Type: Very low dose, potential single-shot, self-replicating mRNA vaccine devoid of viral material or co-adjuvants. The vaccine is based on its STARR™ (Self-Transcribing And Replicating RNA), which combines self-replicating RNA with LUNAR® (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA) lipid-mediated delivery system into a single solution to produce proteins inside the human body.
The partners are also using a platform developed at Duke-NUS allowing rapid screening of vaccines for potential effectiveness and safety.
2021 Status: Arcturus said January 4 it received allowance from the FDA of the company’s IND for the Phase II clinical study of its vaccine candidate ARCT-021 following review of data from the Phase I/II study (NCT04480957). The Phase II study had been approved to proceed by the Singapore Health Sciences Authority (HSA), based on the same data as reviewed by the FDA. The Phase I/II study results showed favorable tolerability and both humoral and cellular immunogenicity following administration of ARCT-021.
The Phase II study will enroll 600 participants, with 450 receiving ARCT-021 and 150 receiving placebo. Both older and younger adult participants will be included, Arcturus said. Early interim analyses of safety and immunogenicity will be performed to inform dose selection for a Phase III study, which is targeted to start in Q2 2021, if the Phase II study is successful.
2020 Status: On July 23, Arcturus said Israel secured rights to stockpile and reserve doses of LUNAR-COV19 through an agreement signed with the Israeli Ministry of Health. Delivery of LUNAR-COV19 doses to Israel hinges on achieving near-term clinical and regulatory milestones and other conditions to be set forth in a comprehensive supply agreement that the company and the health ministry aim to finalize within 30 days.
Israel is the second country to reserve doses of LUNAR-COV19. The first is Singapore, where the Health Sciences Authority (HSA) on July 21 approved a Clinical Trial Application (CTA) for a Phase I/II study (NCT04480957) of LUNAR-COV19 by Arcturus and Duke-NUS Medical School. They will initiate human dosing of LUNAR-COV19 “as soon as possible,” Arcturus said.
The healthy volunteer study will evaluate several dose levels of LUNAR-COV19 in up to 108 adults, including older adults. Researchers will follow up with the participants to evaluate safety, tolerability, and the extent and duration of the humoral and cellular immune response.
Also in July, Arcturus released new preclinical data via a Luminex bead assay showing that neutralizing antibody levels in response to a single administration of LUNAR-COV19 at 0.2, 2.0, and 10.0 µg dosages continued to increase over 50 days—a finding the company attributed to the vaccine’s self-replicating mRNA.
Arcturus in July said it formed a Vaccine Platform Scientific Advisory Board (SAB) consisting of experts in virology, infectious disease, vaccine development, and public health. Named to the SAB were:
- Jeff Colyer, MD, CEO of Virtus Consultants and former Governor of Kansas
- Ooi Eng Eong, PhD, BMBS, FRCPath, Professor and Deputy Director of the Emerging Infectious Diseases Programme at the Duke-NUS Medical School
- Frederick G. Hayden, MD, FACP,Professor Emeritus of Clinical Virology and Medicine at Virginia University School of Medicine
- Peter A. Patriarca, MD, Principal of Immuno-Vax and Senior Affiliate Consultant with the Biologics Consulting Group
- Robert T. Schooley, MD, Professor of Medicine and Senior Director of International Initiatives at University of California, San Diego; and
- Jonathan Smith, PhD, Chief Scientific Officer at VLP Therapeutics.
In May, Arcturus announced preclinical data that it said provided strong support for human vaccine clinical trials by providing evidence for an adaptive cellular (CD8+ cells) and balanced (Th1/Th2) immune response from LUNAR-COV19. The results, measured by investigators at the Duke-NUS Medical School in Singapore, augmented previously disclosed preclinical data showing a strong antibody response (anti-spike protein IgG and 100% virus neutralization at a very low vaccine dose) from the program.
An additional study evaluating cell-mediated immunogenicity showed a dose dependent CD8+ T-cell response, with a clear response observed at all doses, as well as a balanced Th1/Th2 CD4+ T-cell response (intracellular cytokine (IFN-γ/IL-4) staining), Arcturus said. The percent of CD8+ T-cells increased from the 4% baseline to 8% with increasing doses of STARR mRNA. The Th1/Th2 ratio for T-helper cells (CD4+) shows a strong TH1 response which does not change with increasing dose, indicating that the immune response remained balanced across all dose levels.
Four days earlier, Arcturus joined Catalent to announce a partnership to support the manufacture of Arcturus’ LUNAR-COV19 for human clinical studies and, if successful, commercialization of the vaccine at Catalent’s drug substance biomanufacturing facility in Madison, WI. The vaccine program will use the facility’s flex-suite, a cGMP manufacturing suite that can produce batches at multiple scales and support Arcturus’ proprietary mRNA manufacturing process.
By combining Arcturus’ low-dose STARR mRNA vaccine technology with Catalent’s scalable cGMP manufacturing capabilities, the companies said they aim to produce millions of doses of LUNAR-COV19 mRNA in 2020 and potentially hundreds of millions of doses annually for worldwide use.
In April, Arcturus announced positive preclinical data for LUNAR-COV19, as measured by Duke-NUS Medical School in Singapore, showing Arcturus’ self-transcribing and replicating (STARR) mRNA induced higher seroconversion relative to conventional mRNA at equivalent doses at all equivalent doses and timepoints. Anti-SARS-CoV-2 IgG and IgM antibody titers were also higher.
Rodents were immunized with a single dose of LUNAR-COV19 vaccine at 0.2, 2, and 10 µg, i.m.). Seroconversion, using a virus neutralization assay (Vero-E6 cells with a SARS-CoV-2 Singapore Clinical Isolate), and IgG/IgM antibody titers were assessed at day 10 and day 19.
Arcturus and Duke-NUS disclosed their partnership to produce a COVID-19 vaccine in March, incorporating Duke-NUS’ genetic correlation system, designed to augment testing of vaccines by tracking genetic changes and their correlations. These gene expression changes can be measured within the first five days following vaccination and the data may also guide dose selection, Arcturus said.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: