Ascendis Pharma A/s · NASDAQ:ASND
Ascendis Pharma A/s — Investor Day (May 2023)
74 slides from Ascendis Pharma A/s's investor day presentation, May 31, 2023
Slide 1: Oncology Program Update
Ascendis Pharma A/S Oncology Program Update May 31, 2023 Exhibit 99.1
Slide 2: Cautionary Note on Forward-Looking Statements
Cautionary Note on Forward-Looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding our prospective product candidates; clinical trial results; the expected timing o
Slide 3: Oncology R&D Day Agenda
Oncology R&D Day Agenda Welcome & Agenda Overview Scott T. Smith, EVP, CFO Vision 3x3 Jan Møller Mikkelsen, President & CEO TransCon™ Platform & Product Innovation Kennett Sprogøe, Ph.D. EVP, Head of Innovation and Research 10:05-10:20 a.m. 10:00 a.m. 10:20-10:35 a.m. Clinical Development Strategy &
Slide 4: Vision 3x3: Our Vision for Oncology
Vision 3x3 Our Vision for Oncology Jan Mikkelsen President & Chief Executive Officer
Slide 5: Vision 3x3: Building a Leading Global Biopharma Company
Vision 3x3: Building a Leading Global Biopharma Company Our goal is to achieve sustainable growth through multiple approaches Obtain regulatory approval for three independent Endocrinology Rare Disease products TransCon hGH for pediatric growth hormone deficiency TransCon PTH for adult hypoparathyro
Slide 6: Why Oncology?
Why Oncology? Very large unmet medical need Large number of clinically validated pathways which are limited by toxicity, efficacy, and ease of administration Suitable for use with the TransCon Technology platform Systemic delivery Localized delivery Potential to address all the aspect of the cancer
Slide 7: Interleukin Overview
Interleukin 2 Overview First immunologic compound in cancer FDA approved for the treatment of metastatic renal cell carcinoma (1992) FDA approved for the treatment for metastatic melanoma (1998) Interleukin shown to be effective in approximately 15% of patients Number of Responding Patients (respons
Slide 8: TransCon Technology Platform & Product Innovation in Oncology
TransCon™ Technology Platform & Product Innovation in Oncology Kennett Sprogøe, Ph.D. EVP, Head of Innovation and Research
Slide 9: TransCon platform suited for amplified and durable immune activation
TransCon platform is uniquely suited for amplified and durable immune activation, with the aim for addressing significant unmet medical need TransCon: An Innovative Technology Platform TransCon technologies combine the benefits of prodrug and predictable release technologies. TransCon soluble prodru
Slide 10: Transient Conjugation: A Powerful, Flexible Platform
Transient Conjugation: A Powerful, Flexible Platform Aromatic Cyclic Imide DKP Carbamate Bicin AEG Pyroglutamate Parent Drug TransCon Carrier TransCon Platform: 3 components TransCon Linker Antibodies, Antibody Fragments, Proteins, Peptides and Small Molecules Soluble Carriers Insoluble Carriers Loc
Slide 11: Stimulating Local Immunity to Achieve Systemic Effect
Stimulating Local Immunity to Achieve Systemic Effect TransCon IL-2 b/g and TransCon TLR7/8 Agonist have been designed mechanistically for monotherapy and synergistic combination effects TransCon TLR7/8 Agonist for long-acting IT delivery Turns the tumor hot Enhances education of T cells Recruits sy
Slide 12: The Immune System in Normal Compared to Inflamed Tissue
