UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction of Incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
|
|
|
|
||
(Address of Principal Executive Offices) |
|
(Zip Code) |
Registrant’s Telephone Number, Including Area Code: (
Not Applicable
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
|
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
|
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
Title of each class |
|
Trading Symbol(s) |
|
Name of each exchange on which registered |
|
|
|
(Nasdaq Global Select Market) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item. 7.01 Regulation FD Disclosure.
On December 5, 2022, Nkarta, Inc. (the “Company”) issued a press release announcing positive updated clinical data from its Phase 1 dose escalation study of NKX019, which such data is discussed in more detail in Item 8.01 of this Current Report on Form 8-K. A copy of the press release is attached hereto as Exhibit 99.1 and incorporated by reference herein.
Also on December 5, 2022 and as previously disclosed, the Company hosted a conference call to discuss the foregoing updated clinical data. A copy of the slide presentation used during the Company’s conference call is attached hereto as Exhibit 99.2 and incorporated by reference herein.
The information in Item 7.01 of this Current Report on Form 8-K (including Exhibit 99.1 and Exhibit 99.2) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be, or be deemed, incorporated by reference in any filings under the Securities Act of 1933, as amended (the “Securities Act”), unless the Company specifically states that the information is to be considered “filed” under the Exchange Act or incorporates it by reference into a filing under the Securities Act or the Exchange Act.
Item. 8.01 Regulation FD Disclosure.
On December 5, 2022, the Company announced positive updated clinical data from its Phase 1 dose escalation study of NKX019 as monotherapy to treat patients with relapsed or refractory (“r/r”) B-cell malignancies.
The updated clinical data from the dose escalation portion of the Company’s NKX019 Phase 1 clinical trial demonstrate that NKX019 was well-tolerated across all dose levels evaluated and showed anti-tumor activity (as described below). There were no reports of dose limiting toxicity, cytokine release syndrome (“CRS”) higher than Grade 3, neurotoxicity/ICANS, or graft-versus-host disease in any of the nineteen patients treated to date. Transient myelosuppression, a manageable toxicity common with lymphodepletion, was the most common higher-grade toxicity reported on trial, regardless of relationship to NKX019. Five patients developed fever within eight hours of NKX019 infusion, and each case resolved within 24 hours. The efficacy data demonstrate that eight out of ten patients with non-Hodgkin lymphoma (“NHL”), including large B cell lymphoma (“LBCL”), responded to NKX019 as monotherapy for an overall response rate (“ORR”) of 80% at the 1 billion and 1.5 billion cell dose levels (the “Higher Dose Levels”). Seven of the ten responding patients with NHL in the Higher Dose Levels achieved a complete response (“CR”, 70%). As previously reported, four patients with NHL were treated at the lower dose of 300 million cells with an ORR of 50% and CR of 25%. Of the patients with leukemia treated with NKX019, three with acute lymphocytic leukemia and two with chronic lymphocytic leukemia, none achieved a response. The dose expansion portion of the Phase 1 clinical trial is currently open for enrollment. The dose expansion will investigate NKX019 as monotherapy both in patients with LBCL who have not previously received autologous CD19 CAR T therapy and in those who have previously received such therapy and will also investigate NKX019 as combination therapy with rituximab, an anti-CD20 monoclonal antibody, in patients with r/r NHL.
Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more data on existing patients become available. The clinical trial program is ongoing, and the final results may be materially different from those reflected in any interim data the Company reports. Further, others, including regulatory agencies, may not accept or agree with the Company’s assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and the value of the Company in general. In addition, the information the Company chooses to publicly disclose regarding a particular study or clinical trial is typically a summary of extensive information, and others may not agree with what the Company determines is the material or otherwise appropriate information to include in its disclosure, and any information the Company determines not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product, product candidate or business.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
Exhibit Number |
|
Description |
|
|
|
99.1 |
|
99.2 |
|
Clinical Program Update Presentation, dated December 5, 2022. |
104 |
|
Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|
|
Nkarta, Inc. |
|
|
|
|
|
Date: December 5, 2022 |
|
By: |
/s/ Alicia Hager |
|
|
|
Alicia J. Hager, J.D., Ph.D. |
|
|
|
Chief Legal Officer |
Exhibit 99.1
Nkarta Announces Updated Clinical Data on Anti-CD19 Allogeneic CAR-NK Cell Therapy NKX019 for Patients with Relapsed or Refractory Non-Hodgkin Lymphoma
SOUTH SAN FRANCISCO, Calif., Dec. 5, 2022 -- Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer cell therapies to treat cancer, today announced positive updated data from its Phase 1 dose escalation study of NKX019 as monotherapy to treat patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL).
