Tag Archives: Pere Santamaria

Parvus Therapeutics (Calgary, Canada) and reprogramming immune cells

An international collaboration of Canadian, Spanish, and US scientists has announced a new therapeutic approach which could reverse autoimmune diseases in a Feb. 17, 2016 news item on Nanotechnology Now,

• Nanotechnology Approach Restores Glucose Regulation and Motor Function in In Vivo Preclinical Models of Diabetes and Multiple Sclerosis, Respectively; Joint Swelling and Destruction Resolved in In Vivo Model of Rheumatoid Arthritis
• Parvus’ Approach Can Be Tailored to Treat Diverse Diseases

A Feb. 17, 2016 Parvus Therapeutics news release (also on EurekAlert), which originated the news item, provides more detail and a strong orientation to marketing communication,

Parvus Therapeutics today announced the publication in Nature of a seminal paper describing the discovery and applications of a novel therapeutic approach employing nanomedicines, referred to as “Navacims”TM, to reprogram white blood cells to become regulatory cells capable of blunting autoimmune responses and restoring the equilibrium of the immune system. Navacims are nanoparticles (NPs) coated with disease-relevant peptide-major histocompatibility complexes (pMHCs) that alter the behavior of pathogenic T lymphocytes by binding directly to their antigen receptors. The peer-reviewed article, titled “Expanding antigen-specific regulatory networks to treat autoimmunity” reports on a body of work, including results in multiple in vivo disease models, built on more than eight years of research by Parvus Founder and Chief Scientific Officer, Pere Santamaria, M.D., Ph.D.

Dr. Santamaria commented, “Autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis, are extraordinarily complex responses of our immune system against some of our own tissues (e.g. pancreas, brain and joints, respectively), leading to chronic organ inflammation, organ dysfunction, and, in some cases, premature death. Blunting these incompletely understood immune responses without suppressing the normal components of our immune system that protect us against infection and cancer is not currently possible.”

“However, our work offers a pharmaceutical solution to this fundamental problem,” Dr. Santamaria continued. “Navacims essentially re-program disease-causing white blood cells to become disease-suppressing cells, known as regulatory cells, leading to sustained therapeutic effects in various spontaneous and experimental autoimmune diseases, as reported in our article in Nature. Essentially, we have found that Navacims can be tailored to treat a wide range of autoimmune diseases, while sharing a common structure. Importantly, they have been shown to affect human white blood cells in the same manner as they do murine cells. Furthermore, Navacims have shown promising safety findings in preclinical in vivo models. Based on our results to date, we believe Navacims represent a therapeutic platform with broad-ranging health care implications.”

Findings being reported in Nature include:

pMHC class II Navacims expanded cognate CD4+ T-cells that consistently have a TR1-like, regulatory T cell surface phenotype, transcriptional pattern and cytokine profile (mouse=human TR1 cells) systemically.

pMHC class II-Navacims designed to target T cells in newly diabetic nonobese (NOD) mice restored normoglycemia (normal blood sugar regulation) in the majority of the mice tested.

Tailored pMHC class II Navacims restored motor function to paralyzed C57BL/6 mice at the peak of Experimental Autoimmune Encephalomyelitis (a model of Multiple Sclerosis).

pMHC class II Navacims, targeting disease-causing T cells in joints, resolved joint swelling and destruction in arthritic mice.

“The findings being reported in Nature represent a scientific advance for Parvus and also a major achievement in the field of Immunology,” said Janice M. LeCocq, CEO of Parvus. “We believe that Dr. Santamaria’s work has the potential to transform the treatment of many of the more than 80 major autoimmune diseases affecting humankind, alleviating the suffering of millions of patients and their families. Over the coming year, we will be dedicating much of our in-house efforts to the advancement of our two lead programs for type 1 diabetes and multiple sclerosis.”

“Dr. Santamaria’s work to target the immune system dysfunction that causes type 1 diabetes represents the kind of innovative work that JDRF believes will eventually get us to a cure for this disease,” said Juvenile Diabetes Research Foundation Vice President of Discovery Research Julia Greenstein, Ph.D. “He and his colleagues have made exciting progress towards possibly developing a new class of drugs that could rebalance certain T-cells and ultimately provide a cure for type 1 diabetes and other autoimmune diseases as well.” The JDRF has funded the work of Dr. Santamaria and his colleagues at Parvus to explore Navacim-based treatments for diabetes.

Parvus’ strategy is to establish partnerships with major pharmaceutical companies to undertake the clinical and commercial development of many of its product pipeline candidates while also reserving rights to others suitable for its own development and commercialization. Parvus currently is engaged in late stage discussions with multiple pharmaceutical companies with regard to the type 1 diabetes (T1D) program. Manufacturing scale-up is now underway to supply upcoming preclinical and clinical studies.

