CED Tight Space Innovation Market Entry Avastin Glioblastoma Proposal

Pump for Convection Enhanced Delivery

Market Analysis Proposal

Company X: Product X Pump for CED 2 Market Analysis Proposal -‐ Confidential

November 29, 2010

Dear Richard, Per our conversations, Harrison Hayes has incorporated valuable feedback from Company X and is pleased to present this PRODUCT X Pump for Convection Enhanced Delivery (CED) Research Proposal.

In this proposal, we present a review of the objectives, scope, and qualitative market research of this project. We will also go into more detail regarding the qualitative research methodology that Harrison Hayes will utilize to obtain unique insights into building the business case for Local Organ Delivery using the PRODUCT X pump for CED. We are highly confident that our ideation methodology and insightful results will exceed your expectations. To complement our work on this project, Harrison Hayes will rely on a dynamic network of KILs (Key Innovation Leaders) who have deep domain expertise and are well respected in their specific disciplines. This assures that our research, ideation and points of view are of the highest value. We would like to thank you for considering Harrison Hayes as your business solution and look forward to a great working relationship. Sincerely, Bill Smith Managing Director Harrison Hayes, LLC Charlotte, NC


OBJECTIVES The primary objective of this research project is to assist Company X in establishing a clear, yet strategic, business case for Local Organ Delivery using the PRODUCT X pump for Convection Enhanced Delivery (CED). This research, while utilizing Harrison Hayes’ qualitative research methodology, will also help provide Company X with insights into identifying extensions of local and/or systemic CED applications. To obtain this data, Harrison Hayes will focus on the assessment in the following areas: The following includes a sample of areas of assessment:

• Build the business case for the intra-‐organ delivery PRODUCT X pump vs. systemic delivery

• Identify Advantages to a CED system in relation to traditional therapeutic approaches

• Identify the target market disease states to generate biggest revenue-‐accretive value of just the Glioblastoma segment and value based on the number of Glioblastomas in the marketplace

• Identify Emerging Markets by identifying worldwide countries to target based on economics and market size

• Determine the time interval for Fast Track of FDA approval of the novel device to expedite product launch

• Identify Benefits vs. High Cost-‐ $100 M goal

• Identify Competitors

• Identify Vendors to include all Pharma companies including Phase II and Phase III drugs that did not make it to market

• Evaluate Compliance and Regulatory Measures to include additional studies needed for FDA approval and extended uses

• Determine the extent that CED system can be extended to other medical offerings by identifying other disease states where small dose rates, over time, methods of treatment are present for future growth (i.e. non-‐brain tumor oncology, diabetes, endocrine, obesity, and/or autoimmune diseases)


BACKGROUND Because primary brain tumors treated with surgery, radiation therapy, and chemotherapy have a poor prognosis, this has led investigators to develop new innovative therapies such as targeted toxins. These large molecules do not cross the blood brain barrier and must be delivered into the brain by a technique known as Convection-‐enhanced delivery (CED). 1 CED is the continuous injection under positive pressure of a fluid containing a therapeutic agent. This technique was proposed and introduced by researchers from the US National Institutes of Health (NIH) in the early 1990s to deliver drugs that would otherwise not cross the blood-‐brain barrier into the parenchyma and that would be too large to diffuse effectively over the required distances where they simply deposited into the tissue. Despite the many years that have elapsed, this technique remains experimental because of both the absence of approved drugs for intraparenchymal delivery and the difficulty of guaranteed delivery to delineated regions of the brain. During the first decade after the NIH researchers founded this analytical model of drug distribution, the results of several computer simulations that had been conducted according to more realistic assumptions were also published, revealing encouraging results. In the late 1990s, one of the authors of the present paper proposed the development of a computer model that would predict the distribution specific to a particular patient (brain) based on obtainable data from radiological images. Several key developments in imaging technology, and in particular, the relationships between image-‐obtained quantities and other parameters that enter models of the CED process have been required to implement this model. Note that delivery devices need further development.2 Advantages A potential advantage of the CED system is the ability of the agent to reach cells that have invaded the peritumoral region and beyond, making it possible to offer hope of significantly reducing the spread of the disease. For large molecules having a 50,000-‐D or greater mass, the diffusive spread will often extend less than 1 mm in a day and only that large if metabolic and other loss mechanisms do not flush it from the parenchyma. The flow of such a fluid co-‐injected with a drug can carry such molecules much farther, however, and in certain idealized scenarios can fill the intervening region with a full concentration of drug per unit of available volume. Volume of Distribution Diffusive spread results in exponentially decreasing concentrations away from a source. When administering these agents, there are a number of pharmacokinetic considerations that must be considered that will directly affect the volume of distribution of the drug being administered and ultimately the therapeutic effect of the agent. A number of different catheter types have been used to perform CED with a hollow fiber design offering several advantages over other variations. Specific parameters have been developed to optimize the placement of the drug delivery catheters in order to enhance drug distribution in the brain. Considerable effort has been expended to identify a reliable way to image the distribution of targeted toxins administered by CED using a combination of magnetic resonance imaging and single photon emission computed tomography. Unfortunately, many infusions performed in tumor patients are unsuccessful due to ventricular/subarachnoid leak or pooling of the drug in necrotic tumor tissue. To date, no targeted toxin clinical trial has demonstrated statistically significant clinical results leading to the universal acceptance of this treatment. Other agents such as standard chemotherapy or liposomal

1 Hall WA. Convection-‐Enhanced Delivery: Neurological Issues. Current Drug Targets. 2009;10(2):126-‐30(5). 2 Raghavan R, Brady ML, et al. Convection-‐Enhanced Delivery of Therapeutics for Brain Disease, and Its Optimization. Neurosurg Focus. 2 Raghavan R, Brady ML, et al. Convection-‐Enhanced Delivery of Therapeutics for Brain Disease, and Its Optimization. Neurosurg Focus. 2006;20(4):E12.


