Parvus Therapeutics Inc. and Genentech Inc. have agreed to develop, manufacture and commercialize Parvus' therapeutics to treat inflammatory bowel, autoimmune liver and celiac diseases. The platform gets the job done without immunosuppression, a singular approach and technology.

"As far as we know, in publicly disclosed data and other company efforts to develop drugs, our technology is unique in that it directly targets the disease and leaves rest of the immune system intact," Parvus President and CEO Curtis Ruegg told BioWorld. "That's a big benefit for patients that have serious warnings in terms of their risk for viral diseases and cancer."

In the deal announced Thursday, Parvus could receive up-front and milestone payments exceeding $800 million, plus royalties on net sales. Parvus will conduct the preclinical development and clinical development activities through phase I.

Genentech will handle clinical development from phase II and beyond.

Ruegg, who is nearing the end of his first full year as president and CEO, said it was too early to name a date for going into the clinic.

Parvus, which means "small" in Latin, is also eligible to receive certain additional milestone payments in other disease areas. Ruegg said it's too early to speculate on what those areas might be.

The deal means actively growing the company, Ruegg added, saying Parvus will be hiring new personnel and moving from its Burlingame, Calif., location to nearby South San Francisco.

The deal with Genentech, centers around Navacims, Parvus' lead products, which are designed to trigger a naturally occurring immunoregulatory mechanism of the mammalian immune system that has evolved to protect against autoimmune disease. Navacims are constructed with peptide-major histocompatibility complex (MHC)-coated nanoparticles, or pMHC-NPs, as a way to load iron into effector T cells. Parvus Chief Science Officer Pere Santamaria, who designed the experiments leading to the development of the therapeutic platform, postulated that he might also be able to use the pMHC-NPs to delete the cytotoxic effector T cells driving disease in a mouse model of type 1 diabetes (T1D). Instead, the pMHC-NPs expanded autoregulatory memory T cells generated by T1D – a population previously uncharacterized by scientists – rather significantly.

At the core of each Navacim is a spherical nanoparticle ranging from 1 nm to 100 nm in diameter that can be manufactured from a variety of materials. The raw nanoparticle is glazed with a surface coating agent that allows for covalent attachment of the protein component, which includes a large MHC protein and a short antigenic peptide expressed during production as a single, fully folded pMHC.

A completed Navacim has a diameter of approximately 60 nm and boasts multiple copies of the pMHC complex covalently attached to the nanoparticulate core. Navacims target and kill antigen-presenting cells and interrupt the process in which cytotoxic effector T-cell lineages in a disease are activated and expanded.

This is the second partnership the company has entered. In April 2017, Parvus joined with pharma giant Novartis AG in a license and collaboration agreement. Although specific terms were not disclosed, Novartis gained exclusive worldwide rights to use technology discovered by Parvus to develop and commercialize products to treat T1D and agreed to foot the bill for clinical development and commercialization. Parvus is primarily responsible for conducting the ongoing preclinical work for the T1D program and filing the IND in collaboration with Novartis through a joint steering committee. Parvus received an up-front payment and research funding to support preclinical activities. In addition, Parvus is eligible to receive downstream development, regulatory and sales milestone payments, as well as product royalties. Novartis also made an equity investment in Parvus.

While Ruegg said he couldn't discuss the status of the Novartis deal, he did say the company is "actively looking at adding additional resources to advance the program more rapidly."

Parvus was incubated at the University of Calgary until 2012, when it raised its first angel round of about $5 million. Julia McFarlane, Diabetes Canada Professor of the Cumming School of Medicine at the University of Calgary, worked with Santamaria in the research leading to the discovery of Navacims.

In 2016, Santamaria and collaborators described in a Nature paper how, using the nanoparticle-based approach, they triggered the formation of regulatory T cells in animal models of multiple autoimmune diseases. And T cells were not the only cells affected by treatment with the pMHC-NP complexes. Experiments showed that treatment also led to the formation of inhibitory B cells that secreted the anti-inflammatory cytokine interleukin-10. Although the existence of such inhibitory B cells has been known for some time, the work reported by Parvus was the first documentation of a method to expand them in vivo, enabling more detailed study, according to Santamaria. (See BioWorld Today, Feb. 22, 2016.)

No Comments