On August 16, 2021 CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), reported financial results for the second quarter and first half of 2021 and provided business update (Press release, CureVac, AUG 16, 2021, View Source [SID1234586627]).
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"Large parts of the world are still under-vaccinated against SARS-CoV-2, making effective vaccines necessary to prevent further evolution of the virus and to avoid renewed restrictions on public life," said Franz-Werner Haas, Chief Executive Officer of CureVac. "While the recently reported final data from our pivotal Phase 2b/3 study have fallen short of expectations in older adults, our first-generation COVID-19 vaccine candidate, CVnCoV, has shown a solid efficacy profile in the age group of 18 to 60. We are reaffirming our intention to seek regulatory approval with the European Medicines agency and are currently submitting extensive clinical data to the agency to allow for the assessment of CVnCoV’s public health benefit. Insights from our COVID-19 development program are feeding into all areas of our pipeline, where we are pursuing a broader technology approach and multivalent as well as combination vaccine formats, as part of the large infectious diseases program jointly developed with GSK. This includes our second-generation COVID-19 vaccine candidate, CV2CoV, which is advancing on track to enter clinical development in Q4 2021. In parallel, we are accelerating the development of the organization and the expansion of our manufacturing capacity, including the capacity for more clinical trials, while creating a strong development focus for The RNA Printer via a separate operational infrastructure for this strategic key project."
"Our financing activities, as well as the extension of our GSK partnership in the first half of 2021, provide an important financial foundation for accelerating our business expansion, while hedging the associated scale-up costs," said Pierre Kemula, Chief Financial Officer of CureVac. "We closed the first half of 2021 with approximately €1.36 billion in cash, which allows us to further grow our infrastructure for commercial product development in all areas and manufacturing supported by new members to the CureVac management team. While we are working toward regulatory approval of CVnCoV, we are expanding our clinical pipeline through the broad infectious disease portfolio we are developing together with GSK, including our second-generation COVID-19 vaccine program."
Selected Business Updates
Executing on Corporate Development and Business Transformation
CureVac is rapidly advancing the corporate transformation from a research-oriented biotech to a commercial-ready biopharma company. Continued build-up of a commercial infrastructure was recently supported by the appointment of two new CureVac management team members that bring deep international expertise and experienced leadership.
Dr. Malte Greune was appointed to the CureVac Management Team as Chief Operating Officer on July 1, 2021. He will be focused on further enabling CureVac’s comprehensive strategy for expansion of all commercial manufacturing activities and operations for mRNA vaccines and therapeutics. On August 1, 2021, Dr. Klaus Edvardsen joined CureVac as Chief Development Officer to advance the technology platform and grow the CureVac clinical development pipeline in all therapeutic areas.
Prophylactic Vaccines
CVnCoV – First-Generation COVID-19 Vaccine Candidate
CVnCoV is CureVac’s first-generation vaccine candidate in its clinical COVID-19 vaccine program. Based on optimized, non-chemically modified mRNA, CVnCoV was shown to be well tolerated at a 12µg dose and to induce robust immune responses comparable to those observed in recovered COVID-19 patients.
Pivotal Phase 2b/3 (HERALD) in Europe and Latin America
The pivotal Phase 2b/3 study (HERALD), initiated in December 2020, enrolled approximately 40,000 participants in ten countries in Europe and Latin America in the predefined age groups of 18 to 60 and above the age of 60. Of those participants, approximately 75% were enrolled in sites in Latin America and 25% were enrolled in sites in Europe.
On June 30, 2021, data of the final analysis was reported based on 228 adjudicated COVID-19 cases, occurring at least two weeks after administration of the second dose. In the unprecedented context of 15 different virus variants circulating within the study population at the time of final analysis, CVnCoV demonstrated an overall vaccine efficacy of 48% against COVID-19 disease of any severity across all age groups. CVnCoV demonstrated significant protection among participants in the age group of 18 to 60, with an efficacy of 53% against disease of any severity, including single non-respiratory mild symptoms. Protection against moderate to severe disease was calculated to be 77% in the age group of 18 to 60. In the same age group, CVnCoV provided 100% protection against hospitalization or death. In participants above 60 years, the available data did not enable a statistically significant determination of efficacy. The data further confirmed the favorable safety profile of CVnCoV in all age groups.