preparations have been delivered by CED. Non-‐neoplastic neurological diseases are being considered for treatment by CED and treating different locations of the brain other than the cerebral hemispheres are under investigation. Relevant Research Studies In 2005, Peregrine Pharmaceuticals Inc. developed Cotara, a monoclonal antibody specific for tumor necrosis factor (TNF) linked to radioactive iodine 131. It was designed to target TNF associated with dead or dying tissue usually found inside tumors. Once the conjugate is attached to the TNF, the radioactive isotope kills neighboring cells. Peregrine received regulatory approval in India in 2006 for a new clinical trial of the candidate in Glioblastoma multiforme, a deadly form of brain cancer. The goal of the trial was to provide clinical data that could be combined with the dosimetry and safety data being gathered from the ongoing US study to speed up clinical and commercial development of the agent. The study enrolled 40 Glioblastoma patients who had experienced their first relapse. They were given a single infusion of Cotara directly into the brain tumor, using a CED system. Primary endpoints were to confirm safety and determine median survival time and median time to progression. In 2006, NeoPharm Inc. conducted a Phase III clinical trial of its cintredekin besudotox (IL13-‐PE38QQR) candidate for treating recurrent Glioblastoma multiforme (GBM). Sandeep Kunwar of the University of California at San Francisco (UCSF) presented updated results of Phase I/II studies and results from a Phase I/II subset analysis at the 74th Annual Meeting of the American Association of Neurological Surgeons in San Francisco on April 24, 2006. The data showed that GBM patients in the trials continued to experience prolonged survival. The candidate was a conjugate of interleukin-‐13 (IL-‐13) and a truncated form of Pseudomonas bacterial exotoxin. The IL-‐3 portion of the recombinant protein targets the molecule to cancer cells, which the toxin kills. Updated data for the 45 GBM patients treated in the Phase I/II intraparenchymal setting showed an overall median survival time of 44.0 weeks, with survival increasing to 53.6 weeks for the 26 patients with two or more optimally placed catheters. Also, in a long-‐term follow-‐up Phase I study 22 GBM patients treated with cintredekin besudotox via convection enhanced delivery had a median survival of more than one year (57.4 weeks). Sixteen of these patients with two or more optimally placed catheters had a median survival of 69.9 weeks. In addition, four patients at UCSF remain alive with a median follow-‐up of more than three and half years (188 weeks), including one patient with a follow-‐up of almost five years (244 weeks) who is still progression free. An independent statistical analysis of the Phase I/II data confirmed that catheter placement was a key prognostic factor related to prolonged survival. Information from these trials was incorporated into the design of the pivotal Phase III trial. Being able to comprehend intracranial conditions is critical to patients who have had traumatic brain injury (TBI). Parameters that are typically monitored in TBI patients include blood pressure, intracranial pressure, local brain tissue oxygen tension, and jugular venous oxygen saturation. Even in advanced institutions, other physiological metrics (brain glucose, lactate, pyruvate, and pH) that are prone to affect patient outcomes are usually monitored intermittently. A new development at the University of Cincinnati promises to shed more light on the brain by means of a ‘lab-‐on-‐a-‐tube’ (LOT) device. This device is capable of draining cerebrospinal fluid (CSF) during the process of monitoring parameters such as pressure, oxygen content, temperature, and glucose within the intracranial space. This LOT has several benefits over current brain monitoring techniques, including low invasiveness as it requires only one hole to be drilled into the skull. Next, the tube’s diameter can be contracted or expanded to adjust to intracranial and intravascular locations and helps mitigate trauma associated with existing techniques. The spirally-‐rolled microchannels


enable in vivo calibration of the biosensors with the added advantage of allowing convection-‐enhanced and targeted drug delivery. PRODUCT X Pump The PRODUCT X Pump was developed by Company X in 2008 as a new alternative for intra-‐organ CED of active agents, specifically in-‐brain drug delivery for patients with Glioblastoma. The goal of the PRODUCT X Pump is to demonstrate feasibility and therapeutic interest of a microfluidic injection module for low flow and low pressure delivery of an active agent in the cerebral tissue through an intraparenchymal catheter. Initial evaluation of therapeutic performance was on an experimental pathological animal model (swine with Glioblastoma). Company X has partnered with CEA-‐Leti, INSERM, Vetagro Sup, and Tronics for the animal studies. The PRODUCT X Pump implements a micropump-‐based fluidic module (MEMS) technology, a chip made from 2 bonded silicon wafers, assembled with piezo-‐electric ceramic for actuation. The pump itself is slim (3x1 cm2), ultra light (0.5g), flexible (up to 100µl/min, resolution 200 nl), has a viscosity compatibility up to 10 cps, and a flow rate stable on a wide range of inlet and outlet pressure (up to +/-‐ 250mbar). It is biocompatible -‐ the drug is in contact with silicon oxide (glass) and the fluidic interface is made of biocompatible polymer and UV-‐cured glue. The intra-‐organ delivery offered by the PRODUCT X Pump is desirable over systemic delivery because of lower peripheral drug concentration, leading to decreased systemic toxicity and side effects. This poses the potential for increased or decreased dosages, as needed. CED has the ability to overcome intratumoral pressure, eliminating backflow and tissue resistance, resulting in higher intratumoral and peritumoral active agent concentrations. The continuous positive pressure infusion allows treatment of larger tumor volume. On site back-‐pressure measurement is thought to enable on site localization of catheter tip, possibility to have real-‐time follow-‐up of infusion, and the capability to detect infusion issues and/or overpressure inside the tumor. Local CED is an important development in treating primary or metastatic brain tumors because the blood/brain barrier cannot be overcome by most molecules delivered systemically. There is currently no successful treatment. Higher local concentrations of active principles can induce stronger therapeutic effects (i.e. tumor stabilization or regression); local delivery means lower peripheral concentration/less detrimental side effects as compared to systemic delivery. Glioblastoma is the current target for PRODUCT X Pump utilization. This type of tumor has a nearly 100% fatal prognosis. The average life expectancy after diagnosis is less than 1 year due to its infiltrative nature and high proliferation/growth/recurrence rates. There is no known curative treatment and it has not been properly addressed by traditional treatments (i.e. surgery, radiotherapy, chemotherapy). While Glioblastoma is the main focus for the PRODUCT X Pump, there are many extensions of local/systemic CED in other therapeutic areas that are worth exploring (See Appendix). One important emerging targeted therapy is Roche’s monoclonal antibody, Avastin, which was recently withdrawn by the FDA due to toxic side effects. The PRODUCT X Pump offers hope to therapies such as Avastin, as it offers a new delivery method that may allow patients exposure to the full concentration of the active agent while minimizing exposure to the toxic side effects.


PROJECT SCOPE It is our understanding that Company X would like an independent review of

market entry and expansion options for its intra-‐organ convection-‐enhanced delivery (CED) of active agents, intended for in-‐brain delivery for the treatment of Glioblastoma. Harrison Hayes will provide an in-‐depth market analysis into this area including identification and assessment of market entry, impact and expansion, barriers and inhibitors into market entry, acceptance, and penetration; market transition; adoption drivers and inhibitors, and potential for adoption; life cycle management; competitive intelligence and reaction; economic impact; reimbursement issues including pricing elasticity and reaction; and make specific recommendations as to mechanisms to improve Company X’s value generation from this product.

METHODOLOGY Primary Research Harrison Hayes proposes to begin the project by meeting with the Company

X project team to conduct due diligence and review currently available research. The purpose of this meeting is to verify the scope of the assignment, answer questions, and review the timeline. Harrison Hayes actively engages our clients in collaborative, interactive dialogue throughout the project. We suggest weekly meetings to review and assess the direction and progress of the project.

Primary research for this project will be divided into two (2) modules. Module I will be comprised of a panel of Key Innovation Leaders (KILs) and Module II will consist of a Voice of the Customer (VOC) survey. These two primary, qualitative Research Modules will serve as the foundation of the project as a whole and best allow Harrison Hayes to fulfill the project’s objectives.

METHODOLOGY Module I

Research Module I will begin by identifying and recruiting a customized panel of Key Innovation Leaders (KILs) (Table 1) and developing a project specific study guide/questionnaire. The Key Innovation Leader (KIL) questionnaire will be developed through a collaborative effort with Company X in order to ensure that the focus of this project is being addressed. The questionnaire is to be used as a platform for exploration and discussion. All interviews will be conducted directly by Harrison Hayes’ Principals and Research Team who have the autonomy to probe deeper and maneuver through unique issues that arise during discussion with the KILs – what we refer to as improvisational interviewing. Our Research Team is able to select the most appropriate questions to ask each KIL due to our extensive knowledge and involvement with the project’s goals. These interviews are conducted individually, which allows us to focus directly on the expertise that each KIL possesses. Improvisational interviewing yields valuable qualitative interview data unlike structured interview surveys. Instead of merely moving from question to question, our Research Team is


able to adapt based on KILs’ response to questions, thus obtaining additional insight. To complement our Primary Qualitative KIL research we will concurrently perform secondary research from syndicated, internal, and public sources. We believe secondary research will provide us with useful data regarding the identification and assessment of barriers to market entry and expansion including competitive reaction, risks of cannibalization, and reimbursement issues. We will also look to uncover social (e.g., regulatory policy changes) and economic trends. Our Secondary Research Methodology and its role in the project’s outcome are discussed in further detail below. Harrison Hayes believes that through the effective marrying of primary KIL insight and secondary research – along with our partnership with the Company X project team – we can obtain uncommon insight into the potential for tactical market entry and expansion within the CED space.

Examples of Key Innovation Leaders (KILs)

• Health Care Providers (e.g. Oncologists, Internists, etc.) • Public Health and Forecasting Experts • Public Health Law and Policy Experts • Regulatory Experts • Managed Care Experts • Medical Reimbursement Experts • Medical Insurance Experts • Academic Researchers and Experts in Personalized Medicine and

Healthcare • Academic Researchers and Experts in Oncology

Examples of Potential Questions for Selected Key Innovation Leaders (KILs)

1.) What applications or disease states would benefit most to utilize a

Product X pump?

2.) What are the advantages to the CED system?

3.) Will intracranial infusion become the treatment of choice for intracranial tumors?

4.) Will Nanotechnology allow for the segregation of tumors from systemic circulation to reduce exposure of chemotherapy and thus, side effects?

5.) How safe is the product?

6.) What are the possible side effects?

7.) How will infections be prevented from the indwelling catheter?


8.) Will using host specific stem cells translate to treating cancer in the host?

9.) How do you monitor therapeutic effect and measure “real-‐time”

therapy?

10.) What will be the effects of CED placement regarding pain, length of stay?

11.) Will CED treatment be inpatient or outpatient?

12.) How would you prove a lower drug concentration is possible?

13.) Would a lower drug concentration decrease systemic toxicity?

14.) What is the predicted success rate?

15.) How do you monitor regression of tumor or remission?

16.) Can this be game changing for all future treatments of tumors?

17.) What will be the impact of selective gene therapy on CED’s?

18.) How will stem cells impact the treatment of cancer?

19.) How will stem cells impact other disorders?

20.) How do you overcome hurdles to high cost?

21.) What is the price point to make a profit?

22.) How do you get “buy-‐in” from surgeons?

23.) How will Oncologists feel about this type of treatment?

24.) What types of Vendors do you use?

25.) What are the targeted countries to launch the product?

26.) What does the clinical data show in humans?

27.) What are the regulatory issues with nanoscaffolds?

28.) Will the FDA approve a Fast Track application for Glioblastoma due

to the severe outcome and limited effective treatment options?


Table 1: Examples of Key Innovation Leaders

Person's Name Title/Expertise

Amy Achter Director Corporate Innovation, Kimberly Clark.

Andrea S. Hunt Vice President of Innovation and Strategic Initiatives, Baxter.

Andreas A. Linninger

Professor at University of Illinois at Chicago; Department of Bioengineering and Chemical Engineering. Author of "Prediction of convection-‐enhanced drug delivery to the human brain."

Andrew N. Pollak, MD Chief of Orthopaedic Traumatology and Associate Director of Trauma at the R Adams Cowley Shock Trauma Center, University of Maryland Medical Center

Antonio Fioravanti, PhD

Department of Neurosurgery, Bellaria-‐Maggiore Hospital, Azienda USL of Bologna, Italy and author of "Treatment Options for Recurrent Glioblastoma: Pitfalls and Future Trends."

Ariel Gilert, PhD

Faculty of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa, Israel. Author of "Nano to micro delivery systems: targeting angiogenesis in brain tumors."

Arun Bhatia Sr. Manager, Marketing and Corporate R&D Innovation at Baxter Healthcare.

Bakhtiar Yamini, MD

Dr. Bakhtiar Yamini specializes in neuro-‐oncology, and he is an expert in minimally invasive neurosurgery for children and adults. This includes using sophisticated stereotactic techniques that allow for three-‐dimensional surgical planning. Dr. Yamini also has a strong interest in vascular neurosurgery and spine surgery at the University of Chicago Medical Center.

Becky Walter Director Innovation Design and Testing, Kimberly Clark.

Brad A. Ward, MD

Dr. Ward is a board-‐certified neurosurgeon who has extensive experience in the treatment of disorders of the brain, spine and peripheral nerves. He is in private practice at The Center for Orthopedic and Neurosurgical Care and Research in Bend, Oregon. Currently serving as this organization's president.

Catherine G. Hawthorne, MD President of Orthopaedic Rehabilitation Association.

Catherine Jacobson

(Rush University Medical Center, Chicago, Ill.). Ms. Jacobson is CFO and treasurer at Rush University Medical Center in Chicago. Ms. Jacobson, whose career at Rush began in 1996, previously served as vice president for program evaluation, assistant to the president and chief compliance officer for Rush before being named acting CFO in 2002.

Charles-‐Marc Samama, MD, PhD

Professor and Chairman in the Department of Anaesthesiology and Intensive Care of the Hotel-‐Dieu University Hospital in Paris, France. He is board certified to practice anaesthesiology and intensive care medicine.

Ching-‐iao Tsai, MD Professor, Neurological Institute, Taipei Veterans General Hospital and National Yang-‐Ming University, Taiwan. Delegate of The World Federation of Neurology.

Christopher T. Born, MD Chief of Orthopedic Trauma at Rhode Island Hospital within the Department of Orthopaedic Surgery of Brown University.

Claude Ecoffey, MD Department of Anesthesiology and Surgical Intensive Care, Bicetre Hospital, Le Kremlin Bicetre, France.



Claudette Yasell

President of the American Brain Tumor Association. A certified medical editor and writer and active member of the American Medical Writer’s Association, Yasell’s professional career reflects her passion for communication and medicine.

Colleen Blye

(Catholic Health Initiatives, Denver). Ms. Blye was named senior vice president of finance and treasury and CFO in January for 78-‐hospital CHI. Ms. Blye joined CHI in 1989 and previously served as vice president of financial services. Before that she was CFO for St. Joseph Medical Center in Reading, Pa. Her first job in healthcare finance was as an auditor with Ernst & Young in Philadelphia.

D. David Glass, MD Chair, Foundation for Anesthesia Education and Research.

Darell D. Bigner, MD, PhD

He is the Edwin L. Jones, Jr. and Lucille Finch Jones Cancer Research Professor, Director of the Preston Robert Tisch Brain Tumor Center at Duke, and Director of the Pediatric Brain Tumor Foundation Institute at Duke. Dr. Bigner is also Co-‐Program Leader of the Duke Comprehensive Cancer Center’s Neuro-‐Oncology Program, Vice-‐Chairman of Investigative Pathology, Director of the Preuss Laboratory for Brain Tumor Research, Editor-‐in-‐Chief of the Journal of Neuro-‐Oncology, and Chairman of the Scientific Review Board of the National Cancer Center, the Brain Tumor Society, and the Pediatric Brain Tumor Foundation.

David A. Reardona, MD

Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, and author of "Therapeutic Advances in the Treatment of Glioblastoma: Rationale and Potential Role of Targeted Agents."

David N. Louis, MD

Pathologist-‐in-‐Chief-‐Massachusetts General Hospital. Dr. Louis' own pathology practice and research focuses on brain tumors, with an emphasis on the application of molecular diagnostics to glioma classification. He has contributed over 300 original articles, reviews and chapters to the literature. His laboratory was the first to demonstrate that molecular approaches could subdivide malignant gliomas biologically and that molecular approaches could predict the response of malignant gliomas to therapies.

Dawn Houghton Senior Director Corporate Innovation at Kimberly-‐Clark.

