ITIL-168 / Instil Bio - LARVOL DELTA

DELTA-1: ITIL-168 in Advanced Melanoma (clinicaltrials.gov) - P2 | N=29 | Terminated | Sponsor: Instil Bio | N=130 ➔ 29 | Trial completion date: Aug 2028 ➔ Feb 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2024 ➔ Feb 2023; Business Decision

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

DELTA-2: A phase 1, open-label, multicenter study of ITIL-168, an autologous tumor-infiltrating lymphocyte (TIL) cell therapy, with pembrolizumab in patients with advanced solid tumors (SITC 2022) - P1 | "Treatment will include lymphodepleting chemotherapy (the dosage of cyclophosphamide and fludarabine will be adjusted based on cohort and patient comorbidities) followed by a single infusion of ITIL-168 and up to 8 doses of high-dose IL-2 (figure 1). Secondary endpoints include manufacturing success rate, objective response rate per modified RECIST v1.1, duration of response, progression-free survival, and overall survival. The study opened in July 2022 and is currently recruiting patients."

Clinical • IO biomarker • P1 data • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

Development of an optimized and scalable manufacturing process for TIL isolated from digested and cryopreserved tumors (AACR 2022) - P2 | "ITIL-168 manufacturing was feasible from a variety of tumor types and consistently produced a robust TIL product irrespective of tumor histology from melanoma, cervical, lung, and cutaneous carcinomas. This TIL manufacturing process is being utilized in DELTA-1 (NCT05050006), a Phase 2 multicenter clinical study of ITIL-168 in adult patients with advanced melanoma across multiple cohorts. ITIL-168 may have the potential to treat solid tumors beyond melanoma and plans for a multicancer study are currently underway."

IO biomarker • Cervical Cancer • Lung Cancer • Melanoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

DELTA-2: ITIL-168 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Instil Bio | N=27 ➔ 0 | Trial completion date: Aug 2028 ➔ Dec 2022 | Active, not recruiting ➔ Withdrawn | Trial primary completion date: Feb 2024 ➔ Dec 2022

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial withdrawal • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

Instil Bio Announces Prioritization of Genetically Engineered CoStAR-TIL Program with ITIL-306 in Advanced Solid Tumors and Reduction in Workforce (GlobeNewswire) - "Instil is discontinuing its ITIL-168 clinical programs, the DELTA-1 trial in advanced melanoma and the DELTA-2 trial in NSCLC, cervical cancer, and head and neck squamous cell carcinoma. After an analysis of the potential scenarios to restart and complete a registration-enabling cohort in advanced melanoma in the DELTA-1 trial, the Company has decided to prioritize the CoStAR-TIL platform."

Discontinued • Cervical Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

DELTA-1: A global, multicenter, phase 2 study of ITIL-168, an unrestricted autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in adult patients with advanced cutaneous melanoma (SITC 2022) - P2 | "Patients will receive 5 days of lymphodepleting chemotherapy (cyclophosphamide ×2 days overlapping with fludarabine ×5 days) followed by a single ITIL-168 infusion and supportive IL-2. The primary analysis will occur ≥6 months after the first posttreatment disease assessment of patients in the cohort 1 modified intent-to-treat population. Enrollment has expanded into Canada and Europe."

Clinical • IO biomarker • P2 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF • IL2

DELTA-2: ITIL-168 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=27 | Active, not recruiting | Sponsor: Instil Bio | Recruiting ➔ Active, not recruiting

Enrollment closed • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

DELTA-1: A global, multicenter phase 2 study of ITIL-168, an unrestricted autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in adult patients with advanced cutaneous melanoma (SITC 2021) - "Patients will receive 5 days of lymphodepleting chemotherapy (cyclophosphamide ×2 days overlapping with fludarabine ×5 days) followed by a single ITIL-168 infusion (≥5×109 cells) and supportive short course high-dose IL-2. Two interim analyses will occur after 20 patients in cohort 1 have been followed for ≥28 days (safety) and evaluated for response ≥3 months after ITIL-168 infusion (futility). The primary analysis will occur when all patients in the cohort 1 modified intent-to-treat population have been followed for ≥6 months after the first posttreatment disease assessment."

Clinical • IO biomarker • P2 data • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • BRAF

DELTA-1: A global, multicenter, phase 2 study of ITIL-168, an unrestricted autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in adult patients with advanced cutaneous melanoma. (ASCO 2022) - P2 | "Pts will receive 5 days of lymphodepleting chemotherapy (cyclophosphamide ×2 days overlapping with fludarabine ×5 days) followed by a single ITIL-168 infusion (≥5×109 cells) and supportive short-course, high-dose IL-2. DELTA-1 opened for enrollment in September 2021. Updated site information will be given at the time of presentation."

Clinical • IO biomarker • P2 data • CNS Disorders • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • Transplantation • BRAF

DELTA-1: ITIL-168 in Advanced Melanoma (clinicaltrials.gov) - P2 | N=130 | Active, not recruiting | Sponsor: Instil Bio | Recruiting ➔ Active, not recruiting

Enrollment closed • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Instil Bio Announces Voluntary Pause of Enrollment in Ongoing Clinical Trials Related to Manufacturing (GlobeNewswire) - "Instil Bio, Inc...announced that it has voluntarily paused enrollment in its ongoing clinical trials of ITIL-168 and ITIL-306 and has notified regulatory authorities in the United States, Canada, and the UK. No regulatory agencies, including the FDA, have notified the Company of a clinical hold in any of its clinical trials....The voluntary pause by the Company was instituted following a recent decrease in the rate of successful manufacturing of ITIL-168, resulting in the inability to dose some patients whose individual product of ITIL-168 was not successfully manufactured....The Company has commenced an end-to-end analysis of its manufacturing processes and upon completion of this analysis, plans to take corrective actions to improve the rate of manufacturing success and resume the study....The Company intends to provide an update on the manufacturing analysis by early Q1 2023."

