CureVac NV Profilis
CureVac N.V. operates as a clinical-stage biopharmaceutical company.
The company engages in developing a new class of transformative medicines based on messenger ribonucleic acid that has the potential to improve the lives of people. The company’s product portfolio includes clinical and preclinical candidates across multiple disease indications in prophylactic vaccines, oncology and protein therapy.
In the company’s clinical pipeline for prophylactic vaccines, it is advancing the company’s Messenger ribonucleic acid (mRNA) vaccine candidate, CVnCoV, against coronavirus (SARS-CoV-2), for which it initiated a Phase 1 dose-escalation trial in healthy volunteers in June 2020, a Phase 2a clinical trial in older adults in September 2020 and a pivotal Phase 2b/3 clinical trial in December 2020. For the Phase 1 clinical trial, the company reported positive interim results on November 10, 2020, enabling it to select a recommended dose of 12g to advance in the Phase 2a, as well as in the pivotal Phase 2b/3 clinical trial. The Phase 2a clinical trial is a partially observer-blind, multi-centered, controlled, dose-confirmation trial, and is fully enrolled with 674 participants. Based on the detection of a relevant number of novel coronavirus 2019 disease (COVID-19) infections in the Phase 2a clinical trial, on March 31, 2021, the company submitted a protocol amendment to include a secondary endpoint for vaccine efficacy. The secondary endpoint is expected to allow for the collection of relevant efficacy data in the total population of the trial with a focus on the subgroup of approximately 270 participants above the age of 60. The company expects to report a first data readout for the Phase 2a clinical trial in the second quarter of 2021. Furthermore, on March 27, 2021, it filed a protocol amendment for the Phase 2a clinical trial to enroll approximately 40 adolescent participants between the ages of 12 and 17 in Panama and Peru, which is expected to start near the end of April 2021.
This Phase 2 clinical trial would be a non-randomized, open label clinical trial, which is expected to enroll 180 participants at sites in France, and is expected to start in the second quarter of 2021. The company’s pivotal Phase 2b/3 trial is a randomized, observer-blind, placebo-controlled, multicentered study to evaluate efficacy and safety of CVnCoV, which has successfully completed recruitment, with approximately 40,000 participants. It expects to conduct a first case-driven interim analysis in the second quarter of 2021, depending on the infection rate of SARS-CoV-2 in clinical trial participants. An additional Phase 3 trial to evaluate the safety, reactogenicity and immunogenicity of CVnCoV in adults with an elevated risk of severe COVID-19 infection due to comorbidities was recently started. Selected comorbidities include obesity, chronic cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease (COPD), HIV, type 2 diabetes mellitus and post-renal transplantation. This additional Phase 3 clinical trial is expected to enroll approximately 1,200 participants at multiple sites in Belgium.
Furthermore, in early May, the company plans to initiate a Phase 3 flu-co-administration study with our partner Bayer to assess compatibility of CVnCoV with established seasonal vaccines. The co-administered Phase 3 clinical trial is expected to enroll 1,000 participants in Argentina, Columbia and Peru. It would evaluate the safety, reactogenicity and immunogenicity of CVnCoV co-administered with a licensed quadrivalent influenza vaccine versus separate administration of the two vaccines in adults 60 years and older. In February 2021, the company initiated a rolling submission with the European Medicines Agency (EMA), which would allow the EMA to assess CVnCoV’s compliance with standards for vaccine efficacy, safety and pharmaceutical quality as a prerequisite for a formal market authorization application. The rolling submission process with the EMA was started with the submission of a first preclinical data package and was recently advanced with two additional packages, including CMC data, as well as first clinical data from its dose-escalation Phase 1 trial.
In addition, in April 2021, the company initiated a rolling submission with Swissmedic, Switzerland’s authority responsible for the authorization and supervision of therapeutic products, which would also allow Swissmedic to review the safety, effectiveness and pharmaceutical quality as a prerequisite for a formal market authorization application.
Product Portfolio
The company’s major proprietary programs comprise:
The company’s lead vaccine candidate CVnCoV against SARS-CoV-2, which it has an advanced in response to the global pandemic due to COVID-19. Based on the results of preclinical studies, the company initiated a Phase 1 clinical trial in June 2020 and a Phase 2a clinical trial in September 2020. In November 2020, it reported positive interim Phase 1 data and selected a recommended dose of 12µg for further clinical testing. In December 2020, the company initiated a pivotal Phase 2b/3 trial.