Dean G. Sotereanos, MD

Co-‐Director, Hand and Upper Extremity Surgery Fellowship; Vice Chairman, Orthopaedic Network Development; Professor of Orthopaedic Surgery. Member of more than a dozen professional and scientific societies and has served on many of their national committees for educational and research activities. He is internationally renowned as an upper extremity surgeon and currently focuses on the hand, elbow and shoulder.

Donald D. Trunkey, MD Professor of Surgery, Section of Trauma/Critical Care, Oregon Health & Science University and Chair of The American Association for the Surgery of Trauma.

Doug Dietz Industrial designer / Global Design at GE Healthcare.

Douglas W. Laske, MD

Douglas W. Laske, MD works at Fox Chase Cancer Center as a member of the Fox Chase Temple: Neuro-‐Oncology Program. Author of "Convection-‐enhanced delivery of macromolecules in the brain" article. He is one of the inventors of and has a patent on Convection-‐enhanced drug delivery.



Ángel Rubio, MD

Full Professor of Condensed Matter Physics, Nano Bio Spectroscopy Group, Dpt. F´ısica de Materiales, Facultad de Qu´ımicas and Centro F´ısica de Materiales CSIC-‐UPV/EHU, leading expert in the treatment of Glioblastoma Multiforme.

Gregory I. Bain, MD, PhD

He exclusively practices upper limb surgery. He is a member of the Australian Hand Surgery Society, the Australian Shoulder and Elbow Society and the Australian Sports Medicine Federation as well as a number of International Associations.

E. .I Gusev, MD Resident of the Russian Society of Neurologists, Department of Neurology, Russian State Medical University, Moscow, Russia.

E. Antonio Chiocca, MD, PhD

Professor of Neurosurgery, Chairman, Department of Neurosurgery, Dardinger Family Endowed Chair in Oncological Neurosurgery, James Cancer Center & Solove Research Institute, Ohio State University Medical Center.

Edward H. Oldfield, MD

He joined the Department of Neurosurgery at the University of Virginia in 2007 where he leads a multidisciplinary effort in the treatment of pituitary tumors and contributes to the research program in the Department of Neurosurgery. He holds the Crutchfield Chair in Neurosurgery and is a Professor of Neurosurgery and Internal Medicine.

Enrico Franceschi

Department of Medical Oncology, Bellaria-‐Maggiore Hospital, Azienda USL of Bologna, Italy and author of "Treatment Options for Recurrent Glioblastoma: Pitfalls and Future Trends."

Eric C. Holland, MD, PhD

Vice Chair, Translational Research, Department of Neurosurgery Director, Brain Tumor Center, Emily Tow Jackson Chair in Oncology, Memorial Sloan Kettering Cancer Center.

Erik Kemper Interaction & User Centered Designer / Global Design, GE Healthcare.

Ernest B Marsolais, MD Fellow of the American Academy of Orthopaedic Surgeons. Computerworld Smithsonian Science Award in Medicine presented June 6, 1994, Washington, D.C.

Erwin Van Meir, PhD Professor of Neurosurgery, Hematology and Medical Oncology, Emory University Winship Cancer Institute.

Fred H. Hochberg, MD Associate Professor, Department of Neurology, Massachusetts General Hospital.

G. Yancey Gillespie, PhD Professor of Surgery, Microbiology, Cell Biology, University of Alabama at Birmingham.

Giorgio Ivani, MD

Chairman, Division Pediatric Anesthesiology and Intensive Care, Regina Margherita Children's Hospital, Italy. Past President of The European Society of Regional Anesthesia and Pain Therapy.

Helmut Trimmel, MD Director, Department for Anesthesiology, Emergency Medicine and Intensive Care General Hospital of Wiener Neustadt, Austria.

Henry S. Friedman, MD

Deputy Director, The Preston Robert Tisch Brain Tumor Center at Duke. Henry S. Friedman, MD, is an internationally recognized neuro-‐oncologist with a career-‐long interest in the treatment of children and adults with brain and spinal cord tumors. He has written hundreds of articles on both the clinical and laboratory investigation of these neoplasms.



Hideo Yamamura M.D., Ph.D., F.R,C.A., F.I.C.A.E.

Prof. Emeritus, School of Medicine, Tokyo University; Former President, All Japanese Acupuncture Associations; Former Dean, School of Medicine, Tokyo University; Former Chairman, Dept. of Anesthesiology, School of Medicine, Tokyo University, Japan.

Hiroshi Ueda, PhD Professor, Division of Molecular Pharmacology and Neuroscience Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Howard Fine, MD Chief of the neuro-‐oncology branch at the NCI’s Center for Cancer Research. He has treated Glioblastoma for 22 years.

Hugo van Aken, MD

Chairperson of the National Anaesthesiology Societies Committee, professor and chairman of the Department of Anaesthesiology and Intensive Care Medicine, University Hospital Westfälische Wilhelms-‐Universität Münster/Germany. Editor-‐in-‐Chief for Current Opinion in Anaesthesiology and Editor for Baillière's Best Practice in Research and Anaesthesiology.

Issam A. Awad, MD

Isaam has expertise in neurosurgery. He is skilled in the surgical management of neurovascular conditions affecting the brain and spinal cord, including cerebral aneurysms, cerebrovascular malformations, and hemorrhagic stroke and skull base tumors at the University of Chicago Medical Center.

J. Tracy Watson, MD Professor, Orthopaedic Traumatology, Fellowship Director and Chief of the Orthopaedic Traumatology Division

James Ausman, MD, PhD

Expert in cerebrovascular diseases, complex neurosurgical problems and microsurgery. Physician of Neurological surgery at Ronald Regan UCLA Medical Center.

James B. Powell Jr., MD Professor of Neuro-‐Oncology at Duke University.

James P. Stannard, MD Chair of the Department of Orthopaedic Surgery, J. Vernon Luck Sr. Distinguished Professor in Orthopaedic Surgery at University of Missouri Health System.

Jan C. Buckner, MD Professor of Oncology, Chair, Division of Medical Oncology, Mayo Clinic, author of "Evolving Therapeutic Concepts in Glioblastoma: Augmenting Chemoradiation."

Jasti Sambasiva Rao, PhD Head, Department of Cancer Biology & Pharmacology at University of Illinois College of Medicine at Peoria (UICOM-‐P).

Jeffrey N. Bruce, MD, FACS Director, Bartoli Brain Tumor Research Laboratory, Co-‐Director, Brain Tumor Center Columbia University College of Physicians and Surgeons.

José De Andrés, MD, PhD

Associate Professor of Anesthesia, Valencia University Medical School; Chairman, Department of Anesthesiology and Critical Care; Director of the Multidisciplinary Pain Management Center.

K. Y. Mok, MD Treasurer of The Hong Kong Neurological Society, Department of Medicine-‐Ruttonjee Hospital, Hong Kong.

Kathleen Lamborn, MD

Adjunct Professor Emeritus of Neurological Surgery. Principal Investigator, Brain Tumor Research Center. Dr. Lamborn, a biostatistician, works with Brain Tumor Research Center (BTRC) investigators and trainees in the design and analysis of BTRC research studies.

Katie Szyman Senior Vice President-‐Strategy and Innovation, Medtronic.

Kenneth D. Aldape, MD Professor of Pathology, Division of Pathology and Laboratory Medicine at UTMD Anderson Cancer Center.



Kevin Brennan

(Geisinger Health System, Danville, Pa.). Mr. Brennan is executive Vice President and CFO at Geisinger and is treasurer of the Geisinger Foundation. Mr. Brennan previously served as CFO of the Penn State Geisinger Health System and, before joining Geisinger, as regional vice president of finance and vice president of managed care with the Franciscan Health System with responsibilities covering eight hospitals and affiliates in its Mid-‐Atlantic Region.

