Juno Files for IPO as CAR Therapies Continue to Advance

As its chimeric antigen receptor (CAR) T cell and high-affinity T cell receptor (TCR) products continue to advance in clinical trials, Juno Therapeutics, Inc, filed a registration statement for an initial public offering (IPO) of its common stock on November 17.

Following this announcement, on November 18, the company also announced that the FDA had granted an orphan drug designation to the CAR T cell product JCAR015 for acute lymphoblastic leukemia (ALL).

Juno made a dramatic debut as a company. In its Series A round, which concluded in April 2014, Juno raised $176 million. Juno raised an additional $134 million by August 2014 — for a total of $310 million in investment in less than 12 months. Juno’s financial success has been predicated on the promise of four products in their clinical pipeline: JCAR015, JCAR017, JCAR014 (all of which target CD19), and JTCR016 (which targets WT-1).

JCAR015 is being investigated in two phase I clinical trials. One trial will examine high dose therapy and autologous stem cell transplantation followed by infusion of JCAR015 in patients with relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL; NCT01044069). In the other trial, JCAR015 will be analyzed in patients with precursor B cell ALL, the setting in which the agent gained its orphan drug designation (NCT01840566).

JCAR017 will be looked at in a phase I/II trial of pediatric and young adult patients with relapsed/refractory CD19-positive leukemia (NCT02028455), whereas JCAR014 will be looked at in a phase I/II trial of patients with CD19-positive chronic lymphocytic leukemia, ALL, and NHL (NCT01865617).

The CAR T-cell therapies explored by Juno are a form of adoptive cell therapy in which the patient’s T cells are cultured and then primed to specifically recognize target tumor cells, prior to infusion back into the patient. In early findings, patients with B cell ALL treated with CD19 targeted T cells experienced a complete response rate of 88%.

While Juno’s CAR T cell products target CD19, a cell surface marker for lymphocytes present on many B cell malignancies, its TCR T cell product works differently. JTCR016 targets WT-1, an intracellular protein overexpressed in several cancers, including acute myeloid leukemia (AML), breast, colorectal, non-small cell lung, ovarian, and pancreatic cancers. However, the agent is not yet being looked at in solid tumors.

JTCR016 is being evaluated in a phase I/II trial of patients with high-risk or relapsed AML, myelodysplastic syndrome, or chronic myeloid leukemia following allogeneic hematopoietic cell transplantation.

Despite the excitement surrounding Juno’s financials, competition in this therapeutic area is abundant. CAR T cell therapies are being developed collaborations between Novartis and the University of Pennsylvania (CTL019) as well as between Kite Pharma and the NCI (KTE-C19).

In early trials, CTL019 demonstrated complete remissions in 27 of 30 pediatric and adult patients with relapsed/refractory ALL. As a result of these data, CTL019 was granted a breakthrough therapy designation by the FDA in July 2014 as a potential treatment for pediatric and adult patients with relapsed/refractory ALL, marking the first such designation for a CAR T cell therapy.

In August 2014, findings from an ongoing phase I/IIa trial of KTE-C19 were published in the Journal of Clinical Oncology. In this analysis, the treatment demonstrated an overall response rate of 92% in patients with advanced B-cell malignancies, with a complete remission rate of 61.5% and the partial response rate of 30.8%.