Acuitas Therapeutics

Last updated
Acuitas Therapeutics Inc.
FormerlyAlCana Technologies
Company type Private
Industry
FoundedFebruary 2009;15 years ago (2009-02)
Founder
Headquarters Vancouver, Canada
Website acuitastx.com

Acuitas Therapeutics Inc. is a Canadian biotechnology company based in Vancouver, British Columbia. The company was established in February 2009 to specialize in the development of delivery systems for nucleic acid therapeutics based on lipid nanoparticle (LNP) technology, a key component of the mRNA vaccines deployed for COVID-19. [1] [2]

Contents

History

Inex Pharmaceuticals

Pieter Cullis was among several scientists experimenting with liposomes in the early 1980s, fascinated by their properties in many aspects of human biology. [3] Cullis discovered he could load cancer drugs into liposomes, inspiring him and several colleagues at the University of British Columbia to form Inex Pharmaceuticals in 1992. [4] One of Inex's co-founders was Thomas Madden, who had recently emigrated to Canada from the United Kingdom to complete post-doctoral studies in biochemistry. [5]

Tekmira Pharmaceuticals

To improve the prospects of successfully advancing gene therapy techniques, Cullis developed and patented a new form of lipid nanoparticle designed to deliver genetic material to recipient cells. [6] From 1994 onward, a series of patents were filed describing the technology Cullis and his colleagues created, including the addition of a chemical called polyethylene glycol (PEG) to further increase the LNP's ability to pass into cells. [7] [8] [9] [10] [11] [12]

Several spinoff companies emerged based on the research and intellectual property, including Protiva Biotherapeutics (which focused gene therapies based on RNAi). [13] In 2001, Inex was developing topotecan with GlaxoSmithKline and by 2004 was in the research stage of preparing their own targeted cancer vaccine program. [14] [15] However, Cullis left the company after the Food and Drug Administration declined to approve their chemotherapy products. [16] Inex then downsized and rebranded to Tekmira Pharmaceuticals. [17] This led to $28.5 million in funding from “large biotechnology companies” for further development of anti-cancer drugs and RNA therapeutics for other diseases. [18]

Acuitas

Madden, Cullis and Michael Hope then founded AlCana Technologies in February 2009, later changing its name to Acuitas Therapeutics. [2] With early financial support from the National Research Council Canada's Industrial Research Assistance Program (NRC IRAP), the company spent several years establishing its research and development capabilities and building out its staff. [1] This led to its development of a viable lipid nanoparticle platform that showed promise for use in a variety of medical applications including chemotherapy, gene therapy and genetic vaccines. By 2012, the company had decided to focus on LNP development for the delivery of mRNA. [19]

The Natural Research Council Canada awarded Acuitas a $173,020 grant in September 2013 and a $498,640 grant in February 2015 to continue their research and development. [20] [21]

In April 2016, Acuitas entered into a development and option agreement with German biotechnology company CureVac to jointly develop a product incorporating Acuitas' LNP technology with CureVac's mRNA materials. [22] [23] The encapsulated mRNA product described under the agreement was commissioned for use in in vitro and animal testing for pre-clinical trials of a vaccine candidate. Acuitas also worked on developing an mRNA vaccine against rabies. [24]

COVID-19

According to president and CEO Thomas Madden, Acuitas began working towards a COVID-19 vaccine in February 2020. The company also partnered with CureVac and Imperial College London for their own vaccine trials. [25] [24] Madden noted that the mRNA vaccine platform would allow for rapid development of updated vaccines in case the SARS-CoV-2 virus evolved beyond the immunity generated by the initial formulation, though additional clinical testing would still be required. [24] He also stated that the Pfizer–BioNTech COVID-19 vaccine would stop the spread of the virus and infection in vaccinated individuals.

On December 9, 2020, Acuitas released a statement celebrating Health Canada's approval of Pfizer and BioNTech's BNT162b2 COVID-19 vaccine, [26] stating they had “made history” due to their collaboration through the LNP delivery system, “a key element… in the development of this vaccine.” [27] As a privately held company, Acuitas doesn't publicly publish its earnings. However, Madden stated the company's annual revenues were "more than tens of millions of dollars" as of the end of 2020, having increased by 75% in the prior several years leading up to the COVID-19 crisis and expectations to grow by "at least that amount" through to 2022. [5]

Acuitas entered a long-term partnership with Science World in January 2022. [28] [29] In April 2022, Acuitas completed an agreement with Korean biotechnology company GC Biopharma to develop vaccines and therapeutics using their joint LNP-mRNA platform. [30] In June 2022, Acuitas donated $25,000 to the Brain Tumour Foundation of Canada to create the Frazer Anderson Pediatric Research Grant. [31] The company entered an agreement with genetic editing company Arbor Biotechnologies in August 2022 to target rare liver diseases, combining Acuitas' LNP technology with Arbor's CRISPR gene editing capabilities. [32]

In June 2023, Bayer announced it had entered a partnership with Acuitas to use its lipid nanoparticles to deliver in vivo gene editing products to the liver. [33]

Organization

Partners

Acuitas has partnered with several pharmaceutical companies and universities to collaboratively advance specific product candidates, as well as to support the broader development of the personalized medicine sector. It is a member of BIOTECanada, a biotechnology industry association, [34] and Life Sciences British Columbia. [35] It has participated in research published by the University of Pennsylvania, Mount Sinai Health System, Chulalongkorn University, Thomas Jefferson University, and BioNTech. [36]

Acuitas is a sponsor of the Vancouver-based Student Biotechnology Network. [37]

Ownership

Rumours circulated in early 2022 that Prime Minister Justin Trudeau owned a 40% stake in Acuitas, either directly or through the Trudeau Foundation. [38] This was refuted by the Office of the Prime Minister, CEO Thomas Madden and co-founder Pieter Cullis. [39]

Related Research Articles

<span class="mw-page-title-main">Liposome</span> Composite structures made of phospholipids and may contain small amounts of other molecules

A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes.

<span class="mw-page-title-main">Cationic liposome</span>

Cationic liposomes are spherical structures that contain positively charged lipids. Cationic liposomes can vary in size between 40 nm and 500 nm, and they can either have one lipid bilayer (monolamellar) or multiple lipid bilayers (multilamellar). The positive charge of the phospholipids allows cationic liposomes to form complexes with negatively charged nucleic acids through ionic interactions. Upon interacting with nucleic acids, cationic liposomes form clusters of aggregated vesicles. These interactions allow cationic liposomes to condense and encapsulate various therapeutic and diagnostic agents in their aqueous compartment or in their lipid bilayer. These cationic liposome-nucleic acid complexes are also referred to as lipoplexes. Due to the overall positive charge of cationic liposomes, they interact with negatively charged cell membranes more readily than classic liposomes. This positive charge can also create some issues in vivo, such as binding to plasma proteins in the bloodstream, which leads to opsonization. These issues can be reduced by optimizing the physical and chemical properties of cationic liposomes through their lipid composition. Cationic liposomes are increasingly being researched for use as delivery vectors in gene therapy due to their capability to efficiently transfect cells. A common application for cationic liposomes is cancer drug delivery.

<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

<span class="mw-page-title-main">PEGylation</span> Chemical reaction

PEGylation is the process of both covalent and non-covalent attachment or amalgamation of polyethylene glycol polymer chains to molecules and macrostructures, such as a drug, therapeutic protein or vesicle, which is then described as PEGylated. PEGylation affects the resulting derivatives or aggregates interactions, which typically slows down their coalescence and degradation as well as elimination in vivo.

<span class="mw-page-title-main">Solid lipid nanoparticle</span> Novel drug delivery system

Lipid nanoparticles (LNPs) are nanoparticles composed of lipids. They are a novel pharmaceutical drug delivery system, and a novel pharmaceutical formulation. LNPs as a drug delivery vehicle were first approved in 2018 for the siRNA drug Onpattro. LNPs became more widely known in late 2020, as some COVID-19 vaccines that use RNA vaccine technology coat the fragile mRNA strands with PEGylated lipid nanoparticles as their delivery vehicle.

<span class="mw-page-title-main">Moderna</span> American biotechnology company

Moderna, Inc. is a pharmaceutical and biotechnology company based in Cambridge, Massachusetts, that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to carry instructions for proteins to produce an immune response. The company's name is derived from the terms "modified", "RNA", and "modern".

Leaf Huang is a Fred Eshelman Distinguished Professor in the UNC Eshelman School of Pharmacy and a Professor UNC/NC State joint Biomedical Engineering department. He has authored and co-authored over 570 peer reviewed articles and as of 2017 carries an h-index of 138.

<span class="mw-page-title-main">Arbutus Biopharma</span> Canadian Bio Tech Company

Arbutus Biopharma Corporation is a publicly traded Canadian biopharmaceutical company with an expertise in liposomal drug delivery and RNA interference, and is developing drugs for hepatitis B infection.

Arcturus Therapeutics Holdings Inc. is an American RNA medicines biotechnology company focused on the discovery, development and commercialization of therapeutics for rare diseases and infectious diseases. Arcturus has developed proprietary lipid nanoparticle RNA therapeutics for nucleic acid medicines including small interfering RNA (siRNA), messenger RNA (mRNA), gene editing RNA, DNA, antisense oligonucleotides, and microRNA.

