Max Ciarlet

Responsible for developing, supporting, and managing the clinical development strategy for Icosavax candidate vaccines.

Provided scientific support, such as clinical trial data analyses, for vaccine candidates and ongoing vaccine programs, including in-depth overall strategy for clinical development plans. Provided input and guidance in preparation of clinical trial-related documentation, including regulatory submissions.

Provided active support to clinical teams to facilitate proper transfer of ongoing Phase 1 clinical trials and potential future vaccine candidates to ensure seamless continuity of vaccine assets from Novartis Vaccines to GSK by providing (i) scientific and medical input, (ii) all relevant documentation, and (iii) feedback and perspective.

Franchise and clinical head to provide scientific and medical input to define the overall strategy for the Early and Exploratory Clinical Development (EECD) Team. Managed new paradigms in exploratory clinical development by (i) promoting open innovation in vaccines, (ii) bridging preclinical evaluation and first-in-man Phase 1 clinical studies, (iii) advancing proof of concept tools and approaches, (iv) managing risk in early and exploratory clinical development, (v) reviewing innovative clinical trial design, regulatory approaches, and (vi) evaluating biomarkers in early development with the goal of avoiding the futility and expense of carrying ineffective novel vaccines into full scale clinical development by applying current methods to assess safety. Evaluated several vaccine candidates or new formulations of vaccines, including an engineered RSV F subunit vaccine candidate (intended for maternal immunization), adjuvanted trivalent influenza virus, and novel RNA vaccine platforms, which resulted in initiating three phase 1 clinical trials for different targets. Responsibility to drive consensus or a common understanding of early and exploratory clinical development programs. Clinical lead and direct responsibility for clinical development plans (CDPs) of the different vaccine candidates. Represented Novartis in meetings with health authorities, the scientific community, and Scientific Advisory Boards with KOLs. Supervised scientific and operational activities by providing input and guidance including study design, development of protocol and protocol-related documents, coordination of the development or identification of necessary serology assays, and accountability to integrate the documentation for regulatory submissions and other interactions with regulatory/health authorities and ethical review committees. Supported selection of phase 1 clinical units for trials, including interacting with potential CROs.

Clinical lead to provide scientific and medical input and contribute to and define the overall strategy for the Early and Exploratory Clinical Development Cluster. Clinical lead responsible for managing new paradigms in exploratory clinical development, promoting open innovation in vaccines (while applying knowledge from pharma), bridging preclinical evaluation and “traditional” first-in-man Phase I clinical studies, advancing proof of concept tools and approaches, managing risk in early and exploratory clinical development, reviewing innovative clinical trial design, regulatory approaches, and evaluating biomarkers in early development with the goal of avoiding the futility and expense of carrying ineffective novel vaccines into full scale clinical development by learning current methods to assess safety. Clinical lead within several novel adjuvants or vaccines, including an RSV F subunit vaccine candidate (intended for maternal immunization), parvovirus B19, adjuvanted trivalent influenza virus, and novel RNA vaccine platforms. Coordinate scientific and operational activities necessary by providing input and guidance for to, study design, development of protocol and protocol-related documents (including an ICF that allows genetic testing), preparation of CTA, coordination of the development or identification of necessary serology assays, and accountability to integrate the documentation for regulatory submissions and other interactions with regulatory/health authorities and ethical review committees provide assistance in preparation of toxicology study plans. Provide assistance in selection of phase I clinical units for trials. Form relationships with relevant KOLs. Represent NVD in meetings with health authorities, the scientific community, and Scientific Advisory Boards with KOLs. Member of the PATH’s Scientific Advisory Board for vaccine development, including overall strategy, technical guidance, and clinical development. Manage, mentor and develop associates.

