Human Papillomavirus-Related Solid Tumors

PARIS, France I October 04, 2024 I 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: 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 profile and 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. https://www-embopress-org.libproxy1.nus.edu.sg/doi/full/10.15252/emmm.202317723 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. https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC11164992/ 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. https://www-tandfonline-com.libproxy1.nus.edu.sg/doi/full/10.1080/14760584.2024.2374287 . SOURCE: TheraVectys

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

HB-200 monotherapy induced a robust increase in circulating tumor-specific CD8+ T cells in all evaluable Phase 1 patients with heavily pretreated HPV16+ head and neck cancer T cell responses were high quality, durable and suggest an association with clinical benefit based on disease control Totality of data reinforce the value proposition of HOOKIPA’s arenaviral platform in driving T cell responses necessary for tumor control NEW YORK and VIENNA, Austria, Nov. 03, 2023 (GLOBE NEWSWIRE) -- HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, today announced updated Phase 1 clinical, biomarker and translational data on HB-200 as a monotherapy in heavily pretreated patients with recurrent/metastatic Human Papillomavirus 16-positive (HPV16+) head and neck cancer. The data show HB-200 monotherapy induced robust, high-quality and durable tumor-specific T cell responses, which showed a trend of clinical benefit measured by a 44 percent disease control rate in a difficult-to-treat patient population. The data were presented in a poster presentation (abstract #679) at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting. “The data presented at SITC expand the body of evidence that HB-200 monotherapy has the ability to induce targeted T cells necessary for tumor control, which can translate into tumor shrinkage and encouraging clinical activity, especially in a difficult-to-treat population,” said Joern Aldag, Chief Executive Officer at HOOKIPA. “As the data have matured, we have consistently delivered best-in-class T cell activation, and we continue to see the durability and functionality of tumor-specific T cells induced by HB-200. We look forward to sharing continued analyses of HB-200 across all arms of our trial in the future.” HB-200 Phase 1 biomarker results (NCT04180215) As of March 31, 2023, 93 patients with HPV16+ recurrent/metastatic cancer were treated in the Phase 1 trial of HB-200. The goal of the trial was to determine the recommended dose for further evaluation in a Phase 2 study. All patients were heavily pretreated with a median of 3 prior therapies (range 1-11). Biomarker and translational data results HB-200 demonstrated a robust increase in tumor-specific CD8+ T cells in all evaluable patients with HPV16+ head and neck cancers. These results are from intracellular staining of blood samples from 35 patients across all four dose levels tested in Phase 1. An analysis of 29 of these patients—treated at either the recommended phase 2 dose (RP2D) or RP2D-1—showed that T cell increases were rapid and sustained for at least 8 months, and T cell function improved over time with repeat dosing. Quantity and quality of T cells are considered important for tumor infiltration and subsequent tumor control. Importantly, paired biopsy data suggest an association between the induction of robust, high-quality, tumor-specific T cells after HB-200 treatment and best overall response. Paired biopsy data from 13 heavily pretreated patients show that patients who achieved disease control after treatment with HB-200 monotherapy generally had greater CD8+ T cell infiltration in tumors and the tumor microenvironment compared to patients with a best overall response of disease progression. Additional Phase 1 data The poster presentation also includes updated clinical activity and safety data from the Phase 1 study. As of the August 7 data cut-off, there were 27 evaluable patients with HPV16+ head and neck cancers who received HB-200 at the at RP2D or RP2D-1. Among these difficult-to-treat patients, HB-200 demonstrated a 44 percent disease control rate, with 1 confirmed partial response and 11 patients with stable disease. While overall survival is still maturing, median overall survival is approximately 13 months, with a median follow-up period of 6.3 months. Phase 1 data also consistently demonstrate that HB-200 was generally well tolerated among 93 patients treated across all dose-level cohorts. Treatment-related adverse events grade 3 or above were reported in 11.8 percent of patients (n=11), while those leading to treatment discontinuation were reported in only 2.2 percent of patients (n=2). This favorable tolerability pro the potential of HB-200—and arenaviral immunotherapies in general—to be safely combined with other immunotherapies. Data presentation details: Title: Characterization of tumor-specific CD8+ T cell responses in patients with recurrent/metastatic HPV16-positive head and neck cancer receiving HB-200 monotherapy as second or later-line treatment