HB-201 / Hookipa Pharma - LARVOL DELTA

H-200-001: A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov) - P1/2 | N=198 | Completed | Sponsor: Hookipa Biotech GmbH | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Jan 2025 | Trial primary completion date: Jun 2025 ➔ Jan 2025

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

A Study of HB-202/HB-201 in People With Human Papilloma Virus 16-Positive Head and Neck Squamous Cell Cancer (HPV 16+ HNSCC) (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Phase classification: P2 ➔ P1

Phase classification • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study of HB-202/HB-201 in People With Human Papilloma Virus 16-Positive Head and Neck Squamous Cell Cancer (HPV 16+ HNSCC) (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Active, not recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study of HB-202/HB-201 in People With Human Papilloma Virus 16-Positive Head and Neck Squamous Cell Cancer (HPV 16+ HNSCC) (clinicaltrials.gov) - P2 | N=3 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Recruiting ➔ Active, not recruiting | N=51 ➔ 3

Enrollment change • Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

H-200-004: A Study of HB-202/HB-201 With Pembrolizumab in Patients With HPV16+ Recurrent/Metastatic Oropharyngeal Cancer (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: Hookipa Biotech GmbH | N=450 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Metastases • Trial withdrawal • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

H-200-001: A Phase 1/2 Study in Patients with HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov) - P1/2 | N=200 | Active, not recruiting | Sponsor: Hookipa Biotech GmbH | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Phase 2/3 Study of HB-202/HB-201 With Pembrolizumab in Patients With HPV16+ Recurrent/Metastatic Oropharyngeal Cancer (clinicaltrials.gov) - P2/3 | N=450 | Not yet recruiting | Sponsor: Hookipa Biotech GmbH

Metastases • New P2/3 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

HB-200 arenavirus-based immunotherapy plus pembrolizumab as first-line treatment of patients with recurrent/metastatic HPV16-positive head and neck cancer: Updated results. (ASCO 2024) - P1/2 | "HB-200 comprises an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively. Updated data of HB-200 arenavirus-based immunotherapy plus pembrolizumab continued to demonstrate a favorable safety profile and promising clinical activity as 1L treatment in patients with HPV16+ PD-L1+ R/M HNSCC and confirms previously reported data. The results suggest that the subgroup of patients with PD-L1 CPS ≥20 may benefit more from this treatment, which warrants further development in a randomized pivotal study. Clinical trial# NCT04180215."

Clinical • IO biomarker • Metastases • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • PD-L1

Neoadjuvant HPV16-specific arenavirus-based immunotherapy HB-200 plus chemotherapy followed by response-stratified de-intensification in HPV16+ oropharyngeal cancer: TARGET-HPV. (ASCO 2024) - P1/2 | "Building on our OPTIMA II results demonstrating that neoadjuvant chemotherapy/nivolumab led to deep responses in 71% of patients who went on to receive reduced radiation (RT), we hypothesized that adding HB-200 to chemotherapy to drive HPV16-specific anti-tumor immunity would be safe and effective to further deepen responses and facilitate more de-escalation. In this Phase 1 dose escalation investigator-initiated study, patients with non-metastatic HPV16+ OPC were treated with escalating doses of HB-201 single vector (Arm A) or HB-202/201 alternating vector (Arm B) x3 with neoadjuvant carboplatin AUC5 on day 1 and paclitaxel 100mg/m2 on days 1/8/15 of a 21-day cycle for 3 cycles. Deep responders (≥50% tumor shrinkage) received transoral robotic surgery (TORS) alone or RT to 50Gy +/- cisplatin, while non-responders (<50% shrinkage) received 50 or 70Gy of RT with cisplatin... Neoadjuvant HB-200/chemotherapy is safe and feasible with early efficacy signal in this..."

Clinical • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • CD8

A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Hookipa Biotech GmbH | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Mar 2024 ➔ Jun 2025

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

A Study of HB-202/HB-201 in People With Human Papilloma Virus 16-Positive Head and Neck Squamous Cell Cancer (HPV 16+ HNSCC) (clinicaltrials.gov) - P2 | N=51 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

HB-200 arenavirus-based immunotherapy plus pembrolizumab as a first-line treatment of patients with recurrent/metastatic HPV16 positive head and neck cancer (ESMO 2023) - P1/2 | "HB-200 is comprised of an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively. Conclusions Preliminary data with HB-200 arenavirus-based immunotherapy plus pembrolizumab demonstrate a favorable safety profile and preliminary efficacy when given as a 1L treatment of patients with R/M HPV16+ PD-L1+ HNSCC. Clinical trial# NCT04180215."

Clinical • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8

Characterization of tumor specific CD8+ T cell responses in patients with recurrent/metastatic HPV16-positive head and neck cancer receiving HB-200 monotherapy as second or later line treatment in a phase 1 study (SITC 2023) - "HB-200 is comprised of an alternating sequence of two replicating attenuated arenavirus vectors derived from LCMV (HB-201) and Pichinde virus (HB-202), respectively, expressing the same non-oncogenic HPV16 E7E6 fusion protein. Conclusions HB-200 monotherapy induces promising HPV16+ tumor-specific T cell responses and tumor infiltration in heavily pre-treated patients. This immune response coupled with clinical benefit in monotherapy suggests that HB-200 may enhance and strengthen current immunotherapy approaches by targeting specific tumor antigens."

Clinical • Metastases • Monotherapy • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IFNG

A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer (clinicaltrials.gov) - P1 | N=10 | Terminated | Sponsor: Hookipa Biotech GmbH | N=27 ➔ 10 | Recruiting ➔ Terminated; Sponsor decision.

