PDC – A true innovation

The PDC compounds are composed to enable efficient distribution in the body, enabling a wide therapeutic window (i.e. a wide margin between effective doses and doses that give unacceptable side effects), and an optimized benefit risk profile. The PDCs are designed around two components: a peptide carrier and a cytotoxic payload. The PDCs are lipophilic which allows a rapid diffusion into cells. The peptide carrier utilizes the altered metabolism of cancer cells to hydrolyze PDC into active hydrophilic metabolites, which lead to an enrichment in cancer cells.

the Peptide Drug Conjugate, PDC, platform

Melflufen – The first PDC with an alkylating payload

Melflufen is the first PDC with an alkylating payload. The drug utilizes peptidases and esterases that are overexpressed in multiple myeloma cells, to release a toxic payload inside cells, leading to DNA damage ang killing of cancer cells. Melflufen has demonstrated effect on cancer cells that have lost the important tumor suppressor TP53. It has been developed for relapsed refractory multiple myeloma, through a comprehensive preclinical and clinical program, that lead to accelerated approval by the FDA in US in February 2021, and full marketing approval by EMA in August 2022 and MHRA in UK in November 2022 (see regulatory status of melflufen here).

OPD5 – follow-up PDC

OPD5 is a new chemical entity adapted from melflufen. It was initially aimed at high dose treatment for myeloablation ahead of stem cell transplant but can be formulated for conventional dose in either multiple myeloma or other hematologic or solid tumors. OPD5 is a Phase 1 ready asset. The first Phase 1/2 study was approved by regulatory authorities and ethics committees but was terminated before including the first patient.

OPDC3 – Next generation PDC

OPDC3 builds on the clinical experience of melflufen. Like melflufen, OPDC3 generates an enrichment of alkylating payloads in cancer cells.  In addition, it is designed to prevent the cytotoxic payload to be transported out of cancer cells, a common mechanism of cancer cells resistance to cytotoxic agents. These unique properties may translate into an even more effective and well tolerated therapeutic option. This warrants further evaluation in clinical studies in either hematologic or solid tumors. OPDC3 is currently in late preclinical development.