The Immune System in Normal Compared to Inflamed Tissue Tissue resident immune cells survey all organs and act as first responders in response to threats Local chemokines attract effector cells from blood and surrounding tissue Local cytokines such as IL-2 proliferate, activate and potentiate the im
Slide 13: The Immune System in Cold versus Hot Tumors
The Immune System in Cold versus Hot Tumors Tcirc: Circulating T cells, NK: Natural killer cells, APC: Antigen presenting cell, TRM: Tissue resident T cell (effector & memory), CTL: Cytotoxic T cell (CD8+), Tmem: Memory T cell (CD4+), Th1 & Th2: T helper 1 or 2 cell, M1 & M2: M1- or M2-like macropha
Slide 14: Optimal Product Design Parameters
Optimal Product Design Parameters Ideal TLR agonist Design Sustained high local concentration Potent pro-inflammatory TLR agonist Pharmacology / PD Sustained inflammation in the tumor, with high cyto- and chemokine release Convenient dosing Clinical Clinical activity in injected and non-injected tum
Slide 15: TransCon TLR7/8 Agonist: Using TransCon Hydrogel Technology
TransCon TLR7/8 Agonist: Using TransCon Hydrogel Technology for Targeted Intratumoral Exposure TransCon TLR7/8 Agonist
Slide 16: Sustained Local Intratumoral Release of Resiquimod
pH and temperature dependent linker cleavage Local depot of drug loaded TransCon hydrogel carrier Sustained Local Intratumoral Release of Resiquimod Using TransCon hydrogel enables high local concentration of resiquimod with low systemic exposure
Slide 17: TransCon TLR7/8 Agonist: Turning the Tumor Hot
TransCon TLR7/8 Agonist: Turning the Tumor Hot TransCon TLR7/8 Agonist is designed for high intratumoral exposure over several weeks with minimal systemic exposure and to turn the tumor hot using a potent TLR agonist1 Local and abscopal effect expected via increased antigen presentation in tumor & d
Slide 18: TransCon IL-2 b/g: Sustained Release of Non-alpha IL-2
TransCon IL-2 b/g: Sustained Release of Non-alpha IL-2 Using Validated Prodrug Technology TransCon IL-2 b/g
Slide 19: TransCon IL-2 b/g Best-in-Class Design
TransCon IL-2 b/g Best-in-Class Design Rosen D, et al. AACR annual meeting. 2020; Poster 4507. TransCon linker slowly releases IL-2 b/g TransCon carrier IL-2 b/g TransCon linker TransCon IL-2 b/g (Prodrug) Active IL-2 b/g % Release of IL-2 b/g TransCon IL-2 b/g in vitro release kinetics TransCon IL-
Slide 20: TransCon IL-2 β/γ: Built on Years of Learnings
TransCon IL-2 β/γ: Built on 30 Years of Learnings TransCon IL-2 b/g is designed to enhance both local and systemic immune responses and synergize with hot tumor biology 1Data on file 2Bioconjugate Chem. 2004, 15, 6, 1304–1313 Variant β/γ Bias Potency reduction1 Size2 (Radius) IL-2 No n/a 2 nm IL-2 β
Slide 21: Two Products Designed for Monotherapy and Synergistic Mode of Action
Two Products Designed for Monotherapy Effects and Synergistic Mode of Action Tcirc: Circulating T cells, NK: Natural killer cells, APC: Antigen presenting cell, TRM: Tissue resident T cell (effector & memory), CTL: Cytotoxic T cell (CD8+), Tmem: Memory T cell (CD4+), Th1: T helper 1 cell, M1: M1 mac
Slide 22: Optimal Product Design Parameters
Optimal Product Design Parameters Ideal TLR agonist Design Sustained high local concentration Potent pro-inflammatory TLR agonist Pharmacology / PD Sustained inflammation in the tumor, with high cyto- and chemokine release Convenient dosing Clinical Clinical activity in injected and non-injected tum
Slide 23: Clinical Development Strategy & Clinical Updates
Clinical Development Strategy & Clinical Updates Stina Singel, M.D., Ph.D. EVP, Head of Clinical Development, Oncology
