The anti-cancer drug developed by Biond Biologics, which the Israeli startup will now try on humans in clinical trials with France-based multinational Sanofi, takes a multipronged approach to fighting tumors, activating three kind of cells in the immune system at the same time.
Paris-based multinational pharma firm Sanofi signed a licensing agreement earlier this month for Biond’s flagship anti-tumor drug BND-22, a cancer immunotherapy medication.
Under the terms of the agreement, Biond will receive an upfront payment of $125 million in cash and up to $1 billion in potential development, regulatory and sales milestones, as well as tiered double-digit royalty payments, the Israeli firm said in a statement. Biond will lead the first-in-human Phase 1a clinical trial of the drug, evaluating its safety and tolerability. Afterwards, Sanofi will take on development responsibilities and commercialization of the drug, Biond said.
“Immune oncology is about activating the immune system to fight cancer — and usually it is one drug that activates one kind of cell, either T-cells, or other cells,” said Tehila Ben-Moshe, the CEO and co-founder of the firm, in a phone interview.
The drug developed by Biond, however, is special in that it “activates three different kinds of immune cells at the same time — macrophages, T-cells and natural killer (NK) cells,” which have been shown to play a key role in fighting cancer.
“Because the drug activates three different pathways, we hope it will give a strong and sustained anti-tumor response and show significant benefit,” she said.
The drug is a biological antibody that binds specifically to a receptor, called ILT2, that is present on the immune cells. When cancer cells are present, ILT2 binds with a protein that is expressed by the cancer cells. This binding generates inhibitory signals inside three different immune cells, which decreases their anti-cancer activity, thus making the immune reaction to the cancer weaker.
When the antibody developed by Biond binds with the ILT2, it doesn’t allow ILT2 to bind with the cancer cells.
By binding to ILT2, this antibody “does not allow the tumor cells to generate inhibitory signals — it is an antibody that blocks inhibitory signals,” said Ben-Moshe. “So now, without this inhibition, these immune cells can do what they need to do. They become much more activated and can generate anti-tumor activity.”
Unlike many other drugs, BND-22 was not discovered and developed in a university lab but rather by the team of entrepreneurs and scientists at Biond, who set up the company in 2016 with the purpose of making inroads in the growing and promising field of immuno-oncology. Immuno-oncology is the study and development of treatments that leverage the body’s own immune system to fight cancer.
Biond is led by Ben-Moshe, a former CEO of cCAM Biotherapeutics, which was acquired by German drugmaker Merck in 2015. Biond’s other co-founder, chief financial officer Ori Shilo, is also the founder of the publicly traded biopharmaceutical firm RedHill Biopharma. He has over 15 years of experience in investment banking in the pharma industry.
Biond’s advisers include players in the immuno-oncology field including Alan Korman, former VP of Immuno-Oncology Discovery at Bristol-Myers Squibb, and Dr. Jeff Weber, deputy director of Perlmutter Cancer Center, NYU Langone Medical Center.
“When we began, we had many ideas and we knew that this is the field that we wanted to work on, but we didn’t know that ILT2 would be our lead program,” said Ben-Moshe. After detailed studies of scientific literature, the scientists realized that the ILT2 was a “central and important pathway,” and focused their work in that direction. “Everything was done in-house.”
The firm hasn’t published research in peer-reviewed journals, she said. But before acquiring the license to the drug, Sanofi officials spent over six months carefully reviewing all of the work done. “The partnership validates our science and the way we are working,” she said.
The two firms will now continue to develop the drug together by performing the clinical trials.
Since the announcement of the deal last week, the firm has received Investigational New Drug (IND) approval by the US Food and Drug Administration and can now proceed with clinical trials, which the firm expects will start by mid-2021 in the US and Israel.
The initial focus will be on solid tumors, said Itay Friedman, VP of clinical development at the firm, in which the ILT2 receptor may play an important role in the progression of the disease.
Ben-Moshe is cautious with her hopes for the drug. In pre-clinical experiments the company found that the drug has a “very strong anti-tumor activity.” But only testing on humans will really prove that, she said. “We cannot know until we do the experiments and we won’t have the data for 2-3 years at least.”
Besides the BND-22 drug, Biond is working in parallel on other developments. These include BND35, which prevents the suppression of lymphocytes by other immune cells and improves their immune activity against cancers.
The firm has also found what it says is a new regulatory mechanism in lymphocytes, called CD28 shedding, that if dysregulated, makes the cancer-fighting lymphocytes inactive, so they do not attack the tumor cells.
“We were the first that described this CD28 regulatory mechanism, and what we are trying to do is design a drug that will restore the right function of this CD28 molecule. By restoring this function, lymphocytes are once again active and can attack the tumor sites,” said Ben-Moshe.
In addition, the firm is trying to find a way to enable antibodies — which are big proteins — to penetrate cancer cells and bind targets within cells, rather than only by attaching themselves to the outside of these cells as all immuno-therapy drugs developed to date do.