In recent months, four PhDs and a professor have been splitting their time between Jerusalem and northern Israel. With an investment of roughly $2.5 million, they have established a 1,000 square meter (11,000 square foot) assembly plant at the Lavon industrial park in the Galilee, just north of Carmiel.
On the first floor of the plant, a robot sits next to a small window overlooking forklifts. It’s turning plastic handles on a kind of carousel, placing sealing rings on them. Soon, large cartons of these handles will be transported to the second floor, where the windows are bigger, the view is greener, and the machinery is quieter. The second-floor also has its own robot, and it sprays glue with a precision of within the microns and sends the final product on to a conveyor belt where a sponge is attached.
“This machine saves the work of six people and is capable of producing 40,000 units a day,” says Guy Krief of the firm Salignostics. In the coming weeks, the company will begin commercial production of its Salistick, the world’s first rapid pregnancy test that makes use of a woman’s saliva. Krief is one of five inventors of the product.
The test kits, development of which began six years ago in a university student lab in Jerusalem, were recently approved by the European Union and the Israeli Health Ministry for use by the public. The group of entrepreneurs have also gotten approval to sell a home COVID test for use at a stage when patients are still asymptomatic – but also very contagious. In the coming years, they hope to launch testing products to diagnose malaria, angina pectoris (which tests for the presence of troponin protein) and for helicobacter pylori bacteria. All of the tests will make use of the same little handle that is being manufactured at the Galilee facility.
The advantage of testing saliva is clear. Unlike blood or urine, saliva is easy to collect and can be easily tested anywhere, but unlike blood and urine, which are almost completely stable in their biological composition and properties, there’s a big problem with spit.
“It has a lot of bothersome characteristics,” says Krief, who is Salignostics’ deputy CEO for business development. “It varies among people and also for the same individual. Your saliva will be an entirely different liquid now and in another two hours when it comes to viscosity and its production of enzymes.”
Cleaning the saliva
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If that’s the case, how can a company base testing on saliva? It’s due to an approach that the company developed. “It’s a matter of saliva and not paper,” says the company’s president, Prof. Aaron Palmon. The little test strips in plastic cases that we are currently familiar with for coronavirus tests use an old technology. The test paper in the case has stripes with chemicals that bind with the protein whose presence is being tested for. When the two bind, the stripes change color.
Palmon claims that this technology isn’t being used to diagnose a range of other diseases because the pharmaceutical companies are focussed on the wrong thing. Instead of trying to adapt the paper, they should be investigating changing saliva, he says. “If you change the saliva, even simple technologies can reveal what’s happening in it.”
There is a primary protein in saliva called amylase, Palmon explains, that breaks down sugars. It controls half the fluid and, together with other materials, obscures the biological markers indicating the presence of diseases. Salignostics processes the saliva to remove those other materials and concentrates those components to indicate a person’s physiological condition.
“Without the chemical treatment that we perform on the saliva, you wouldn’t see anything in it,” Palmon says. “And this capability is what enables us to develop diagnostic products based on saliva.”
Another challenge that the company had to address was the volume of saliva required to have the test come out properly. This required designing the handle so they would have visual indication showing when enough saliva had been collected.
The company chose to develop a pregnancy test first due to its massive financial potential – a market with an estimated value of $2 billion – and because pregnancy tests are inexpensive and available and can be easily purchased for research and comparison.
“In the pregnancy test market, there aren’t 20 brands,” Krief says. “There are two or three positioned in the premium segment and that, with the help of marketing gimmicks such as a digital feature, manage to control large portions of the market.”
Salignostics will also market its test as a premium product, for providing a better user experience and highlighting the fact that the user does not need to wait for the first urine of the morning and that a female can do the test with their partner. The company is convinced that if it links up with a strong player in the field, its product can garner a major share of the market.
“We’ve done market research among a range of populations, and we’ve seen that even before educating the public about the product and marketing it, about 70 percent of women would prefer to do a saliva pregnancy test,” Krief says. “At the last Medica convention in Germany, which is perhaps the center stage in the world for medical equipment, our pavilion with the saliva pregnancy tests was 100 percent full, opening up 50 distribution channels for us around the world, which of course is not relevant to a company of our size.”
Stem cells and fund raising
Salignostics recently raised $8 million. The sum is in addition to another $8 million that was raised between 2017 and 2019, as well as $3 million that it received in grants, in part from the Israel Innovation Authority and the RADx program, which is funded by the U.S. National Institutes of Health. According to Israel’s registrar of companies, the main investor in Salignostics is Avigdor Orlinsky, via a limited partnership by the name of the Diagnostic Future, which holds a 56 percent stake in the company.
Salignostics was born in a salivary gland molecular medicine lab at the dental school of Hebrew University of Jerusalem. The company was formed under the direction of Prof. Palmon, who until recently was the dean of the dental school. The other founders began their involvement as four doctoral and postdoctoral students at the lab.
“There was special interaction among them. They came from various backgrounds and thought differently,” Palmon recounted. “I told them, 'When we finish this lab, we will launch a startup,' because I have never seen a team as nice as yours.”
Palmon insists that technology such as Salignostics’ could only have been developed at an academic institution, where the motives are research-related rather than financial. “You work for three years before you see success. Commercial firms would have already shut us down,” he said.
The lab staff at the time was divided into two sections, working on various tasks related to research on saliva and preparing it for use as a diagnostic tool. The first team included Krief and Omer Deutsch, who is now the CEO of Salignostics. They dealt with the characteristics of saliva and researched the proteins that might serve as markers for various diseases.
Deutsch researched pancreatic cancer and Krief managed to find indications of the development of celiac disease from saliva samples. Deutsch has a dual doctorate in dental medicine and biology while Krief has a doctorate in biology and a background in biotechnology.
The second group consisted of Reluca Cohen and Yoav Neumann, who now both have doctorates in biology. Their research centered around the use of stem cells to restore salivary glands. The two focused on the medical challenges for patients with head and neck cancer who undergo radiation and which as a result of their salivary glands are damaged, depriving them of a normal amount of saliva. That can have major consequences such as a dry mouth, sores and infections, and even difficulty eating or speaking.
Neumann, who is now Salignostics’ project director, developed ways to isolate cells from saliva tissue, and Cohen, who is currently the company’s chief scientific officer, furthered Neumann’s research by restoring salivary glands’ functionality in mice that had undergone radiation treatment.
Hebrew University entered an agreement with Salignostics that transferred intellectual property to the company in exchange for royalties that the university is to receive from the sale of the products based on it.