Prodrug is an important concept in drug design. A prodrug is administered in an inactive form, and is then converted to an active metabolite in vivo. Prodrugs are often designed to selectively release the parent drugs in the diseased tissues.
Prodrug strategy is always used in the design of small molecule drugs. CytomX Therapeutics (NASDAQ: CTMX) applied the concept to create antibody prodrugs that remains inactive until it reaches the tumor. The antibody prodrugs are called probody for short.
The probody concept was proposed by Prof. Patrick Daugherty who co-founded CytomX in February 2008. The design and preclinical data of anti-EGFR probody CTX-023 have been disclosed in the journal Science Translational Medicine.
The probody consists of an authentic IgG heavy chain and a modified light chain. A masking peptide is fused to the light chain through a peptide linker that is cleavable by tumor-specific proteases. The masking peptide prevents the probody binding to healthy tissues, thereby minimizing toxic side effects.
CytomX’s lead candidate is an anti-PDL1 probody called CX-072. The drug is expected to be better than other anti-PDL1 antibodies because the probody does not significantly inhibit the PDL1 pathway outside of the tumor. The company anticipates filing an IND in 2016H2.
CytomX was named as a Fierce 15 biotech company by FierceBiotech in 2013. The company has filed Form S-1 for a $100 million IPO. Third Rock is the biggest investor, with 31% of the stock. Strategic partners include Bristol-Myers Squibb, Pfizer and ImmunoGen (NASDAQ: IMGN).
 Sci Transl Med. 2013, 5(207), 207ra144.