E6 x HPV E7

- Data show that Vaxart’s HPV vaccine constructs stimulate specific T cell immune responses, reduce tumor size, and increase survival in an animal model of human papillomavirus (HPV)-related tumorigenesis - - Results suggest that Vaxart’s mucosal vaccine platform holds promise in enabling a novel, non-invasive treatment for HPV-related cervical dysplasia - SOUTH SAN FRANCISCO, Calif., Aug. 28, 2024 (GLOBE NEWSWIRE) -- Vaxart, Inc. (Nasdaq: VXRT) today announced the publication of preclinical data demonstrating the potential of its mucosal vaccine technology platform in enabling therapeutic vaccination against HPV-related cervical dysplasia. The data show that Vaxart’s HPV vaccine constructs can stimulate a potent immune response against the HPV16 proteins E6 and E7 that are known to transform healthy cells into malignant cells. The data, reported in the current issue of Vaccines, also shows that administration of a mucosal vaccine against these proteins in mice with HPV-expressing tumors led to reductions in tumor size and increased survival. Persistent HPV infection plays a causative role in most cases of cervical dysplasia, which leads to cervical cancers if left untreated. While prophylactic HPV vaccines are highly effective if administered prior to infection; they have not demonstrated a therapeutic effect on established infections. “The preclinical data published in Vaccines demonstrate that our mucosal vaccines stimulate T cells to destroy HPV-expressing cells, reducing the size of HPV-derived tumors and increasing the survival of mice bearing these tumors,” said Dr. Sean Tucker, Vaxart’s Founder and Chief Scientific Officer. “While additional studies are needed to further characterize the immune stimulating and anti-tumor activity of our HPV-vaccine, these initial findings suggest that our mucosal vaccine platform could open the door to a non-invasive approach designed to prevent the progression to cervical cancer. As our mucosal vaccine candidates can be administered easily and are stable at room temperature, they also have potential to address global inequities associated with the treatment of HPV-related cancers.” In this study published in Vaccines, the therapeutic potential of this platform was assessed in mice bearing HPV-expressing tumors. Animals were treated with vaccine candidates expressing wildtype E6 and E7 antigens from HPV16, engineered E6 and E7 that disrupt their malignant transformation potential, and fragments of E6 and E7 predicted to stimulate an immune response. Key findings from the study include: All vaccines generated a specific T cell response to HPV16 E6 and E7 in mice.All vaccines caused significant reductions in tumor volume and increased survival compared to control groups.Concurrent administration of anti-PD-1 with vaccination further increased animal survival in small and large tumor models compared to vaccination alone.Vaccination led to significant increases in intra-tumoral T cells, including T cells that create a cytotoxic tumor environment, compared with an empty control vaccine.Vaccination led to the generation of antigen-specific cytotoxic T cells. These results suggest that rAd5 vaccines delivered to a mucosal surface may have therapeutic potential in the treatment of HPV-derived cervical dysplasia and might be used to stimulate immune responses against other cancer-related proteins. Vaxart is continuing to evaluate its HPV vaccine candidates. About Vaxart Vaxart is a clinical-stage biotechnology company developing a range of oral recombinant vaccines based on its proprietary delivery platform. Vaxart vaccines are designed to be administered using pills that can be stored and shipped without refrigeration and eliminate the risk of needle-stick injury. Vaxart believes that its proprietary pill vaccine delivery platform is suitable to deliver recombinant vaccines, positioning the company to develop oral versions of currently marketed vaccines and to design recombinant vaccines for new indications. Vaxart’s development programs currently include pill vaccines designed to protect against coronavirus, norovirus and influenza, as well as a therapeutic vaccine for human papillomavirus (HPV), Vaxart’s first immune-oncology indication. Vaxart has filed broad domestic and international patent applications covering its proprietary technology and creations for oral vaccination using adenovirus and dsRNA agonists. Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding Vaxart’s strategy, prospects, plans and objectives, results from preclinical and clinical trials and the timing of such results, vaccine efficacy and safety, commercialization agreements and licenses, and beliefs and expectations of management are forward-looking statements. These forward-looking statements may be accompanied by such words as “should,” “believe,” “could,” “potential,” “will,” “expected,” “anticipate,” “plan,” and other words and terms of similar meaning. Examples of such statements include, but are not limited to, statements relating to Vaxart’s ability to develop and commercialize its product candidates, including its vaccine booster products; Vaxart’s expectations regarding clinical results and trial data, and the timing of receiving and reporting such clinical results and trial data; and Vaxart’s expectations with respect to the effectiveness of its product candidates. Vaxart may not actually achieve the plans, carry out the intentions, or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, expectations, and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Vaxart makes, including uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement, and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates, and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from the clinical studies; decisions by regulatory authorities impacting labeling, manufacturing processes, and