The Aptuit Center for Drug Discovery & Development Verona, Italy. Uncommon Expertise. Exceptional Results.

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1 The Aptuit Center for Drug Discovery & Development Verona, Italy Uncommon Expertise. Exceptional Results.

2 2 The Aptuit Center for Drug Discovery & Development Verona, Italy Aptuit in Verona: uncommon expertise, exceptional results A knowledgeable scientific group, comprised of some of the industry s foremost drug discovery and development experts, forms a collaborative team at The Aptuit Center for Drug Discovery & Development in Verona, Italy. They are specialists with uncommon expertise in neuroscience, antibacterial, oncology, cardiovascular, respiratory and other key therapeutic areas. Together, with our other development sites in the US and the UK, these experts stand among Aptuit s vast, global assembly of talented people with Heads for Science and Hearts for Service. Essential throughout the development process is the Project Manager who serves as the client s advocate and ensures exceptional results. Focused on the fastest, most efficient and lowest risk option, Aptuit s Project Managers are highly experienced professionals who fully understand that the client and Aptuit are most effective when working together in a partnership that is flexible, trustworthy and transparent.

3 The Best of Both Worlds: a CRO and an R&D Engine The Aptuit facilities in Verona, Italy, combine the proven efficiency of a Contract Research Organization (CRO) with the established scientific expertise of an accomplished and successful Research and Development engine. When compared to typical CROs, it is significant that the experience of much of the scientific staff has been attained within the pharmaceutical industry, rather than simply for the pharmaceutical industry. Scientists at the facilities have advanced a large number of molecules from early discovery through clinical development with low attrition rates on many target classes. Their expertise in multiple therapeutic areas imparts a strong measure of confidence and credibility for pharmaceutical clients. Working as a highly integrated team, Aptuit scientists take a solution-driven approach, progressing compounds efficiently, expeditiously and economically. GMP authorization for both API and drug manufacturing and testing facilities are in place with regulatory inspections performed by AIFA, the Italian Drug Agency, and the FDA. Preclinical facilities for biological studies are fully GLP certified by the Italian Ministry of Health according to OECD principles. GCP compliance has also been determined for testing of human samples and management of clinical studies. 3

4 4 The Aptuit Center for Drug Discovery & Development Verona, Italy Integrated Knowledge: a unique, dynamic differentiator Integrated Knowledge captures all that is exceptional about The Aptuit Center for Drug Discovery & Development. The term stands for the essence of what clients whether they represent large, multinational companies or emerging biotechs can anticipate as a unique, reliable and consistent advantage when they select Aptuit as their partner. Specifically, Integrated Knowledge represents layer upon layer of the insights and understanding of a collaborative group of multidisciplinary scientific experts and their support teams who routinely have access to the most advanced technologies. The Integrated Knowledge of scientific professionals in Drug Design & Discovery, Preclinical Biosciences, Chemistry, Manufacturing & Control (CMC), and Clinical Sciences is a significant and dynamic Aptuit differentiator. Integrated Knowledge is the driving force in taking the client s molecule through to finished drug product with maximum efficiency.

5 Benefits for both integrated and stand alone services Whether clients choose an Integrated Service Offering or select stand alone services, they experience the Integrated Knowledge of scientists at The Aptuit Center for Drug Discovery & Development, who share an insatiable quest for learning and are able to grasp all the subtleties and implications of the entire picture. Their all-encompassing vision of the process, always in the spirit of sharing their individual knowledge with each other, allows for a deeper, greater understanding of the parameters set forth by the client. Significantly, the broadened perspective of Integrated Knowledge allows for the identification of challenges that may surface later on in the process. Therefore, as the process unfolds, Integrated Knowledge mitigates risks by anticipating potential problems and suggesting preemptive solutions. The Aptuit Integrated Service Offering Target Validation DISCOVERY Services Target To Lead Lead To Candidate Development Services Preclinical Development Clinical Development Computational Chemistry Medicinal Chemistry DMPK & Bioanalysis Structural and Analytical Sciences Pharmacology & Safety Pharmacology API Development & Manufacturing Pharmaceutical development & Manufacturing Toxicology & Pathology Clinical sciences 5

