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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 o

Key Takeaway: Ascendis Pharma A/S Virtual Oncology R&D Day November 20, 2020 Exhibit 99.1 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 sta

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Ascendis Pharma A/S Virtual Oncology
R&D Day November 20, 2020 Exhibit 99.1
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 future results of operations and financial position,
including our business strategy, prospective products, availability of funding, clinical trial results, product approvals and regulatory pathways, collaborations, licensing or other arrangements, the scope, progress, results and costs of developing
our product candidates or any other future product candidates, the potential market size and size of the potential patient populations for our product candidates, timing and likelihood of success, plans and objectives of management for future
operations, the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates, and future results of current and anticipated products, are forward-looking statements. These forward-looking
statements are based on our current expectations and beliefs, as well as assumptions concerning future events. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially
from the results discussed in the forward-looking statements. These risks, uncertainties and other factors are more fully described in our reports filed with or submitted to the Securities and Exchange Commission, including, without limitation, our
most recent Annual Report on Form 20-F filed with the SEC on April 3, 2020 particularly in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations".
In light of the significant uncertainties in our forward-looking statements, you should not place undue reliance on these statements or regard these statements as a representation or warranty by us or any other person that we will achieve our
objectives and plans in any specified timeframe, or at all. Any forward-looking statement made by us in this presentation speaks only as of the date of this presentation and represents our estimates and assumptions only as of the date of this
presentation. Except as required by law, we assume no obligation to update these statements publicly, whether as a result of new information, future events, changed circumstances or otherwise after the date of this presentation. This presentation
concerns product candidates that are or have been under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration, European Medicines Agency or other foreign regulatory authorities. These
product candidates are currently limited by U.S. Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated. Oncology product rights owned by
Ascendis Pharma Oncology Division A/S (a wholly owned subsidiary of Ascendis Pharma A/S). Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo and TransCon are trademarks owned by the Ascendis Pharma Group. November 2020
Ascendis Pharma A/S.
Virtual Oncology R&D Day Agenda
Welcome & Agenda Overview Scott T. Smith, SVP, CFO Vision 3x3 Jan M ller Mikkelsen, President & CEO TransConTM Platform & Product Innovation Kennett Sprog e, Ph.D., SVP, Head of Innovation and Research 9:01-9:05 a.m. 9:00 a.m.
9:05-9:20 a.m. TransCon TLR7/8 Agonist & TransCon IL-2 b/g Juha Punnonen, M.D., Ph.D., SVP, Head of Oncology Stina Singel, M.D., Ph.D., Head of Clinical Development, Oncology Q&A 10:00-10:30 a.m. 9:20-10:00 a.m.
Vision 3x3 Jan M ller Mikkelsen
Company Overview Create best-in-class
products addressing unmet medical needs by applying TransCon technologies to parent drugs with clinical proof-of-concept Endocrinology rare disease TransCon hGH: pediatric GHD BLA (PDUFA June 25, 2021) and MAA submitted; adult GHD phase 3
trial ongoing TransCon PTH: Submitted US, Canadian and European regulatory filings to initiate adult HP phase 3 trial TransCon CNP: Phase 2 ACcomplisH ongoing and ACcomplisH China Trial1 initiated for achondroplasia Build leading market positions
for each product candidate with commercial focus on maximizing global reach Strategic investment in VISEN Pharmaceuticals for endocrinology rare disease products in China Oncology First IND filing expected for TransCon TLR7/8 Agonist by year-end
2020 TransCon IL-2 b/g IND filing or similar expected in Q3 2021 As of September 30, 2020, cash, cash equivalents and marketable securities of 957.5 million 1Through VISEN Pharmaceuticals
Vision 3x3: Building a Leading
BioPharma Company Our Goal is to Achieve Sustainable Growth through Multiple Approaches Obtain regulatory approval for three independent Endocrinology Rare Disease products TransCon Growth Hormone for pediatric growth hormone deficiency TransCon PTH
for adult hypoparathyroidism TransCon CNP for achondroplasia Grow Endocrinology Rare Disease pipeline through Global clinical reach Pursuing 9 total indications, label optimization, and life cycle management New endocrinology products Establish
global commercial presence for our Endocrinology Rare Disease area Build integrated commercial organization in North America and select European countries Establish global commercial presence through partners with local expertise and infrastructure
