Arcturus Therapeutics

Last updated
Arcturus Therapeutics Holdings Inc.
Company type Public
Nasdaq:  ARCT
Industry Pharmaceutical industry
Founded2013;11 years ago (2013)
FounderJoseph Payne and Pad Chivukula
Headquarters San Diego, California, US
Key people
ProductsARCT-810 for treatment of OTCD; received FDA Orphan Drug Status on 27 July 2019; Phase 1 Clinical Trials in Healthy Volunteers Initiated on 05 June 2020, ARCT-021 Vaccine for COVID-19; Phase 1/2 Initiated 22 July 2020, Phase 2 Initiated 9 January 2021
RevenueIncrease2.svg $21 Million(2019) [1]
Number of employees
124
Website www.arcturusrx.com

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.

Contents

The company develops RNA therapeutics for the treatment of rare diseases such as ornithine transcarbamylase deficiency, and respiratory diseases such as cystic fibrosis. As of 2021, vaccine medicines include a vaccine candidate for COVID-19 and an influenza vaccine in the preclinical development phase. [2]

History

Founded in 2013 by Joseph Payne and Pad Chivukula, Arcturus Therapeutics is headquartered in San Diego, California, USA. Initially, they developed a proprietary lipid nanoparticle delivery system called Lunar, able to safely deliver therapeutic RNA or DNA to target cells inside a patient's body. [3]

In September 2017, Arcturus Therapeutics merged with Alcobra Ltd., an Israeli pharmaceutical company. [4] In February of 2018, Joseph Payne was dismissed as president and CEO by the Arcturus Therapeutics board of directors at that time. [5] In the aftermath, as the largest shareholder, Joseph Payne filed formal requests to hold a meeting of shareholders for the purpose of selecting new members to the Arcturus Therapeutics board of directors. Under applicable law, Arcturus’ board must have honored Payne’s request by establishing a meeting date and convening said meeting within a clearly defined timeframe. Rather than adhering to the law, the Board ignored the applicable deadlines and opted to postpone the shareholder meeting indefinitely. [6] [7] [8] Joseph Payne subsequently filed legal proceedings with the Israeli Court which ruled in favor of upholding shareholder rights by sanctioning the meeting of shareholders. [9]

In April of 2018, the Arcturus Therapeutics board of directors at the time filed their own complaint against Joseph Payne and his nominees to the board. [10] In May of 2018, a legal settlement was agreed upon: 4 new directors were appointed to the board (Peter Farrell, Andrew Sassine, James Barlow and Magda Marquet) resulting in the resignation of Stuart Collinson, Daniel Geffken, David Shapiro, and Craig Willett. Other key terms of the settlement agreement included mutual releases of all parties and the agreement by Arcturus Therapeutics and Joseph Payne to terminate all pending litigation. [11]

Products

Lunar

Lunar is a lipid nanoparticle drug delivery system which targets specific cells inside the body to deliver a payload of RNA into the cell. [12] [13] Once release of the RNA into the cell occurs, the normal translational machinery of the cell can interact with the RNA to make a functional protein with a therapeutic effect. Prior to the Lunar technique, efficient in vivo delivery has also been challenging because existing lipid nanoparticles at the time could cause liver damage and elicit a strong immune response. [14]

This lipid nanoparticle delivery system has been used to deliver ornithine transcarbamylase messenger RNA to liver cells in order to treat citrin deficiency and ornithine transcarbamylase deficiency. [15] OTCD is the most common urea cycle disorder, which impacts an individual's ability to remove toxic waste products from the body. In collaboration with the Salk Institute for Biological Studies in La Jolla, California, successful delivery of a Factor IX messenger RNA to the liver was reported, which suggested viability of the approach to potentially treat diseases requiring protein replacement. [14] Researchers at the MD Anderson Cancer Center also showed the application of mRNA delivered in nanoparticles using the Lunar platform for the treatment of malignancy in intracerebral glioma. [16]

In 2019, a drug named ARCT-810 which uses Lunar, received FDA orphan drug status for treating ornithine transcarbamylase deficiency. [17] The orphan drug designation is granted to drugs capable of treating rare diseases that affect less than 200,000 people in the United States, and grants seven years of marketing exclusivity after approval. [18] On April 13, 2020, it was announced that the company's investigational new drug application for Phase 1b study in patients with OTCD was allowed to proceed by the U.S. FDA. [19] Clinical trials in patients began in June 2020. [20]

