aldoxorubicin (INNO-206) / LadRx, Xoma - LARVOL DELTA

QUILT-3.091 NANT Chordoma Vaccine vs Radiation in Subjects With Unresectable Chordoma. (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: ImmunityBio, Inc. | Phase classification: P1b/2 ➔ P1/2

Phase classification • Chordoma • Oncology • Solid Tumor

Case report: PD-L1-targeted high-affinity natural killer cells and IL-15 superagonist N-803-based therapy extend overall survival of advanced metastatic pancreatic cancer patients. (PubMed, Front Oncol) - "From late 2019 to 2021, single-patient Investigational New Drug (spIND) protocols for five mPC patients were designed and approved that generally comprised combined Abraxane (nab-paclitaxel) and gemcitabine therapy with experimental therapeutics N-803, PD-L1-targeted high-affinity natural killer (PD-L1 t-haNK) cells, and aldoxorubicin, a serum albumin-binding doxorubicin prodrug. Some patients also received stereotactic body radiation therapy (SBRT), cyclophosphamide, pembrolizumab, nivolumab, and/or experimental ETBX-051 (brachyury) and/or ETBX-061 (MUC1) vaccines...The OS of 13, 26.9, and 23.2 months for three patients is particularly notable. The findings here support the ongoing clinical investigations of N-803 and PD-L1 t-haNK cells in combination therapy."

Journal • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9 • MUC1 • PD-L1

Machine learning-enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations. (PubMed, Brief Bioinform) - "In summary, our effective comprehensive virtual screening workflow successfully repurposed two novel drugs (aldoxorubicin and quarfloxin) as promising anti-Mtb candidates. The verification results provide useful information for the further development and clinical verification of anti-TB drugs."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

QUILT-3.071: QUILT 3.071: NANT Colorectal Cancer (CRC) Vaccine (clinicaltrials.gov) - P1/2 | N=2 | Terminated | Sponsor: ImmunityBio, Inc. | Phase classification: P1b/2 ➔ P1/2 | N=332 ➔ 2 | Active, not recruiting ➔ Terminated; low enrollment

Enrollment change • Metastases • Phase classification • Trial termination • Colorectal Cancer • Oncology • Solid Tumor

LadRx Planning NDA Submission under 505(b)(2) for Aldoxorubicin and Other Updates (Businesswire) - "LadRx Corporation...is pleased to announce that the Company is restarting a process to seek marketing approval of aldoxorubicin under the provisions of the FDA’s Section 505(b)(2)....In 2017, following discussions between LadRx and the FDA...LadRx initiated work to assemble the data to support a marketing approval under section 505(b)(2) for aldoxorubicin for the treatment of soft tissue sarcoma. While this work was ongoing, LadRx entered a license agreement with Nantcell...which stopped the 505(b)(2) process. With the termination of the aldoxorubicin license agreement between LadRx and NantCell in June 2024, LadRx regained control of aldoxorubicin....Subject to receiving additional funding, LadRx plans to request a pre-NDA meeting with the FDA mid-2025 to confirm the requirements that were discussed between the Company and the FDA prior to the out-licensing of aldoxorubicin in 2017."

FDA event • Soft Tissue Sarcoma

QUILT-88: Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=328 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Oct 2024 ➔ Oct 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Recurrent pancreatic cancer treated with N-803 and PD-L1 t-haNK followed by an EGFR-targeted nanocell drug conjugate. (PubMed, Oncologist) - "The epidermal growth factor receptor-targeted antibody-nanocell conjugate E-EDV-D682 provides tumor-targeted chemotherapy in the form of its anthracycline metabolite PNU159682 (nemorubicin) cargo and is currently being studied in combination with immunomodulatory EDVs delivering the adjuvant α-galactosyl ceramide (GC)...Under the initial single-patient Investigational New Drug (spIND) protocol, the patient received N-803, PD-L1 t-haNK cells, and the albumin doxorubicin conjugate aldoxorubicin for ~27 months...Due to progression, a second spIND protocol was designed whereby the patient received E-EDV-D682 plus EDV-GC for more than 24 months, which resulted in stable disease and the patient's continued survival at the time this report was written. The patient's extended survival despite the dire prognosis associated with recurrent mPC points to the merits of this temporal combination regimen in overcoming immuno-chemo resistance with enhanced immune activity..."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • EGFR • IL15 • PD-L1

QUILT-3.080: NANT Pancreatic Cancer Vaccine (clinicaltrials.gov) - P1/2 | N=3 | Terminated | Sponsor: ImmunityBio, Inc. | Phase classification: P1b/2 ➔ P1/2 | N=173 ➔ 3 | Unknown status ➔ Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

