Candidate: Vaccine

Category: RNA, VAX

Type: mRNA-based coronavirus vaccine encoding the full-length spike protein of SARS-CoV-2 and formulated with lipid nanoparticles (LNP). The vaccine uses nucleotides without chemical modifications in the mRNA, and is designed to provide a strong and balanced activation of the immune system.

2021 Status: Bayer has agreed to join CureVac to support its development of CVnCoV, the companies said January 7. Under the agreement, whose value was not disclosed, Bayer agreed to support the development, supply, and operations of CureVac within “key territory” markets that include the European Union (EU) and unspecified additional countries. While CureVac will remain the EU Marketing Authorization Holder for CVnCoV, Bayer agreed to provide services for the vaccine that include clinical operations, regulatory affairs, pharmacovigilance, medical information, and supply chain performance.

Not covered by the agreement is manufacturing of CVnCoV, though Bayer is testing whether it can offer production capacity toward the vaccine, a CureVac spokesman told The Wall Street Journal. “We are prepared to pull out all the stops for this,” Bayer CEO Werner Baumann confirmed January 17 to the German newspaper Welt am Sonntag.

2020 Status: CureVac said December 14 it advanced CVnCoV into a pivotal global Phase IIb/III trial. CVnCoV is under study in the Phase IIb/III HERALD trial (NCT04652102), a randomized, observer blind, placebo-controlled study designed to assess the safety and efficacy of the vaccine in adults at a dose of 12 µg. The study is expected to include more than 35,000 participants in Europe and Latin America.

The trial’s Phase IIb component will assess safety, reactogenicity and immunogenicity in study participants stratified according to age (>18 and >60 years old), initially at clinical testing sites in Europe and South America, while the Phase III portion of the trial will further assess safety and efficacy. An interim analysis is set to be carried out within the first quarter of 2021.

On November 17, CureVac announced plans to accelerate the expansion of its manufacturing network to deliver pandemic-scale volumes of its COVID-19 vaccine candidate, CVnCoV, through agreements with CDMO partners for each key manufacturing step for CVnCoV. The company said it expects to significantly increase its existing manufacturing capacities for CVnCoV to up to 300 million doses in 2021 and up to 600 million doses in 2022.

To that end, CureVac said, it is currently developing an additional large-scale production facility at its headquarters in Tübingen, Germany, supported by the European Investment Bank (EIB). CureVac’s CVnCoV manufacturing network will tap into expertise and capacity across Germany, France, the Netherlands, Belgium, Spain, and Austria, as well as potentially Sweden, Poland, Italy, and Ireland.

The European Union has agreed to purchase up to 405 million doses of CureVac’s CVnCoV vaccine, European Commission President Ursula von der Leyen said on November 16. The deal was to be authorized by the Commission the following day. The price was not disclosed.

The purchase agreement calls for the EU to buy an initial 225 million doses, with an option to buy another 180 million. The deal will bring to 1.8 billion the number of COVID-19 vaccine doses procured by the EU.

On November 12, CureVac announced initial stability data showing that CVnCoV remained stable and within defined analytical specifications for at least three months when stored at a standard refrigerator temperature of 5° C (41° F), and for up to 24 hours at room temperature as a ready-to-use vaccine.

CureVac reported positive interim data November 2 from its ongoing Phase I dose-escalation study evaluating the safety, reactogenicity and immunogenicity of CVnCoV. CureVac said the data supported its decision to advance the 12µg dose of CVnCoV in its upcoming pivotal Phase IIb/III study, set to start before the end of 2020.

The Phase I study (NCT04449276) has enrolled 284 healthy individuals aged 18 to 60 years as of. Individuals were vaccinated intramuscularly with CVnCoV at escalating dose levels of 2, 4, 6, 8 and 12µg on days 1 and 29. At all tested dose levels, immunogenicity data showed induction of binding antibody titers, translating into relevant titers of virus neutralizing antibodies. However, at 12µg, Geometric Mean Titers (GMTs) of binding antibodies increased to the level measured in 67 symptomatic convalescent COVID-19 patients.