Cancer treatments may vary depending on what type of cancer is being targeted, but one challenge remains in all of them: it is incredibly difficult to target without killing good cells. Cancer drugs and therapies all have very low selective toxicity. However, with the help of nanotechnology and RNA silencing, new and better treatments may be on the horizon for certain forms of cancer.

Owais Mohammad is an Indian immunologist, nano-technologist and a professor at the interdisciplinary biotechnology unit of the Aligarh Muslim University. Known for his studies on nanotechnology-based vaccine and drug delivery, Owais is the author of two books, Trypanothione reductase: a potential anti-leishmanial drug target and Antimicrobial properties of clove oil: clove oils as antimicrobial agent. He has also co-edited two books, Modern Phytomedicine: Turning Medicinal Plants into Drugs and Combating Fungal Infections: Problems and Remedy, and has contributed chapters. His studies have also been documented by way of a number of articles and ResearchGate, an online repository of scientific articles has listed 60 of them. He is a recipient of the Rashtriya Gaurav Award of the India International Friendship Society. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the highest Indian science awards, for his contributions to biosciences in 2007. His work has been displayed on cover pages of FEMS Immunol. Med Microbiology for all the issues of Year 2006 and Molecular Medicine in May–June issue of Year 2007.

mRNA vaccine Type of vaccine

An mRNAvaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into immune cells, which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen or by a cancer cell. These protein molecules stimulate an adaptive immune response that teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles that protect the RNA strands and help their absorption into the cells.

<span class="mw-page-title-main">Katalin Karikó</span> Hungarian-American biochemist (born 1955)

Katalin "Kati" Karikó is a Hungarian-American biochemist who specializes in ribonucleic acid (RNA)-mediated mechanisms, particularly in vitro-transcribed messenger RNA (mRNA) for protein replacement therapy. Karikó laid the scientific groundwork for mRNA vaccines, overcoming major obstacles and skepticism in the scientific community. Karikó received the Nobel Prize in Physiology or Medicine in 2023 for her work, along with American immunologist Drew Weissman.

<span class="mw-page-title-main">ALC-0315</span> Chemical compound

ALC-0315 is a synthetic lipid. A colorless oily material, it has attracted attention as a component of the SARS-CoV-2 vaccine, BNT162b2, from BioNTech and Pfizer. Specifically, it is one of four components that form lipid nanoparticles (LNPs), which encapsulate and protect the otherwise fragile mRNA that is the active ingredient in these drugs. These nanoparticles promote the uptake of therapeutically effective nucleic acids such as oligonucleotides or mRNA both in vitro and in vivo.

<span class="mw-page-title-main">Drew Weissman</span> American physician and immunologist (born 1959)

Drew Weissman is an American physician and immunologist known for his contributions to RNA biology. Weissman is the inaugural Roberts Family Professor in Vaccine Research, director of the Penn Institute for RNA Innovation, and professor of medicine at the Perelman School of Medicine at the University of Pennsylvania (Penn).

SM-102 is a synthetic amino lipid which is used in combination with other lipids to form lipid nanoparticles. These are used for the delivery of mRNA-based vaccines, and in particular SM-102 forms part of the drug delivery system for the Moderna COVID-19 vaccine.

Pieter Rutter Cullis is a Canadian physicist and biochemist known for his contributions to the field of lipid nanoparticles (LNP). Cullis and co-workers have been responsible for fundamental advances in the development of nanomedicines employing lipid nanoparticle (LNP) technology for cancer therapies, gene therapies and vaccines. This work has contributed to five drugs that have received clinical approval by the US Food and Drug Agency (FDA), the European Medicines Agency, and Health Canada.

<span class="mw-page-title-main">Intracellular delivery</span> Scientific research area

Intracellular delivery is the process of introducing external materials into living cells. Materials that are delivered into cells include nucleic acids, proteins, peptides, impermeable small molecules, synthetic nanomaterials, organelles, and micron-scale tracers, devices and objects. Such molecules and materials can be used to investigate cellular behavior, engineer cell operations or correct a pathological function.

BIOTECanada, or the Industrial Biotechnology Association of Canada, is a Canadian biotechnology industry association based in Ottawa, Ontario. It is an industry-funded membership organization composed of over 250 national and international pharmaceutical and gene therapy companies, medical device manufacturers, agricultural science businesses, law firms, academic institutions, research and development networks, advertising agencies, insurance companies and financial services firms.

Intranasal drug delivery occurs when particles are inhaled into the nasal cavity and transported directly into the nervous system. Though pharmaceuticals can be injected into the nose, some concerns include injuries, infection, and safe disposal. Studies demonstrate improved patient compliance with inhalation. Treating brain diseases has been a challenge due to the blood brain barrier. Previous studies evaluated the efficacy of delivery therapeutics through intranasal route for brain diseases and mental health conditions. Intranasal administration is a potential route associated with high drug transfer from nose to brain and drug bioavailability.

References

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