Seven of ten patients treated at the higher dose levels in a three-dose regimen showed a complete response (70% CR), including two patients with aggressive large B cell lymphoma (LBCL), one patient with mantle cell lymphoma (MCL), and one patient with marginal zone lymphoma (MZL). No dose limiting toxicity, neurotoxicity / ICANS, graft versus host disease (GvHD), or >Gr3 cytokine release syndrome (CRS) were observed in the study.
“NKX019 continues to demonstrate impressive single-agent activity, preliminary durability and an encouraging safety profile as an off-the-shelf, on-demand cell therapy for heavily pre-treated patients with NHL,” said Paul J. Hastings, President and CEO of Nkarta. “Based on this initial success, we recently opened dose expansion
cohorts to explore combination and single-agent regimens in patients with LBCL, an especially aggressive form of lymphoma, and to address the large unmet need in patients who have received prior autologous CAR T therapy. We remain committed to improved access for patients through the integration of cell therapy into the broader outpatient setting.”
Nkarta plans to provide updates from the NKX019 program, including data from the dose expansion cohorts, in 2023.
Evaluating NKX019 in r/r B cell malignancies
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses NK cells engineered to target the B-cell antigen CD19, a clinically validated target for B-cell cancer therapies. The NKX019 Phase 1 study is evaluating the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle therapy in patients with r/r B cell malignancies.
As of November 28, 2022, 19 patients were enrolled and dosed. Fourteen patients entered the study with a diagnosis of non-Hodgkin lymphoma (NHL), 7 of which were aggressive large B cell lymphoma (LBCL). Patients had received a median of 4 prior lines of therapy (range of 2 to 10). To date, enrollment has included patients with aggressive disease characteristics and extensive lesions throughout the body. Patients were enrolled at clinical trial sites in Australia (13) and the United States (6).
“Autologous CAR T cell therapy has undeniably changed the NHL treatment landscape, but the possibility of severe toxicity and the limited access of these therapies leave many potentially eligible patients without a cellular therapy option,” said Michael Dickinson, M.D., Lead, Aggressive Lymphoma disease group, Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, and investigator in the NKX019 trial. “In the data so far, NKX019 has shown encouraging anti-tumor activity, including in patients with aggressive histologies, who are the patients who are most in need.”
Safety in NKX019
NKX019 was well tolerated. No ICANS, GvHD, or >Gr3 CRS were observed in the study. No dose-limiting toxicities were observed. Five patients developed fever within 8 hours of NKX019 infusion, and each resolved within 24 hours. 2 of the 5 patients were assessed to have infusion-related reactions, 2 patients were assessed to have CRS, despite the rapid onset and rapid resolution not common in CRS, and one patient had both entities described in two separate cycles. The most common higher-grade adverse events were myelosuppression - a condition resulting in fewer red blood cells, white blood cells and platelets, which is common in this patient population post lymphodepletion. (See table 1.) The emerging safety profile of NKX019 is positively differentiated from those of many cell therapies.
NXK019 Safety (Table 1)
|
|
|
|
Grade 3/4 AEs in > 1 subject |
Total (N=19) |
Subjects with any ≥ Grade 3 AEs |
16 (84%) |
Neutrophil count decreased |
12 (63%) |
Platelet count decreased |
8 (42%) |
Febrile neutropenia |
5 (26%) |
Anemia |
4 (21%) |
WBC count decreased |
3 (16%) |
Lymphocyte count decreased |
2 (11%) |
Treatment emergent adverse events regardless of relationship based on interim data from open clinical database as of 28 November 2022
|
Clinical Activity in NXK019
Nineteen patients who received NKX019 were assessed (See table 2). In the two highest dose cohorts (1 B cells x 3 and 1.5 B cells x 3), 8 out of 10 patients with NHL achieved an objective response (80% ORR) and 7 out of 10 achieved a complete response (70% CR). 5 of 6 patients with NHL in the cohort receiving 3 doses of 1 billion cells achieved a response (83% ORR), and 4 of 6 achieved a complete response (67% CR rate). 3 of 4 patients with NHL in the cohort receiving 3 doses of 1.5 billion cells achieved a response (75% ORR) and a complete response (75% CR). For all cohorts in the dose finding portion (300 M cells x 3, 1 B cells x 3, and 1.5 B cells x 3), 10 of 14 patients with NHL achieved an objective response (71% ORR) and 8 of 14 achieved a complete response (57% CR). 3 patients with ALL and 2 patients with CLL were treated, with no response observed.
