ASO Delivery Breakthrough: Secarna and Celanese Partner to Develop Long-Acting Implantable ASO Therapeutics

‍‍‍‍| Research Team of the Drug Hunter Club

A Major Constraint of ASO:Frequent dosing

As an innovative therapy, ASO is also a commercially validated treatment method. The development of antisense oligonucleotide drugs has been rapid since the emergence of ASO technology in 1978, with the first ASO drug receiving FDA approval in 1998, 20 years later. To date, various new technologies have emerged in the ASO field, and 11 drugs have been approved by the FDA.

However, compared to siRNA that accumulates in cellular endosomes, ASO, as an earlier oligonucleotide therapeutic technology, requires more frequent and higher-dose administration due to differences in its mechanism of action, resulting in a certain medication burden in terms of both compliance and drug toxicity:

Based on VitalDose® EVA Technology, achieving ASOLong-acting sustained release

To address the drug delivery bottleneck for ASOs, this collaboration between Celanese and Secarna will leverage Celanese's VitalDose drug delivery platform and Secarna’s ASO drug discovery and development platform to develop ASO-eluting implants.These implants have the potential to reduce dosing frequency, minimize off-target immune responses, enhance targeting, and provide better patient outcomes for a range of indications.

Specifically, the VitalDose drug delivery platform utilizesVitalDose^®EVAThis long-acting sustained-release drug technology,The low-temperature micropulverization of EVA polymers gives them broad molecular compatibility, meeting the chemical and physical requirements of many pharmaceutical formulations. This technology platform is compatible with proteins, peptides, small molecules, and RNA therapies.：

• VitalDose®EVA can be processed at low temperatures to accommodate sensitive biologics;

• In addition, it has a wide range of solubility characteristics and is suitable for small molecule drugs.

• This ethylene-vinyl acetate can be processed using various production methods and is compatible with other excipients to meet specific drug formulation, release, and delivery requirements.

In terms of controlled-release capability,VitalDose® EVA can achieve highly controllable release rates through flexible design and preparation, thereby achieving specific drug release profiles ranging from several months to years.As shown in the figure below,(1) VitalDose® EVA containing 40% vinyl acetate is used as a drug matrix, (2) VitalDose® EVA containing 18% vinyl acetate on the exterior of the implant is used as a rate-controlling membrane.This forms a kind ofLevel ZeroRelease CharacteristicsHigh drug-loading delivery system.

(Note: Zero-order release refers to the drug release rate that does not change over time, meaning the rate remains constant during the drug release period, also known as constant elimination.)

VitalDose®EVA has biostability, therefore it canLong-term (e.g., months to years) designed dosing curve(Zero-order, first-order, or other non-linear curves). In addition, the sustainability of the polymer allows for reliable performance when necessary.Remove implant to discontinue treatment. While maintaining the required mechanical properties, it can also achieveHigh drug load (>75%)。

Therefore, VitalDose® EVA is suitable for long-acting indications. Common applications includeSubcutaneousAndOphthalmic ImplantsAndVaginal Insert, which can meet unmet clinical and patient needs across multiple therapeutic areas, including oncology, ophthalmology, central nervous system, infectious diseases, and women's health.

With reliable controlled-release performance,VitalDose® EVA hasApproved for use in some parenteral drug products in the United States and Europe, providing drug release lasting several months to years.And it has been proven to stably release ASO within one year.

Travoprost Based on VitalDose® EVA TechnologyIntraocular ImplantiDose TR，Approved by the FDA on December 14 last year for reducing intraocular pressure (IOP) in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG).

iDose TR is a sterile anterior chamber implant containing 75 micrograms of a novel travoprost formulation, approved for single-dose administration. It is implanted in the eye through minimally invasive surgery. After implantation, 75 micrograms of the novel, preservative-free proprietary travoprost formulation are continuously eluted into the anterior chamber via membrane-controlled diffusion.Thereby achieving 24/7 drug release；Continuously release therapeutic levels of travoprost for at least one year。

Travoprost is a prostaglandin analog used to reduce intraocular pressure (IOP). Once all the travoprost is released, the iDose TR can be removed and replaced with a new one. As an implant, it also offers a promising alternative to daily eye drop treatments and may alleviate adherence issues associated with daily eye drops.

Notably, iDose TR is a first-of-its-kind, long-duration anterior chamber drug therapy designed to continuously deliver a proprietary formulation of travoprost at therapeutic levels 24/7 over an extended period within the eye.This product enhances the standard of care by addressing the widespread issue of patient non-adherence and chronic side effects associated with topical glaucoma medications.

In 2023,CelaneseAnnouncement of Advancing Celanese VitalDose^® EVADevelopment initiatives for drug delivery platforms include a research agreement with Johns Hopkins University for continuous delivery to the suprachoroidal space of the eye and a collaboration with Alessa Therapeutics to advance cancer treatments.

Secarna Pharmaceuticals: Global Leader in Third-Generation ASO

For decades, antisense oligonucleotides have been optimized through chemical modifications. These changes enhance the stability, targeting affinity, pharmacokinetic properties, and productive cellular uptake of ASOs. Moreover, they reduce unnecessary stimulation of the immune system and other potential side effects. Since its establishment, Secarna has become a global leader in the discovery and development of third-generation ASOs.Secarna addresses the aforementioned issues and generates ASO candidates that meet the highest safety and efficacy standards by utilizing its own focused molecular design and selection strategies, along with tailored development solutions., thereby minimizing the possibility of ASO treatment-related complexity.

Secarna's proprietaryCustomized LNAplus™ PlatformCurrently applied to discover, test, and select antisense oligonucleotides (ASO) for preclinical and clinical development. LNAplus™ covers all aspects of drug discovery and preclinical development and has been proven to be fast, reliable, scalable, and efficient, capable of targeting challenging or currently undruggable targets to discover new antisense-based therapies.

Currently, Secarna Pharmaceuticals GmbH & Co. KG ownsMore than 20Discovery and development programs, including proprietary pipeline projects and collaborative projects. With several high-value and innovative programs, Secarna has validated its platform across various indications such as cardiometabolic, immuno-oncology, fibrosis/inflammatory diseases, and central nervous system disorders.

Source: Official websites of respective companies

Featured Article Recommendations

"Views"Click 1