| Aspreva Pharmaceuticals CORP Item 1A Risk Factors |
| Risks Related to Our Business We anticipate that substantially all of our revenue for the foreseeable future will be from royalties based on sales of CellCept and we may not be able to sustain our profitability |
| We were incorporated in 2001 and have a limited operating history |
| Since our inception through December 31, 2005, we have incurred cumulative losses from operations of dlra5dtta5 million |
| Our losses to date have resulted primarily from general and administrative costs relating to our operations and costs related to the clinical development of CellCept for autoimmune indications |
| In accordance with the terms of our agreement with Roche, commencing April 1, 2005, we became entitled to a royalty based on an equal sharing of incremental net sales of CellCept in non-transplant indications above a negotiated baseline less a distribution fee, payable on a quarterly basis |
| This baseline was originally set in July 2003 at CHF 134 million, and is subject to an annual price index adjustment |
| In July 2005, Roche and Aspreva agreed that the baseline for 2005 would be CHF 123 million, after taking into account the price index adjustment and, for the time being, excluding Japan as a licensed territory under the agreement |
| Although we were profitable for 2005, future operating results and profitability are not certain and we may not sustain our profitability |
| Our operating results may fluctuate from period to period for a number of reasons |
| In budgeting our operating expenses, some of which are fixed in the short term, we assume that revenues will continue to grow |
| Even a relatively small revenue shortfall or a small increase in operating expenses may cause our results to be below expectations |
| A revenue shortfall or increase in operating expenses could arise from any number of factors including: • lower than expected revenues on commercial sales of CellCept; • higher than expected operating expenses as we further develop CellCept for autoimmune indications, seek additional collaborations and operate as a public company; • higher than expected levels of marketing expenses and the expenses of potentially launching CellCept and any future products for our targeted indications; and • fluctuations in currency exchange rates |
| We anticipate that substantially all of our revenue for the foreseeable future will be from royalties based on sales of CellCept pursuant to our agreement with Roche |
| Our revenue is dependent on Roche and our mutual ability to track product sales arising from the use of CellCept by transplant patients |
| The methodology for accurately tracking sales of CellCept that has been agreed to may be a source of dispute with Roche, which may negatively affect our revenue and our relationship |
| 18 _________________________________________________________________ If we and Roche are unable to successfully manage our collaboration, the development and commercialization of CelICept for autoimmune indications may be delayed or prevented |
| Our collaboration with Roche involves a complex sharing of control over decisions, responsibilities, costs and benefits |
| Development and promotional activities related to CellCept in the autoimmune indications are approved by a joint committee, consisting of an equal number of our representatives and Rocheapstas representatives |
| In the event that the joint committee is unable to reach consensus on an issue, the dispute will be referred to senior management of both parties |
| Unless and until senior management reaches agreement on such dispute, neither party will have the right to implement any changes to the status quo that would result from resolution of such matter |
| Although we are responsible for compiling and preparing all applications for regulatory approval of CellCept in autoimmune indications, Roche has the ultimate decision making authority to submit these applications to the appropriate regulatory authorities |
| If Roche does not approve the application we prepared, or requires that we revise or modify the application, this could result in delays in receipt of regulatory approvals |
| In addition, Roche may develop and commercialize, either alone or with others, products that are similar to, or competitive with, CellCept |
| Roche may also change the focus of its development and commercialization efforts and dedicate fewer resources to CellCept or our collaboration |
| If we do not satisfy our obligations under the Roche agreement or if the agreement is terminated we may be forced to limit or cease our operations |
| Our agreement with Roche requires us to use commercially reasonable efforts to conduct three clinical trial programs for CellCept in autoimmune indications pursuant to an agreed upon development plan |
| Roche may allege that we are in breach of a material obligation under our agreement and seek to litigate the allegation |
| If Roche is successful in such litigation, Roche may either be awarded damages based upon such breach or the agreement might be terminated |
| After 2011, either party may terminate the agreement if there is a lack of non-transplant sales over the baseline for a prolonged period |
| In addition, if CellCept is withdrawn from or recalled in any given country, either party may terminate the agreement with respect to that country |