The company’s vaccine program, CV7202, is in a Phase 1 clinical trial as a vaccine candidate against rabies. In January 2021, Phase 1 data was published in a scientific journal. The company is assessing the timeline for advancing CV7202 into a Phase 2 clinical trial.
The company’s lead oncology program, CV8102, is in a Phase 1 dose escalating clinical trial for four types of cancers as a monotherapy and in combination with anti-PD-1. In February 2021, the company initiated the expansion of its Phase 1 study to confirm the safety, tolerability and efficacy of CV8102 in patients with advanced melanoma at 600µg, the selected dose to be advanced in a Phase 2 clinical trial.
The company’s key partnered programs comprise:
The company has partnered with Boehringer Ingelheim for the development of BI1361849, which is a therapeutic vaccine candidate designed to elicit antigen-specific immune responses against tumor-associated antigens frequently overexpressed in patients with non-small cell lung cancer, or NSCLC. BI1361849 is being studied by the Ludwig Institute for Cancer Research in a Phase 1/2 clinical trial in NSCLC, in combination with durvalumab, a PD-L1 inhibitor, and tremelimumab, an anti CTLA-4 antibody.
The company has partnered with CRISPR Therapeutics for the development of novel Cas9 mRNA constructs for use in gene editing therapeutics, with improved properties, such as increased potency, decreased duration of expression and reduced potential for immunogenicity. CRISPR Therapeutics has a license to the improved constructs in three of their in vivo gene editing programs.
The company has a strategic partnership with Genmab B.V. (Genmab) to leverage its mRNA technology platform to develop up to four mRNA based novel therapeutic antibodies. This represents the first publicly announced strategic partnership focused on differentiated mRNA-based antibodies.
The company has received grants from the Bill & Melinda Gates Foundation to develop prophylactic vaccines designed to prevent picornaviruses, influenza, malaria and rotavirus.
The company is collaborating with the Coalition for Epidemic Preparedness Innovations (CEPI) on various vaccine projects, including its first generation COVID-19 vaccine candidate, CVnCoV, and the development of programs against Lassa virus and yellow fever. Further, it is collaborating with CEPI on the development of its RNA Printer. The company also has various academic collaborations, including with SERI for target discovery research in mRNA-based eye therapy, and Yale University for target discovery research in mRNA-based pulmonary therapy.
Oncology
mRNA is a versatile platform for cancer vaccine development allowing to encode a range of antigens from full length tumor associated antigens to neoepitopes. The company is taking multiple approaches in oncology to induce tumor-specific immune responses in patients:
Intratumoral therapy: Intratumoral injection of immunostimulating agents into tumors is an alternative to classic vaccination to induce a therapeutic immune response. The company’s lead oncology product candidate, CV8102, is based on a complex of single stranded non-coding RNA with a polymeric peptide carrier, which has been shown to activate the TLR7, TLR8 and RIG-I pathways. These pathways activate the innate immune system upon detection of RNA molecule. The company is evaluating CV8102 in a Phase 1 clinical trial for the treatment of four types of solid tumors. It is also investigating mRNAs encoding immunostimulating proteins for intratumoral therapy. The company has shown in various animal models that intratumoral injection of mRNA encoding immunostimulating proteins, such as cytokines, could induce regression of the injected tumors and prolong survival of the animals. It is testing different mRNA constructs and formulations in preclinical studies to achieve optimal expression of proteins in the tumor. The company is also exploring combinations of mRNA encoding different immunostimulating proteins in order to demonstrate optimal therapeutic level in tumor models that are refractory to immunotherapies like anti-PD-1 agents.
Novel Cancer Vaccines
The company is also working on discovery of novel vaccines against tumor-associated antigens, which are antigens that are overexpressed in tumor tissues with no or little expression on healthy tissues, using its lipid nanoparticle (LNP) formulations. It is known that these antigens are often less immunogenic than neoantigens and require optimized design to improve their presentation to immune cells, as well as vaccine formulation with strong immunostimulating properties (vaccine adjuvant effect) to enable the induction of relevant immune responses.
