA or initiate a phase 2 study. Furthermore, AsiDNA is assumed to generate no revenue and only have minor carrying costs for company industrial property. For all these reasons, it was decided to deprioritize AsiDNA clinical investigation..."

Pipeline update • Trial status • Oncology • Solid Tumor

Study to Assess Safety and Efficacy of AsiDNA in Combination with Olaparib in Participants with Recurrent Solid Tumors (clinicaltrials.gov) - P1/2 | N=3 | Completed | Sponsor: Valerio Therapeutics | Recruiting ➔ Completed | Phase classification: P1b/2 ➔ P1/2 | N=115 ➔ 3 | Trial completion date: Apr 2027 ➔ Oct 2023 | Trial primary completion date: Dec 2026 ➔ Oct 2023

Combination therapy • Enrollment change • Pan tumor • Phase classification • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

A Phase Ib/II Study on AsiDNA™ in Association with Re-irradiation in Children, Adolescents and Young Adults with relapsing High-grade Glioma (ISPNO 2024) - "Considering the low PFS as well as lack of efficacy on PD markers, the DSMB recommended stopping the study."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Medulloblastoma • Oncology • Solid Tumor

The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest. (PubMed, NAR Cancer) - "Mechanisms comparable to those identified in vitro were detected both in vivo, in the intestine and ex vivo, in precision cut lung slices. Collectively, the results suggest that AsiDNA™ can partially protect healthy tissues from radiation toxicity by triggering a G1/S arrest in normal cells."

Journal • Fibrosis • Immunology • Oncology • Respiratory Diseases • CDKN1A

Combination DNA Damage Response (DDR) Inhibitors to Overcome Drug Resistance in Ovarian Cancer. (PubMed, Cancer Treat Res) - "DDRi-DDRi combinations such as PARPi-ATRi, PAPRi-WEE1i and PARPi-AsiDNA can overcome multiple resistance mechanisms to PARP inhibition. In addition, DDRi-DDRi combinations can provide viable treatment options for patients with platinum-resistant disease. In the present chapter we discuss rationale of DDRi-DDRi strategies that capitalize on genomic alterations found in ovarian cancer and other solid tumors and may provide in the near future new treatment options for these patients."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Preliminary results of an open-label, multicentric, phase Ib/II study to assess the safety and efficacy of AsiDNA, a DNA repair inhibitor, in addition to PARP inhibitor in patients with relapsed platinum sensitive ovarian cancer already treated with PARPi for at least 6 months (RevoCAN) (ESMO 2023) - "Methods Patients (pts) who received a PARPi (niraparib, olaparib or rucaparib) in maintenance after platinum-based therapy for at least 6 months and who had an isolated increase of CA125 according to Rustin criteria without RECIST progression were includable. Study was stopped after 12 pts (the company stopped the fabrication of AsiDNA™ for new pts). Conclusions AsiDNA in addition to PARPi in pts with biological progression under PARPi is safe, and stabilization (> 6 months) has been observed in 3 pts."

Clinical • P1/2 data • Oncology • Ovarian Cancer • Solid Tumor

AsiDNA Children, Adolescents and Young Adults (clinicaltrials.gov) - P1/2 | N=8 | Terminated | Sponsor: Institut Curie | Trial completion date: Dec 2023 ➔ Sep 2023 | Suspended ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Sep 2023; IDMC recommendations

Trial completion date • Trial primary completion date • Trial termination • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

AsiDNA Children, Adolescents and Young Adults (clinicaltrials.gov) - P1/2 | N=8 | Suspended | Sponsor: Institut Curie | N=34 ➔ 8 | Trial completion date: May 2025 ➔ Dec 2023 | Recruiting ➔ Suspended | Trial primary completion date: May 2024 ➔ Dec 2023

Enrollment change • Trial completion date • Trial primary completion date • Trial suspension • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

REVOCAN: Safety and Efficacy of AsiDNATM, a DNA Repair Inhibitor, Administered Intravenously in Addition to PARP Inhibitors in Patients With Relapsed Platinum Sensitive Ovarian Cancer Already Treated With PARP Inhibitors Since at Least 6 Months (clinicaltrials.gov) - P1/2 | N=26 | Recruiting | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris | Trial primary completion date: Oct 2021 ➔ Oct 2023

Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • BRCA • MUC16

Onxeo Reports Full Year 2022 Financial Results and Provides Clinical Development Updates (Businesswire) - "In 2023, the Company will continue to pursue its value creation strategy based on the development of its therapeutic innovations until proof of concept in humans, with the following main milestones: AsiDNA™: (i) Enrollment to continue in the U.S. phase 1b/2 trial in combination with Olaparib in ovarian, breast and prostate cancers to identify the RP2D in combination with Olaparib; (ii) Clinical updates expected in the second half of 2023 from phase 1b/2 trials conducted in France and European Union under the sponsorship of academic centers; (iii) Submissions for publications in international scientific journals of the results of preclinical or clinical studies as part of the development plan to demonstrate the potential of AsiDNA."

Clinical data • Enrollment status • P1/2 data • Preclinical • Brain Cancer • Breast Cancer • CNS Tumor • Genito-urinary Cancer • Glioma • Gynecologic Cancers • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Study To Assess Safety And Efficacy Of AsiDNA In Combination With Olaparib In Participants With Recurrent Solid Tumors (clinicaltrials.gov) - P1b/2 | N=115 | Recruiting | Sponsor: Onxeo | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Pan tumor • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

AsiDNA® treatment protects healthy cells from anticancer treatment toxicity (AACR 2022) - P1 | "We monitored cell survival, DNA damage (comet assays) and repair (53BP1 and Rad51 foci), DNA-PK (HSP90 and H2AX phosphorylation) and PARP (PARylation) activation, cell cycle modulation and p53 dependency to identify mechanisms underlying the effects of AsiDNA on healthy cells. In vivo, long-term treatment of several patients with carboplatine+/-paclitaxel + AsiDNA showed no increase of chemotherapies toxicities allowing longer periods of disease control and suggesting a protective effect of AsiDNA. These findings suggest that the combination of AsiDNA with anticancer treatments should provide a means to attenuate therapy-induced toxicity, while showing the well-documented synergy in tumor cells, thus providing an opportunity to increase the therapeutic window."

Clinical • Oncology • HSP90AA1 • RAD51 • TP53BP1

ONXEO Provides Update on the Development Program For Its First-in-class Drug Candidate AsiDNA (Businesswire) - "Additionally, AsiDNA^TM is being evaluated in Children and young adults with recurrent high-grade glioma (HGG). This phase 1b/2 trial, sponsored by Institut Curie, is being conducted within the framework of the European ITCC consortium. The trial is evaluating the safety and clinical activity of AsiDNA^TM in combination with radiotherapy in children or young adults with recurrent HGG. The trial has already been opened at 8 clinical trial sites in France and 5 patients have been enrolled. To date, the combination has been well tolerated. Further trial site activation is planned for 2023 in Italy, the Netherlands, and Germany."

Trial status • Brain Cancer • CNS Tumor • Glioma • Oncology

ONXEO Provides Update on the Development Program For Its First-in-class Drug Candidate AsiDNA (Businesswire) - P1b/2 | N=26 | REVOCAN (NCT04826198) | "The REVOCAN study is an open label, multicenter, phase 1b/2 study evaluating the safety and efficacy of AsiDNATM, in combination with PARP inhibitors in patients with relapsed platinum sensitive ovarian cancer already under treatment with a PARP inhibitor....The combination of AsiDNATM and PARPi was generally well tolerated with no new safety signals or dose limiting toxicities. The IA also demonstrated encouraging clinical activity with six patients achieving a stable disease (SD) and one patient demonstrating a complete response (CR) with disease control rate of around 70%. The study continues to enroll patients. The detailed results of the IA will be published by the investigator."