| If the agreement is terminated in its entirety or in a given country we may be forced to limit or cease our operations |
| Our agreement with Roche contains provisions requiring us to comply with applicable laws and regulations, including restrictions on the promotion of approved drugs for off label uses |
| If it were determined by the FDA or other regulatory authority that we violated the rules relating to off label promotion in connection with our pre-approval communications regarding CellCept, we may be deemed by Roche to be in material breach of the agreement |
| If we fail to cure any material breach of the agreement, Roche may commence legal action for damages and/or seek to terminate our agreement |
| If Roche does not manufacture, distribute, price or sell CellCept at levels which generate sufficient revenue for us to operate, we may have to limit or cease our operations |
| We do not own or operate any manufacturing or distribution facilities |
| Roche, not Aspreva, controls the manufacture of CellCept and we have no alternative supplier |
| If we are unable to obtain adequate supplies of CellCept from Roche for our clinical trials, they could be delayed or prevented |
| In addition, if there is a shortage of CellCept, Roche may decide to allocate available supplies of CellCept to purchasers for use in transplant indications and not autoimmune or other indications, thereby reducing our revenues |
| Roche is solely responsible for distributing and selling CellCept, and setting the price, including all discounts and rebates, of CellCept |
| Rocheapstas control over the manufacture, distribution, pricing and sale of CellCept exposes us to a number of risks which are outside our control including: • Roche may fail to comply with FDA-mandated current good manufacturing practices or similar regulations in other jurisdictions resulting in mandated production halts or limitations; • Roche may experience manufacturing quality or control issues which halt or limit CellCept production; • a manufacturing plant may be closed as a result of a natural disaster or work stoppage; • Roche may experience short or long-term supply problems, or problems distributing CellCept, including difficulties importing or exporting supplies or products; • Roche may decrease its efforts to market and promote CellCept for the transplant indications thus lowering the visibility of CellCept in the market; and • Roche may set a low price for CellCept or give discounts or rebates that effectively lower the price of CellCept, which in either case could reduce our revenues |
| However, we may in the future outsource the manufacturing of CellCept for our clinical trials to third parties other than Roche, subject to approval from Roche and the FDA 19 _________________________________________________________________ The expiration of Rocheapstas patents covering CellCept may reduce our revenue as competitors may seek to sell generic versions of CellCept |
| Roche owns the patents covering the composition of matter of CellCept |
| The United States patent covering CellCept expires in May 2009 |
| Counterparts of this patent expire in most European countries in late 2010 or early 2011, but in some instances expire as early as 2007 |
| Roche patents covering the process for manufacture of CellCept expire in the United States in July 2012, and in most other countries in July 2013 |
| We and Roche expect that following expiration of all these patents competitors may manufacture and sell generic versions of CellCept, at a lower price, which would reduce CellCeptapstas revenues |
| In certain jurisdictions, including most Canadian provinces, legislation mandates generic substitution for brand name drugs |
| If competitors devise a means to manufacture CellCept which does not infringe Rocheapstas patents covering the process for manufacture, competitors may seek to sell generic versions of CellCept upon expiration of the composition of matter patents, which occurs in some countries as early as 2007 |
| If we obtain an orphan drug designation and FDA approval of CellCept for an indication, we would be entitled to seven years of marketing exclusivity for that orphan drug indication |
| In January 2006, we were granted orphan drug designation for CellCept’s use in myasthenia gravis |
| However, if a competitor obtained approval of a generic form of CellCept for another indication, such as transplant use, physicians would not be prevented from prescribing the generic drug for the orphan indication during the period of marketing exclusivity |
| Such prescribing practices could adversely affect the sales of CellCept for the orphan indication |
| We may incur significant liability if it is determined that we are promoting the "e off-label "e use of drugs or are otherwise found in violation of federal and state regulations in the United States or elsewhere |
| Physicians may prescribe drug products for uses that are not described in the productapstas labelling and that differ from those approved by the FDA or other applicable regulatory agencies |
| Such off-label uses are common across medical specialities |
| We are aware that some physicians are prescribing CellCept for the treatment of certain autoimmune diseases, although neither we nor Roche are permitted to promote CellCept for the treatment of any autoimmune diseases, and the FDA and other regulatory agencies have not approved the use of CellCept for any autoimmune indications |
