Placenta cells are unique. They are the youngest, most potent cells of the human body – and they can help the body heal itself.
The Israeli-European company Pluristem is harnessing those cells to treat conditions arising from severe infection, inflammation or obstructed blood flow and, more recently, COVID-19. The company takes cells from placentas donated after birth and grows them in a 3-D bioreactor that mimics the conditions of the human body. Injected into patients, the new cells secrete a cocktail of proteins in reaction to the patient’s condition. That exchange helps the patient’s body regenerate itself.
Says Chen Franco-Yehuda, Pluristem’s chief financial officer, “It’s like a little engine.”
That little engine may help patients suffering from complications from coronavirus infection – pulmonary hypertension, lung fibrosis, or acute kidney and gastrointestinal injury. The therapies also could potentially reduce the deadly symptoms of pneumonia and pneumonitis, while boosting patients’ immune systems. The European Investment Bank (EIB) is supporting Pluristem with a €50 million investment.
Pluristem has treated COVID-19 patients through compassionate-use programmes in Israel and the United States. Compassionate-use programmes allow unapproved drugs or treatments to be tried on patients.
The company reported preliminary data on April 7 from the Israeli programme, which focused on seven patients suffering from acute respiratory failure and inflammatory complications resulting from COVID-19. All of the patients treated were in intensive care and on respirators.
After seven days of treatment, all these patients were still alive. Four out of six patients showed improved respiratory function, while three were being weaned off respirators.
In the US, Pluristem treated one patient suffering from respiratory failure at the Holy Name Medical Center in New Jersey under a compassionate-use programme. The New Jersey hospital was part of a Phase III study using the company’s cell therapies to treat critical limb ischemia, an obstruction of the blood flow to lower extremities like hands, feet or legs. Untreated, critical limb ischemia can lead to amputation or death.
European clinical trials
The nature of the compassionate-use studies makes it difficult to draw definite conclusions about the treatment’s effectiveness. For that reason, Pluristem applied in the EU and the US to start Phase II clinical trials.
In Europe, the trials will be conducted in Germany at the Berlin-Brandenburg Center for Regenerative Therapy and the Berlin Centre for Advanced Therapies at Charité University of Medicine, where Pluristem already had a Phase III trial underway to test critical limb ischemia and recovery following hip fracture. Clinical trials will also allow Pluristem to apply for regulatory approval to register and market its products.
The idea is to start the COVID-19 trials in Germany and Italy, potentially expanding those trials to other European countries. The EIB will invest €50 million in non-dilutive, venture debt financing that should cover about half of Pluristem’s R&D costs in Europe and help get treatments to the market. Pluristem recently established an R&D subsidiary in Germany.
The European Investment Bank funds will be disbursed in three tranches, following the completion of different milestones. The EIB investment is backed by a guarantee from the European Fund for Strategic Investments, the financial pillar of the Investment Plan for Europe.
“We were able to react quickly and provide non-dilutive, long-term financing, allowing Pluristem to speed up their key clinical trials,” says Anna Stodolkiewicz, an EIB investment officer.
Placenta cell compatibility
A huge advantage of placenta cells is that they can be injected into any patient, regardless of blood type, DNA or tissue compatibility.
Normally, patients treated with cell therapies would need to take immunosuppressant drugs to stop their bodies from rejecting the treatment. But the neutral nature of placenta cells makes those treatments unnecessary. “Think about a surrogate mother and a baby,” Pluristem’s Franco-Yehuda says. “Even if the mother is not a match to the baby, her body still won’t attack the baby, because of the placenta.”
One complication from COVID-19 is the over-activation of the immune system, which in some cases results in the fatal shutdown of multiple organs. Pluristem’s therapy “has immunomodulatory and tissue repair properties that prevent over-activating the immune system and may even be able to reverse it,” says Petia Manolova, a senior EIB economist.
Along with the COVID-19 trials, Pluristem continues to develop therapies to treat disorders like severe infections, inflammations, muscle injuries, blood disorders and critical limb ischemia, most commonly caused by late stage diabetes.
The other advantage is the source of the cells. The placenta are collected after the delivery of healthy, full-term babies, from women under 35 years old who underwent an elective caesarean section. “Those cells can then be used for the good of human kind,” says Auvo Kaikkonen, a senior Life Sciences specialist at the EIB.
Mimicking the body
Pluristem was born in a bioreactor.
The company was created in Haifa, Israel, in 2003 after the founders, led by Zami Aberman, acquired the patents for a bioreactor developed by the Israeli Institute of Technology and the Weizmann Institute of Science. Aberman pushed the company to think of ways to exploit the bioreactor technology, and Pluristem started to experiment with placenta cells.
“At the time, no one knew that those cells were different from other kinds of cells,” Franco-Yehuda says.
The three-dimensional reactor mimics the conditions of the human body, enabling cells to grow. The technology allows Pluristem to produce a large number of treatments – up to 20 000 – from one placenta. Mass production is a key advantage during a global pandemic.
Growing the cells is one thing, but how do you get a treatment to the patient?
The company has created a cold chain distribution process to ensure that cells aren’t damaged or destroyed. That distribution method gives the cells a shelf life, meaning they can be stored for future treatments.
The company, which is publicly traded on Nasdaq and the Tel Aviv Stock Exchange, has raised about $350 million so far to pay for technological development and clinical trials. About 60% of the senior management is female. While Pluristem currently has no revenue, it plans to start selling its products commercially in coming years.
Franco-Yehuda says the EIB’s involvement gives Pluristem a solid partner in Europe – a large potential market. “The EIB backing is an important milestone for Pluristem and a good stamp of confidence on our vision,” she says.