The work being reported in Nature was led by Dr. Pere Santamaria and largely executed at the University of Calgary, Cumming School of Medicine (animal models of disease) and the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (humanized mouse work), with significant contributions from investigators at Institutions in Europe and the US. Further, Innovate Calgary, the technology-transfer and business-incubation center for the University of Calgary, provided early support for the transfer of the Navacims technology to and incubation of Parvus Therapeutics, which was organized as a separate entity in 2012.

It should be noted that this intervention has been tested on ‘humanized’ mice and, at this point, there don’t seem to have been any human clinical trials. At a guess I’d say we’re still several years away from this therapeutic intervention reaching the market, should it prove to be successful in humans.

Here’s a link to and a citation for the paper,

Expanding antigen-specific regulatory networks to treat autoimmunity by Xavier Clemente Casares, Jesus Blanco, Poornima Ambalavanan, Jun Yamanouchi, Santiswarup Singha, Cesar Fandos, Sue Tsai, Jinguo Wang, Nahir Garabatos, Cristina Izquierdo, Smriti Agrawal, Michael B. Keough, V. Wee Yong, Eddie James, Anna Moore, Yang Yang, Thomas Stratmann, Pau Serra, & Pere Santamaria. Nature (2016) doi:10.1038/nature16962 Published online 17 February 2016

This paper is behind a paywall.

Alberta’s Domino (point-of-care diagnostic) and Navacim (nano drug delivery) competing for $175,000 prize

It’s interesting that two nanomedicine products are in contention for TEC Edmonton‘s NanoVenture Prize. It’s a new prize category for the business accelerator in this, their 10th anniversary year. From TEC Edmonton’s March 27, 2012 news release,

The NanoVenturePrize finalists are Aquila Diagnostics of Edmonton and Calgary’s Parvus Therapeutics.

Aquila Diagnostics uses the Domino nanotechnology platform developed at the University of Alberta to provide on-site, easy-to-use genetic testing that can quickly test for infectious diseases and pathogens in livestock. The mobile diagnostic platform is portable, low-cost, fast and easy to use.

Parvus Therapeutics’ breakthrough nanomedicines may hold the cure for difficult-to-treat autoimmune diseases like type 1 diabetes, multiple sclerosis and inflammatory bowel disease. Parvus’ new Navacim medicines are nanoparticles coated with immune system proteins that can target specific autoimmune conditions.

The University of Alberta has issued its own April 24, 2012 news release by Bryan Alary about the Domino,

Dubbed the Domino, the technology—developed by a U of A research team—has the potential to revolutionize point-of-care medicine. The innovation has also earned Aquila Diagnostic Systems, the Edmonton-based nano startup that licensed the technology, a shot at $175,000 as a finalist for the TEC NanoVenturePrize award.

“We’re basically replacing millions of dollars of equipment that would be in a conventional, consolidated lab with something that costs pennies to produce and is field portable so you can take it where needed. That’s where this technology shines,” said Jason Acker, an associate professor of laboratory medicine and pathology at the U of A and chief technology officer with Aquila.

The Domino employs polymerase chain reaction technology used to amplify and detect targeted sequences of DNA, but in a miniaturized form that fits on a plastic chip the size of two postage stamps. The chip contains 20 gel posts—each the size of a pinhead—capable of identifying sequences of DNA with a single drop of blood.

Each post performs its own genetic test, meaning you can not only find out whether you have malaria, but also determine the type of malaria and whether your DNA makes you resistant to certain antimalarial drugs. It takes less than an hour to process one chip, making it possible to screen large populations in a short time.

“That’s the real value proposition—being able to do multiple tests at the same time,” Acker said, adding that the Domino has been used in several recently published studies, showing similar accuracy to centralized labs.

Linda Pilarski, an oncology professor at the University of Alberta (mentioned in my Jan. 4, 2012 posting about her diagnostics-on-a-chip work), and her team developed Domino according to the April 25, 2012 news item on Nanowerk,

In 2008, her team received $5 million over five years from Alberta Innovates Health Solutions to perfect and commercialize the technology. As an oncologist, Pilarski is interested in its pharmacogenomic testing capabilities, such as determining whether breast cancer patients are genetically disposed to resist certain drugs.

“With most cancers you want to treat the patient with the most effective therapeutic as possible,” she said. “That’s what this does: it really enables personalized medicine. It will be able to test every patient at the right time, right in their doctor’s office. That’s currently not feasible because it’s too expensive.”

This product is intended for the market but not the one you might expect (from the April 25, 2012 news item on Nanowerk),

Along with its versatility, two key selling points are affordability and portability, with each portable box expected to cost about $5,000 and each chip a few dollars, says Aquila president David Alton. It’s also designed to be easy to use and rugged—important features for the livestock industry, the company’s first target market. [emphasis mine] The Domino will be put through trials within a year at one of the country’s largest feedlots in southern Alberta.

Alton credits Aquila’s relationship with the U of A, not just for the research but for the business relationship with TEC Edmonton that has helped the company license and patent Domino. TEC Edmonton is a joint venture between the U of A and Edmonton Economic Development Corporation with resources and expertise to help startups in the early stages of operations.

