CureVac(CVAC) - 2021 Q4 - Annual Report

Vaccine Development - The company has advanced its second-generation COVID-19 vaccine candidate, CV2CoV, to a Phase 1 clinical trial as of March 30, 2022, with plans for a pivotal study potentially starting in Q4 2022[501]. - The Phase 1 study of CV7202, a prophylactic vaccine candidate against rabies, demonstrated protective antibody titers above the WHO threshold after two doses of 1μg of mRNA[499]. - The company is developing a differentiated multivalent influenza vaccine candidate, CVSQIV, with a Phase 1 dose-escalation study initiated in February 2022 involving up to 240 healthy adult participants[512]. - The second-generation mRNA vaccine program CV2CoV for SARS-CoV-2 is currently in Phase 1 clinical study, showing improved immune responses compared to the first-generation candidate[629]. - The CVSQIV influenza vaccine candidate is also in Phase 1 clinical study, featuring multiple non-chemically modified mRNA constructs targeting four different influenza strains[630]. - The rabies vaccine candidate CV7202 has induced adaptive immune responses above WHO protective thresholds at low dose levels in Phase 1 clinical trials[631]. - The company is developing prophylactic vaccines for infectious diseases with high mortality rates in developing countries, in partnership with the Bill & Melinda Gates Foundation[633]. mRNA Technology and Manufacturing - The company has manufactured thousands of mRNA constructs and obtained manufacturing authorization for over 80 products since 2000, with plans to build a fourth GMP large-scale production facility capable of supplying hundreds of millions of doses[505]. - The company has invested in building in-house manufacturing infrastructure to produce mRNA-based medicines efficiently and cost-effectively at commercial scale[505]. - The company has developed a versatile mRNA technology platform, RNAoptimizer, which focuses on protein design, mRNA optimization, and delivery to improve safety, stability, and expression[536][537]. - The company’s mRNA production process is independent of the encoded protein, allowing for higher efficiency, greater speed, and lower costs in developing mRNA-based therapies[531]. - The company has identified over one million 5' and 3' UTRs to improve translation and stability of therapeutic mRNAs[579]. - The cap structure of mRNA is optimized to improve translation efficiency and reduce immunogenicity, enhancing overall therapeutic efficacy[577]. - The company’s mRNA constructs are designed to evade innate immune recognition, allowing sustained protein translation[575]. Clinical Trials and Efficacy - The company has a long track record of clinical trials since 2008, which has accelerated development in new therapeutic areas and approaches[538]. - The lead oncology product candidate CV8102 is currently in a Phase 1 clinical trial for treating solid tumors, activating multiple immune pathways[636]. - CV8102, the company's lead candidate, is in a Phase 1 clinical trial for treating four types of solid tumors, with 58 patients enrolled as of June 21, 2021[652][653]. - Preliminary results from the Phase 1 trial show 1 complete response and 2 partial responses in the single-agent cohort, and 2 partial responses in the combination cohort[654][655]. - The company aims to confirm the safety and efficacy of CV8102 at a 600 µg dose in the ongoing Phase 1 trial expansion, which has enrolled 30 patients with PD-1 refractory melanoma[656][657]. - The mechanism of action for CV8102 involves activating immune responses by mimicking viral infections, potentially leading to tumor-specific T cell activation[658][659]. - The Phase 1 clinical trial is designed to evaluate the maximum tolerated dose and safety of CV8102, with secondary endpoints focused on anti-tumor activity[667]. Delivery Systems and Optimization - The company utilizes a combination of delivery systems tailored to specific diseases, considering factors like immunogenicity and targeted tissue type[595]. - The company has extensively tested over 40 different delivery solutions and selected the most efficient lipid nanoparticle (LNP) technologies for licensure[602]. - The proprietary CVCM delivery technology offers advantages such as stability, low excipient to cargo ratio, and immunosilence, making it suitable for sensitive tissues like the eye and lung[606][610]. - The CVCM formulation allows for high levels of protein expression following intrapulmonary administration, indicating its effectiveness for lung delivery[614]. - The company is exploring multiple delivery systems for mRNA, including the CVCM delivery system for lung and eye diseases[648][649]. Strategic Partnerships and Intellectual Property - The company has entered into strategic partnerships with leading biopharmaceutical companies, including GSK, to expand the applications of its technology platform[506]. - The company aims to selectively seek strategic partnerships to expedite the discovery and development of product candidates, aiming to mitigate drug development risk while retaining economic rights to strategically important candidates[516]. - The company is exploring strategic acquisitions or in-licenses of complementary technology or assets to enhance its mRNA technology platform, which has been optimized over 21 years[517]. - The company intends to strengthen its intellectual property portfolio to protect advancements in its technology platform, manufacturing processes, and product candidates[518]. - As of March 23, 2022, the company owns approximately 1,056 issued patents worldwide, including 85 issued U.S. patents and 62 issued European patents[507]. Safety and Adverse Events - 100% of patients experienced at least one adverse event, with 38% experiencing grade 3 adverse events[694]. - The most common adverse events included fatigue (34%), injection site pain (21%), and influenza-like illness (16%) among all patients[694]. - CV8102 is administered weekly for the first five cycles, totaling eight injections or until disease progression[689]. - The study continues with dose escalation for both single-agent CV8102 and the combination with anti-PD-1 therapy[690].