PSCA

LOS ANGELES, June 12, 2024 /PRNewswire/ -- A team of investigators at City of Hope funded by the Prostate Cancer Foundation (PCF) reports that patients with advanced prostate cancer can be safely treated with chimeric antigen receptor (CAR) T cell therapy. The results of their first-in-human phase 1 clinical trial, which also showed promising therapeutic activity, were published today in Nature Medicine. "This represents an important advance against metastatic castration-resistant prostate cancer (mCRPC) which continues to claim more than 30,000 men's lives each year," said Howard R. Soule, PhD, Executive Vice President, Chief Science Officer and Lori and Michael Milken Chair of the Prostate Cancer Foundation. "PCF is proud to invest in this crucial work which advances our mission to end death and suffering from prostate cancer, and we look forward to seeing their future progress with PSCA-directed CAR T cell therapy." Saul Priceman, PhD, City of Hope associate professor, Department of Hematology & Hematopoietic Cell Transplantation, and team developed CAR T cells that target prostate stem cell antigen (PSCA), which is highly expressed in prostate cancer. The phase 1 trial treated 14 PSCA-positive patients with mCRPC, which had spread beyond the prostate and no longer responded to hormone treatment, using the PSCA-directed CAR T-cell therapy. Patients' own immune system T cells were reprogrammed in a laboratory with a CAR to recognize and attack the PSCA protein on the surface of cancer cells. The CAR T cells were then infused back into the patients who were monitored for a 28-day study period. "Our trial's major finding is that PSCA-directed CAR T cells are safe and do work against mCRPC," said Priceman. "This opens up the opportunity to continue to develop this type of cellular immunotherapy for these patients, who currently have no other effective treatment options." The goal of the phase 1 study was to examine the therapy's safety and dose-limiting toxicities and gather preliminary data on efficacy of the approach. To assess the safety of CAR T cells alone, patients received a single infusion of 100 million CAR T cells without having prior lymphodepletion chemotherapy, which is routinely used in blood cancers to improve the efficacy of CAR T cell treatment. This was followed by incorporation of lymphodepletion at the same CAR T cell dose. Researchers found that with lymphodepletion, there was a side effect of cystitis, or irritation of the bladder. Since PSCA is also found in the bladder, it is likely the CAR T cells attacked the bladder cells, causing inflammation, they concluded. Historically, cyclophosphamide, which is part of the lymphodepletion regimen, can also cause cystitis. When the team reduced the dose of cyclophosphamide, the toxicity was largely mitigated in patients. Four of the 14 patients had declines in their PSA levels, which is a biomarker of disease progression in prostate cancer, including one patient with significant decline. Furthermore, imaging showed therapeutic responses in some of the treated patients. One patient's PSA level decreased by 95% and the cancer that had spread to his bones and soft tissue also declined. He experienced this positive response for approximately eight months. Five of the 14 patients had mild or moderate cytokine release syndrome, a systemic inflammatory response characterized by fever, nausea, fatigue, and other symptoms, and considered a common and treatable side effect of CAR T cell therapy. One limiting factor of the therapy's effectiveness is that CAR T cells did not persist in patients at high levels beyond the 28-day monitoring period. This is a common challenge in solid tumor CAR T cell therapy that the researchers will address in a phase 1B trial using the PSCA-CAR T cell therapy in a repeat dosing strategy and in combination with radiation to enhance anti-tumor activity. The City of Hope trial is currently enrolling patients. This body of work was leveraged into a 2022 PCF TACTICAL (Therapy ACceleration To Intercept Cancer Lethality) Award which supports large-scale, pioneering, multi-institutional team research projects addressing metastatic, lethal prostate cancer. The team with principal and co-investigators from the University of Pennsylvania, City of Hope, Children's Hospital of Philadelphia, the National Cancer Institute, the National Institute on Aging, the University of Southern California, and The Corporal Michael J. Crescenz VA Medical Center were awarded $10 million over three years to fund their project Developing Engineered Cell Therapies for Metastatic Castrate-Resistant Prostate Cancer to Increase Efficacy and Decrease Toxicity. About the Prostate Cancer Foundation The Prostate Cancer Foundation (PCF) is the world's leading philanthropic organization dedicated to funding life-saving prostate cancer research. Founded in 1993 by Mike Milken, PCF has been responsible for raising more than $1 billion in support of cutting-edge research through more than 2,250 research projects at 245 leading cancer centers, with a global footprint spanning 28 countries. Since PCF's inception, and through its efforts, patients around the world are living longer, suffering fewer complications, and enjoying better quality of all life. PCF is committed to creating a global public square for prostate cancer, in service to our mission of ending death and suffering from the disease. Learn more at pcf.org. MEDIA CONTACT: Staci L. Vernick Prostate Cancer Foundation svernick@pcf.org/press@pcf.org 610-812-6092 View original content to download multimedia: SOURCE Prostate Cancer Foundation

