TORREYA INSIGHTS Torreya Insights is a professional and data services company spun out of Torreya Partners, a New York-based boutique, financial advisory firm. We assist life science companies in all aspects of the business development process. Our consulting engagements usually focus on helping our clients raise capital, locate suitable assets for acquisition, or find potential partners for further asset development. We also perform financial valuations, market assessment, and quantitative fairness opinion analyses. Our data services include subscriptions to three databases: AvaRx, Licensing Dynamics, and Financing Dynamics. • AvaRx is a searchable dynamic database of more than 2,000 licensing opportunities across various therapeutic areas and stages of development. • Licensing Dynamics is a Customer Relation Management (CRM) database designed for pharmaceutical industry out-licensing, which has contact information of over 16,000 executives. • Financing Dynamics is designed to assist our clients in raising capital, and contains information on about 900 funds and 3,000 investors. Torreya Insights' team members have deep industry knowledge and connections. Our reputation is built on quality advice and positive outcomes for our clients. 2 AVARX WWW.AVARX.COM About AvaRx: AvaRx is a searchable, dynamic database of business development opportunities in the pharmaceutical industry. The name is an abbreviation of “Available Pharmaceutical Products” and is pronounced “A (as in apple)-Va-Rex.” AvaRx launched in December 2013 and is maintained by Torreya Insights staff. Benefits: Simple to use No initial cost - any registered user may search for opportunities and/or list an opportunity Continually curated and subjected to quality controls • • Staff of highly educated experts adding and reviewing information Partnership with Torreya Partners, a leading life sciences advisor, enhances timelineness and quality of information The information is substantially more useful than that which is found in other information services that have pharmaceutical business development opportunities: • Most other services catalog thousands of assets in development – some of which could be good candidates for licensing deals, but do not isolate actionable, fresh business development opportunities 3 GETTING AN ACCOUNT If you don’t have an account: Go to the AvaRx site www.avarx.com Click on “Become a Free Member” or “Join / Sign Up” Fill in your information, including your name and company Click the “Register” button Your account will be created and you will be logged in automatically You can go to “My AvaRx” and fill out more information You are now ready to search for opportunities 4 MANAGING YOUR STATUS The first time that you log in to AvaRx, you become a “Registered User,” at no cost. With this status, you can: Search through over 1,000 opportunities List one asset View very detailed information on those opportunities Upgrading to “Premium Subscriber” enables you to: Search for additional opportunities AvaRx’s “Freemium” subscription structure allows for free searches of a large number of business development opportunities. List more than one asset View contact information for each asset 5 BENEFITS OF A PREMIUM SUBSCRIPTION Searching for assets Listing assets Proprietary listings – Over 600, mostly late stage or less obvious opportunities. Undisclosed listings – Approximately 30 highly actionable listings through Torreya Insights contacts. Non-confidential presentations and other documents (over 2,000). Contact details of business development professionals. Excel/PDF Export – Export list of results from searches to an accessible format. Messaging – Contact counterparties using the My AvaRx messaging system to set up meetings about opportunities. List unlimited number of assets. List undisclosed assets (manage confidentiality). Access buy-side preferences and contacts through a Customer Relationship Management database, Licensing Dynamics. Access analytic tool to see who is viewing your asset/s. Other benefits: High impact advice (teaser feedback, call list generating) from our experienced staff. Monthly calls with bankers of new and exciting listings. PRICING AND BENEFITS COMPARISON Registered User Premium (Single User) Premium (Corporate) Free $2,500* $6,000# Number of Seats† 1 1 3 Number of Undisclosed Item Calls / Month 0 3 9 Number of Listings to Create 1 Up to 25 Unlimited P P P P P P P P P P P P P P P P P P Benefits Comparison Quarterly Subscription Rate Access Over 1,000 Listings Search by Indication, Phase of Development, etc. Screen Buyside Dealmakers / Get Contacts Access Analytical Reports on Your Listings Access to Messaging Access Proprietary Listings Access Non-Confidential Documents Access Contact Information for Opportunities * $8,000 per annum if prepaid. # $20,000 per annum if prepaid. † Pricing for large enterprise subscriptions is available upon request 7 SEARCH FIELDS Refine searches in several categories: • • • • • • • Therapeutic area (“TA”) - e.g., Urology, Endocrinology Indication - e.g., Alzheimer’s Disease Development phase - e.g., Phase I Situation - e.g., Licensing Opportunity, Generic Drug Territories available - e.g., Worldwide, China Molecule type - e.g., Antibody Route of Administration - e.g., Intravenous Form very specific queries (e.g. “Phase 1, Urology, Rights Available - Japan.”) Carry out text searches – by drug name, company name, etc. 8 NAVIGATING THE SEARCH RESULT PAGE Search assets in the Opportunities page. You can search by drug name. You can refine a search by narrowing or expanding search terms. Also search by Company, Therapeutic Area, and Situation This button allows you to save a search. Saved searches can be viewed in “My AvaRx”. If you “peek” you can see a brief profile. Quick description Customize searches by checking and unchecking category search terms. Clicking “more” expands the list of visible search terms within a category. Terms are listed in descending order of the number of such asset types found in AvaRx. The pen icon opens a more extensive, alphabetized search page for the creation of compound searches. Share this item with a colleague (via email). You can track developments for a specific asset. This is also a good way to bookmark. “More” opens up a detailed profile of the asset. 9 NAVIGATING THE PRODUCT LISTING Clicking “Company Profile” gets all information in Avarx on a company. Company address, phone and web site. Also a link to Google maps in order to get directions. This is the right contact for BD discussions, including phone and email details. Non-confidential documents on the business development opportunity, including a non-confidential overview and scientific posters. Name of company and drug candidate “Track It” allows you to follow this listing over time Summary of key details, including phase of development, TA, indications, territories available and situation Overview of the business development opportunity, including disease state, name of drug and pertinent details on a deal. Description of MOA, biology, chemistry work and links to publications, if available. Narrative history of clinical trial work, including outcomes. If the compound is preclinical, then preclinical data will be discussed. Description of territories where the opportunity is already licensed. 10 THERAPEUTIC AREAS Search using 47 therapeutic areas (TA’s). The AvaRx TA taxonomy is different than the ICD-9 system, which is organ-centric. In particular, while the primary focus is on organ system classification (e.g., Gastroenterology), there is also reference to major areas of disease etiology (e.g., Infectious disease- viral, Fibrosis). The AvaRx TA terms are intended to match the interests of pharmaceutical business development professionals who often search for opportunities that match physician groupings (e.g., Endocrinologists, Pediatricians), rather than organ systems per se. There are also a few TA’s included that specify the end customer for a product (Animal Health, Biodefense). 11 INDICATIONS Search over 500 disease indications. We have set indications generally by the disease descriptions employed by the companies listed in our database. Some indications, such as “Acetaldehyde Toxicity,” are rarely used, whereas others, such as “Parkinson’s Disease,” are very common. Wherever possible, we attempt to consolidate identical indications such as HIV and AIDS into “HIV / AIDS.” We have also included some catch-all indications, such as “Neurodegenerative Diseases (General).” However, when listing or searching, it is best to use specific terms. 12 DEVELOPMENT PHASES There are seven phases of development of a drug candidate - starting in the research phase and ending in the marketing phase. Research / Discovery Phase Conducting chemistry and biology work on potential drug candidates, but a lead candidate has not yet entered pharmacology studies. Preclinical Includes situations where a lead drug candidate has entered pharmacology studies all the way up to the point where an IND is active but no humans have been tested with a drug. Phase I First human studies have begun on a drug candidate. This includes situations up to where a dose-ranging Phase 2 study has begun. Quite a few companies (particularly in oncology) refer to first studies in patients at Phase I/II trials. We generally classify these as Phase Ib studies and include them in Phase I, unless there is an active comparator in use or a large number of patients studies in a multiple ascending dose setting. Phase II IIa IIb Dose ranging and dose confirmation studies have begun. This covers situations where Phase II studies for a drug candidate are just beginning to when a company has completed Phase II studies but has not yet commenced Phase III studies. Phase III Either starting Phase III, in Phase III trials or has completed Phase III trials without having yet applied for regulatory approval. NDA/BLA Filed Pivotal studies for a drug have been completed and a company has filed for regulatory approval anywhere in the world. On Market A drug candidate has been approved and is either commercially available or soon to be available anywhere in the world. 