HPV16 Infection

SINGAPORE, May 12, 2024 /PRNewswire/ -- SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, announced first preclinical data of its novel human papillomavirus (HPV)-specific T cell receptor-engineered T (TCR T) cell therapy armored with an TGFβRII-41BB immunoswitch – SCG142 – in an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting in Baltimore, Maryland. In preclinical studies, SCG142 demonstrated superior CD8+ and CD4+ TCR T cell proliferation and tumor inhibition both in-vitro and in-vivo compared to conventional TCR T without immunoswitch, including tumor rechallenge models. Importantly, SCG142 functionality is CD8 co-receptor independent, transferring desired effector functions also to CD4+ T cells and promoting longer persistence and improved proliferation of T cells. In addition, SCG142 exhibited high functional avidity and can recognize both genotypes HPV-16 and HPV-52, with a favorable safety profile with no alloreactivity or off-target toxicity in relevant toxicology models. "SCG142 is a novel and differentiated HPV-specific TCR T cell therapy with preclinical efficacy in various tumor types with expression of HPV-16- and HPV-52 genotypes. We're excited to demonstrate that armoring the TCR-T cells with the chimeric switch receptor didn´t change the favorable safety profile but helped to overcome the immune inhibitory signal of TGF-β, which can be crucial for effective treatment of solid tumors", said Dr. Susanne Wilde, Head of Preclinical Research of SCG Cell Therapy. "These promising results underscore the potential of SCG142 to provide new solutions for patients in a variety of HPV-16- and HPV-52 expressing cancers. Based on these encouraging data, we are eagerly advancing SCG142 towards clinical trials", she added. About SCG142 SCG142, an autologous HPV-specific TCR T cell therapy holding the promise as the best-in-class product. Utilizing SCG's proprietary GianTCRTM technology, high affinity and high avidity natural TCRs can be isolated to target against intracellular antigens presented through major histocompatibility complex (MHC) in solid tumors. Study results showed that SCG142, a fully natural HPV specific TCR armoured with chimeric switch receptor, has the potential to specially target HPV-16 and HPV-52-positive tumor cells in various HPV-related tumor types, generating CD8 co-receptor independent T cell functionality and sustained anti-tur activity. About Human Papillomavirus and Cancers Human papillomavirus (HPV) infection is the most common sexually transmitted infection. Nearly all sexually active people are infected with HPV and around half of these infections occur with a high-risk HPV type, which can lead to cancer development.1 As such, HPV infection accounts for more than 90% of anal and cervical cancers, about 70% of vaginal and vulvar cancers, and 60% of penile and oropharyngeal cancers, and it causes an estimated 630,000 cancers worldwide each year2x. About SCG Cell Therapy SCG is a leading biotechnology company focusing on the development of novel immunotherapies in infections and its associated cancers. The company targets the most common cancer-causing infections: helicobacter pylori, HPV, HBV and EBV, and develops a broad and unique pipeline of TCR-based cellular immunotherapy products against infection- associated cancers. With the proprietary GianTCRTM TCR screening platform, in house viral vector production and AutoCellTM, a fully closed and automatic cell therapy manufacturing system, the company covers the entire value chain from new target research and discovery, manufacturing, and clinical development. For more information about SCG, please visit us at . [1] HPV and cancer. National Cancer Institute. (2023, October 18) [2] Basic information about HPV and cancer. Centers for Disease Control and Prevent (2023, September 12) SOURCE SCG Cell Therapy Pte Ltd

