resiquimod SR (TransCon TLR7/8 Agonist) / Ascendis - LARVOL DELTA

Neoadjuvant combined immunotherapy with intratumoral TransCon TLR7/8 Agonist and systemic TransCon IL-2 β/y or pembrolizumab in patients with locally advanced oral cancer-a monocentric experience. (PubMed, Cancer Immunol Immunother) - "Neoadjuvant intratumoral TransCon TLR7/8 Agonist-based combination immunotherapy was feasible in this small prospective cohort of patients with locally advanced OSCC and was accompanied by consistent remodeling of the tumor immune microenvironment. Because of the limited number of patients and the premature termination of the parent trial, no conclusions on efficacy or on comparative tolerability can be drawn."

Clinical • Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD163 • CD68 • CD8 • IL2

IL Believe: A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other Anticancer Therapies in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=320 | Active, not recruiting | Sponsor: Ascendis Pharma Oncology Division A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Breast Cancer • Cervical Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • CTLA4

transcendIT-101: A Study of TransCon TLR7/8 Agonist With or Without Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=188 | Terminated | Sponsor: Ascendis Pharma Oncology Division A/S | Active, not recruiting ➔ Terminated; The Sponsor made the decision to close enrollment to prioritize our efforts on TransCon IL-2 ß/g.

Trial termination • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

BelieveIT-201: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=27 | Terminated | Sponsor: Ascendis Pharma A/S | Completed ➔ Terminated; The Sponsor made the decision to close enrollment as part of a strategic portfolio review.

Trial termination • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

BelieveIT-201: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=27 | Terminated | Sponsor: Ascendis Pharma A/S | Trial primary completion date: Dec 2024 ➔ Mar 2025

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

transcendIT-101: A Study of TransCon TLR7/8 Agonist With or Without Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=188 | Active, not recruiting | Sponsor: Ascendis Pharma Oncology Division A/S | Trial primary completion date: May 2025 ➔ Jan 2026

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

BelieveIT-201: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=27 | Completed | Sponsor: Ascendis Pharma A/S | Active, not recruiting ➔ Completed | Trial completion date: Jul 2027 ➔ Mar 2025 | Trial primary completion date: Apr 2025 ➔ Dec 2024

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

BelieveIT-201: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Ascendis Pharma A/S | Recruiting ➔ Active, not recruiting | N=92 ➔ 27

Combination therapy • Enrollment change • Enrollment closed • Metastases • Surgery • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

transcendIT-101: A Study of TransCon TLR7/8 Agonist With or Without Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=188 | Active, not recruiting | Sponsor: Ascendis Pharma Oncology Division A/S | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Ascendis Pharma Reports Third Quarter 2024 Financial Results (GlobeNewswire) - "Oncology Programs:...Recently, we closed enrollment to dose expansion cohorts involving TransCon TLR7/8 Agonist in the transcendIT-101 and IL Believe trials to prioritize our efforts on TransCon IL-2 b/g."

Enrollment closed • Solid Tumor

IL Believe: A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other Anticancer Therapies in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=473 | Recruiting | Sponsor: Ascendis Pharma Oncology Division A/S | Trial completion date: Aug 2027 ➔ Aug 2029 | Trial primary completion date: May 2026 ➔ Aug 2027

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • HER2 Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • IL2

TransCon IL-2 β/γ alone or in combination with pembrolizumab, standard of care chemotherapy or TransCon TLR7/8 agonist in advanced/metastatic solid tumors: Updated results of the phase 1/2 IL Believe study. (ASCO 2024) - P1/2 | "TC-IL2 β/γ alone and in combination with P or TransCon TLR7/8 Agonist is generally well-tolerated with meaningful clinical responses in heavily pre-treated patients with anti-PD-(L)1 relapsed or refractory disease. Initial evaluation of biomarkers shows a sustained significant expansion and activation of CLs, elevated levels of cytokines and chemokines in blood without the corresponding expansion of Tregs or eosinophils."

Combination therapy • IO biomarker • Metastases • P1/2 data • Head and Neck Cancer • Lung Cancer • Melanoma • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CXCL10 • IFNG • IL2 • ISG20

Ascendis Pharma Reports First Quarter 2024 Financial Results (GlobeNewswire) - "New data from the ongoing Phase 1/2 IL-Believe Trial has been accepted for a poster presentation at the American Society for Clinical Oncology (ASCO) May 31-June 4. The presentation will provide initial data from the combination of TransCon IL-2 β/γ and TransCon TLR7/8 Agonists in patients with melanoma who have progressed on anti-PD1 therapy. During the fourth quarter of 2024, plan to provide a clinical update from the Phase 2 indication-specific, dose expansion cohorts from our TransCon IL-2 β/γ and TransCon TLR7/8 Agonist clinical trials."

P1/2 data • P2 data • Melanoma • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Ascendis Pharma Reports Fourth Quarter and Full Year 2023 Results (GlobeNewswire) - "Anticipated 2024 Milestones:...(i) TransCon IL-2 β/γ (onvapegleukin alfa): During the fourth quarter of 2024, plan to provide a clinical update from the Phase 2 portion of indication-specific, dose expansion cohorts in the IL Believe trial; (ii) TransCon TLR7/8 Agonist: During the fourth quarter of 2024, plan to provide a clinical update from the Phase 2 portion of indication-specific, dose expansion cohorts in the transcendIT-101 trial."

