PSMA-Positive Tumor

Vironexis’s off-the-shelf, single-dose gene therapies aim to deliver cancer treatments that are safer, more effective and long-lasting, and more easily manufactured and administeredLeveraging its TransJoin™ platform, Vironexis has built a pipeline of more than 10 product candidates for blood-based cancers, solid tumor metastasis prevention and a cancer vaccineVironexis’s foundational technology is based on pioneering, published research led by Timothy Cripe, M.D., Ph.D., at Nationwide Children’s HospitalVironexis’s $26 million seed financing was led by Drive Capital and Future Ventures, with participation from Moonshots Capital and Capital FactoryVironexis plans to advance its first two oncology programs into the clinic in Q4 2024 and 2025, respectively SAN DIEGO, Sept. 12, 2024 (GLOBE NEWSWIRE) -- Vironexis Biotherapeutics, focused on transforming the future of cancer treatment by pioneering AAV-delivered T-cell immunotherapy, launched from stealth today, unveiling its TransJoin™ AAV Gene Therapy Platform and a pipeline of more than ten product candidates for blood-based cancers, solid tumor metastasis prevention, and a cancer vaccine. Vironexis’s $26 million seed financing was led by Drive Capital and Future Ventures, with participation from Moonshots Capital and Capital Factory. The company has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for VNX-101, its first gene therapy product candidate, for the treatment of CD19+ acute lymphoblastic leukemia. Vironexis anticipates initiating patient enrollment of a Phase 1/2 trial of VNX-101 in the fourth quarter of 2024, which will mark the first-ever clinical trial of an AAV-delivered cancer immunotherapy. VNX-101 has received both Fast Track Designation and Rare Pediatric Disease Designation from the FDA. “We’re excited to launch Vironexis from stealth and reveal our noteworthy progress advancing AAV-delivered T-cell immunotherapy,” said Samit Varma, co-founder and CEO of Vironexis. “Our novel technology builds on the power of T-cell immunotherapy while overcoming key shortcomings and challenges of existing approaches such as CAR-T and bispecific antibodies. We believe we have the opportunity to dramatically improve upon the safety, efficacy and durability of these drug classes, while streamlining manufacturing and significantly lessening the burden of treatment for patients. Our focus on execution has yielded an expansive pipeline and a clinic-ready lead program in just three years. We’re working as quickly as possible to transform the future of cancer treatments for patients.” TransJoin enables a patient’s body to express an engineered transgene that redirects T cells throughout the body to tumor cells. The proprietary technology requires only a single dose and provides a bridge that joins together T cells and tumor cells to promote long-term, continuous T cell-mediated tumor killing. The foundational technology for TransJoin was licensed from Nationwide Children’s Hospital. In 2022, research led by Timothy Cripe, M.D., Ph.D., Chief of the Division of Pediatric Hematology/Oncology/Bone and Marrow Transplant, describing the TransJoin technology was published in Science Advances [link here to paper]. Dr. Cripe is one of Vironexis’s co-founders, along with Mr. Varma, a seasoned biotechnology and gene therapy company entrepreneur, and Brian Kaspar, Ph.D., a notable gene therapy scientist-entrepreneur who founded AveXis, Inc. (acquired by Novartis) and pioneered the AAV gene therapy ZOLGENSMA®. “AAV is a proven delivery technology with multiple approvals since 2017. Recognizing the pivotal impact of AAV delivery for the treatment of rare diseases, we believed its unique ability to enable long-term, continuous expression of a therapeutic protein could be the missing link to overcome the myriad challenges associated with first-generation T-cell immunotherapies like CAR-T. We subsequently demonstrated the potential of this approach in the preclinical setting,” said Dr. Cripe. “It’s thrilling to now be on the cusp of seeing how this technology translates in the clinical setting. Our ultimate goal is to help a vastly broader population of patients realize the tremendous benefits of T-cell immunotherapy.” Vironexis is in the process of obtaining pre-IND input from the FDA for its second program, VNX-202, as a treatment for the prevention of metastatic HER2+ cancer (including breast cancer and other tumor types), and plans to start dosing patients in a Phase 1/2 clinical trial in 2025. The company’s other current product candidates include treatments for BCMA/GPRC5D+ multiple myeloma, CD19/20+ B-cell lymphoma; treatments to prevent metastases