safety that could affect the availability or commercial potential of any product candidate, including the possibility that Vaxart’s product candidates may not be approved by the FDA or non-U.S. regulatory authorities; that, even if approved by the FDA or non-U.S. regulatory authorities, Vaxart’s product candidates may not achieve broad market acceptance; that a Vaxart collaborator may not attain development and commercial milestones; that Vaxart or its partners may experience manufacturing issues and delays due to events within, or outside of, Vaxart’s or its partners’ control; difficulties in production, particularly in scaling up initial production, including difficulties with production costs and yields, quality control, including stability of the product candidate and quality assurance testing, shortages of qualified personnel or key raw materials, and compliance with strictly enforced federal, state, and foreign regulations; that Vaxart may not be able to obtain, maintain, and enforce necessary patent and other intellectual property protection; that Vaxart’s capital resources may be inadequate; Vaxart’s ability to resolve pending legal matters; Vaxart’s ability to obtain sufficient capital to fund its operations on terms acceptable to Vaxart, if at all; the impact of government healthcare proposals and policies; competitive factors; and other risks described in the “Risk Factors” sections of Vaxart’s Quarterly and Annual Reports filed with the SEC. Vaxart does not assume any obligation to update any forward-looking statements, except as required by law. Contacts Vaxart Media Relations:Mark HerrVaxart, Incmherr@vaxart.com(203) 517-8957 Investor Relations:Matt SteinbergFINN PartnersIR@vaxart.com(646) 871-8481

Researchers have developed a model of Kaposi sarcoma that could expedite the development of new drugs to treat the disease, which is the most common cancer in people living with HIV. Researchers at UNC Lineberger Comprehensive Cancer Center, after decades of research efforts, have developed a mouse model of Kaposi sarcoma that could be key to the development of new drugs to treat the disease. Kaposi sarcoma is a cancer that is the most common cancer in people living with HIV. The findings appeared in Cell Host & Microbe. "This is an important development as we have created the first animal model ever of Kaposi sarcoma. Animal models are essential to move new drugs from the laboratory bench into clinical trials," said UNC Lineberger's Dirk Dittmer, PhD, senior corresponding author, co-leader of the UNC Lineberger Virology Research Program and director of the UNC Viral Genomics Core. "Before this, only repurposed drugs from other cancers were used to treat Kaposi sarcoma, but now we can start investigating entirely new compounds to help treat what can be a lethal cancer." About 20% of all human cancers arise from viruses or require viral infection as an essential cofactor. The Kaposi sarcoma-associated herpes virus (KSHV) was discovered in 1994 and is associated with Kaposi's sarcoma as well as B-cell cancers. KSHV-associated diseases affect internal organs and are ultimately fatal. In the U.S., the diseases are found primarily in immunosuppressed people such as those who are HIV-positive or are transplant patients. Worldwide, an estimated 34,270 cases of Kaposi sarcoma were diagnosed, and 15,086 deaths reported in 2020, with twice as many cases and deaths occurring in men compared to women. Africa accounted for 73% of new cases and 86.6% of the deaths from Kaposi sarcoma worldwide. The disease is endemic, and not HIV-related, in some southern and eastern African countries. Aside from animal models, one way to study cancer is to look at tumor cells in the lab. But according to Dittmer, Kaposi sarcoma tumor cells are very finicky and dependent on signaling molecules and blood supply, which is why they don't survive in a laboratory culture dish. Therefore, researchers have been focusing on developing animal models that would mimic, as closely as possible, the disease in humans. One of the challenges the researchers faced in developing their model was the fact that two types of genes are transcribed into proteins in the Kaposi sarcoma mouse model. Normally when a virus infects a cell, the cell dies as the virus replicates, which is a process called cell lysis; the genes that are needed for the virus to propagate itself are lytic genes. Cancer viruses are different as they enter a quiet state, called latency, where only the genes that help the infected cell survive are expressed. The mouse model the researchers developed is complex as a bit of both types of genes were needed. Cervical cancer and its related virus, HPV (human papilloma virus), offers a good comparison for the challenge of developing a Kaposi sarcoma mouse model. The KSHV genome is 20 times larger than HPV. HPV has two cancer-causing genes, E6 and E7, so to mimic the disease in animals, researchers only needed to design two mice, one for each gene. KSHV may have as many as 10 cancer-causing genes that all work together so it would be way too difficult to develop that many mice, hence the virtue of their single model, Dittmer noted. "Another of the key virtues of our new mouse model is that it helps us understand angiogenesis, or new blood vessel formation. Without angiogenesis cancer cells are deprived of oxygen and die," Dittmer said. "In this mouse model, we can study angiogenesis blocking drugs better than ever before. If new drugs work against Kaposi sarcoma, they will also likely work against lesser-angiogenic tumors, which would be a major plus." For next steps, the researchers hope that others will pursue drug and vaccine development based on a new understanding of fundamental aspects of KSHV provided by their mouse model, including possible development of a much-needed primate model for human KSHV and Kaposi sarcoma.