6 6 The Aptuit Center for Drug Discovery & Development Verona, Italy Fully integrated services from a single site The facility s broad range of integrated capabilities includes Drug Design and Discovery, Preclinical Biosciences, Chemistry, Manufacturing and Control (CMC), Clinical Sciences and Integrated Drug Discovery and Development programs. For clients, fully integrated drug discovery and development services from a single site deliver a number of tangible benefits such as reduced timelines, cost effectiveness, elimination of technical or informational transfers and efficiency to provide rapid solutions. Successful processes are in place to advance the client s molecule from discovery to finished product. Drug Design and Discovery Rapid Solutions Reduced Timelines Preclinical Biosciences Integrated Drug Discovery and Development Improved Efficiency Chemistry, Manufacturing and Control Cost Effectiveness Clinical Sciences

7 Experts in overcoming early development challenges The breadth of Aptuit s capabilities in Verona bring added value to clients who are accustomed to dealing with several suppliers. Clients experience convenience, time and cost savings, and an exceptional level of quality performance that is the result of well established collaborative expertise. Among the other notable capabilities available from The Aptuit Center for Drug Discovery & Development are Integrated Non-Human Primate Facilities and Applied Immunology services. A full range of exploratory/ preliminary, regulatory, investigative, customized and fit for purpose studies can be conducted. AAALAC accredited animal facilities and procedures are used. In addition, preclinical development studies of vaccine/viral vector/gene therapy, such as GLP biodistribution and virus shedding, are available. 7

8 8 The Aptuit Center for Drug Discovery & Development Verona, Italy Drug Design & Discovery from Target to Lead to Candidate Aptuit s comprehensive Drug Design & Discovery processes are led by scientists with experience in target identification and validation of preclinical candidate molecules. Core discovery services, available as a fully integrated offering or as stand alone services, include: Computational Chemistry, Medicinal Chemistry, Discovery Biology, Pharmacology, Drug Metabolism and Pharmacokinetics (DMPK), Safety Assessment, and Analytical Discovery Support. In addition, expertise in Toxicology, Pharmaceutical Development and Clinical Sciences capabilities are brought into the process for a truly translational approach. Aptuit can provide Drug Design & Discovery solutions exceeding those normally associated with CRO offerings, providing a versatile range of valueadded business options best suited to individual client needs. Among these unique options are bundled Drug Design & Discovery and Preclinical Biosciences services. The bundled Aptuit offering of these services from a single site delivers integrated capabilities of the highest quality at substantial cost savings.

9 A comprehensive range of Drug Discovery capabilities n Hit Identification: featuring UHit, Aptuit s comprehensive, alternative approach that employs Virtual HTS computational screening through 2D/3D descriptors and structure-based ligandbased de novo design, and Discovery Biology, targeting activity and selectivity screens (affinity and/or functional in recombinant cell lines or native tissue) n Integrated Lead Optimization: an advanced approach that relies on fully integrated research units, multi-factorial optimization and a Fit-for-Purpose strategy n Fast-Follower, Knowledge-Based & Back-up Strategies: innovating new chemistry for existing drugs/scaffolds to improve safety and efficacy profiles n Exploratory Development Assessment: including preliminary Safety and DMPK when there is a low quantity or poor quality of available API n Translational Biology and Safety Strategy: Bench to Bedside research that expedites the translation of scientific discoveries into clinical practice n IP Boost and Generation Engine n Due Diligence and Consulting Hit Identification Integrated Lead Optimization Due Diligence and Consulting DISCOVERY SERVICES Fast-Follower, Knowledge- Based & Back-up Strategies IP Boost and Generation Engine Translational Biology and Safety Strategy Exploratory Development Assessment 9

10 10 The Aptuit Center for Drug Discovery & Development Verona, Italy Preclinical Biosciences, taking a customized approach The Preclinical Biosciences team at The Aptuit Center for Drug Discovery & Development can perform the full spectrum of preclinical studies, with the assurance of accurate and balanced assessments even when meeting the tightest deadlines. Scientists employ best-in-class technologies to find the solutions that suit client s requirements. From laboratories within the Verona site, they share their expertise in Microbiology, Pharmacology and Safety Pharmacology, Toxicology & Pathology, Drug Metabolism & Pharmacokinetics and Preclinical and Clinical Bioanalysis. The integrated Aptuit team is distinguished by specialized preclinical capabilities. A legacy of success in applied immunology services and in conducting studies for biotherapeutics are notable. Preclinical Biosciences offers expertise in CNS disease, antibacterials, substance abuse, oncology, cardiovascular and other key therapeutic areas.

