Immunotherapy for cancer is one of the hottest fields of research among the biotech companies of the Route 1 corridor. Simply put, it is the science of using the body’s immune system to fight cancer. For example, Opvido and Yerevoy, brought to market by Bristol-Myers Squibb, and Keytruda, made by Merck, are among the most commonly used immunotherapy drugs for several kinds of cancer.
These relatively new drugs, all of which have been approved by the FDA in the last decade, are typically used for people for whom conventional radiation and chemotherapy have not been effective. About one in three cancer patients respond very well to these drugs, part of a class known as checkpoint inhibitors. They work by blocking a signaling pathway that normally puts the brakes on the immune response, effectively giving the green light for the immune system to attack the cancerous cells.
In approximately 30 percent of patients, these drugs are often able to destroy all traces of cancerous tumors. In the biotech industry, their tumors, the ones that are receptive to immunotherapy treatment, are called “hot.” But in the remaining 70 percent, the tumors are deemed “immunologically cold” and the therapy seems completely ineffective. One question for cancer researchers is, why doesn’t immunotherapy work for everyone? And for those who don’t respond, is there a way to change that?
OncoSec, a company that has recently set up its headquarters in central New Jersey, is currently working on one possible answer to that question.
On the second floor of 24 N. Main St. in Pennington, a more than a century-old building that was once the fire house and later the Borough Hall, Daniel J. O’Connor, CEO of OncoSec, pulls up two photos on his computer. The first is a person’s ankle, ridden with melanoma tumors. Foothills of red, angry growths rise up around the ankle bone, signs of a life threatening disease taking hold. In the second, taken several months later, the growths are just about gone.
The photos are a dramatic illustration of what O’Connor believes is a new frontier in immunotherapy: turning those cold tumors hot.
OncoSec’s technology is based on the work of Adil Daud, an oncologist and melanoma specialist at the University of California San Francisco and scientific founder of the company. Daud developed a multi-step process to make cancerous tumors good targets for immunotherapy drugs.
Daud’s work focused on using a molecule called IL-12, a pro-inflammatory signaling cytokine, which encourages the immune system to attack. If cancer cells could be induced to produce IL-12, tumors throughout the body could theoretically become “hot” to immunotherapy drugs such as Keytruda.
To get the cells to produce IL-12, Daud decided to use plasmids, which are snippets of DNA that can be introduced into cells to change how they function. But simply injecting plasmids into a tumor would not be enough, since the plasmids would normally remain outside the walls of the cancer cells. The treatment, trademarked Immunopulse, begins with injecting trillions of copies of plasmids into a tumor. But to make those cells permeable, OncoSec follows up the injection with a probe that creates a series of short electrical pulses, which weaken the cell membranes enough to allow the plasmids to enter. After that, IL-12 is produced by the cell, the immune system recognizes the area as a target, and as an added effect “learns” to attack other cancerous cells throughout the body.
OncoSec in partnership with Merck is currently running a clinical trial of about 48 melanoma patients who are being treated with the Immunopulse system in combination with Keytruda. If this trial shows good results, the treatment will be well on its way to approval, since the FDA has granted it the “fast-track” status for orphan drugs.
If successful, one of the appealing aspects of the treatment is its cost. Plasmids are relatively inexpensive to make in a lab, and the second part, the electrical pulse probe and the machine to which it is attached, is small enough to keep on a desktop and would cost $10 to $20,000 to a doctor.
“I think the day of the cytokine has now arrived,” O’Connor says. “It was theorized a decade ago by Doctor Daud. He was a bit of a visionary, because what has happened in the intervening years is that the checkpoints have been the first wave of successful immunotherapies. The only limitation is that they typically work in a minority of patients that receive them.”
O’Connor, a Pennington resident, is no stranger to the Central New Jersey biotech sector. From 2013 through 2017, O’Connor was CEO at Advaxis, a College Road East-based company that used genetically modified bacteria to precisely target cancer cells.
A native of Westfield, O’Connor is the son of an antique store owner father and homemaker mother. He graduated from Boston University with an English degree and joined the Marines after graduation, serving in the Gulf War in 1990 as a captain. Following his military service, O’Connor went to law school at Dickinson and became a criminal prosecutor. His next career change took him to ImClone, where he was general counsel. ImClone, which was an early pioneer in a targeted cancer therapy research, a field related to immunotherapy.