in GD2+ neuroblastoma, HER2+ gastric cancer, PSMA+ and MSLN+ pancreatic cancer, B7H3+ ostersarcoma and GP350+ nasopharyngeal cancer; a cancer vaccine for GP350+ nasopharyngeal cancer; and a treatment for CD19+ systemic lupus erythematosus, which Vironexis plans to partner for further development. Molly Bonakdarpour, Partner at Drive Capital commented, “As a portfolio investment, Vironexis offers an ideal blend of groundbreaking technology, impressive preclinical data, the potential for vast patient impact, and a founding team with deep, relevant expertise and a proven track record of company formation, strategic thinking, and successful execution. Vironexis’s notable productivity in a very short timeframe has been remarkable. We look forward to its upcoming transition to a clinical-stage company.” Steve Jurvetson, Co-Founder of Future Ventures, added, “We were drawn not only to the novelty of the TransJoin technology but also to its broad applicability, spanning treatments for blood-based cancers, solid tumor metastasis prevention, and cancer vaccines, as well as immune disorders. The versatility of this platform is truly standout, and the Vironexis team’s progress in rapidly building a pipeline that explores the expanse of these opportunities is extraordinary.” How TransJoin Works Vironexis’s TransJoin technology is designed to enable the expression of a secreted T cell engager that binds the tumor cell on one side (changeable depending on the product candidate indication target) and T cells via CD3 on the other side. CD3 is a protein that helps promote T-cell recognition of and activation against cancer cells. Following a single, one-time intravenous infusion, the TransJoin technology instructs the liver to continuously secrete the bispecific protein into the bloodstream to redirect T cells to tumor cells. TransJoin provides a bridge that joins T cells and tumor cells, resulting in long-term, consistent serum levels of the therapy and, thus, long-term, consistent T-cell-mediated tumor cell killing. TransJoin’s extremely low-dose AAV delivery minimizes toxicity and adverse events. About Vironexis Biotherapeutics Vironexis is focused on transforming the future of cancer treatment by pioneering AAV-delivered T-cell immunotherapy. Our TransJoin™ AAV Gene Therapy Platform enables the creation of off-the-shelf, single-dose gene therapies designed to overcome the key challenges and shortcomings of current immunotherapies, including CAR-T and bispecific antibodies. Our current pipeline includes more than ten product candidates for blood-based cancers, solid tumor metastasis prevention, and a cancer vaccine. Our lead program, VNX-101, for the treatment of CD19+ acute lymphoblastic leukemia, is anticipated to begin clinical trials in the fourth quarter of 2024. Visit us at vironexis.com and follow us on LinkedIn and X. Vironexis Media Contact:Liz MeloneMelone Communications, LLCliz@melonecomm.com

A new startup attempting to develop AAV gene therapies to treat cancer emerged from stealth Thursday morning with $26 million in seed funding — and a plan to quickly get into the clinic. Vironexis Biotherapeutics is aiming to get a Phase 1/2 trial up and running in October for what it describes as an “off-the-shelf” gene therapy, a term that has historically been connected to allogeneic CAR-T. Such therapies have proven difficult to develop, as they continue to face questions about their durability. And the FDA has not approved any. But rather than giving patients re-engineered white blood cells from donors, Vironexis’ gene therapy is designed to deliver an engineered gene. The gene prompts the body to continuously create a protein that links tumor-fighting T cells on one side and tumor cells on the other. CEO Samit Varma likened the process to an immunotherapy that the body produces itself. What Vironexis means by “off-the-shelf” is that there is no individualized manufacturing process for its therapy like for autologous CAR-T, where a patient’s own white blood cells are removed, genetically modified and then readministered, Varma told Endpoints News . Instead, its process allows the therapy to be made in bulk and stored in freezers at treatment sites. “The human immune system is the most powerful drug in the world, and so we’re leveraging that power by introducing this gene that can then identify these tumor cells,” Varma said. Timothy Cripe, a co-founder whose research at Nationwide Children’s Hospital helped launch the company, also said he believes the approach is safer than traditional CAR-T. With the program, called VNX-101, the immune-fighting reaction ramps up more slowly as the protein continues to be expressed