Patrick Soon-shiong of ImmunityBio discusses the quest to orchestrate NK and T cells. biospace

patrick soon-shiong_immunitybio

Dr. Patrick Soon-shiong, MD / Courtesy of Immunity Bio

Three decades after first writing about how Natural Killer Cells (NK) worked, Dr. Patrick Soon-shiong, MD, and his company, ImmunityBio, Inc. they’re in the final stages of what to expect U.S. Food and Drug Administration Approval of their drug N-803 (Anktiva) for the treatment of bladder cancer.

In the late 1980s, Soon-Sheong was a professor and surgeon at the UCLA School of Medicine, specializing in pancreatic cancer and organ transplantation. But he had a dilemma dealing with the body’s immune system that both hindered and helped what he was trying to accomplish. NK cells were responsible for causing organ rejection while the same cells killed cancer in the pancreas.

Continuing the earlier efforts of Dr. Anthony M. Sun, MD, of Connaught Laboratories in Toronto, who had been experimenting with rats to reverse diabetes, Soon-Shiong applied flax to gel-formed islets derived from seaweed. Enhanced encapsulation method. They designed a purified formula that improved how the islets pass insulin, glucagon, oxygen, and hormones, while blocking antibodies and T cells in the immune system that would otherwise destroy the islets.

“I’ve been following this for my whole career, trying to figure out how to organize NK cells and T cells,” Soon-shiong told biospace,

Soon-Shiong then performed the world’s first encapsulated human islet transplant, the first engineered islet cell transplant, and the first pig-to-man islet cell transplant in a diabetic patient.

In addition to trying to organize the rooms, Soon-shiong was also choreographing business deals to further his research. His business acumen generated revenue that led to his most successful medical achievement to date, Abraxane (paclitaxel), which is helping to finance his future endeavors, including Enactiva. But it was not without family turmoil.

In 1991, along with his brother, Soon-shiong co-founded VivoRX, which was followed by a second startup called VivoRX Pharmaceuticals. a legal battle Between the brothers forced Soon-cheon to drop out of VivoRX. He left VivoRx Pharmaceuticals and changed its name to American Bioscience. Soon-Shiong also founded a second company called American Pharmaceutical Partners and acquired two money-losing factories for it. He was soon able to turn those businesses into money-makers.

Soon-shiong used the proceeds for research and development to improve the generic chemotherapy drug paclitaxel. They called their reworked version of paclitaxel abraxane, and it performed better in clinical trials and was less likely to cause an allergic reaction.

Abraxane is an albumin-bound form of paclitaxel, now indicated for the treatment of breast cancer, non-small cell lung cancer, pancreatic cancer, ovarian cancer, cancer of the fallopian tubes and primary peritoneal cancer.

In 2005, the FDA approved Abraxane and US pharmaceutical stocks rose 47%.

Shortly after the FDA’s decision, Soon-cheon announced that it would combine its publicly traded American pharmaceutical with privately held American Bioscience, of which it owned 80%. To do so, American Pharmaceutical will issue 86 million new shares to American Bioscience. Wheeling and Dealing added nearly $2.5 billion to Soon-Shiong’s assets, while smaller investors questioned the ethics of the transaction.

Fifteen months after the companies merged, Soon-shiong split them into two new businesses, APP Pharmaceuticals and Abraxis, which owned the rights to Abraxane.

In 2008 and 2010, Soon-shiong sold two of his companies for a total of $9.1 billion. The poor kid in South Africa had the American dream.

In addition to his work in the life sciences industry, the liberal Soon-shiong has used his wealth for some of his other interests. A self-proclaimed news junkie, he bought Los Angeles Times And San Diego Union-Tribune, As a big fan of basketball, he bought a minority position in the Los Angeles Lakers by taking an ownership stake in team legend Ervin “Magic” Johnson and received courtside seats for their games.

But medical science is Soon-shiong’s primary focus, which brings us to the here and now.

Soon-shiong’s clinical-stage immunotherapy company, ImmunityBio, which he founded in 2014, had already received breakthrough therapy and fast track designations from the FDA for N-803 when the company submitted a biologics license application in May. did.

N-803 is a first-in-class IL-15 superagonist, as well as Bacillus Calmette-Guérin (BCG) intended for the treatment of BCG-responsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without Ta is for. or T1 disease.

If N-803 is approved, it would be the first FDA-approved immunotherapy since BCG in 1990 that can be delivered directly to the bladder to induce natural killer cells and T cells. It will also be the first FDA-approved product from the Culver City, California company.