| Although the FDA and other regulatory agencies do not regulate a physicianapstas choice of treatments, the FDA and other regulatory agencies do restrict communications on the subject of off-label use |
| Companies may not promote drugs for off-label uses |
| Accordingly, prior to approval of any autoimmune indications for CellCept, we may not promote CellCept for such indications |
| The FDA and other regulatory agencies actively enforce regulations prohibiting promotion of off-label uses and the promotion of products for which marketing clearance has not been obtained |
| A company that is found to have improperly promoted off-label uses may be subject to significant liability, including civil and administrative remedies as well as criminal sanctions |
| Notwithstanding the regulatory restrictions on off-label promotion, the FDA and other regulatory authorities allow companies to engage in truthful, non-misleading, and non-promotional speech concerning their products |
| We engage in medical education activities and communicate with investigators and potential investigators regarding our clinical trials |
| Although we believe that all of our communications regarding CellCept are in compliance with the relevant regulatory requirements, the FDA or another regulatory authority may disagree, and we may be subject to significant liability, including civil and administrative remedies as well as criminal sanctions |
| We and our collaborators are also subject to the US federal False Claims Act and US federal Anti-Kickback law |
| We have developed a comprehensive compliance program that seeks to establish internal controls to facilitate adherence to the rules and program requirements to which we are and will become subject |
| If, however, we are determined to have violated these and other laws, we could incur significant penalties and be subject to criminal prosecution |
| Roche might deem any such determination by a governmental authority to constitute a material breach of our agreement |
| In addition, managementapstas attention could be diverted and our reputation and our ability to enter into future collaborations could be damaged |
| If CellCept and any future products do not gain meaningful market acceptance we are not likely to generate significant revenues or sustain profitability |
| The degree of market acceptance for any product that we commercialize will depend on a number of factors, including: • acceptance by physicians and patients of each product as safe and effective; • potential advantages over existing or alternative therapies, including cost; • actual or perceived safety of similar classes of products; • relative convenience and ease of administration; 20 _________________________________________________________________ • reimbursement policies of government and third-party payors; • effectiveness of our sales, marketing and medical education efforts; and • scope of the product label approved by the FDA and other regulatory agencies |
| Hospitals or physicians may not choose to administer CellCept or any future product to the entire intended market, if at all |
| If CellCept and any future products do not achieve meaningful acceptance in their intended markets or if the intended market is smaller than anticipated, we are not likely to generate significant revenues or maintain profitability |
| Any failure or delay in obtaining additional capital may curtail the development or commercialization of CellCept or any future products |
| We expect that our future need for additional capital will be substantial |
| The extent of this need will depend on many factors, some of which are beyond our control, including: • our ability to develop and obtain regulatory approval for CellCept and any future products in our targeted indications; • our ability to establish marketing and sales capabilities and the costs of launching CellCept and any future products for our targeted indications; • the extent of costs associated with protecting and expanding our patent and other intellectual property rights; • market acceptance of CellCept and any future products for our targeted indications; • future payments, if any, we receive or make under existing or future collaborative arrangements; • the timing of regulatory approvals needed to market products for our targeted indications; • the need to acquire licenses for new products or compounds; and • compliance with rules and regulations implemented by the US Securities and Exchange Commission, Canadian provincial securities regulatory authorities, the NASDAQ National Market and the Toronto Stock Exchange |
| We have no committed sources of additional capital |
| Funds may not be available to us in the future on favorable terms, if at all, and we may be required to delay, reduce the scope of, or eliminate research and development efforts or clinical trials for CellCept or other future products |
| We may also be forced to curtail or restructure our operations, obtain funds by entering into arrangements with collaborators on unattractive terms or relinquish rights to technologies or product candidates that we would not otherwise relinquish in order to continue our operations |
| If we are not successful in establishing additional collaborations we will not be able to grow our business |
