Long‐term persistence of immune response to the AS04‐adjuvanted HPV‐16/18 vaccine in Chinese girls aged 9‐17 years: Results from an 8‐9‐year follow‐up phase III open‐label study

Q4 · MEDICINE

Article

Author: Jiang, Yunyu ; Folschweiller, Nicolas ; Jiang, Johny ; Jastorff, Archana ; Poncelet, Sylviane ; Xu, Yabin ; Ma, Zhilong ; Xie, Yan ; Xiao, Hui ; Zhang, Yanqiu ; Karkada, Naveen ; Hu, Yuemei ; Struyf, Frank ; Lu, Xiangbin ; Zhang, Xiang ; Borys, Dorota ; He, Yilin

Abstract:

Aim:

In 9‐17‐year‐old Chinese girls, the AS04‐adjuvanted HPV‐16/18 vaccine (AS04‐HPV‐16/18) given as three‐dose schedule induced high antibody levels, which were noninferior 1 month after the third dose to those observed in 18‐25‐year‐old Chinese women in a large efficacy study. We assessed the persistence of antibodies 8‐9 years after vaccination in the same subjects.

Methods:

This follow‐up phase III, open‐label study (NCT03355820) included subjects who had received three doses of AS04‐HPV‐16/18 in the initial trial (NCT00996125). Serum antibody concentrations were assessed by ELISA and compared to antibody persistence observed in 18‐25‐year‐old Chinese women 6 years after first vaccination in the efficacy study (NCT00779766).

Results:

Out of the 227 enrolled subjects, 223 were included in the per‐protocol immunogenicity analysis. Mean interval from first AS04‐HPV‐16/18 dose to blood sampling was 101.4 months (8.5 years). For antibodies against HPV‐16 and ‐18, 8.5 years after first vaccine dose all subjects remained seropositive and antibody. Geometric mean concentrations (GMCs) were 1236.3 (95% confidence interval [CI]: 1121.8; 1362.4) and 535.6 (95% CI: 478.6; 599.4) ELISA Units/mL, respectively. These seropositivity rates and antibody GMCs were higher than those observed 6 years after first vaccination of 18‐25‐year‐old women.

Conclusion:

Sustained anti‐HPV‐16 and ‐18 immune responses were observed 8‐9 years after AS04‐HPV‐16/18 vaccination of 9‐17 year‐old Chinese girls that were higher than the ones observed 6 years after first vaccination in Chinese adult women in whom AS04‐HPV‐16/18 efficacy against cervical intraepithelial neoplasia of grade ≥2 was demonstrated.

01 May 2020·European journal of medicinal chemistry

A series of novel aryl-methanone derivatives as inhibitors of FMS-like tyrosine kinase 3 (FLT3) in FLT3-ITD-positive acute myeloid leukemia

Article

Author: Spiekermann, Karsten ; Elz, Sigurd ; Kuster, Bernhard ; Pilsl, Bernadette ; Sellmer, Andreas ; Böhmer, Frank D ; Dove, Stefan ; Beyer, Mandy ; Henninger, Sven Julian ; Mahboobi, Siavosh ; Pongratz, Herwig ; Polzer, Harald ; Fiebig, Heinz-Herbert ; Krämer, Oliver H ; Wirth, Lukas ; Klaeger, Susan

Mutants of the FLT3 receptor tyrosine kinase (RTK) with duplications in the juxtamembrane domain (FLT3-ITD) act as drivers of acute myeloid leukemia (AML). Potent tyrosine kinase inhibitors (TKi) of FLT3-ITD entered clinical trials and showed a promising, but transient success due to the occurrence of secondary drug-resistant AML clones. A further caveat of drugs targeting FLT3-ITD is the co-targeting of other RTKs which are required for normal hematopoiesis. This is observed quite frequently. Therefore, novel drugs are necessary to treat AML effectively and safely. Recently bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. In order to optimize these agents we synthesized novel derivatives of these methanones with various substituents. Methanone 16 and its carbamate derivative 17b inhibit FLT3-ITD at least as potently as the TKi AC220 (quizartinib). Models indicate corresponding interactions of 16 and quizartinib with FLT3. The activity of 16 is accompanied by a high selectivity for FLT3-ITD.

