Our client asked us to conduct a risk assessment and due diligence of a small molecule oncology compound that had been identified from a phenotypic screen. The molecule was in a Phase I/II clinical trial for a range of tumor types.


Our technical evaluator reviewed the results of numerous experiments that had been designed to deconvolute the mechanism of action. The data suggested that the molecule was potentially acting through multiple mechanisms of action, specifically a highly promising, difficult to drug, oncogenic pathway. The majority of the studies had been conducted at a highly regarded academic cancer center and were of good quality. However, there was limited in vivo data to support the key contentions of the mechanism of action.

Nevertheless, the data showed that the compound had in vivo efficacy in several models, especially when combined with the standard of care. The toxicology studies had been appropriately designed and conducted and the results did not appear to be of significant concern. The clinical development (two ongoing Phase I clinical trials) was too early to draw meaningful conclusions. However, we noted that the clinical development plan had been empirically developed, rather than rationally based on mechanism of action. The IP was sound and the CMC/formulation was adequate for the particular stage of development.

A major risk for our client was the attractiveness of the molecule to a partner. Pleiotropic mechanisms are generally unfavorable to pharma, who prefer to see potent and selective activity against a well-defined, high-interest target. We cautioned our client that the target company would need to generate compelling evidence of efficacy (and safety) to attract significant partnering interest from big pharma.


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