| Our long-term success depends upon our ability to identify drugs and drug candidates with significant potential and to acquire the rights for those indications from multiple collaborators, thus creating multiple sources of revenue |
| We face intense competition from other companies for collaborative arrangements with pharmaceutical and biopharmaceutical companies, and there are no barriers prohibiting other companies from adopting our business model |
| Pharmaceutical and biopharmaceutical companies may also decide to pursue new indications for their products themselves, rather than enter into collaborative arrangements to develop new indications |
| In addition, accurate sales tracking may be difficult or impossible under future collaborations which may preclude a collaboration or lead to disputes once a collaboration has been established |
| We currently only have one collaboration |
| If we are unable to enter into additional collaborations, we will continue to be dependent upon Roche for substantially all our revenues, and we will be limited in our ability to grow our business |
| In addition, the fact that we are collaborating with Roche, or other potential collaborators, may be viewed negatively by other potential collaborators, making them less likely to enter into arrangements with us |
| The terms and conditions of any future collaboration agreements may be less favorable than our agreement with Roche |
| Our strategy is to seek collaborations with pharmaceutical and biopharmaceutical companies to develop and commercialize new indications |
| Any new collaborations that we may secure will likely involve drugs or drug candidates, or collaborators, with characteristics different from CellCept or Roche |
| These characteristics may include: • costs to manufacture, distribute and sell; • patent terms; • expenditures by our collaborators on research and development; • size and difficulty of development programs for potential product indications; 21 _________________________________________________________________ • competitive threats; and • other factors relevant to the development and commercialization of such products |
| We expect that any new collaborations will be highly negotiated, and the above characteristics all may play a role in the financial terms of such collaborations, possibly resulting in any or all of the following: • our payment of upfront or milestone fees for product rights; • greater clinical trial expenses; • longer timelines to approval; • lower revenue sharing percentages; • shorter agreement periods; or • less than global product rights |
| In addition, any new collaboration agreement may provide that we only begin sharing revenue with our collaborator after some long period of time after entering into such collaboration, or after some specific action or approval over which we may have limited control |
| If we fail to establish sufficient marketing and sales promotion capabilities, or enter into successful arrangements with third parties to conduct these activities, we may be unable to generate sufficient revenue to continue our operations |
| Roche is solely responsible for distributing and selling CellCept |
| If we obtain approval of CellCept for autoimmune indications, or any future products, we intend to market and promote them through our own sales promotion force in the United States and certain other countries |
| We currently have no sales promotion capabilities, limited marketing capabilities, limited infrastructure to support such activities, and have limited experience in the commercialization of pharmaceutical products |
| We may not be able to attract and retain qualified marketing or sales promotion people or be able to establish an effective sales promotion force |
| In countries where we do not have a sales promotion force, we may establish relationships with third parties |
| However, we may not be able to enter into such arrangements on favorable terms or at all and to the extent that we enter into such arrangements, our revenue will depend on their efforts, which may not be successful |
| If product liability lawsuits are successfully brought against us, we will incur significant liabilities and may be required to limit the commercialization of our product candidates |
| Our use of CellCept and other products in clinical trials, and our future promotion of any products, may expose us to product liability claims and associated adverse publicity |
| We have a global product clinical trial insurance policy, with aggregate coverage of dlra10dtta0 million, for countries not requiring a local insurance policy (including USA and Canada) |
| In addition, we have policies in varying amounts for all the other countries in which we are conducting clinical trials, and which do not fall within the scope of our global policy |
| Our insurance coverage may not protect us against any or all of the product liability claims which could be brought against us in the future |
| Prior to the commercialization of CellCept in autoimmune indications, we expect to obtain product liability insurance for potential claims associated with our promotion of CellCept |
| However, we may not be able to obtain or maintain adequate insurance coverage at a commercially reasonable cost or in sufficient amounts or scope to protect us against potential losses |
| Roche is obligated to indemnify us for any product liability claims, except if the claims arise due to false or misleading promotional activity on our part |