13 ROUTES OF ADMINISTRATION / MOLECULE TYPE You can search by route of administration (e.g., intranasal, oral). There are seventeen labels for route of administration. Catheter Implant Inhalation Injection Intraocular Intrathecal Intratracheal Intravaginal Intravenous Intravesical Nasal Oral Rectal Sublingual/buccal Topical Transdermal Unknown You can also search by type of molecule (e.g., small molecule, antibody). There are five types of molecules. Antibody Other Macromolecule Peptide Protein Small Molecule Most cases where “other macromolecule” is referred to constitute vaccines or some type of RNA-based therapy. 14 TERRITORIES (Rights Available) We have divided the world into 14 territories and have included one catch-all for worldwide rights. If a product has worldwide rights listed, this means that the business development opportunity has yet to be regionalized and there are likely no licensing deals signed yet. We selected the territories based on the size of pharma consumption by territory and the history of requests for regional rights to products at Torreya Insights. Territories For Search Worldwide Africa Asia ex China Korea Japan Australia/New Zealand Canada China Europe India Japan Korea Latin America Middle East Russia and CIS Turkey USA Russia & CIS Canada Europe USA Turkey China Mid East Africa Latin America Korea Japan Asia except CH JP KR India Australia and New Zealand ! Key Point: If you would like to search everything available in Europe, you have to search for Worldwide and Europe. 15 SITUATION FIELDS Situations Describe Aspects of a Search That Go Beyond Phase of Development and Therapeutic Areas Many users of AvaRx look beyond therapeutic areas or development phase for specific situations that fit a business strategy. We have attempted to capture these situations based on dialogue with users over the years. There are 40 situation types (e.g., active sale process, mature branded products). Cancer / Oncology Situations In addition, AvaRx includes hundreds of opportunities in oncology. Thus, navigating the available oncology business development opportunities is challenging. We have found that many licensing professionals focused on oncology are interested in specific strategies for stopping cancer (e.g., altering cancer metabolism). As a result, to ease the search process, we have classified oncology business development opportunities into a number of strategies for slowing cancer. 16 SITUATION FIELDS Situation Description 505 (b) 2 Product A drug being developed with little change from a previously approved drug (change in dose, administration, combination, active ingredient, Rx to OTC) through an expedited approval pathway. Active Process (Sale or Licensing) The company is known to be running an active business development process, typically with the help of an external financial advisor. Big Pharma / Biotech A top 20 pharmaceutical company is out-licensing a drug candidate or mature product. Programs for Out-licensing Bigger Deal ($200mm+) Refers to potential transactions where the expected value exceeds $200 million. Biosimilar Drug Biosimilars or (follow-on biologics) are terms used to describe officially approved subsequent versions of innovator biopharmaceutical products made by a different sponsor following patent and exclusivity expiry on the innovator product. Cell Therapy A situation where a cellular product is used for medicinal purposes. Often, a cell therapy involves an autologous therapy where a patient's own cells are removed, processed and then reinserted with expected benefit. Diagnostic AvaRx also includes many diagnostic opportunities. Typically, we include therapeutically-relevant molecular diagnostics, but other types are also included. Diagnostics - Imaging Refers to the availability of an imaging technology with a diagnostic purpose. Distressed Situation Assets that are held by bankrupt, financially distressed or restructured companies are identified by this situation flag. Often, the intellectual property of an asset remains available long after a company ceases to operate. AvaRx includes a number of distressed assets as certain buyers specifically seek bargains based on companies that have encountered operational or financial difficulty. Drug Delivery Technology This flags technologies that are available to deliver a drug in a novel way. Drug delivery technologies include: Transdermal Patches, Inhalables, Needle-Free Injectables, Subcutaneous, and Stimuli-Responsive. Gene Therapy The most common form of gene therapy involves inserting a normal gene to replace an abnormal gene. Other approaches include swapping an abnormal gene for a normal one, repairing an abnormal gene, or altering the degree to which a gene is turned on, or off. The latter approach is often flagged using the situation "RNA-based therapy.” 