Anktiva (nogapendekin alfa inbakicept-pmln) / ImmunityBio - LARVOL DELTA

NAI, An IL-15 Superagonist, A New Class Of Lymphocyte Stimulating Agent (LSA) Prolongs OS In NSCLC By Reversing Lymphopenia (IASLC-WCLC 2025) - P2 | "Introduction : Prior to the approval of Nogapendekin alfa inbakicept (NAI), an IL-15 superagonist which stimulates lymphocytes important in immunogenic cell death (Natural killer cells, CD4+ CD8+ T cells and memory T cells), no treatment existed to address lymphopenia as measured by the absolute lymphocyte count (ALC) in the CBC differential...Lymphopenia is addressed for the first time with availability of this new class of lymphocyte stimulating agent (LSA), NAI. When ALC is maintained ≥1,500 with NAI, the immune system is effectively activated (chemo-free), and median OS is significantly prolonged at 21.1 months, HR: 0.33 (95% CI:0.16,0.65) P=0.0009."

IO biomarker • Lymphopenia • Febrile Neutropenia • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • CD4 • CD8

Nogapendekin alfa inbakicept: “The committee discussed the issues identified in this application”; Non-muscle invasive bladder cancer (European Medicines Agency) - CHMP Final Minutes of the meeting on 19 - 22 May 2025: “The committee adopted the CHMP recommendation and scientific discussion together with the list of questions”

CHMP • Bladder Cancer • Genito-urinary Cancer • Oncology

Elevated uric acid induces erectile dysfunction in rats by interacting with MLCK and inhibiting its ubiquitin-mediated degradation. (PubMed, Commun Biol) - "Mechanistically, uric acid enters corpus cavernosum smooth muscle cells, interacting with MLCK at N803 to inhibit its ubiquitination by E3 ligase NEDD4L, stabilizing MLCK and increasing MLC2 phosphorylation, and leading to corpus cavernosum contraction. Pharmacological uric acid-lowering (febuxostat, benzbromarone, 3170) or MLCK inhibition (ML-7) restores erectile function in rats. Our findings reveal the key molecules and mechanisms of hyperuricemia-induced erectile dysfunction, which provides evidence for hyperuricemia or gout patients to control uric acid levels and prevent erectile dysfunction."

Journal • Preclinical • Cardiovascular • Erectile Dysfunction • Gout • Inflammatory Arthritis • Metabolic Disorders • Rheumatology • Targeted Protein Degradation

Advancements in bladder cancer immunotherapy: a focus on intravesical approaches. (PubMed, Front Pharmacol) - "Novel combinations, such as sasanlimab (a PD-1 monoclonal antibody) with BCG, have improved event-free survival in high-risk non-muscle-invasive bladder cancer (NMIBC). Intravesical anti-PD-1/PD-L1 agents like pembrolizumab and nadofaragene firadenovec have demonstrated efficacy and safety in BCG-unresponsive NMIBC, leading to regulatory approval. Additionally, BCG combined with immunostimulatory protein complexes (e.g., N-803) achieved high complete response rates while preserving quality of life...Promising results have also been observed with intravesical oncolytic immunotherapy combined with systemic anti-PD-1 therapy in cisplatin-ineligible MIBC. These advancements underscore the potential of intravesical and systemic immunotherapies to improve bladder cancer outcomes and warrant further investigation."

Journal • Review • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

ImmunityBio Reports Q2 Earnings Release Reflecting 60% Increase in Revenue in Q2 2025, With Year-to-Date Sales of $43 Million and 246% Unit Growth Since J-code (Businesswire) - "In the second quarter of 2025, ImmunityBio reported $26.4 million in revenue, representing a 60% increase from $16.5 million in the first quarter of 2025. This growth reflects continued commercial traction of ANKTIVA in combination with BCG in BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without Papillary tumors. The first half 2025 sales of $42.9 million represents a 246% increase in unit volume during the first two quarters of 2025 since the J-code approval versus the last two quarters of 2024. The Company ended the quarter with $153.7 million in cash, cash equivalents and marketable securities as of June 30, 2025."