Slide 24: Removing the Immune Brakes Is Not Sufficient for Majority of Tumors
Removing the Immune Brakes Is Not Sufficient for Majority of Tumors Hirsch et al. 2019 British Journal of Cancer 120:3–5, Reproduced with permission from Springer Nature Primary and acquired resistance to immune checkpoint inhibitors limit the benefit from checkpoint inhibitors Response rate (ORR) o
Slide 25: Melanoma First Solid Tumor to Benefit from Checkpoint Inhibitors
Melanoma is the First Solid Tumor to Demonstrate Benefit from Checkpoint Inhibitors Reprinted from Eur J Cancer, Vol /edition number, Ugurel et al., Survival of patients with advanced metastatic melanoma: The impact of MAP kinase pathway inhibition and immune checkpoint inhibition - Update 2019, 202
Slide 26: Many Patients Do Not Benefit Sufficiently from Checkpoint Inhibitors in Melanoma
Many Patients Do Not Benefit Sufficiently from Checkpoint Inhibitors in Melanoma Adapted from Ugurel et al. Eur J Cancer 2020; 130:126-138 Unmet Need Anti-CTLA4 + anti-PD-1 Anti-PD-1 Anti-CTLA4
Slide 27: Novel Approaches Are Needed in Melanoma
Novel Approaches Are Needed in Melanoma Checkpoint inhibition is not sufficient here Adapted from Ugurel et al. Eur J Cancer 2020; 130:126-138 Unmet Need Anti-CTLA4 + anti-PD-1 Anti-PD-1 Anti-CTLA4
Slide 28: Product Candidates in Oncology: TransCon TLR7/8 Agonist
Product Candidates in Oncology TransCon TLR7/8 Agonist
Slide 29: Resiquimod: TLR7/8 Agonist
Resiquimod: TLR7/8 Agonist 1,2 Small molecule agonist of both TLR7 and TLR8 TLR7: mainly expressed in dendritic cells (DCs), to some extent in B cells, monocytes, macrophages TLR8: primarily expressed in DCs, monocytes, macrophages Potent activator of the innate immunity Elevates proinflammatory cyt
Slide 30: transcendIT-101 Oral Presentation at SITC 2022
transcendIT-101 Oral Presentation at SITC 2022 Intratumoral TransCon TLR7/8 Agonist RP2D declared at 0.5mg/lesion Generally well-tolerated with 1 DLT (grade 3 injection site reaction) from 23 patients treated in dose escalation cohorts, as monotherapy or in combination with pembrolizumab PK data sho
Slide 31: TransCon TLR7/8 Agonist Has Monotherapy Anti-Tumor Activity
TransCon TLR7/8 Agonist Has Monotherapy Anti-Tumor Activity Locally and Systemically Datacut 21 Sept 2022 Clinical activity observed with partial response (PR) with monotherapy, including abscopal effect in non-injected lesions, which we continue to see in additional patients
Slide 32: Product Candidates in Oncology: TransCon IL-2 b/g
Product Candidates in Oncology IL-2 Selective for the IL-2Rb/g TransCon IL-2 b/g
Slide 33: Aldesleukin – Higher Lymphocyte Count Correlated with Better Efficacy
Aldesleukin – Higher Lymphocyte Count Correlated with Better Efficacy Rosenberg 1998 Ann Surg 228(3):307-19. 600,000 IU/kg (0.037 mg/kg) IV every 8 hours by for max 14 doses. Following 9 days of rest, the schedule is repeated for another 14 doses, for a max of 28 doses per course, as tolerated. -Pro
Slide 34: Maximizing IL-2 Therapy Limited by Toxicity or Insufficient Expansion
Maximizing IL-2 Therapy Has So Far Been Limited by Toxicity or Insufficient Lymphocyte Expansion and Short Drug Exposure Aldesleukin Reprinted from Blood, 107(6):2409, Ahmadzadeh and Rosenberg , IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients, Copyright 2006, wi
Slide 35: Sustained Immunological Activation Potentially Increases Effectiveness