Enrollment change • Phase classification • Trial termination • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

QUILT-3.090: NANT Squamous Cell Carcinoma (SCC) Vaccine: Subjects With SCC Who Have Progressed (clinicaltrials.gov) - P1/2 | N=4 | Terminated | Sponsor: ImmunityBio, Inc. | N=65 ➔ 4 | Unknown status ➔ Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

Enrollment change • Trial termination • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

QUILT-88: Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=328 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial primary completion date: Jun 2024 ➔ Oct 2024

Metastases • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

QUILT-3.067: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With TNBC Who Have Progressed on or After Standard-of-care Therapy. (clinicaltrials.gov) - P1/2 | N=9 | Terminated | Sponsor: ImmunityBio, Inc. | N=79 ➔ 9 | Trial completion date: Oct 2023 ➔ Jan 2024 | Active, not recruiting ➔ Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

Enrollment change • Trial completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Acid-sensitive prodrugs; a promising approach for site-specific and targeted drug release. (PubMed, Eur J Med Chem) - "These prodrugs include albumin-binding prodrugs (Aldoxorubicin and DK049), polymeric micelle (NC-6300), polymer conjugates (ProLindac™), and an immunoconjugate (IMMU-110). The article encompasses a broad spectrum of studies focused on the development of acid-sensitive prodrugs for anticancer, antibacterial, and anti-inflammatory agents. Finally, the challenges associated with the acid-sensitive prodrug strategy are discussed, along with future directions."

Journal • Review • Infectious Disease • Oncology

Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=135 | Completed | Sponsor: ImmunityBio, Inc. | Unknown status ➔ Completed | Phase classification: P2b ➔ P2

Metastases • Phase classification • Trial completion • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

LadRx and ImmunityBio Mutually Agree to Terminate Aldoxorubicin License (Businesswire) - "LadRx Corporation...is pleased to announce that the Company and NantCell, Inc...together with NantCell’s parent company ImmunityBio, Inc. ('ImmunityBio'), have agreed to a mutual termination of the license of aldoxorubicin entered into in 2017...With the termination of the license agreement between LadRx and NantCell, LadRx regains control of aldoxorubicin...XOMA consented to the mutual termination of the LadRx-NantCell agreement in order to facilitate the return of the program to LadRx...The agreement between LadRx and XOMA regarding future royalties and milestones associated with arimoclomol is not affected by the termination of the aldoxorubicin license between LadRx and NantCell....'we continue to march LADR-7 towards the clinic and remain on track for filing an IND application for LADR-7 in the third or fourth quarter of 2024.'"

IND • Licensing / partnership • CNS Disorders • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma (clinicaltrials.gov) - P2 | N=126 | Completed | Sponsor: ImmunityBio, Inc. | Unknown status ➔ Completed | Phase classification: P2b ➔ P2

Metastases • Phase classification • Trial completion • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

QUILT-3.070:Pancreatic Cancer Vaccine: Subjects With Pancreatic Cancer Who Have Progressed on or After Standard-of-care Therapy (clinicaltrials.gov) - P1/2 | N=4 | Terminated | Sponsor: ImmunityBio, Inc. | N=173 ➔ 4 | Unknown status ➔ Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

Enrollment change • Trial termination • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

QUILT-88: Combination Immunotherapy Plus Standard-of-Care Chemotherapy Versus Standard-of-Care Chemotherapy for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=328 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

QUILT-3.067: NANT Triple Negative Breast Cancer (TNBC) Vaccine: Molecularly Informed Integrated Immunotherapy in Subjects With TNBC Who Have Progressed on or After Standard-of-care Therapy. (clinicaltrials.gov) - P1/2 | N=79 | Active, not recruiting | Sponsor: ImmunityBio, Inc. | Trial completion date: Jan 2023 ➔ Oct 2023 | Trial primary completion date: Dec 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Physalis Mottle Virus-Like Nanocarriers with Expanded Internal Loading Capacity. (PubMed, Bioconjug Chem) - "Specifically, the A31C and S137C mutants show a greater than 10-fold increased rate of reactivity towards thiol-reactive small molecules, and PhMV Cys1 (A31C), PhMV Cys2 (S137C), and PhMV Cys1+2 (double mutant) VLPs display up to three-fold increased internal loading of the small molecule chemotherapeutics aldoxorubicin and vcMMAE and up to four-fold increased internal loading of the MRI imaging reagent DOTA(Gd). These results further improve upon a promising plant virus-based nanocarrier system for use in targeted delivery of small-molecule drugs and imaging reagents in vivo."