| In the event a product liability claim is brought against us, we may be required to pay legal and other expenses to defend the claim and, if such a claim is successful, damage awards not covered by our insurance |
| We may also be obligated to indemnify our collaborators |
| Defending any product liability claim or claims could require us to expend significant financial and managerial resources |
| If our competitors are able to develop and market products that are preferred over CellCept or other product candidates that we may develop, we may not be able to generate sufficient revenues to continue our operations |
| We may not be able to contend successfully with competitors |
| The biotechnology and pharmaceutical industries are highly competitive and subject to significant and rapid technological change as researchers learn more about diseases and develop new technologies and treatments |
| Our current and potential competitors generally include major multinational pharmaceutical companies, biopharmaceutical firms, specialty pharmaceutical companies, universities and other research institutions |
| In the transplant market, CellCept currently competes with Novartis &apos product, Myfortic |
| If CellCept is approved for any autoimmune indications, Novartis may choose to also pursue clinical trials and regulatory approval for the same indications |
| If approved, CellCept will also compete with immunosuppressants, such as steroids and cytotoxic agents, including cyclophosphamide, cyclosporine and azathioprine |
| A cytotoxic agent is an anti-cancer substance that acts by killing or preventing the division of cells |
| In addition, we are aware of several companies that have products in development or on the market that may be competitive with CellCept in lupus nephritis, myasthenia gravis and pemphigus vulgaris |
| Some of the companies have commenced clinical trials for products targeting the same markets and indications that we are addressing |
| 22 _________________________________________________________________ The existence of these products, other products or treatments of which we are not aware, or products or treatments that may be developed in the future may reduce the marketability of CellCept and any future products, particularly to the extent such products: • are more effective; • have fewer or less severe adverse side effects; • have better patient compliance; • receive better reimbursement terms; • are accepted by more physicians; • are more adaptable to various modes of dosing; • have better distribution channels; • are easier to administer; or • are less expensive |
| Some of our competitors, either alone or together with their collaborators, have substantially greater financial resources and larger research, development and regulatory staffs than we do |
| In addition, many of our competitors, either alone or together with their collaborators, have significantly greater experience than we do in discovering, developing, manufacturing and marketing products |
| Additional mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated in our competitors |
| If we are unable to effectively manage our expected future growth, we may be unable to develop or commercialize CellCept or any other product candidate successfully |
| In 2005, we increased our number of employees by 53 and, as of December 31, 2005, we had 106 employees |
| In order to continue the development and potential commercialization of CellCept for autoimmune indications and enter into new collaborations we will need to expand our clinical development, regulatory, marketing and sales promotion capabilities |
| We currently have operations in Canada, the United States, the United Kingdom, and Switzerland |
| Our ability to manage our global operations and expected growth will require us to continue to improve our operational, financial and management controls, reporting systems and procedures |
| We may not be able to make such improvements in an efficient or timely manner and may discover deficiencies in existing systems and controls |
| Our ability to develop and commercialize products for new indications and compete effectively, and our future financial performance will depend, in part, on our ability to manage any future growth effectively |
| We depend on our executive officers, and if we are not able to retain them or recruit additional qualified personnel, we may be unable to successfully develop or commercialize CellCept |
| Our success depends upon the continued contributions of our executive officers and scientific and technical personnel |
| We are highly dependent on Richard M Glickman, our Chief Executive Officer, Noel F Hall, our President, Bruce Cousins, our Chief Financial Officer, and Reinhard WA Baildon, our Executive Vice President, Clinical and Regulatory Affairs |
| Due to the specialized knowledge that each of our executive officers possess with respect to CellCept and our operations, the loss of service of any of our executive officers could delay or prevent the successful completion of the clinical trials necessary for the commercialization of CellCept for lupus nephritis, myasthenia gravis or pemphigus vulgaris and could harm our relationship with Roche |
| We carry key man life insurance coverage of dlra1dtta2 million for each of Richard M Glickman and Noel F Hall |