NKX019 Clinical Activity (Table 2) |
||||||
|
|
|
|
|
|
|
|
300 M cells x 3 |
1 B cells x 3 |
1.5 B cells x 3 |
|||
|
ORR (CR, PR) |
CR |
ORR (CR, PR) |
CR |
ORR (CR, PR) |
CR |
All NHL |
2/4 (50%) |
1/4 (25%) |
5/6 (83%) |
4/6 (67%) |
3/4 (75%) |
3/4 (75%) |
LBCL# |
1/3 |
0/3 |
1/2 |
1/2 |
1/2 |
1/2 |
MCL |
- |
- |
1/1 |
1/1 |
- |
- |
FL |
1/1 |
1/1 |
2/2 |
1/2 |
2/2 |
2/2 |
MZL |
- |
- |
1/1 |
1/1 |
- |
- |
|
|
|
|
|
|
|
Leukemia |
|
|
|
|
|
|
ALL |
0/1 (0%) |
0/1 (0%) |
0/2 (0%) |
0/2 (0%) |
- |
- |
CLL |
- |
- |
- |
- |
0/2 [1/2 SD] |
0/2 |
#LBCL includes DLBCL and FL3b
ALL: acute lymphoblastic leukemia; CLL: chronic lymphocytic leukemia; CR: complete response; FL: follicular lymphoma; LBCL: large B-cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; NHL: non-Hodgkin lymphoma; ORR: overall response rate; PR: partial response
About the NKX019 Clinical Trial
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells engineered to target the B-cell antigen CD19, a clinically validated target for B-cell cancer therapies. The dose-finding portion of the NKX019 Phase 1 study evaluates the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle monotherapy following lymphodepletion in patients with r/r B-cell malignancies. Patients must have received at least two prior therapies. Patients that received prior autologous CAR-T therapy were not eligible.
Patients in the NKX019 trial received a cycle of treatment consisting of lymphodepletion with 3 days of fludarabine and cyclophosphamide followed by NKX019 cells in a three-dose regimen where cells were given on Days 0, 7, and 14. Patients received doses of 300 million, 1 billion, or 1.5 billion cells three times in a cycle. Based on tumor response and tolerability assessment, patients are eligible to receive additional treatment cycles, including patients with progressive disease to observe whether NKX019 can reverse progression. Disease assessment was performed by investigator review according to the 2014 Lugano response criteria for patients with NHL and NCCN response criteria for patients with ALL.
The dose-expansion portion of the Phase 1 clinical trial of NKX019 will investigate NKX019 as combination therapy with rituximab, an anti-CD20 monoclonal antibody, in patients with r/r non-Hodgkin lymphoma, as well as NKX019 as monotherapy in patients with large B-cell lymphoma (LBCL) who previously received autologous CD19 CAR T-cell therapy. The dose expansion will also further investigate NKX019 as monotherapy in patients with LBCL who have not previously received autologous CD19 CAR T-cell therapy.
Conference Call Information
Nkarta management will discuss the NKX019 results on Monday, December 5, 2022, at 8:00 a.m. ET. To access the live webcast, please register online on the Investors section of Nkarta’s website: https://ir.nkartatx.com/events-and-presentations. An archived webcast and accompanying slides will be available on the Company’s website approximately two hours after the event.
About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.
About Nkarta
Nkarta is a clinical-stage biotechnology company advancing the development of allogeneic, off-the-shelf natural killer (NK) cell therapies for cancer patients. By combining its cell expansion and cryopreservation platform with proprietary cell engineering technologies and CRISPR-based genome engineering capabilities, Nkarta is building a pipeline of future cell therapies engineered for deep anti-tumor activity and intended for broad access in the outpatient treatment setting. For more information, please visit the company’s website at www.nkartatx.com.
Forward-looking statements
Forward-looking statements include, among others, statements of Nkarta’s future expectations, plans and prospects. These may include statements concerning Nkarta’s expectations regarding any or all of the following: the therapeutic potential of NKX019, as a monotherapy and/or in combination with rituximab, for the treatment of B-cell malignancies, including NHL; the tolerability and safety profile of NKX019; the accessibility and potential outpatient administration of NK cell therapies, including NKX019; plans and timelines for the continued and future clinical development of NKX019; and plans and timelines for the availability or future presentation of NKX019 clinical data. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements.
Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more data on existing patients become available. The clinical trial program is ongoing, and the final results may be materially different from those reflected in any interim data we report. Further, others, including regulatory agencies, may not accept or agree with Nkarta’s assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and the value of the company in general. In addition, the information Nkarta chooses to publicly disclose regarding a particular study or clinical trial is typically a summary of
extensive information, and you or others may not agree with what Nkarta determines is the material or otherwise appropriate information to include in Nkarta’s disclosure, and any information Nkarta determines not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product, product candidate or business.
These and other risks and uncertainties are described more fully in Nkarta’s filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of Nkarta’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, filed with the SEC on November 9, 2022, and Nkarta’s other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Nkarta undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Nkarta Media/Investor Contact:
Greg Mann
Nkarta, Inc.
gmann@nkartatx.com
5 December 2022 NEXT GENERATION Natural Killer Cells Engineered to Beat Cancer Exhibit 99.2
Forward-looking statements This presentation contains forward‐looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, regarding future events and the future results of the company that are based on current expectations, estimates, forecasts, and projections about the industry in which the company operates and the future of our business, future plans and strategies, projections, anticipated trends and events, the economy, and other future conditions, and the beliefs and assumptions of the management of the company. Words such as “address,” “anticipate,” “believe,” “consider,” “continue,” “develop,” “estimate,” “expect,” “further,” “goal,” “intend,” “may,” “plan,” “potential,” “project,” “seek,” “should,” “target,” “will,” variations of such words, and similar expressions are intended to identify such forward-looking statements. Such statements reflect the current views of the company and its management with respect to future events and are subject to inherent risks, uncertainties, and changes in circumstances that are difficult to predict and may be outside our control. Therefore, you should not rely on any of these forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, the company's actual results, performance, or achievements could differ materially from the results expressed in, or implied by, these forward-looking statements. Please see section entitled “Risk Factors” in our annual, quarterly and other filings with the Securities and Exchange Commission for a description of these risks and uncertainties. This presentation has been prepared by the company based on information it has obtained from sources it believes to be reliable. Summaries of documents contained in this presentation may not be complete. The company does not represent that the information herein is complete. The information in this presentation is current only as of the date on the cover, and the company's business or financial condition and other information in this presentation may change after that date. The company undertakes no obligation to update any forward‐looking statements in order to reflect any event or circumstance occurring after the date of this presentation or currently unknown facts or conditions. Interim data from clinical trials are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more data on existing patients become available. The clinical trial program is ongoing, and the final results may be materially different from those reflected in any interim data the company reports. Further, others, including regulatory agencies, may not accept or agree with the company’s assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and the value of the company in general. In addition, the information the company chooses to publicly disclose regarding a particular study or clinical trial is typically a summary of extensive information, and you or others may not agree with what the company determines is the material or otherwise appropriate information to include in its disclosure, and any information the company determines not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product, product candidate or business.