The company has demonstrated in a preclinical model that an optimized LNP formulated mRNA vaccine, encoding a TAA, that is also a self-antigen, could induce cellular and anti-tumoral immune responses and single-agent therapeutic activity. These immune responses led to single-agent therapeutic effect in the B16F10 tumor model that does not respond to anti-PD-1 antibodies alone. The therapeutic effect of the vaccine was further enhanced by concomitant systemic anti-PD-1 antibody treatment. Based on these encouraging data, it is developing vaccine candidates targeting tumor associated antigens for different indications. The company focuses on indications and settings with a high medical need showing a low response rate to anti-PD-1 antibodies alone or indications with minimal residual disease after standard of care surgery (adjuvant setting) and intends to use the vaccines to prevent cancer relapse. The company is also developing novel vaccine targeting various neoantigens. It has demonstrated that LNP formulated mRNA vaccines encoding are also able to induce T cell responses against model neoantigens.
Prophylactic Vaccines
The company’s approach to the development of prophylactic vaccines is focused on:
CVnCoV for SARS-CoV-2: The company’s most advanced mRNA vaccine program against SARS-CoV-2 is being evaluated in Phase 1, Phase 2a and Phase 2b/3 clinical studies. Positive interim data reported for its Phase 1 clinical trial showed that, as of the cutoff date of October 31, 2020, the company’s vaccine candidate induced relevant antibody titers. The quality of the immune responses observed in vaccinated and healthy volunteers was found to be comparable to the immune response identified or detected in convalescent sera taken from recovered COVID-19 patients, thereby closely mimicking the immune response observed after a natural COVID-19 infection.
CV7202 for Rabies: The company’s advanced program, CV7202, is a rabies vaccine candidate in a Phase 1 clinical trial. CV7202 induced adaptive immune response as shown by rabies-specific virus-neutralizing antibody titers (VNTs) above the World Health Organization thresholds considered to be protective, 28 days after the second dose in all subjects, at the lowest 1µg and 2µg dose levels.
CV-SSIV for influenza: As part of the company’s influenza program, it has evaluated mRNA-based influenza vaccines starting with a monovalent influenza vaccine followed by seasonal cocktails based on influenza hemagglutinin, or influenza HA. In preclinical studies, the company demonstrated that the multivalent mRNA vaccines induced hemagglutination inhibition, or HI, titers above the accepted threshold for protective immunity in ferrets and non-human primates, or NHPs.
Respiratory Syncytial Virus, or RSV vaccine: The company’s approach for the RSV program is based on delivering mRNAs encoding for the RSV F (fusion) protein. Based on in vivo challenge studies in cotton rat, it has demonstrated that the company’s mRNA vaccines induce high levels of virus neutralizing antibodies, protect animals against RSV infection, without any signs of lung pathology.
Other prophylactic vaccines: In partnership with the Bill & Melinda Gates Foundation, the company is developing prophylactic vaccines for prevention of other infectious diseases associated with high mortality in the developing world, including malaria and rotavirus.
The company’s has collaborations focused on:
Therapeutic Antibodies: The company is also developing mRNAs therapies to produce antibodies systemically using the liver as a bioreactor for subsequent secretion and systemic distribution of the antibodies to primary organs affected by a disease. The company’s collaboration with Genmab, a global leader in antibody discovery and design, would allow the company to work with novel antibodies produced using its mRNA technology. This partnership represents the first-ever publicly disclosed mRNA antibody focused deal and would allow the company to optimize and manufacture mRNA encoded antibodies for Genmab.
Eye Diseases: Using the company’s CureVac Carrier Molecule (CVCM) delivery system that enables different routes of delivery to the eye, it is investigating development of mRNA-based treatments for undisclosed ophthalmic indications. The company has a collaboration with SERI for its discovery efforts.
Lung Diseases: The CVCM delivery system is also suited for the delivery of mRNA to the lung, administered as either an aerosol or a dry powder formulation. The company has a collaboration with Yale University focused on discovery of novel molecular targets in pulmonary diseases.
Strategy
The key components of the company’s strategy are to continue to invest in its proprietary technology platform to be the major mRNA platform company; utilize a rational disease selection approach to minimize clinical and commercial risk for its programs and broader platform; rapidly advance its major product candidates through clinical development and regulatory approval; continue to invest in its manufacturing capabilities across all manufacturing steps from starting material to formulation to further add scale and flexibility for potential commercialization; selectively seek strategic partners to develop and commercialize product candidates in certain therapeutic areas and geographies; seek strategic acquisitions or in-licenses of technology or assets that are complementary to its programs and technology platform; and strengthen and expand its intellectual property portfolio to protect its scientific and technical know-how.