Out of the 228 adjudicated cases, 204 were sequenced to identify the variant causing the infection. Approximately 86% of these cases were caused by Variants of Concern ( 51%) and Variants of Interest ( 35%), the latter including the Lambda strain first identified in Peru ( 21%) and B.1.621, first identified in Colombia ( 14%). Approximately 3% of cases were attributable to the original SARS-CoV-2 virus. The remaining 11% were caused by less-explored strains. In the age group of 18 to 60, across strains of higher prevalence, strain-dependent vaccine efficacy ranged from approximately 42% (B.1.621 variant, first identified in Colombia) up to 67% (Gamma variant) against any severity of disease. The Delta variant was not represented in the pool of adjudicated cases and could therefore not be separately assessed.
Regulatory Pathway
CureVac intends to apply for regulatory approval of CVnCoV with the European Medicines Agency (EMA), to leverage the vaccine’s strengths in the age segment of the population where it provides demonstrated protection. Within the rolling submission initiated with the EMA in February 2021, submission of comprehensive clinical data packages is ongoing and is expected to be finalized toward the end of the third quarter. The potential subsequent application for conditional approval will be informed by continuing interactions with EMA.
Recent Amendments to the Clinical CVnCoV Development Program
The protocol amendment for the ongoing Phase 2a study in Peru and Panama, filed in March 2021 for the enrollment 40 adolescent participants between the ages of 12 and 17, has been withdrawn. A separate study to test CVnCoV in this highly important age-group is currently being prepared.
The Phase 3 trial, started in April 2021 to evaluate the safety, reactogenicity and immunogenicity of CVnCoV in adults with an elevated risk of severe COVID-19 infection due to comorbidities, is ongoing. Due to the advancement of the vaccination program in Belgium where the study is conducted, including this particularly vulnerable population, the study will continue with a reduced number of 131 recruited participants.
The flu-co-administration study, planned to be initiated together with Bayer to assess compatibility with established seasonal vaccines in case of seasonal COVID-19 vaccinations, is currently being redesigned based on inconclusive efficacy of CVnCoV in adults above the age of 60 in the HERALD study.
A Phase 2 study, focusing on immunogenicity and a deep characterization of immune responses in older adults above the age of 65 compared to younger adults was cancelled based on inconclusive efficacy of CVnCoV in adults above the age of 60 in the HERALD study.
CV2CoV – Second-Generation COVID-19 Vaccine Candidate
CV2CoV is CureVac’s second-generation vaccine candidate in its COVID-19 vaccine program, featuring a new mRNA backbone, jointly advanced with GSK. The optimized mRNA backbone targets improved intracellular mRNA translation for increased and extended protein expression, resulting in earlier and stronger immune responses compared to CVnCoV.
Preclinical Study of CV2CoV on Immune Responses and Protection against Virus Challenge
On August 16, CureVac published preclinical data, characterizing immune responses as well as the protective efficacy of CV2CoV and CureVac’s first-generation vaccine candidate, CVnCoV, against SARS-CoV-2 challenge in non-human primates. The study assessed cynomolgus macaques vaccinated with 12µg of either the first- or second-generation vaccine candidate. Better activation of innate and adaptive immune responses was achieved with CV2CoV compared to CVnCoV, resulting in faster response onset, higher titers of antibodies and stronger memory B and T cell activation. Higher antibody neutralizing capacity was observed with CV2CoV across all selected variants, including the Beta, Delta and Lambda variants. During challenge with the original SARS-CoV-2 virus, animals vaccinated with CV2CoV were found to be better protected based on highly effective clearance of the virus in the lungs and nasal passages. The full manuscript of the preclinical data is available on the pre-print server bioRxiv.
Following the current preclinical development of CV2CoV, a Phase 1 clinical trial is expected to start in Q4 2021.
Oncology
CV8102 – Cancer immuno-modulator in solid tumors
CureVac’s lead oncology candidate, CV8102, is being assessed in a Phase 1 dose-escalation study, evaluating tolerability and activity as a single agent and in combination with systemic anti-PD-1 antibodies. An expansion part of the Phase 1 trial, announced in February 2021, aims to confirm the safety, tolerability and efficacy of CV8102 at a preferred 600μg dose in 40 patients with a focus on PD-1 refractory melanoma. As of July 6, 12 out of 30 patients had been successfully recruited to receive intra-tumoral injections of CV8102 in combination with PD-1 antibodies. In the group assigned for CV8102 single-agent treatment, recruitment has been completed with 10 out of 10 patients. Updates on the progress of the trial are expected at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress and the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting later this year.