42 percent objective response rate (ORR) was observed among 19 evaluable patients with recurrent/metastatic head and neck cancer in the first-line setting—doubling historical ORR reported with pembrolizumab alone1 Strong immunogenicity and activation of antigen-specific CD8+ T cells observed Data reinforce HOOKIPA’s commitment to start a randomized trial of HB-200 in combination with pembrolizumab as 1st-line treatment of recurrent/metastatic HPV16+ head and neck cancer in 2024 Data presented at the European Society for Medical Oncology Congress 2023 NEW YORK and VIENNA, Austria, Oct. 22, 2023 (GLOBE NEWSWIRE) -- HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, today presented updated data from its ongoing Phase 2 trial of HB-200 in combination with pembrolizumab in patients with recurrent/metastatic Human Papillomavirus 16-positive (HPV16+) head and neck cancer. The preliminary data presented at the European Society for Medical Oncology (ESMO) Congress 2023 showed a 42 percent confirmed objective response rate (ORR) and disease control rate (DCR) of 74 percent across 19 evaluable patients treated with HB-200 in combination with pembrolizumab in the 1st-line, checkpoint inhibitor (CPI)-naïve setting, doubling the 19 percent ORR for pembrolizumab alone1. Best overall response for the evaluable population included one patient with a confirmed complete response, seven patients with confirmed partial responses, and six patients with stable disease. All evaluable patients were alive at the data cutoff (DCO), and the median follow-up time at DCO was 8.3 months. Median overall survival and progression-free survival data are still maturing. Importantly, results showed significant activation of antigen-specific CD8+ T cells, the body’s primary driver of tumor killing activity. Out of 17 patients with available peripheral blood mononuclear cells (PMBC) samples, all patients showed an increase of tumor antigen-specific circulating HPV16+ CD8+ T cells. These T cell activation data are consistent with previously reported monotherapy data for HB-200. “We have observed objective response rate, disease control rate, and activation of antigen-specific T cells which demonstrate the potential of the intended mechanism to stimulate the immune system to combat tumors. We have also observed generally favorable tolerability to date among the patient population, supporting the investigational therapy’s potential in combination settings,” said Dr. Alan L. Ho, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator. “We continue to see encouraging results in the first-line patient setting for our HB-200 trial in combination with pembrolizumab as we have consistently observed patient responses that are double the ORR observed in standard of care treatments alone—reinforcing previously reported data,” said Joern Aldag, Chief Executive Officer at HOOKIPA. “These results give us great conviction to proceed with our planned randomized trial.” Results: HB-200 in combination with pembrolizumab in the 1st-line setting (NCT04180215)As of the DCO, August 7, 2023, the updated interim efficacy analysis included 19 evaluable patients with at least two imaging assessments out of the first 20 patients with HPV16+ recurrent/metastatic head and neck cancers treated with HB-200 in combination with pembrolizumab in the 1st-line setting as part of the Phase 2 trial. Of the intent-to-treat population (n=20) one patient was not evaluable due to COVID-related death prior to the first tumor scan. All patients received HB-200 intravenously every three weeks for the first five doses and every six weeks thereafter. HB-200 is a 2-vector investigational therapy with alternating administration of Lymphocytic Choriomeningitis Virus (LCMV), and Pichinde Virus (PICV) vectors, encoding the same HPV16 E6/E7 antigens. HB-200 in combination with pembrolizumab demonstrated promising initial anti-tumor activity with a 42 percent ORR (8 of 19 evaluable patients with confirmed responses by investigator assessment under RECIST 1.1) among CPI-naïve patients with 1st-line recurrent/metastatic HPV16+ PD-L1+ head and neck cancer. These data represent a doubling of the 19 percent ORR