LOS ANGELES--( BUSINESS WIRE )--Researchers with City of Hope ® , one of the largest cancer research and treatment organizations in the United States, will present new findings at the AACR Annual Meeting, which will take place April 5 to 10 in San Diego. This year, City of Hope doctors and scientists will also present data during AACR’s Press Program and a clinical trials plenary session: Monday, April 8, 2024, at 8:30 a.m. Research by Ajay Goel, Ph.D., M.S. , City of Hope professor and chair, Department of Molecular Diagnostics and Experimental Therapeutics, and Caiming Xu, Ph.D., a postdoctoral fellow in Goel’s lab, will be presented at an AACR press conference. The abstract is titled “ An exosome-based liquid biopsy for non-invasive, early detection of patients with pancreatic ductal adenocarcinoma: A multicenter and prospective study .” Sunday, April 7, 2024, at 1 to 3 p.m. Sumanta Kumar Pal, M.D. , City of Hope chair, kidney and bladder cancer disease team, will present on “ CTX130 allogeneic CRISPR-Cas9-engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Long-term follow-up and translational data from the Phase 1 COBALT-RCC study ” during a clinical trials plenary session called, Beyond Immune Checkpoint Inhibition: Novel Immunotherapy Strategies . Additional data presentations include: “Multi-omics characterization of molecular features and global-local genomic ancestry analysis of colorectal cancer in Hispanic-Latinos” Minisymposium session 3932: Monday, April 8, 2024, 3:35 to 3:50 p.m. To investigate why Hispanic/Latino colorectal cancer (CRC) patients in Los Angeles face mortality rates up to 20% higher than their Caucasian counterparts, City of Hope’s Enrique Velazquez Villarreal, M.D., Ph.D., M.P.H., M.S. , City of Hope assistant professor, Department of Integrative Translational Sciences, and John D. Carpten, Ph.D. , City of Hope's chief scientific officer, Irell & Manella Cancer Center Director's Distinguished Chair and Morgan & Helen Chu Director's Chair of the Beckman Research Institute, along with a team of researchers, searched for mutations in CRC tumors by utilizing molecular profiling technologies. Results yielded important insights into the molecular characterization of CRC tumors and the multifaceted clinical and genomic heterogeneity within Hispanic/Latino populations, as well as crucial information on CRC tumor heterogeneity and the tumor microenvironment. “Microbiome modification impacts PSCA directed chimeric antigen receptor (CAR) T cell therapy for prostate cancer” Poster presentation 6676/7: Wednesday, April 10, 2024, 9 a.m. to 12:30 p.m. John Murad, Ph.D., a staff scientist in the laboratory of Saul J. Priceman, Ph.D. , City of Hope associate professor, Department of Hematology & Hematopoietic Cell Transplantation, and colleagues developed methods to evaluate the impact of microbiome manipulation in the team’s established syngeneic PSCA+ prostate cancer mouse model. They found that the model was sensitive to microbiome modulation and that the use of patient-derived human fecal matter transfers can significantly impact PSCA-CAR T cell directed anti-tumor responses. Late-Breaking Presentation Wednesday, April 10, 2024, from 9 a.m. to 12:30 p.m. Stephen Gruber, M.D., Ph.D., M.P.H. , vice president, City of Hope National Medical Center, Evan and Ming Hsieh Family Director’s Chair of the Center for Precision Medicine and medical oncologist, will report on findings from an international team of researchers’ work investigating “ Artificial intelligence measures of tumor infiltrating lymphocytes predict colorectal cancer-specific and overall survival .” His presentation is titled “Late-Breaking Research: Bioinformatics, Computational Biology, Systems Biology, and Convergent Science 3.” Symposiums and Educational Sessions Marcel van den Brink, M.D., Ph.D. , president of City of Hope Los Angeles and City of Hope National Medical Center, and Deana and Steve Campbell Chief Physician Executive Distinguished Chair, will lead a major symposium as chair of The Microbiome and Treatment Response to Cancer Therapy , to be held on Tuesday, April 9, 2024, from 10:15 a.m. to 11:45 a.m. He will also present on “ The role of the intestinal microbiome in cancer immunotherapy ,” discussing clinical and preclinical studies that demonstrate how changes in the gut microbiome can affect outcomes after hematopoietic cell transplantation and CAR T cell therapy. John D. Carpten, Ph.D. , will chair and serve as a featured speaker for the presentation “ Molecular Profiling in Breast Cancer and Racial/Ethnic Minorities: Dedicated to the Memory of Edith P. Mitchell .” Michael Caligiuri, M.D. , City of Hope professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, is the chair for an educational session on Saturday, April 6, 2024, from 12:30 to 2 p.m. titled, The Road to Entrepreneurship . Industry experts will discuss how to get started, review criteria and find investors. Michael Caligiuri, M.D. , will also chair the inaugural AACR event called From Cancer Discoveries to Patients on April 4 and 5. The event brings together leaders in clinical research, biotech and the investment community as part of AACR’s commitment to expediting the advancement of lifesaving cancer discoveries. About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines , as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHope™ . For more information about City of Hope, follow us on Facebook , X , YouTube , Instagram and LinkedIn .

