onvapegleukin alfa (TransCon IL-2 β/γ) / Ascendis - LARVOL DELTA

Select Highlights & Anticipated 2025 Milestones:…TransCon IL-2 β/γ (onvapegleukin alfa) (GlobeNewswire) - "In our IL-Believe trial, 70 patients with late-stage platinum-resistant ovarian cancer (PROC) (median 4 prior lines of therapy; 67% previously treated with at least 2 lines of taxane-containing therapy) have been enrolled. Data continued to suggest that TransCon IL-2 β/γ dosed every three weeks in combination with weekly paclitaxel is generally well-tolerated, with the majority of TransCon IL-2 β/γ-related treatment-emergent adverse events (TEAEs) being Grade 1 or 2 in severity. We expect to provide median overall survival (OS) data for this cohort of 70 patients in the first quarter of next year as the dataset continues to mature."

Enrollment status • P1/2 data • Platinum resistant • Ovarian Cancer

Updated clinical data from TransCon IL-2 β/γ + paclitaxel for platinum resistant ovarian cancer (PROC) in the IL believe trial (ESMO 2025) - P1/2 | "Clinical responses with TransCon IL-2 β/γ (TC IL-2 β/γ; onvapegleukin alfa) in combination with standard of care (SOC) chemotherapy (paclitaxel, docetaxel or pemetrexed) were previously reported showing that TC IL-2 β/γ plus weekly paclitaxel had the best potential for clinical benefit among the chemotherapies evaluated (Yeku et al, ESMO24)...Conclusions Data suggests that TC IL-2 β/γ in combination with paclitaxel for PROC was generally well-tolerated with meaningful clinical responses in heavily pre-treated patients. Sustained and specific expansion of cytotoxic lymphocytes was observed."

Clinical data • IO biomarker • Platinum resistant • Oncology • Ovarian Cancer • Solid Tumor • CD8 • IL2 • PD-1

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

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

Ascendis Pharma Reports First Quarter 2025 Financial Results (TradingView) - "Select Highlights & Anticipated 2025 Milestones...Clinical development of TransCon IL-2 β/γ continues, including ongoing investigation of clinical activity in platinum-resistant ovarian cancer...Total revenue for the first quarter of 2025 was €101.0 million, compared to €95.9 million during the same period in 2024."

Clinical • Commercial • Platinum resistant • Ovarian Cancer • 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=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

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

First results from phase II dose expansion cohort of transcon IL-2 β/γ in combination with standard of care chemotherapy for platinum resistant ovarian cancer (PROC) in the IL Believe trial (ESMO 2024) - P1/2 | "Clinical responses with TransCon IL-2 β/γ (TC-IL-2 β/γ, onvapegleukin alfa) +/- pembrolizumab in heavily pre-treated patients with anti-PD-(L)1 relapsed or refractory solid tumors have been reported (Starodub et al, ESMO23). Here, encouraging preliminary results from the PROC cohort are provided. In this PROC cohort (progression within 6 months after completing prior platinum-based therapy), patients received the recommended phase 2 dose of 120 μg/kg TC-IL-2 β/γ IV Q3W plus physician's choice of paclitaxel, docetaxel, or pemetrexed until disease progression or unacceptable toxicity... Initial data suggest that TC-IL-2 β/γ in combination with chemotherapy for PROC is generally well-tolerated with meaningful clinical responses in heavily pre-treated patients. Preliminary evaluation of biomarkers shows a sustained and specific expansion of CLs."

Combination therapy • P2 data • Oncology • Ovarian Cancer • Solid Tumor • IL2

Ascendis to Present First Results from Platinum-Resistant Ovarian Cancer (PROC) Cohort of the Phase 1/2 IL-Believe Trial at ESMO 2024 (GlobeNewswire) - P1/2 | N=393 | IL Believe (NCT05081609) | Sponsor: Ascendis Pharma Oncology Division A/S | "Ascendis Pharma A/S...announced initial data showing signs of clinical activity in heavily pre-treated patients with platinum-resistant ovarian cancer (PROC) treated with TransCon IL-2 β/γ...in its ongoing Phase 1/2 IL-Believe Trial of TransCon IL-2 β/γ. First results will be shared in Poster 762P at ESMO 2024....Of the 18 patients (median age 64 years) included in the initial data, 14 were efficacy evaluable patients who had 1 or more post-baseline tumor assessment(s), plus an additional 4 who discontinued treatment before the first post-baseline tumor assessment due to disease progression or death. Anti-tumor clinical responses were observed in 29% (4/14) of the efficacy evaluable patients (2 confirmed and 2 unconfirmed partial responses in patients who had received three to seven prior lines of treatment...suggesting clinical activity in heavily pre-treated patients."