“We see a huge potential market for the technology and we’re looking at applying the technology developed here at the U of A to markets first in Alberta and then globally, to address important health issues here and throughout the world.”

Given that the originator is an oncologist I really wasn’t expecting the first market to be livestock industry.

I have had a little less luck getting information about Parvus Therapeutics’ Navacim technology as they’ve not issued a news release about their competition for this prize but I did find some information on their website, from an April 8, 2010 news release about the Navacim technology being featured in a Popular Science article,

Parvus Therapeutics reports that an article entitled “Nanotech Vaccine Successfully Cures Type-1 Diabetes in Mice” has been published at the website of Popular Science. The article, authored by Alessandra Calderin, describes the Parvus Navacim technology and includes remarks from Parvus’ Founder and Chief Scientific Officer, Dr. Pere Santamaria.

The article notes that,

“The technology behind the nanovaccine, following further research, may prove widely applicable to treat other autoimmune diseases, like arthritis and multiple sclerosis, as well.”

You may want to take a look at the news brief by Calderin. Here’s more about the technology, from the Introducing Navacims webpage on the Parvus Therapeutics website,

Our nanotechnology-based therapeutic platform and Navacims, the therapeutic candidates, are the result of two related discoveries: A new class of immune cell, and a new way to treat autoimmunity that these cells provide. Here we provide a very brief summary of how these discoveries came about and what they have led to since.

This summary is also intended as a roadmap to the contents of this technology section of our website, which we will role out over a period of weeks and adapt based on reader feedback and requests. The casual reader may find the background information helpful, while our professional colleagues will probably want to get straight down to the technical details and published papers. We have tried to design the content to cater to all tastes and it can be read in any order, although like all good stories, we highly recommend starting at the beginning.

As with the remainder of our site, we have injected a little colour and a little humour to keep your spirits up if the science appears a little daunting. In all, we have attempted to strike a balance between scientific detail and general accessibility and if you think we have that balance wrong, or you feel something is missing, please let us know — via the form on the Contacts page — and we will try to put it right. We love to hear from you.

The Story So Far

[1] In a series of experiments, only tangentially related to our current activities, we designed p-MHC-coated nanoparticles (NPs) as a way to load iron into effector T-cells and have them ferry the iron to the pancreas so we could visualize pancreatic islet cell inflammation in-vivo, in real-time — this amounts to the use of a Magnetic Resonance Imaging (MRI) contrast agent.

[2] It occurred to us that we might be able to use these p-MHC-NPs to delete the high avidity cytotoxic effector T cells driving disease in the NOD mouse model of type 1 diabetes (T1D).

[3] Too our surprise, therapy did not delete, but rather, very significantly expanded autoregulatory T cell pools.

[4] After careful analysis we were able to conclude that:

pMHC-NPs, now called Navacims, selectively expand a population of low avidity autoregulatory memory T cells that the disease itself generates — this population of cells was previously unknown to science. These cells target and kill antigen presenting cells (APCs), and consequently, interput the process whereby all the cytotoxic effector T cell lineages active in a disease are activated and expanded.

Navacims also directly deplete the high avidity cytotoxic effector T cells cognate to the pMHC carried by the nanoparticle. This removes one lineage of cells that cause damage in disease, but given the many antigens, and consequently the many T cell lineages, the overall therapeutic effect of removing one type is inconsequential compared to the indirect effect of the Navacim on APCs that removes all lineages.

The removal of APCs and the concomitant loss of multiple cytotoxic effector T-cell lineages that drive disease amounted to a cure for T1D in the NOD mouse model.

[5] We believe that Navacims have the potential to become the long sought after ideal treatment for autoimmunity; a therapeutic that restores immunological tolerance — the principal problem in autoimmunity — while depleting autoreactive cells that mediate the damaging effects of disease.

[6] Navacims appear to be safe and very well tolerated in animal experiments that have lasted many months, although we caution that we have yet to complete formal toxicological studies.

[7] Navacims are highly modular and a family of Navacims can be almost identical, differing only in the very short antigenic peptide that gives each one its specificity for a particular disease.

[8] Because they are so similar, we beleive that industry-standard manufacturing processes will need few if any modifications in order to produce a particular Navacim.

[9] We have protected our discoveries with patent applications in the United States, Europe, Canada, and beyond.

[10] Our work has been published in top-ranked peer-reviewed journals and showcased in the best of the popular science publications.

Good luck to both companies in their future endeavours.

ETA April 30,2012: According to the April 27, 2012 article in the Edmonton Journal, Parvus Therapeutics won the $175, 000 prize in TEC Edmonton’s new prize category.,

This year’s awards, the 10th consecutive, added a new category for nanotechnology firms. TEC partnered with Alberta Innovates — Technology Futures for the new award. Calgary’s Parvus Therapeutics, which makes medicine aimed at autoimmune diseases such as Type 1 diabetes and multiple sclerosis, beat out Edmonton’s Aquila Diagnostic Systems for first place. The category’s prizes totalled $175,000 in cash and services.