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

QUILT 3.076 phase 1 study of memory-like cytokine-enriched natural killer (M-CENK) cells plus N-803 in locally advanced or metastatic solid tumors. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT04898543 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Metastases • P1 data • Oncology • Solid Tumor

Association of lymphopenia rescue and CA19-9 levels with overall survival following IL-15 superagonist N-803 and PD-L1 t-haNK chemo-immunotherapy for 3rd line or greater metastatic pancreatic cancer. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04390399 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Lymphopenia • Metastases • Hematological Malignancies • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

ImmunityBio to Showcase Advances for Bladder and Prostate Cancer at American Urological Association (AUA) Annual Meeting (Businesswire) - "ImmunityBio...will announce new clinical findings for ANKTIVA (nogapendekin alfa inbakicept-pmln) in non-muscle invasive bladder cancer carcinoma in situ (NMIBC CIS) and updated data on papillary disease without CIS at the American Urological Association Annual Meeting (AUA 2025)....Oral presentation provides update from QUILT-3.032 on durable complete responses to ANKTIVA plus BCG in BCG-unresponsive non-muscle invasive bladder cancer carcinoma in situ (NMIBC CIS) with or without Ta/T1 papillary disease and papillary disease alone. ImmunityBio to present keynote events on NMIBC and experience in prostate cancer, unveiling lymphopenia, the Absolute Lymphocyte Count (ALC) biomarker for all tumor types, and the ‘Cancer BioShield’."

Clinical data • Bladder Cancer • Prostate Cancer

Generation of cytokine-induced memory-like PD-L1 t-haNK (NK-92®) cells (AACR 2025) - "We show here that the Natural Killer cell line NK-92®, or 'activated' NK (aNKTM), can acquire a memory-like phenotype upon overnight induction with IL-12, IL-18, and the IL-15 superagonist N-803, as evidenced by increased steady-state IFNγ secretion (>50-fold increase) and up-regulation of CD25. This increase would then drive upregulation of PD-L1 expression on neighboring tumor cells, creating an expanding wave of targets sensitized to killing by PD-L1 t-haNK cells. A next generation, memory-like PD-L1 t-haNK cell line equipped with inducible safety switch features to remove the need for irradiation and extend their half-life in patients is being developed and would constitute a promising "off-the-shelf" cellular therapy against immunologically cold cancers."

IO biomarker • Oncology • IFNG • IL12A • IL18 • IL2RA • PD-L1

Immunogenic modulation with the ATR inhibitor tuvusertib enhances NK-mediated killing of prostate cancer [WITHDRAWN] (AACR 2025) - "Furthermore, tuvusertib treatment increased PD-L1 expression on the DU145 cells, which is associated with enhanced donor NK killing in the presence of avelumab and augmented sensitivity to PD-L1 t-haNK cells.Next, the anti-tumor effect of combining tuvusertib with N-803 (provided by ImmunityBio, Culver City, CA, USA) was investigated. Furthermore, tuvusertib synergized with N-803, resulting in a superior anticancer response. This provides a rationale for further investigation of this combination therapy."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • TNFRSF10B

Update of Product Revenue, Net Preliminary Results of Operations (Businesswire) - "With a permanent J-code (J9028) awarded in January 2025, ImmunityBio’s Q1 2025 ANKTIVA unit sales volume grew 150% over unit sales volume in Q4 2024; For the three-month period ended March 31, 2025, ImmunityBio achieved estimated net product revenue of approximately $16.5 million, surpassing net product revenue of $7.2 million in the prior quarter, a 129% quarter-over-quarter increase; ANKTIVA sales momentum continues to trend upward in 2025, with sales volume in March representing a 69% increase month-over-month from February."

Sales • Bladder Cancer

ImmunityBio Announces FDA Submissions of Supplemental BLA for NMIBC Papillary Disease (Businesswire) - "In Q1, ImmunityBio completed the submission to the FDA of an sBLA for the use of ANKTIVA plus BCG in BCG-unresponsive NMIBC in the papillary indication. Subject to regulatory approvals, the addition of the papillary indication expands the patient population benefiting from this therapy beyond the currently approved indication of bladder carcinoma in situ (CIS) with or without papillary disease and allows more patients to avoid the high morbidity and mortality associated with radical cystectomy. The data submitted to the FDA included efficacy results demonstrating durable complete remissions in patients with BCG unresponsive NMIBC papillary disease. In 88% and 82% of subjects, the probability of avoiding surgical removal of the bladder was achieved for as long as 2 and 3 years respectively, following treatment with ANKTIVA plus BCG."

