Two unlikely partners, Sony Corporation ‘ Biotechnology devision and Astellas Pharma have signed a collaborative research agreement to discover and develop a novel Antibody-drug Conjugate (ADC) technology platform based on Sony’s unique polymeric material called KIRAVIA™ Backbone.

Sony’s KIRAVIA Backbone is created using the organic polymer technology cultivated in KIRAVIA Dyes™ *, which Sony independently developed and licensed to reagent manufacturers. It features a high degree of freedom in design, as the three-dimensional structure is programmed and polymerized using an automatic synthesizer.

Concept image of an antibody-drug conjugate with a KIRAVIA™ Backbone. Image courtesy: © 2023 Sony Corporation.

Antibody-drug conjugates using this novel backbone, are expected to increasing efficacy and reducing side effects caused by anti-cancer drugs.

Linker chemistry
In every antibody-drug conjugates, the linker links the antibody to the cytotoxic payload. Hence, in the development of novel antibody-drug conjugates, the design of these linkers is of essential importance, because it impacts the efficacy and tolerability of the ADC.

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The linker needs to provide sufficient stability during systemic circulation and should not release the cytotoxic payload before it reaches its intended target, thus resulting in minimum off-target effects. However, following internalization in the target cell, the linker also allows for the rapid and efficient release of the cytotoxic payload in an active form inside the tumor cells, ultimately killing the cancer cell. Hence, the technology to create effective linkers, designed to conjugating antibodies and the drugs payload, is challenging. The seemingly contradictory requirements of stability and release are considered to be a key characteristic of an ADC.  Balancing the linker-chemistry to modulate both stability and payload release to achieve optimal pharmacokinetics (PK-) profiles of active payloads and desired efficacy, is required and remains the focus in the development of better-performing ADCs. [1][2][3][4]

The collaborative research between Sony and Astellas Pharma leverages the flexibility in design and resulting properties such as high capacity and solubility of Sony’s KIRAVIA Backbone as a linker, to effectively deliver anti-cancer drugs to targeted cells in a stable manner, aiming to further enhance therapeutic efficacy by achieving high Drug-to-Antibody Ratio (DAR).

While increasing the number of drugs to be added, and, as a result, creating an ADC with a high drug-to-antibody ratio, it is highly stable, such as loading multiple types of drugs, improving water solubility (prevention of aggregation), and cleaving by reacting with intracellular enzymes. Synthesis of linkers with functional properties and selective drug release is expected.

Joint research
The two companies jointly began exploratory research of new linker technology aimed at creating a new ADC platform in July 2022, and the expected profile was obtained in feasibility studies using human cancer cells. Under this agreement, Sony and Astellas will jointly develop and optimize a new ADC platform using the KIRAVIA Backbone as a linker.

In addition, Astellas will conduct non-clinical trials of development candidates.

in order to build a drug discovery platform not limited to ADC, the two companies have agreed to continue discussions on expanding research partnerships to create new value by combining Sony’s cutting-edge technology with Astellas’ renowned pharmaceutical capabilities.

“Sony’s life science business has accumulated substantial knowledge in the field of cell analysis,” said Katsunori Ogawa, Head of Life Science & Technology Business Unit at Sony Corporation.

“Through this collaboration, Sony is striving to contribute to the medical and drug discovery fields and provide further social value by leveraging Sony’s technological capabilities in the development of anti-cancer drugs therapy, which are expected to grow.”

“We are pleased to enter into a joint research agreement with Sony,” said Yoshitsugu Shitaka, Ph.D., Chief Scientific Officer (CScO), Astellas Pharma.

“Astellas is working to create innovative drugs from a multifaceted perspective called the Focus Area approach, which identifies combinations of biology, therapeutic modality or technology and diseases with high unmet medical needs,” he said

“The partnership will further strengthen our ability to utilize suitable modalities. It is our expectation that the collaboration will lead to the continuous creation of innovative drugs for patients around the world,” Shitaka concluded.

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Note: * Sony’s KIRAVIA Dyes™ are organic polymers with fluorescent dyes loaded precisely on a novel backbone developed by Sony, based on proprietary technology. This family of fluorescent dyes can be used on both spectral and conventional flow cytometers. Designed for ease of use, KIRAVIA Dyes do not require a special buffer system or sample preparation protocol. This class of dyes employs a unique organic backbone that separates fluorophores to minimize quenching effects, thus allowing optimal and higher fluorophore to protein (F:P) ratios, surpassing what is possible with direct conjugations of single fluorophores like FITC.

Reference
[1] Nolting B. Linker technologies for antibody-drug conjugates. Methods Mol Biol. 2013;1045:71-100. doi: 10.1007/978-1-62703-541-5_5. PMID: 23913142.
[2] Sheyi R, de la Torre BG, Albericio F. Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate. Pharmaceutics. 2022 Feb 11;14(2):396. doi: 10.3390/pharmaceutics14020396. PMID: 35214128; PMCID: PMC8874516.
[3] Su D, Zhang D. Linker Design Impacts Antibody-Drug Conjugate Pharmacokinetics and Efficacy via Modulating the Stability and Payload Release Efficiency. Front Pharmacol. 2021 Jun 23;12:687926. doi: 10.3389/fphar.2021.687926. PMID: 34248637; PMCID: PMC8262647.
[4] Su Z, Xiao D, Xie F, Liu L, Wang Y, Fan S, Zhou X, Li S. Antibody-drug conjugates: Recent advances in linker chemistry. Acta Pharm Sin B. 2021 Dec;11(12):3889-3907. doi: 10.1016/j.apsb.2021.03.042. Epub 2021 Apr 6. PMID: 35024314; PMCID: PMC8727783.

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