Two recent publications showcase an exciting advance in the development of a promising cancer therapeutic by The Institute of Cancer Research, London and illustrate the crucial role that Seda’s formulation design expertise and laboratory capabilities can play during discovery/preclinical development.

Seda design prototype formulations for challenging/poorly soluble compounds to maximise oral bioavailability. During the drug discovery/preclinical phase, such formulations can be used to reach higher plasma concentrations than would be achievable with standard formulations.

In this case, we supported The Institute of Cancer Research (ICR) in their efforts to test and optimise their series of BCL6 degraders as potential therapeutics for B-cell lymphomas. Due to poor solubility, exposure following oral dosing in preclinical species plateaued at around 5 mg/Kg. Our formulation enabled broadly dose proportional increases in exposure up to 50 mg/Kg, facilitating development of PKPD understanding and generation of key efficacy data for this promising series of compounds.

At Seda, we take a science driven and pragmatic approach to preclinical formulation design, which involves matching a formulation composition to the intrinsic properties of the molecule. The key driver for formulation design under these circumstances is to elevate the compound’s solubility in gastrointestinal fluids, for which there are several strategies available to Seda. Our lead strategy for animal studies is the development of oral solutions using well-precedented solubilisers, for which we perform biorelevant testing to understand the likely fate of the formulation upon administration. The data package is fit for purpose, minimizing compound usage, and facilitating rapid decision making and project progression whilst maximizing the likelihood of success. For information on the broader range of oral formulation services we offer please visit our website Oral Drug Delivery | Seda (sedapds.com).

It seems that BCL6 inhibitors could serve as a crucial building block for novel rationally designed combinatorial therapies geared towards more effectively eradicating lymphomas with less toxicity than current regimes. We are delighted to have contributed to the advancement of promising therapies.

The results of the preclinical research performed by ICR, featuring formulation development work led by Seda’s Shanoo Budhdeo have been recently published in the Journal of Medicinal Chemistry:

Discovery of an In Vivo Chemical Probe for BCL6 Inhibition by Optimization of Tricyclic Quinolinones (acs.org)

Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo (acs.org)

Find out more about Seda’s preclinical formulation development capabilities here: Laboratory Services | Seda (sedapds.com)