Sipuleucel-T (Dendreon Corporation)

On the heels of early, but promising, cancer vaccine data released at this year’s American Association for Cancer Research (AACR) annual meeting, Corner Therapeutics on Thursday  detailed how its two technology platforms can supercharge the modality. The biotech also announced a $54-million series A that will help put its first vaccine to the clinical test next year. In addition to the financing, which was led by Ziff Capital Partners and saw participation from Cockrell Interests, Tanis Ventures, and Sandia Holdings, Corner also has grant funding from the Bill & Melinda Gates Foundation to apply its technology to infectious diseases, including HIV, influenza and COVID-19.The company’s tech is designed to elicit a strong, long-lasting immune response by activating dendritic cells – the so-called “apex regulators” of the immune system because they are the only cell type that can stimulate new T cell responses. While the idea of dendritic cell-associated cancer vaccines is not new, Corner has come a long way from the earliest iteration at Dendreon Therapeutics and the long and messy history of its Provenge (sipuleucel-T). The FDA approved the immunotherapy in 2010 to treat prostate cancer, but at the time it was seen as an expensive and difficult-to-use treatment – with questionable efficacy – and failed to be a commercial success, leading to a bankruptcy declaration from Dendreon in 2014. The company has since managed to turn its business around and began earning a profit in 2018. For more, see ViewPoints: Now officially walking, Dendreon sets its sights on running. Powering up dendritic cellsThere are two major differences between Dendreon and Corner’s vaccine work, CEO  Steven Altschuler told FirstWord. He previously was CEO of the Children’s Hospital of Philadelphia from 2000 to 2015 and also co-founded Spark Therapeutics, serving as chair until Roche acquired the gene therapy company for $4.3 billion in 2019.First, the biotech’s products will be in vivo, while Provenge is an ex vivo therapy that sources dendritic cells from a patient and exposes them to antigens before readministration. And second, Corner’s first platform is intended to promote a heightened state in dendritic cells – not just activated, but “hyper”activated. Dendritic hyperactivation was first discovered more than eight years ago by scientific co-founder Jonathan Kagan, a professor of paediatrics at Harvard Medical School. He found that when dendritic cells are in this state – triggered when the body sends both “infection” and “tissue damage” signals – stronger CD8+ T cell responses are generated, thanks to a pair of cellular processes that don’t occur during normal activation.Within dendritic cells, inflammasomes form and secrete IL-1β, a cytokine known to generate new, and reactivate existing, memory T cells. Additionally, a mass migration of dendritic cells to the lymph nodes – the primary T cell meet-up zone – is triggered. “These extra stimuli that we can apply makes a world of difference in terms of generating cellular immunity,” Altschuler said.A protein antigen-based vaccine developed with Corner’s hyperactivation platform will comprise three components: a proprietary oxidised lipid to send the “damage” signal, a TLR7/8 agonist to activate the “infection” signal, and the disease antigens. According to Altschuler, the modality is antigen-agnostic and can use neoantigens sourced from a cancer patient to create a personalised treatment, or incorporate a viral antigen for an off-the-shelf infectious disease vaccine. A STINGing immune boostIn tandem, Corner is developing a catalytic adjuvant technology intended to boost the power of mRNA-based vaccines by activating a well-known immune pathway: STING.While STING agonists have struggled to show efficacy in clinical cancer trials, Altschuler said Corner’s tactic causes continuous pathway activation.The company has developed an mRNA-encoded enzyme that reacts with naturally occurring cellular DNA to catalyse the formation of cGAMP, which is a precursor of the STING pathway.“What we have found is that this mechanism induces very profound antigen-specific T cell responses,” Altschuler said, adding that the platform is “very flexible and in effect, antigen-agnostic.”As an example of the platform’s potential power, Altschuler pointed to mRNA-based cancer vaccines already in development, such as Moderna’s mRNA-4157 (V940). At AACR, the biotech shared new data showing that the individualised neoantigen therapy, in combination with partner Merck & Co.’s anti-PD-1 antibody Keytruda (pembrolizumab), led to a response rate of 27.3% in 22 patients with unresectable, metastatic HPV-negative head and neck squamous cell cancer (HNSCC).If Corner’s catalytic adjuvant technology was incorporated into an mRNA-based vaccine, “we would expect our platform to enhance the efficacy of those vaccines because of this much better T cell response,” Altschuler said, which could in turn confer longer immunity.

BARCELONA, Spain I September 17, 2023 I La Merie Publishing released its newest product reviewing the pipeline of PSMA-targeted therapy candidates in R&D: PSMA-Targeted Therapy Pipeline Review Target: Prostate Specific Membrane Antigen (PSMA) Product Category: Antibody; Cells; Radiopharmaceuticals This product provides basic information on approved therapeutics and therapy candidates in research and development targeting PSMA. This product consists of: This product is delivered on the very same day of purchase by e-mail containing competitor and project history reports in pdf format and database credentials. Reports are prepared on the same day. An estimated 268,000 new cases of prostate cancer in the United States are expected in 2022. Although the overall 5-year survival rate is over 95%, only about one in three patients live past 5 years if metastases are present, and prostate cancer remains the second leading cause of cancer deaths in men after lung cancer. Prostate cancer typically transitions from hormone sensitive to castration resistant, and patients with metastatic castration-resistant prostate cancer (mCRPC) survive for only about 2–3 years. In addition to androgen deprivation therapy (ADT), there have been a number of therapies approved in the mCRPC setting over the past two decades, including taxane chemotherapy (docetaxel and cabazitaxel), immunotherapy (sipuleucel-T and pembrolizumab), androgen receptor pathway inhibitors (ARPIs; abiraterone and enzalutamide), and targeted therapies such as poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib). Despite the increasing size of this armamentarium, the vast majority of patients with CRPC progress and novel agents are urgently needed to improve survival while maintaining quality of life. Prostate specific membrane antigen (PSMA) expression is prevalent in prostate cancer, preserved during malignant transformation, and increases in response to anti-androgen therapies, making it a commonly targeted tumor associated antigen for prostate cancer. PSMA mainly serves as a binding target for delivery of a variety of payloads, including, but not limited to, cytotoxic drugs in antibody-drug conjugtes, recruitment of cytotoxic T-cells in bispecific antibodies or directly PSMA-targeted chimeric antigen receptor T-cells. PSMA is also an important binding target for delivery of radioactive payloads in targeted radioligand therapy, whereby binding molecules can be small molecules, peptides and antibodies. A variety of radioligands are being evaluated or already been approved, including lutetium 177, actinium 225, thorium 227, cupper 67, or iodine 131. The report “ PSMA-Targeted Therapy Pipeline Review ” can be acquired at La Merie Publishing’s online store: https://lamerie.com/report/psma-targeted-therapy-pipeline-review/ About La Merie Publishing La Merie Publishing is an independent business information provider for the biotechnology and pharmaceutical industry. La Merie Publishing prepares brief and full reports. La Merie Publishing products can be purchased in the online store www.lamerie.com and from selected Resellers. La Merie Publishing offers the service of custom report preparation for corporate clients, including, but not limited to, pipeline analysis reports, drug profiles and any other competitive intelligence elaboration of interest. SOURCE: La Merie Publishing