and accumulates over time. The first kind of cancer Vironexis wants to attack is CD19-positive acute lymphoblastic leukemia, a setting where two autologous CAR-Ts are currently approved: Novartis’ Kymriah and Gilead and Kite’s Tecartus. Varma said the FDA granted the program IND clearance and that the company already has manufactured enough of VNX-101 to begin the trial next month. Vironexis also plans to expand to other areas at a steady march, and it expects another program called VNX-202 to start a basket trial for HER2-positive cancers in 2025. Design-wise, VNX-202 contains the same AAV delivery vehicle as VNX-101, but researchers replaced the gene responsible for the anti-CD19 proteins with a gene for HER2. Varma said its approach can allow the company to go into many different cancer settings with few modifications. So far, Vironexis has conducted preclinical testing for BCMA-, PSMA- and GD2-positive cancers, among several others. They’re also “actively” in discussions for a Series A, he said, and hopes to raise one “within the next several months.” Also co-founding Vironexis is Brian Kaspar, the former AveXis founder and CSO who helped develop the SMA gene therapy Zolgensma and was let go after it was acquired by Novartis following a data manipulation scandal in 2019. Kaspar has denied any wrongdoing. In an interview Wednesday, Kaspar said he hopes Vironexis can follow the commercialization path AveXis and Novartis laid out with Zolgensma, which he added other gene therapy companies have struggled with. Varma also noted that he’s worked with Kaspar at multiple companies since AveXis and that the due diligence always comes back clean. “This is actually our fourth company, post-AveXis departure, that Brian and I have done together, and in each one of those, it’s been a massive amount of diligence,” Varma said. “It’s been investigated by probably 12 different top law firms in the country, every time we did an acquisition or anytime we raised money.” Drive Capital and Future Ventures led the seed round, with Moonshots Capital and Capital Factory also participating.

Crescendo Biologics presents preclinical data on lead clinical candidate CB307 and unveils its first ‘2 in 1’ immune cell engager CB699 at AACR 2024 Preclinical data demonstrate strong rationale for ongoing Phase 1b POTENTIA trial investigating conditional CD137 (4-1BB) agonist CB307 as monotherapy and in combination with pembrolizumab in patients with prostate cancer Simultaneous publication in prestigious Clinical Cancer Research journal, including research generated through successful collaboration with The Institute of Cancer Research, London Crescendo also debuts CB699, a mesothelin-directed, CD137 and CD40 dual agonist demonstrating tumour-targeted activation of T, NK, and B lymphocytes Cambridge, UK, 10 April 2024 – Crescendo Biologics Ltd (Crescendo), a clinical stage immuno-oncology company developing novel, targeted immune cell enhancing therapeutics, has presented preclinical data at the 2024 American Association for Cancer Research (AACR) Annual Meeting on its two leading programmes: Clinical programme CB307 a ‘1st and only’ in class CD137 (4-1BB) x PSMA bispecific for end-stage prostate cancer patientsFirst ‘2 in 1’ immune cell engager CB699, a mesothelin (MSLN) directed molecule designed to target both CD40 and CD137 These programmes are derived from Crescendo’s proprietary Humabody® VH platform which is associated with superior tumour penetration compared to traditional antibodies. Theodora Harold, CEO at Crescendo Biologics, commented: “Crescendo employs a tumour-targeted approach to directing immune cell activation against cancer. The data from our two lead programmes highlight the potential of immuno-oncology therapies that are potent and long-lasting, yet well-tolerated by patients. “The pharmacology data we have shared on CB307, underpins its clinical development in PSMA+ metastatic castration-resistant prostate cancer (mCRPC), which continues at pace in our ongoing Phase 1b trial. CB699 is a pipeline programme which has excited us with its potential and I am delighted that we have been able to share our early research at this year’s conference. These preclinical findings support this candidate’s progression into clinical development, and we look forward to providing further insights as the programme matures.” Abstract #5313: CB307: A dual targeting costimulatory Humabody® VH therapeutic for treating PSMA-positive tumoursThe functional activity of CB307, a first-in-class CD137 x PSMA bispecific Humabody®, designed to achieve a longer lasting anti-cancer effect whilst avoiding systemic toxicity, was assessed in preclinical