Advance a high value oncology pipeline with one IND or similar filing each year Create a third independent therapeutic area with a diversified pipeline
TransCon Technology Platform &
Product Innovation Kennett Sprog e, Ph.D. SVP, Head of Innovation and Research
The Evolution of TransCon Technology
Precise release of active drug, from a prodrug, without changing the molecule's biology TransCon technology reversibly conjugates a drug to a carrier and predictably releases the unmodified drug under physiological conditions Vision of
Ascendis Founding Scientists The Historical Challenge The Revolutionary Solution Conventional technologies (protein enlargement and encapsulation) are associated with altered biology and unpredictable drug release To combine prodrug and predictable
release technologies into one platform to ensure tailored delivery of unmodified drug
Transient Conjugation: A Powerful,
Flexible Platform Parent Drug Soluble Carriers Insoluble Carriers Antibodies, Antibody Fragments, Proteins, Peptides and Small Molecules Aromatic Cyclic Imide DKP Carbamate Bicin AEG Pyroglutamate TransCon Carrier TransCon Prodrug: 3 components
TransCon Technology: The TransCon
Linker Cleaves in an enzyme-independent fashion, ensuring reproducible drug release; in vitro to in vivo correlation with high predictability TransCon linkers remain covalently bound to the carrier molecule after release of the unmodified parent
drug Enables tunable design of prodrugs with dosing frequency from daily up to six months or more Carrier Drug Drug Carrier pH 7.4; 37 C
TransCon Technology: Sustained
Systemic Release Parent drug is transiently bound to a TransCon linker-soluble carrier moiety, which inactivates and shields parent drug from clearance Designed to distribute released molecule like the parent drug; linker-carrier is cleared renally
Following injection, the linker is designed to autocleave at a specific rate to predictably release unmodified parent drug TransCon carrier TransCon linker Parent drug (inactive) Unmodified parent drug (active) Receptor Linker cleavage dependent
upon pH and temperature Renal clearance Prodrug (inactive)
Parent drug is transiently bound to
TransCon linker-hydrogel carrier, which inactivates, shields parent drug and prevents clearance Designed to provide sustained high local drug levels with low systemic exposure; hydrogel degrades into small polymers that are renally cleared Following
injection, the linker is designed to autocleave at a specific rate to predictably release unmodified parent drug TransCon Technology: Sustained Localized Release Linker cleavage dependent on pH and temperature Parent drug (inactive) Unmodified
parent drug (active) TransCon hydrogel carrier Receptor Renal clearance TransCon linker Prodrug (inactive)
TransCon IT: Potential Paradigm
Shift in Intratumoral Delivery TransCon Intratumoral (IT) addresses the problems of conventional IT administration including rapid clearance from the tumor, high systemic exposure and toxicity Data on file. TransCon IT is designed to stay in the
tumor and slowly release the drug ensuring high tumor drug concentration and low systemic exposure Systemic concentration of released drug Tumor concentration of released drug Single TransCon IT Dose in Mice Concentration (ng/mL SD)
Algorithm Used in Endocrinology Used
to Build Oncology Pipeline Unmet Medical Need Clinically Validated Parent Drug TransCon Technology Suitability Clearly Differentiated Product Established Clinical & Regulatory Pathway Large Addressable Market Higher Value, Lower Risk Pipeline
Our unique algorithm for product innovation has resulted in clinical validation of 3 out of 3 product candidates in endocrinology rare diseases We are continuing to apply our algorithm to build a pipeline in oncology and are committed to entering a
3rd therapeutic area
TransCon Enables Multi-level Patent
Protection As of December 31, 2019. TransCon prodrugs eligible for new composition of matter IP TransCon prodrugs are new chemical entities Enables new patent life for prodrugs of parent drugs A multi-layered patent strategy is applied to
protect our assets Composition of Matter > 150 Issued Patents >300 Patent Applications Pending Device Dose Regimen Process TransCon Carriers TransCon Linkers Product Concepts
Our vision is to leverage TransCon
technologies to turn the body's immune system into the therapeutic - to improve patient outcomes TransCon: An Innovative Technology Platform TransCon technologies combine the benefits from prodrug and predictable release technologies
with the known biology of the parent drug Technology validated within endocrinology with a high success rate in multiple clinical programs; TransCon hGH BLA/MAA filed Building on the success in endocrinology, we apply our algorithm for
product innovation to help select our oncology pipeline Developed an intratumoral platform that aims to transform IT administration of small molecules, peptides, proteins, antibody fragments and antibodies TransCon prodrugs are new chemical
entities eligible for new composition of matter IP
Oncology Juha Punnonen, M.D., Ph.D.
