HIV-1 vaccine(University of Oxford)

PARIS--(BUSINESS WIRE)-- #LentiHPV07 -- TheraVectys, a biotechnology company that designs and develops lentiviral vector-based vaccines and immunotherapies against infectious agents and cancers , announces that the first patient has been enrolled in the Phase I/IIa clinical trial evaluating the onco-therapeutic vaccine Lenti-HPV-07 for the treatment of human papillomavirus (HPV)-induced cancers. This study will include 36 patients in a dose-escalation protocol conducted at several cancer centers in the United States. Selection and inclusion of these patients are already underway. The Lenti-HPV-07 vaccine is based on the lentiviral vector technology platform developed by Pasteur-TheraVectys Joint Laboratory and pioneered by TheraVectysfor for nearly 20 years. The highly promising preclinical studies results on the Lenti-HPV-07 vaccine candidate, published in September 2023 in EMBO Molecular Medicine (1) and in June 2024 in NPJ Vaccines (2), showed that after a single intramuscular injection the vaccine was able to induce a strong cellular immune response against the E6 and E7 antigens of HPV16 and HPV18, resulting in: complete elimination of HPV-induced tumors in 100% of individuals, regardless of tumor size, a very long-lasting immune memory, notably based on anti-tumor cytotoxic CD8 + T cells, essential for avoiding relapses, which are responsible for a large proportion of deaths, profound remodeling of the tumor microenvironment, elimination of metastases in 100% of individuals, and a strong synergy of Lenti-HPV-07, even at a sub-optimal dose, with treatments such as anti-PD1 1 antibodies. Aims and methodology of the human trial The open-label Phase I/IIa trial will evaluate the safety of ascending doses of Lenti-HPV-07, determine its immunogenicity pro assess the preliminary efficacy through the Objective Response Rate. It will include two groups of patients with oropharyngeal or cervical cancers induced by HPV-16 or HPV-18, all of whom will be clinically and immunologically followed for one year. Group A will consist of patients with recurrent/metastatic cancers who have not responded to multiple lines of treatment, including immunotherapies. These patients will receive two intramuscular injections of Lenti-HPV-07, one month apart. Group B will be composed of patients with newly diagnosed, treatment-naïve, locally advanced cancers. Patients in Group B will receive a single intramuscular injection of Lenti-HPV-07. The trial comprises 2 parts: a dose escalation and dose expansion. In the dose escalation portion participants are enrolled successively to receive increasing doses of Lenti-HPV-07. Safety will be carefully monitored after each dose and before proceeding to enrolment at a higher dose. Enrolment and dose escalation in each arm A and B will be conducted independently. In each arm, when 18 participants will have received Lenti-HPV-07 treatment in the dose-escalation portion and the safety results will be satisfying, a dose-expansion portion of the trial will be open to treat 18 additional patients at the Optimal Biological Dose . In total, 72 patients with HPV + cancer will be enrolled in this Phase I/IIa clinical trial. In terms of safety, TheraVectys has already completed a Phase I clinical trial on a therapeutic HIV-1 vaccine based on an integrative lentiviral vector. Over a 5-year follow-up, this clinical trial revealed no notable side effects or genotoxicity. The ongoing Lenti-HPV-07 clinical trial uses a non-integrative lentiviral vector, which reinforces the safety of the approach. It should be noted that since group B patients are newly diagnosed and untreated, their immune systems will not have been affected by other chemo- or radiotherapy treatments. These patients will receive standard care, often including anti-PD1 treatments, one month after treatment with Lenti-HPV-07. TheraVectys has shown in animal models that the Lenti-HPV-07 vaccine acts synergistically with treatments such as anti-PD1, increasing the efficacy of anti-PD1 immunotherapy alone by a factor of 4 (1, 2). Professor Christian Bréchot, Medical Director of TheraVectys commented: “ The inclusion of the first patient in the Phase I/IIa trial represents a key milestone for TheraVectys. It is the achievement of more than 2.5 years of preparation, from first interaction with the FDA, production of the vaccine, performance of the preclinical studies, review and approval by the regulatory authorities till sites preparation. The careful selection of adequate partners and the development of a cooperative relationship have been key in successfully building the project.” Pierre Charneau, head of the Pasteur-TheraVectys Joint Laboratory and founder of TheraVectys, said : “With the launch of this study, we are proud to bring our product to a new phase of its development. We expect the preliminary results on safety and