Journal

XOMA Acquires Royalty and Milestone Economics to Phase 3 First-In-Class Orphan Disease Asset for Niemann-Pick Disease Type C (NPC) and Phase 2 Oncology Asset (GlobeNewswire) - "XOMA Corporation...announced today it has acquired the royalty and milestone rights associated with two assets from LadRx Corporation...aldoxorubicin, an albumin-linked formulation of doxorubicin....Should aldoxorubicin be approved for marketing, XOMA will receive a mid-single-digit to mid-teens royalty rate on aldoxorubicin commercial sales depending upon the indication, in addition to potential milestone payments of up to $343 million in development and commercial milestones. LadRx will be entitled to receive up to $6 million in certain pre-specified milestones associated...and aldoxorubicin. XOMA acquired these royalty and milestone interests for $5 million."

M&A • Brain Cancer • Breast Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Glioma • Kaposi Sarcoma • Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Soft Tissue Sarcoma • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer

Overall survival in patients with metastatic or locally advanced pancreatic cancer following chemoradiation with novel combination of aldoxorubicin, N-803 IL-15 superagonist, and PDL1- NK cell therapy. (ASCO-GI 2023) - P2 | " We report data from a multi-center study, on 83 3rd line or greater, subjects treated with low dose, chemo radiation Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV); Cyclophosphamide (50 mg PO BID) and low dose SBRT. Historical 3 month median OS in 3rd line metastatic pancreatic cancer patients has been exceeded. A doubling of survival in 3rd line is seen in QUILT 88 investigating a novel combination immunotherapy protocol of low-dose chemoradiation, N-803 and PDL1 t-haNK therapy. Updated data will be presented."

Clinical • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

NANT cancer vaccine an orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T cell therapy in patients with third line or greater metastatic pancreatic cancer. (ASCO-GI 2019) - P1b/2; "Treatment will occur in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, oxaliplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, engineered allogeneic high affinity CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral vector-based CEA vaccine (Ad-CEA), yeast vector-based RAS vaccine (Ye-RAS), and an IgG1 PD-L1 inhibitor, avelumab. Secondary endpoints include ORR, DCR, PFS, and OS. A maximum of 24 patients will be enrolled."

Clinical • Immunogenic cell death • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Highlights From the 2022 ASH Annual Meeting and Exposition (THE ASCO POST) - "The 2022 American Society of Hematology (ASH) Annual Meeting and Exposition took place in the vibrant city of New Orleans. The meeting brought together tens of thousands of participants from across the world to present and discuss the results of studies that ranged from hypothesis-generating to practice-changing. Below are short summaries of some of the data we thought were most compelling this year."

Online posting

Promising survival and disease control in third-line or greater metastatic or locally advanced pancreatic cancer patients following chemo-radiation and novel combination of aldoxorubicin, N-803 IL-15 superagonist, and PDL1- NK cell therapy. (ASCO-GI 2022) - P2 | " We report data from a multi-center study, on 55 3rd line or greater, subjects treated with low dose, chemo radiation Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV); Cyclophosphamide (50 mg PO BID) and low dose SBRT. Historical 3 month median OS in 3rd line metastatic pancreatic cancer patients has been exceeded. Early safety and promising efficacy is seen in QUILT 88 investigating a novel combination immunotherapy protocol of low-dose chemoradiation, N-803 and PDL1 t-haNK therapy. Updated data will be presented."

Clinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Phase 2 Quilt 88 trial of DAMP inducers combined with IL15 superagonist, N-803, and anti–PD-L1 NK cell therapy more than doubles historical overall survival in patients with third- to sixth-line advanced pancreatic cancer. (ASCO 2022) - P2 | "Patients were treated every 4 weeks with low dose DAMP inducing chemo modulating therapy including Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV), Aldoxorubicin HCl (150 mg/m2 IV), Cyclophosphamide (50 mg PO BID) and low-dose SBRT. Early safety and efficacy is seen in QUILT 88 of the novel immunotherapy combination of DAMP inducers, NK and T cell activation, and PDL1 t-haNK cell therapy in Pancreatic Cancer. OS in 3rd line (6.3 months) exceeds historical results of 3 months across 19 trials (Manax ASCO GI 2019) and compares favorably with the 6.1 months in 2nd line patients in NAPOLI-1."

Clinical • IO biomarker • P2 data • Anemia • Cardiovascular • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pancreatic Cancer • Solid Tumor • Thrombocytopenia • IL15