FDA filing • Bladder Cancer

ImmunityBio Announces FDA Submissions for Expanded Access of ANKTIVA to Treat Lymphopenia (Businesswire) - "In Q2, the company submitted to the U.S. Food and Drug Administration (FDA) an Expanded Access Protocol (EAP) for ANKTIVA for the treatment of lymphopenia as a BioShield against the adverse effects of chemotherapy, radiation and checkpoint inhibitors, following authorization of a Regenerative Medicine Advanced Therapy (RMAT) designation for this indication in Q1."

FDA filing • Oncology

QUILT-3.032: A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2/3 | N=190 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Oct 2028 ➔ Mar 2029 | Trial primary completion date: Apr 2025 ➔ Oct 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

The Power of ANKTIVA to Overcome Lymphopenia through NK & Memory T Cells to Achieve Durable Responses in Urological Diseases – Duration Matters | Sponsored by ImmunityBio (AUA 2025) - "Sponsored by ImmunityBio"

Lymphopenia • Hematological Malignancies • Urology

An Update on QUILT-3.032: Complete Responses to N-803 plus BCG Therapy in BCG-Unresponsive Bladder Carcinoma In Situ (CIS) With or Without Ta/T1 Papillary Disease (AUA 2025) - P2/3 | "These findings derived from the fully-enrolled cohort A of QUILT 3.032, demonstrate the stability of the CR rate and confirm the durability of responses in participants with BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease. They further demonstrate a positive association between achievement of a CR and both PFS and cystectomy avoidance. These updated results, together with previously reported safety and quality-of-life, indicate a favorable risk:benefit ratio for patients with bladder CIS +/- Ta/T1 papillary disease treated with N-803 plus BCG."

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

ImmunityBio to Host Key Opinion Leader and Investor Meeting to Provide Updates on Clinical Programs and ANKTIVA Commercial Launch (Businesswire) - "ImmunityBio, Inc...announced details about its Investor Day program to be held on Tuesday, April 15, 2025, at 10:00 am PDT....The discussions will include clinical and regulatory updates on the company’s bladder cancer program, regenerative medicine advanced therapy (RMAT) designations, including results on non-small cell lung cancer (NSCLC) and metastatic pancreatic cancer trials, as well as lymphopenia rescue data related to these trials (Cancer BioShield)."

Clinical • Bladder Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

N-803 Clinical Development Programs in NMIBC (EAU 2025) - "Sponsored by ImmunityBio."

Clinical • Bladder Cancer

N-803: A First-in-Class IL-15 Receptor Superagonist (EAU 2025) - "Sponsored by ImmunityBio."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • IL15

Reducing HIV Persistence in Lymph Nodes by Interleukin-15 (IL-15) Receptor Super-agonist (N-803) in Acute HIV Infection (clinicaltrials.gov) - P2 | N=14 | Active, not recruiting | Sponsor: Thai Red Cross AIDS Research Centre | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2024 ➔ Jun 2025

Enrollment closed • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Transforming non-muscle invasive bladder cancer (NMIBC) treatment: FDA approval of Anktiva in combination with BCG. (PubMed, Ann Med Surg (Lond)) - No abstract available

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

Matching-Adjusted Indirect Comparisons (MAIC) of TAR-200 vs FDA Approved Novel Agents in Bacillus Calmette-Guerin (BCG) Unresponsive High-Risk (HR) Non-Muscle Invasive Bladder Cancer (NMIBC) with Carcinoma in Situ (CIS) (ISPOR 2025) - "OBJECTIVES: FDA has approved pembrolizumab (pembro), nadofaragene firadenovec-vncg (nadofaragene), and nogapendekin alfa inbakicept-pmln (NAI) + BCG for the treatment of patients with BCG-unresponsive HR NMIBC with CIS. TAR-200 demonstrated statistically significant clinical benefit in CR rate at any time over FDA approved novel agents in BCG-unresponsive HR NMIBC with CIS and at first disease assessment compared to NAI + BCG. Further analyses will be conducted once additional follow-up is available for TAR-200."

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

Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption (clinicaltrials.gov) - P1 | N=118 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting | N=46 ➔ 118

Enrollment change • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

RV550: IL-15 Superagonist N-803 With ART in Acute HIV Infection Enhances T and NK Cell Proliferation (CROI 2025) - "DISCLAIMER: The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, the National Institutes of Health, the Department of Health and Human Services, or the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. The investigators have adhered to the policies for protection of human subjects as prescribed in AR-70-25."