Clinical representative of the GPT. Accountability and direct responsibility for (i) CDPs reflecting the overall clinical and regulatory of the viral vaccine clinical programs (RSV, CMV, parvovirus B19), (ii) all clinical trial documents (protocols, informed consents, diary cards, and case report forms, clinical study reports); and (iii) the integrated documentation for regulatory submissions and other interactions with regulatory/health authorities and ethical review committees. Core member of the global project team to provide scientific and medical input to define the overall strategy of the viral vaccine programs. Clinical representative for the cross-strategy team for potential maternal vaccines (in particular to RSV and influenza virus vaccines). Clinical representative to support and liaise with other leaders from different functional areas in vaccine program-related deliverables. Conducted evaluation of additional vaccine programs (in-house and third party), and prospective due diligence as clinical representative (including review of CMC and clinical documents, commenting on the scope, overall strategy, deliverables and timelines in support of Business Development and Licensing). Core member of PATH’s Scientific Advisory Board for vaccine development, including overall strategy, technical guidance, and clinical development of non-replicating rotavirus vaccine candidates for developing world populations. Managed, and mentored clinical associates.

Develop Clinical Development Plans (CDPs) and responsible for translating the CDPs into clinical trials. Responsible for clinical sections of regulatory submissions. Support Cluster Head in oversight of CDP/trial execution and manage team members. Partner with Clinical Research Scientist (CRS) and/or biostatistician to ensure implementation of clinical trials. Accountable for development of clinical protocols, investigator’s brochures, study related documents (informed consents, diary cards, case report forms), and analysis plans that fit the strategy of the CDP. Work with Regions team to translate study concept into study execution according to the CDP. Responsible for Cluster related safety monitoring activities, including, but not limited to, review of serious adverse events, analysis of safety signals, review of safety related listings of data from clinical trials. Responsible for Annual Safety Report/Periodic Safety Update Recording. Support the Cluster Head in representing NVD in meetings with health authorities, the scientific community, and Advisory Boards with Key Opinion Leaders (KOLs). Contribute to the operational and administrative management of the Cluster.

Head of Product Development Team (PDT) for the rotavirus vaccine program. Clinical development Lead overseeing clinical trials, global strategy and activities in the developed and developing world (Africa and Asia). Experience working with global partners, such as PATH and WHO. Oversight of all activities related to the clinical trial process (including operational compliance and site selection), review monitoring reports, overall design and implementation of clinical trials, including logistics operations, site visits to establish selection and assist and evaluate operation, and general outsourcing (in both developed and developing countries). Active role on protocol development and implementation, evaluation of protocols, investigator's meetings, and assay design. Responsibilities for global strategy and execution of all activities of clinical program, including managing all activities of the program and ensuring that the proper resources are aligned and timelines are maintained. Scientific expert lead for generating the analytical data for the critical characterization activities for the Biologics License Application (BLA)/World Marketing Application (WMA), including complete physical, biochemical, antigenic, and molecular characterization of live vaccines and characterization of all process-related impurities. Close interaction with Regulatory Affairs staff to assist with planning, review and advice on manufacturing processes, and emerging issues related to vaccine development or safety. Ensure regulatory compliance. Direct collaboration with Medical Affairs & Policy staff to develop near and long-term plans for engaging the medical and scientific community, including participating in Advisory Boards, Expert Input Forums, and individual consultant services. Authoring of Global Clinical Development Plans and several primary worldwide regulatory filing documents. Assistance in developing medical education programs. Knowledge of global health issues.

Responsabilities/accomplishments: (1) As lead Clinical Monitor, designed and implemented clinical trials, including primary input into all aspects of key or pivotal clinical study protocols (study design, study placement, study monitoring, data management, and analysis and summary of clinical findings); (2) Work closely with the Operations group (CROps) and SPMSD to organize operations of clinical studies, such as data management, clinical sample management and testing, Serious Adverse Event (SAE) management, and site monitoring management; (3) . Worked closely with Medical Program Clinical Specialists (MPCSs) to provide support and guidance; (4) Provided supplemental material to support regulatory filings of the program of RotaTeq® in the US, the European Union (EU), Canada, and Mexico; (5) Provided feedback and answered regulatory questions about the filing of RotaTeq®; (6) Assisted Regulatory Affairs to support Clinical Study Applications (CSAs) and other regulatory documents; (7) Facilitated update of the Clinical Investigator’s Confidential Informational Brochure (CIB); (8) Participated in the Rotavirus Advisory Committee Meeting; (9) Provided strong support to Merck vaccine Division (MVD) at national and international Launch Meetings, and Speaker’s Training and HSAcademy Training Meetings; (10) Served as International Speaker at several Key Opinion Leaders (KOL) and Ministry of Health (MOH) Meetings in Central and South America as requested by MVD; (11) Interacted with Rotavirus Working Group and ACIP to support universal recommendation of rotavirus vaccination; (12) Member of the RotaTeq® Meetings: Product Development Team (PDT), Clinical Supplies Subteam (CSS), Biological License Application Meeting (BLA/IMA), Clinical Research & Regulatory Subteam (CRRS), and Joint Project Team (JPT); (13) Co-chair of the Clinical Assay Subteam (CAST) for the program of RotaTeq®.