17 SITUATION FIELDS (CONTINUED) Situation Description Generic Drug A generic drug is identical -- or bioequivalent -- to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. It’s usually discounted to the brand. A product that would be used principally in a hospital / acute care setting. Hospital Product Hostile Takeover Situation The acquisition of one company by another (called the acquirer) that is accomplished, not by coming to an agreement with the target company's management, but, by going directly to the company's shareholders or fighting to replace management in order to get the acquisition approved. Licensing Opportunity This is a situation where a company seeks to license a product to a development and/or commercialization partner - often in multiple territories. Manufacturing Plant or Technology Mature Branded Products This is a situation where a manufacturing facility or manufacturing technology is available. Named Patient Candidate Refers to a drug that is still in clinical trials for a serious disease where there are no effective treatments available. Such a drug can be a candidate for use on a named patient basis. In many countries, once a drug has been shown in a trial to be effective it can be used on a named patient basis or "compassionate use" basis. There are a number of companies that specialize in the distribution of such drugs. See http://en.wikipedia.org/wiki/Named_patient_programs Naturals, Nutritionals and Medical Foods This flags drug candidates that have either a natural origin or usage as a food product. Quite a few drug candidates were developed from substances found in nature. Many such candidates can be employed as drugs if appropriate regulatory steps are taken, or instead may be able to come to market sooner as socalled medical foods or even OTC products because their ingredients are regarded as safe. A drug candidate where the number of potential patients is small. There is frequently an opportunity for a high price given the rarity of patients. Orphan Product Refers to a situation where a drug has been on the market for some time and is receiving little to no promotion. Such drug candidates typically generate good cash flow and are highly sought after even though they may have little to no patent life remaining. Certain types of specialty pharmaceutical companies seek to enhance the revenues from such drugs through authorized generic programs, renewed promotion, repositioning of a brand or increases in price. 18 SITUATION FIELDS (CONTINUED) Situation Description OTC / Consumer Product An over-the-counter pharmaceutical product that is sold directly to consumers through a retail or internet channel. Also included are other health-related consumer products. Potential M&A Deal AvaRx analysts believe that a company is (or will soon be) open to exploring a sale transaction or merger. Protein Platform A technology for peptide, antibody engineering or development of other protein types. Radiopharmaceutical Radiopharmaceuticals are agents used to diagnose certain medical problems or treat certain diseases. They may be given to the patient in several different ways. For example, they may be given by mouth, given by injection, or placed into the eye or into the bladder. Radiopharmaceuticals are radioactive agents. This asset was recently sold. It will be removed soon from AvaRx listings. Recently Sold Research/Drug Technology A technology that can be used for biological or chemistry research in a drug development setting. Also includes technologies that would directly advance the drug development process. Reverse Merger Candidate A public company that may have cash but lacks a viable asset. This company is a good candidate for merging with a private company with an asset. A reverse merger occurs when a private company becomes a public company by purchasing control of the public company. The shareholders of the private company usually receive large amounts of ownership in the public company and control of its board of directors. Once this is complete, the private and public companies merge into one publicly traded company. RNA-Based Therapy A therapy that involves RNAi, control of microRNA, antisense technologies or other approaches to the control of RNA. Royalties Royalties are cash flow streams that are generally a percent of the sales of a pharma products. This field identifies royalties and similar assets for groups that are interested in their acquisition. Specialty Pharma Marketed Products Stem Cells A company or situation where a company with marketed products is open to a transaction. Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair system for the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. A number of business development opportunities listed in AvaRx involve stem cells. 