On April 30, 2024 Valerio Therapeutics S.A. (Euronext Growth Paris: ALVIO), hereafter "Valerio Therapeutics" or the "Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR) and driver oncogenes, reported its consolidated results for the fiscal year ending December 31, 2023 (Press release, Valerio Therapeutics, APR 30, 2024, View Source [SID1234642467]).
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Dr. Shefali Agarwal, Chairwoman of the Board of Directors and CEO, stated: "I am delighted to announce that the first patient has been dosed with VIO-01 in the first-in-human study VIO-01-101. VIO-01 is the latest optimized drug candidate derived from Valerio Therapeutics’ proprietary PlatON platform of DNA decoy therapeutics, specifically designed to revolutionize cancer treatment. VIO-01, as a next-generation pan-DDR DNA decoy, represents a paradigm shift in therapeutic approach. It is meticulously crafted to not only abrogate multiple DNA repair pathways but also to unleash a potent immune response by activating the STING pathway which plays a pivotal role in identifying DNA abnormalities and mobilizing the immune system to target and eliminate cancer cells. Our commitment to advancing science, pushing boundaries, and making a meaningful impact on cancer treatment remains unwavering. Together, with the support of our dedicated team and the medical community, we look forward to bringing VIO-01 one step closer to transforming the landscape of cancer care."
FY 2023 FINANCIAL RESULTS*
Consolidated income statement (IFRS)
In thousands of euros
31/12/2023 31/12/2022
Revenues 1,800 1,443
Operating expenses, of which:
R&D expenses
(21,054) (19,008)
(11,054)
Other recurring operating income 200 450
Recurring operating income/loss (19,053) (17,115)
Other non-recurring operating income and expenses (1,234) 389
Operating income/loss after income from equity affiliates (20,288) (16,727)
Financial result (39) (2,549)
Tax (17) (285)
Loss (20,344) (19,562)
*Audit procedures on the consolidated accounts have been carried out. The certification report will be issued once the management report has been verified.
Revenues for full-year 2023 totaled €1,8 million corresponding to lump-sum royalties due from Biogen under a license agreement for a non-strategic product.
Operating expenses rose from €19.0 million in 2022 to €21.1 million in 2023, mainly due to:
Personnel expenses, which increase from €8.6 million to €9.3 million, as a result of the reinforcement of the teams, and more specifically to the recruitment of highly qualified scientists as well as the indemnities paid to the former employees who left the Group in 2023.
External expenses increased from €9.4 million to €10.3 million, due to R&D activities, with a focus in 2023 on the clinical development of AsiDNA and on the optimization and preclinical development of VIO-01.
The financial result was a loss of (39) thousand euros.
After taking into account these various items of income and expense, the net result is a loss of €20.34 million compared to a loss of €19.56 million recorded in the previous year.
FINANCIAL STRUCTURE
As of December 31, 2023, the Group had a cash position of €6.8 million, compared with €14.6 million at December 31, 2022. The outstanding financial debt at the end of 2023 amounted to €9.0 million, which includes state-backed loans obtained in February 2021.
The financial statements have been prepared on a going concern basis. This principle has been retained by the Board of Directors on the basis of a cash position of 6.8 million euros on December 31, 2023 and the financing commitments received from its main shareholders Invus and Financière de la Montagne, in an amount of 5 million euros. The Group will thus be able to finance its activities at least until the end of the fourth quarter of 2024 on the basis of its financing plan.
2023 HIGHLIGHTS AND RECENT DEVELOPMENTS
AsiDNA
AsiDNA is a first-in-class DNA Decoy which traps and sequesters DNA-PK, a complex of proteins involved in the DNA Damage Response. AsiDNA thus induces inhibition of DNA-PK-dependent DNA repair in tumor cell, which nevertheless continues its replication cycle, but with damaged DNA, thus leading to cell death. AsiDNA is used in combination with other tumor DNA damaging agents such as radiotherapy and chemotherapy, or in combination with inhibitors of a specific repair pathway such as PARPi or other targeted therapies, to increase their efficacy, notably by abrogating any resistance to these treatments, without increasing toxicity. AsiDNA specifically targets tumor cells and has a very favorable safety profile in humans observed in four Phase 1/1b clinical studies.
The Company continued the clinical development of AsiDNA in 2023.
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 to focus efforts on development of VIO-01, our second-generation drug candidate.