O’Connor says he has been fascinated with immunotherapy since learning about it at ImClone. “It started out as an intuition or belief that immunotherapy was going to be the future of cancer research and cancer therapy,” he says.
“What, in the last five years, has really motivated me, is seeing it firsthand in clinical trials and personal experience. Seeing the side effects of chemotherapy has really put a very fine point on the need for immunotherapies. The entire premise is trying to avoid toxic therapies if we can. Everybody knows that chemotherapy and radiation therapy and surgery have saved so many people’s lives and are very effective medicines, but they come with a pretty heavy price.
“I wanted to be associated with what I perceived to be the future of cancer research, and having personally seen the effects of chemotherapy renewed my motivation to really push therapies which work and which use the body’s immune system which don’t carry the same side effects.”
(When O’Connor speaks of “personal experience,” he is referring to a colleague at ImClone whom he later brought over to Advaxis, as well as another colleague from a job he had in the insurance industry.)
O’Connor also has personal experience with the electro pulse probe, having tried it on himself. “Pain is subjective, but I wouldn’t describe it as painful,” he says, accompanied by slight twitching of the local muscles.
OncoSec is a public company listed on NASDAQ. According to its SEC filings, OncoSec was founded in Nevada in 2008 as “Netventory Solutions,” and was in the business of providing online inventory services to small and medium sized companies. In 2011 the company acquired the electric pulse technology from another biotech company, Inovio, for $3 million, and changed its name to OncoSec and moved to San Diego. At the time, the company shared a board chair, Atvar Dhillon, with Inovio.
Melanoma is the first target of the Immunopulse system, since it is on the surface of the skin and is easy to reach with the electrical probe.
OncoSec got its start in San Diego and still has its research lab there. However, it opened an office in Pennington this year, when O’Connor came on board. Currently the office has about four people working there, but this number is likely to increase to about 10 by the end of the summer, O’Connor says.
Clinical trial management, finance, human resources, administration, and other office functions are all taking place in New Jersey or will be in the future. “New Jersey is the medicine chest of the world and has a rich ecosystem for drug development,” O’Connor says, explaining the move across the country.
In addition to the available pool of employees, the state’s economic development department offers a program that allows pre-revenue companies such as OncoSec to sell their tax loss credits to other businesses — trading their tax credits for instant cash. The program requires OncoSec to have 10 employees, which is another reason for staffing up. “Getting cash today is tremendously helpful,” O’Connor says.
O’Connor was also able to get a bargain on real estate, opting to move into a building that had been on the market for a long time. Downtown Pennington also offers a community feel, and several restaurants within walking distance. (Emily’s and Vito’s are early favorites for OncoSec’s small workforce.)
O’Connor says that saving money on rent is crucial for a company at his stage. While he could have gotten a fancier office than the Main Street building (built in 1891) somewhere else, he prefers to spend every dime possible on getting the clinical trial data that will allow OncoSec to move forward with Immunopulse. “We want to make sure we use our dollars wisely,” he says.
The lab is staying in San Diego because “moving a lab is no small undertaking,” O’Connor says.
OncoSec expects to get results from the study soon and present its preliminary results at a medical conference later this year. An earlier trial showed promising results among a small group, 11 out of 23 subjects showed their tumors either shrinking significantly or going away entirely.
The company is also recruiting subjects for a trial of its IL-12 therapy technology in patients of “triple negative” breast cancer (a kind of cancer that does not respond to several other forms of therapy.) They are also recruiting for a second triple negative breast cancer trial which will use IL-12 in combination with Keytruda.
Immunopulse could be on the market for melanoma as early as 2020 if all goes well, and O’Connor says this could help literally thousands of patients. In addition to melanoma, OncoSec is working on treating breast cancer and lymphomas, both of which are in reach of the existing technology. OncoSec is also working on another type of probe to reach cancers that are deeper in the body, and is interested in other kinds of cancer that do not always respond to immunotherapy, such as renal cell cancer, lung cancer, head and neck cancer, and bladder cancer.
A version of this story first appeared in the U.S. 1 Newspaper.