HCW9218 / HCW Biologics, ImmunityBio - LARVOL DELTA

HCW9218 for Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=21 | Completed | Sponsor: ImmunityBio, Inc. | Active, not recruiting ➔ Completed | N=60 ➔ 21

Enrollment change • Trial completion • Oncology • Pancreatic Cancer • Solid Tumor

HCW9218 in Select Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Masonic Cancer Center, University of Minnesota | Active, not recruiting ➔ Completed | Trial completion date: Feb 2026 ➔ Feb 2025

Trial completion • Trial completion date • Solid Tumor

Development of analytical methods for detection of anti-drug antibodies neutralizing IL-15 and TGF-β RII activity. (PubMed, J Immunoassay Immunochem) - "Interestingly, circulating TGF-β present in sera mimicked the action of NAb by binding to soluble TGF-β RII resulting in higher baseline neutralization activity. These methods proved to be suitable for detection of ADAs and NAbs in HCW9218 clinical samples or analogs sharing similar receptor/cytokine subunits and/or downstream signaling pathways."

Journal • IL15 • TGFB1

Enhancing Anti-HIV Activity of duo CAR-T Cells by Combining TGF-ß Inhibition with IL-15 Stimulation (IMMUNOLOGY 2025) - "duoCAR-T cells treated with HCW9218, but not control variants, showed increased cytotoxicity and HIV suppression under TGF-ß conditions. The HCW9218 cytokine-based scaffold holds promise as an adjunctive therapy to enhance CAR-T efficacy, offering potential for a more durable anti-HIV-1 immune response.Keywords: Cells T Cells; Infections Viral; Molecules Cytokines; Processes Inflammation; Techniques/Approaches Gene Therapy"

CAR T-Cell Therapy • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4 • CD8 • IL15 • STAT5

HCW Biologics Reports Fourth Quarter and Fiscal Year 2024 Business Highlights and Financial Results (GlobeNewswire) - "Clinical Development Results:...As of December 31, 2024, the Company was required to close the Phase 2 clinical study to evaluate HCW9218 in combination with neoadjuvant chemotherapy in ovarian cancer sponsored by the University of Pittsburgh Medical Center, as required under the Settlement Agreement, due to lack of enrollment."

Trial termination • Ovarian Cancer

Augmenting HIV-Specific CAR-T Cell Functionality by Treatment With Novel Cytokine-Based Scaffold (CROI 2025) - "Conclusions HCW9218 neutralizes TGF-β activity and thereby prevents TGF-β-mediated inhibition of duoCAR-T cell proliferation, cytotoxicity, and HIV suppression. HCW9218 may serve as an adjunct therapy to increase the anti-HIV activity of duoCAR-Ts in PLWH with elevated levels of TGF-β to enable sustained anti-HIV immune responses."

CAR T-Cell Therapy • IO biomarker • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4 • CD8 • IL15 • STAT5 • TGFB1

Antitumor Activity of Neoadjuvant Chemotherapy with or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Haider Mahdi | N=33 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Metastases • Trial withdrawal • Oncology • Ovarian Cancer • Solid Tumor • CD8

PHASE 1 STUDY OF HCW9218, A BIFUNCTIONAL TGF- Β ANTAGONIST/IL-15 PROTEIN COMPLEX, IN PATIENTS WITH ADVANCED, RECURRENT SOLID TUMORS (IGCS 2024) - "Eighteen received at least one cycle of HCW9218. Demographics are shown in Table 1. HCW9218 was dosed at 0.25, 0.50, 0.80, and 1.2 mg/kg (n = 3/cohort with 6 patients in the expansion phase)."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • CD8 • IL15 • TGFB1

Antitumor Activity of Neoadjuvant Chemotherapy With or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Haider Mahdi | Not yet recruiting ➔ Recruiting | Phase classification: P1b ➔ P2 | Trial completion date: Jan 2027 ➔ Jan 2028 | Trial primary completion date: Jan 2024 ➔ May 2026

Enrollment open • Metastases • Phase classification • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Solid Tumor • CD8

HCW Biologics Reports Fourth Quarter 2023 and Fiscal Year End Financial Results And Business Highlights (GlobeNewswire) - P1b/2 | N=60 | NCT05304936 | Sponsor: HCW Biologics | P1 | N=18 | NCT05322408 | "The Phase 1 clinical trial to evaluate HCW9218 in solid tumors and the Phase 1b clinical trial to evaluate HCW9218 in pancreatic cancer were completed in February 2024. In the Phase 1 study, over 70% of patients with ovarian cancer (5/7) showed evidence of stable disease. In the Phase 1b study, 13% (2/15) of patients who participated in the study showed evidence of stable disease. The first Phase 2 clinical study to evaluate HCW9218 in patients with ovarian cancer will be sponsored by the University of Pittsburgh Medical Center. This fully randomized trial will have one arm of the study treating patients with HCW9218 with a neoadjuvant chemotherapy."