In clinical development
The company initiated a multi-center Phase 1b/2 trial to evaluate 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 who have progressed despite initial treatment with PARP inhibitors. This clinical trial started in January 2023, with the activation of the first clinical study site in the United States, Next Oncology in San Antonio.
In addition, during the first half of the year, Valerio Therapeutics continued its two trials conducted in collaboration with two academic research centers of excellence in oncology:
The Revocan phase 1b/2 investigator sponsored trial evaluating the addition of AsiDNA to combat PARP inhibitor resistance in second-line maintenance treatment of recurrent ovarian cancer.
The Phase 1b/2 trial evaluating AsiDNA in combination with radiotherapy in recurrent high-grade glioma in children, an indication with a particularly poor prognosis.
vio-01
VIO-01, formerly OX425, is a Pan-DDR DNA Decoy Targeting Multiple Proteins & Repair Pathways and represents the most optimal drug candidate selected to enter preclinical development. VIO-01 traps several DDR Proteins Inhibiting Different DNA Repair Pathways. VIO-01 reaches the nucleus and acts as a decoy for several DNA repair enzymes. It has an increased resistance to nucleases and plasmatic stability.
Valerio Therapeutics presented new preclinical data confirming the pan-DDR DNA decoy effect of VIO-01 and the high anti-tumor activity in tumor models independently from the homologous recombination repair status on April 19, 2023, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Also, the Company presented new preclinical data confirming VIO-01’s capability to abrogate several DNA repair pathways and induce a drug-driven synthetic lethality, without the need of a combined treatment.
VIO-01 underwent late-stage IND-enabling preclinical development in 2023, with the execution of regulatory toxicology and ADME/PK studies. This package allowed IND submission to FDA followed by approval to start first-in-human clinical trial.
NEXT Oncology San Antonio, the first site for the Phase 1/2 (VIO-01-101) study investigating VIO-01 has been activated and has dosed the first patient.
3rd generation of PlatON platform
Valerio Therapeutics continued to optimize the PlatON platform to develop more potent assets coupled to innovative technologies, with the objective to combine PlatON platform’s DNA decoys with the targeted protein degradation strategy offered by PROTACs (PROteolysis-TArgeting Chimeras) technology. PROTACs technology and other tumor specific targeting options may be a novel class of heterobifunctional molecules that can selectively degrade target proteins within cells. This approach offers several advantages over the other molecules involved in modulating the DNA damage response, such as increased selectivity and reduced toxicity. This specific strategy involves generating DecoyTAC combining our vectorized DNA decoy molecules capable of efficient cell penetration with a linker+E3 ligand promoting the complete degradation of the target proteins, thereby presenting a novel mechanism of action.
The exploration of the convergence of PROTACs and DNA Decoys aims to not only propose new therapeutic modalities against DDR proteins but also against transcription factor proteins that are challenging to target. Through these efforts, the Company strives to advance the field of oncology drug development and contribute to the treatment of cancer patients.
Evolution of the R&D portfolio
Changes from the portfolio presented in the 2022 annual financial report are as follows:
The Phase 1/2 of the trial AsiDNA in the U.S., in combination with the PARP inhibitor Olaparib enrolled three patients in 2023.
Postponement of the preliminary results of the Revocan study to the first half of 2023, instead of the second half of 2022, due to slowed enrollment.
Preclinical development of VIO-01 (formerly OX425), with the execution of regulatory toxicology and ADME/PK studies and the filing of an Investigational New Drug (IND) application with the FDA in October 2023.
Governance
The Annual General Meeting of June 6, 2023, renewed the terms of Financière de la Montagne, represented by Mr. Nicolas Trebouta, and Mr. Robert Coleman as directors for three years.
The Board of Directors is currently composed of 7 members, 6 men and 1 woman, including 3 independent members.
2024 OUTLOOK
In 2024, 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:
VIO-01
Execute the clinical study VIO-01-101 for VIO-01
Recruitment and dosing of patients for the Phase 1/2 (VIO-01-101).
AsiDNATM
Deprioritization of AsiDNA clinical investigation to focus efforts on developing VIO-01, our second-generation development candidate.
PlatON
Continued optimization of PlatON platform by developing DecoyTAC, leveraging the unique DNA Decoy MoA and the targeted protein degradation (PROTAC), and expanding the targets beyond DDR.