Sustained Immunological Activation Potentially Increases Effectiveness While Lowering Toxicity Risk IV three times a day in ICU for 5 days, rest 9 days, repeat for max 28 doses as tolerated (Proleukin product insert) IV outpatient once every 3 weeks until progressive disease or unacceptable toxicity
Slide 36: IL-Believe Phase 1/2 Trial Design and Next Steps
IL-Believe Phase 1/2 Trial Design and Next Steps Study designed to define maximum tolerated dose and assess preliminary anti-tumor efficacy Dose Escalation (“3+3” Design) Ph2 Dose Expansion at RP2D Combination with pembrolizumab: Ongoing Cohort 3 TransCon IL-2 b/g + chemo PROC Cohort 4 TransCon IL-2
Slide 37: TransCon IL-2 b/g Dose Escalation Status
Monotherapy: Completed Combination with pembrolizumab: Ongoing TransCon IL-2 b/g Dose Escalation n=4; no DLTs TransCon IL-2 b/g Phase 1 Trial Dose Escalation Status n=4; no DLTs n=5, 1 DLT n=3; no DLTs n=5; no DLTs n=5; no DLTs n=8, no DLTs n=5; no DLTs Study status as of 18 May 2023 enrolling Monot
Slide 38: Preliminary Safety Overview Monotherapy Dose Escalation
TransCon IL-2 b/g Phase 1 Preliminary Safety Overview Monotherapy Dose Escalation *Primary reason for study discontinuation in End of Treatment (EOT) is death due to progressive disease **Subject discontinued treatment due to AEs (including CRS, myalgia and worsening cancer pain) Events Dose (mg/kg)
Slide 39: Preliminary Safety Overview Monotherapy Dose Escalation
TransCon IL-2 b/g Phase 1 Preliminary Safety Overview Monotherapy Dose Escalation Events Dose (mg/kg) Subjects with Any 20 N=4 n (%) 40 N=3 n (%) 80 N=5 n (%) 120 N=8 n (%) 160 N=5 n (%) Dose Limiting Toxicity (DLT) 0 (0) 0 (0) 0 (0) 0 (0) 1 (20) (1) G3 Worsening CRS Grade ≥3 TEAEs related to TransC
Slide 40: Preliminary Safety Overview Monotherapy Dose Escalation
TransCon IL-2 b/g Phase 1 Preliminary Safety Overview Monotherapy Dose Escalation Events Dose (mg/kg) Subjects with Any 20 N=4 n (%) 40 N=3 n (%) 80 N=5 n (%) 120 N=8 n (%) 160 N=5 n (%) Dose Limiting Toxicity (DLT) 0 (0) 0 (0) 0 (0) 0 (0) 1 (20) (1) G3 Worsening CRS Grade ≥3 TEAEs related to TransC
Slide 41: Absolute Lymphocyte Count and Eosinophils One Week After First Dosing
Absolute Lymphocyte Count (ALC) and Eosinophils One Week After First Dosing ALC on C1D8 (x1000 cells/mL) 20 mg/kg 40 mg/kg 80 mg/kg 120 mg/kg 160 mg/kg mean 1.4 2.4 3.1 5.2 5.1 median 1.5 2.0 3.4 4.5 4.7 Absolute lymphocyte count Eosinophils EOS on C1D8 (x1000 cells/mL) 20 mg/kg 40 mg/kg 80 mg/kg 12
Slide 42: Cytotoxic Immune Cells and Treg Cells One Week After First Dosing
Cytotoxic Immune Cells (CD8+ T and NK cells) and Regulatory T (Treg) Cells One Week After First Dosing Normal range – calculated from normal range of CD4+ T cells: Liotta et al., 2010 - Frequency of regulatory T cells in peripheral blood and in tumour-infiltrating lymphocytes correlates with poor pr
Slide 43: TransCon IL-2 β/γ Changes Lymphocyte Composition Towards Cytotoxic Lymphocytes
TransCon IL-2 β/γ Changes the Lymphocyte Composition Towards a Majority of Cytotoxic Lymphocytes One Week After First Dosing Average cell count per dose-level - calculated from ALC and Flow Cytometry results *Cell count based on all available data RP2D
Slide 44: Monotherapy Dose Escalation Status of Efficacy-Evaluable Patients
TransCon IL-2 b/g Phase 1 Monotherapy Dose Escalation Status of Efficacy-Evaluable Patients Data Cut Apr 28, 2023 HNSCC 3 + MSS CRC 3 - Sigmoid Colon 3 - SCLC 2 + Esophageal 2 - HNSCC 2 + Ovarian 3 - Pancreatic 3 - Ovarian 4 - Breast 9 - Cholangiocarcinoma 4 - RCC 4 + MSI-h CRC 5 + Pancreatic 4 - TN
