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From Lab Formulation Development to CTM Manufacturing of KO-947 Injectable Drug Products: a Case Study and Lessons Learned

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Abstract

Formulation development of KO-947-K mesylate injectable drug products was described. Solution formulations were initially attempted, and key parameters such as drug concentration, buffer, pH, complexing agent, and tonicity modifying agent were carefully evaluated in the lab setting, mainly focusing on solubility and chemical stability. A lead solution formulation was advanced to a scaleup campaign. An unexpected stability issue was encountered, and the root cause was attributed to the heterogeneous liquid freezing process of the formulated solution at −20°C, which had not been captured in the lab setting. A lyophilized product was then designed to overcome the issue and supplied to the phase I clinical trial.

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Acknowledgements

We wish to thank Mrs. Caryn Peterson and Mr. Dennis Hester for useful discussions, Dr. Antonio Gualberto and Dr. Catherine Scholz for clinical inputs, and Dr. Tiffany Montellano and Dr. Blake Tomkinson for reviewing the manuscript.

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Author notes

  1. Xiaohu Deng

    Present address: Vividion Therapeutics Inc., San Diego, California, 92130, USA

Authors and Affiliations

  1. Kura Oncology Inc., 12730 High Bluff Drive, Suite 400, San Diego, California, 92130, USA

    Xiaohu Deng, Pingda Ren & Wanping Mai

  2. Wellspring Biosciences Inc., 10770 Wateridge Cir. Unit 120, San Diego, California, 92121, USA

    Yi Wang

  3. WuXi AppTec Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Pilot Free Trade Zone, Shanghai, 200131, China

    Yuanyang Zhang, Yinwei Xie & Huazhen Chen

  4. WuXi Biologics Co., Ltd., 299 Fute Zhong Road, Waigaoqiao Pilot Free Trade Zone, Shanghai, 200131, China

    Hongbing Wu

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  1. Xiaohu Deng
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  2. Pingda Ren
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Correspondence to Xiaohu Deng.

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Deng, X., Ren, P., Mai, W. et al. From Lab Formulation Development to CTM Manufacturing of KO-947 Injectable Drug Products: a Case Study and Lessons Learned. AAPS PharmSciTech 22, 168 (2021). https://doi.org/10.1208/s12249-021-02059-x

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  • DOI: https://doi.org/10.1208/s12249-021-02059-x

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