MCL-1 Inhibitor Drugs: Overcoming Cardiotoxicity and Unlocking Potential for Combination Therapies

MCL-1 inhibitors have shown promise in treating cancer, particularly in aggressive hematologic malignancies. However, cardiac-related safety issues have hindered progress. Newer drugs are being developed with short half-lives and pulsed dosing to reduce cardiac exposure. Indirect targeting of MCL-1, such as inhibiting cyclin-dependent kinases, is also being explored. Protein degradation approaches, like PROTACs, and other techniques are offering new opportunities for drug discovery. The commercial potential of MCL-1 inhibitors will depend on how well these strategies fit with precision medicine practices.

MCL-1 inhibitors have shown promise in treating cancer, particularly in aggressive hematologic malignancies. However, cardiac-related safety issues have hindered progress. Newer drugs are being developed with short half-lives and pulsed dosing to reduce cardiac exposure. Indirect targeting of MCL-1, such as inhibiting cyclin-dependent kinases, is also being explored. Protein degradation approaches, like PROTACs, and other techniques are offering new opportunities for drug discovery. The commercial potential of MCL-1 inhibitors will depend on how well these strategies fit with precision medicine practices.

GT Biopharma, Inc. (NASDAQ: GTBP) has recently announced significant progress in its Phase 1 dose escalation trial evaluating GTB-3650, a second-generation TriKE natural killer (NK) cell engager for the treatment of relapsed or refractory (r/r) CD33 expressing hematologic malignancies [1]. The trial, which is evaluating the safety and efficacy of GTB-3650, has successfully completed Cohorts 1 and 2 with no observed safety or tolerability issues. This has allowed the company to initiate dosing in Cohort 3, with the first patient completing the first week of cycle 1. The company plans to release initial Phase 1 results later in 2025 following the completion of additional dose cohorts.

AbSci Corp (ABSI) is set to release its Q2 2025 earnings on August 12, 2025. The market is anticipating a quarterly revenue of $1.43 million and an earnings per share (EPS) of -$0.21 [2]. The company has been under scrutiny for its financial performance and has faced several challenges, including increased research and development expenses and a decline in revenue. Despite these challenges, AbSci Corp has made significant strides in its drug discovery and development efforts, initiating Phase 1 clinical trials for ABS-101 and planning to initiate a Phase 1 trial for ABS-201 in early 2026 [1].

The commercial potential of MCL-1 inhibitors will depend on how well these strategies fit with precision medicine practices. The development of newer drugs with short half-lives and pulsed dosing, as well as indirect targeting and protein degradation approaches, offers promising avenues for reducing cardiac exposure and improving safety profiles. As companies like GT Biopharma and AbSci Corp continue to innovate in drug discovery and development, the market will closely watch their progress and the impact of these advancements on precision medicine practices.

References:
[1] https://www.biospace.com/press-releases/gt-biopharma-advances-into-cohort-3-of-gtb-3650-phase-1-trial-following-safety-review-of-cohort-2
[2] https://www.ainvest.com/news/absci-corp-options-imply-significant-post-earnings-price-movement-2508/