For discovering, testing and selecting antisense oligonucleotides (ASOs) for pre-clinical and clinical development, Secarna employs its proprietary, customized LNAplus™ drug discovery platform.
Antisense therapy is a form of treatment for a broad range of diseases caused or maintained by aberrant gene expression. The genetic information of a cell is stored in the form of a double-stranded DNA in the nucleus. In a process known as transcription, genetic information stored in the DNA is transcribed into RNA. The resulting RNA can either have regulatory functions or code for proteins. ASOs are synthetic, chemically modified, short, single-stranded DNA sequences complementary to the aberrantly expressed target RNA and are designed to specifically bind only to their target RNA. Chemical modifications increase stability against degradation as well as cellular uptake and binding affinity to the target, and reduce unwanted side effects. After the ASO binds to the target RNA, the target RNA is degraded by cellular mechanisms and cannot exert its regulatory functions or be translated into proteins that promote development and progression of diseases.
Our unique platform encompasses all aspects of drug discovery and pre-clinical development, enabling us to discover novel therapies for challenging or currently undruggable targets. We start our drug discovery process with bioinformatic analysis of the target RNA, providing us with sufficient information to select and synthesize relevant ASO drug candidates. These are then tested in our labs for efficacy and potency of target knockdown as well as safety aspects in relevant cell lines or primary cells. Candidates with promising activity and a favorable safety profile are further investigated for therapeutic activity in vitro and progress to in vivo tolerability testing and subsequent investigation of therapeutic activity in in vivo disease models.
We pair our convincing technical capabilities with strong expertise and a global network: Secarna works with a team of experts in the field of antisense drug discovery and development, an international network of highly recognized KOLs as well as a validated partnership model.
Oligofyer™ allows us to fully screen all relevant databases for every possible n-mer ASO per target. ASOs with a potential for sequence-dependent off-target effects and sequences having potentially toxic sequence motifs will be eliminated, cross reactivity with other species – if required – is also considered.
With Oligofyer™, we filter for ASOs with strongly enhanced probability for efficacy and rationally design ASO molecules with an exceptionally high hit rate.
The bioinformatic system directs selection of typically 100 to 500 molecules per target entering in vitro screens in relevant cell systems.
In vivo delivery without GalNAc possible
Since its inception, Secarna has become a global leader in discovering and developing exclusively 3rd generation ASOs.
Secarna minimizes the potential of ASO therapy-related complexities (e.g. unintended immune system responses, liver and kidney toxicities) and ensures potent activity in a variety of organs and tissues after systemic delivery, via sugar-free (N-acetylgalactosamine: GalNAc) delivery. By using the Company's own focused molecule design and selection strategies as well as customized development solutions Secarna addresses the aforementioned matters and generates ASO candidates meeting the highest safety and efficacy requirements.
We start the in silico screening and selection process by analyzing all potential ASO sequences. Depending on the size of the target sequence up to several hundred thousand possible candidates are analyzed for their potential to suppress their target specifically and potently. Typically, 100 to 500 ASOs are subsequently selected for first in vitro screening in cell lines or primary cells. In a streamlined selection and optimization process, candidates with the highest activity and safety profile progress to further testing. At the end of this process, we select a hand full of candidates for in vivo testing. Information gained at different steps is then used to improve properties of short-selected compounds, leading to drug candidates with an optimal profile for subsequent pre-clinical development.
Rapid develoment candidate generation in ~24 weeks
Our LNAplus™-based ASOs are characterized by excellent stability and target selectivity and affinity. Employing state-of-the-art chemistry, we achieve aproximately 10-fold increased potency compared to preceding generations of ASOs.
Furthermore, our antisense oligonucleotides do not require conjugation, transfection or delivery reagents to exert their in vitro and in vivo activity in various cell types, tissues and organs. IC50 values of Secarna’s molecules are routinely in the nanomolar range without the support of delivery systems.
Consequently, our molecule’s therapeutic window is expected to be greatly wider when compared to preceding generations of ASOs and alternative modalities.
Our state-of-the-art high throughput platform is ideally positioned to expand the universe of druggable targets and has been validated by in-house projects and in partnerships with academic and industry collaborators. It has successfully proven to be fast, reliable, scalable, efficient and provides for a uniquely integrated workflow.