New P2 trial • P1 data • Trial status • Ovarian Cancer • Pancreatic Cancer

HCW9218 in Select Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2027 ➔ Feb 2026 | Trial primary completion date: Jan 2027 ➔ Feb 2025

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

HCW9218 for Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=60 | Active, not recruiting | Sponsor: HCW Biologics | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2 ➔ P1/2

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

HCW Biologics Reports Third Quarter 2023 Financial Results And Recent Business Highlights (GlobeNewswire) - "The Company expects to complete the initial phase of both of its ongoing clinical studies in cancer indications in late 2023 or early 2024."

Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Investigator Sponsor of HCW Biologics’ Phase 1 Clinical Trial Presented Human Data Readout and Anti-Cancer Mechanism of Action of HCW9218 at 38th SITC Annual Meeting (GlobeNewswire) - P1 | N=24 | NCT05322408 | "Highlights of data presented at SITC include: 87% (13/15) had >4 lines of prior therapy. Tumor types included: Ovarian (n=6), Colorectal (n=4), Rectal (n=3), and Liver (n=2); Analysis of patients’ pre- and post-treatment blood and tumor biopsy specimens revealed that HCW9218 induced National Killer ('NK') cell and CD8⁺ T cell activation, proliferation, and infiltration into the tumor microenvironment which correlated with disease stabilization; CW9218 significantly reduced blood levels of TGF-β in cancer patients in a dose-dependent manner, without causing treatment-emergent skin lesions and bleeding events previously reported with TGF-β antagonists in clinic....With these strong results as a foundation, we believe we will be in a position to pivot to initiate our first Phase 2 clinical trial this year.'"

New P2 trial • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hepatocellular Cancer • Liver Cancer • Oncology • Ovarian Cancer • Rectal Cancer • Solid Tumor

Pre-clinical and first-in-human studies of HCW9218, a bifunctional TGF-β antagonist/IL-15 protein complex, in advanced solid tumors (SITC 2023) - P1 | "5 mg/kg in heavily pretreated advanced solid tumor patients resulted in immune cell activation, proliferation, and infiltration into the tumor microenvironment without causing unacceptable toxicity. HCW treatment presents a promising approach to enhancing the antitumor activity of immune checkpoint inhibitors in patients with solid tumors."

IO biomarker • Metastases • P1 data • Preclinical • Breast Cancer • Melanoma • Oncology • Solid Tumor • CD8 • IL15 • TGFB1

Efficient generation of CD8+ TSCM CD19 chimeric antigen receptor T-cells (CAR-T cells) by treatment with novel cytokine-based scaffolds (SITC 2023) - "Methods HCW Biologics has developed a bifunctional fusion molecule (HCW9218), which incorporates the extracellular domain of TGFβRII and an IL-15/IL-15 receptor α complex into a tissue factor-based scaffold...Our results indicated that treatment with cytokine scaffolds generate a large population of CD19 CAR-Ts with an early memory T-cell phenotype which should enhance the persistence of CAR-Ts in patients. This strategy will likely enhance long-term in vivo survival of CAR-T therapy and enable sustained suppression of relapsed/refractory B-cell malignancies."

CAR T-Cell Therapy • Hematological Malignancies • Leukemia • Oncology • CD8 • IL15 • IL21 • IL7 • TGFB1

Masonic Cancer Center, University of Minnesota to Present Data in Poster Presentation Human Data Readout for Phase 1 Study to Evaluate HCW9218 in Solid Tumors at SITC 38th Annual Meeting (GlobeNewswire) - "HCW Biologics Inc...will have a human data readout at the 38th Annual Meeting of the Society for Immunotherapy of Cancer ('SITC') from an ongoing Phase 1 clinical trial to evaluate HCW9218 in patients with chemo-refractory/chemo-resistant solid tumors, conducted by the Masonic Cancer Center, University of Minnesota. The poster will be presented by Melissa A. Geller, M.D., M.S., Professor and Division Director of Gynecologic Oncology in the Department of Obstetrics, Gynecology and Women’s Health at the University of Minnesota, a Principal Investigator for this study."

P1 data • Preclinical • Oncology • Solid Tumor

HCW Biologics Participating at H.C. Wainwright 25th Annual Global Investment Conference in New York on September 11 – 13, 2023 (GlobeNewswire) - "HCW Biologics Inc...will participate in the H.C. Wainwright 25th Annual Global Investment Conference in New York City....The update on clinical development will include a Phase 1 clinical trial to evaluate HCW9218 in solid tumors, sponsored by The Masonic Cancer Center, University of Minnesota ('UMN'). UMN is now dosing patients at the highest dose level. Due to clinical protocol requirements, dosing of the remaining patients is expected to take place in the next 3 to 6 months....In a second ongoing clinical study, a Company-sponsored Phase 1b/2 clinical trial to evaluate HCW9218 in advanced pancreatic cancer, the Company expects this study to be completed in the first half of 2024."

