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

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

Tumor growth inhibition mediated by a single dose of intratumoral TransCon™ TLR7/8 agonist was associated with activated circulating T and B cells and sustained low levels of systemic cytokines (SITC 2021) - P1/2 | "The increase in activated B, T, and NK cells in blood was associated with induction of a potent anti-tumor response, further supporting TransCon TLR7/8 Agonist as a novel and potentially efficacious PRRA therapy. A clinical trial to evaluate its safety and efficacy in cancer patients is currently underway (transcendIT-101; NCT04799054)."

IO biomarker • Oncology • CCL2 • CCL3 • CD4 • CD8 • CXCL1 • CXCL10 • ICOS • IFNG • IL1B • IL6 • TNFA

A Single Dose of Intratumoral TransCon™ TLR7/8 Agonist Monotherapy Promoted Sustained Activation of Antigen Presenting Cells Resulting in CD4+ and CD8+ T cell Activation and Tumor Growth Inhibition (SITC 2021) - P1/2 | "These preclinical data further support TransCon TLR7/8 Agonist as a novel and potentially efficacious PRRA therapy. A clinical trial to evaluate safety and efficacy of TransCon TLR7/8 Agonist as monotherapy, and in combination with pembrolizumab, in cancer patients has been initiated (transcendIT-101; NCT04799054)."

IO biomarker • Monotherapy • Oncology • CD4 • CD69 • CD8 • CD86 • GZMB • ICAM1 • ICOS

Dose Escalation Data from transcendIT-101, Ascendis Pharma’s Phase 1/2 Trial of TransCon TLR7/8 Agonist in Patients with Advanced Solid Tumors, Presented at SITC 2022 (GlobeNewswire) - "The dose escalation data from transcendIT-101, presented by Diwakar Davar...suggests that intratumoral TransCon TLR7/8 Agonist was safe and well-tolerated alone or in combination with pembrolizumab; that it demonstrated target immune system engagement in injected and non-injected tumors along with a systemic immune response; and that it showed early signs of clinical activity alone or in combination with pembrolizumab."