| We do not carry key man life insurance for any of our other executive officers |
| We have employment agreements with each of our executive officers; however, each may terminate their employment upon notice and without cause or good reason |
| We currently are not aware that any executive officer is planning to leave or retire |
| Our success also depends in part on our ability to attract and retain highly qualified scientific, commercial and administrative personnel |
| In order to pursue our product development and commercialization strategies, we will need to attract and hire additional personnel with experience in a number of disciplines, including clinical testing, government regulation, sales and marketing, drug reimbursement and information systems |
| There is intense competition for personnel in the fields in which we operate |
| We have not experienced difficulty to date in attracting and retaining the personnel we require |
| If, however, we are unable to continue to attract new employees and retain existing employees, we may be unable to continue our development and commercialization activities |
| 23 _________________________________________________________________ We may incur losses associated with currency fluctuations and may not be able to effectively hedge our exposure |
| Our operations are in many instances conducted in currencies other than the US dollar and fluctuations in the value of currencies relative to the US dollar could cause us to incur currency exchange losses |
| All amounts paid by Roche to us will be in Swiss Francs |
| In addition, we currently conduct some operations and incur a portion of our expenses in Canadian dollars, pounds sterling and other foreign currencies |
| Although we have implemented currency hedging techniques during 2005 to mitigate the impact of currency fluctuations on our financial results, these techniques do not eliminate the effects of currency fluctuations with respect to anticipated revenues or cash flows, and, as they are short term in nature, do not protect us from prolonged periods of currency fluctuations |
| CellCept net sales are denominated in multiple currencies and will be converted to Swiss Francs by Roche for the purpose of calculating amounts to be paid to us |
| To the extent the Swiss Franc increases in value relative to these other currencies, the total aggregate value of CellCeptapstas net sales will decrease and the amount, if any, that we are entitled to may be reduced |
| Risks Related to Regulatory Matters We will not be able to commercialize our product candidates if our clinical trials do not demonstrate safety and efficacy in humans |
| We are currently not authorized to market CellCept for autoimmune indications in any jurisdiction, and we may never be authorized to market CellCept for any autoimmune indication |
| The development and commercialization of CellCept for autoimmune indications, and any future products, are subject to extensive and rigorous regulation by the US federal government, principally the FDA, other federal, state and local agencies, and governmental authorities elsewhere |
| Prior to marketing CellCept for any autoimmune indication, we must conduct, at our own expense, extensive clinical trials to demonstrate with substantial evidence to the satisfaction of the FDA and other regulatory authorities that CellCept is safe and effective for the indication |
| We have no prior experience as a company in conducting clinical trials |
| Preclinical studies and clinical trials are expensive, can take many years and have uncertain outcomes |
| In addition, the regulatory approval procedures vary among countries and additional testing may be required in some jurisdictions |
| It may take several years to complete the requisite clinical trials, and a product candidate may fail any stage of testing |
| Difficulties and risks associated with clinical trials may result in our failure to receive regulatory approval to market CellCept for autoimmune indications or our inability to commercialize any future products for new indications |
| The FDA, other regulatory authorities, our collaborators, or we may suspend or terminate clinical trials at any time |
| The commencement and completion of our clinical trials could be delayed or prevented by several factors, including: • delays in obtaining regulatory approvals to commence or continue a study; • delays in identifying and reaching agreement on acceptable terms with prospective clinical trial sites; • insufficient quantities of the study drug; • slower than expected rates of patient recruitment and enrollment or the inability to reach full enrollment; • inconclusive or negative interim results during clinical trials, including lack of effectiveness or unforeseen safety issues; • death of, or serious adverse effects experienced by, one or more patients during a clinical trial even if the reasons are not related to the study drug, including the advanced stage of the patientapstas disease or medical condition; • uncertain dosing issues; • inability to monitor patients adequately during and after treatment; • inability or unwillingness of contract laboratories to follow good laboratory practices; • inability or unwillingness of clinical investigators to follow our clinical protocols or good clinical practices generally; and • inability or unwillingness of other third parties to perform data collection and analysis in a timely or accurate manner |