11 Experienced in the preclinical development of GTMPs The Preclinical Biosciences group is comprised of molecular and cellular biologists, immunologists and toxicology/pathology experts who are dedicated to projects related to the development of Gene Therapy Medicinal Products (GTMPs). The team can perform GLP studies for GTMPs that include integrated parallel toxicology/ pathology, efficacy and biodistribution studies, with flexible study plans to accelerate preclinical development. Before the release of the GTMP, quality tests on produced batches are performed, including: titer determination, pseudotyping identity (for viral vectors), residual DNA contamination, stability studies and transgene identity. A key component of GTMP development is quality control testing, including: Titer determination Pseudotyping identity (for viral vectors) Residual DNA contamination Stability studies Transgene identity 11

12 12 The Aptuit Center for Drug Discovery & Development Verona, Italy CMC Services, all under one roof in Verona Aptuit clients can rely on fully integrated Chemistry, Manufacturing & Control (CMC) services from the Verona site. Well established capabilities in Chemical Development and Manufacturing, Pharmaceutical Development, Analytical and Physical Science and Clinical Supply conjoin to make Aptuit the ideal CMC partner. The seamless integration of drug substance and drug product services, all performed under one roof in Verona, provides clients with a distinctive advantage: every aspect of their project is accomplished by a single, unified, collaborative team. Aptuit s CMC team takes the big picture approach in the development of both drug substance (API) and drug product. The broadened perspective of Integrated Knowledge enables scientists to address early findings that foresee potential issues that might surface later on in the process, avoiding or mitigating the risks of unexpected delays and costs.

13 Complementary Vision, a novel way to deliver services Aptuit has initiated a new way of delivering CMC services, known as Complementary Vision. This harmonized approach encompasses all of the services that precede and follow the CMC profile. Cost efficiency and time saving benefits through the design of the dosage form that best fits the preclinical/ clinical needs are the result of this novel approach. CMC clients can rely on a combination of in silico, in vitro and in vivo services. The results substantiate the design, development and selection of the most effective dosage form for the intended clinical use, throughout the application of biopharmaceutics from early to late development stages. A comprehensive review process is undertaken for generic drugs to meet up-to-date regulatory requirements. Expertise in API development and manufacturing ensures the timely delivery of the required quality of API to support both toxicological and clinical studies. Aptuit also provides the required analytical support, including method development and validation and batch release. Lean Six Sigma business processes are in place, helping to ensure total quality management. 13

14 14 The Aptuit Center for Drug Discovery & Development Verona, Italy Clinical Sciences: early understanding to maximize success From the onset, the Clinical Sciences group can partner with clients in the design of the most efficient clinical plans for the client s compound. And through innovative and custom tailored approaches, clients benefit from an early understanding of their compound s safety and efficacy profile, prior to First In Man studies. It s an advantage that results in valuable time and cost savings. A range of capabilities combine in a rapid decision making process for an early establishment of efficacy, acceptable safety and pharmacokinetic profile. They include the design, implementation and analysis of Positron Emission Tomography (PET) brain studies, human laboratory models, the adoption of advanced methodologies in modeling and simulation and translational medicine strategy.

15 A well established network of collaborative expertise Clinical Sciences experts are skilled in recommending and placing studies with imaging centers that are best suited to client projects. It s Aptuit s expertise in PK analysis and PK/PD correlation that allows for the objective interpretation of the resulting data to best investigate target enhancement in the living brain and to determine the time course. Clinical Science experts physicians, clinical pharmacologists, statisticians, pharmacokineticists, data managers, programmers, and study managers work together in the design, implementation, analysis and interpretation of healthy volunteer and patient studies in multiple therapeutic areas and across clinical phases. An established network of collaborative expertise is in place, with access to multiple Phase I Units and academic/clinical centers. Clients gain added confidence in Aptuit when learning that the Clinical Sciences group has successfully advanced more than 20 NCEs to FIM, conducted 15 Phase II clinical studies eight that have reached Proof of Concept. The group has implemented over 100 Clinical Pharmacology and Experimental Medicine studies. 15

