Regulon is an oncology-focused drug delivery company leveraging proprietary and differentiated tumor-targeting nanotechnology to develop improved branded versions of leading chemotherapy drugs. Regulon’s lead product, Lipoplatin for pancreatic cancer (same drug under the name Nanoplatin for non-small cell lung cancer, NSCLC), is a liposomally encapsulated cisplatin nanoparticle. Cisplatin is the most widely-used chemotherapy drug, the gold standard for epithelial malignancies with applications to over 50% of human cancers. Lipoplatin nanoparticles, loaded with cisplatin are uptaken by tumors and metastases (10 to 200-fold higher than normal tissue) by leaking through the compromised endothelium of tumor vasculature sprouted during neoangiogenesis, a process known as extravasation, and by the avidity of tumors for nutrients with Lipoplatin disguised as a nutrient with its lipid shell. Moreover, Lipoplatin nanoparticles fuse with the cell membrane thus emptying their toxic payload directly inside the cytoplasm of the cell bypassing the cell membrane barrier often impermeable by cisplatin especially in resistant tumors.
Thus, the significant advantages of this formulation are:
(i) high encapsulation efficiency (>95%) avoiding further purification to rid of the free drug that results in instability of liposomes and waste of the expensive active pharmaceutical ingredient;
(ii) longevity in body fluids because of PEGylation which is essential for the passive targeting of the nanoparticle to tumors;
(iii) extravasation through blood microvessels and concentration into primary tumors and metastases using the compromised endothelium of tumor vasculature; in human studies this concentration attains levels up to 200-fold higher in tumors compared to platinum drug levels in the adjacent normal tissue;
(iv) penetration through the cell membrane thus reaching the cytoplasm target in cancer cells.
Additional emerging properties unique to Lipoplatin are:
(v) the nanoparticle can attack also the cell membrane of tumor vasculature (endothelium) unlike the naked drug, cisplatin, used only in epithelial malignancies; this way Lipoplatin can exert anti-angiogenesis properties;
(vi) it has shown antimetastasis potential in vitro;
(vii) negligible toxicity in a Phase II monotherapy study as second line against non-small cell lung cancer (only Grade 1 toxicities) with a therapeutic efficacy unlike any other drug in monotherapy studies (38% partial response and 43% stable disease).
(viii) Lipoplatin has shown success in all cancer indications tested thus far (NSCLC, pancreatic, urinary bladder, gastric, breast, head & neck cancers); it has certainly strong potential in additional cancers where cisplatin is used broadly (testicular, ovarian, cervical, endometrial and many others).
Published Phase III studies show a lower toxicity with improved therapeutic index in adenocarcinomas of the lungs compared to cisplatin; this feature was not shown by other platinum blockbuster drugs (carboplatin, oxaliplatin). In a randomized Phase III in NSCLC, a statistically significant reduction of neutropenia, nephrotoxicity and asthenia of cisplatin was demonstrated by its replacement with Lipoplatin. Also in a randomized Phase III in nonsquamous-NSCLC the partial response for the Lipoplatin arm was 59% compared to 42% for the cisplatin arm and the difference was statistically significant (p=0.036).