reported for pembrolizumab alone1 and are consistent with previously reported HB-200 data. Eight patients responded including one with a confirmed complete response and seven with confirmed partial responses. Another six patients achieved stable disease representing a DCR of 74 percent (14 of 19 patients). While recruitment is ongoing, based on these data, HOOKIPA is preparing to start a randomized trial of HB-200 in combination with pembrolizumab as 1st-line treatment of recurrent/metastatic HPV16+ PD-L1+ head and neck cancers in 2024. ImmunogenicityTumor-specific CD8+ T cell levels induced by HB-200 in combination with pembrolizumab are unprecedented and consistent with levels observed with HB-200 monotherapy. Among the 17 patients with available peripheral blood mononuclear cells (PMBC) samples, all patients showed an increase in the percent of tumor antigen-specific circulating HPV16+ CD8+ T cell responses per intercellular cytokine staining analysis. Peak percentage of antigen-specific circulating HPV16+ CD8+ T cell responses reached up to 31 percent with a median of 3.36 percent. Max response on treatment vs. before treatment of systemic HPV-16 E7 and E6 specific T cells measured by ELISPOT showed that the median fold-increase for these patients’ total tumor specific T cells was a 451-fold increase over baseline, with the maximal increase of 4,000-fold. Safety and tolerability profileResults from the HB-200 in combination with pembrolizumab in 1st-line patients arm of the Phase 2 part of the trial showed that HB-200 was generally well tolerated among 20 patients treated. Two patients (10 percent) showed serious adverse events related to the treatment with HB-200 or pembrolizumab. Only one patient (5 percent) discontinued due to a treatment-related adverse event (related to pembrolizumab). The updated safety profile adds to the previously reported safety and tolerability data from all 132 patients across all arms of the trial who received HB-200 monotherapy or HB-200 in combination with pembrolizumab. This generally favorable tolerability profile highlights the potential of HB-200—and arenaviral immunotherapies in general—to be successfully combined with other immunotherapies where tumor antigen-specific T cell induction is of potential benefit. ESMO HB-200 Poster Presentation Title: HB-200 Arenavirus-Based Immunotherapy Plus Pembrolizumab as a First-Line Treatment in Patients with Recurrent/Metastatic HPV16-Positive Head and Neck CancerPresenter: Dr. Alan L. Ho, Head and Neck Oncologist at Memorial Sloan Kettering Cancer Center and a trial investigatorSession Date: October 22, 2023Poster Board Number: 921PAbstract Number: 2212 About HB-200HB-200 is HOOKIPA’s lead oncology candidate engineered with the company’s proprietary replicating arenaviral vector platform. HB-200 is an alternating 2-vector immunotherapy designed to focus the immune response against the encoded antigen. It comprises two single-vector compounds with arenaviral backbones based on LCMV and PICV. Both encode and express an identical E7E6 fusion protein, comprising well characterized tumor-specific antigens for HPV16+ cancers. 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 was 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 CancersHuman 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 HOOKIPAHOOKIPA 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 www.hookipapharma.com. 1 Harrington et al. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Journal of Clinical Oncology. 2023;41(4);790-802. Forward Looking StatementsCertain 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 risk that interim or preliminary data may differ from final data from 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 www.sec.gov and HOOKIPA’s website at www.hookipapharma.com. Investors and others should note that we announce material financial information to our investors using our investor relations website (https://ir.hookipapharma.com/), 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: MediaInvestorsInstinctif PartnersMichael Kaiser, Investor Relationshookipa@instinctif.com michael.kaiser@hookipapharma.com +44 (0) 7457 2020+1 (917) 984-7537