P2 data • Cervical Cancer • Melanoma • Non Small Cell Lung Cancer • Ovarian Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Ascendis Pharma Introduces Vision 2030 (GlobeNewswire) - "Selected Key Updates:...Oncology: (i) During the fourth quarter of 2024, expect to complete enrollment in BelieveIT-201, a Phase 2 trial in advanced head and neck squamous cell carcinoma (HNSCC); (ii) During the fourth quarter of 2024, plan to provide a clinical update from the Phase 2 portion of indication-specific, dose expansion cohorts in the IL-Believe Trial."

Enrollment status • P2 data • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

IL Believe: A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or Chemotherapy or TransCon TLR7/8 Agonist in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies (clinicaltrials.gov) - P1/2 | N=393 | Recruiting | Sponsor: Ascendis Pharma Oncology Division A/S | Trial completion date: May 2025 ➔ Aug 2027 | Trial primary completion date: Jan 2025 ➔ May 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Small Cell Lung Cancer • Solid Tumor • IL2

transcendIT-101: A Study of TransCon TLR7/8 Agonist With or Without Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=220 | Recruiting | Sponsor: Ascendis Pharma Oncology Division A/S

Trial completion date • Head and Neck Cancer • Melanoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Ascendis Pharma Reports Third Quarter 2023 Financial Results (GlobeNewswire) - "Corporate Highlights: (i) TransCon IL-2 β/γ:...Enrollment continues in the Phase 2 portion in indication-specific cohorts; first patient dosed with TransCon IL-2 b/g and TransCon TLR7/8 Agonist in combination. Initial data from indication-specific cohorts expected in the second half of 2024; (ii) TransCon TLR7/8 Agonist: Enrollment continues in Phase 2 portion of transcendIT-101, a Phase 1/2 trial to evaluate TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab in dose escalation and dose expansion. Initial data expected in the second half of 2024."

P1/2 data • Trial status • Solid Tumor

TransCon TLR7/8 agonist induces sustained local and systemic immune activation in patients with solid tumors (SITC 2023) - P1/2 | "However, systemic resiquimod administration may lead to unacceptable toxicities...5 mg/lesion) as monotherapy every 3 weeks while the remaining 14 patients received combination therapy with staggered dosing of pembrolizumab in cycle 1 (administered 7 days after TransCon TLR7/8 Agonist) and same day dosing every 3 weeks at subsequent cycles...Increased numbers of immune cells in a non-injected lesion indicate distant anti-tumor immune effects. Currently patient enrollment continues into dose-optimization and indication-specific cohorts."

Clinical • IO biomarker • Oncology • Solid Tumor • CD68 • CD8 • CXCL10 • HLA-B • HLA-C • TNFA

BelieveIT-201: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=92 | Recruiting | Sponsor: Ascendis Pharma Oncology Division A/S | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Surgery • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Ascendis Pharma Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "Enrollment continues in the Phase 2 portion of transcendIT-101 at the recommended Phase 2 dose (RP2D) in four indication-specific cohorts. Topline/interim analysis from Phase 2 dose-expansion cohorts expected in 2024."

Enrollment status • P2 data • Oncology • Solid Tumor

BelieveIT-201: TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=92 | Not yet recruiting | Sponsor: Ascendis Pharma Oncology Division A/S

Combination therapy • Metastases • New P2 trial • Surgery • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Degradable hydrogel for sustained localized delivery of anti-tumor drugs. (PubMed, J Pharm Sci) - P1/2 | "Resiquimod, a TLR7/8 agonist, and axitinib, a vascular endothelial growth factor tyrosine kinase inhibitor, were chosen as anti-cancer drugs. In summary, TransCon Hydrogel technology allows localized sustained-release drug delivery for cancer therapy enabling high local drug concentrations while at the same time ensuring low systemic drug exposure over weeks with a single injection, which may improve the therapeutic index and improve efficacy, while minimizing systemic adverse events. A hydrogel prodrug of resiquimod, TransCon TLR7/8 agonist, is currently being investigated in clinical trials of patients with solid tumors (NCT04799054)."

Journal • Endocrine Disorders • Growth Hormone Deficiency • Growth Hormone Deficiency (Pediatric) • Immune Modulation • Oncology • Pediatrics • Solid Tumor

Ascendis Pharma Oncology Program Update Highlights Latest Clinical Data for Product Candidates (GlobeNewswire) - P1/2 | N=220 | transcendIT-101 (NCT04799054) | Sponsor: Ascendis Pharma Oncology Division A/S | "Additional follow-up indicates further clinical activity in patients receiving TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab....Preliminary results showed that TransCon TLR7/8 Agonist was well-tolerated both as a monotherapy and in combination with pembrolizumab."

P1/2 data • Head and Neck Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Ascendis Pharma to Host Oncology Program Update on May 31 (GlobeNewswire) - "The event will feature presentations by an outside oncology expert and Ascendis senior management on the company’s two immuno-oncology product candidates, TransCon IL-2 β/γ and TransCon TLR7/8 Agonist, being investigated as both mono- and combination therapies. Topics will include clinical development strategy and clinical development program updates, including monotherapy clinical data on TransCon IL-2 β/γ used to define the recommended Phase 2 dose."

Clinical • P1 data • Oncology • Solid Tumor