Lunar-COV19

ARCT-021 and Starr

In response to the COVID-19 pandemic, Arcturus partnered with Duke–NUS Medical School to develop a COVID-19 vaccine using a combination of self-replicating mRNA with a Lunar delivery platform which increases the level and duration of expression of a therapeutic protein). [21] The company also partnered with Catalent and Recipharm, contract development and manufacturing organizations, to manufacture multiple batches of Arcturus' COVID-19 mRNA vaccine candidate. [22] [23] Lunar-COV19 clinical trials in healthy volunteers began in July 2020. [24] Phase 2 clinical trials were approved in the United States and Singapore by the FDA and HSA, respectively in December 2020. [25]

Next-generations

On 2 August 2021, ARCT-154 started a clinical trial in Vietnam for next-generation development. [26] The next day, the firm announced that the application of approval for the clinical trial Phase I/II in Singapore called ARCT-165. Also application of ARCT-154 for phase I/II. [2]

Other projects

Lunar-CF is a project in collaboration with the Cystic Fibrosis Foundation to treat cystic fibrosis. [27]

Lunar-FLU is a wholly owned program to protect against the influenza virus. Arcturus is combining its self-replicating mRNA Starr technology with Lunar to develop a prophylactic vaccine against influenza.

Lunar-GSD is a project in collaboration with Ultragenyx to treat glycogen storage disease type III. [28]

Lunar-Rare is a project in collaboration with Ultragenyx to develop therapeutic candidates for rare disease targets.

Lunar-HBV is a project in collaboration with Janssen to develop medicines for the treatment of hepatitis B virus infection. [29]

Lunar-NASH is a project in collaboration with Takeda to develop medicines for non-alcoholic steatohepatitis (NASH) and other gastrointestinal disorders. [30]

Lunar-RPL is a project in collaboration with Synthetic Genomics to develop improved technology for vaccines and therapeutics. [31]

Lunar-AH is a project in collaboration with Synthetic Genomics to develop infectious disease prophylactic vaccines.

Related Research Articles

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

Ornithine is a non-proteinogenic α-amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl.

<span class="mw-page-title-main">Ornithine transcarbamylase deficiency</span> Medical condition

Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder, is the final enzyme in the proximal portion of the urea cycle, responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females.

<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">Plus Therapeutics</span> U.S. healthcare company

Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for adults and children with rare and difficult-to-treat cancers. The company is headquartered in Austin, Texas, United States.

<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".

Alnylam Pharmaceuticals, Inc. is an American biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics for genetically defined diseases. The company was founded in 2002 and is headquartered in Cambridge, Massachusetts. In 2016, Forbes included the company on its "100 Most Innovative Growth Companies" list.

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

Intellia Therapeutics, Inc. is an American clinical-stage biotechnology company focused on developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. The company's in vivo programs use intravenously administered CRISPR as the therapy, in which the company's proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia's ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases.

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.

RNA therapeutics are a new class of medications based on ribonucleic acid (RNA). Research has been working on clinical use since the 1990s, with significant success in cancer therapy in the early 2010s. In 2020 and 2021, mRNA vaccines have been developed globally for use in combating the coronavirus disease. The Pfizer–BioNTech COVID-19 vaccine was the first mRNA vaccine approved by a medicines regulator, followed by the Moderna COVID-19 vaccine, and others.

<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">Ultragenyx</span>

Ultragenyx is an American biopharmaceutical company involved in the research and development of novel products for treatment of rare and ultra-rare genetic diseases for which there are typically no approved treatments and high unmet medical need. The company works with multiple drug modalities including biologics, small molecule, gene therapies, and ASO and mRNAs in the disease categories of bone, endocrine, metabolic, muscle and CNS diseases.

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.

<span class="mw-page-title-main">ARCT-021</span> Vaccine candidate against COVID-19

ARCT-021, also known as LUNAR-COV19, is a COVID-19 vaccine candidate developed by Arcturus Therapeutics.

<span class="mw-page-title-main">PTX-COVID19-B</span> Vaccine candidate against SARS-CoV-2 (COVID-19)

PTX-COVID19-B is a messenger RNA (mRNA)-based COVID-19 vaccine, a vaccine for the prevention of the COVID-19 disease caused by an infection of the SARS-CoV-2 coronavirus, created by Providence Therapeutics—a private Canadian drug company co-founded by Calgary, Alberta-based businessman Brad T. Sorenson and San Francisco–based Eric Marcusson in 2013. A team of eighteen working out of Sunnybrook Research Institute in Toronto, Ontario developed PTX-COVID19-B in less than four weeks, according to the Calgary Herald. Human trials with sixty volunteers began on January 26, 2021, in Toronto.

<span class="mw-page-title-main">ARCT-154</span> Vaccine candidate against COVID-19

ARCT-154, also known as VBC-COV19-154 in Vietnam, is a COVID-19 vaccine candidate developed by Arcturus Therapeutics. For its development, Arcturus collaborated with Vinbiocare, a Vietnamese company, for support with clinical trials and manufacturing.