Next generation platform built for: CAR NK cells driving a revolution in off-the-shelf cell therapy Allogeneic, off-the-shelf, and on demand Industrialized manufacturing Outpatient administration Targeting receptor CAR NK Cell OX40 costimulatory domain CD3ζ signaling moiety CAR membrane bound IL-15 Blood cancers and solid tumors
Best response for 6 additional patients treated since April update Follow-up on patients from April update, including multiple patients with durability beyond 6 months Tolerability and clinical impact of additional cycles of NKX019 Deepening Consolidation Retreatment Outpatient administration in multiple patients Opening of dose expansion cohorts NKX019: Key topics for discussion
NKX019 for the Treatment of Relapsed / Refractory B-Cell Malignancies Clinical Data as of 28 November 2022
CAR T-cell therapy is not accessible to most patients with NHL Only 20-30% of patients with LBCL that can benefit from cell therapy receive it Potential for toxicity requires close proximity to an intensive care unit Need for specialized sites as >25% of patients require ICU care Grade 3+ CRS: 13 to 49%, Grade 3+ ICANS / neurotoxicity: 18 to 31% Only 30-40% of patients with LBCL treated with CAR T-cell therapy have 6-month CR No ability to re-dose for incomplete response Outcomes among those that relapse is poor Autologous CAR T-cell therapy has set the bar for cellular therapies in relapsed / refractory NHL but has limitations YESCARTA USPI; KYMRIAH USPI; BREYANZI USPI; Azoulay et al, 2020; Tomas, et al. 2022. CAR: chimeric antigen receptor; CR: complete response; CRS: cytokine release syndrome; ICANS: immune cell associated neurotoxicity syndrome; ICU: intensive care unit; LBCL: large B-cell lymphoma; NHL: non- lymphoma; USPI: U.S. Prescribing Information. NKX019
r/r CD19+ B-cell malignancies Received >2 prior lines of therapy ECOG PS 0 or 1 CAR T-cell therapy naïve (dose-finding phase) Endpoints: Safety and tolerability Anti-tumor activity Pharmacokinetics NKX019 for B-cell malignancies: A multicenter, open-label, phase 1 study NKX019 3 doses per 28-day cycle Lymphodepletion Cyclophosphamide 300 mg/m2/day IV (dose-finding phase) Fludarabine 30 mg/m2/day IV Days -5 to -3 Efficacy assessment* Day 28 Day 0 Day 7 Day 14 Dose 1 Dose 2 Dose 3 NCT05020678 EOT Visit Post-treatment follow-up Subjects with initial clinical benefit and subsequent progression may receive retreatment *Efficacy based on: Lugano criteria for NHL; 2018 iwCLL guidelines for CLL; NCCN v1.2020 for B-ALL CAR: chimeric antigen receptor; CR: complete response; ECOG PS: Eastern Cooperative Oncology Group performance status; EOT: end of therapy; r/r: relapsed/refractory; iwCLL: International Workshop on Chronic Lymphocytic Leukemia; NCCN: National Comprehensive Cancer Network. Multiple cycles allowed to deepen response for subjects tolerating and benefiting from treatment Subjects in CR may receive additional cycle as consolidation Key Inclusion Criteria
Patients who were treated with NKX019 were heavily pre-treated and had a poor prognosis 50% 4 7 of 14 patients with NHL had aggressive LBCL Median lines of prior therapy NKX019 Total (N=19) Age, median (range) 59 (21-82) Baseline ECOG PS 1 13 Australia/US 13/6 Diagnosis Large B cell lymphoma (LBCL)# IPI 3+ 7 3 (43%) Follicular lymphoma (FL) FLIPI high risk 5 3 (60%) Marginal zone lymphoma (MZL) 1 Mantle cell lymphoma (MCL) 1 Chronic lymphocytic leukemia (CLL) 2 B-cell acute lymphoblastic leukemia (B-ALL) 3 Prior lines of therapy, median (range) 4 (2 - 10) DLBCL: diffuse large B-cell lymphoma; ECOG PS: Eastern Cooperative Oncology Group performance status; FL3b: follicular lymphoma grade 3b; FLIPI: Follicular Lymphoma International Prognostic Index; LBCL: large B-cell lymphoma; NHL: non-Hodgkin lymphoma. #LBCL includes 6 DLBCL and 1 FL3b.
NKX019 was well-tolerated up to 1.5 B cells / dose No ICANS / neurotoxicity, GVHD, Grade 5 or dose-limiting toxicities One (5%) Grade ≥ 3 infection No treatment-related AEs leading to discontinuation of NKX019 Myelosuppression, consistent with standard lymphodepletion, was the most common Grade ≥ 3 toxicity and manageable Treatment-emergent AEs regardless of relationship. Grade 3/4 AEs in >1 subject Total (N=19) Subjects with any ≥ Grade 3 AEs 16 (84%) Neutrophil count decreased 12 (63%) Platelet count decreased 8 (42%) Febrile neutropenia 5 (26%) Anemia 4 (21%) WBC count decreased 3 (16%) Lymphocyte count decreased 2 (11%) AE: adverse event; GVHD: graft versus host disease; ICANS: immune effector cell-associated neurotoxicity syndrome. WBC: white blood cell count.