immunogenicity a couple of months after all patients in one group will have received their last injection.” HPV causes almost all cervical cancers, as well as many oropharyngeal and anogenital cancers. The preventive HPV vaccines currently available essentially induce HPV-neutralizing antibodies and thus prevent infection, but have no effect on chronic HPV infections or established tumors. In comparison to Lenti-HPV-07, the immunotherapeutic potential of mRNA-based vaccine technology has only been shown to be effective against very small HPV-related tumors, with early relapse in almost 50% of treated animals (3). In contrast, in the preclinical study conducted by Pasteur-TheraVectys Joint Laboratory, Lenti-HPV-07 immunotherapy was active against large tumors, which are notoriously more difficult to control, demonstrating the superior efficacy of the lentiviral vector-based vaccine platform. A recent publication of a cross-sectional comparison of the most relevant vaccine strategies tested to date in preclinical anti-HPV immuno-oncotherapy showed that lentiviral vector-based approaches were the most effective at eliminating tumors, while providing the longest-lasting memory (4). About lentiviral vector technology TheraVectys is Institut Pasteur’s exclusive licensee for all human and animal vaccine applications of lentiviral vectors worldwide. Thanks to its interaction with dendritic cells, this technology stimulates the body’s natural immune defenses, particularly T cells, more effectively than other vaccine strategies. The technology is based on the natural attraction of lentiviral vectors for dendritic cells and on their ability to induce directly in these cells a sufficiently long-lasting and highly effective endogenous antigenic presentation of the antigens encoded by the vector. Dendritic cells programmed in this way play a key and unique role in the development of T cell responses, the main effectors against tumor cells. About TheraVectys TheraVectys Biotech, specialist in immunotherapy, is based on more than 20 years of research on lentiviral vectors and brings an innovative technology to the field of vaccinology. Research is carried out in the Pasteur-TheraVectys Joint Laboratory under the scientific direction of Pierre CHARNEAU , inventor and pioneer of lentiviral technology, and Laleh MAJLESSI , Director of Research in Immunology. Christian BRECHOT , the former General Director of Institut Pasteur and INSERM, is the Medical Director of TheraVectys. Estelle BESSON , Director of Clinical Operations, coordinated and supervised the preparatory work required to obtain FDA approval, including production of the vaccine, regulatory preclinical studies, preparation of the IND filing, selection and implementation of the clinical trial in collaboration with TheraVectys’ partners. The biotech’s work is based on a proprietary platform for delivering cytotoxic T-cell vaccines in response to critical unmet medical needs. The technology used is at a clinical stage. TheraVectys’ technology and its worldwide license area address a broad spectrum of infectious diseases, cancers and viral cancers, positioning it at the origin of a genuine revolution in the field of vaccination. Our aim: To make profound improvements to global health. Our approach: Strategic industrial partnerships to take our vaccine candidates from proof of concept to clinical trials and marketing. TheraVectys S.A. 28 rue de Dr Roux, Institut Pasteur, Paris, France Chairman TheraVectys: Jean CHALOPIN - Scientific Director: Pierre CHARNEAU 1 Immune checkpoint inhibitors; PD1 = programmed cell death protein-1 References 1. Douguet L*, Fert I*, Lopez J*, Vesin B*, Le Chevalier F, Moncoq F, Authié P, Nguyen TM, Noirat A, Névo F, Blanc C, Bourgine M, Hardy D, Anna F, Majlessi L £ , Charneau P £ . (2023) Full Eradication of Pre-clinical Human PapillomaVirus-Induced Tumors by a Lentiviral Vaccine. EMBO Mol Med . *Co-first authors, £ Senior authors. 2. Fert I*, Douguet L*, Vesin B*, Moncoq F, Noirat A, Authié P, Ciret S, Le Chevalier F, Blanc C, Vitrenko Y, Charneau P £ , Majlessi L £ , Anna F £ . (2024) T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector. NPJ Vaccines. *Co-first authors, £ Senior authors. 3. Ramos da Silva J, Bitencourt Rodrigues K, Formoso Pelegrin G, Silva Sales N, Muramatsu H, de Oliveira Silva M, Porchia B, Moreno ACR, Aps L, Venceslau-Carvalho AA et al (2023) Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice. Sci Transl Med 15: eabn3464 4. Demidova A*, Douguet L*, Fert I*, Wei Y*, Charneau P, Majlessi L. (2024) Comparison of preclinical efficacy of immunotherapies against HPV-induced cancers. Exp Rev Vacc. *Co-first authors. . Contacts Press contact TheraVectys Anna Véronique EL BAZE – avelbaze@kbzcorporate.com

