Yet another biotech entered the COVID-19 vaccine race, this time with preclinical data supporting evidence for an adaptive cellular (CD8+ cells) and balance (Th1/Th2) immune response data from Arcturus Therapeutics Holdings Inc., a clinical-stage messenger RNA medicines company focused on the discovery, development, and commercialization of therapeutics for rare diseases and vaccines.
What is significant about Arcturus Therapeutics Holdings (Arcturus) most recent findings?
The company reported earlier in May that new results augment previously disclosed preclinical data, evidencing a strong antibody response (anti-spike protein IgG and 100% virus neutralization at a very low vaccine dose) from the program. Together, the available data indicate that LUNAR-COV-19 is effectively activating the two fundamentally important components of the adaptive immune response, offering evidence in support of an investment to commence human vaccine trials.
When would human clinical trials commence?
The company reported in its press release that a clinical trial would be on track later in the summer.
Were there any clinical investigational sites involved that can verify this data?
Yes. Research investigators at Duke-NUS Medical School in Singapore were involved, according to the company. In fact, according to Professor Ooi Eng Eong, Deputy Director of the Emerging Infectious Diseases Program at Duke-NUS Medical School, “These extended preclinical studies, conducted in partnership with Arcturus, establish a comprehensive and highly compelling package of data to support clinical trials.” The Singapore-based investigator certainly considers the results promising and “an even more compelling case for a clinical trial.”
Comments from the Company on the evidence
Chief Scientific Officer Pad Chivukula, PhD, reported that “A vaccine approach that elicits a broader immune response by activating both humoral (i.e., antibodies) and cellular (T-cells) immunity has the potential to provide more potent clinical protection. Our preclinical LUNAR-COV19 data confirms this broad immune response.”
What did an additional study involving an evaluation of cell-mediated immunogenicity reveal?
Led by Professor Ooi Eng Eong’s lab at Duke-NUS, he reports that the results reveal a dose-dependent CD8+ T-cell response, evidencing a clear response observed at all doses, in addition to a well balanced Th1/Th2 CD4+ T-cell response (intracellular cytokine (IFN-y/IL-4) staining). The percent of CD8+ T-cells increased from 4% to 8% with increasing doses of STARR™ mRNA. The Th1/Th2 ration for T-helper cells (CD4+) reveal a strong TH1 response, which doesn’t change with increasing dose, suggesting that the immune response remains balanced across dosage levels.
The company reported a single administration of LUNAR-COV19 STARR™ mRNA induced a higher anti-spike protein IgG response than conventional mRNA at equivalent doses, and particularly at lower doses. Moreover, the IgG response also continued to increase at a much greater rate over the 30-day post-vaccination period than conventional mRNA.
Key Position by Company?
A vaccine approach that elicits a broad and balanced immune response by activating humoral and cellular immunity can provide more effective protection.
What is a key advance of the company’s self-replicating mRNA vaccine?
The potential to activate both of these important components of adaptive immunity and the reported preclinical LUNAR-COV-19 data suggests a robust and balanced immune response.
How did the research team determine seroconversion?
The team determined seroconversion using a quantitative plaque reduction neutralization assay (using SARS-CoV-2 Singapore Clinical Isolate)—measuring neutralizing antibody titers detected in serum at day 30.
What subjects were used in the preclinical research?
Rodents immunized with a single intramuscular dose (0.2, 2, and 10ug) of the LUNAR-COV19 vaccine.
Results after 30 days?
By day 30, post-vaccination, 80% of vaccinated mice with 0.2 ug LUNAR-COV-19 elicited antibodies that neutralized 50% of SARS-CoV-2 at titers 20 and above. For more information, see the underlying source and accompanying data tables.
About Arcturus Therapeutics
Founded in 2013 and based in San Diego, Arcturus, a clinical-stage company, is publicly traded (Nasdaq: ARCT) and focuses on mRNA medicines and vaccines with enabling technologies including 1) LUNAR lipid-mediated delivery, 2) STARR mRNA Technology, and 3) mRNA drug substance along with drug product manufacturing expertise.
Arcturus’ diverse pipeline of RNA therapeutic candidates includes programs to potentially treat Ornithine Transcarbamylase (OTC) Deficiency, Cystic Fibrosis, Glycogen Storage Disease Type 3, Hepatitis B, non-alcoholic steatohepatitis (NASH), and a self-replicating mRNA vaccine for SARS-CoV-2.
The company positions that its versatile RNA therapeutics platforms can be applied toward multiple types of nucleic acid medicines, including messenger RNA, small interfering RNA, replicon RNA, antisense RNA, microRNA, DNA, and gene editing therapeutics. Their products are covered—they report by an extensive patent portfolio (187 patents and patent applications issued in the U.S., Europe, Japan, and China as well as other countries).
This intellectual property has led to collaborations with companies such as Janssen Pharmaceuticals (part of Johnson & Johnson), Ultragenyx Pharmaceutical, Inc., Takeda Pharmaceutical Limited, CureVac AG, Synthetic Genomics Inc., Duke-NUS, Catalent Inc., and the Cystic Fibrosis Foundation.
Business & Finance
With a share price of $38.94, the company market capitalization is $752 million. Its 52-week high/low has been a significant $5.75 to $62.97. The company is projected to lose about $30 million and holds about $59 million in the bank. Owned by a substantial number of institutional and mutual fund shareholders, since the advent of the pandemic, the share lifted from $14.10 in early March to its price today.
What about its STARR™ Technology?
The STARR™ Technology platform combines self-replicating mRNA with LUNAR®, a leading nanoparticle delivery system, into a single solution to produce proteins inside the human body. The versatility of the STARR™ Technology affords its ability upon delivery into the cell to generate a protective immune response or drive therapeutic protein expression to potentially prevent against or treat a variety of diseases. The self-replicating RNA-based therapeutic vaccine triggers rapid and prolonged antigen expression within host cells, resulting in protective immunity against infectious pathogens. This combination of the LUNAR® and STARR™ technology is expected to provide lower dose requirements due to superior immune response, sustained protein expression compared to non-self-replicating mRNA-based vaccines, and potentially enable them to produce vaccines more quickly and simply.
Lead Research/Investigator for Preclinical Vaccine Research
Professor Ooi Eng Eong, Deputy Director of the Emerging Infectious Diseases Program at Duke-NUS Medical School