Kim (Guenther) Menard

Senior Medical Communications Officer at the University of Pennsylvania School of Medicine. Kim joined Penn Medicine following nearly four years in the healthcare practice of a leading public relations agency in Chicago, where she specialized in a range of therapeutic areas, including oncology, hematology, neurology, infectious diseases and pediatric obesity. She has broad experience in media and advocacy relations and led medical communications surrounding numerous data publications, medical meeting presentations, and regulatory announcements.

Krystof Bankiewicz, MD, PhD

Currently professor in the Neurosurgery and Neurology Departments at UCSF (San Francisco, CA). Throughout his career, he has maintained a strong focus on the development of practical approaches to gene and cell replacement therapies, and has displayed a remarkable ability to synthesize several individual technologies into powerful new approaches to the treatment of such serious disease as brain cancer and neurodegenerative disorders of the brain, including Parkinson's disease.

Linda M. Liau, MD, PhD Researcher at Jonsson Comprehensive Cancer Center at UCLA.

Maciej S. Lesniak, MD, MHCM

Dr. Maciej Lesniak is one of the nation’s leading experts in neuro-‐oncology. Dr. Lesniak is the director of neurosurgical oncology and neuro-‐oncology research in the University of Chicago Brain Tumor Center. He is the professor of Surgery and Director of Neuro-‐oncology Research at the University of Chicago Medical Center.

Mahadevabharath R Somayaji, PhD

Dr. Mahadevabharath R. Somayaji received his PhD degree in Chemical Engineering in 2008 from University of Illinois at Chicago. The focus of his doctoral research was in the development of a novel computational platform for predicting drug distribution in the human brain and optimal design of personalized brain drug delivery. Author of "Prediction of convection-‐enhanced drug delivery to the human brain."

Marc Van de Velde, MD, PhD President of The European Society of Regional Anaesthesia and Pain Therapy, Department of Anesthesiology, UZ Leuven, Belgium.

Marcelle Machluf, PhD

Faculty of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa, Israel. Author of "Nano to micro delivery systems: targeting angiogenesis in brain tumors."

Martin Tramèr, PhD Editor-‐In-‐Chief, European Journal of Anaesthesiology.

Maurizio Solca, MD

Anaesthesia and Intensive Care Medicine, Azienda Ospedaliera de Melegnano, Presi Sul Naviglio, Ospedale"A. Ubedlo", Cernusco sul Naviglio, Italy and Council Member of the European Society of Anaesthesiology.



Michael Andrew Rogawski PhD

Professor and chairman of the Department of Neurology at the University of California, Davis School of Medicine. Inventor of Apparatus and Methods for Treating Epilepsy Using Convection-‐Enhanced Delivery. He is a member of the editorial boards of Molecular Pharmacology, CNS Neuroscience & Therapeutics, Current Neuropharmacology, BMC Pharmacology, and Cellular and Molecular Neurobiology. He is executive editor of Neuropharmacology; co-‐editor of Epilepsy Currents, the official journal of the American Epilepsy Society; and associate editor of Neurotherapeutics, the journal of the Americans.

Michael Blaszyk

Catholic Healthcare West, San Francisco. Mr. Blaszyk is executive vice president and CFO for CHW. Mr. Blaszyk, who has 30 years of healthcare experience, provides financial oversight for more than $10.6 billion in annual spending. Prior to joining the system, he was senior vice president and CFO at University Hospitals Health System in Cleveland and before that he served as managing partner of the Northeast Region Health Care Provider Consulting Practice for William Mercer and as executive vice president of Boston Medical Center.

Michael D. Prados, MD

Director of the Department's Translational Research Program, Dr. Prados has over 20 years' experience at UCSF in treating and supervising the treatment of both adults and children who have brain tumors. The National Cancer Institute's North American Brain Tumor Consortium, which sponsors trials of treatment regimens for brain tumors, is based at UCSF under Dr. Prados' leadership, and he is principal investigator of the Pediatric Brain Tumor Consortium site at UCSF.

Michael Hüpfl, MD

Chief Physician, St. John Ambulance Service Vienna, Medical University of Vienna, Department of Anaesthesiology Intensive Care and Pain Medicine Austria.

Michael L.J. Apuzzo, MD

Michael L.J. Apuzzo is the Jr. Professor of Neurological Surgery and Radiation Oncology, Biology, and Physics at the Keck School of Medicine of USC. He is director of neurosurgery at the USC Kenneth Norris, Jr. Cancer Hospital and is director of the Center for Stereotactic Neurosurgery and Associated Research there. Apuzzo established one of the world's first central nervous system tumor immunology laboratories and simultaneously developed programs for the study of refinements of microsurgical techniques of intra-‐ and trans cerebral surgeries for the management of intracranial neoplasms.

Michael Weller, MD

Department of Neurology-‐University Hospital Zurich. Development of novel approaches of immunotherapy for malignant brain tumors; Definition of resistance mechanisms of cancer stem cells to irradiation and chemotherapy; Initiation and conduct of clinical trials in Neuro-‐Oncology

Mitchel S. Berger MD

Professor and Chairman, Department of Neurological Surgery; Director, Brain Tumor Surgery Program; Director, Neurosurgical Research Centers, Brain Tumor Research Center. Dr. Berger's main clinical interests are the treatment of brain and spinal cord tumors in adults and children and of epilepsy related to brain tumors. Dr. Berger is Director of the Adult Hydrocephalus and Shunt Program, and he also practices in the Neuro-‐Oncology Program and the Radiosurgery Program.



Nicholas Peppas, PhD

Director of Departments of Chemical Engineering and Biomedical Engineering, and Division of Pharmaceutics at University of Texas at Austin. Nicholas Peppas was the recipient of the 2010 Acta Biomaterialia Gold Medal Award, one of the most prestigious awards in biomaterials science recognizing “excellence in research and development”. He was elected President of the Biomedical Engineering Council of Chairs.

Nicolás Samprón, MD Specialist in Neurosurgery at The Hospital Universitario Donostia and has incorporated a new Glioblastoma multiforme treatment protocol.

Paolo Pelosi, MD, PhD

Associate Professor in Anesthesia and Intensive Care, Universita' dell'Insubria Varese Italy -‐ Visiting Professor at University of Aachen and President of the European Society of Anaesthesiology.

Patrick Y. Wen, MD

Center for Neuro-‐Oncology, Dana Farber/Brigham and Women’s Cancer Center, Boston and author of "Therapeutic Advances in the Treatment of Glioblastoma: Rationale and Potential Role of Targeted Agents"

Paul Borron Business Development -‐ Biochemist & Immunologist at RTI Health Solutions. Grant Reviewer at National Institutes of Health.

Paul R. Knight III, M.D., Ph.D. Chair, American Society of Anesthesiologist Committee on Research.

Peter C. Burger, MD Professor of Pathology; Professor of Neurological Surgery; Professor of Oncology; Pathology Department at John Hopkins Hospital.

Peter M. Black, M.D., Ph.D.

Dr. Peter Black has been Neurosurgeon-‐in-‐Chief at both the Brigham and Women's Hospital and the Children's Hospital since 1987. He is also the Franc D. Ingraham Professor of Neurosurgery at Harvard Medical School.

Phyllis Lantos

(New York-‐Presbyterian Hospital, New York City, N.Y.). Ms. Lantos is executive vice president, treasurer and CFO at New York-‐Presbyterian Hospital. Ms. Lantos joined the system in 2000 as senior vice president and CFO and was named executive vice president in 2007. She previously served as deputy chief operating officer at Yale University School of Medicine and as vice president of financial management services at Montefiore Medical Center. Ms. Lantos earned both her undergraduate and master’s degrees from the Massachusetts Institute of Technology.