P1/2 data • Ovarian Cancer

Ascendis Pharma Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "Oncology Programs:...Initial results from the Phase 2 dose expansion cohort of the IL-Believe Trial of TransCon IL-2 β⁄γ in combination with chemotherapy in platinum-resistant ovarian cancer (PROC) will be presented later this month at the European Society for Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain."

P2 data • Ovarian Cancer

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 Presents New Data and Updated Results from Phase 1/2 IL-Believe Trial at ASCO 2024 (GlobeNewswire) - P1/2 | N=393 | IL Believe (NCT05081609) | Sponsor: Ascendis Pharma Oncology Division A/S | "Ascendis Pharma...reported new and updated results from its ongoing Phase 1/2 IL-Believe Trial of TransCon IL-2 β⁄γ in a poster presentation at ASCO 2024....Data included the first presentation of Phase 2 dose expansion Cohort 4...in post anti-PD-1 melanoma and new analyses of patients from dose escalation cohorts....As of the April 16, 2024 data cutoff, confirmed clinical responses were observed in 40% (two out of five) of efficacy-evaluable patients from Cohort 4, suggesting potential synergy of Ascendis Pharma’s two novel immunotherapy agents....Monotherapy (n=4): 1 confirmed partial response (PR) in colorectal cancer; Combination with pembrolizumab (n=2): 1 confirmed complete response and 1 confirmed PR in small-cell lung cancer; Combination with TransCon TLR7/8 Agonist (n=5): 2 confirmed PRs in melanoma."

P1/2 data • Colorectal Cancer • Melanoma • Small Cell Lung Cancer

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

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

Phase I/II dose escalation and dose expansion study of TransCon IL-2 β/γ alone or in combination with pembrolizumab: Determination of recommended phase II dose (RP2D) for monotherapy (ESMO 2023) - P1/2 | "The RP2D for monotherapy was determined at 120 mcg/kg IV every 3 weeks while dose escalation continues for combination therapy. PK data indicated a half-life of at least 35 hours and PD data confirm durable activation and expansion of cytotoxic immune cells from TransCon IL-2 β/γ."

Combination therapy • Monotherapy • P1/2 data • P2 data • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Pancreatic Cancer • Solid Tumor • IL2 • MSI

Ascendis Presents Updated and New TransCon IL-2 β⁄γ Monotherapy and Combination Therapy Data Confirming Clinical Activity Across Tumor Types at ESMO 2023 (GlobeNewswire) - P1/2 | N=317 | IL Believe (NCT05081609) | Sponsor: Ascendis Pharma | "The data included longer-term follow up of previously presented TransCon IL-2 β⁄γ monotherapy data from the IL-Believe Trial, and was the first presentation of dose escalation data informing recommended Phase 2 dose (RP2D) for TransCon IL-2 β⁄γ in combination with a checkpoint inhibitor....Anti-tumor clinical responses were observed with TransCon IL-2 β⁄γ both as monotherapy (colorectal cancer with confirmed partial response (PR)) and in combination with pembrolizumab (small cell lung cancer (SCLC), 1 with confirmed PR and, subsequent to the August 15, 2023 data cutoff, 1 ongoing with an unconfirmed complete response)....we continue enrolling into indication-specific cohorts and look forward to sharing preliminary data from these cohorts in the second half of 2024.'"

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Ascendis Pharma Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "Enrollment initiated in the Phase 2 portion in indication-specific cohorts, with expected 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

Phase 1/2 dose escalation and dose expansion study of TransCon IL-2 β/γ alone or in combination with pembrolizumab: Initial results from dose escalation. (ASCO 2023) - P1/2 | "TransCon IL-2 β/γ is generally well-tolerated as monotherapy and in combination with pembrolizumab. The pharmacodynamics data confirm a durable activation and expansion of IL-2Rβ/γ+ cytotoxic immune cells over IL-2Rα+ eosinophils and Tregs. Clinical trial information: NCT05081609."

Combination therapy • P1/2 data • Anemia • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • Thrombocytopenia • IL2

Ascendis Pharma Oncology Program Update Highlights Latest Clinical Data for Product Candidates (GlobeNewswire) - P1/2 | N=317 | IL Believe (NCT05081609) | Sponsor: Ascendis Pharma Oncology | "At RP2D, TransCon IL-2 β/γ was generally well-tolerated with no DLT observed, no vascular leak syndrome and no grade 3 or 4 cytokine release syndrome. As designed, the non-alpha TransCon IL-2 β/γ expanded local and systemic cytotoxic immune effector cells (CD8+ T and NK cells) without clear effect on Tregs and eosinophils. RP2D for combination therapy with checkpoint inhibitor dose escalation data expected in the third quarter of 2023 and will be presented at a scientific congress in the fourth quarter."

P1/2 data • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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