CV-8102

CureVac presented data on its immunity activator CV8102 late last week. CureVac is rethinking development of immunity activator CV8102 in the wake of the publication of data from a checkpoint inhibitor combination trial, vowing to only consider further clinical studies if the drug candidate is paired with “a defined mRNA cancer vaccine.” CV8102 is a non-coding, non-capped RNA designed to activate innate and adaptive immunity. The candidate entered the clinic in 2014, when CureVac began testing it in combination with a rabies vaccine. Studies of the RNA prospect in cancer indications got underway in 2017 with a trial to evaluate the effect of injecting CV8102 into tumors. The German biotech presented data from the completed expansion part of the study late last week. In the 30-subject anti-PD-1 combination cohort, 17% of participants experienced a partial response. None of the 10 subjects who received CV8102 as a single agent responded to the RNA candidate. CureVac has revised its plans for the molecule since seeing the data.  “In the context of our current strategic focus on the development of novel mRNA-based cancer vaccines, data from the planned proof-of-principle studies and parallel progress in the discovery of new tumor-specific antigens will provide the basis for any potential integration of CV8102 into this priority program as a strong immune-modulatory adjunct,” the company wrote. “Further clinical development of CV8102 will only be considered in combination with a defined mRNA cancer vaccine.”  While the new position shuts off the prospect of CureVac establishing CV8102 as an enhancer of immune checkpoint inhibitors, it leaves the door open to it emerging as an enabler of molecules in the biotech’s own pipeline.  CureVac was once focused on a cancer vaccine, CV9104, but the failure of that candidate in a phase 2b clinical trial set back that side of the business. This year, the biotech has moved to reinvigorate its work in the area, inking a research and option agreement with myNEO and buying Frame Cancer Therapeutics.

TÜBINGEN, Germany and BOSTON, MA, USA I November 11, 2022 I CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid (“mRNA”), today announced data from the Phase 1 expansion study of CV8102, the company’s non-coding RNA candidate in oncology. Preliminary results from the completed Phase 1 expansion study in patients with PD-1 refractory melanoma confirm a robust safety profile of CV8102 as a single agent and in combination with anti-PD-1 antibodies. Preliminary efficacy was observed in a cohort of 30 patients treated in combination with anti-PD-1 antibodies, 40% of whom were pretreated with anti-CTLA-4 antibodies. As of June 15, 2022, in the anti-PD-1 combination cohort, five out of 30 patients (17%) experienced a partial response according to RECIST 1.1. Responses appeared durable for up to one year from the start of treatment. No objective responses were observed in the 10 patients of the single-agent cohort, 50% of whom were pretreated with anti-CTLA-4 antibodies. The data will be presented today at the 37 th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), held in Boston, Massachusetts. Extensive analysis of immune cell activation was performed to better understand CV8102’s mobilization of the immune system against injected tumors as well as non-injected tumors. The data confirm that single agent or combination treatment, after the first dose, activated systemic pathways of immune response. Preliminary analysis of the tumor microenvironment in a subgroup of patients showed the positive outcome of increased infiltration of T cells, following intra-tumoral injection in 4 out of 8 (single agent cohort) and 10 out of 18 (anti- PD1 combination cohort) analyzed paired biopsy samples. “The data we collected in the heavily pretreated patients of our Phase 1 expansion study further confirm the safety and immuno-modulatory activity of CV8102,” said Ulrike Gnad-Vogt, interim Chief Development Officer at CureVac. “As a non-coding RNA, CV8102 is designed to mimic a viral infection of the tumor and to induce an adaptive immune response against a broad panel of tumor antigens. The preliminary efficacy we see in the small group of pretreated patients further validates this technology. Given our strategic focus on developing a meaningful portfolio of mRNA-based therapeutic cancer vaccines, we will seek to assess CV8102’s potential as a complementary technology.” Final results are expected in H1 2023 and will be submitted for publication in a peer reviewed journal. CV8102 is being tested in a fully recruited dose-escalation and expansion Phase 1 study to confirm its safety, tolerability and efficacy as a single agent and in combination with licensed anti-PD-1 antibodies. Preliminary results from the completed dose-escalation part of the study in a range of solid tumors, were previously reported at the European Society for Medical Oncology (ESMO) conference in September 2021. About CV8102 CV8102 is a single-stranded non-coding RNA optimized to maximize activation of cellular receptors that normally detect viral pathogens entering the cells, such as toll-like receptors 7 and 8 (TLR7/8), and retinoic acid inducible gene I (RIG-I), mimicking a viral infection of the tumor. CV8102 is designed to recruit and activate antigen-presenting cells at the site of injection to present tumor antigens released from tumor cells to T cells in the draining lymph node. This potentially leads to activation of tumor-specific T cells, which can kill tumor cells at the injected site, but also at distant non-injected tumor lesions or metastases. The Phase 1, open-label, dose escalation and expansion study of CV8102 aims to assess safety, tolerability and efficacy of CV8102 as a single agent and in combination with licensed PD1-antibodies. Preliminary results from the completed dose-escalation part in patients with advanced melanoma, cutaneous squamous cell carcinoma, squamous cell carcinoma of head and neck or adenoid cystic carcinoma were reported at the European Society for Medical Oncology (ESMO) conference in September 2021. The expansion part of the study focuses on patients with PD-1 refractory melanoma treated with a recommended dose of 600µg. About CureVac CureVac (Nasdaq: CVAC) is a global biopharmaceutical company in the field of messenger RNA (mRNA) technology, with more than 20 years of expertise in developing, optimizing, and manufacturing this versatile biological molecule for medical purposes. The principle of CureVac’s proprietary technology is the use of optimized mRNA as a data carrier to instruct the human body to produce its own proteins capable of fighting a broad range of diseases. In July 2020, CureVac entered in a collaboration with GSK to jointly develop new products in prophylactic vaccines for infectious diseases based on CureVac’s second-generation mRNA technology. This collaboration was later extended to the development of second-generation COVID-19 vaccine candidates, and modified mRNA vaccine technologies. Based on its proprietary technology, CureVac has built a deep clinical pipeline across the areas of prophylactic vaccines, cancer therapies, antibody therapies, and the treatment of rare diseases. CureVac N.V. has its headquarters in Tübingen, Germany, and has more than 1,000 employees across its sites in Germany, the Netherlands, Belgium, Switzerland and the U.S. Further information can be found at www.curevac.com . SOURCE: CureVac