Slide 45: Monotherapy Dose Escalation Status of Efficacy-Evaluable Patients
TransCon IL-2 b/g Phase 1 Monotherapy Dose Escalation Status of Efficacy-Evaluable Patients Data Cut Apr 28, 2023 HNSCC 3 + MSS CRC 3 - Sigmoid Colon 3 - SCLC 2 + Esophageal 2 - HNSCC 2 + Ovarian 3 - Pancreatic 3 - Ovarian 4 - Breast 9 - Cholangiocarcinoma 4 - RCC 4 + MSI-h CRC 5 + Pancreatic 4 - TN
Slide 46: Monotherapy Dose Escalation Status of Efficacy-Evaluable Patients
TransCon IL-2 b/g Phase 1 Monotherapy Dose Escalation Status of Efficacy-Evaluable Patients Data Cut Apr 28, 2023 HNSCC 3 + MSS CRC 3 - Sigmoid Colon 3 - SCLC 2 + Esophageal 2 - HNSCC 2 + Ovarian 3 - Pancreatic 3 - Ovarian 4 - Breast 9 - Cholangiocarcinoma 4 - RCC 4 + MSI-h CRC 5 + Pancreatic 4 - TN
Slide 47: Patient 1: Heavily Pre-treated Metastatic Colorectal Cancer
Patient 1: Heavily Pre-treated Metastatic Colorectal Cancer Patient with metastatic colorectal cancer (CRC): Tumor genetics: Microsatellite Instability High (MSIh); BRAF V600E Prior 5 lines of systemic treatments, including nivolumab, all with Best Overall Response of Stable Disease (SD) Started on
Slide 48: Patient 2: Heavily Pre-treated Metastatic Pancreatic Cancer
Patient 2: Heavily Pre-treated Metastatic Pancreatic Cancer Patient who progressed after 3 prior lines of systemic treatment Widely metastatic pancreatic cancer including liver and lung involvement TransCon IL-2 b/g monotherapy treated since June 2022 Long stable disease ongoing ~1 year on treatment
Slide 49: Recommended Phase 2 Dose for TransCon IL-2 b/g
Recommended Phase 2 Dose (RP2D) for TransCon IL-2 b/g Determined from Multiple Observations Aiming to cure more cancer patients safely with amplified and durable immune activation Safety Profile: generally well-tolerated with no DLT out of 8 patients dosed; no vascular leak syndrome; no grade 3 or 4
Slide 50: Next Steps: Phase 2 Indication-Specific Cohorts
Next Steps: Phase 2 Indication-Specific Cohorts 1/2L=1st or 2nd line; 2/3L=2nd or 3rd line; HNSCC=head and neck squamous cell cancer; cSCC=cutaneous squamous cell cancer; HPV=human papilloma virus; NSCLC=non-small cell lung cancer; PROC=platinum resistant ovarian cancer Broad clinical development pl
Slide 51: Multiple Combination Opportunities to Optimize Treatment
Multiple Combination Opportunities to Optimize Treatment TransCon IL-2 b/g IO combinations Cytotoxics Antibodies Adjuvants Targeted therapies Chemotherapies Bispecifics Antibody-drug conjugates Naked antibodies Cellular therapies Cancer vaccines Innate immune activators (TransCon TLR7/8 Agonist) Che
Slide 52: Oncology Program Summary and Future Directions
Oncology Program Summary and Future Directions TransCon IL-2 b/g Phase 1 monotherapy dose escalation complete with RP2D determined at 120mg/kg IV every three weeks in May 2023 Clinical activity observed with monotherapy anti-tumor response in CRC and long stable disease in pancreatic cancer TransCon
Slide 53: Investigator Perspectives
Investigator Perspectives Diwakar Davar, M.D., Associate Professor Clinical Director of Melanoma and Skin Cancer Program, University of Pittsburgh Medical Center (UPMC), Hillman Cancer Center
Slide 54: Disclosures and Funding – Dr. Davar
