On November 11, 2022 Nutcracker Therapeutics, Inc., a biotechnology company dedicated to developing transformative RNA therapies through its proprietary technology platform, reported the first set of preclinical data for its lead oncology mRNA therapeutic, NTX-250, at the 37th annual Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting (Press release, Nutcracker Therapeutics, NOV 11, 2022, View Source [SID1234623903]). The data demonstrate that NTX-250 has the ability to elicit strong anti-tumor responses in C3.43 murine tumor models and induces an immune response in non-human primates specific to human papillomavirus (HPV).
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NTX-250 is being developed for tumors driven by HPV16, which includes cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN). Key highlights of the data include:
NTX-250 induced complete regression of large tumors – greater than 120 mm3 in volume – resulting in long-term, tumor-free survival of all 10 treated animals
This result was accompanied by markers of strong tumor infiltration of CD8+ T cells, CD4+ antigen-presenting cells and natural killer (NK) cells
Successful modulation of the tumor microenvironment (TME) was also observed through the upregulation of interferon-gamma (IFN-γ) and other key immunomodulators
The translational potential of NTX-250 was assessed in cynomolgus monkeys (n=2), where it was seen that administration of 3 doses of NTX-250 induced strong HPV16-specific responses
"We’re excited to share Nutcracker Therapeutics’ first set of data on NTX-250 with the scientific community," commented Chief Medical Officer Robert J. Schott, M.D. "It’s been our long-held belief that the RNA drug class presents a unique opportunity to create safe and effective immunotherapies. The preclinical data we presented today is compelling in this regard, and shows that NTX-250 is able to induce a strong immune response and completely regress tumors in a murine model."
NTX-250 is composed of three unique and synergistic mRNA molecules in a mRNA therapeutic. This triple mechanism is designed to induce a robust antitumor T-cell response in addition to opening the tumor microenvironment to enhance immune cell activity and reduce immunosuppression. All three components have been shown to enhance long-term efficacy against HPV-driven tumors in model systems.
More than 90 percent of cervical cancers and CIN lesions, and 70 percent of head and neck cancers, are linked to infections with high-risk HPV. HPV16 is the most prevalent high-risk strain, accounting for nearly half of infections. The company believes that there is an increasing need to not just target cervical cancer itself, but also CIN, as a significant percentage of women with high-grade CIN lesions progress to invasive cancer, if left untreated.
"Developing a therapy that includes all the necessary cancer-killing components efficiently is uniquely suited to mRNA," Dr. Schott elaborated. "Nutcracker Therapeutics’ proprietary RNA development platform was created to bring forward therapies, such as NTX-250, quickly and efficiently.
"Designing the three individual mRNAs, manufacturing the mRNA molecules, and encapsulating them within our Nutshell delivery vehicles was done using our end-to-end workflow within our platform," Dr. Schott continued. "We look forward to using our in-house technology and expertise to develop much-needed therapies for other types of cancer."
A Phase I clinical trial for NTX-250 is planned for 2023, pending the clearance of an Investigational New Drug application by the Food and Drug Administration.