“This is one of the first opportunities to show that N-803 actually activates and enhances NK cells and T cells and drives memory T cells for your innate immune system to treat cancer and infectious diseases, Soon-shiong, who turns 70 in July, said.

What are the challenges in developing the N-803?

“It’s a biology,” Soon-shiong said. “It’s really a paradigm shift in the sense that we want to preserve your immune system. So, the challenge is, how do we break the 40-year current standard of care, where we’re going to have high-dose chemotherapy and high-dose chemotherapy.” radiation, which reverses your NK cells and T cells. So, we need to find ways to address this and in 2017, I am happy to say that oncology center of excellence Under (Director) Dr. (Richard) Pajdur gave us the opportunity to launch it under the Quilt Trial Programme.

N-803 aims to reduce the chances that a patient will need surgery and its tremendous cost.

“Patients who are unresponsive to BCG have to undergo a surgical procedure called radical cystectomy,” Soon-shiong said. “Unfortunately, this is fraught with 9% mortality, 60% morbidity, high costs, terrible quality of life, bladder loss in elderly patients, nephritis infections, hospital visits, and it is one of the most expensive procedures in health care for cancer. So, there was a great need to avoid radical cystectomy and we followed [FDA] Guidance in test design. ,

The BLA submission for BCG-unresponsive NMIBC is based on data from 171 subjects from Phase I and II trials in bladder cancer and 84 subjects treated in the ImmunityBio pivotal Phase II/III trials. Quilt 3032 Study of the combination of N-803 and BCG. According to the study data there was a 71% complete remission rate. Patients who had failed previous treatments saw a more than 50% increase in both response and median duration compared to FDA-approved options, Endo’s Valstar (valrubicin) and Merck’s Keytruda (pembrolizumab), a systemic checkpoint for this indication. inhibitory therapy.

“You can see a significant reduction of cystectomy with a median duration of response of 26.6 months and a very tolerable profile. [It] validates this hypothesis using natural killer cells and T cells. You can have durable memory,” Soon-Shiong said.

information Presented The Quilt 3032 study by the company at the annual meeting of the American Society of Oncology also showed that there was 96% avoidance of bladder cancer progression at 24 months, that patients had a 91% survival rate for cystectomy and 100% for this. There was total existence. Bladder cancer in respondents.

Additionally, n-803 showed promising in the treatment of pancreatic cancer.

one in Phase II Quilt 88 Clinical Trials, patients with advanced pancreatic cancer treated with the Nant cancer vaccine, N-803, and off-the-shelf PDL1-targeted high-affinity NK cell infusions showed median overall survival rates compared to historical survival data showed more than twice as much. The median survival for patients with third- to sixth-line pancreatic cancer was 6.2 months.

Soon-Shiong holds over 200 patents and ImmunityBio is currently working on 27 clinical trials. To keep the research going, Soon-shiong is spending his own money to support those projects.

“I personally have made a significant investment and I will continue to do so. We need it, but I am confident that the data and results will generate the appropriate resources we need, given what we are doing,” Soon-Shiong said.

Wall Street is the one group that needs convincing that ImmunityBio is on the right track. The company’s stock has declined nearly 90 per cent in the last 14 months. But Soon-xiong has nothing to do with it.

“Wall Street follows rather than leads and we need to lead,” he said. “We care about shareholders, but what we have to do is generate biological value. Abraxane was proof of that when we were developing a vaccine and it was made public in 2001.

“If you go back and look at the history of American Pharmaceutical Partners, it follows exactly the same strategy where the stock drops to single digits and nobody believes this drug will be approved and it’s no longer a drug.” Billion dollars is on sale. So, I think you just have to have complete faith in the science that we do, and the validity of each application.”

Soon-shiong’s work on the N-803 could have additional benefits, such as fighting COVID-19. In 2020, he was selected by the federal government to participate in “Operation Warp Speed,” which was set up to accelerate the development of vaccines.

“I have said since 2020 when COVID broke that unless we make a vaccine that is not only antibody-based but T cell and NK cell-based, we will never stop transmission. More importantly, an antibody-based vaccine would actually enhance the mutational evolution of this virus and create what we now see in front of us today,” Soon-shiong said.

If Enactiva is approved by the FDA, what will it mean for Soon-shiong personally?

“It would be the first recognition, all the way to the FDA if it was approved, that in fact, you don’t need chemotherapy,” he said. “If you can take a patient’s own immune system and activate it, you can achieve complete remission.”

A final decision by the FDA on N-803 is expected in 2023.


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