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Cervical Cancer • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Hookipa Biotech GmbH

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

A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Hookipa Biotech GmbH | Trial completion date: Aug 2023 ➔ Jun 2025 | Trial primary completion date: Aug 2023 ➔ Jun 2025

IO biomarker • Metastases • Trial completion date • Trial primary completion date • Tumor mutational burden • Cervical Cancer • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TMB

A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Hookipa Biotech GmbH | Trial primary completion date: Jun 2023 ➔ Mar 2024

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

A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Hookipa Biotech GmbH | Trial completion date: Mar 2023 ➔ Aug 2023 | Trial primary completion date: Feb 2023 ➔ Aug 2023

IO biomarker • Metastases • Trial completion date • Trial primary completion date • Tumor mutational burden • Cervical Cancer • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TMB

In vitro and in vivo characterization of non-oncolytic engineered arenavirus vectors for cancer immunotherapy (AACR 2022) - P1/2 | "The designated vectors, HB-201 (LCMV) and HB-202 (PICV), are currently in an ongoing Phase I/II open labelled clinical trial of HB-201 single vector therapy and HB-202/HB-201 alternating two-vector therapy in patients with treatment-refractory HPV16+ cancers (NCT04180215). In a therapeutic setting of the TC-1 tumor model, both vectors were comparably effective, showing major infiltration of CD8+ T cells into the tumor microenvironment, tumor growth delay and a significantly prolonged survival already after a single administration. In this data set we have confirmed the strong immunogenicity of the engineered arenavirus platform leading to efficient tumor control in a relevant mouse model for HPV16+ cancers, which further supports the clinical development of our novel arenavirus platform."

Preclinical • Oncology • CD8

A Phase 1/2 Study in Patients With HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Other Cancers (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Hookipa Biotech GmbH | Trial completion date: Jun 2022 ➔ Jun 2025 | Trial primary completion date: Jan 2022 ➔ Jun 2023

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

A Study HB-201 in Patients With Newly Diagnosed HPV16+ Oropharynx or Locally Advanced Cervical Cancer (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Hookipa Biotech GmbH | Trial completion date: Dec 2022 ➔ Mar 2023 | Trial primary completion date: Oct 2022 ➔ Feb 2023

IO biomarker • Trial completion date • Trial primary completion date • Cervical Cancer • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TMB

Recommended phase 2 dose (RP2D) of HB-200 arenavirus-based cancer immunotherapies in patients with HPV16+ cancers. (ASCO 2022) - P1/2 | "HB-201 and HB-202/HB-201 were generally well tolerated and showed preliminary antitumor activity in heavily pre-treated patients with HPV16+ solid tumors. DL3 was selected as RP2D for HB-201 monotherapy. In the Phase 2 part of the study a combination of HB-201 at 5 × 106 units IV Q3W with pembrolizumab is being tested in HPV16+ HNSCC patients."

Clinical • IO biomarker • P2 data • CNS Disorders • Head and Neck Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

HB-201 and HB-202, an arenavirus-based immunotherapy, induces tumor T cell infiltration in patients with HNSCC and other HPV16+ tumors (AACR 2022) - P1/2 | "In this updated dataset, we show that HB-201 and HB-202/HB-201, rapidly induce unprecedented E6/E7 specific T cell levels in circulation following a single dose. Furthermore, these data are seen in conjunction with a pronounced increase of post-treatment CD8+ T cells in tumor, suggesting E6/E7 specific T cell infiltration. Our arenavirus vectors expressing the E7E6 fusion antigen demonstrate an attractive and safe therapy for patients with treatment refractory HPV16+ cancers."

Clinical • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • CD8 • IFNG • PD-L1

HOOKIPA Pharma Reports Second Quarter 2022 Financial Results and Corporate Updates (GlobeNewswire) - "Phase 2 HB-200 data in combination with pembrolizumab in HPV16+ head and neck cancer: First-line initial data expected in the second half of 2022, Second-line initial data expected in the second half of 2022....The Phase 2 trial will proceed with alternating 2-vector therapy alone and in combination with pembrolizumab, which will help inform the randomized Phase 2 trial planned to start in the first half of 2023."

P2 data • Trial status • Gastrointestinal Cancer • Head and Neck Cancer • Oncology

HOOKIPA announces positive Phase 1 data and Phase 2 plans for HB-200 program for the treatment of advanced head and neck cancers at ASCO (GlobeNewswire) - P1/2 | N=200 | NCT04180215 | Sponsor: Hookipa Biotech GmbH | "The poster presented at ASCO provided updated anti-tumor activity on 43 Phase 1 patients with HPV16+ HNSCC who received therapy intravenously every three weeks for the first five doses and every six weeks thereafter, which is the route and frequency selected for further evaluation in Phase 2 cohorts. The 43 patients were comprised of 20 persons who received single-vector HB-201 and 23 who received alternating 2-vector HB-202/HB-201....In addition, decreases in visceral lesions were predominantly seen in patients who received 2-vector therapy: 59 percent of patients on HB-202/HB-201 compared to 18 percent on HB-201. Further, HB-202/HB-201 demonstrated an 80 percent disease control rate, which compares favorably to historical disease control rates achieved by pembrolizumab in recurrent/metastatic HNSCC patients, specifically 35 percent overall and 40 percent in the HPV+ subset, based on peer-reviewed published data."

P1 data • Head and Neck Cancer • Oncology