A minority of patients experienced transient and manageable infusion-related effects 5/19 patients (26%) developed fever within 8 hours that resolved within 24 hours In contrast, CAR T-cell therapy–associated CRS has a median onset of 2-5 days and a median duration of 5-8 days Grade 1/2 infusion-related reactions (IRR) listed as expected side effect in Investigator’s Brochure No apparent association between symptoms and response * Lee, ASTCT. YESCARTA USPI; KYMRIAH USPI; BREYANZI USPI. CAR: chimeric antigen receptor; CRS: cytokine release syndrome; G: grade. Patient Grade* Investigator assessment Anti-IL-6 therapy Steroids Description of event #1 G1 IRR N N Fever within 8 hours; resolved with antipyretics and did not recur #2 G1 IRR N N Fever within 5 hours; resolved with antipyretics and did not recur #3 G2 CRS N N Fever and hypotension within 8 hours; resolved with antipyretics and did not recur G1 CRS N N Fever within 6 hours; resolved with antipyretics and did not recur #4 G3 CRS Y Y Fever and hypoxia within 5 hours; fever resolved within 24 hours and did not recur #5 G1 IRR N N Tachycardia (no fever) within 3 hours; resolved within 24 hours without intervention G2 CRS Y N Fever with hypotension and hypoxia within 6 hours; symptoms resolved within 24 hours after treatment and did not recur
Peak IL-6, IFNγ, IL-10, and IL-8 levels were marginally above baseline throughout treatment for most patients Severe (Grade > 3) CRS in those receiving CAR T-cell therapies is generally associated with ~100-fold changes of multiple serum cytokines No Grade > 3 CRS observed to date with NKX019 No association was observed between elevated serum cytokines and clinical response Cytokine elevation was generally modest across all patients CAR: chimeric antigen receptor; CR: complete response; CRS: cytokine release syndrome. M. Davila et al., Sci Transl Med. 2014; Hay et al., Blood, 2017.
NKX019 showed monotherapy activity across multiple histologies 300 M Cells × 3 Doses 1 B Cells × 3 Doses 1.5 B Cells × 3 Doses ORR (CR, PR) CR ORR (CR, PR) CR ORR (CR, PR) CR All NHL 2/4 1/4 5/6 (83%) 4/6 (67%) 3/4 (75%) 3/4 (75%) LBCL# 1/3 0/3 1/2 1/2 1/2 1/2 MCL - - 1/1 1/1 - - FL 1/1 1/1 2/2 1/2* 2/2 2/2 MZL - - 1/1 1/1 - - Leukemia 0/1 0/1 0/2 0/2 0/2 0/2 ALL 0/1 0/1 0/2 0/2 - - CLL - - - - 0/2 [1/2 SD] 0/2 New since April 2022 * PR deepened to CR since April 2022 8/10 ORR (80%), including 7/10 CRs (70%) observed at higher dose levels in NHL #LBCL includes DLBCL and FL3b. ALL: acute lymphoblastic leukemia; CLL: chronic lymphocytic leukemia; CR: complete response; DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; FL3b: follicular lymphoma grade 3b; LBCL: large B-cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; NHL: non-Hodgkin lymphoma; ORR: overall response rate; PR: partial response.
NKX019 monotherapy elicited complete responses with early durability across NHL histologies; most responses occurred after a single cycle 1 1.5 B FL CR 2 1.5 B LBCL CR 3 1.5 B FL CR 4 1.5 B LBCL SD 5 1.0 B LBCL CR 6 1.0 B MZL CR 7 1.0 B FL CR 8 1.0 B MCL CR 9 1.0 B FL PR 10 1.0 B LBCL SD 11 300 M FL CR 12 300 M FL3b PR 13 300 M LBCL PD 14 300 M LBCL PD CR: complete response; FL: follicular lymphoma; FL3b: follicular lymphoma grade 3b; LBCL: large B-cell lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; PD: progressive disease; PR: partial response; SD: stable disease. Best Response Patient Cells CR PR Indeterminant SD PD Death Transplant Eligible for Retreatment NHL Subtype 8 patients achieved CR with NKX019 monotherapy 5 after a single cycle 3 with PR deepened to CR with additional cycles 7 received consolidation cycle Retreatment planned with 1.5 B dose for 3 patients New since April 2022
Nearly every patient with NHL treated with NKX019 experienced tumor reduction Notes: 1. Tumor size is calculated as sum of the product of the perpendicular diameters (SPD). 2. One patient discontinued due to clinical progression without SPD assessment. 3. One patient did not have any target lesions. The SPD was calculated based on measurable non-target lesions. CR: complete response; NHL: non-Hodgkin lymphoma; PD: progressive disease; PR: partial response. Best Response CR PR SD PD
Higher cell doses correlated with higher peak measured concentration (Cmax) Peak concentration trended higher in patients achieving CR Higher peak concentrations of NKX019 correlated with complete responses and higher doses of NKX019 6.7 = Lower limit of quantification Cmax, given as transgene copies/μg of DNA. Dose Level Cmax All subjects CR Non-CR 300 M cells n 5 1 4 Median (range) < 6.7 (< 6.7-393) 393 (393) < 6.7 (< 6.7-234) 1 B/1.5 B cells n 14 7 7 Median (range) 156.9 (< 6.7-567.0) 298 (< 6.7-567.0) < 6.7 (< 6.7-481) CMAX, peak detected concentration; CR: complete response.