<span class="mw-page-title-main">COVID-19 vaccine clinical research</span> Clinical research to establish the characteristics of COVID-19 vaccines

COVID-19 vaccine clinical research uses clinical research to establish the characteristics of COVID-19 vaccines. These characteristics include efficacy, effectiveness, and safety. As of November 2022, 40 vaccines are authorized by at least one national regulatory authority for public use:

Gritstone bio is a clinical-stage American biotechnology company which develops cancer and infectious disease immunotherapies and vaccines. It was founded in August 2015 as Gritstone Oncology, Inc., and is based in Emeryville, California.

Pieter Rutter Cullis is a Canadian physicist and biochemist known for his contributions to the field of lipid nanoparticles (LNP). Lipid nanoparticles are essential to current mRNA vaccines as a delivery system. Prof. Cullis is best known for the development of ionizable cationic lipids. These lipids are able to complex with negatively charged nucleic acids at low pH (≈4.0) where they are positively charged because they have a pKa if approximately 6.4. They reduce or eliminate toxicity associated with cationic lipids at physiological pH of 7.4 because they adopt a net neutral charge. Finally, they enable endosomal escape because they again become positively charged in acidified endosomes and promote formation of non-bilayer structures by interaction with negatively charged lipids. These properties are critical to the function of the mRNA vaccines and are rapidly enabling gene therapy in clinical settings.

Kathryn Ann Whitehead is an American chemical engineer who is a professor at Carnegie Mellon University. Her research considers the development of nanomaterial-based drug delivery systems for gene therapy, oral macromolecular delivery systems, and maternal and infant therapeutics. She is an elected Fellow of the American Institute for Medical and Biological Engineering in 2021 and Fellow of the Controlled Release Society.

<span class="mw-page-title-main">Acuitas Therapeutics</span> Canadian biotechnology company

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.