| Delays or failures in obtaining regulatory approvals may: • delay or prevent the commercialization of any product that we develop for new indications; 24 _________________________________________________________________ • diminish any competitive advantages; • reduce or eliminate revenue from the sale of CellCept and any future products; and • adversely affect our ability to attract new collaborators |
| The results of early clinical trials do not necessarily predict the results of later clinical trials |
| We are aware that Roche conducted three phase III clinical trials for CellCept in the treatment of rheumatoid arthritis which did not demonstrate efficacy |
| Even if we believe the data collected from clinical trials of drugs are promising, such data may not be sufficient to support approval by the FDA or any other regulatory authority |
| The FDA or other regulatory authorities could also interpret our data differently, which could delay, limit or prevent regulatory approval |
| We expect to rely in part on the results of CellCept clinical trials that were previously performed by or on behalf of Roche and on clinical trials that were previously performed or are being performed by third-party physicians |
| These trial results may not be predictive of the results of the clinical trials that we plan to conduct for the purposes of our targeted indications |
| In addition, the results of prior clinical trials may not be acceptable to the FDA or other regulatory authorities because the data may be incomplete, outdated or not otherwise acceptable for inclusion in our submissions for regulatory approval for CellCept in autoimmune indications |
| Even if CellCept or any future product candidate receives regulatory approval, we and our collaborators may still face development and regulatory difficulties that may delay or impair future sales |
| If we or our collaborators obtain regulatory approval for CellCept for any of our targeted indications, or any other product, we and our collaborators will continue to be subject to extensive regulation by the FDA, other federal authorities, certain state agencies and regulatory authorities elsewhere |
| These regulations will impact many aspects of our operations and the drug manufacturerapstas operations including manufacture, record keeping, quality control, adverse event reporting, storage, labelling, advertising, promotion, sale and distribution, export and personnel |
| The FDA and state agencies may conduct periodic inspections to assess compliance with these requirements |
| We, together with our collaborators, will be required to conduct post-marketing surveillance of the product |
| We also may be required to conduct post-marketing studies |
| Our or our collaborators &apos failure to comply with applicable FDA and other regulatory requirements, or the later discovery of previously unknown problems, may result in restrictions including: • delays in commercialization; • refusal by the FDA or other similar regulatory agencies to review pending applications or supplements to approved applications; • product recalls or seizures; • warning letters; • suspension of manufacturing; • withdrawals of previously approved marketing applications; • fines and other civil penalties; • injunctions, suspensions or revocations of marketing licenses; • refusals to permit products to be imported to or exported from the United States; and • criminal prosecutions |
| Post-approval marketing laws and regulations in other jurisdictions generally provide for the same types of sanctions that may be imposed in the United States |
| We may experience delays in patient enrollment, which would delay regulatory approval of CellCept in autoimmune indications and possibly reduce our revenues |
| Our ability to obtain, and the timing of, regulatory approval for CellCept in any autoimmune indication depends in part on our ability to successfully complete clinical trials of CellCept in that autoimmune indication |
| The ability to complete clinical trials depends, in part, on the rate of patient enrollment and patient retention, which is a function of many factors, some of which are beyond our control |
| In particular, because some of our clinical trials will be blinded so that some patients receive CellCept and others receive another drug or a placebo, and because CellCept is marketed for transplant indications and prescribed by physicians, patients may not want to participate in a clinical trial in which they could receive a placebo or drug other than CellCept |
| 25 _________________________________________________________________ If third-party clinical research organizations do not perform in an acceptable and timely manner, our clinical trials could be delayed or unsuccessful |
| We have limited experience as a company in conducting and managing clinical trials, and rely on third parties, including contract research organizations, outside consultants and principal investigators to assist us in managing, monitoring and conducting our clinical trials |
| We rely on these parties to assist in the recruitment of sites for participation in clinical trials, to maintain positive relations with the clinical sites and to ensure that these sites conduct the trials in compliance with the protocol and our instructions |