Successive rounds of NKX019 are feasible and effective at achieving clinical responses Median interval between treatment cycles was 8 days Lymphodepletion was given at the beginning of each 28-day cycle of therapy and was well-tolerated 40% of eligible patients received NKX019 in the outpatient setting after first cycle Mandatory 24-hour admission after each dose in the first cycle Increased outpatient utilization observed with increased experience On demand availability of NKX019 facilitated successive treatment cycles and outpatient administration
CAR T-cell therapy–naïve LBCL cohort Improved access and favorable safety profile Comparable CR rate to autologous CAR T CAR T-cell therapy–experienced LBCL cohort CD19 expression persists in >90% of those who fail CAR T-cell therapy; outcomes for these patients are poor1 NKX019 offers NK-driven cytotoxicity and superior sensitivity to CD19 antigen2 Rituximab combination cohort Dual antigen targeting through ADCC and improved anti-tumor activity of NKX0193 CAR T-naïve and CAR T-experienced NKX019 expansion cohorts are now open, each using 1.5 B cell dose and updated lymphodepletion 2 3 NKX019 has greater cytotoxicity than CAR T cells against a low CD19 expressing cell line Effector:Target Ratio NKX019 has enhanced tumor cell killing when combined with rituximab 1. Tomas, et al. Leukemia 2022; 2.Dickinson, et al. ASH 2021; 3.Thome, et al. SITC 2022. ADCC: antibody-dependent cell-mediated cytotoxicity; CAR: chimeric antigen receptor; CR: complete response; LBCL: large B-cell lymphoma.
NKX019 remains on track for potential registration-enabling studies Allogeneic and off-the-shelf cell therapy to improve patient access Evaluation of monotherapy activity as well as in combination with rituximab Strong cash position: $395 million as of September 30, with runway into 2025 Clinical data strengthen Nkarta’s position in the NHL therapeutic landscape 18 2022 2023 2024 H1 H2 H1 H2 H1 H2 NKX019 NHL Potential for fast track / RMAT / breakthrough therapy designation H1 H2 H1 H2 H1 H2 Pivotal Trials Monotherapy Dose Expansion: CAR T-naïve LBCL cohort Phase 1 Dose Finding: B cell malignancies Monotherapy Dose Expansion: CAR T-experienced LBCL cohort Rituximab Combination Dose Expansion: CAR T-naïve and -experienced CAR: chimeric antigen receptor; LBCL: large B-cell lymphoma; NHL: non-Hodgkin lymphoma; Ph: phase.
Building on earlier data, NKX019 monotherapy continues to be well-tolerated with promising anti-tumor activity Six additional patients with r/r NHL have been treated since prior data cut-off Earlier reported PR deepened to CR CR rate improved to 70% from previous update of 50% On-demand availability for administration in the outpatient setting No DLTs, ICANS, GVHD, or Grade > 3 CRS At highest dose levels, 8 of 10 patients with NHL responded (80% ORR), and 7 of 10 patients achieved complete responses (70% CR) CRs observed in multiple NHL histologies, including 50% CR in LBCL Nearly every patient with NHL treated with NKX019 had tumor reduction Deepening of response and consolidation of CR achieved with multiple cycles Potential for retreatment should tumor recur Deep responses with durability exceeding 6 months in multiple patients Expansion cohorts now open for enrollment NKX019 is an accessible, off-the-shelf CAR NK cell therapy with encouraging activity and safety profile CAR: chimeric antigen receptor; CR: complete response; CRS: cytokine release syndrome; DLT: dose-limiting toxicity; GVHD: graft versus host disease; ICANS: immune effector cell-associated neurotoxicity syndrome; LBCL: large B-cell lymphoma; NHL: non-Hodgkin lymphoma; ORR: overall response rate: Ph: phase; r/r: relapsed/refractory.