The first cell therapies for cancer employ T cells turned into targeted tumor fighters. Nkarta Therapeutics set out to show that a different type of cell can offer a new and potentially better twist on cancer immunotherapy. Now the biotech has early clinical data showing that not only does the use of natural killer (NK) cells work in two different types of blood cancers, it also offers potential safety and efficacy advantages over the first generation of T cell therapies.
The preliminary results reported Monday are from two Phase 1 dose-finding studies. Both have small samples of patients, but the positive early data are an encouraging sign for the company specifically and for the field of NK cell therapy developers broadly. The stock price of South San Francisco-based closed Monday at $18.72, a nearly 141% increase over Friday’s closing price.
Natural killer cells are a type of white blood cell that carry cancer-killing enzymes. Nkarta develops its therapies by sourcing NK cells from healthy donors and engineering these cells to better go after cancer targets and to last longer in the body. Using donor NK cells enable Nkarta to offer an “off-the-shelf” cell approach unlike CAR T-therapies, the highly personalized first generation of cancer cell therapies made by engineering a patient’s own T cells.
Nkarta has two lead NK cell therapies. The first, NKX101, is in early clinical development in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In both types of cancer, the treatment is being evaluated in patients who had relapsed or had not responded to earlier cancer treatments. The Phase 1 test of NKX101 enrolled 21 patients: 17 with AML and four with MDS. The results show that the best responses were from the two highest doses with three of five AML patients achieving a complete response to the treatment along with hematologic recovery, which means that blood cell types that were either too low or too high have returned to normal levels. In two of the three responders, no signs of the disease were detected after treatment.
The second Nkarta drug, NKX019, is being evaluated in relapsed or refractory B cell cancers. As of last Thursday, 13 patients were enrolled and dosed in the Phase 1 study. Ten of those patients were diagnosed with non-Hodgkin lymphoma; five of those cases were characterized as aggressive large B cell lymphoma. The company reported Monday that three of six patients who received the higher dose level showed a complete response to the treatment. One of those patients had aggressive diffuse large B cell lymphoma and another patient had mantle cell lymphoma.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
In both Phase 1 studies, Nkarta reported no dose-limiting problems, nor any adverse events resembling the excessive autoimmune responses and brain toxicities associated with CAR T-treatments.
“We’re excited to see our CAR NK co-lead candidates, NKX101 and NKX019, show such striking early single-agent activity in heavily pretreated patient populations, with an exceptional safety profile without the side effects associated with CAR T cell therapies,” Paul Hastings, president and CEO of Nkarta, said in a prepared statement. “These encouraging data across multiple indications further validate Nkarta’s best-in-class NK cell platform, as we seek to transform cancer treatment by bringing together the safety advantages of NK cells with an off-the-shelf modality designed to make the benefits of cell therapy accessible in a community setting.”
Sami Corwin, an analyst at William Blair, wrote in a research note that although the patient numbers are small, the Nkarta cell therapies pass the 30% complete response efficacy threshold set by non-engineered NK cell therapies. She added that NKX019’s early results show efficacy comparable to what was achieved by cord blood-derived NK cell therapies developed by MD Anderson Cancer Center (partnered with Takeda Pharmaceutical), Fate Therapeutics’ induced pluripotent stem cell-derived CAR-NK therapy, and CAR T-therapies. Furthermore, William Blair sees CAR-NK cell therapies as having a better safety profile compared to CAR T.
Nkarta said it is continuing to enroll patients in both of its Phase 1 studies; study participants will receive the high 1.5 billion NK cell three-dose regimen. Data from these studies, including follow-up data and updates from the high dose group, will be presented at a future medical meeting.
In an investor presentation, Nkarta said NKX101has the potential for regulatory approval in relapsed or refractory AML with data from the single-arm expansion group. The company added that there is potential to move this therapy into earlier lines of treatment. For NKX019, Nkarta said the higher 1.5 billion NK cell regimen offers the potential to improve and deepen responses to treatment. The company is planning to test the drug in expansion groups patients previously treated with CAR T therapy, as well as large B cell lymphoma patients who have not previously received CAR T. Nkarta expects to post the next data update for both programs in the second half of this year.
Nkarta has plenty of company in the chase for off-the-shelf NK cell therapies that offer better efficacy than CAR T. Other NK cell therapy developers include Shoreline Biosciences, which has partnerships with Gilead Sciences and BeiGene; Bristol Myers Squibb-partnered Century Therapeutics; Wugen; and new startup Indapta Therapeutics.