Sales • Bladder Cancer

Initial Data Shows 100% Disease Control in 5 Out of 5 Patients With Recurrent Glioblastoma With Two Patients in Near Complete Response Treated With ImmunityBio’s ANKTIVA, NK Cell Therapy Plus Optune Gio Device (Businesswire) - "Of the 5 patients treated to date, 3 responded of which 2 at near complete response and the remaining 2 having stable disease to date."

P2 data • Glioblastoma

First-in-Class Lymphocyte Stimulating Agent (LSA) Nogapendekin Alfa Inbakicept (NAI) Increases Absolute Lymphocyte Count (ALC) in Randomized Trial in Non-Small Cell Lung Cancer (NSCLC) (ESMO 2025) - No abstract available

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ImmunityBio Reports Q2 Earnings Release... (Businesswire) - "Non-Small Cell Lung Cancer (NSCLC): ImmunityBio has launched ResQ201A, a randomized controlled trial (RCT), in the U.S., evaluating its IL-15 superagonist N-803 in combination with tislelizumab, a PD-1 CPI from BeOne Medicines in patients with second-line lung cancer who were progressing on checkpoint inhibitors (CPIs). The Company has also submitted clinical trial applications for ResQ201A in the EU and the UK, with Canada expected to be submitted in early Q3 2025, and with plans underway to submit in Asia."

Trial status • Non Small Cell Lung Cancer

Pembrolizumab + N-803 Alone or in Combination With PD-L1 t-haNK Cells for Resectable Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Enrollment open • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

ImmunityBio, Inc...announced the Michael E. DeBakey Department of Veterans Affairs (VA) Medical Center in Houston recently became the first VA hospital in the Houston region... (Businesswire)

Commercial • Bladder Cancer

FDA Approval Summary: Nogapendekin Alfa Inbakicept-pmln with BCG for BCG-unresponsive carcinoma in situ. (PubMed, Clin Cancer Res) - "Patients received N-803 400 μg administered intravesically with TICE BCG once a week for 6 weeks as induction therapy, a second induction course if complete response (CR) was not achieved at month 3, and maintenance N-803 with BCG weekly for 3 weeks at months 4, 7, 10, 13, and 19 (for a total of 15 maintenance doses). The most common adverse reactions were increased creatinine, dysuria, hematuria, urinary frequency, urinary urgency, and urinary tract infection. This article summarizes the data and FDA thought process supporting the approval of N-803 with BCG."

FDA event • Journal • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Nephrology • Oncology • Solid Tumor

INTERRUPT-HIV: Interleukin-15 to Promote Post-ART Control of HIV (clinicaltrials.gov) - P2 | N=20 | Enrolling by invitation | Sponsor: Michael Peluso, MD

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

QUILT-505: PD-L1 t-haNK, N-803 IL-15sa and Cetuximab for Recurrent, Metastatic HNSCC (clinicaltrials.gov) - P2 | N=25 | Recruiting | Sponsor: Glenn J. Hanna | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Phase 3 Clinical Trial ResQ201A of N-803 (NAI), Tislelizumab and Docetaxel Vs. Docetaxel Monotherapy for Advanced NSCLC Resistant to ICI Therapy (IASLC-WCLC 2025) - P3 | "Important assessments are changes in the tumor size, if any, and how long it lasts, referred to as the disease control rate, the objective response rate, and progression-free survival. Determination of safety is very important, therefore vital signs and changes in laboratory tests will be recorded, as well as adverse events (AEs) of all severity using the NCI CTCAE v5.0 system."

Clinical • IO biomarker • Metastases • Monotherapy • P3 data • Bladder Cancer • Esophageal Cancer • Genito-urinary Cancer • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Solid Tumor • ALK

Phase 3 Trial ResQ201A of NAI Plus Tislelizumab and Docetaxel Vs. Docetaxel Monotherapy for Advanced or Metastatic NSCLC Resistant to ICI Therapy (IASLC-WCLC 2025) - P3 | "2024; 19(10) Suppl.] have demonstrated the potential for the IL-15 receptor superagonist nogapendekin alfa inbakicept (NAI; or N-803) as a novel lymphocyte stimulating agent (LSA) to enhance ICI efficacy, prolonging progression-free survival (PFS) and overall survival (OS) when used in combination with an ICI. Secondary efficacy endpoints are the immune disease control rate (iDCR - iCR + iPR + iSD [≥ 2 months]) per iRECIST; progression-free survival (iPFS), overall response rate (iORR) and duration of response (iDOR). Safety is assessed by AEs and SAEs graded using the NCI CTCAE v5.0."

