What question did this study set out to answer?

The aim is to evaluate the pharmacokinetics and efficacy of TB-008, a novel CDK9 degrader, in preclinical models.

April 5, 2026Cancer Research0 citations

Abstract 5797: PK/PD and preclinical ADME characterization of TB-008, a first-in-class CDK9 degrader in xenograft models

NNNarayana I. NarasimhanNorwood Hospital MKMahesh KoiralaOak Ridge Associated Universities IDIsabelle DussaultNorwood Hospital

Key Points

The aim is to evaluate the pharmacokinetics and efficacy of TB-008, a novel CDK9 degrader, in preclinical models.
Conducted preclinical studies using Balb/c-nude mice for efficacy evaluation.
Analyzed pharmacokinetics following intraperitoneal administration.
Utilized in-silico models for pharmacokinetics and bioavailability predictions.
Achieved >95% tumor growth inhibition in triple negative breast cancer xenograft models.
TB-008 demonstrated ∼90% bioavailability with a half-life of 1 hour.
In-silico models predicted significant drug concentration in various tissues.

Abstract

Abstract Targeted protein degradation (TPD) offers a promising therapeutic strategy by removing, rather than inhibiting, disease-driving proteins. Cyclin-dependent kinase 9 (CDK9) is a key oncogenic regulator implicated in multiple hematologic and solid tumors. TB008 is a rationally designed CDK9-targeting PROTAC developed using an AI-driven degrader platform to achieve high affinity, selectivity, and favorable pharmacologic properties. Preclinical studies have demonstrated potent, selective CDK9 degradation with downstream suppression of oncogenic targets such as c-MYC and MCL-1. TB008 has shown robust antiproliferative and pro-apoptotic activity across cancer cell lines and strong tumor growth inhibition 95% in triple negative breast cancer xenograft model which support further development of TB008 as a CDK9-directed therapeutic candidate. Pharmacokinetics in Balb/c-nude mice (efficacy study species) has shown that TB-008 is rapidly absorbed following an intraperitoneal dose with ∼90% bioavailability and a half-life of 1 hr. Interestingly, in-silico PK and bioavailability analysis does predict that there is a 90% decrease in drug concentration in mouse plasma within the first hour after administration. Furthermore, also based on in-silico evaluation, it is also predicted that higher drug concentration will be in the GI tract, lungs, plasma, spleen and portal vein. Even with the relatively short half-life, the high tumor growth inhibition observed in xenograft studies confirms the potency and fast kinetics of TB-008 in effecting the degradation of the tumor CDK9. We have initiated studies in mouse xenograft models to better understand the PK/PD and design optimal dosing regimens. Also, we will report the efficacy of TB-008 in additional xenograft models. Additional preclinical ADME data and PK in higher nonclinical species will be reported. Citation Format: Narayana Narasimhan, Mahesh Koirala, Isabelle Dussault, Lindy Yan, Oscar Kashala, Zoser Mohamed, Mario DiPaola, . PK/PD and preclinical ADME characterization of TB-008, a first-in-class CDK9 degrader in xenograft models abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5797.

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