Meet the maker of the powdered vaccine that hopes to immunize 4m. Israelis
Israel signed with Arcturus back in July, soon after it struck a deal with Moderna.
By MAAYAN JAFFE-HOFFMANArcturus CEO Joseph Payne(photo credit: Courtesy)Israel is “first in line, or at least in the front position of that line” – along with Singapore – to receive four million doses of a vaccine being developed by the small California-based messenger RNA therapeutics company known as Arcturus, according to its CEO Joseph Payne. Israel signed with the company back in July, soon after it struck a deal with Moderna, Inc., although it is rarely mentioned by the prime minister as one of the possible solutions to the coronavirus crisis. Earlier this month, Arcturus reported positive interim Phase I/II study results for its LUNAR-COV19 vaccine. Now, Payne told The Jerusalem Post, “I look forward to playing a key role” in vaccinating Israel. Based on the interim results, a robust immune response was observed at all doses evaluated, and increased through approximately day 43. The study has also thus far shown a favorable safety and tolerability profile in both younger volunteers (ages 21-55) and older ones (ages 56-80). The Phase I/II trial of the vaccine is being carried out in collaboration with Singapore’s Duke-NUS Medical School. There are 106 participants. LUNAR-COV19 utilizes the company’s Self-Transcribing and Replicating mRNA (STARR) technology and its LUNAR lipid-mediated delivery to produce a low-dose, potential single-shot vaccine, which is not dissimilar to the Moderna and Pfizer vaccines. Pfizer announced the final results from the late-stage trial of its COVID-19 vaccine this week, which showed that it is 95% effective. The company is applying for emergency US authorization within days. PAYNE SAID that the Phase I/II trial should be complete within weeks and then later-stage clinical trials would begin, which in a best-case scenario would be completed by spring 2021 – and the vaccines, which can be manufactured quickly, can then be distributed. He told the Post that the country’s doses will cost Israel approximately $275 million and that they “won’t trickle in like other vaccines. It may be in two lots, but not more.” He also said that he does not expect any lag time between regulatory approval and distribution. “Some people get approved and then manufacture,” Payne said. “We intend to have stockpiled doses ready to distribute when they are approved.” Arcturus’s LUNAR-COV19 is unique because of its low dosage – likely only one 7.5 microgram dose versus two 30 microgram doses for Pfizer and two 100 microgram doses for Moderna – although Payne said that the company is also evaluating a potential low-dose booster. “The single shot is important for compliance,” Payne explained. “You look at efficacy in clinical trials, but you also have to ask what will be the compliance of the patient population – what percentage will come in for both doses. With Arcturus’s potential one shot you would get 100% compliance.” The other difference, which could be a game-changer for the company, is that Arcturus is evaluating a powdered version of the vaccine – “lyophilized” in science-speak. “It means that the water has been removed,” Payne explained. “This is not as simple as freeze drying meat or pineapple. It takes a considerable amount of science, resources and time to know how to carefully remove the water from these vaccines and leave just the powder. If we can do it successfully, it will dramatically improve supply chain logistics.” He explained that water degrades RNA and hence the vaccine has to be frozen. In Pfizer’s case, its vaccine has to be stored at negative 70 degrees Celsius, complicating storage and delivery. “If you take it out of the freezer and it starts to melt, then you need to either use it immediately or throw it away,” Payne said, whereas “a lyophilized version is more stable.” HE SAID that the technology for creating the powdered vaccine was already being developed before coronavirus through a partnership the company has with Johnson & Johnson in their research efforts toward RNA therapeutics for hepatitis B that could more easily stored and shipped all over the world, including to less affluent countries. “We just applied the learning to the COVID-19 vaccine product, so we are ahead of the game,” he said. Finally, with respect to manufacturing, the company received a financial commitment of $45m. up front from the Singapore Economic Development Board to fund the manufacturing of the vaccine. “If you take into consideration the manufacturing timelines, then we are in good shape,” he said. Payne said he has been confident that his vaccine would work since the preclinical animal trials. And he still believes it, especially after the positive results reported by Moderna and Pfizer. “Seeing the excellent efficacy in Pfizer and Moderna bodes well for Arcturus and increases the probability of our success – no doubt.” Recall, the mRNA vaccines being developed will be the first-ever brought to market for human patients. Payne admitted that by the time of the vaccine’s release, there would not be any long-term studies since companies are all making efforts to fast-track their human trials in order to help reduce worldwide infection and death. But he said that while “mRNA vaccines are cutting edge, they are beautifully simple” at the same time. In other words, while the Moderna, Pfizer and Arcturus vaccines are based on new vaccine technologies, they are asking our bodies to do something they do every day: protein synthesis, the process where cells make proteins, according to Michal Linial, professor of biological chemistry at the Hebrew University of Jerusalem. She said these mRNA vaccines are simply delivering a specific mRNA sequence to our cells. Once the mRNA is in the cell, human biology takes over. Ribosomes read the code and build the protein, and the cells express the protein in the body. SOME SCIENTISTS have expressed concern that there could be some side effects to mRNA vaccines, such as local and systemic inflammatory responses that could lead to adverse autoimmune conditions. An article published by the National Center for Biotechnology Information, a division of the National Institutes of Health, said other risks include the biodistribution and persistence of the induced immunogen expression; possible development of auto-reactive antibodies; and toxic effects of any non-native nucleotides and delivery system components. Payne said that he believes vaccination is a key weapon in the battle against coronavirus, but noted that he does not believe it will eradicate the disease. “The harsh reality is that COVID is likely here to stay,” he said, predicting that people will likely need to be vaccinated annually rather than once in their lifetime. He said vaccination could be a key in getting the spread of the virus under control and stopping the destructive effect it is having on the world’s economy. Arcturus has deep roots in Israel, which is one of the reasons it first approached the Jewish state about its vaccine – before almost any other country. The company, which merged with Israel’s Alcobra Ltd. in 2017, still has a handful of Israelis among the company’s staff of 120. He said that Israel’s Health Ministry reviewed the company’s preclinical data early on and trusted it enough to prepay for the vaccines. Now, Payne is hopeful that Arcturus will have a chance “to repay that trust” by providing enough vaccines to protect the country.