Mahmoud Hafez, MD

Dr. Mahmoud Hafez the head of the Orthopaedic Unit at October 6 University, Egypt. He has a track record in research with more than 35 international publications including 11 book chapters.

Raymond Sawaya, MD

Dr. Raymond Sawaya has been the Chairman of the Department of Neurosurgery at the University of Texas M. D. Anderson Cancer Center in Houston since the department was established in 1990. He also serves as the Director of the Brain Tumor Center at M. D. Anderson and since 2005 has served as Professor and Chairman, Department of Neurosurgery, at Baylor College of Medicine. Dr. Sawaya is the recipient of numerous awards, including the Anne C. Brooks & Anthony D. Bullock, III, Distinguished Chair in Neurosurgery.

Raymond Tak-‐Fai Cheung, MD Delegate of the World Federation of Neurology, University Department of Medicine, Queen Mary Hospital, Hong Kong.



Ricardo Díez Valle, PhD

Department of Neurosurgery, The Department of Neurosurgery at Clínica Universidad de Navarra. The use of a fluorescence microscope enabled one of the most aggressive types of brain tumor to be completely removed in 83% of the cases, according to the results obtained in a series of patients with Glioblastoma that were treated by the Clínica’s neurosurgeons, the conclusions of which have been published in the Journal of Neuro-‐Oncology.

Richard Kdolsky, MD Associate Professor of the Department for Trauma Surgery in the Medical University of Vienna, Austria.

Richard Rothberger

(Scripps Health, San Diego). Mr. Rothberger, who has logged 30 years of healthcare financial experience, is corporate executive vice president and CFO for Scripps, a position he assumed in 2001.

Robert A. Probe, MD Chair, Department of Orthopedic Surgery, Director, Division Orthopaedic Trauma at Scott and White Healthcare.

Robert Sneyd, MD, MA, MB, Bchi,r FRCA

Vice-‐Dean and Professor of Anaesthesia at Peninsula College of Medicine and Dentistry based in Plymouth within the UK. Elected Consultant Member of The Royal College of Anaesthetists.

Russell Lonser, MD

He is Chair of the Surgical Neurology Branch in NINDS and Program Director for the NINDS Neurological Surgery Residency Training Program. His laboratory studies drug delivery for treatment of neurologic disorders, as well as investigates tumor biology and treatment.

Sarah J. Nelson, PhD

Margaret Hart Surbeck Distinguished Professor, Department of Radiology and Biomedical Imaging, Co-‐Chair, Department of Bioengineering and Therapeutic Sciences. Director, Center for Non-‐Invasive Imaging and Metabolomics and the Surbeck Laboratory of Advanced Imaging, University of California, San Francisco.

Sergey A. Klyushnikov, MD Institute of Neurology, Dept. of Neurogenetics, Russian Academy of Medical Sciences, Russia.

Sonia Tejada, PhD

Department of Neurosurgery, The Department of Neurosurgery at Clínica Universidad de Navarra. The use of a fluorescence microscope enabled one of the most aggressive types of brain tumor to be completely removed in 83% of the cases, according to the results obtained in a series of patients with Glioblastoma that were treated by the Clínica’s neurosurgeons, the conclusions of which have been published in the Journal of Neuro-‐Oncology.

Stephan Kapral, MD Professor of Anesthesiology and Intensive Care Medicine Department of Anesthesiology and General Intensive Care, UKH Linz, Austria.

Stephen Walulik Sr. Director of Operations, Biomet Spine and Trauma.

Susann Brady-‐Kalnay, PhD Associate professor of molecular biology and microbiology at Case Western Reserve University.

Terry Magnuson, PhD Sarah Graham Kenan Professor, Vice Dean for Research, School of Medicine Chair, Department of Genetics, University of North Carolina at Chapel Hill.



Theodore Miclau III, MD

He currently serves on the Board of Directors for the Orthopaedic Trauma Association (OTA), Orthopaedic Research Society, and the American Academy of Orthopaedic Surgery. He is the third vice president of the Orthopaedic Research Society. He also serves on the Board of Directors of the Foundation for Orthopaedic Trauma, where he was a founding member, and the San Francisco General Hospital Foundation.

Timothy Cloughesy, MD Director, UCLA Neuro-‐Oncology Program; Clinical Professor.

Timothy J. Bray, MD

Clinical Professor of Orthopaedic Surgery at UCD Medical Center and maintains a clinical affiliation with the University of Nevada School of Medicine. President, Orthopaedic Trauma Association.

Victor A. Levin, MD

World-‐renowned expert in brain tumor research and treatment. Dr. Levin has authored almost 400 publications in his 40-‐year research career. He developed and edited a multidisciplinary textbook of neuro-‐oncology titled Cancer in the Nervous System. He is likely responsible for coining the term "neuro-‐oncology". Dr. Levin is the founder and first president (1995-‐97) of the Society for Neuro-‐Oncology.

Vladimir P. Torchilin, PhD Director, Center for Pharmaceutical Biotechnology and Nano medicine at Northeastern University, Boston, Mass.

Wai-‐Kwan Alfred Yung, MD

Chairman and Professor of Neurology, Margaret & Ben Love Chair in Clinical Cancer, Department of Neuro-‐Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

Warren M. Zapol, MD Director, Anesthesia Center for Critical Care Research, Emeritus Anesthetist-‐in-‐Chief, Massachusetts General Hospital.

Webster K. Cavenee, PhD Professor of Medicine, Cancer Genes and Genome, Program Director, Ludwig Institute for Cancer Research, University of California, San Diego.

Yasuhiko Tabata, MD Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Japan.

Bob Blendon, PhD Professor of Health Policy and Political Analysis in both the Harvard University School of Public Health and the John F. Kennedy School of Government.

Kerry Weems

Senior Vice President and General Manager, Health Solutions, formerly held the position of Administrator of the Centers for Medicare and Medicaid Services and was also Vice Chairman of the American Health Information Community.

Jacob Hacker, PhD

Stanley B. Resor Professor of Political Science at Yale University, and a Resident Fellow at the Institution for Social and Policy Studies. He is also a Fellow at the New America Foundation in Washington, D.C., and a former Junior Fellow of the Harvard Society of Fellows. He is an expert on the politics of U.S. health and social policy.

Len Nichols, PhD

Highly respected healthcare economist, headed New America's Health Policy Program from 1995 until 2010, when he left to become a professor of health policy and director of the Center for Health Policy Research and Ethics at George Mason University

Arnold Milstein, PhD

Consultant and Chief Physician at Mercer Health & Benefits and Medical Director of the Pacific Business Group on Health (PBGH). His work focuses on health care purchasing strategy, the psychology of clinical performance improvement, and clinical innovations that reduce total health care spending and improve quality. He was elected to the Institute of Medicine, is a Congressional MedPAC Commissioner and is a faculty member at UCSF’s Institute for Health Policy Studies.

John M. Welton, PhD, RN

Associate professor in the College of Nursing at the Medical University of South Carolina in Charleston. His research interests include the financial and business aspects of nursing care, nursing intensity, and performance and quality of inpatient nursing care.

Don Muse, PhD

Associate at Muse & Associates, formerly with the Congressional Budget Office, the Center for Medicare and Medicaid Services (CMS), and the U.S. Senate Finance Committee.


