Three decades in the pharmaceutical industry will help put things in perspective.
It is one advantage Tim Moore, head of technical operations at Kite Pharma, can bring after joining the cancer immunotherapy biotech this spring following 12 years at Genentech.
And it is the kind of perspective that helps Moore see parallels between the current development of cell therapy and the emergence of monoclonal antibodies in oncology twenty years ago.
“Cell therapy is very unique,” Moore said. “The attitude towards cell therapy reminds me of the attitude towards monoclonal antibodies in the 1990’s. There was a lot of skepticism, but they are now widely used in different therapeutic areas, including oncology.”
Kite Pharma, which specializes in engineered autologous cell therapies, is currently focusing on advancing treatments for aggressive blood cancers. The company is also involved in solid-tumor research through a partnership with the National Cancer Institute (NCI).
Moore is optimistic Kite’s development work will keep the biotech at the forefront of cancer immunotherapy. But Kite faces stiff competition from other biotechs like Juno Therapeutics and Bluebird Bio, as well as from big pharma companies like Novartis.
When the present looks like the past
T-cell cancer therapies have shown tremendous promise, demonstrating high response and remission rates in early clinical trials. But they are also highly individualized, involving the extraction of T-cells from a patient, followed by genetic engineering to render those cells more effective at attacking cancer. The T-cells are then reintroduced into the patient’s body.
Moore concedes there are skeptics who doubt whether T-cell therapies can work in large populations of patients. But he remains confident they will eventually change the standard of care in oncology, much like the introduction of monoclonal antibodies did before.
Throughout the 1990’s, researchers worked on developing monoclonal antibodies to make them clinically and commercially viable, despite the skepticism of the medical community.
Then in the mid-2000s, Genentech launched two of the most widely used antibody-based treatments for cancer - Rituxan in 2006, and Avastin in 2009. Eli Lilly also introduced its drug Erbitux around that same time. Together these monoclonal antibodies, along with others, were approved to treat a wide array of cancers and racked up billions in sales.
Moore sees the current state of cancer immunotherapy as nearing a period of growth similar to that development.
“We have some learning to do, but there’s no doubt that T-cell therapy is going to continue to develop and gain momentum. It’s going to work,” Moore said.
Rapid development of KTE-C19
David Chang, head of R&D and chief medical officer at Kite, is focused on accelerating that development, both independently and through a number of strategic partnerships with other pharma companies.
For the last three years, Chang has worked to advance Kite’s primary CAR-T candidate, known as KTE-C19, aiming to launch sometime in 2017. KTE-C19 targets the CD19 antigen, which is expressed on the cell surface of B-cell blood cancers.
KTE-C19 first made headlines in late 2013 when Kite presented data at the annual American Society of Hematology meeting. The data showed KTE-C19 helped to shrink tumors in patients with diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin lymphoma with a particularly dismal five-year survival rate.
Three months later, the FDA granted an orphan drug designation for the DLBCL indication. By summer 2014, Kite had gathered more data showing a 92% objective response rate among patients with advanced b-cell malignancies. While that study tested KTE-C19 on only 13 patients, the strength of the data prompted Kite to file an investigational new drug application and move KTE-C19 into a Phase 1/2 clinical trial for DLBCL.
Kite’s current development program for KTE-C19, known as Zuma, now includes four pivotal trials. The biotech expects its Zuma-1 study to yield interim results sometime in the second half of this year.
Where to focus?
Kite has racked up a number of other orphan drug designations, including for primary mediastinal B-cell lymphoma, mantle-cell lymphoma, acute lympoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL).
Kite is conducting trials designed to evaluate KTE-C19 for these blood cancers, but the aim is to secure approval for DLBCL first, and then proceed from there.
It all comes down to the numbers and the size of the unmet medical need according to Chang, who made a strategic decision to pursue the DLBCL indication first.
"DLBCL has a much larger market than ALL—a total of 10,000 [patient deaths] versus 1,400 [patient deaths]—from which we can generate a treatable market,” said Chang.
Based on the efficacy seen in phase 1, coupled with the medical need for new treatments for DLBCL, Chang believes the current study should give Kite the data it needs to take KTE-C19 to the FDA.
“Phase 2B data should be sufficient to secure conditional FDA approval,” Chang said.
Since the company was founded in 2009, Kite has been aggressive in partnering with other companies, government-funded research agencies, and academic institutions.
On the institutional side, Kite has partnered with the National Cancer Institute (NCI) and the National Institutes of Health in the US, along with the Netherlands Cancer Institute and Leiden University in Europe. Kite also has partnership agreements with other companies, including Amgen, Bluebird Bio, Alpine and, most recently, Roche.
Just over two months ago, Kite and Roche announced they would launch a clinical trial to study KTE-C19 in combination with Roche’s anti-PDL1 antibody atezolizumab, which won FDA approval last month for treatment of bladder cancer.
The two companies hope to test whether leveraging the PD-L1 pathway could improve the CD19 response. This is particularly relevant for Kite because the PD-L1 protein is overexpressed in one-third of patients with DLBCL.
Combination therapies have become much more common in immuno-oncology as biopharma companies hope to extend the promising response rates to a greater percentage of patients.
Although Kite’s clinical development is continuing apace, the company has run into some manufacturing problems lately.
In mid-March, the NIH suspended production at two facilities which manufacture sterile and infused products for use in clinical studies. One of those facilities, an NCI laboratory, had been working with Kite to manufacture T-cell therapies for a number of its collaborative trials.
While this sparked some concerns regarding Kite’s clinical development program, Moore said this event did not impact the KTE-C19 trials. Kite has been using outside vendors and its own clinical sites for that program.
But it does set back work on some collaborative trials for T-cell therapies that NCI was studying.
The headache also highlights the challenge of manufacturing cell therapies. Producing cell therapies for use in a clinical trial setting is one thing, commercial scale is another.
Kite has reached the point where larger-scale manufacturing is on the horizon. Last February, the company leased a 44,500 square-foot manufacturing facility in El Segundo, CA, close to the Los Angeles airport.
The facility was retrofitted for cellular therapy process validations in order to prepare for a biologic license application later this year.
“It is important that the facility is close to LAX,” Moore said. “This is a vein-to-vein process, and the airport is a key point in the supply chain.”
CAR-T’s highly individualized and complex manufacturing processes also raises the question of cost. But Moore is optimistic.
“There is a lot of opportunity to continually improve the cost of goods. As you scale up operations, costs will come down,” Moore said.
“We are collaborating with GE on a next-generation manufacturing project, which will automate key parts of the T-cell manufacturing process that have always been unautomated.”
Kite expects to burn through between $235 and $250 million dollars in 2016 (although this includes other expenses besides R&D and capital expenditures). At the end of the first quarter, the company has roughly $577 million cash and equivalents on hand.
While that is more than enough to keep the lights on, continued progress in KTE-C19’s clinical development is crucial.
On Monday, June 6, Kite will be presenting the most up-to-date data from its CAR-T cell therapy pipeline at ASCO, which should give a better sense of the likelihood of a 2017 FDA filing for KTE-C19.