Per dose level, the trial included up to 10 participants who had previously tested positive for a COVID-19 infection (seropositives) to further evaluate the safety and immunogenicity of CVnCoV in this sub-population. CureVac said it intends to provide detailed Phase I data in a scientific journal “in the coming weeks.”

On September 29, CureVac said the first participant has been dosed in its Phase IIa trial (CV-NCOV-002; NCT04515147), a dose-confirmation study of CVnCoV being conducted in Peru and Panama. The trial is expected to enroll 691 healthy participants in two distinct groups: older adults ages 61 and above, and younger participants 18 to 60 years old.

Participants will receive two vaccinations at intervals of 28 days. Different dose levels will be investigated, starting at 6 µg, with the aim of confirming safety and evaluating reactogenicity of the vaccine in older adults. The trial’s first comprehensive data in older adults is expected later in the fourth quarter of 2020. The humoral immune response after administration of CVnCoV will be assessed, and the safety database expanded, to prepare for the launch of a Phase IIb/III trial that is set to enroll approximately 30,000 participants starting in the fourth quarter of 2020.

CureVac said September 4 that it was notified by the German Federal Ministry of Education and Research (BMBF) that it is expected to receive up to €252 million ($298 million) to support development of CVnCoV. The grant is also expected to fund rapid expansion of vaccine production, with payments tied to achieving milestones. CureVac said it expected to receive up to €103 million ($122 million) in 2020 and up to €149 million ($176 million) in 2021.

CureVac and the European Commission said August 20 they concluded exploratory talks toward an agreement allowing all EU member states to purchase up to 225 million doses of CVnCoV, with an option for an additional purchase of 180 million doses, once the vaccine is proven safe and effective. The vaccine is in a Phase I clinical trial in Germany and Belgium, with first results expected early in the fourth quarter. Depending on the results of the Phase 1 trial, CureVac said, it may also launch a Phase IIb/III clinical trial also in Q4 2020.

On August 14, CureVac launched a very successful initial public offering (IPO), with shares opening at $44 a share and closing at $55.90—more than triple the $16 IPO price. The company had projected total gross proceeds of approximately $213.3 million, based on the sale of 13,333,333 shares at $16 a share. CureVac also granted the underwriters a 30-day option to purchase up to an additional 1,999,999 common shares at the IPO price, less underwriting discounts and commissions.

CureVac estimated in its prospectus it would generate $182.7 million, most of which (approximately $150 million) is intended for use toward funding clinical development of its CVnCoV vaccine against SARS-CoV-2 through the completion of the Phase III clinical trial. Another aproximately $50 million is intended to fund the expansion of short-term manufacturing capabilities.

CureVac on August 4 appointed Igor Splawski, PhD as Chief Scientific Officer overseeing the company’s mRNA biology research, including its COVID-19 vaccine effort. Splawski was previously Executive Director of the Novartis Institutes for BioMedical Research (NIBR), where he also served as Site Head of the NIBR Biologics Center in Cambridge, MA

CureVac also named Franz-Werner Haas, PhD, LLD, LLM, as CEO; he was promoted in March from Deputy CEO to Acting CEO and Chief Operating Officer after Ingmar Hoerr, a former CEO and founder who returned to the helm in March, then took a medical leave of absence.

On July 20, CureVac said its mRNA vaccine program and rabies vaccine research program were not included in its potentially more than £866 million (over $1.1 billion) agreement with GlaxoSmithKline (GSK) to research, develop, manufacture, and commercialize up to five mRNA-based vaccines and monoclonal antibodies (mAbs) targeting infectious disease pathogens. The deal includes an equity investment of £170 million through which GSK agreed to take a 10% stake in CureVac.

CureVac said July 6 it entered into a €75 million (about $89 million) loan agreement with the European Investment Bank, the lending arm of the European Union. The loan is designed to support company expansion of its GMP certified production capabilities, and accelerate the completion of its fourth production site in Tübingen, Germany. The EIB financing will be provided in three €25 million ($29.6 million) tranches upon completion of pre-defined milestones.