Trial suspension • Cutaneous Melanoma • Genito-urinary Cancer • Gynecologic Cancers • Kidney Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor

"$TIL Voluntarily paused enrollment in ITIL-168 and ITIL-306 trials pending outcome of manufacturing analysis and implementation of corrective actions" (@BioStocks)

DELTA-1: A global, multicenter, phase 2 study of ITIL-168, an unrestricted autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in adult patients (pts) with advanced cutaneous melanoma (ESGCT 2022) - No abstract available

Clinical • P2 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

DELTA-1: ITIL-168 in Advanced Melanoma (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Instil Bio | Trial completion date: Dec 2027 ➔ Aug 2028 | Trial primary completion date: Jun 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

DELTA-2: ITIL-168 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: Instil Bio | Not yet recruiting ➔ Recruiting

Enrollment open • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

Instil Bio Reports Second Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Second Quarter 2022 Highlights and Anticipated Milestones - Enrollment ongoing in DELTA-1, a Phase 2 trial of ITIL-168 in advanced melanoma with registrational intent: Instil is targeting completion of enrollment in 1H 2023 for the registrational cohort and expects top-line safety and efficacy data in early 2024, which could potentially support a biologics license application (BLA) submission and a European Medicines Agency marketing authorization application (MAA) filing."

Enrollment status • P2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

DELTA-1: ITIL-168 in Advanced Melanoma (clinicaltrials.gov) - P2; N=130; Recruiting; Sponsor: Instil Bio

Clinical • New P2 trial • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF • MRI

DELTA-2: ITIL-168 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: Instil Bio

New P1 trial • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

Instil Bio Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Enrollment Ongoing in DELTA-1, Instil expects top-line safety and efficacy data in 2023 which could potentially support BLA submission and a European Medicines Agency marketing authorization application (MAA) filing. Instil remains on track to file an IND for a Phase 1 study of its first genetically engineered CoStAR-TIL, ITIL-306, in multiple solid tumor indications in H1 2022."

IND • P2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

Instil Bio Announces Poster Presentations at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "The results demonstrated that CoStAR broadly enhances effector function of T cells including cytolytic activity, cytokine secretion and proliferation of T cells. CoStAR did not stimulate T cells on its own, but only increased T-cell function in the presence of signals activating both the tumor-reactive TCR and the CoStAR molecule. Additionally, data were presented that showed CoStAR was transduced at high efficiency (greater than 40%) into primary ovarian cancer TILs and effector function of CoStAR-TIL was increased over untransduced TILs when cocultured with autologous tumor cells...'We continue to look forward to the upcoming Phase 1 first-in-human study of ITIL-306 which we expect to initiate in the first half of 2022'. The company also presented a trial-in-progress poster for DELTA-1, the ongoing Phase 2 study of ITIL-168 in advanced melanoma."

New P1 trial • P2 data • Preclinical • Cutaneous Melanoma • Melanoma • Oncology

Instil Bio Reports Third Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Readiness to Initiate DELTA-2 in H1 2022: Preparations are on track to initiate enrollment in DELTA-2, a Phase 1 study of ITIL-168 in non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), cervical cancer, and cutaneous squamous cell carcinoma (CSCC). Enrollment in DELTA-2 is planned to initiate in H1 2022."

Enrollment status • New P1 trial • Cervical Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Instil Bio Receives IND Clearance to Initiate a Phase 2 Clinical Trial for Patients with Advanced Melanoma (GlobeNewswire) - "Instil Bio, Inc...reported clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate DELTA-1, a global Phase 2 clinical trial of ITIL-168 in patients with advanced melanoma whose disease has relapsed after a PD-1 inhibitor and, if positive for a BRAF-activating mutation, a BRAF inhibitor...Topline safety and efficacy results are expected in 2023 and, if positive, are anticipated to support the submission of a biologics license application (BLA) to the FDA in 2023 and a Marketing Authorization Application (MAA) to the European Medicines Agency in 2024."

BLA • European regulatory • IND • P2 data • Melanoma • Oncology

Instil Bio Receives Orphan Drug Designation for ITIL-168 in Melanoma (GlobeNewswire) - “Instil Bio…received orphan drug designation (ODD) from the U.S. Food and Drug Administration (FDA) for the treatment of melanoma stages IIB to IV with its ITIL-168 TIL therapy.”

Orphan drug • Melanoma • Oncology • Skin Cancer • Solid Tumor

"$TIL Instil Bio Receives Orphan Drug Designation for ITIL-168 in Melanoma https://t.co/hwWjvChJn5" (@stock_titan)

Orphan drug • Melanoma • Oncology • Solid Tumor

Instil Bio Presents Clinical Data in Metastatic Melanoma in a Late-Breaking e-Poster at the 2021 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - P=NA, N=21; ‘”This presentation highlights the potential for ITIL-168 to produce deep and durable remissions in patients with advanced melanoma’… Among the 21 patients, 14 (67%) achieved an objective response, with four (19%) achieving a complete response. All complete responders remained in remission at the time of data cutoff with those remissions ranging in duration from 30 months to over 80 months from TIL infusion. With a median duration of follow-up of 52.2 months, the median overall survival was 21.3 months with nearly half of patients experiencing long term survival. Side effects of treatment were largely transient, self-limited and generally attributable to the lymphodepleting chemotherapy regimen and post-TIL IL-2 treatment. The company plans to submit these results for peer-reviewed publication in 2021.”

Clinical data • Melanoma • Oncology