METHODOLOGY Module II

Research Module II will include the identification and recruitment of Key Customers and developing a project specific Voice of the Customer (VOC) questionnaire. VOC studies measure current unmet needs and near-‐term emerging opportunities, but do not address futuristic needs. We will look to these Key Customers to provide valuable insight into the stated and unstated unmet needs, emerging opportunities, and potential business gaps as they pertain to Company X’s Product X CED system. Like the KIL study, the VOC questionnaire will be developed through a collaborative effort with Company X in order to ensure that the focus of this project is being properly addressed. The questionnaire will be used as a platform for exploration and discussion. All interviews will be conducted directly by Harrison Hayes’ Principals and Research Team utilizing improvisational interviewing where the Team has the autonomy to probe deeper and maneuver through unique issues that arise during discussions with the Key Customers. Improvisational interviewing again yields valuable qualitative interview data, as our Research Team is able to adapt based on the Key Customers’ response to questions, thus obtaining valuable additional insight into the Key Customer’s perspective. Our Research Team selects the most appropriate questions to ask each Key Customer due to our extensive knowledge and involvement with the project’s goals.

Examples of Key Customers

• Purchasing and Procurement Executives at Cancer Centers and Hospitals specializing in Oncology

• Practicing Oncologists with a specialty in Glioblastoma

• Sales Representatives for: Company X, Novartis, Pfizer, Merck, Medtronic, etc.

METHODOLOGY Secondary Research & Trend Spotting Harrison Hayes has an extensive proprietary database of secondary research

that will add exceptional value to obtaining a complete understanding of market opportunities, barriers, and inhibitors within the CED market space. Subsequent content will provide some interesting findings uncovered from preliminary secondary research.

Syndicated Harrison Hayes has established relationships with a variety of syndicated information providers.


Publicly Available Harrison Hayes conducts significant market research within the public domain. We have expertise in identifying key market data through journal and trade publications, online subscription databases, market research data hubs, proprietary data sources and archival research. Internal One of Harrison Hayes’s key assets is the market research previously conducted that resides “in-‐house.” Our ability to leverage this data significantly reduces the time constraints associated with providing the required deliverables.

TREND SPOTTING & ANALYSIS

Trending analysis focuses on identifying market viability, interest, acceptance and penetration, and barriers to entry and expansion, and requires primary and secondary research to uncover emerging patterns and opportunities for a drug-‐device combination within the CED market space.

We do not guess trends; we detect, analyze, and evaluate them to make

evidentially supported projections. Because Company X’s KIL’s have significant insight into the current state of CED market space issues, they are on the cutting edge of trends and function as a valuable resource for understanding the commercial innovation, viability, and drug-‐device product-‐ and technology-‐specific market trends. Examples of trends that we will uncover include:

• Assessment of the market reaction and acceptance for Local Organ delivery using the PRODUCT X pump within the CED space

• Changing trends in drug, device, and drug-‐device regulatory and reimbursement environment

• Adoption drivers for innovative drug-‐device products • Lag time between early adopters, late adopters and others • Changing trends in use of systemic vs. local applications

Trending research is an integral part of a successful research initiative, and Harrison Hayes is confident that our trend spotting methods will afford Company X the necessary insight on CED space market dynamics.


FINAL REPORT Strataject Report™

Our final deliverable for this project is an Internalized Strategy Report (Strataject Report™). This report is the culmination of all primary and secondary research and activities that have taken place over the duration of the engagement. This report serves as an action plan illustrating key areas for life cycle management; competitive intelligence and reaction and the risks of cannibalization; market entry, expansion, impact, reaction, acceptance, and penetration; barriers and inhibitors to market entry, acceptance, and penetration; market transition; and reimbursement issues including pricing elasticity and reaction. We will do the same for customer segments including timing of adoption, previously unidentified adopters, and lag time between adoption by different segments, competitive reaction, and market penetration. Harrison Hayes will make a recommendation of actions within each of these areas to improve Company X’s position and improve value generation.

Harrison Hayes will schedule a time to present and discuss our findings and recommendations to Company X. During this meeting, we will discuss in detail our front-‐end research, findings, and recommendations for Company X supported by both primary and secondary research.


PROJECT FEES

Option A: Modular Breakdown of Project Plan Activities/Deliverables:

Option B: Modular Breakdown of Project Plan Activities/Deliverables:

Activity Weeks Fee

Key Innovation Leader Study 20-25 KIL Interviews 6-8 $65,000

Voice of the Customer Study 10 VOC Interviews (Concurrent with KILs) 4-6 $37,500

Secondary Research (Concurrent with KIL/VOC) 2-4 $25,000

Final Report 1-2 $10,000

Total Project Duration and Fee 10-12 $137,500

Activity Weeks Fee

Key Innovation Leader Study 35 KIL Interviews 6-8 $85,000

Voice of the Customer Study 20 VOC Interviews (Concurrent with KILs) 4-6 $65,500

Secondary Research (Concurrent with KIL/VOC) 2-4 $25,000

Final Report 1-2 $10,000

Total Project Duration and Fee 10-12 $185,500


Travel expenses will be billed at cost. Company X will approve all travel expense prior to incurring any costs.

Company X Harrison Hayes, LLC Signature: _________________________ Signature: ______________________ Name: ____________________________ Name: _________________________ Title: _____________________________ Title: __________________________ Date: _____________________________ Date: __________________________


APPENDIX Figure 1: Project Layout

Possible Extensions of CED’s The following is a list of potential extensions of the CED application that may be explored to identify other therapeutic areas that may benefit from its development.

• Glioblastoma 1. Local Infusion of Chemotherapy (CpG) 2. Local infusion of Lymphokine Activated Killer(LAK) cells

• Other Oncology 1. Already Encapsulated tumors 2. Encapsulate Tumors

§ Nanoscaffold/Macropores • Encapsulate • Interconnect Latticework • Connect to CED • Infuse with Chemo

• Extension of CED 1. Chronic Pain

§ Epidural § Peripheral Nerve § Joint § Post surgical

• Selective Nerve rather than wound

Glioblastoma implantation and local infusion of monoclonal antibody

Specifications definition


• Better control (vs OnQ, etc) § Other

2. Stem Cell Infusion § Nerve Growth Factors (NGF)

• Spinal Cord Injuries • Nerve Palsy’s • Demyelization Disorders

§ Parkinson § Endocrine Replacent

• Diabetes, Thyroid • ETC

§ Organ • Cardiovascular

o Re-‐perfuse old MI o Defects (ASD, VSD) o Valve Disorders

• Others o Injectible stem cell activators o Granulocyte colony stimulating factor (G-‐CSF) o Mobilizes stem cells

• Future of transplantation/organ injury o Rebuilding damaged organs/tissue o Delivering local doses of medicine o Delivering local gene therapy o Determine cell function and survival o Correcting primary or secondary deficiencies

3. Psychiatric Disorders § Schizophrenia

• Local Infudion of Dopamine – Prefrontal Cortex o PPI – pre pulse inhibition o LI – latent inhibition