19 ONCOLOGY SITUATION FIELDS Situation Description Oncology - Androgen Modulator Androgen modulators attempt to control the spread of cancer by depriving tumors of sex hormones, such as estrogen, testosterone,or progesterone. Oncology - Angiogenesis Inhibitor Angiogenesis inhibitors attempt to control the spread of cancer by depriving tumors of vasculature needed for the delivery of blood and oxygen. Oncology - Antibody-Drug Conjugate Antibody Drug Conjugates or ADCs are a new class of highly potent biopharmaceutical drugs designed as a targeted therapy for the treatment of people with cancer. Oncology - B7 Immune Checkpoint Immune checkpoints are inhibitory pathways hardwired into the immune system that are crucial for maintaining the level of immune responses in peripheral tissues in order to minimize collateral tissue damage. A checkpoint protein may create the opportunity for multiple products to be developed, depending on function. Oncology - Cancer Metabolism That cancers display an altered cellular metabolism was first recognized almost a century ago, notably in Otto Warburg's description of a switch in glucose metabolism from oxidative phosphorylation to glycolysis — the Warburg effect. A number of companies are developing drugs that promise to disrupt cancer metabolism as a way of shutting down a tumor's growth. Oncology - Cancer Stem Cells Cancer stem cell therapies attempt to kill specific progenitor cell types that propagate the growth of a tumor, but do not themselves form the bulk of the tumor. Refers to therapies that interfere with the process of cell replication through the cell cycle or, alternatively, trigger cellular self-destruction (apoptosis). Refers to therapies that are toxic to cells. Such approaches include various forms of chemotherapy (e.g., docetaxel, doxorubicin) but can also involve other cell killing methods. Therapies that cause various types of growth signals to a cancer cell to be turned off (e.g., an EGFR inhibitor). Oncology - Cell Cycle Arrest / Apoptotics Oncology - Cytotoxic Oncology - Growth Factor Inhibitors Oncology - Kinase Inhibitors Oncology - Targeted Approaches (Cell Surface Markers) Oncology - Tumor Microenvironment / ZFPs Oncology - Vaccines / Immunotherapy / Non-B7 Oncology - Vascular Disrupting Agents Refers to the broad class of tyrosine kinase inhibitors. These are cell surface markers that are involved in cellular signaling and are often involved in the propagation of cancer. Refers to therapies that target a specific cellular marker that is overexpressed on a specific type of cancer. Refers to therapies that change the environment of a tumor, or that involve zinc finger proteins as a strategy to prevent the spread of cancer. Refers to immunologic approaches to cancer that do not involve modulation of the B7 checkpoint system. Therapies that kill cancer by destroying part, or all of their vasculature, which, in turn, deprives them of a regular supply of blood and oxygen. 20 HOW TO LIST WITH AVARX There are two ways to enter a listing into AvaRx: • • Self-Serve: You can use our listing form to add a new entry on your own. The following pages show you how to do this. Assisted: If you have a complex entry, or many listings, we can put the listings in for you – assuming you are Premium Subscriber. Key Frequently Asked Questions: Q: What if I would like to list a disease that is not on the list? A: Let us know and we will set up the indication for you. Q: Can I enter an undisclosed listing where the listing company and product are not identified? A: Yes. To do this you need to be a Premium Subscriber. You will need help from us to have such entries set up and will need to agree with us on how we can get interested parties over to you (e.g. forward emails to you). Q: Can I enter a product as an investment bank, broker or consultant? A: Yes. You can enter on a self-serve, or assisted basis too, if you are a third party agent for an owner of a product. You can’t enter listings, however, if your firm is not retained to represent a product. 21 HOW TO LIST A NEW ENTRY ON YOUR OWN On the home page, click “Add a Deal Opportunity” on the lower right hand corner This will put you into the listing editor for a new listing On the Opportunities page, click “Add Listing” on the upper right hand corner Fill out the form, as appropriate: • • • • • The thumbnail would be a graphic image of your company’s logo, or an image of the product’s brand name, if you prefer. Name would be the name of the product Therapeutic area would be one of the therapeutic categories in AvaRx Indication is a disease area Rights available, Molecule type, Route of Administration, Phase and Situation have been previously described. 22 FILLING OUT THE FIELDS Description – should be a one or two sentence synopsis of the business development opportunity. Avoid promotional phrasing, such as “amazing”, but do mention the product name, phase of development, latest clinical data and results, if relevant, and indication in which it is used. Situation Overview – should provide an overview of the drug candidate, as you see fit, including a quick description of the medical need, the drug, relevant history and where you hope things are going. You could also comment on partnering status and intentions here. It’s also possible to comment here on IP, CMC, or other pertinent topics not covered elsewhere. Mechanism of Action – should describe MOA and, if desired, links to publications. Clinical Trials – should provide information on past and current clinical trials, including number of patients, disease states, outcomes, etc. Partners by Region – should indicate which territories have been partnered already and to whom, and which territories are still available. Contact – which registered user should be the point of contact for interested parties. Company – which company you represent Visibility – you should generally select registered users, which would make the entry visible only to registered users in AvaRx. “Anonymous users” would make the entry available to anyone coming to the site, “Subdomain” makes entry viewable only to people at your company and “Subscribers” would make the entry only viewable to premium subscribers of AvaRx. Submit – clicking submit at the top of the page will send the asset to our content team for review and approval. 23 MyAvaRx GIVES YOU FURTHER CONTROL On the home page, click on MyAvaRx to get to a control panel for AvaRx. From the control panel, you can see any recent alerts set up for you and also see a list of recent pages visited and actions taken. This is called your Activity Log. Using the blue buttons on the left, you can make a number of changes: • • • • • You can change your user profile (e.g., address details) You can change your account settings, including your subscription level You can set preferences (e.g., how and whether you get alerts) See which companies you track Get into the messaging system 24 USER PROFILE EDITOR This editor allows you to set up your bio, address details, import your picture and enter your email. When you are done using the editor, it is critical to click on the “Save” button (Top right hand corner) 25 KEY CONTACTS ON AVARX TEAM Margaux Stack-Babich Craig Ferrier VP, Knowledge Management P: 1-212-331-7821 E: margaux@avarx.com margaux@torreyainsights.com • Manages content team and responsible for news / productions • Co-Founder of Torreya Insights • Previously at MSNBC • B.A. Fordham University VP, Product Development P: 1-212-331-7822 E: craig@avarx.com • Leads product development • Manages business development and alliances • Co-Founder of Torreya Insights • Past experience in web startups • B.S., University of Monaco Monika Trzcinska, Ph.D. Mara Grbic Walton, MPH VP, Research Solutions P: 1-212-331-7821 E: mtrzcinska@torreyainsights.com • Leads the research & consulting business of Torreya Insights • Frequent contributor of ideas to AvaRx with interest in CNS • Previously in business development at Repligen • Ph.D., Neuroscience, University of Ottawa Director, Knowledge Managemnt P: 1-212-331-7829 E: mwalton@torreyainsights.com • Reviews AvaRx content listings and identifies new listings that fit client interests. • Strong interest in oncology and therapeutics for lifethreatening diseases • Masters in Public Health, Columbia University. Suzanne Schultz Jason Liberman Director, Knowledge Solutions P: 1-212-331-7826 E: sschultz@torreyainsights.com • Manages relationships with AvaRx customers • Assists in marketing, sales and the customer experience • Previous experience in research and medical sales • B.A. Business, Thomas More College Director, Knowledge Products P: 1-212-331-7841 E: jliberman@torreyainsights.com • Plays a leadership role in sales at Torreya Insights • Maintains relationships with a number of key customers • Past experience at American Orthopedics in Marketing role • MBA, Hofstra Chris Opler Chief Technology Officer P: 33-640-206-512 E: copler@torreyainsights.com • Lead information architect for AvaRx, managing four developers. • On Galileo LEOP Software Team and satellite projects for the European Space Agency • Studied at George Mason Univ. Adam Cooper Director of Content and QC P: 1-212-331-7828 E: acooper@torreyainsights.com • Leads AvaRx content operations and quality control • Previously at Conde Nast, Scholastic & Fenway Partners • Earned B.S. from U of Wisconsin in Cartography and Computer Sci, Phi Beta Kappa Kristen Frederick VP, Marketing and Operations P: 1-212-331-7843 E: kristen@torreya.com • Manages finance, admin, web site, trade shows and marketing for Torreya Insights • Finance & Marketing background • Previously at Cowen & Co. • MBA, Pace University 26 OTHER SERVICES OFFERED BY TORREYA INSIGHTS Torreya Insights’ mission is to be a high value information service provider to business development professionals in the biopharmaceutical industry. Thus, in addition to AvaRx, Torreya Insights offers several other services: Customer Relationship Management (CRM) Solutions. These are integrated software solutions for out-licensing and biotech professionals: Licensing Dynamics – a web-based software system that combines 16,000 industry contacts for out-licensing, matching of therapeutic and geographic interests to specific companies and people, as well as private recording of communications with those people (emails and phone calls). Financing Dynamics – a web –based software system that allows companies in search of capital to find the right investors for their opportunity. Allows to determine whether money is available and what are investor’s interests. Research and Consulting Services This area of Torreya Insights presently works with customers that want structured assistance in solving specific problems that use our databases (e.g., support in a search & evaluation project in a new therapeutic area that is structured around AvaRx). We have built a skilled research team for a growing group of client requests. 27