Pheast, a company focused on macrophage regulation, is advancing its lead drug candidate, PHST001, into first-in-human clinical trials. The drug targets CD24, a 'don't eat me' signal that is highly expressed in certain cancers, particularly ovarian and breast cancers. This milestone follows a partnership with Lonza for manufacturing the drug substance and product, marking a significant step in Pheast's development.
Discovery and Development of PHST001
The development of PHST001 stems from research conducted by Amira Barkal, Pheast's principal founder and chief development officer, in Irving Weissman's lab at Stanford University. Barkal's work focused on understanding macrophages and identified CD24 as a novel target for macrophage regulation relevant to specific cancer types. According to Roy Maute, CEO and cofounder of Pheast, Barkal's research demonstrated that blocking CD24 could have a significant impact on certain cancers.
CD24 as a Target
CD24 functions similarly to CD47, a well-studied 'don't eat me' signal that blocks phagocytosis. However, CD24 is considered a more specialized signal. "CD24 is a more specialized ‘don’t eat me’ signal," Maute explained. "As we’ve studied it, we’ve come to understand it as something that’s a bit more context dependent and dynamic than CD47."
Maute further elaborated on the differences between CD24 and CD47: "Whereas CD47 is sort of this ubiquitous baseline signal that macrophages are looking for, CD24 is more narrowly expressed by a subset of tissues, and it’s upregulation on cancers where it’s present is much more dramatic than on CD47. When we block [CD24], we get a much more potent effect than one can achieve by blocking CD47."
Manufacturing and Scaling
Pheast has partnered with Lonza for the manufacturing of PHST001. The collaboration covers cell-line development and drug substance production in Visp, as well as drug product manufacturing in Basel, Switzerland. This partnership ensures that Pheast has the necessary supply of PHST001 for its clinical trials. According to Maute, Pheast invested significant effort in protein engineering to optimize the antibody, resulting in a well-expressed and robustly humanized variant suitable for large-scale manufacturing.
Clinical Outlook
As Pheast moves forward with clinical trials, the company is drawing insights from CD47 programs to inform its scaling expectations. However, Maute acknowledged that the optimal dosing for CD24 inhibition is still unknown. The company's approach included research on animal immunizations, wild-type mouse hosts, and humanized mice to identify a suitable antibody clone. The initial clinical trials will be crucial in determining the efficacy and safety profile of PHST001.
