Application for Funding by German Federal Ministry of Education and Research ACcelerated and Expedited R&D of mRNA vaccine against SARS-CoV-2: ACE-mR-CoV Submitted by CureVac AG Friedrich-Miescher-Strasse 15 72076 Tübingen, Germany Project Lead: Submitted on July 14, 2020 - confidential – I

Project description: Table of content List of Abbreviations ............................................................................................................. IV List of Tables ....................................................................................................................... VII List of Figures ...................................................................................................................... VII 1.    Introduction .................................................................................................................... 1 a. Brief description of the applying company/institution ................................................... 1 b.      Executive Summary in tabular form ............................................................................ 1 2.    Objectives ...................................................................................................................... 2 a. Scientific and/or technical working objectives of the project ........................................ 2 i.     Objectives of clinical development, including objectives for adjustments/ expansions of manufacturing, processing and filling capacities within the clinical trial process.......... 5 ii. Objectives regarding collaboration with development and production partners during clinical trials .................................................................................................................... 6 iii. Further objectives after market approval e.g. targeted production capacity, cooperation with licensees and other partners (scale-up and scale-out) ......................... 7 3.    State of the art; previous work ........................................................................................ 7 a. Quality and development status of the preparatory work ............................................. 7 i.     Clinical trial .............................................................................................................. 8 ii.    Vaccine production .................................................................................................12 iii.   Declaration on intellectual property rights ...............................................................16 b.      Previous work of the applicant ...................................................................................19 4.    Detailed description of the work plan .............................................................................22 a. Milestone Schedule ...................................................................................................22 b. Plans to accelerate the development/expansion of clinical trial and production capacities..........................................................................................................................32 i.     Acceleration of development ..................................................................................32 ii.    Expansion of clinical trial capacities .......................................................................32 iii.   Expansion of production capacities ........................................................................32 c.      Risk assessment, mitigation and avoidance ...............................................................37 5.    Exploitation and Dissemination Plan..............................................................................43 a. Brief overview ............................................................................................................43 b. Aspects of economic, scientific and technical exploitation prior to marketing authorisation .....................................................................................................................44 c.      Aspects of exploitation after marketing authorisation .................................................46 6.    Division of labour/cooperation with third parties .............................................................46 7.    Financing of the project, cost estimates .........................................................................49 Own contribution, BMBF contribution, third-party financing ...............................................49 References: ..........................................................................................................................63 Annex 1 - Milestone Planning ...............................................................................................64 Annex 2 – Scientific Advises from Authorities .......................................................................64 Annex 3 – CureVac AG Risk Assessment Policy, Version 0.2 ..............................................64 II

Annex 4 - Investigator’s Brochure “mRNA based SARS-CoV-2 Vaccine IB", Version 2.0 .....64 Annex 5 – Clinical Study Protocol, Study CVnCoV-001 ........................................................64 III

List of Abbreviations AE                   Adverse Event AESI                 Adverse Event of Special Interest AP                   “Arbeitspaket” (Working Package) BMGF                 Bill & Melinda Gates Foundation CEPI                 Coalition for Epidemic Preparedness Innovations CI                   Confidence Interval CTA                  Clinical Trial Approval CMC                  Chemistry Manufacturing and Controls CMO                  Contract Manufacturing Organisation CVnCoV               CureVac novel Coronavirus Vaccine CPE                  Cytopathic Effect CRO                  Contract Research Organisation DART                 Developmental And Reproductive Toxicology DNA                  Deoxyribonucleic Acid DP                   Drug Product DSMB                 Data Safety Monitoring Board EC                   Ethics Committee EEA                  European Economic Area EFD                  Embryo-Fetal Development EMA                  European Medicines Agency EP                   European EUL                  Emergency Use Listing FACS                 Fluorescence-Activated Cell Sorting FAIR Principles      Findable, Accessible, Interoperable and Reusable Principles FAMHP                Federal Agency for Medicines and Health Products FDA                  Food and Drug Administration FEED                 Fertility and Early Embryo Development FIH                  First In Human FLI                  Friedrich-Loeffler-Institut GAVI                 Global Alliance for Vaccines and Immunisation IV

