KB707 / Krystal Biotech - LARVOL DELTA

Inhaled KB707, a novel HSV-based immunotherapy, as a monotherapy in patients with advanced solid tumor malignancies affecting the lungs: Efficacy and safety results from a phase 1/2 study. (ASCO 2025) - P1/2 | "KB707 administered by inhalation was safe and well tolerated. The MTD was not reached, and the monotherapy recommended Phase 2 dose is 109 PFU. Single agent anti-tumor effects were observed, including in heavily treated NSCLC patients."

Clinical • Metastases • Monotherapy • P1/2 data • Gene Therapies • Herpes Simplex • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • IL12A • IL2

Krystal Biotech Announces First Quarter 2025 Financial and Operating Results (GlobeNewswire) - "Enrollment is ongoing in the Company’s KYANITE-1 study, a Phase 1/2 open label, multi-center, dose escalation and expansion study evaluating inhaled KB707, as monotherapy or in combination, in patients with locally advanced or metastatic solid tumors of the lung...A clinical update on the monotherapy cohort from KYANITE-1 is expected to be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting next month....The Company continues to enroll in OPAL-1, a Phase 1/2 open label, multi-center, dose escalation and expansion study evaluating intratumoral KB707, either as monotherapy or in combination, in patients with locally advanced or metastatic solid tumor malignancies."

Enrollment status • P1/2 data • Non Small Cell Lung Cancer • Solid Tumor

Krystal Biotech Announces Fourth Quarter and Full Year 2024 Financial and Operating Results (GlobeNewswire) - "The Company continues to enroll in OPAL-1, a Phase 1/2 open label, multi-center, dose escalation and expansion study evaluating intratumoral KB707, either as monotherapy or in combination, in patients with locally advanced or metastatic solid tumor malignancies."

Enrollment status • Cutaneous Melanoma • Melanoma • Solid Tumor

KYANITE-1: A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Krystal Biotech, Inc. | N=140 ➔ 200 | Trial completion date: Feb 2027 ➔ Feb 2028 | Trial primary completion date: Feb 2027 ➔ Feb 2028

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

OPAL-1: A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Krystal Biotech, Inc. | N=140 ➔ 240 | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Jul 2026 ➔ Jul 2027

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

Krystal Biotech Announces Early Evidence of Monotherapy Activity in Heavily Pre-Treated Patients with Advanced Non-Small Cell Lung Cancer (GlobeNewswire) - P1/2 | N=140 | KYANITE-1 (NCT06228326) | Sponsor: Krystal Biotech, Inc. | "A total of 37 patients were enrolled and received at least one dose of inhaled KB707, including 17 patients with a diagnosis of advanced NSCLC....As of the data cut-off, 11 NSCLC patients were evaluable for response with at least one radiographic scan and RECIST v1.1 evaluation....In this NSCLC patient analysis cohort, an ORR of 27%, with three partial responses, has been achieved. DCR to date has been 73% with 7 out of 11 patients still remaining on treatment. Duration of treatment for patients included in the analysis ranged from 10.3 to 33.3 weeks as of data cut-off....Among the same 11 evaluable NSCLC patients, the ORR in target lung lesions specifically was 36%, with three partial responses and one complete response, and DCR was 82%....The Company expects to disclose detailed and updated results of KYANITE-1 at future scientific conference(s)."

P1/2 data • Non Small Cell Lung Cancer

KYANITE-1: A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs (clinicaltrials.gov) - P1/2 | N=140 | Recruiting | Sponsor: Krystal Biotech, Inc. | Phase classification: P1 ➔ P1/2 | N=80 ➔ 140

Enrollment change • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

OPAL-1: A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=140 | Recruiting | Sponsor: Krystal Biotech, Inc. | Phase classification: P1 ➔ P1/2 | N=80 ➔ 140

Enrollment change • Phase classification • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

Krystal Biotech Announces Third Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Intratumoral KB707 for the treatment of injectable solid tumors: The Company expects to report initial interim data for KB707 before the end of the year."

P1 data • Oncology • Solid Tumor

Krystal Biotech Announces First Quarter 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "In April, the Company successfully completed enrollment in Cohort 3 of the Phase 1 OPAL-1 clinical study in patients with locally advanced or metastatic solid tumor malignancies....Based on the current rate of enrollment, the Company expects to report interim data in 2H 2024."

P1 data • Trial status • Basal Cell Carcinoma • Melanoma • Oncology • Osteosarcoma • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma

Krystal Biotech Announces First Patient Dosed in Phase 1 Clinical Trial of Inhaled KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors of the Lung (GlobeNewswire) - "Krystal Biotech, Inc...announced today that the first patient was dosed in its Phase 1 clinical trial (KYANITE-1) evaluating inhaled KB707, a modified HSV-1 vector designed to deliver genes encoding both human interleukin-12 (IL-12) and interleukin-2 (IL-2) to the lung, for the treatment of patients with locally advanced or metastatic solid tumors of the lung....'With a deep pipeline of active clinical trials, we are looking forward to data readouts starting later in 2024, which we expect will showcase the breadth and potential of our proprietary, HSV-1 based gene delivery platform'."

P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

An HSV-1-based vector for local delivery of IL-12 and IL-2 reshapes the immune landscape leading to tumor clearance and systemic immune surveillance (AACR 2024) - "Durable targeted delivery to the tumor microenvironment (TME) is a promising therapeutic strategy to overcome these clinical limitations, prompting the development of KB707, a replication-defective herpes simplex virus type 1 (HSV-1)-based vector encoding human IL-12 and -2, for the treatment of solid tumors...Interestingly, although IL-2 alone has been shown to promote immune suppression and tumor outgrowth by mediating regulatory T cell (Treg) expansion and infiltration in certain contexts, the frequency of Tregs in treated vs. control tumors was substantially reduced after first and repeat dosing. Together, these results support a mechanism by which vector-driven local expression of IL-12 and IL-2 can expand and activate effector T cells both in the TME and systemically while simultaneously repressing Tregs, consistent with the previously described inhibition of primary tumor outgrowth, abscopal effects on secondary tumors, and prevention of recurrence observed with..."