The loan is being financed through the €400 million ($474 million) Infectious Diseases Finance Facility of Horizon 2020, the EU research and innovation program for 2014-2020.

Tesla co-founder and CEO Elon Musk tweeted July 2 that his company “as a side project, is building RNA microfactories for CureVac & possibly others,” in a follow-up to an earlier tweet that day in which he praised CureVac’s mRNA technology: “In principle, I think synthetic RNA (and DNA) has amazing potential. This basically makes the solution to many diseases a software problem.”

Musk is expected to apply CureVac’s The RNA Printer™, a transportable, down-scaled, automated mRNA printing platform for which CureVac was awarded a $34 million contract by the Coalition for Epidemic Preparedness Innovations (CEPI). The RNA Printed is designed to provide a rapid supply of lipid-nanoparticle (LNP)-formulated mRNA vaccine candidates targeting known pathogens that include Lassa Fever, Yellow Fever, and Rabies—and enable rapid response to new and previously unknown pathogens.

In June, CureVac launched its Phase I clinical trial for CVnCoV following approval by the German Health Authority Paul-Ehrlich-Institute (PEI) and the Belgian Federal Agency for Medicines and Health Products (FAMHP).

The Phase I dose escalation clinical trial is recruiting 168 healthy subjects between ages 18-60 and will target a dose range of 2 µg to 8 µg. The trial’s aim is to determine the optimal dose as well as to evaluate the safety and immune profile of the vaccine in humans.The trial will be conducted in Germany and Belgium. First subjects will be vaccinated at the Institute for Tropical Medicine in Tübingen and the Ghent University Hospital (Belgium), the Tropical Institute of the University Hospital Munich, LMU (Germany), and the Hannover Medical School (Germany).

In parallel with the trial, CureVac is producing “large quantities” of vaccine at its GMP-certified large-scale mRNA production facility in Tübingen, Haas said in a statement.

Two days earlier, CureVac said the Federal Republic of Germany will invest €300 million ($337 million) in CureVac through the German state-owned developmemt bank Kreditanstalt für Wiederaufbau (KfW). Funds from the capital raise will be used toward the development of the company’s pipeline and mRNA platform technology, as well as the expansion of business activities, CureVac said. According to a draft agreement, the KfW will hold an approximately 23% stake in CureVac.

CureVac’s head of communications, Thorsten Schüller, told GEN in April that the company was on track to launch its vaccine into clinical trials by this summer, in line with its projection in a March 17 telephone briefing. He noted that CureVac’s SARS-CoV-2 vaccine isn’t its first using mRNA technology; the company has been testing its lipid nanoparticle mRNA rabies vaccine in human clinical trials, with results that he said have exceeded expectations: “We have indeed seen a long-lasting immune response in our preclinical studies with our mRNA-based vaccines.”

Also in March, the European Commission offered up to €80 million ($88 million) toward scaling up development and productions of the vaccine. The Coalition for Epidemic Preparedness Innovations (CEPI) awarded the company up to $8.3 million in January for accelerated vaccine development, manufacturing and clinical tests.

CureVac has denied a report in the German newspaper Welt am Sonntag that the administration of President Donald Trump sought to lure German-based CureVac to the U.S. with funding to produce its vaccine exclusively for the American market after then-CEO Dan Menichella visited the White House March 2 with other biopharma executives, while Germany’s government pressed for the company to stay in Tübingen and produce its vaccine for Germany and Europe.

U.S. ambassador to Germany, Richard Grenell denied the German news report via Twitter, but an unnamed German Health Ministry spokeswoman confirmed Germany’s interest in CureVac developing vaccines domestically in a statement to Reuters. Menichella resigned on March 11, and was succeeded by Hoerr, who just five days later took a temporary leave of absence for medical reasons “not caused by coronavirus,” the company said.


COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA

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