GLP       Good Laboratory Practice GMP       Good Manufacturing Practice H0        Hypotheses 0 HA        Health Authorities IB        Investigator Brochure lgG       Immunoglobulin G IM        intramuscular IND       Investigational New Drug iSRC      internal Safety Review Committee IVT       In Vitro Translation KfW       Kreditanstalt für Wiederaufbau LNP       Lipid Nanoparticle MAA       Marketing Authorization Approval MERS      Middle East Respiratory Syndrome mRNA      messenger Ribonucleic Acid MS        Milestones n         Number (as in Sample Size) N protein Nucleocapsid protein NHP       Non-Human Primates ORF       Open Reading Frame PBMC      Peripheral Blood Mononuclear Cell pDNA      plasmid DNA PCT       Patent Cooperation Treaty PEI       Paul-Ehrlich-Institute PPND      Pre- and Postnatal Development PRA       Pharmaceutical Research Associates R&D       Research & Development RBD       Receptor Binding Domain RNA       Ribonucleic Acid ROW       Rest of the World RSV       Respiratory Syncytial Virus SAE       Serious Adverse Event V

SARS      Severe Acute Respiratory Syndrome S protein Spike protein US        United States VNT       Virus Neutralizing Titer WB        Western Blot WHO       World Health Organization YOA       Years of Age µg        Microgram VI

List of Tables Table 1: Executive Summary .............................................................................................. 1 Table 2: Release analytics .................................................................................................15 Table 3: Main milestones with timelines ...........................................................................23 Table 4: Comparison Table 1g vs. 10g up-scale ..............................................................33 Table 5: Materials and Slot availability .............................................................................36 Table 6: Summary on key risks, their impact and likelihood of CVnCoV development 39 Table 7: Labour/cooperation with third parties ................................................................47 Table 8: Main milestones with timelines ...........................................................................50 Table 9: Milestone volumes ...............................................................................................50 Table 10: Total costs per category ....................................................................................50 Table 11: Total costs per work package ...........................................................................50 Table 12: Batch Production Costs ....................................................................................52 Table 13: Overview of batch production ...........................................................................53 Table 14: AP 1: CMC Development & Manufacturing .......................................................55 Table 15: AP 2: Clinical Development – Dose confirmation in Elderly Phase IIa, Study 002 .......................................................................................................................................55 Table 16: Phase IIa - Elderly study ....................................................................................56 Table 17: AP 3: Clinical Development – Special populations, Phase II/III – AP 3 ...........56 Table 18: Clinical Studies Special Populations ................................................................56 Table 19: AP 4: Clinical Development – Efficacy Phase IIb/III, Study 004 and Concomitant Vaccination Study 010 .................................................................................57 Table 20: Phase IIb/III Investigator Fees and other costs corresponding costs ............58 Table 21: AP 5: Clinical Development – non interventional study ..................................58 Table 22: Additional non-interventional study .................................................................58 Table 23: AP 6: Regulatory Affairs – interactions with regulatory authorities ...............58 Table 24: AP 7: Manufacturing for Clinical Development – Risk mitigation and stockpiling for Phase IIb/III ................................................................................................59 Table 25: AP 8: Preclinical Development: Fulfillment of regulatory requirements for the marketing authorization (MAA, marketing authorization application) for the market entry in the EU ....................................................................................................................60 Table 26: AP9: Production at risk......................................................................................61 Table 27: Ramp-up of production capacity ......................................................................62 List of Figures Figure 1: Timeline of major activities until Marketing Authorization Application (MAA) approval by EMA. ................................................................................................................ 4 Figure 2: High level clinical development plan for CVnCoV for Phase I to III studies (trials 001-010). .................................................................................................................... 5 Figure 3: SARS-CoV-2 mRNA induces high levels of humoral and cellular immune responses in mice. .............................................................................................................10 Figure 4: Manufacturing overview .....................................................................................13 Figure 5: Overview of drug substance (mRNA) production steps including analysis ..14 Figure 6: Overview of drug product production steps including analysis .....................15 Figure 7: CMC Planning 2020 ............................................................................................23 Figure 8: Flow chart for Phase IIb/III study 004. ...............................................................27 Figure 9: CureVac's risk management process ...............................................................37 Figure 10 : Work package timelines ..................................................................................51 VII