Disclosures and Funding – Dr. Davar Grants/Research Support (institutional): Arcus, CellSight Technologies, Immunocore, Merck, Regeneron Pharmaceuticals Inc., Tesaro/GSK. Consultant: ACM Bio, Ascendis Pharma, Clinical Care Options (CCO), Gerson Lehrman Group (GLG), Merck, Medical Learning Group (MLG
Slide 55: Metastatic Pancreatic Cancer on TransCon IL-2 b/g Monotherapy
Metastatic Pancreatic Cancer on TransCon IL-2 b/g Monotherapy NEW SLIDE – PENDING VETTING mm=millimeter; RECIST v1.1=Response Evaluation Criteria for Solid Tumors version 1.1; PR=partial response; CR=complete response; PD=progressive disease; SD=stable disease Datacut 17 May 2023 Diagnosed metastati
Slide 56: Metastatic Pancreatic Cancer with Long Stable Disease
Metastatic Pancreatic Cancer with Long Stable Disease on TransCon IL-2 b/g Monotherapy Visit Sum of Diameters in mm (% change from baseline) Target Lesion Response Non-target Response New Lesion RECIST v1.1 Overall Response Baseline 64.6 Week 9 63.5 (-2%) SD Non-CR/Non-PD No SD Week 18 70.4 (+9%) SD
Slide 57: 2nd Generation IL-2 Agonists Aim to Harness T cells and NK cells
2nd Generation IL-2 Agonists Aim to Harness T cells and NK cells REF: 1Raker VR, Cells 2020; 2Hashimoto M, Nature 2022; 3Deak LC, Nature 2022 CONFIDENTIAL Augmenting PD-1 Efficacy without Additional Costim (CD28) or Coinhibition (CTLA-4, TIM-3, LAG-3) Interleukin-2 (IL-2) is a T cell growth factor t
Slide 58: 2nd Generation IL-2 Agonists: Drug and Company Landscape
2nd Generation IL-2 Agonists Aim to Harness T cells and NK cells CONFIDENTIAL Drug (Company) Description Phase Indications Nemvaleukin alfa (Alkermes) IL-2-CD25 fusion 3 Ovarian cancer (ARTISTRY-7) Nemvaleukin alfa (Alkermes) IL-2-CD25 fusion 2 Cutaneous and mucosal melanoma (ARTISTRY-6) 1 Single ag
Slide 59: Overcoming Checkpoint Inhibitor Resistance with Innate Agonists
Overcoming Immune Checkpoint Inhibitor Resistance in Cancer with Innate Agonists1 1Demaria, Nature 2019 Harnessing innate immunity in cancer therapy Targeting anti-microbial immunity for anti-tumor effects (TLR7/8/9, RIG-I, STING, NLRP3) Amplification of immune response (APC activation; co-stimulato
Slide 60: Toll-Like Receptors: Well-Validated Targets
Toll-Like Receptors (TLRs): Well-Validated Targets for Activation of Innate and Adaptive Immunity1 Activate innate immunity in particular antigen presenting cells (APCs) Prime and expand cytolytic and helper T cells Activate and expand cytotoxic lymphocytes Resiquimod has been clinically evaluated a
Slide 61: Resiquimod: TLR7/8 Agonist
Resiquimod: TLR7/8 Agonist1,2 Small molecule agonist of both TLR7 and TLR8 TLR7: mainly expressed in plasmacytoid dendritic cells (pDCs), to some extent in B cells, monocytes, macrophages and conventional dendritic cells (DCs) TLR8: primarily expressed in conventional DCs, monocytes, macrophages and
Slide 62: transcendIT-101 Trial Open Cohorts
transcendIT-101 Trial Open Cohorts Phase 1/2, Open-label, Dose Escalation and Dose Expansion Study of TransCon TLR7/8 Agonist Alone or in Combination with Pembrolizumab in Participants with Locally Advanced or Metastatic Solid Tumor Malignancies (ClinicalTrials.gov: NCT04799054) Part 1: Monotherapy
Slide 63: transcendIT-101 Safety and Pharmacokinetics Overview
transcendIT-101 Safety and Pharmacokinetics Overview Safety: TransCon TLR7/8 Agonist was generally well-tolerated with a low incidence of DLTs (1 grade 3 injection site reaction) from 23 patients treated in dose escalation cohorts, as monotherapy or in combination with pembrolizumab All TEAEs relate
Slide 64: Patient Status by Investigator Assessment per RECIST v1.1