Study indicates clear route to market despite not meeting the primary endpoint of 6 months' overall response rate (ORR) in the entire population In a predefined subgroup of patients there was a doubling of ORR (51.9% vs 26.7% for placebo) and improved overall survival which sets the stage for a confirmatory Phase 3 trial OEGSTGEEST, The Netherlands, Dec. 12, 2023 /PRNewswire/ -- ISA Pharmaceuticals B.V. (ISA), a clinical-stage immunotherapy company, today announced positive anti-tumor response data with ISA101b, an HPV16 directed therapeutic cancer vaccine given in combination with Libtayo®, an anti-PD1 checkpoint inhibitor (CPI). The data were generated in the OpcemISA trial, a large scale randomized double blind study that is ongoing in patients with advanced oropharyngeal cancer (OPC), a type of head and neck cancer. It is the first time that the combination of a tumor-specific therapeutic vaccine and a CPI has generated such high response rates, albeit in a predefined subpopulation of metastatic cancer patients. ISA101b is a therapeutic cancer vaccine targeting cancers caused by the human papillomavirus type 16 (HPV16). More than 60 percent of head-and-neck cancers are HPV16-related, and incidence rates are going up. ISA101b elicits a powerful and targeted T-cell immune response to the HPV16 virus. OPC is a solid cancer with a high unmet medical need that does not always respond to immunotherapy. Best responses in the OpcemISA trial are found in a subcategory of patients with characteristics suitable for immunostimulatory treatments. Study design & results A total of 199 first- and second-line patients with recurrent/metastatic HPV16+ OPC were enrolled in the OpcemISA trial. Patients were randomized to receive either ISA101b plus CPI, or placebo plus CPI. The primary endpoint was the objective response rate (ORR) at 6 months, confirmed by independent central review. The secondary endpoints included drug safety, progression free survival (PFS) and overall survival (OS). Further details can be found at clinicaltrials.gov (NCT03669718). Whereas the addition of ISA101b to the CPI led to a doubling of the ORR (from 26.7% to 51.9%) in a large subgroup of patients, the study as a whole did not meet this primary endpoint. Patients in the aforementioned subgroup, predefined based on a validated biomarker, also showed a clear overall survival benefit compared to the placebo arm. ISA101b was well tolerated. Gerben Moolhuizen, Chief Executive Officer of ISA, said, "Recurrent and/or metastatic head and neck cancer is notoriously difficult to treat. Patients suffering from this terrible disease need new treatment options. In our OpcemISA study, ISA101b shows compelling results in a large, predefined subset of patients. This provides us with a clear development path to make ISA101b a treatment option for these patients." Phase 3 and beyond ISA is preparing for a confirmatory Phase 3 trial in this subpopulation of patients. This subgroup represents an important proportion of head and neck cancer patients, and an attractive commercial opportunity. The OpcemISA trial was part of a clinical collaboration between ISA and Regeneron. Regeneron has elected not to exercise its option on the ISA101b asset. ISA is currently in discussions with potential partners with interest in ISA101b and ISA's technology platform in general. About ISA Pharmaceuticals ISA Pharmaceuticals is an immunotherapy company developing treatments for various cancers and infectious diseases. ISA has best-in-class technology to stimulate and activate the human immune system, specifically T cells, to fight diseased or infected cells. Its lead asset ISA101b is in late-stage clinical trials for human papillomavirus type 16 (HPV16)-induced cancers in a collaboration with biotechnology company Regeneron. Other assets are in preclinical stage development and include immunotherapies to treat patients that suffer from cancers that over-express PRAME or chronic hepatitis B. For more information, please visit . About ISA101b ISA101b immunotherapy targets human papillomavirus type 16 (HPV16) positive cancers. It induces strong and specific T-cell immune responses to the HPV16 virus, and (re-)establishes a powerful and targeted T-cell immune response against infected and/or cancerous cells and tissues. ISA101b is using ISA's proprietary Synthetic Long Peptide (SLP®) technology.. In September 2021 ISA101b was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of recurrent and metastatic HPV16 positive oropharyngeal cancer (OPC). SOURCE ISA Pharmaceuticals