Collaborations
In July 2020, the company entered into collaboration and license agreement with GSK, pursuant to which it would collaborate with GlaxoSmithKline Biologicals SA (GSK) to research, develop and commercialize prophylactic and therapeutic non-replicating mRNA-based vaccines and antibodies targeting infectious disease pathogens.
In December 2019, the company entered into collaboration and license agreement with Genmab to research and develop up to four differentiated mRNA-based antibody products, to be selected by Genmab, based on the combination of the company’s proprietary RNAntibody technology with Genmab’s proprietary antibody technology for the treatment of human diseases.
For each option that the company has exercised under the development and option agreement with Acuitas, the company has entered into a non-exclusive license agreement with Acuitas Therapeutics Inc. (Acuitas) with respect to such optioned product, all based on the same form agreement, which the company collectively refers to as the Acuitas License Agreements. Under the Acuitas License Agreements, Acuitas grants the company a non-exclusive, non-transferable, sublicensable (subject to certain conditions) worldwide license under Acuitas’s LNP technology to develop, manufacture and commercialize licensed products directed to the optioned targets.
In 2017, the company entered into development and license agreement with CRISPR Therapeutics (CRISPR Therapeutics Agreement), pursuant to which the company would develop novel Cas9 mRNA constructs for use in gene editing therapeutics. Under the terms of the CRISPR Therapeutics Agreement, the company granted CRISPR Therapeutics AG (CRISPR Therapeutics) a worldwide, exclusive (even to the company), sublicensable (subject to certain conditions) license under certain intellectual property rights that are reasonably necessary or useful to develop, manufacture or commercialize products comprising Cas9 mRNA constructs, and under any patents controlled by the company that arise from inventions discovered under the CRISPR Therapeutics Agreement to develop, manufacture and commercialize three of CRISPR Therapeutics’ in vivo gene-editing programs for certain diseases. CRISPR Therapeutics granted the company an exclusive (even as to CRISPR Therapeutics), worldwide, cost-free sublicense to manufacture products comprising Cas9 mRNA constructs for CRISPR Therapeutics.
In 2015, the company entered into development and intellectual property agreement with Tesla Grohmann Automation GmbH (Tesla Grohmann) pursuant to which Tesla Grohmann agreed to design, develop, and manufacture certain automated manufacturing machines on the company’s behalf.
Sponsored Collaboration Agreements
Yale Collaborative Research Agreement
In 2019, the company entered into a collaborative research agreement, which the company refers to as the Yale Agreement, for research in mRNA-based pulmonary therapeutic candidates with Yale University, or Yale. Under the Yale Agreement, Yale would perform discovery research on targets related to pulmonary diseases and present therapeutic candidates to the company for preclinical and subsequent clinical development.
Schepens Institute Research Agreement
In 2019, the company entered into a Sponsored Research Agreement, which it refers to as the Schepens Agreement, with SERI, pursuant to which SERI agreed to perform certain research activities for mRNA-based eye therapy candidates. Under the Schepens Agreement, SERI granted it an exclusive option to initiate negotiations for an exclusive or non-exclusive license to SERI’s interest in any inventions developed under the Schepens Agreement. SERI additionally granted the company an exclusive option to negotiate an exclusive license to certain background intellectual property. As of December 31, 2020, the company have provided approximately $0.9 million in funding to SERI under the Schepens Agreement.
Intellectual Property
Patents
As of January 15, 2020, the company owned approximately 63 issued U.S. patents, 125 pending U.S. patent applications, 882 issued foreign patents (including 57 European patents, which have been validated in various European countries resulting in a total of approximately 608 national patents in European countries), 390 pending foreign patent applications (including 73 pending European patent applications) and 23 pending Patent Cooperation Treaty, or PCT, patent applications, including four pending U.S. patent applications, 18 foreign patent applications and two PCT patent applications that are jointly owned with third parties. These patents include claims relating to the company’s RNAoptimizer technology platform, CV8102, BI 1361849 (formerly CV9202), CV7202, CV-SSIV, its COVID-19 vaccine candidate and the company’s CVCM delivery system.