Project description

1. Introduction
a. Brief description of the applying companyj/institution

CureVac is a leading global clinical-stage biopharmaceutical company with 20 years of
expertise in developing a new class of transformative medicines based on messenger
ribonucleic acid (mRNA) that has the potential to improve the lives of people. Our vision is to
revolutionize medicine and open new avenues for developing therapies by enabling the body
to make its own drugs. mRNA plays a central role in cellular biology in the production of
proteins in every living cell. We are the pioneers in successfully harnessing mRNAs designed
to prevent infections and to treat diseases by mimicking human biology to synthesize the
desired proteins. Our technology platform is based on a natural approach to optimize mRNA
constructs that encode functional proteins that replace defective or missing proteins using the
cell’s intrinsic translation machinery. Our current product portfolio includes clinical and
preclinical candidates across multiple disease indications in oncology, prophylactic vaccines
and protein therapy. Our lead clinical programs, CV8102 for the treatment of four types of solid
tumors and CV7202 for potential vaccination against rabies, have generated promising early
efficacy and safety results in clinical trials. Furthermore, we have rapidliy advanced our mRNA
vaccine candidate against coronavirus (SARS-CoV-2) through preclinical studies. We initiated
the first Phase 1 clinical trial on June 18, 2020, upon the granting of the permission by the
German Health Authority Paul-Ehrlich-Institute (PEI) and the Belgian Federal Agency for
Medicines and Health Products (FAMHP) on June 17, 2020. On June 15, 2020, the German
Federal Ministry of Economics and Energy announced its commitment to invest 300 million
Euros in CureVac through the Kreditanstalt für Wiederaufbau (KfW). CureVac has also entered
into collaborations with multinational corporations and organizations, including Boehringer
Ingelheim, Genmab, CRISPR Therapeutics, the Bill & Melinda Gates Foundation, the Coalition
for Epidemic Preparedness Innovations (CEPI) and others. The company is headquartered in
Tübingen, Germany with sites in Frankfurt and Boston, USA.

b. Executive Summary in tabular form

Table 1: Executive Summary

Applicant CureVac AG
Friedrich-Miescher-Str. 15
72076 Tübingen

Germany

Project Manager:

(companyjinstitution, project
manager)

Vaccine technology (max. Lipid nanoparticle (LNP) formulated mRNA consisting of
140 characters) sequence optimized, mRNA using naturally occurring
nucleotides.

Target Antigen (max. 140 Full length spike SARS-CoV-2 virus antigen with 2 proline amino
characters) acid substitutions (K986P; V987P).

Status of preclinical Preclinical development program including immunogenicity

development, (max. 100 characterization in vitro and in rodent models, GLP-repeat-dose

words) toxicology in rats enabling approval and start of first in human
trial (Phase 1, CVnCoV-001) in June 2020. Further non-clinical
development to support clinical development clinical
development and marketing authorization ongoing including
mitigation strategy to provide a 2"d generation vaccine.

 

Main milestones (MS) with timelines

 

CureVac’s SARS-CoV-2 project aims to provide a safe and effective vaccine to prevent
diseases induced by SARS-CoV-2 (COVID-19). The clinical candidate CVnCoV (CureVac
novel Coronavirus vaccine) is an mRNA-based severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) vaccine encapsulated in lipid nanoparticles (LNPs) for intramuscular (IM)
injection. The preclinical and analytical work of CVnCoV was successfully conducted to enable
approval of a first in human (FIH) trial in Germany and Belgium (CVnCoV-001) by PEI and
FAMHP, respectively. GMP (Good Manufacturing Practice) manufacturing supplied sufficient
material to conduct the initial development program. Supply of GMP material for the early
clinical phases, Phase 1 and 2 has been secured and supply for Phase 3 as well as initial
market supply in 2021 is currently secured. An accelerated interaction with the COVID-19
European Medicines Agency (EMA) pandemic task force (COVID-ETF) is planned by
August/September 2020 to reach alignment on the path forward to gain (conditional) approval
by EMA as soon as feasible. Objective is to achieve an early approval via the conditional
approval pathway of EMA in early 2021 followed by approval during second half of 2021. In
scope are all age groups and at risk population including elderly as well as special populations,
i.e. subjects with comorbidities, immunocompromised persons, pregnant women as well as the
pediatric population. A further main objective is to secure expanded GMP manufacturing to be
able to protect a large number of the population in Germany, Europe but also worldwide. As
this is a novel virus against which currently no efficacious prophylactic vaccine exists, CureVac
is including a targeted risk mitigation program to provide an improved vaccine in case of
limitation in safety and/or efficacy of the current clinical candidate as fast follow-on product
potentially entering into clinical trials by end of 2020. A further major objective is to increase

2

and reserve required production capacities to ensure sufficient and sustainable supply beyond 2021. Figure 1 shows the timeline of the major activities planned until approval by EMA. Details on work packages and timelines can be found in the respective sections of this application and in the Milestone Planning (Annex 1). 3