01 Jan 2019·JAMA oncologyQ1 · MEDICINE

Combining Immune Checkpoint Blockade and Tumor-Specific Vaccine for Patients With Incurable Human Papillomavirus 16–Related Cancer

Q1 · MEDICINE

Article

Author: Kim, Young Uk ; Tran, Hai ; Kies, Merrill ; Massarelli, Erminia ; Feng, Lei ; Rodriguez Canales, Jaime ; William, William ; Lee, J. Jack ; Zecchini Barrese, Tomas ; Wang, Jing ; Johnson, Faye ; Glisson, Bonnie ; Bernatchez, Chantale ; Guo, Ming ; Wistuba, Ignacio ; Melief, Cornelis J. ; Ferrarotto, Renata ; Haymaker, Cara ; Li, Lerong ; Curran, Michael ; van der Burg, Sjoerd H.

Importance:

In recurrent human papilloma virus (HPV)-driven cancer, immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies produces tumor regression in only a minority of patients. Therapeutic HPV vaccines have produced strong immune responses to HPV-16, but vaccination alone has been ineffective for invasive cancer.

Objective:

To determine whether the efficacy of nivolumab, an anti-PD-1 immune checkpoint antibody, is amplified through treatment with ISA 101, a synthetic long-peptide HPV-16 vaccine inducing HPV-specific T cells, in patients with incurable HPV-16-positive cancer.

Design, Setting, and Participants:

In this single-arm, single-center phase 2 clinical trial, 24 patients with incurable HPV-16-positive cancer were enrolled from December 23, 2015, to December 12, 2016. Duration of follow-up for censored patients was 12.2 months through August 31, 2017.

Interventions:

The vaccine ISA101, 100 μg/peptide, was given subcutaneously on days 1, 22, and 50. Nivolumab, 3 mg/kg, was given intravenously every 2 weeks beginning day 8 for up to 1 year.

Main Outcomes and Measures:

Assessment of efficacy reflected in the overall response rate (per Response Evaluation Criteria in Solid Tumors, version 1.1).

Results:

Of the 24 patients (4 women and 20 men; 22 with oropharyngeal cancer; median age, 60 years [range, 36-73 years]), the overall response rate was 33% (8 patients; 90% CI, 19%-50%). Median duration of response was 10.3 months (95% CI, 10.3 months to inestimable). Five of 8 patients remain in response. Median progression-free survival was 2.7 months (95% CI, 2.5-9.4 months). Median overall survival was 17.5 months (95% CI, 17.5 months to inestimable). Grades 3 to 4 toxicity occurred in 2 patients (asymptomatic grade 3 transaminase level elevation in 1 patient and grade 4 lipase elevation in 1 patient), requiring discontinuation of nivolumab therapy.

Conclusions and Relevance:

The overall response rate of 33% and median overall survival of 17.5 months is promising compared with PD-1 inhibition alone in similar patients. A randomized clinical trial to confirm the contribution of HPV-16 vaccination to tumoricidal effects of PD-1 inhibition is warranted for further study.

Trial Registration:

ClinicalTrials.gov identifier: NCT02426892.

News (Medical) associated with A-002 (eTheRNA)

26 May 2023

·www.biospace.com

Transgene to Present Data on its Two Therapeutic Cancer Vaccines at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting

Presentations include new data further demonstrating the immune responses induced by TG4001 and recently updated results from the adjuvant Phase I trial of neoantigen vaccine TG4050 in head and neck cancer STRASBOURG, France--(BUSINESS WIRE)-- Regulatory News: Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, announced two poster presentations at the 2023 American Association of Clinical Oncology (ASCO) annual meeting to be held in Chicago, IL (June 2-6). The posters will highlight that in challenging clinical settings: ✓ TG4001 induced T-cell responses against HPV16 antigens in the ongoing Phase II trial. ✓ TG4050: 100% of the patients treated with the individualized therapeutic cancer vaccine developed multiple functional T cell responses against targeted neoantigens, which may be associated with an improved outcome in patients with head and neck cancer in the adjuvant setting. Details for the presentations are as follows: TG4001 Abstract Title: Immunogenicity and clinical activity of tipapkinogen sovacivec (TG4001), an HPV-16 cancer vaccine: A randomized phase 2 study in advanced anogenital cancers. Abstract Number: 2630 Session Title: Developmental Therapeutics—Immunotherapy Session Date and Time: Saturday, June 3, 2023, 8:00 AM-11:00 AM (CDT) Link to the abstract: click here TG4050 Abstract Title: Safety and immunogenicity of TG4050: A personalized cancer vaccine in head and neck carcinoma. Abstract Number: 6082 Session Title: Head and Neck Cancer Session Date and Time: Monday, June 5, 2023, 1:15 PM-4:15 PM (CDT) Link to the abstract: click here The abstracts are available on Transgene’s website. *** About TG4001 TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA), which is engineered to express HPV16 antigens (E6 & E7) and an adjuvant (IL-2). TG4001 is designed to have a two-pronged antiviral approach: to alert the immune system specifically to cells presenting the HPV16 E6 and E7 antigens, that can be found in HPV16-related tumors, and to further stimulate the infection-clearing activity of the immune system through interleukin 2 (IL-2). TG4001 has been administered to more than 350 individuals, demonstrating good safety and promising efficacy results [1]. Its mechanism of action and good safety pro TG4001 an excellent candidate for combinations with other therapies in HPV-mediated solid tumors. It is currently evaluated in a multi-center, open label, randomized Phase II trial (NCT03260023) designed to compare the efficacy of the combination of TG4001 and avelumab versus avelumab alone in patients with advanced, recurrent and/or metastatic HPV16-positive anogenital cancers who have disease progression after a maximum of one line of systemic treatment, or who are not eligible for first-line chemotherapy. About TG4050 TG4050 is an individualized immunotherapy being developed for solid tumors that is based on Transgene’s myvac® technology and powered by NEC’s longstanding artificial intelligence (AI) expertise. This virus-based therapeutic vaccine encodes neoantigens (patient-specific mutations) identified and selected by NEC’s Neoantigen Prediction System. The prediction system is based on more than two decades of expertise in AI and has been trained on proprietary data allowing it to accurately prioritize and select the most immunogenic sequences. TG4050 is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to recognize and destroy tumor cells based on their own neoantigens. This individualized immunotherapy is developed and produced for each patient. TG4050 is being evaluated in two Phase I clinical trials for patients with HPV-negative head and neck cancers (NCT04183166) and ovarian cancer (NCT03839524), and has shown promising initial results. About Transgene Transgene (Euronext: TNG) is a biotechnology company focused on designing and developing targeted immunotherapies for the treatment of cancer. Transgene’s programs utilize viral vector technology with the goal of indirectly or directly killing cancer cells. The Company’s clinical-stage programs consist of a portfolio of therapeutic vaccines and oncolytic viruses: TG4050, the first individualized therapeutic vaccine based on the myvac® platform, TG4001 for the treatment of HPV-positive cancers, as well as TG6002, BT-001 and TG6050, three oncolytic viruses based on the Invir.IO® viral backbone. With Transgene’s myvac® platform, therapeutic vaccination enters the field of precision medicine with a novel immunotherapy that is fully tailored to each individual. The myvac® approach allows the generation of a virus-based immunotherapy that encodes patient-specific mutations identified and selected by Artificial Intelligence capabilities provided by its partner NEC. With its proprietary platform Invir.IO®, Transgene is building on its viral vector engineering expertise to design a new generation of multifunctional oncolytic viruses. Additional information about Transgene is available at: Follow us on social media: Twitter: @TransgeneSA and LinkedIn: @Transgene Disclaimer This press release contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. The occurrence of any of these risks could have a significant negative outcome for the Company’s activities, perspectives, financial situation, results, regulatory authorities’ agreement with development phases, and development. The Company’s ability to commercialize its products depends on but is not limited to the following factors: positive pre-clinical data may not be predictive of human clinical results, the success of clinical studies, the ability to obtain financing and/or partnerships for product manufacturing, development and commercialization, and marketing approval by government regulatory authorities. For a discussion of risks and uncertainties which could cause the Company’s actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risque”) section of the Universal Registration Document, available on the AMF website ( ) or on Transgene’s website ( ). Forward-looking statements speak only as of the date on which they are made, and Transgene undertakes no obligation to update these forward-looking statements, even if new information becomes available in the future. View source version on businesswire.com: Contacts Transgene: Lucie Larguier Director Corporate Communications & IR +33 (0)3 88 27 91 04 investorrelations@transgene.fr Media: MEDiSTRAVA Consulting David Dible/Sylvie Berrebi +44 (0)203 928 6900 transgene@medistrava.com Source: Transgene View this news release online at:

ImmunotherapyClinical ResultASCOVaccinePhase 1

06 Dec 2011

·www.biospace.com

Anthera Pharmaceuticals, Inc. Promotes Dr. Debra Odink to Chief Technology Officer

HAYWARD, Calif., Dec. 5, 2011 /PRNewswire/ -- Anthera Pharmaceuticals, Inc. (Nasdaq: ANTH), a biopharmaceutical company developing therapeutics to treat serious diseases associated with inflammation and autoimmune disorders, today announced Dr. Debra Odink has been promoted to the role of Chief Technology Officer and Senior Vice President. "Over the past several years, Debra's increasing roles, responsibility and scientific leadership has been critical to the success of Anthera's development programs," said Paul F. Truex, President and Chief Executive Officer. "As Chief Technology Officer, Debra's strong oversight will continue to drive the advancement and execution of our corporate strategy." Dr. Odink joined Anthera in 2005 and has been serving as the Senior Vice President of Pharmaceutical Research and Development since that date. She has over eighteen years of global pharmaceutical chemistry and product development experience. Prior to joining Anthera, she served as the Vice President of Product and Process Development at Peninsula Pharmaceuticals where she was responsible for the company's manufacturing and product development strategies for assets licensed to the company. Additionally, she has held various positions at Elan Pharmaceuticals and Roche where she contributed to development efforts for multiple new drug candidates. Dr. Odink holds various patents for novel drug formulations and is author of multiple publications. She obtained her Bachelor of Science in Chemistry at California State University Stanislaus and her Ph.D. in Inorganic Chemistry at the University of California Davis. About Anthera Pharmaceuticals Anthera Pharmaceuticals is a biopharmaceutical company focused on developing and commercializing products to treat serious diseases associated with inflammation, including cardiovascular and autoimmune diseases. Anthera has one Phase 3 clinical program, A-002, and two Phase 2 clinical programs, A-623 and A-001. A-002 and A-001 inhibit a novel enzyme target known as secretory phospholipase A2, or sPLA2. Elevated levels of sPLA2 have been implicated in a variety of acute inflammatory conditions, including acute coronary syndrome and acute chest syndrome, as well as chronic diseases such as stable coronary artery disease, or CAD. Anthera's Phase 2 product candidate, A-623, targets elevated levels of B-lymphocyte stimulator, or BLyS, which has been associated with a variety of B-cell mediated autoimmune diseases, including systemic lupus erythematosus, or lupus. For more information, please visit . Safe Harbor Statement Any statements contained in this press release that refer to future events or other non-historical matters, including statements that are preceded by, followed by, or that include such words as "estimate," "intend," "anticipate," "believe," "plan," "goal," "expect," "project," or similar statements, are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on Anthera's expectations as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially as set forth in Anthera's public filings with the SEC, including Anthera's Annual Report on Form 10-K for the year ended December 31, 2010 and Quarterly Report on Form 10-Q for the quarter ended September 30, 2011. Anthera disclaims any intent or obligation to update any forward-looking statements, whether because of new information, future events or otherwise, except as required by applicable law. CONTACT: Bianca Nery of Anthera Pharmaceuticals, Inc., bnery@anthera.com or 510.856.5586. SOURCE Anthera Pharmaceuticals, Inc.

100 Deals associated with A-002 (eTheRNA)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
HPV16 positive solid tumors	IND Approval	CN	Nanjing Aoluo Biotechnology Co., Ltd.	24 Jan 2024
Head and Neck Neoplasms	Preclinical	BE	eTheRNA immunotherapies NV	01 Dec 2020

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