Patient Status by Investigator Assessment per RECIST v1.1 (by indication) Data cut-off 02February 2023 SD=Stable Disease; PR=Partial Response; PD=Progressive Disease In TransCon TLR7/8 Agonist monotherapy cohorts: 2 of 11 (18%) participants had a partial response (1 confirmed and 1 unconfirmed) and
Slide 65: Pharmacodynamic Markers Confirm Target Engagement and Mechanism
Pharmacodynamic Markers Confirm TransCon TLR7/8 Agonist Target Engagement and Mechanism of Action Intratumoral recruitment of Macrophages and CD8+ T cells Induction and sustained elevation of intratumoral TLR7/8 and Type I IFN pathway gene expression CD68+ Macrophages CD8+ T cells
Slide 66: Main Classes of TLR Agonists in Clinical Development
Main Classes of TLR Agonists in Clinical Development TransCon TLR7/8 agonist Vidutolimod BDB001 4 arm pegylated Resiquimod NKTR-262 Discontinued Intratumoral TLR7/8 agonist Sustained Release Intratumoral TLR7/8 agonist Systemic TLR7/8 agonist Intratumoral TLR9 agonist VLP Salt form Resiquimod TAC-00
Slide 67: TLR Agonist and Molecule Engineering Comparison
TLR agonist and molecule engineering Sustained exposure Schedule Route of administration Limited systemic exposure Early and sustained CXCL10 levels Indications under clinical evaluation and combination treatment Development status TransCon TLR7/8 Agonist ü Q3W or Q6W Intratumoral ü ü transcendIT-10
Slide 68: Summary of Investigator Perspective
Summary of Investigator Perspective on TransCon IL-2 b/g and TransCon TLR7/8 Agonist Immune checkpoint inhibitors have transformed the management of patients with multiple advanced cancers but have some limitations. PD-1/PD-L1 interaction is utilized by cancer but also self-reactive T cells that esc
Slide 69: Closing Remarks
ascendis LA pharma Closing Remarks
Slide 70: TransCon TLR7/8 Agonist Primes Immune Cells Locally
TransCon TLR7/8 Agonist Primes Immune Cells Locally for Systemic Antitumor Effect Intratumoral TransCon TLR7/8 Agonist uses the injected tumor to elicit systemic anti-tumor effects Safety Profile: generally well-tolerated with low systemic side effects Long effective half-life with low Cmax Sustaine
Slide 71: TransCon IL-2 b/g Provides a Systemic Immune Boost
TransCon IL-2 b/g Provides a Systemic Immune Boost Aiming to cure more cancer patients safely with amplified and durable immune activation Safety Profile: generally well-tolerated with no DLT out of 8 patients dosed; no vascular leak syndrome; no grade 3 or 4 cytokine release syndrome Long effective
Slide 72: TransCon IL-2 b/g: Potential Best-in-Class IL-2 Therapy
TransCon IL-2 b/g: Potential Best-in-Class IL-2 Therapy TransCon IL-2 b/g1 5-kDa pegylation, TransCon Technology THOR-7072 30-kDa pegylation Recommended Phase 2 Dose (monotherapy) 120 mg/kg Q3W 24 mg/kg Q3W3 Retains high potency compared to Aldesleukin Yes No Effective half life > 35 h 9-12 h Non-Al
Slide 73: Next Steps for Ascendis' Immunotherapy Program
Next Steps for Ascendis’ Immunotherapy Program Heterogeneity across cancers, organs, and patients requires diversity of approaches to achieve benefit for patients TransCon IL-2 b/g and TransCon TLR7/8 Agonist both showed acceptable safety profile and single-agent clinical activity Optimally position
Slide 74: Q&A Session
Q&A Session Email questions to: IR@ascendispharma.com ©2023 Ascendis Pharma. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon and Skytrofa are trademarks owned by the Ascendis Pharma Group.