Periodic Reporting for period 2 - TAONas-LUAD (Therapeutic Antisense Oligonucleotides Targeting NUMB Alternative Splicing in Lung Adenocarcinoma)
Periodo di rendicontazione: 2023-04-01 al 2024-09-30
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for most of the cases. Within NSCLC, lung adenocarcinomas (LUAD) represent 1/3 of all lung cancer cases. Despite advances in research and clinical care, current treatments remain ineffective resulting in <25% survival beyond 5 years. Due to the high heterogeneity of molecular abnormalities driving lung cancers, targeted therapies are applicable to only a limited subset of patients with identifiable target mutations, leaving a substantial unmet need for novel treatments for lung cancer. TAONas-LUAD aims to develop and eventually bring to the market a disruptive approach to lung cancer therapy, joining efforts with a consortium of 4 international partners. The therapy is based upon the use of chemically modified antisense oligonucleotides (AONs) to modulate alternative splicing of our target gene to inhibit cancer cell proliferation and reduce tumor growth. Supported by a previous ERC PoC, results from administrating these AONs in cancer cell lines in vitro and in vivo, showed a decrease in tumor cell growth and extended the survival of animals harboring a human tumor xenograft. Our specific objectives include optimizing and formulating our AONs to improve its delivery and effectiveness, investigating different routes of administration, producing GMP-like batches of the best candidate and carrying out regulatory pre-clinical studies in two species. The project also plans to establish the Regulatory roadmap, strength the IP strategy of the technology and develop a Business Development Plan with the goal of incorporating a new spin-off company.
Since the start of the project, a lead AON has been selected and tested using five different chemical modifications. A quick in vivo assay of NSG mice with A549 orthotopic xenografts was established to accelerate the optimization process and increase reproducibility of the results when assessing the therapeutic effectiveness of lead compounds and formulations. Preliminary tests of different chemistries and formulations combinations were conducted using three administration routes. Out of the multiple combinations, we have demonstrated that one optimized chemistry with two different formulations efficiently inhibit cancer cell proliferation and reduce tumor growth in vitro and in vivo with intranasal administration. Currently, we are evaluating the effects of this combinations with intravenous administration.
The therapy we are developing has the potential to significantly transform the treatment landscape for lung adenocarcinomas (LUAD) and other cancers. Given that lung cancer is the leading cause of cancer-related deaths worldwide, with an extremely low survival rate beyond five years, the need for more effective, less toxic, and widely applicable treatments is urgent. The use of Antisense Oligonucleotides (AONs) to regulate alternative splicing (AS) represents a groundbreaking approach. The results of our project so far are encouraging, as the expansion of active chemical modifications and the effects of formulation with lung targeting properties showed remarkable effects inducing alternative splicing in our quick in vivo assays. Through upcoming pre-clinical studies with two species, our project aims to bring this therapy to clinical trials, marking the first application of AON-based splicing modulation in clinical oncology.
Seeking to boost the development of our therapy, we have worked on the incorporation of a spin off company, that will articulate the exploitation of the resulting products. In this sense, a Go-to-Market strategy, full Business Plan and preliminary cost-effectiveness analysis have been performed as critical milestones for the launch of the spin-off company. Our team has also been actively participating in trainings and initiatives to bring together an experienced and complementary team that is leading the incorporation of the company, proving our commitment to bringing this therapy to market. Moreover, TAONas-LUAD’s core technology is protected by one patent family that has been recently granted by the United States Patent and Trademark Office and that is under examination by the European Patent Office and expected to be granted soon. Additionally, a strengthened IP strategy is under development, expanding the future spin-off’s portfolio with a new platform and additional targets.
Lung adenocarcinoma accounts for almost 800.000 new cases each year worldwide, representing a significant portion of the global cancer burden. Our AON-based therapy holds the potential to directly benefit this large patient population, offering a more effective and less toxic alternative to current treatments. However, the impact of our therapy extends far beyond its immediate application to LUAD. Given the misregulation of our target gene in a variety of other cancers, including skin squamous cell carcinoma, breast invasive carcinoma, prostate cancer, and hepatocarcinoma, these cancers represent substantial potential markets, where our AONs could be employed effectively.
Seeking to boost the development of our therapy, we have worked on the incorporation of a spin off company, that will articulate the exploitation of the resulting products. In this sense, a Go-to-Market strategy, full Business Plan and preliminary cost-effectiveness analysis have been performed as critical milestones for the launch of the spin-off company. Our team has also been actively participating in trainings and initiatives to bring together an experienced and complementary team that is leading the incorporation of the company, proving our commitment to bringing this therapy to market. Moreover, TAONas-LUAD’s core technology is protected by one patent family that has been recently granted by the United States Patent and Trademark Office and that is under examination by the European Patent Office and expected to be granted soon. Additionally, a strengthened IP strategy is under development, expanding the future spin-off’s portfolio with a new platform and additional targets.
Lung adenocarcinoma accounts for almost 800.000 new cases each year worldwide, representing a significant portion of the global cancer burden. Our AON-based therapy holds the potential to directly benefit this large patient population, offering a more effective and less toxic alternative to current treatments. However, the impact of our therapy extends far beyond its immediate application to LUAD. Given the misregulation of our target gene in a variety of other cancers, including skin squamous cell carcinoma, breast invasive carcinoma, prostate cancer, and hepatocarcinoma, these cancers represent substantial potential markets, where our AONs could be employed effectively.