16 16 The Aptuit Center for Drug Discovery & Development Verona, Italy Aptuit INDiGO, addressing today s challenges A significant solution to overcoming the time and cost challenges of drug development is Aptuit INDiGO. This accelerated development process uses integrated, parallel development tracks to advance API to regulatory submission in as few as 26 weeks. In just 52 weeks, compounds can progress from candidate selection to regulatory submission, a highly desirable alternative to the industry average of 122 weeks. By adding 30 additional weeks, Aptuit INDiGO takes the compound into the clinical phase and provides human safety, tolerability and pharmacokinetics results from First In Man studies. To date, Aptuit s multidisciplinary teams of experts have successfully implemented more than 60 Aptuit INDiGO packages across a wide range of therapeutic areas for small and large molecules, drug product changes, and post FIM and IP extension opportunities. Aptuit INDiGO can be customized to advance your molecule from candidate selection to FIM/POC studies World class preclinical safety/dmpk & solid state chemistry Quality-by-design principles applied in earliest stages Seamless data and knowledge integration throughout project Regulatory documentation preparation & Clinical Sciences Reduced service provider monitoring

17 Accelerated development, real time data When performed at The Aptuit Center for Drug Discovery & Development and other global sites, Aptuit INDiGO addresses other industry challenges by providing an integrated approach. The accelerated process overcomes the negative effects of dealing with multiple outsourcing companies or incurring difficulties created by inefficient handoff between multidisciplinary groups. Aptuit INDiGO also delivers a real time, high quality data package with interpretation in key development areas, not something that is commonly found when clients are working with other CROs. Optimized timelines are achieved by using integrated, parallel development tracks Industry average based on Tufts CSDD analysis: 122 weeks (Compared with Aptuit INDiGO 52 week package) As few as 26 weeks from API availability to Regulatory Submission As few as 52 weeks from Candidate Selection to Regulatory Submission Only 30 additional weeks from Regulatory Submission to FIM study report 17

18 18 The Aptuit Center for Drug Discovery & Development Verona, Italy Aptuit s global family of world class facilities Aptuit s facilities in Verona have made a substantial contribution to Aptuit s global family of worldwide centers of drug discovery and development. From seven strategically located sites around the world, including a strategic partner in India, Aptuit people serve more than 600 clients. This client base spans small companies that may not maintain in-house technical expertise to multinational companies who turn to The Aptuit Center for Drug Discovery & Development to outsource large, integrated projects. It is significant that Aptuit is involved in 20% of the 10,000 molecules that are under development at any given time. Harrisonville, Missouri West Lafayette, Indiana Oxford, England Glasgow, Scotland Aptuit Corporate Headquarters, Greenwich, Connecticut

19 Specialized capabilities at key locations In addition to providing fully integrated services from its Verona site, Aptuit offers specialized services from other facilities: n SSCI, a division of Aptuit, located in West Lafayette, Indiana, and recognized around the world for its solid state chemistry leadership n Aptuit s Glasgow, Scotland site, known for its sterile fill finish and formulation development for a range of dosage forms n API facilities in the United States and Europe, along with a strategic partner in India, feature strong competencies in API development and manufacture including process R&D, analytical and chemical development, preclinical and clinical supply, high potency APIs and cytotoxics, pilot manufacturing and commercial scale manufacturing Throughout this global enterprise, a synergy of collaborative expertise delivers related services that include consulting services from the industry s foremost regulatory and legal experts. These consummate professionals are among the many Aptuit people at global locations who bring their Heads for Science and Hearts for Service to create a streamlined drug discovery and development process for biotechnology and pharmaceutical innovators. Glasgow, UK Oxford, UK Verona, Italy Greenwich, CT West Lafayette, IN Harrisonville, MO 19

20 The Aptuit Center for Drug Discovery & Development Verona, Italy Via Alessandro Fleming Verona (VR) Italy For information about Aptuit s services, please contact us: in Europe: in the US: us at: expertise@aptuit.com The sculptures featured prominently throughout this brochure can be found in the lobby and building exterior of the Aptuit Verona facility. Created by Novello Finotti and Pino Castagna, they symbolize the felicitous union of the theory and practice of scientific research in the evolution of mankind. Sculpture by Novello Finotti and Pino Castagna, Grande Scorticato by Novello Finotti, APT/BRO/VERONASITE/12/12/V001