Trial completion date • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Pancreatic Cancer • Refractory Ovarian Cancer • Solid Tumor

HCW Biologics Reports Second Quarter 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "R&D expenses for the quarter ended June 30, 2022 and 2023 were $2.0 million and $1.6 million, respectively, a decrease of $353,216, or 18%. R&D expenses for the six months ended June 30, 2022 and 2023 were $3.8 million and $3.9 million, respectively, an increase of $112,921, or 3%. The change is primarily attributable to a decrease in preclinical expenses and manufacturing costs and an increase in costs associated with clinical trial activities. As of June 30, 2023, the Company anticipates it has the required supplies of its lead molecules, HCW9218 and HCW9302, in place to provide for planned clinical development activities for the next 24 months...In first half of 2023, IND-enabling activities focused on additional research studies required for the Company’s IND submission. The Company expects to submit an IND application for permission to conduct a clinical trial to evaluate HCW9302 in an autoimmune disorder by the end of 2023."

Commercial • IND • Oncology • Solid Tumor

HCW Biologics Reports Second Quarter 2023 Financial Results and Recent Business Highlights (GlobeNewswire) - "In a Phase 1 clinical trial to evaluate HCW9218 in the treatment of chemo-refractory/chemo-resistant solid tumors, sponsored by the Masonic Cancer Center, University of Minnesota, the first patient was dosed in the expansion phase of the trial....The Company expects this trial to be completed in the second half of 2023 and intends to disclose human clinical data from this trial and the mechanism of action underlying HCW9218 anti-cancer activities at a major industry conference prior to the end of the year. In a Company-sponsored Phase 1b clinical trial to evaluate HCW9218 in the treatment of chemo-refractory/chemo-resistant pancreatic cancer, the trial has completed two dose escalation cohorts and has begun a third, with no dose-limiting toxicity to date. The Company expects this trial to be completed late in 2023 or early 2024, with a human clinical data readout in the first half of 2024."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Bifunctional immunotherapeutic HCW9218 facilitates recruitment of immune cells from tumor draining lymph nodes to promote antitumor activity and enhance checkpoint blockade efficacy in solid tumors (AACR 2023) - P1, P1b/2 | "Collectively, the results of this studydemonstrated that HCW9218 treatment of mice bearing solid tumors resulted in modulating the TdLN immune landscape and invigorating T cells for enhanced checkpoint blockade therapy. HCW9218 are currently in two clinical trials (clinicaltrials.org: NCT05322408, NCT05304936) against chemo-resistant/refractory solid tumors."

Checkpoint block • Checkpoint inhibition • Clinical • Immune cell • Oncology • Solid Tumor • CD8 • HAVCR2 • IL15 • PTPRC • TGFB1

HCW Biologics Poster Presentation at AACR Annual Meeting 2023 (GlobeNewswire) - "HCW Biologics Inc...today announced that data for the mechanism underlying HCW9218 against solid tumors will be presented at the 2023 Annual Meeting of the American Association for Cancer Research to be held in Orlando, Florida from April 14 – April 19, 2023."

Preclinical • Oncology • Solid Tumor

Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice. (PubMed, Aging Cell) - "Long-term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases."

IO biomarker • Journal • Preclinical • Diabetes • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • TGFB1

HCW9218 for Advanced Pancreatic Cancer (clinicaltrials.gov) - P1b/2 | N=60 | Recruiting | Sponsor: HCW Biologics | Trial completion date: Apr 2023 ➔ Feb 2025 | Trial primary completion date: Mar 2023 ➔ Jan 2025

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

HCW Biologics Enters CRADA with National Cancer Institute (GlobeNewswire) - "HCW Biologics Inc...announced that under a Cooperative Research and Development Agreement (CRADA), the National Cancer Institute (NCI) and HCW Biologics Inc. (HCW Biologics) will collaborate to perform a Phase 1b/2 clinical study to evaluate the safety and tolerability of HCW Biologics’ proprietary agent, HCW9218, in patients with advanced/metastatic pancreatic cancer. The CRADA is entitled, A Phase 1b/2 Study of HCW9218, a Bifunctional TGF- β Antagonist/IL-15 Protein Complex, for Advanced Pancreatic Cancer'."

Licensing / partnership • Gastrointestinal Cancer • Oncology • Pancreatic Cancer