In a joint statement, Taiho Pharmaceutical Co, a subsidiary of Otsuka Holdings Co., and Araris Biotech announced that the companies have entered into a definitive agreement confirming Taiho’s acquisition of the a Swiss biotechnology company.
The acquisition, which follows a research collaboration between the two companies in November 2023, is expected to be completed in first half of 2025.
Taiho Pharmaceutical will pay US $ 400 million at closing, with the potential for additional milestone payments of up to US $ 740 million.
Best-in-class ADCs
Araris is a spin-off company of the Paul-Scherrer-Institute in Switzerland and pioneering the development of best-in-class ADCs with superior design, high linker
solubility and simple manufacturing that address the shortcomings of current generation ADCs.
Antibody-drug Conjugates are designed to selectively deliver cytotoxic drugs (payloads) to cancer cells by attaching them to antibodies that bind specifically to cancer cells through linkers.
Foundational technology
Foundational to its approach is its novel, proprietary ADC linker platform AraLinQ™.
The inker technology enables site-specific payload attachment to a privileged attachment site on a specific amino acid (Q295) within the antibody IgGFc framework.
When a payload is attached to this site, the antibody still maintains nearly identical performance (e.g. pharmacokinetics and effector functions) to the unconjugated, original antibody. In addition, the linker-payload is connected to the antibody through a very strong peptide bond resulting in exceptional stability in the blood stream and therefore, avoidance of healthy tissue damage. However, once entering a cancer cell via antibody mediated internalization, the linker can be easily broken to release the payload and kill the cancer cell.
All three of these properties are key factors to enable the most efficient payload delivery and maximum ADC efficacy.
Hydrophobic vs hydrophilic linkers
While some ADC linkers can be hydrophobic, not all ADC linkers are inherently hydrophilic, and the hydrophilicity of the linker is a crucial factor in ADC design, impacting factors like stability and aggregation, which, in turn, can reduce its efficacy and increase the risk of off-target effects. Hydrophobic ADCs may also be cleared more rapidly from the bloodstream, reducing their therapeutic window.
AraLinQ™ linkers are, however, hydrophilic, rendering them soluble in water-based solutions like blood. Improved solubility leads to decreased clumping, allowing the ADC to properly bind to cancerous cells without the need to further edit the antibody/payload structures. In addition, this linker can have unique branching structures which makes it possible to create ADCs that carry multiple payloads of different types.
AraLinQ™ can also generate ADCs in one step using off-the-shelf (ready-to-use) antibodies that are native or engineered. The process is fast, cost-efficient and can be easily upscaled without the need for custom antibody synthesis, and result in ADCs with improved efficacy and tolerability compared to stochastically conjugated ADCs, but precisely controlling the drug load and attaching multiple payload moieties on the antibody has been a challenge. By demonstrating precise control over drug loading and enabling the attachment of multiple payloads, Araris is overcoming these challenges and providing new technologies for ADC design.
To-date, Araris’ technology platform has generated highly uniform, stable and potent ADC therapeutic candidates that have demonstrated a wider range of safety and increased
antitumor effect compared to conventional ADCs in preclinical studies. [1][2]
“We’re pleased to see that our ADCs were well tolerated overall even at high doses, and the impressive efficacy demonstrated by our ADCs underscores the potential of this approach,” noted Philipp Spycher, Ph.D., Co-founder, Chief Scientific Officer at Araris Biotech.
Araris is also advancing three products for the treatment of hematological
and solid tumors developed using its unique AraLinQ™ technology, which are currently
in the preclinical stage. These products are anticipated to enter into clinical trials
between 2025 and 2026.
Drug discovery platform
Taiho Pharmaceutical, in addition to antimetabolites, has established and created novel
drugs through its proprietary small molecule drug discovery platform, Cysteinomix,
enhancing cancer treatment and contributing to patient care.
The drug discovery technology platform is specifically designed to creating drugs that form covalent bonds with a specific amino acid (cysteine) present in target proteins. Covalent drugs, due to their mechanism of action, can offer advantages such as enhanced efficacy and extended duration of action compared to traditional reversible drugs. This technology platform has led to the creation of multiple in-house pipelines, including an FGFR inhibitor approved in the U.S. in 2022.
By acquiring Araris’ innovative ADC drug discovery technology platform along with Cysteinomix, Taiho will further expand its ongoing development portfolio in the field of
oncology.
“We are very pleased to have entered into this agreement with Araris.
AraLinQTM is an innovative technology that enables next-generation ADC drug
discovery,” noted Masayuki Kobayashi, President and Representative Director of Taiho Pharmaceutical.
“We are confident that the addition of Araris’ knowledge, experience and
technology platform in ADC drug discovery, as well as its development pipeline, will
lead to further expansion and strengthening of Taiho’s drug discovery capabilities and
portfolio. Going forward, together with Araris, we will strive to develop innovative
drugs that can contribute to patients globally,” Kobayashi said.
Quantum leap
“Araris’ unique ADC technology represents a quantum leap for the ADC field, potentially offering precise payload delivery of multiple mechanisms of action simultaneously to the tumor, with less toxicity,” said Dragan Grabulovski, CEO and Co-founder of Araris commented.
“We are proud to combine with Taiho, our partner since November 2023,
whose significant cancer expertise will support us in turbo-charging the clinical
development of our potent ADC candidates in hematological and solid tumors,” Grabulovski added.
Validation
“This acquisition validates Araris’ position as one of the most exciting ADC companies in the
market. Having worked with Araris closely during its collaboration, Taiho knows the
potential of Araris’ proprietary AraLinQ™ technology and is best placed to accelerate
these transformative treatments to patients,” concluded Dima Kuzmin, Managing Partner of 4BIO Capital and Chairman of Araris.
With the acquisition, Araris will become a wholly owned subsidiary of Taiho
Pharmaceutical and will continue its business, research and development activities at
its current location in Zurich, Switzerland.
References
[1] Attinger-Toller I, Probst P, Bertrand R, Stark R, Santimaria R, Renard E, Fay R, Grabulovski D, Schlereth B, Spycher PR. A CD79b targeting ADC with superior anti-tumor activity and therapeutic index [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2910. [Link]
[2] Attinger-Toller I, Probst P, Kallenberger L, Renard E, Bertrand R, Fay R, Santimaria R, Maurhofer P, Grabulovski D, Schlereth B, Spycher PR. Targeting NaPi2b with a novel dual TOP1i ADC that shows excellent biophysical properties and high efficacy in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB124. [Link]
Featured image: Used with permission under the Unsplash License.
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