Israeli startup BiomX, which is developing a treatment that selectively kills specific bacteria, last week completed a $24 million financing round. The company was founded in 2015 on the basis of research by two Weizmann Institute scientists: Dr. Eran Elinav, a specialist in microbiome – the mix of bacteria in the human body (he is also known from DayTwo, which developed an app for nutritional consultation according to a person's individual composition of bacteria), and Professor Rotem Sorek, an expert in genetic engineering and bacterial genetics. The third founder is MIT Professor Timothy K. Lu, who specializes in genetic engineering of anti-bacterial viruses.
The round was BiomX's first since being founded in the FutuRx incubator in Rehovot, managed by Einat Zysman. All three of the incubator's franchise holders - the OrbiMed Israel Partners venture capital fund; Johnson & Johnson Innovation (JJDC), pharmaceutical and medical devices company Johnson & Johnson's venture capital arm; and Takeda Ventures, the venture capital fund of Takeda Pharmaceutical Company - invested in BiomX. The new investors in the company were the Seventure fund, which specializes in microbiome investments, the Mirae fund, and Japanese fund SBI, represented in Israel by Dr. David Ben-Ami.
BiomX is developing drugs based on phages – special viruses aimed against specific bacteria, in contrast to conventional antibiotics, which kill all bacteria, including good bacteria, and which make other bad bacteria, which they are not aimed at, resistant to them.
In principle, the company's products can replace antibiotics, with their general effect on bacteria, with a more selective treatment for any condition currently treated through antibiotics. In the future, they could also be suitable for other diseases in which manipulation of the body's bacterial population is likely to change the course of the disease. Medical research has been discovering more and more such conditions in recent years.
The company's first products are designed for treatment of acne and H. pylori bacteria. In the future, BiomX plans to develop products for treatment of inflammatory intestinal diseases (colitis and Crohn's Disease), and for prevention and treatment of cancer.
Microbiome is one of the current hot spots in medicine. Our bodies appear to contain the same quantity of bacteria as human cells, and the body's bacteria probably weigh about as much as the brain. The genetic diversity of the body's bacteria is much greater than that of its cells, and the variance between two people in the composition of their bacteria is greater than the genetic variance between their body cells.
Bacterial composition is currently believed to affect the development of many diseases, especially intestinal diseases, but also obesity and diabetes, skin diseases, neurological diseases, and even cancer. The use of antibiotics kills many bacteria, and has a harsh and inadequately understood effect on the body's bacteria.
Proof of viability
Proof that treatment by changing bacterial composition instead of using indiscriminate antibiotics can be effective has been obtained from the success of treatment by implanting feces from a healthy person in a sick one. This treatment completely eliminated deadly bacteria called C. diff, even in cases in which no antibiotic was effective. Antibiotics killed a considerable proportion of the population of sick bacteria, but also of the healthy bacteria. When the bacteria once again multiplied, it was easier for the disease bacteria to multiply within the intestine, because there was less competition from other bacteria. When healthy feces were implanted, however, the good bacteria multiplied, blocking the intestine and preventing the C. diff bacterial population from returning and taking up space, even if a few of them survived.
With all due respect to feces, the future of microbiome probably lies in orally administered drugs that will more precisely change the intestinal bacterial composition by adding or subtracting specific bacteria. That is where BiomX comes into the picture.
BiomX executive VP strategy and business development Assaf Oron says, "BiomX has developed a platform with two elements. One is the ability to detect with precision what bacteria are missing, and which existing bacteria are causing damage. The second is the ability to selectively attack unnecessary bacteria." "Current estimates are that there are 100 trillion bacteria in the intestine," Oron says. "How do we know which bacteria affect a disease?" Comparison of the composition of bacteria in a patient with that of a healthy person is not enough, because of the large number of bacteria. Using Sorek's technology, the company has developed a system that makes it possible to detect which bacteria are having an effect (i.e. are RNA-coding) in a patient or during an attack of the disease.
The next stage is to eliminate the undesirable bacteria. Oron says that this can be done with phages - viruses that selectively attack specific bacteria. For bacteria that cause acne, for example, there is a phage that attacks them individually. Today, adolescents suffering from acne use antibiotics daily, or several times a day, for an average of six months. The potential damage to the population of good bacteria is significant. Treatment with the phage, on the other hand, harms only the undesirable bacteria. Oron notes that phages have other advantages over antibiotics. When they find the one type of bacteria they want to attack, they use it to multiply, and become even more specifically effective in the place where those bacteria are located. They are also expert in demolishing the bacterial colonies and penetrating them.
Q: You let the virus multiply within the body without any limitation?
Oron: "There's nothing to fear from these phages, because they are found in our bodies naturally. All I do is temporarily strengthen them against the bacteria. In the long term, when the acne bacteria are eliminated, the phage can no longer multiply, and the balance in its proportion in the body is restored." Israeli company Foamix Pharmaceuticals Ltd.(Nasdaq:FOMX) is currently conducting trials aimed at showing that acne can be treated using antibiotic that can be smeared on the face. Oron says, "The acne bacteria are found on a follicle, so it will be difficult for an antibiotic smeared on the skin to reach all of them. The phage, on the other hand, is administered through the bloodstream, and reaches the follicle." What happens when there is no natural phage for a certain disease in the body? Another disease caused by a single known type of bacteria is H. pylori, which causes ulcers and intestinal cancer. 20% of H. pylori cases do not respond to the existing antibiotics. This is where Professor K. Lu enters the picture by engineering new phages. Oron explains, "We're now on the way to engineering a special phage against H. pylori." Do any phage-based drugs exist?
Oron: "There are no drugs. There is a product used in food, for example in meat, to destroy specific bacteria in meat without deluging all of us and the environment in antibiotics. Anyone who eats this meat is in effect eating a phage-based drug, which has been approved for marketing by the US Food and Drug Administration (FDA) food division. There is another microbiome company working on a phage for treating sinusitis." The acne product is the most simple and accessible application of BiomX's system; it does not utilize all of its potential capabilities. The H. pylori product is slightly more complex, because it requires designing a new phage, but it still does not require Sorek's system, which analyzes which bacteria directly affect the disease.Treatment of the intestine
The company will apply these three aspects to the treatment of inflammatory intestinal diseases (Crohn's Disease and colitis) by finding the ideal intestinal composition for the intestine for preventing and treating these diseases, and by compounding a cocktail of probiotics (adding the bacteria that are missing in the composition) and phages (in order to eliminate the harmful bacteria in the composition) for treatment of the disease.
An even more ambitious goal is immuno-oncological treatment. "The promising new drugs, such as Keytruda, completely change the course of cancer in certain people, but are not so effective for others. One hypothesis is that the difference in the response depends on the person's intestinal bacterial composition. We're now engaged in an initial project to map the differences between those who respond and those who do not, so that it will be possible in the future to change the bacterial composition before administering the drug, thereby improving its effectiveness," Oron says.
"We want to devise projects at various levels of aspiration and complexity, so that as the segment develops, we will ready ahead of time with solutions," Oron declares. The company will enter clinical trials for its first products in one or two years, while products like the treatment for inflammatory intestinal diseases and the process of adjusting a cancer patient's body for treatment with an immuno-oncological drug could take many years.
Oron adds, "The pharma companies are sitting on the fence where microbiome is concerned. Almost no company has these capabilities in its R&D department, while on the other hand, almost all of them have expressed interest. They will therefore have to acquire technologies from outside. A number of projects have been purchased in the early development stages." BiomX's CEO is Jonathan Solomon, who previously managed a company that developed a drug for Alzheimer's Disease.