References

  1. ↑ "Arcturus Therapeutics Holdings Revenue 2012-2021 | ARCT".
  2. 1 2 "Arcturus Announces Approval of Singapore Clinical Trial Application to Advance ARCT-154 and ARCT-165, Next Generation STARR™ mRNA Vaccines Targeting SARS-CoV-2 Variants of Concern, in a Phase 1/2 Study". Arcturus Therapeutics. 3 August 2021.
  3. ↑ Encyclopedia of Information Science and Technology, Fourth Edition. edited by Khosrow-Pour.
  4. ↑ "Alcobra Ltd. and Arcturus Therapeutics, Inc. Agree to Merge | Arcturus Therapeutics, Inc". ir.arcturusrx.com. Retrieved 2022-03-25.
  5. ↑ "Arcturus Therapeutics board fires CEO". Globes. 2018-05-02. Retrieved 2022-03-25.
  6. ↑ Payne, Concerned Shareholder of Arcturus Therapeutics, Joseph (2018-04-13). "Arcturus Therapeutics Founder Joseph Payne Disappointed by Board's Desperate Attempt to Delay Meeting and Avoid Shareholder Accountability". GlobeNewswire News Room (Press release). Retrieved 2022-03-25.{{cite press release}}: CS1 maint: multiple names: authors list (link)
  7. ↑ Payne, Concerned Shareholder of Arcturus Therapeutics, Joseph (2018-04-23). "Arcturus Therapeutics Founder Joseph Payne Dismisses Board's Baseless Lawsuit as Desperate Entrenchment Tactic". GlobeNewswire News Room (Press release). Retrieved 2022-03-25.{{cite press release}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Payne, Concerned Shareholder of Arcturus Therapeutics, Joseph (2018-05-02). "Arcturus Therapeutics Founder Joseph Payne Successfully Prevents Board's Egregious Attempt to Dilute Shareholders". GlobeNewswire News Room (Press release). Retrieved 2022-03-25.{{cite press release}}: CS1 maint: multiple names: authors list (link)
  9. ↑ Payne, Concerned Shareholder of Arcturus Therapeutics, Joseph (2018-05-14). "Arcturus Therapeutics Founder Joseph Payne Welcomes Court Decision to Set Date and Agenda of Extraordinary General Meeting to Vote for New Board Members". GlobeNewswire News Room (Press release). Retrieved 2022-03-25.{{cite press release}}: CS1 maint: multiple names: authors list (link)
  10. ↑ Payne, Concerned Shareholder of Arcturus Therapeutics, Joseph (2018-05-23). "Arcturus Therapeutics Founder Joseph Payne Calls for an End to Company's Frivolous and Costly Lawsuits; Applauds Court Decision and Welcomes June 25, 2018 EGM Date". GlobeNewswire News Room (Press release). Retrieved 2022-03-25.{{cite press release}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Payne, Joseph (2018-05-29). "Arcturus Therapeutics Appoints Four New Directors and Reaches Settlement Agreement with Founder Joseph E. Payne". GlobeNewswire News Room (Press release). Retrieved 2022-03-25.
  12. ↑ Teruki, Yanagi (28 June 2016). "Lipid Nanoparticle-mediated siRNA Transfer Against PCTAIRE1/PCTK1/Cdk16 Inhibits In Vivo Cancer Growth". Molecular Therapy: Nucleic Acids. 5 (6): e327. doi:10.1038/mtna.2016.40. PMC   5022131 . PMID   27351680.
  13. ↑ Stein, Richard (26 May 2017). "Better Targeting, Delivery of RNAi Therapies". Genetic Engineering & Biotechnology News. 37 (11): 1, 14–17. doi:10.1089/gen.37.11.02.
  14. 1 2 Ramaswamy, Suvasini (7 March 2017). "Systemic delivery of factor IX messenger RNA for protein replacement therapy". PNAS. 114 (10): E1941–E1950. Bibcode:2017PNAS..114E1941R. doi: 10.1073/pnas.1619653114 . PMC   5347596 . PMID   28202722.
  15. ↑ Damase, Tulsi Ram; Sukhovershin, Roman; Boada, Christian; Taraballi, Francesca; Pettigrew, Roderic I.; Cooke, John P. (2021). "The Limitless Future of RNA Therapeutics". Frontiers in Bioengineering and Biotechnology. 9: 628137. doi: 10.3389/fbioe.2021.628137 . ISSN   2296-4185. PMC   8012680 . PMID   33816449.
  16. ↑ Yaghi, Nasser (1 March 2017). "Immune modulatory nanoparticle therapeutics for intracerebral glioma". Neuro-Oncology. 9 (3): 372–382. doi:10.1093/neuonc/now198. PMC   5464307 . PMID   27765835.
  17. ↑ "Arcturus Therapeutics Receives Orphan Drug Designation". Drug Development and Delivery. 28 June 2019.
  18. ↑ "Designating an Orphan Product: Drugs and Biological Products". FDA Website. 24 Jul 2019.
  19. ↑ "Safety, Tolerability, and Pharmacokinetics of ARCT-810 in Stable Adult Subjects With OTC Deficiency - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Retrieved 2020-07-27.
  20. ↑ "Arcturus Therapeutics Announces First Healthy Volunteer Dosed in Phase 1 Study of ARCT-810 for Ornithine Transcarbamylase (OTC) Deficiency". Arcturus Therapeutics. Retrieved 2020-07-27.
  21. ↑ "Coronavirus: Clinical trials for Singapore's vaccine project could start in August". The Straits Times . 15 April 2020. Retrieved 27 April 2020.
  22. ↑ "With Arcturus, Catalent bags another COVID project". Bioprocess Insider. 2020-05-06. Retrieved 2020-05-08.
  23. ↑ "Recipharm signs agreement with Arcturus Therapeutics to support the manufacture of LUNAR[®]-COV19 (ARCT-021) vaccine candidate". Recipharm. Retrieved 2021-03-12.
  24. ↑ "Phase 1/2 Ascending Dose Study of Investigational SARS-CoV-2 Vaccine ARCT-021 in Healthy Adult Subjects". clinicaltrials.gov. Retrieved 2020-07-27.
  25. ↑ Arcturus Therapeutics, Inc. (2021-03-02). "A Phase 2 Randomized, Observer-Blind, Placebo-Controlled Study to Assess the Safety, Reactogenicity, and Immunogenicity of the SARS CoV-2 Vaccine ARCT-021 in Healthy Adult Participants" . Retrieved 12 March 2021.
  26. ↑ "Arcturus to start clinical trial of COVID-19 vaccine in Vietnam". Reuters. 2 August 2021. Retrieved 3 August 2021.
  27. ↑ Lopez, Jose Marques (25 June 2018). "RNA Therapy for CF shows promise in preclinical studies". Cystic Fibrosis News Today.
  28. ↑ "mRNA therapeutics". Adis Insights, Springer. Arcturus Therapeutics/Ultragenyx Pharmaceutical. 21 June 2019.
  29. ↑ Adams, Ben (19 October 2017). "Johnson & Johnson, RNA biotech Arcturus combine for hepatitis B work". Fierce Biotech.
  30. ↑ Elvidge, Suzanne. "Mixed results in NASH for Gilead". BioPharma Drive.
  31. ↑ Kotok, Allan (31 October 2017). "RNA Meds Companies Partner on Human, Animal Vaccines". Science Business.
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