Vaccine was shown to induce immunity against Prostate Stem Cell Antigen (PSCA) previously Full protein targeting expands the Self-Assembling Vaccine (SAV) platform's potential targets NEW YORK, Nov. 20, 2023 /PRNewswire/ -- Voltron Therapeutics, Inc., a Lucius Partners portfolio company, today announced that it has finalized the protocol for a Dose-Ranging Efficacy Study of VTX-0P4, a protein-based cancer vaccine targeting Prostate Stem Cell Antigen (PSCA). PSCA is a key target in the treatment of Prostate Cancer. The ability of the SAV to target full proteins, as well as peptides, demonstrates that Voltron's vaccine platform has the potential to target dozens of oncology and infectious disease targets – collectively multi- billions of dollars of market potential. The pre-clinical trial is expected to commence in December. Voltron recently demonstrated immunogenicity against PSCA in a double blind pre-clinical trial conducted at the Vaccine and Immunotherapy Center at the Massachusetts General Hospital. In that trial VTX-0P4 significantly augmented T-Cell responses when compared to controls against this important tumor target while, once again, exhibiting a very clean safety profile. The magnitude of these responses were comparable to those seen in the Company's prior HPV E6/E7 studies, which subsequently translated into significant increases in survival and reductions in tumor progression in a mouse model of HPV induced cancer. This strongly suggests VTX-0P4 can address PSCA or other tumor antigen expressing cancers with a full protein approach. Pat Gallagher, Voltron's Chief Executive Officer commented, "In our HPV-related cancer proof of concept trial, Voltron validated that targeting hot spot epitopes, E6/E7, can lead to highly statistically significant increases in survival, reduced tumor growth, and increased tumor infiltration by beneficial immune T Cells. By using a full protein in our PSCA trial to attack solid tumors of interest, we are systematically moving into more complex targeting approaches that provide increased flexibility in developing treatments for additional cancer types and infectious diseases. As with our HPV design, this trial will also evaluate the specific vaccine as monotherapy and in combination with a Checkpoint Inhibitor (PD-1)." The SAV Platform's novel mechanism of action offers a promising solution for rapid development and production of vaccines at a reduced cost. It utilizes the same backbone for all vaccines, but with different 'targeting warheads,' allowing cost-effective production for specific cancer or infectious disease targets. With the SAV, 'targeting warheads' may potentially include different types of antigens including proteins, peptides, polysaccharides or nucleic acids. Importantly, utilizing the same core immune activating component across all the vaccines, MTBHSP70, reduces regulatory risks by largely eliminating off-target inflammation inherent in standard adjuvants. Additionally, this utilizes an expression system Voltron has already translated to good manufacturing processes production for clinical testing. "We are excited to initiate Voltron's PSCA pre-clinical efficacy trial," said James Ahern, Managing Partner of Laidlaw & Company and co-founder of Lucius Partners. "With success, we will have two immune-oncology vaccines that potentially address six unique cancers to move toward first-in-human trials. We will continue to build on our successful programs to address patient needs and create shareholder value." About Voltron Therapeutics, Inc. Voltron Therapeutics, Inc., a Delaware corporation, was founded in 2017 to lead and accelerate the development of the Vaccine and Immunotherapy Center (VIC), and the Massachusetts General Hospital's novel Self Assembling Vaccine technology in a variety of indications, including in Oncology and Emerging Infectious Diseases. Voltron holds an exclusive worldwide license to this technology. With the work of our world class team of researchers and development team, this technology has shown positive results in certain pre-clinical studies and initial proof of concept in two infectious diseases (including Lassa Fever) as well as three oncology indications (HPV Related Cancers). For more information, please visit . About Lucius Partners, LLC Lucius Partners is a consultancy that provides a broad suite of services to help healthcare companies grow, achieve milestones and generate value for their shareholders. Forward Looking Statements This press release includes "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include, but are not limited to, statements that relate to the advancement and development of the VaxCelerate Platform, the commencement of clinical trials, the availability of data from clinical trials and other information that is not historical information. When used herein, words such as "anticipate", "being", "will", "plan", "may", "continue", and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Voltron's current expectations and various assumptions. Voltron believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Voltron may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, market conditions and any Voltron filings made with the Securities and Exchange Commission. Consequently, forward-looking statements should be regarded solely as Voltron's current plans, estimates and beliefs. Investors should not place undue reliance on forward-looking statements. Voltron cannot guarantee future results, events, levels of activity, performance or achievements. Voltron does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by law. Contact: Chris Bastardi [email protected] 917-484-1587 Julie Roginsky [email protected] SOURCE Lucius Partners