Responsibilities/accomplishments: (1) Scientific Expert Lead for generation of analytical data for critical characterization activities of RotaTeq® for the Biologics License Application (BLA) / World Marketing Application (WMA), which included complete physical, biochemical, antigenic, and molecular characterization of RotaTeq® and the characterization of all process-related impurities; (2) Scientific Lead for validation of residual Vero cell DNA assay for the program of RotaTeq® and the BLA/WMA; (3) Authored CMC sections for the Biologics License Application (BLA) / World Marketing Application (WMA) of RotaTeq®; (4) Key member of the extensive and comprehensive investigation of the Rotavirus Serotype G3 Serum Neutralizing Antibody (SNA) Task force; (5) Member of the Rotavirus Analytical Sub-team (AST), and Ad-hoc member of the Rotavirus Transfer Technology Team (TTT); (6) Coordinated outsourcing projects with two outside biotechnology laboratories and two academic laboratories; (7) Conducted audits/inspections of research investigational laboratories to ensure compliance with applicable Good Clinical Practice (GCP) regulations/guidelines; (8) Interacted with Vaccine Pharmaceutical Research & Development (VPR&D) to generate critical data for the BLA/WMA in behalf of the program of RotaTeq®; (9) Lead for initial efforts to transfer the validated assay to measure residual Vero cell DNA in rotavirus vaccine bulks; (10) Assisted in the development of cell-based assays for the oncology program; (11) Continuously mentored direct reports and laboratory staff members; (12) Provided scientific and professional training to direct reports and laboratory personnel; (13) Established Standard Operating Procedures (SOPs).

Responsibilities/accomplishments: (1) Established a new animal model of age-dependent rotavirus-induced diarrheal disease in rats with unique features amenable to investigate rotavirus infection and pathogenesis; (2) Analyzed the immunogenicity and protective efficacy of rotavirus 2/6-virus-like particles in mice by several immunization routes; (3) Identified cell lines resistant to rotavirus infection that bind rotavirus but lack the appropriate receptor required for cell entry, but if cell entry is bypassed, the cells are permissive for rotavirus; (4) Developed methods and reagents applicable to identify the rotavirus cellular receptor on polarized intestinal epithelial cells and ultimately, in the rat model of rotavirus infection; (5) Obtained extramural funding for a pilot/feasibility project from the Texas Gulf Coast Digestive Diseases Center; (6) Studied rotavirus-cell interactions and determined that the VLA-2 integrin plays a role at a post-attachment level; (7) Postulated that the initial interaction of rotavirus strains with sialic acid residues on the cell surface correlates with P genotype, not VP7 or species of origin; (8) Evaluated serum antibody responses against the rotavirus enterotoxin NSP4 in children after vaccination with the rhesus rotavirus (RRV) tetravalent vaccine; (9) Postulated that rotavirus can escape the gastrointestinal tract and result in antigenemia and viremia; (10) Supervised several rotation and graduate students, and guest researchers; (11) Continued to author peer-reviewed scientific publications, and book and encyclopedia chapters; (12) Continued to be primary author of abstracts/presentations at scientific meetings.