NTX-471 had similar activity to conjugates of existing anti-CD47 therapeutics, without anemic side effects Mice treated with mNTX-250 for HPV-16-transformed tumors became tumor-free and remained so after tumor rechallenge EMERYVILLE, Calif.--(BUSINESS WIRE)-- Nutcracker Therapeutics, Inc., a biotechnology company dedicated to developing transformative RNA therapies through its proprietary technology platform, today presented preclinical data for two of its therapeutic candidates: its latest therapeutic candidate, NTX-471, which targets CD47; and the company’s lead mRNA candidate targeting human papillomavirus (HPV)-driven tumors, NTX-250. These data were presented at the Society for Immunotherapy of Cancer’s (SITC’s) 38th Annual Meeting. CD47 molecules are transmembrane glycoproteins that signal macrophages not to eat the cells on which they are expressed by binding to signal regulatory protein alpha (SIRPa). Anemia is the most common adverse effect of CD47-targeting molecules, since red blood cells also express CD47. NTX-471 is being developed to specifically target CD47 on cancerous cells with unique mRNA-encoded compositions. Nutcracker’s scientists engineered bivalent, tetravalent, hexavalent, and octavalent RNA-encoded SIRPa proteins and bispecific SIRPa-antiCCR4 molecules. The performance of these molecules were then assessed in vivo and in vitro. Key highlights of the data include: The octavalent variant’s cytotoxic activity was similar to that of anti-CD47 molecules currently in clinical trials. But, most importantly, the Nutcracker molecules showed little-to-no binding to red blood cells in vitro Administering mice with formulated mRNA molecules encoding the tetravalent, octavalent, and bispecific SIRPa fully eradicated established subcutaneous tumors, and resulted in robust protein expression (~10-100ug/ml) with high purity/homogeneity similar to, or better than, DNA-expressed proteins “We’re excited to share our first set of data on NTX-471 with the scientific community,” said Executive Vice President of Research and Early Development Samuel Deutsch, Ph.D. “It’s no secret that anti-CD47 therapeutics have recently hit many roadblocks, and have often struggled to address anemic side effects in patients. Using our proprietary platform and the Nutcracker Manufacturing Unit, our team was able to design and quickly produce multiple RNA molecules to assess in vivo. Through our continued work, we are hopeful that NTX-471 will prove to be a viable solution in using CD47 to eradicate tumor cells, while leaving red blood cells untouched.” Further, Nutcracker presented data on a murine version of its lead candidate, NTX-250, labelled mNTX-250. The lead indication for NTX-250 is cervical intraepithelial neoplasia CIN, a precancerous condition caused by HPV infection, which can progress to cervical cancer if left untreated. HPV-16 is the most prevalent high-risk HPV strain. Nutcracker compared the activity of mNTX-250 to NTX-010. NTX-010 contains IL-12 and LIGHT components found in NTX-250, but lacks HPV antigens (the components of NTX-250 are detailed in previous communications). Key highlights of the data include: Two doses of mNTX-250 treatment eradicated well-established HPV16-transformed tumors, and improved overall survival in mice. The treated animals also generated significant numbers of HPV-16 E7 antigen-specific T cells All treated mice with eradicated tumors showed complete rejection when rechallenged Mice treated with NTX-010 generated fewer HPV16 antigen-specific T cells. When rechallenged, 6 out of 11 NTX-010-treated mice showed tumor growth “We developed our platform, including the Nutcracker Manufacturing Unit, specifically to fast track early R&D work for RNA therapies, and to efficiently produce them once ready for patients," said Chief Executive Officer Igor Khandros, Ph.D. "The data we presented at SITC are a testament to the power of RNA, but also what a solution designed specifically for this modality can enable for drug developers. For example, with NTX-471, delivering mRNA, which encodes anti-CD47 proteins, offers a more straightforward method versus producing the complex proteins using a traditional cell line paradigm. Moreover, modifying the RNA sequence of the prospective anti-CD47 molecule is far more efficient than engineering the final protein product. Our platform has made it possible for Nutcracker to lay a strong and early foundation for our future therapeutic work.” About Nutcracker Therapeutics, Inc. Nutcracker Therapeutics, Inc. is an RNA therapeutics company that has combined the power of advanced engineering with high-precision biosynthesis to deploy a complete RNA platform that encompasses the design, delivery, and manufacturing of RNA medicines. Armed with this high-tech advantage, the company has initiated multiple therapeutic programs with the support of clinical investigators at leading institutions. Nutcracker’s technology platform has the potential to significantly reduce costs and cycle times for RNA therapeutic development, with dramatic advantages in speed and capacity scaling over other RNA manufacturing approaches. For more information, visit .