models. The details of this research have also been published in Clinical Cancer Research, a journal of the AACR. The paper, ‘CB307: A dual targeting costimulatory Humabody® VH therapeutic for treating PSMA-positive tumours’, co-authored by Crescendo scientists and Regius Professor of Cancer Research, Johann de Bono from The Institute of Cancer Research, London, reports: CB307 demonstrated effective activation of both T and NK cells via the co-stimulatory receptor CD137 in a PSMA-dependent mannerIts combination with PD-(L)1 inhibitors showed supra-additive anti-tumour activity, which is retained even in absence of tumour PD-L1 expression, potentially enabling a wider patient population to benefit from checkpoint inhibitor therapiesAlthough prostate cancer has been considered an ‘immunologically cold’ tumour type, the data revealed co-localisation of CD137 and PSMA in metastatic prostate cancer lesions, supporting the use of CB307 in mCRPC Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, comments: “The data shared at AACR and published in Clinical Cancer Research support this novel candidate’s (CB307) clinical evaluation in PSMA+ mCRPC, both as a monotherapy and in combination settings.” Abstract #5302: CB699: A novel mesothelin-binding Humabody® CD40 and CD137 dual-agonist for enhancing immune cell responses against MSLN+ tumoursDerived from the Humabody® VH platform, CB699 is Crescendo’s first candidate in a novel class of tumour antigen-directed CD40 and CD137 dual agonists, designed to enhance the anti-tumour activity of multiple immune cell types. CB699 is a half-life extended CD40 x CD137 x MSLN trispecific molecule. The preclinical studies support Crescendo’s progression of the candidate towards clinical development: Pharmacokinetic data including preclinical dose range finding and half-life of CB699 support clinical development;The results demonstrated CB699’s ability to conditionally enhance both T cell and antigen-presenting cell (APC) signalling axes, providing a comprehensive anti-cancer immune response; andThe trispecific format was able to drive conditional CD40 agonism in the presence of either CD137+ or MSLN+ cells, and similarly, conditional CD137 agonism in the presence of either CD40+ or MSLN+ cells, potentially providing a potent yet safe way to target heterogeneous tumours Both abstracts are available on the AACR website and the posters are available on the Crescendo website under Posters & Publications. -Ends- For more information, please contact: Crescendo BiologicsTheodora Harold, CEO+44 (0) 12 2349 7140investors@crescendobiologics.commedia@crescendobiologics.comICR ConsiliumMary-Jane Elliott, David Daley, Sukaina Virji crescendo@consilium-comms.com About CB307CB307 is Crescendo’s lead clinical candidate, a first-in-class, half-life extended, CD137 x PSMA bispecific Humabody®, designed to deliver a safer and more durable anti-cancer response. CB307 conditionally activates only tumour-specific T cells, exclusively within the tumour microenvironment, using the CD137 co-stimulatory mechanism. Its unique format enables potent, tumour-specific killing, while avoiding systemic toxicity and can be applied to a broad range of PSMA+ cancer indications to address a large unmet medical need. Clinical development of CB307 is on track with the Phase 1b POTENTIA trial ongoing in adult patients with PSMA+ metastatic castration-resistant prostate cancer (mCRPC). POTENTIA (NCT04839991) is an open-label, dose escalation and cohort expansion study to assess the safety, tolerability and preliminary efficacy of CB307 as a monotherapy and in combination with pembrolizumab (KEYTRUDA®). About CB699CB699, a half-life extended CD40 x CD137 x mesothelin (MSLN) trispecific molecule, is the second candidate in Crescendo’s proprietary pipeline of novel, targeted immune-cell-enhancing therapeutics, derived from its Humabody® VH platform. CB699 aims at enhancing immune cell activity against MSLN+ tumours, using both immune cell and APC signalling axes. About Crescendo Biologics Crescendo Biologics is a private, clinical-stage immuno-oncology company developing novel, targeted immune cell-enhancing therapeutics derived from its proprietary Humabody® VH platform. Beyond Crescendo’s proprietary pipeline, the Company has global, multi-target discovery and development collaborations with Takeda and BioNTech, and an exclusive worldwide licensing agreement with Zai Lab. Located in Cambridge, UK, Crescendo is backed by blue-chip investors including Sofinnova Partners, Andera Partners, IP Group, BioNTech, Takeda, Quan Capital and Kreos Capital. Visit www.crescendobiologics.com and follow on LinkedIn and X (Twitter).