in a Phase 1 study Presenter: Dr. Winston Wong, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator Abstract: 679 About HB-200 HB-200 is HOOKIPA’s lead oncology candidate engineered with the company’s proprietary replicating arenaviral vector platform. It comprises two single-vector compounds with arenaviral backbones based on lymphocytic choriomeningitis virus and pichinde virus. Both express the same transgene encoding an E7E6 fusion protein derived from HPV16. HB-200 is an alternating 2-vector immunotherapy designed to further focus the immune response against the encoded antigen. HB-200 in combination with pembrolizumab received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of 1st-line recurrent/metastatic HPV16+ head and neck cancers. About the HB-200 trial (NCT04180215) This Phase 1/2 clinical trial is an open-label trial evaluating HB-200 for the treatment of advanced HPV16+ cancers. Phase 1 assessed various dose levels, regimen, and modes of administration in a post-standard of care setting. Based on safety and tolerability, initial anti-tumor activity and T cell response data, HB-200 advanced for further development in Phase 2. The Phase 2 part of the trial is open label with primary endpoints of efficacy based on objective response and disease control rate as defined by RECIST 1.1 and iRECIST. The trial is evaluating HB-200 in combination with pembrolizumab in the 1st-line and 2nd-line plus settings, as well as HB-200 alone in the post-standard of care setting. About Human Papillomavirus-driven Cancers Human Papillomavirus, or HPV, is a common viral infection estimated to cause about 5 percent of the worldwide cancer burden. This includes up to 60 percent of head and neck, 89 percent of cervical, 78 percent of vaginal, 88 percent of anal, 67 percent of vulvar and 50 percent of penile cancers. While there are numerous HPV types associated with cancer, HPV16 is the most common cause of cancer. Most HPV infections are cleared from the body with no lasting consequences. However, in some cases, HPV DNA becomes integrated into chromosomal DNA. When host cells take up this DNA, they express the HPV E6 and E7 proteins. This uptake can potentially lead to cancer since expression of these proteins leads to alterations in cell cycle control, which in turn predisposes these cells to become cancerous. About HOOKIPA HOOKIPA Pharma Inc. (NASDAQ: HOOK) is a clinical-stage biopharmaceutical company focused on developing novel immunotherapies, based on its proprietary arenavirus platform, which are designed to mobilize and amplify targeted T cells and thereby fight or prevent serious disease. HOOKIPA’s replicating and non-replicating technologies are engineered to induce robust and durable antigen-specific CD8+ T cell responses and pathogen-neutralizing antibodies. HOOKIPA’s pipeline includes its wholly owned investigational arenaviral immunotherapies targeting Human Papillomavirus 16-positive cancers, prostate cancers, and other undisclosed programs. HOOKIPA is collaborating with Roche on an arenaviral immunotherapeutic for KRAS-mutated cancers. In addition, HOOKIPA aims to develop functional cures of HBV and HIV in collaboration with Gilead. Find out more about HOOKIPA online at Forward Looking Statements Certain statements set forth in this press release constitute “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements can be identified by terms such as “believes,” “expects,” “plans,” “potential,” “would” or similar expressions and the negative of those terms. Such forward-looking statements involve substantial risks and uncertainties that could cause HOOKIPA’s research and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including HOOKIPA’s programs’ early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, HOOKIPA’s ability to successfully establish, protect and defend its intellectual property, risks relating to business interruptions resulting from public health crises, the impact of public health crises on the enrollment of patients and timing of clinical results, and other matters that could affect the sufficiency of existing cash to fund operations. HOOKIPA undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see HOOKIPA’s quarterly report on Form 10-Q for the quarter ended June 30, 2023, which is available on the SEC’s website at and HOOKIPA’s website at . Investors and others should note that we announce material financial information to our investors using our investor relations website ( ), SEC filings, press releases, public conference calls and webcasts. We use these channels, as well as social media, to communicate with our members and the public about our company, our services and other issues. It is possible that the information we post on social media could be deemed to be material information. Therefore, we encourage investors, the media, and others interested in our company to review the information we post on the U.S. social media channels listed on our investor relations website. For further information, please contact: Media Investors Instinctif Partners Michael Kaiser, Investor Relations hookipa@instinctif.com michael.kaiser@hookipapharma.com +44 (0) 7457 2020 +1 (917) 984 7537