Responsibilities/accomplishments: (1) Determined that a limited number of serotypes of virus-like particles (VLPs) may be sufficient to provide a broadly protective subunit rotavirus vaccine; (2) Determined that the genotypes of the rotavirus enterotoxin NSP4 cluster according to species of origin; (3) Identified an epitope common to genogroup I of noroviruses; (4) Studied rotavirus pathogenesis in small (mouse, rabbit) laboratory animals; (5) Determined that the simian rhesus rotavirus (RRV) strain is a unique rotavirus strain capable of productive replication and horizontal transmission; (6) Determined that sialic acid-independent rotavirus strains infect polarized epithelial cells efficiently through both the apical and basolateral surfaces, while sialic acid-dependent strains only infect efficiently through the apical surface; (7) Identified potential use of the rotavirus enterotoxin as a novel adjuvant; (8) Supervised several rotation and graduate students, and guest researchers; (9) Continued to author peer-reviewed scientific publications, and book and encyclopedia chapters; (10) Continued to be primary author of abstracts/presentations at scientific meetings.

Responsibilities/accomplishments: (1) Identified the P genotype of lapine rotavirus strains and characterized a newly isolated lapine rotavirus strain; (2) Identified the host range restriction determinants in the rabbit model of rotavirus infection; (3) Postulated that rotavirus disease is age restricted in rabbits; (4) Generated different formulations of rotavirus-like particles in the baculovirus expression system; (5) Evaluated the immune response and protective efficacy of different formulations of candidate virus-like particle (VLP) subunit vaccines against rotavirus; (6) Developed novel diagnostic assays using virus-like particles (VLPs) to detect and type human caliciviruses; (7) Established that human and most animal rotavirus strains infect permissive cells in a sialic acid-independent manner; (8) Continued to author peer-reviewed scientific publications, and book and encyclopedia chapters; (9) Continued to be primary author of abstracts/presentations at scientific meetings.

Responsibilities/accomplishments: (1) Antigenic and molecular characterization of porcine, equine and bovine rotaviruses in South America, (2) Development of diagnostic assays for rotaviruses, (3) characterized (antigenically and molecularly) equine and bovine rotaviruses in Venezuelan herds for the first time; (2) Performed survey of P and G genotypes in equine populations; (4) Confirmed circulation of rotavirus serotype G1 in swine; (5) Studied the antigenic and genetic variation of porcine rotaviruses in South America; (6) Evaluated the rotavirus serotype-specific immune response in 8-week old piglets, and confirmed the presence of common serotypes G3 and G5 VP7 types, as well as an exclusive domain for serotype G11; (7) Authored peer-reviewed scientific publications; (8) Primary author of abstracts/presentations at scientific meetings; (9) Supervised several rotation students and guest researchers; (10) Coordinator and part of the teaching staff of several virology, immunology, and physics graduate-level courses; (11) Directed the undergraduate thesis of Enrique Vásquez (Universidad Católica Andrés Bello, Caracas, Venezuela): “Antigenic analyses of the VP6 protein of human rotavirus strains”.

Analyzed the genetic variability in human and animal rotavirus strains by the RNase A mismatch cleavage method in a similar manner as had been applied to study the subtype divergence and heterogeneity of human respiratory syncytial virus (RSV).

Responsibilities/accomplishments: (1) Generated the only available monotype- and serotype-specific monoclonal antibodies (MAbs) against rotavirus serotype G11; (2) Generated G5 monotype- and serotype-specific MAbs, as well as cross-reactive MAbs against rotavirus serotypes G3 and G5; (3) Identified neutralization epitopes present on the hypervariable regions of VP7 of rotavirus serotypes G3, G5, and G11 by sequence analysis of neutralization-resistant variants; (4) Determined that single point mutations affect serotype reactivity of serotype G11 porcine rotaviruses; (5) Generated MAbs against the rotavirus VP6 protein of porcine and human rotavirus strains; (6) Developed an enzyme-linked immunosorbent assay (ELISA) to detect and serotype porcine rotaviruses directly from stool samples; (7) Determined that rotavirus maturation depends on a high sequestered [Ca2+] in the cisternae of the endoplasmic reticulum; (8) Analyzed the immune responses to rotavirus in piglets; (9) Authored peer-reviewed scientific publications; (10) Primary author of abstracts/presentations at scientific meetings.