IO biomarker • Human Immunodeficiency Virus • Infectious Disease • BCL2 • CD4 • CD8 • PRF1

Gut Microbiome Dynamics and Immune Responses in People With HIV Receiving N-803 (CROI 2025) - "The trends observed in this study highlight the intricate relationships between microbiota diversity and immune markers in HIV infection. Further research with larger sample sizes is necessary to better understand the role of the gut microbiome in modulating immune responses during N-803 therapy and its implications for HIV immunotherapy."

IO biomarker • Human Immunodeficiency Virus • Immune Modulation • Immunology • Infectious Disease • Oncology • CD8 • KLRC1

RV550: Safety and Virologic Outcomes in Blood and Lymph Nodes of N-803 With ART in Acute Infection (CROI 2025) - "While there was some evidence of a faster decline in viremia immediately post N-803 injection, differences in reservoir measurements were overwhelmed by the large fluctuations that occur over the first weeks of ART in acute infection, inter-host variability, and the small number of participants. To further explore the impact of N-803 on viral reservoirs, all eligible and consenting study participants will receive an additional single dose of N-803 followed by ATI until HIV viral load >1,000 copies/ml for a maximum of 4 weeks."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Viral Genetic Traits of Durable Control in Dual Immunotherapy-Treated SHIV-Infected Rhesus Macaques (CROI 2025) - "Background A recent study demonstrated that combined administration of N-803 (IL15 agonist) and the 10-1074 and 3BNC117 broadly neutralizing antibodies (bNAbs) results in durable virologic remission following ART cessation in SHIV-infected, ART-suppressed rhesus macaques (RM). Observed mutational patterns and glycosylation site disruption likely reflect evolutionary responses to pressure from neutralizing antibodies. Phenotypic characterization of the induced SHIV Env mutants will inform the development of HIV cure approaches."

IO biomarker • Human Immunodeficiency Virus • Infectious Disease • IL15

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=55 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

ImmunityBio Reports Sales Momentum & Unit Growth Since Permanent J-code Issuance (J9028) in January 2025 and Financial Results for Year End 2024 (Businesswire) - "With a permanent J-code (J9028) awarded in January 2025, ImmunityBio’s February 2025 ANKTIVA unit sales volume grew 97% over unit sales volume in December 2024; ANKTIVA sales momentum continues to trend upward quarter to date 2025, with sales volume in February representing a 67% increase month-over-month from January; Sales volume in the 2 months in 2025 to date shows a 69% increase over the sales volume in the 2 months prior (November and December 2024) and already exceeds the total units for all of Q4 2024; For the three-month period ending December 31, 2024 prior to permanent J-code approval, ImmunityBio achieved net product revenue of approximately $7.2 million, surpassing net product revenue of $6.0 million in the prior quarter, a 21% quarter over quarter increase."

Sales • Bladder Cancer

ImmunityBio Receives FDA RMAT Designation for ANKTIVA and CAR-NK for the Reversal of Lymphopenia in Patients Receiving Standard-of-Care Chemotherapy/Radiotherapy and in Treatment of Multiply Relapsed Locally Advanced or Metastatic Pancreatic Cancer (Businesswire) - "...RMAT designation follows clinical data of Absolute Lymphocyte Count (ALC) and significant Overall Survival (OS) correlations in QUILT trials across multiple tumor types....Company intends to submit...BLA for the indication of reversal of lymphopenia in patients receiving standard-of-care chemotherapy and/or radiation and for the treatment of locally advanced or metastatic pancreatic cancer, which includes the first-in-class CAR-NK (PD-L1 t-haNK). ImmunityBio to provide data from fully enrolled clinical trials in metastatic pancreatic cancer (QUILT-88) and in checkpoint relapsed NSCLC (QUILT-3.055, NSCLC Cohort) patients, as well as lymphopenia reversal across multiple tumor types (QUILT-3.055, All Cohorts), with supportive data of lymphocyte proliferation in healthy volunteers (QUILT-1.004). In addition, ImmunityBio intends to file an Expanded Access Policy (EAP) for ANKTIVA and PD-L1 t-haNK in combination with standard of care chemotherapy/radiotherapy within 15 days..."

FDA event • Non Small Cell Lung Cancer • Pancreatic Cancer