Melanoma • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL12A • IL2 • TNFA

Krystal Biotech to Present at the American Association for Cancer Research 2024 Annual Meeting (GlobeNewswire) - "Krystal Biotech...announced today that the Company will be presenting new preclinical data on local and systemic immune activation following intratumoral injection of the Company’s platform technology encoding murine interleukin-12 (IL-12) and interleukin-2 (IL-2), the species matched equivalent to the Company’s clinical-stage oncology product candidate KB707, at the American Association for Cancer Research (AACR) 2024 Annual Meeting....Intratumoral delivery of HSV-1 encoded IL-12 and IL-2 enhanced local and systemic effector T-cell responses in cold tumor preclinical model."

Preclinical • Oncology

Krystal Biotech Receives FDA Fast Track Designation for Inhaled Oncology Candidate KB707 to Treat Solid Tumors of the Lung (GlobeNewswire) - "Krystal Biotech, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for inhaled KB707 for the treatment of patients with solid tumors with pulmonary metastases that are relapsed or refractory to standard of care therapy....The Company expects to dose the first patient in the open-label, multi-center, monotherapy, dose escalation and expansion Phase 1 clinical study (KYANITE-1) in the first half of 2024."

Fast track designation • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Krystal Biotech, Inc.

Metastases • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Osteosarcoma • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor

A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Krystal Biotech, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2023 ➔ Oct 2023

Enrollment open • Metastases • Trial initiation date • Basal Cell Carcinoma • Cutaneous Melanoma • Melanoma • Non-melanoma Skin Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma

Krystal Biotech Announces Third Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "In October, the first patient was dosed in the Phase 1 (OPAL-1) study to evaluate intratumoral KB707 in patients with locally advanced or metastatic solid tumor malignancies....The Company is on track to file an amendment to the existing KB707 IND in the fourth quarter of 2023 to allow the Company to evaluate inhaled KB707 in a clinical trial to treat tumors in a patient’s lungs. The Company expects to dose the first patient with inhaled KB707 in the first half of 2024."

IND • New trial • Trial status • Solid Tumor

Localized airway delivery of Interleukins-12 and -2 via inhalation of a replication-defective HSV-1-based therapy for the treatment of primary and secondary lung tumors (SITC 2023) - "has developed KB707, a vector encoding human IL-12 and -2 for the treatment of solid tumors...Additionally, a therapeutic benefit of KB703/KB704 therapy has been observed in a model of primary lung tumors. Conclusions Overall, these results highlight the potential of Krystal’s HSV-1-based platform for sustained delivery of IL-12 and IL-2 as a novel immunotherapy for the treatment of primary and secondary lung tumors."

Lung Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IL12A • IL2

A replication-defective, HSV-1-based gene therapy for localized delivery of combinatorial Interleukins-12 and -2 for the treatment of cutaneous malignancies (SITC 2023) - "has developed KB707, a replication-defective herpes simplex virus type 1 (HSV-1)-derived vector encoding human IL-12 and -2, for redosable treatment of solid tumors...Vector treatment resulted in at least some degree of secondary (untreated) tumor growth inhibition, suggesting an abscopal effect, the magnitude of which was directly proportional to the interval between primary and secondary tumor instillation. Conclusions Overall, these results highlight the potential of Krystal’s platform for sustained delivery of IL-12 and IL-2 into the tumor microenvironment as a novel immunotherapy for the treatment of local and distal solid tumors, including cutaneous malignancies."

Gene therapy • IO biomarker • Melanoma • Oncology • Skin Cancer • IL12A • IL2

Krystal Biotech Announces Second Quarter 2023 Financial Results and Operational Highlights (GlobeNewswire) - "In July, the Company announced that the FDA had accepted its IND application to evaluate intratumoral KB707 in a clinical trial to treat patients with locally advanced or metastatic solid tumor malignancies....The Company expects to dose the first patient in the second half of 2023. The FDA also granted KB707 fast track designation to delay disease progression in the treatment of patients with anti-PD-1 relapsed/refractory locally advanced or metastatic melanoma. The Company plans to file an amendment to the existing KB707 IND in the second half of 2023 to allow the Company to evaluate inhaled (nebulized) KB707 in a clinical trial to treat tumors in a patient’s lungs. The Company expects to dose the first patient with inhaled KB707 in the first half of 2024."

IND • Trial status • Melanoma • Oncology • Skin Cancer • Solid Tumor

Krystal Biotech Announces Pipeline Expansion into Oncology and FDA Acceptance of IND Application for Lead Oncology Candidate KB707 (GlobeNewswire) - "Krystal Biotech...announced today that it has expanded its R&D pipeline to oncology and that the US Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application of its lead oncology drug candidate KB707 for the treatment of locally advanced or metastatic solid tumor malignancies....The FDA has accepted the Company’s IND to evaluate intratumoral KB707 in patients with solid tumors accessible by transcutaneous injection, and the Company expects to initiate a Phase 1 study in the second half of 2023. The Company is planning to file an amendment to the KB707 IND in the second half of 2023 to evaluate inhaled KB707 in a clinical trial in the first half of 2024."

IND • New P1 trial • New trial • Oncology • Solid Tumor

A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Krystal Biotech, Inc.

Metastases • New P1 trial • Basal Cell Carcinoma • Cutaneous Melanoma • Melanoma • Non-melanoma Skin Cancer • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma