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- ABL Bio’s N-terminal selective conjugation method results in enhanced stability and lower toxicity while also inducing more efficacy
- NTERM-ADC demonstrates high anti-tumor potency in rats
April 28, 2021, SEONGNAM - ABL Bio, Inc., a South Korean biotech developing bispecific antibody technology for immuno-oncology and neurodegenerative diseases, today announced a publication in the peer-reviewed journal mAbs, that shows ADCs are more stable and less toxic when applied with N-terminal selective conjugation.
The paper, titled: “N-terminal selective conjugation method widens the therapeutic window of antibody-drug conjugates by improving tolerability and stability” demonstrates that NTERM-conjugated ADCs overcome the limitations of narrow therapeutic windows. To support this, the authors synthesized three different ADCs using different methods, including N-terminal selective conjugation, setting trastuzumab as the evaluation standard.
As highlighted in the paper, the NTERM ADC demonstrated a longer half-life than others in a single-dose PK study in rats. While the other ADCs exhibited shorter half-lives of 84.6 hours and 53.2 hours, the half-life of the NTERM-ADC was 118.3 hours.
In addition, the NTERM-ADC showed positive data in a toxicity study performed in rats. To examine the tolerability of ADCs, female rats were injected with each ADC intravenously. No severe side effects were observed in the NTERM-ADC group, whereas other groups displayed severe liver toxicity and thrombocytopenia that resulted in lower survival rates.
Furthermore, the results confirmed the NTERM-ADC’s excellent anti-tumor efficacy. In a rat-xenograft model, the NTERM-ADC group showed complete remission in 5 of 6 rats after a single dose of 2.5 mpk. Even at a lower dose of 1 mpk, it showed 92% of tumor growth inhibition from day 4 to 21. While a lower toxicity could mean a lower potency of the molecule, the NTERM-ADC demonstrated the best efficacy among the three groups in the xenograft model.
ABL’s N-terminal selective conjugation method has been patented in the U.S., South Korea and Australia. Using this conjugation method, the company has developed ABL201, a bispecific antibody therapeutics candidate to treat rare blood cancer.
The publication is available online in the journal website: https://bit.ly/3tYKgjN
About ABL Bio
ABL Bio, Inc. (Kosdaq: 298380) is a South Korean biotechnology company developing antibody therapeutics for immuno-oncology and neurodegenerative diseases. With internal R&D and global partnerships, ABL has developed multiple BsAb platforms, such as ‘Grabody-T,’ ‘Grabody-I’ and ‘Grabody-B’ and built an innovative pipeline of multiple clinical and pre-clinical stage drug candidates. In the oncology area, we have developed Grabody-T, a modular 4-1BB engaging platform that has demonstrated superior efficacy and safety. In the neurodegenerative disorder space, we have developed Grabody-B platform, which is designed to maximize blood-brain barrier (BBB) penetration. Grabody-B is applicable to various CNS targets across a plethora of neurological disorders, potentially providing a breakthrough to address the high unmet medical needs in neurodegeneration. For more information, please visit www.ablbio.com