Study to assess safety and immunogenicity of novel protein nanoparticle vaccine candidates UVAX-1107 and UVAX-1197 in healthy volunteers NEWARK, Del.--(BUSINESS WIRE)-- Uvax Bio, LLC, (“Uvax” or “the Company”) a privately held, clinical-stage vaccine company utilizing rational and computational biology to design and deliver novel 1c-SApNP® protein-based vaccines, today announced the first participant has been dosed in a Phase 1 clinical trial evaluating the Company’s HIV-1 vaccine candidates, UVAX-1107 and UVAX-1197, in healthy volunteers in Australia. “With an estimated 1.3 million people worldwide becoming infected with HIV annually, there is a tremendous unmet need for a vaccine to help protect against HIV-1 infection,” said Ji Li, Ph.D., Uvax Bio CEO. “UVAX-1107 and UVAX-1197 represent an advancement in HIV vaccine technology with industry-recognized innovations in our antigen design and delivery. I am proud of the Uvax Bio team for bringing our promising HIV-1 vaccine candidates into human testing, a significant milestone for the Company.” The first-in-human clinical trial (ACTRN12624000064505) is evaluating two different regimens of the UVAX-1107 and UVAX-1197 vaccines in 34 healthy volunteer adults who meet the study inclusion criteria. The primary endpoints of the study will measure safety and immunogenicity of UVAX-1107 and UVAX-1197 after the primary and boosting dose series being evaluated in parallel arms. The study will also determine whether either vaccine or the combination of both produces the optimal immunological response. Uvax Bio expects to report topline data from the Phase 1 trial in the fourth quarter of 2024. UVAX-1107 and UVAX-1197 utilize Uvax Bio’s 1c-SApNP® platform displaying 20 copies of the native-like, prefusion-stabilized HIV-1 envelope (Env) trimer based on the uncleaved, prefusion-optimized (UFO) design. The novel protein nanoparticle vaccine candidates are designed for active immunization and are intended to prevent HIV-1 infection. In a preclinical toxicology study, UVAX-1107 and UVAX-1197 combined with adjuvant was shown to be safe with no serious adverse events, consistent with previously approved protein-based vaccines. Additionally, a second preclinical immunogenicity study demonstrated immunization with UVAX-1107 and UVAX-1197 elicited robust neutralizing antibody responses against the vaccine-matched virus in 99% of the animals. Furthermore, preliminary screening assays demonstrated appreciable neutralization in serum when tested against a panel of primary HIV-1 isolates. About UVAX-1107 and UVAX-1197 UVAX-1197 and UVAX-1107 are based on Uvax Bio’s proprietary 1c-SApNP® technology displaying 20 uncleaved, prefusion-optimized (UFO) HIV envelope (Env) trimers in wild-type and glycan-trimmed forms (UVAX-1197 and UVAX-1107, respectively). The two antigens differ insofar as UVAX-1197 retains the virus’ wild-type glycan shield, while UVAX-1107 has a portion of the glycan shield removed through glycan trimming (GT). GT is an enzymatic removal of glycans to allow better access to the conserved neutralizing epitopes on HIV-1 Env. This innovative GT strategy was recognized by the International Union of Pure and Applied Chemistry (IUPAC) – who dubbed it “low-sugar vaccination” – as one of the Top Ten Emerging Technologies in Chemistry for 2023. The UFO trimer, 1c-SApNP platform, and glycan trimming strategy were developed by Dr. Jiang Zhu, Associate Professor, Department of Integrative Structural and Computational Biology at Scripps Research in La Jolla, CA. About HIV/AIDS The Joint United Nations Programme on HIV/AIDS estimates that 39 million people worldwide are currently living with HIV, and 1.3 million people became newly infected with HIV in 2022 alone. According to the latest estimates from the Centers for Disease Control and Prevention, there were 32,100 estimated new HIV infections in the U.S. and the rate was 11.5 (per 100,000 people) in 2021. Apart from very rare cases involving bone marrow transplants, there is no cure for HIV, which must be held in check indefinitely with antiviral drugs to keep it from progressing to the deadly immune deficiency condition known as AIDS. About Uvax Bio Uvax Bio, LLC, a spin-off vaccine company from Scripps Research, employs proprietary 1c-SApNP® platform technology invented by Jiang Zhu, Ph.D., of Scripps Research to develop and commercialize prophylactic vaccines for challenging infectious diseases. Uvax Bio holds exclusive worldwide rights to the 1c-SApNP® platform and an expanding portfolio of two clinical and 10 patented preclinical vaccine candidates. In addition to the leading clinical candidates in HIV, Uvax Bio is working to advance its vaccines for influenza, RSV and hMPV. The Company’s technology enables the production of virus-like protein particles that can display 20-60 stabilized antigens targeting a wide range of viral and bacterial diseases. The vaccines are produced using a single-step, universal, cell-based manufacturing process. For more information, visit .