An Israeli company has launched a clinical trial to determine if its innovative microbiome-based therapeutic could increase the responsiveness of some cancer patients to immunotherapy.
The microbiome is gut bacteria – trillions of microorganisms that live in the intestinal tract and play a role in digestion, immunity and many other aspects of health.
Rehovot-based Biomica, a subsidiary of Evogene, dosed its first patients in a Phase I clinical trial at Rambam Health Care Campus last month with a new drug – BMC128 – that is expected to help patients who do not respond to immunotherapy. Specifically, the company hopes the trial will demonstrate the safety, tolerability and preliminary clinical effectiveness of its BMC128 microbiome-based immuno-oncology drug candidate in combination with immune checkpoint inhibitor (ICI) immunotherapy.
BMC128 includes a “rationally designed consortium of microbes” – four unique bacterial strains – selected based on its parent company’s “MicroBoost AI” tech engine and big-data platform. The microbes are designed to restore diversity and specific functionality to the patients’ microbial community, thus improving their responsiveness to immunotherapy.
“The concept of the drug is like probiotics but is based on a limited and precise number of bacteria, which is both more effective and safer,” said Biomica CEO Dr. Elran Haber.
“ICIs are a revolutionary treatment and have demonstrated their efficacy in prolonged survival rates of cancer patients,” he continued. “However, many patients are resistant to ICI, and it has been shown that the gut microbiome plays an important role in this resistance. Based on the compelling pre-clinical results that Biomica has achieved to-date, we are excited to evaluate BMC128 in a clinical setting for the first time.”
BMC128 is administered in a pill, Haber said. The patients are given the drug on a daily basis alongside their immunotherapy treatments, which tend to take place once every four weeks.
The trial is expected to include around a dozen patients suffering from non-small cell lung cancer, melanoma or renal cell carcinoma. Because the trial is open label, the company expects preliminary results in 2023 and the full study to be reported on by the second half of next year.
The trial kicked off following successful preclinical experiments in mice. Those experiments showed when BMC128 was administered in combination with immunotherapy, it resulted in a reduction in tumor volume and improved the survival of animals, compared to treatment with immunotherapy alone.
Treatment with the drug also increased activation of specific populations of cells in the immune system that are known to be involved in the destruction of cancerous tumors.
“In the past, most cancer patients were treated with chemotherapy, which is not very efficient and the side effects are known to be very aggressive,” Haber explained. “When immunotherapy was introduced, it was a revolution for cancer patients. Yet, many cancer patients do not respond to this therapy. The question is why. The answer is that there are significant reasons to believe that a person’s microbiome has an impact on their response to immunotherapy.”
The intersection of AI and biology
In addition to focusing on cancer, the company is also evaluating the use of microbiome treatments for gastrointestinal diseases, such as inflammatory bowel disease, irritable bowel syndrome and infectious diseases.
What makes Biomica unique is the convergence of computational science and AI with biology.
Haber compared the way that Biomica identifies microbes to understanding the staff in a coffee shop. Biomica knows that not only do Haim, Yossi and Adi work in a coffee shop, but which role each person plays: shift manager, waiter or bartender. But it also knows that if Haim is not present, then Yossi can fill in.
“With microbiome, this is just the tip of the iceberg, I believe there is a lot more to come.”
Dr. Roger Pomerantz
“Each bacterium in the microbiome has a different role depending on the total mix of the bacteria in which it is found, and a specific function,” Haber said. “Based on our computational technology, we can identify the specific bacteria and what they do.”
Evogene was one of the first Israeli computational biology companies to be traded on Nasdaq. Today, it is considered to be leading a revolution in the process of discovering and developing products for industries based on life sciences, not only in the realm of human health, but also agriculture.
Haber said the “miracle of microbiome drugs” is that no genetic modification is being done because they are all already found in the human body. This has made the treatments “extremely safe so far; reports on any adverse effects or serious adverse effects were almost none.”
He added that in a next stage, Biomica hopes to be able to predict if patients will respond to immunotherapy and then be able to start their treatment with BMC128 and immunotherapy to improve outcomes.
Getting BMC128 on the market – if the Phase I and later Phase II and Phase III trials are successful – should take between five and 10 more years, Haber noted.
'More to come'
Today, there is no microbiome drug that has been approved by the US Food and Drug Administration, however, there is one that has filed for approval from American-based Seres Therapeutics.
That drug is expected to achieve FDA approval by mid-2023, which would pave the way for companies like Biomica. Haber said there are several other microbiome drug companies that are now undergoing Phase II and Phase III trials, and he expects that in the future others will be approved, too.
Dr. Roger Pomerantz, who led the development of 12 approved small and large molecule drugs, served as the senior clinical advisor for Seres.
He explained that babies who are delivered vaginally receive their microbiome through their mother, but scientists did not really understand the significance of the microbiome until around 15 years ago. Now, they see it as another organ.
The microbiome plays a key role in bodily functions, he said.
“If you were to sterilize a person’s microbiome and keep it sterile, you don’t get sick, you get dead. You have to have your microbiome just like any other organ.”
Over time, scientists have shown the effects of the microbiome on tumors, autoimmune and gastrointestinal diseases and even some neurological disorders. Companies like Seres formed with the aim of developing an entirely new class of potential medicines around microbiomes.
“The big question is what else can we do with this organ,” Pomerantz said. “With microbiome, this is just the tip of the iceberg. I believe there is a lot more to come.”