SVP, Head of Oncology Stina Singel, M.D., Ph.D. Head of Clinical Development, Oncology
TransCon Positioned to Transform
Cancer Therapy TransCon systemic and IT therapies designed to enhance anti-tumor responses by Providing sustained modulation of tumor microenvironments Activating cytotoxic immune cells Tumor cells Immune-suppressing cells Cytotoxic T cells and
other cancer fighters Cold Tumor Hot Tumor No Tumor X Applicable for diverse drug classes and mechanisms of action; opportunity for combination approaches
Oncology Portfolio Strategy Create
best-in-class oncology therapies by applying TransCon systemic and IT technologies to parent drugs addressing clinically validated pathways Improve outcomes with parent drugs that are currently limited by suboptimal efficacy and systemic toxicity
Apply Ascendis' unique algorithm for product innovation to oncology development Build a diversified high-value pipeline addressing multiple indications Two near-term IND candidates with potential synergistic combination effects Enable rapid
path to global commercialization
Intratumoral Treatment Has Been
Challenging 1 Example: STING agonist "plasma half-life ranging from 8 to 28 min" Meric-Bernstam F, et al. ASCO annual meeting, 2019; Oral presentation: Abstract 2507. Treatment of cancer via IT administration of oncolytic virus has
achieved clinical proof of concept with talimogene laherparepvec (T-VEC) in advanced melanoma However, conventional IT treatments face major challenges due to short tumor exposures1, high systemic Cmax and need for frequent dosing TransCon
technology has the potential to overcome the limitations of conventional intratumoral treatments Mins/Hours Concentration Short tumor exposure Systemic exposure Transient effect in tumor1 Significant systemic toxicity Parent drug IT
TransCon technology provides
potential for sustained modulation of tumor microenvironments with infrequent dosing and minimized systemic toxicity TransCon IT Aims to Transform Intratumoral Treatments Slow IT release allows for potential activity in tumor and draining lymph
nodes for weeks or months, while keeping systemic exposure minimal Designed to enable new multi-agent combinations without added toxicity Potential for long dosing interval enabling treatments of hard-to-access tumors Days/Weeks Concentration Long
tumor exposure Low systemic exposure Sustained potent activity in the tumor Minimized systemic toxicity TransCon IT
Two Near-term IND Candidates -
Potential to Expand Pipeline to Address All Steps of the Immunity Cycle TransCon IL-2 b/g Designed to aid T cell and NK cell expansion, priming and activation as well as infiltration of immune cells in tumors (steps 3 and 5). Additional TransCon
Candidates in Preclinical Research TransCon product candidates using systemic and IT approaches have the potential to affect all steps in the immunity cycle. Combination approaches enable impact on all critical steps of anti-tumor response TransCon
TLR7/8 Agonist Designed to activate antigen-presenting cells and enhance antigen presentation and, thereby, promote activation of cytotoxic immune cells (steps 2 and 6).
Product Candidates in Oncology
TransCon TLR7/8 Agonist
Efficacy Each injection designed to
provide sustained exposure in the tumor for months to enhance immune activation Reduce risk of reaching super-high "ablative", non-immunogenic levels Safety Low systemic toxicity expected to reduce dose-limiting adverse events Infrequent
dosing designed to improve practicality and reduce injection-related complications Broad application Essentially all solid tumors are accessible for injection Opportunity for TransCon TLR7/8 Agonist in Solid Tumors Designed for intratumoral,
sustained release with minimal systemic exposure aiming for superior efficacy TransCon TLR7/8 Agonist
TLRs: Innate Immune Sensors of
"Danger" Associated with Pathogens or Cell Death Toll-like receptors (TLRs): Receptors for Pathogen- or Danger- (cell death) Associated Molecular Patterns Activate innate immunity, antigen presenting cells (APCs) in particular Results in
priming and expansion of cytolytic and helper T cells Inhibit suppressive mechanisms limiting anti-tumor responses Bourquin C, et al. Pharmacol Res, 2020; 154:104192. TLRs activate several key pathways critical in host defense against tumors
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 myeloid DCs Potent activator of the innate immunity Elevates proinflammatory cytokines: IL-12, IFNs, TNF-a, IL-1, chemokines Enhances antigen presentation: upregulated MHCII, costimulatory molecules (e.g. CD80/86) Enhances anti-tumor
immunity 1 Vasilakos J and Tomai M. Exp Rev Vaccines, 2013; 12:809-819. 2 Rook A, et al. Blood. 2015;126(25):2765. Resiquimod activates both conventional DCs and pDCs
Resiquimod transiently conjugated to
Last updated: Nov 20, 2020