P1/2 data

AsiDNA (AACR-NCI-EORTC 2022) - No abstract available

Oncology

AsiDNA Children, Adolescents and Young Adults (clinicaltrials.gov) - P1/2 | N=34 | Recruiting | Sponsor: Institut Curie | Active, not recruiting ➔ Recruiting | Trial completion date: Jan 2025 ➔ May 2025 | Initiation date: Feb 2022 ➔ May 2022 | Trial primary completion date: Jan 2024 ➔ May 2024

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Brain Cancer • Glioma • Oncology • Solid Tumor

Inhibition of DNA Repair by Inappropriate Activation of ATM, PARP, and DNA-PK with the Drug Agonist AsiDNA. (PubMed, Cells) - "This pan-nuclear phosphorylation of H2AX correlates with the massive inhibition, at damage sites induced by irradiation, of the recruitment of repair enzymes involved in DSB repair by homologous recombination and nonhomologous end joining. These results highlight the interest in a new generation of DNA repair inhibitors targeting DNA damage signaling."

Journal • Oncology • PARP1 • TP53BP1 • XRCC4

Onxeo: Initial IND Application for AsiDNA Granted “Study May Proceed” by the U.S. FDA (Businesswire) - "Onxeo S.A...announced that the U.S. Food and Drug Administration (FDA) has cleared the initial IND for its first-in-class drug candidate AsiDNA. This is the first US IND Onxeo filed since the US team came on board in April 2022. This FDA decision enables the Company to initiate a Phase 1b/2 multicenter, basket trial to assess the safety and efficacy of AsiDNA in combination with the PARP inhibitor Olaparib in patients with epithelial ovarian cancer, breast cancer and metastatic castration-resistant prostate cancer (mCRPC) who have demonstrated progression on previous PARP inhibitor therapy. The Company plans to initiate the trial in the second half of 2022 at 3-5 potential clinical sites across the United States."

IND • New P1/2 trial • Breast Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Prostate Cancer

AsiDNA Children, Adolescents and Young Adults (clinicaltrials.gov) - P1/2 | N=34 | Active, not recruiting | Sponsor: Institut Curie

New P1/2 trial • Brain Cancer • Glioma • Oncology • Solid Tumor

DNA repair-interfering molecule AsiDNA® overcomes resistance to tyrosine kinase inhibitors in lung cancer (AACR 2022) - "We used EGFR-mutated (PC9 and HCC827) or ALK-translocated (H3122) lung tumor cells as well as a PC9 xenograft model, to assess whether a long-term combination of AsiDNA and TKI (erlotinib or osimertinib for EGFR-mutated and alectinib for ALK-translocated cells) could prevent the emergence of resistances arising from DTC. Inhibition of the DNA repair machinery using AsiDNA efficiently prevented the emergence of resistances to tyrosine kinase inhibitors and point to the therapeutic opportunity of combining AsiDNA and TKI to overcome resistance in clinical situation. These findings should have immediate implications to design drug combination strategies to prevent TKI-induced resistance in lung cancers."

Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PARP1

Onxeo to Present New Preclinical Data Highlighting AsiDNA’s Ability to Fight Tumor Resistance and Protect From Anticancer Treatment Toxicity at AACR Annual Meeting 2022 (Businesswire) - "Onxeo S.A...today announced that it will present new preclinical data confirming AsiDNA™’s abilities to protect from anticancer treatment toxicity and fight tumor resistance during poster and oral sessions at the upcoming American Association for Cancer Research Annual Meeting (AACR Annual Meeting 2022, April 8-13, 2022)....The oral presentation will describe how AsiDNA™ efficiently prevented the emergence of resistances to tyrosine kinase inhibitors in several models of targetable oncogenic addiction and will point to the therapeutic opportunity of combining AsiDNA™ and TKI (tyrosine kinase inhibitors) to overcome resistance in a clinical setting."

Preclinical • Oncology

DRIIV-1: AsiDNA (a DNA Repair Inhibitor) Administered IntraVenously in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Onxeo | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Oncology • Solid Tumor

Translational relevance of the combined treatment PARP inhibitors and AsiDNA in homologous recombination proficient tumors (ESMO-TAT 2022) - "We analyzed the effects of AsiDNA treatment on double strand break repair activities through homologous recombination and assessed the efficacy of the combination with PARPi (Olaparib and Talazoparib) in HRP tumor models. These point to the therapeutic opportunity of combining AsiDNA and PARPi in HRP tumors to overcome intrinsic or acquired resistance in clinical situation."

Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA • BRCA1 • HRD • RAD51

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