Metastases • Monotherapy • P3 data • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • IL15

A Study to Examine Anktiva for the Treatment of COVID-19. (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: ImmunityBio, Inc.

New P2 trial • Infectious Disease • Novel Coronavirus Disease

Traditional and next-generation bacillus Calmette-Guérin based treatment strategies for bacillus Calmette-Guérin unresponsive non-muscle-invasive bladder cancer in the era of emerging therapies. (PubMed, Curr Opin Urol) - "Despite its limited efficacy as monotherapy in unresponsive cases, BCG retains therapeutic relevance as part of combination strategies that enhance its immunologic activity. Emerging data suggest that these BCG-based regimens offer a promising, bladder-sparing alternative for patients who are ineligible for or decline radical cystectomy. Ongoing and future trials will be essential to define optimal combinations and identify which patients are most likely to benefit, thereby enabling appropriate patient selection."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Open Label, Phase 2 Study of CD19t-haNK and N-803 in Combination With Rituximab in Participants With Relapsed/ Refractory B-cell Non- Hodgkin Lymphoma. (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: ImmunityBio, Inc.

New P2 trial • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Therapeutic CD8+ T cell tissue retention and immunomodulation during ART interruption fail to prevent SIV rebound. (PubMed, Proc Natl Acad Sci U S A) - "After ATI and viral rebound, activated SIV-specific CD8+ T cells increased in frequency in LT of FTY720-treated RMs but failed to become cytotoxic or control plasma viremia compared to controls, even when combined with αPD1 and N-803. These findings indicate that LT-localized CD8+ T cells alone may be insufficient to delay or prevent plasma viral rebound during ATI."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • CD4 • IL15

A Phase II Study With a Safety Run-In of the Addition of N-803 to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2 | N=54 | Not yet recruiting | Sponsor: St. Jude Children's Research Hospital | Initiation date: Jul 2025 ➔ Dec 2025

Trial initiation date • Neuroblastoma • Oncology • Solid Tumor • CSF2

INTERRUPT_LC: A Study to Assess Anktiva in Patients With Long Covid-19. (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: ImmunityBio, Inc.

New P2 trial • Infectious Disease • Novel Coronavirus Disease

Immunotherapy Combination: Irradiated PD-L1 CAR-NK Cells Plus Pembrolizumab Plus N-803 for Subjects With Recurrent/Metastatic Gastric or Head and Neck Cancer (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=55 ➔ 18

Enrollment change • Enrollment closed • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

A Phase II Study With a Safety Run-In of the Addition of N-803 to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2 | N=54 | Not yet recruiting | Sponsor: St. Jude Children's Research Hospital

New P2 trial • Neuroblastoma • Oncology • Solid Tumor • CSF2

CARMEN-803: N-803 Maintenance Therapy Post CAR T-cell Therapy in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=13 | Not yet recruiting | Sponsor: University of Utah | Trial completion date: Sep 2029 ➔ Sep 2031 | Trial primary completion date: Sep 2028 ➔ Sep 2030

Trial completion date • Trial primary completion date • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ImmunityBio Reports 60% Increase in Revenue in Q2 2025, with Year-to-Date Sales of $43 Million and 246% Unit Growth Since J-Code with Regulatory Updates (ImmunityBio Press Release) - "Key Highlights: Q2 2025 Revenue Growth with Continued Strong Sales Momentum: $26.4 million, up 60% from Q1 2025, with year-to-date sales of ~$43 million; ANKTIVA Unit Growth Since J-Code: 246% unit sales volume growth in 1H 2025 compared to 2H 2024....Separately, ImmunityBio has applied to the National Comprehensive Cancer Network (NCCN) to seek expansion of the BCG-unresponsive NMIBC guidelines to include papillary-only disease, in addition to the currently recognized CIS with or without papillary disease. The NCCN is expected to review the submission at its August 2025 meeting."

NCCN guideline • Sales • Bladder Cancer