§ Antisocial (as above) § Depression and SSRI’s § Developmental Disorders

• Autism • CP

§ Others 4. Epileptic Disorders


PROJECT MANAGEMENT TEAM Judith Rosall, Director of Market Research Twenty years+ professional experience as a leading Life Sciences (e.g. Biotechnology, Pharmaceuticals, Bioscience, Nanotechnology, Medical Devices, Healthcare), IT, E-‐commerce, and New Media industry analyst. Highly skilled and experienced in quantitative and qualitative market research, including market sizing and forecasting, economic modeling, trends analysis, market segmentation, identification of key players, market share, emerging (tactical and strategic) technology and business process analysis. Judith, as Director of Market Research, has overseen $1M+ continuous information programs, and was responsible for (quantitative and qualitative) primary market research and competitive intelligence to Fortune 100 clients. Judith has also worked with various teams, co-‐operatively developing strategic, long range and tactical market analyses, product portfolios, customer-‐satisfaction surveys, (online) surveys, brand preference on-‐line surveys and market/segment revenue forecasts. Corporate and market research executive management level experience includes Senior Management Roles at Best in Class market research firms, including the Aberdeen Group, Gartner, IDC (International Data Corp, PepsiCo and Qwest Communications). Education Post-‐Graduate Studies: Business Admin. & Mgt., Harvard University, Cambridge, MA MS Telecommunications/Business, University of Colorado, Boulder BS Journalism/Marketing, University of Colorado, Boulder Miriam Sander, PhD, Senior Analyst Proven leader in grant proposal writing and editing, patent editing, and manuscript writing and editing. Created and instructed scientific writing seminars and developed and designed brochures and flyers for scientific products and services. Recipient of the NIH Predoctoral Training Award and Published 45 manuscripts in professional scientific journals, 25 meeting abstracts for presentation at scientific meetings and presented research proposals in justification of research funding and support. Education PhD, Duke University BA, University of North Carolina BA, Brandeis University


Gary L. Freed MD, MPH and Chair Eighteen years of experience in children's health services research and has been the principal investigator of numerous federal, state and foundation-‐funded grants. He has published over 140 peer-‐reviewed articles on child health policy and health economics, physician behavior and interspecialty variation in the provision of preventive services to children. Dr. Freed is the immediate past President of the Society for Pediatric Research, the largest research society in the field of child health. Dr. Freed also serves on several national committees. He is the immediate past Chair of the Department of Health and Human Services National Vaccine Advisory Committee. He is a frequent consultant to state and federal agencies as well as the Institute of Medicine of the National Academy of Sciences and the World Health Organization. He is a member of the American Board of Pediatrics and a Fellow of the American Academy of Pediatrics. Education M.P.H., University of North Carolina at Chapel Hill, 1992 M.D., Baylor College of Medicine, 1987 B.A. (Honors), Biology, University of Texas at Austin, 1983 Amy L. Porter, Director of Licensing Proven leadership in open innovation, deal negotiations, in-‐ and out-‐licensing, strategic portfolio development, intellectual property management, and competitive analysis. Recognized for forward vision, business savvy, creativity, and the insightful integration of technical, business, and legal issues into cohesive deal and portfolio strategies. Excellent oral and written communication skills. Business consultant in open innovation and business development. Projects include assignments for clientele ranging from start-‐up to Fortune 500, as well as curriculum development and teaching for the MBA program at Princeton Center for Management Development. Worked as a Licensing and Business Development Executive for Pfizer (6 years as Senior Director, Licensing), BASF (Director of Business Development), Ariad Pharmaceuticals (Director of Technology Management and Licensing), Stanford University (Senior Licensing Manager) and MIT Medical Technology Licensing Officer). Education Masters of Liberal Arts, Concentration in Management Harvard University, Anticipated 2010. Certified Licensing Professional (C.L.P.) Licensing Executive Society, Certification awarded April 2008. Extensive post-‐graduate coursework in business, life sciences, and computer science Bachelor of Science (cum laude): Pre-‐veterinary Medicine University of New Hampshire, 1978.


Angele Sjong, PhD, Senior Analyst Director of contract manufacturing and oversaw all formulation, scale-‐up, quality control, product claim and chemical stability in the successful launch of numerous medical device products. Created and instructed numerous seminars for medical device engineers; developed curriculum based on twenty years consulting experience with the medical device industry. Provided expert witness testimony in chemistry/materials related to product liability. Lead or co-‐author on over sixty confidential scientific and engineering reports, over fifteen for medical device companies. Education B.S., Chemistry University of California, Berkeley Ph.D., Inorganic Chemistry Yale University M.S., Metallurgical and Materials Engineering Colorado School of Mines William Smith, Managing Director Founder and Managing Director of Harrison Hayes, LLC. Harrison Hayes LLC is a strategic consulting firm with an emphasis on the creation of disruptive innovation strategies, products and platforms. Harrison Hayes has been engaged by over 300 companies conducting over 800 project assignments. Prior to Harrison Hayes, Bill was the Founder and CEO of Addison Whitney, which today, is the third largest branding consultancy in the world. Bill sold Addison Whitney in 1995 to Interpublic Group (NYSE:IPG) and led their Healthcare Acquisition Team for three years which was responsible for over $3 Billion in transactions. He reacquired Addison Whitney in 1998 and repositioned the firm to work exclusively with life science clients. Bill acted in a dual role with Addison Whitney (Chairman) and Harrison Hayes until 2007 when he sold Addison Whitney again to inVentiv Health. Education B.A., Berklee College M.A., Colorado State University Kim E. Miller, Research Assistant Prior to Harrison Hayes, worked with a private firm in the dental implant industry. Assisted the CEO/Founder in industry research, marketing projects and coordinating surgical training sessions within the United States. Previously worked for seven years with a private consulting firm within the Life Science industry as project coordinator, conducted market research and surveys, assisted in identifying in licensing and out licensing opportunities for clients and set meetings between potential licensing candidates. Prior to this position, worked in a government funded hospital to assess treatment for disabled individuals. In this capacity, worked within a multi-‐disciplinary team to evaluate treatment options within physical therapy, occupational therapy, dietary needs, habilitation needs and vocational needs. Education B.S., East Carolina University Master course work in Health Science with a concentration in Management, Western Carolina University


CASE STUDIES

Harrison Hayes was engaged by Wyeth to conduct a Whitespace Innovation Study to Examine

Disruptive Innovation Opportunities in Clinical

Vaccines


Harrison Hayes was engaged by Takeda to conduct a Whitespace Ideation Study to examine the

Future Impact of Nanotechnology on the

Pharmaceutical Industry


Harrison Hayes was engaged by Genentech to conduct a

Whitespace Innovation and Combinatorial Ideation Study to Identify and Create Radical New

Business Models within Healthcare


Biogen Idec engaged Harrison Hayes to conduct a

Combinatorial Ideation Study to Identify Disease and Patient Targets in Oncology through

2025


Harrison Hayes was Engaged by Sanofi-Aventis to examine Disruptive Opportunities

(Product, Technologies, and Yet to be Determined Business

Models) in Healthcare


Harrison Hayes was engaged by Novartis to conduct a Key

Innovation Leader Study to design a Reimbursement and

Access Strategy for Select Portfolio of Products


Eli Lilly sought to identify the brand awareness of its Oncology

franchise brands to discern competitive

positioning strategies and further develop new product offerings.


Abbott engaged Harrison Hayes to conduct a comprehensive innovation and ideation project to identify unmet needs within

their Neuroscience Pipeline with the emphasis on identifying selective NNR compounds

through internal, external and newly created innovation

sourcing.


Amgen Engaged Harrison Hayes to Conduct a Global Landscape

Analysis and Develop a Strategic Roadmap for their Oncology

Product Portfolio


Harrison Hayes was Engaged by Sanofi-Aventis to Conduct a

Whitespace Innovation Study to Examine Disruptive Innovation

Opportunities in Oncology Therapy through 2020


Pfizer engaged Harrison Hayes to conduct a comprehensive

innovation and ideation project to identify unmet needs within

their Oncology Pipeline.


C.R. Bard asked us to provide a market assessment of specialized

catheters in various countries around the world that would

enable them to prioritize which markets to enter first.

CED Tight Space Innovation Market Entry Avastin Glioblastoma Proposal

Presentations & Public Speaking

Transcript of CED Tight Space Innovation Market Entry Avastin Glioblastoma Proposal