Company: Iovance Biotherapeutics
Title: President and Chief Executive Officer
When the Dutch biotech company Acerta Pharma was bought by AstraZeneca in 2016, a board member asked Acerta’s chief operating officer, Maria Fardis, Ph.D., to consider moving to the CEO spot at a tiny California company with a huge opportunity in immuno-oncology—but not much of a plan for seeing it through to commercialization. Fardis was intrigued. The company’s technology, a personalized treatment called tumor infiltrating lymphocytes (TILs), had been developed by cell-therapy pioneer Steven Rosenberg at the National Cancer Institute, and it looked promising for treating melanoma.
When Fardis accepted the job at Iovance (then called Lion Biotechnologies) in June 2016, she brought a deep resume in oncology, having worked on the development of the BTK inhibitors Calquence at Acerta and Ibrutinib at Pharmacyclics, both of which are used to treat blood cancers. Cell therapies like the CAR-T treatments from Kite Pharma and Novartis were starting to show promise in lymphoma and leukemia at about that time, but Fardis saw an opening that she believed Iovance could fill.
“Cell therapy was a wonderful way of using the patient’s immune system to address what really is ultimately an immune-mediated problem—cancer,” Fardis told FiercePharma. “But the other cell therapies were only options for the treatment of hematologic malignancies. I thought we needed to focus more on solid tumors.”
So Fardis came up with a regulatory and commercialization plan for Iovance, and over the next two years boosted the company’s employee base from 20 to 90 to see it through. Now Iovance is fresh off a sit-down at the FDA that resulted in a path forward for its lead TIL, lifileucel, which is in a phase 2 trial for treating metastatic melanoma. Investors have been so optimistic about Fardis’ plan that Iovance’s share price has jumped as high as $19 since she joined.
Iovance’s TILs are derived from T lymphocytes, which are immune cells that have an innate tendency to penetrate tumors and kill cancer cells. Problem is, there aren’t enough of these naturally occurring T lymphocytes to overcome cancer, so Iovance perfected a method of removing the cells from patients, growing them into numbers reaching the billions, and then infusing them back into the body.
In one trial at the NCI of 101 patients, 24% had complete responses, some of which lasted for over four years. The overall response rate in a second small trial was 56%.
“It was clear to me that this works in melanoma,” Fardis said. “What was unclear to me was how to take the product to the patient.”
Indeed, manufacturing personalized cell therapies is a complicated endeavor, and Fardis knew when she started the job that she would need to improve Iovance’s technique for making TILs. The time between the harvesting of TILs and the reinfusion back to patients was somewhere between 5 and 6 weeks, she recalled—too cumbersome to scale the process up for widespread commercialization. So the company invested in its manufacturing infrastructure, getting the process down to 22 days and establishing a technique for freezing the cells so they would be easier to handle. As of December 2017, all clinical trial patients were transitioned to what the company calls its “Gen 2” manufacturing process.
Even though it was clear to Fardis that TILs could work in many tumor types, she wanted Iovance to pour all of its resources into gaining the melanoma approval. But she also wanted to see the science move forward on the other indications, so she started looking for research partners. The company has partnerships with the H. Lee Moffitt Cancer Center and Research Institute and AstraZeneca unit MedImmune. In April 2017, it inked a multiyear partnership with the University of Texas MD Anderson Cancer Center to study TILs in ovarian cancer, sarcomas and pancreatic cancer. Iovance is also investigating the potential of TILs in lung cancer and head and neck cancer.
“Because metastatic melanoma has the highest likelihood of success, we have stay laser-focused on that,” Fardis said. “I can’t use a lot of company resources to explore TIL in every indication, so that’s where we go into collaborations. If something works, we will then decide if the market size is justifiable for us to pick that program up and develop it internally.”
Fardis’ early training prepared her well for the demands of balancing scientific promise with shareholder concerns. She received her Ph.D. in organic chemistry from the University of California, Berkeley, and an MBA from Golden Gate University. She spent much of her early career at Gilead, where she worked not only in oncology, but also in antivirals and cardiovascular drug development.
Fardis is well aware that investors’ high expectations for Iovance stem largely from the 2017 approvals of the first two CAR-T engineered cancer treatments, Novartis’ Kymriah and Gilead’s Yescarta (originally developed by Kite). But while she’s grateful those two products paved a path through the FDA for cell-based treatments, she knows that doesn’t guarantee a smooth regulatory process for lifileucel.
On Oct. 11, Iovance announced that it reached an agreement with the FDA to extend its phase 2 study of lifileucel, with the goal of using the data from the study to support a filing for approval in the second half of 2020. The FDA also granted the company an Regenerative Medicine Advanced Therapy (RMAT) designation, which could allow it to use surrogate endpoints in the trial and to gain accelerated approval. And Fardis is pleased that her vision for commercialization is starting to materialize. “The question is the same for any development program: How are we going to bring this product to patients? The ‘how’ defines the direction, and two years ago I was still thinking, ‘How will we do this?’” Fardis said. “Now I’m envisioning what the infusion bag might look like. I feel we are ready for our next stage of development.”