BI1361849 – Boehringer Ingelheim Collaboration
In June 2021, Boehringer Ingelheim expressed its intention to terminate the 2014 collaboration agreement on BI1361849. The termination will become effective in November 2021. The legacy program, targeting specific immune responses against tumor-associated antigens frequently overexpressed in patients with non-small cell lung cancer (NSCLC), applies an older protamine formulation technology, which reflected the state of the technology development at the time. A Phase 1/2 clinical trial in NSCLC applying BI1361849 as a combination therapy is ongoing. Both companies are currently assessing options to continue a collaboration on CureVac’s RNA technology platform based on state-of-the-art LNP-based formulations.
Financial Update for the Second Quarter and First Half of 2021
Cash Position
Revenues
Revenues amounted to €22.4 million and €32.4 million for the three and six months ended June 30 2021, representing a decrease of €12.1 million and €5.3 million, or 35% and 14%, from €34.5 million and €37.7 million for the same periods in 2020.
The decreases were primarily driven by the second quarter of 2020 having benefitted from a one-time effect whereby €33.1 million in contract liabilities from an upfront payment were recognized as revenue upon termination of our License and Collaboration Agreement with Eli Lilly.
This decrease was partially offset by increased revenues from our collaborations with GSK; in July 2020, GSK and CureVac signed a strategic collaboration agreement for the research, development, manufacturing and commercialization of mRNA-based vaccines and monoclonal antibodies targeting infectious disease pathogens. In April 2021, GSK and CureVac signed the COVID Collaboration and License Agreement for a second-generation COVID-19 vaccine program (CV2CoV). In total, for both programs, in the first six months 2021, revenue of €29.3 million was recognized. In addition, in June 2021, Boehringer Ingelheim informed CureVac of its intention to terminate the collaboration agreement for BI1361849. The termination will become effective in November 2021. As a result of the announced termination, the remaining contract liability, related to the upfront payment, is being recognized over a shorter period through the anticipated termination date. For the first six months of 2021, €2.1 million, compared to €1.0 million in the prior year, was recognized as revenue.
Operating Result
Operating loss amounted to €147.8 million and €263.7 million for the three and six months ended June 30, 2021, representing an increase of €144.6 million and €237.3 million from €3.2 million and €26.4 million for the same periods in 2020. The main driver of the increase in operating loss was higher research and development costs for CVnCoV, our COVID-19 vaccine candidate. These R&D costs consist primarily of costs related to clinical research organizations and to personnel involved in CVnCoV development. We also recognized increased cost of sales mainly due to set-up activities for production processes for our first-generation COVID-19 vaccine candidate, CVnCoV. The increase of cost of sales was also driven by a one-off recognition of expense related to ineffective set-up activities. The growth in general and administrative expenses was mainly due to consulting services for product launch readiness and personnel-related costs from an increased headcount. This increase in expenses was partially offset by a significant increase in other operating Income driven by our grant from the German Federal Ministry of Education and Research (BMBF) for the development and production of our COVID-19 vaccine candidate.
Financial Result (Financial Income and Expenses)
The financial results for the three and six months ended June 30, 2021 were a loss, on a net basis, of €4.4 million and €0.7 million, respectively, representing an increase of €4.4 million and €8.8 million, from a loss of €8.8 million and €9.5 million for the same periods in 2020. Financial result for the six months ended June 30, 2021, was mainly driven by negative interest on cash, which is being held in liquid funds to be available for use for CVnCoV and CV2CoV development and manufacturing activities, but was almost fully offset by foreign exchange gains. The financial result for the six months ended June 30 2020, was mainly driven by interest recognized on convertible loans which were fully repaid in August 2020, and was partially offset by foreign exchange gains
Pre-Tax Loss
Pre-tax losses were €152.2 million and €264.4 million for the three and six months ended June 30, 2021, respectively, compared to €12.0 million and €35.9 million in the same respective periods of 2020.