RNAoptimizer
As of January 15, 2021, the company owned 20 issued U.S. patents, 17 pending U.S. patent applications, 81 issued foreign patents, including in Europe, Canada, China, India, Japan, the Republic of Korea, Singapore, Russia, Mexico and Australia, and 115 pending foreign patent applications and four PCT patent applications relating to its RNAoptimizer technology, including patents and patent applications relating to open reading frame (ORF) optimization, Untranslated region (UTR) optimization, protein optimization and formulation. The company’s RNAoptimizer technology is used in its BI 1361849 (formerly CV9202), CV7202, CV-SSIV and SARS-CoV-2 product candidates. The issued patents are expected to expire between 2022 and 2037, excluding any additional term for patent term adjustments or patent term extensions. If granted, the pending patent applications would be expected to expire between 2022 and 2041, excluding any additional term for patent term adjustments or patent term extensions.
CV8102
As of January 15, 2021, the company owned four issued U.S. patents, three pending U.S. patent applications, 31 issued foreign patents, including in Europe, Brazil, Canada, China, India, Japan, the Republic of Korea, Singapore, Russia, Mexico and Australia, and 24 pending foreign patent applications relating to its CV8102 product candidate. The issued patents are expected to expire between 2028 and 2036, excluding any additional term for patent term adjustments or patent term extensions. If granted, the pending applications would be expected to expire between 2029 and 2037, excluding any additional term for patent term adjustments or patent term extensions.
BI 1361849
As of January 15, 2021, the company owned 12 issued U.S. patents, eight pending U.S. patent applications, 64 issued foreign patents, including in Europe, Canada, China, India, Japan, the Republic of Korea, Singapore, Russia, Mexico and Australia, and 60 pending foreign patent applications relating to its BI 1361849 (formerly CV9202) product candidate. The issued patents are expected to expire between 2022 and 2034, excluding any additional term for patent term adjustments or patent term extensions. If granted, the pending patent applications would be expected to expire between 2022 and 2034, excluding any additional term for patent term adjustments or patent term extensions.
CV7202
As of January 15, 2021, the company owned six issued U.S. patents, four pending U.S. patent applications, 19 issued foreign patents, including in Europe, Canada, China, India, Japan, the Republic of Korea, Singapore, Russia, Mexico and Australia, and 28 pending foreign patent applications relating to its CV7202 product candidate. The issued patents are expected to expire between 2022 and 2034, excluding any additional term for patent term adjustments or patent term extensions. If granted, the pending patent applications would be expected to expire between 2022 and 2037, excluding any additional term for patent term adjustments or patent term extensions.
CV-SSIV
As of January 15, 2021, the company owned eight issued U.S. patents, nine pending U.S. patent applications, 20 issued foreign patents, including in Europe, Canada, China, India, Japan, the Republic of Korea, Singapore, Russia, Mexico and Australia and 36 pending foreign patent applications relating to its CV-SSIV product candidate. The issued patents are expected to expire between 2022 and 2033, excluding any additional term for patent term adjustments or patent term extensions. If granted, the pending patent applications would be expected to expire between 2022 and 2038, excluding any additional term for patent term adjustments or patent term extensions.
COVID-19 Vaccine
As of January 15, 2021, the company owned five issued U.S. patents, 13 pending U.S. patent applications, 19 issued foreign patents, including in Europe, Canada, China, India, Japan, the Republic of Korea, Singapore, Russia, Mexico and Australia, 26 pending foreign patent applications and seven PCT patent applications relating to its COVID-19 product candidate. The issued patents are expected to expire between 2022 and 2033, excluding any additional term for patent term adjustments or patent term extensions. If granted, the pending patent applications would be expected to expire between 2022 and 2041, excluding any additional term for patent term adjustments or patent term extensions.
CVCM Delivery System
As of January 15, 2021, the company owned four issued U.S. patents, two pending U.S. patent applications, 12 issued foreign patents, including in Europe, Canada, China, India, Japan, the Republic of Korea, Singapore, Russia, Mexico and Australia, and 11 pending foreign patent applications relating to its proprietary CVCM delivery system. The issued patents are expected to expire between 2030 and 2037, excluding any additional term for patent term adjustments or patent term extensions. If granted, the pending applications would be expected to expire between 2029 and 2037, excluding any additional term for patent term adjustments or patent term extensions.
Trademarks
As of December 31, 2020, the company owned trademark registrations or registration applications for CureVac, and the CureVac logo in the United States and in certain foreign jurisdictions, including Europe.
Research and Development
The company’s research and development costs were € 113.8 million for 2020.
History
CureVac N.V. was founded in 2000. The company was incorporated pursuant to the laws of the Netherlands in 2020.