| If these third parties fail to perform satisfactorily or do not adequately fulfill their obligations to us, our clinical trials may be delayed or unsuccessful |
| The FDA or other regulatory agencies may inspect some of our clinical sites or our third-party vendors &apos sites, to determine if our clinical trials are being conducted according to current good clinical practices |
| If the FDA or another applicable regulatory agency determines that our third-party vendors are not in compliance with applicable regulations, we may be required to delay, repeat or terminate such clinical trials |
| Any delay, repetition or termination of our clinical trials could prevent or delay the commercialization of CellCept for autoimmune indications and any other future product candidate |
| If government and third-party payors fail to provide coverage and adequate reimbursement rates for our product candidates, our revenues and potential for profitability will be reduced |
| In the United States and elsewhere, our product revenues will depend principally upon the reimbursement rates established by third-party payors, including government health administration authorities, managed-care providers, public health insurers, private health insurers and other organizations |
| These third-party payors are increasingly challenging the price, and examining the cost effectiveness, of medical products and services |
| In addition, significant uncertainty exists as to the reimbursement status, if any, of newly approved drugs, pharmaceutical products or product indications |
| We may need to conduct post-marketing clinical trials in order to demonstrate the cost-effectiveness of products |
| Such studies may require us to commit a significant amount of management time and financial and other resources |
| CellCept is included in various drug compendia as a commercially approved drug in connection with the prevention of organ rejection and certain third party payors provide reimbursement for this use of CellCept because of such inclusion |
| However, CellCept or other future products may not be reimbursed or covered by any of these third-party payors for our targeted indications |
| In some countries other than the United States, particularly the countries of the European Union and Canada, the pricing of prescription pharmaceuticals is subject to governmental control |
| In these countries, obtaining pricing approval from governmental authorities can take six to twelve months or longer after the receipt of regulatory marketing approval of a product for an indication |
| To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of a product that is the subject of a collaboration with us to other available therapies |
| If reimbursement of such products is unavailable or limited in scope or amount or if pricing is set at unsatisfactory levels our revenues could be reduced |
| Domestic and foreign governments continue to propose and pass legislation designed to reduce the cost of healthcare, including drugs |
| In the United States, there have been, and we expect that there will continue to be, federal and state proposals to implement similar governmental control |
| In addition, increasing emphasis on managed care in the United States will continue to put pressure on the pricing of pharmaceutical products |
| For example, the Medicare Prescription Drug Improvement and Modernization Act of 2003 reforms the way Medicare will cover and reimburse for pharmaceutical products |
| The legislation expands Medicare coverage for drug purchases by the elderly and has resulted in a new reimbursement methodology based on average sales prices for certain drugs |
| In addition, the new legislation provides authority for limiting the number of outpatient drugs that will be covered in any therapeutic class |
| As a result of the new legislation and the expansion of federal coverage of drug products, we expect that there will be additional pressure to contain and reduce costs |
| The Medicaid program has recently been modified and state healthcare laws and regulations will soon be amended to conform to the federal changes |
| The new laws and regulations will reduce Medicaid reimbursement |
| Cost control initiatives could decrease the established reimbursement rates that we receive for any products in the future, which would limit our revenues and profitability |
| Legislation and regulations affecting the pricing of pharmaceutical products, including CellCept, may change at any time, which could further limit or eliminate reimbursement rates for CellCept or other products |
| Risks Related to Intellectual Property We may incur significant expenses or be prevented from developing or commercializing products as a result of an intellectual property infringement claim |
| Our commercial success depends in part on our ability to operate without infringing the patents and other proprietary rights of third parties |
| Infringement proceedings in the pharmaceutical and biotechnology industries are lengthy, costly and time-consuming and their outcome is uncertain |
| If we become involved in any patent litigation, interference or other administrative proceedings, we will incur substantial expense and the efforts of our technical and management personnel will be significantly diverted |
| As a result of such litigation or proceedings we could lose our proprietary position and be restricted or prevented from developing, manufacturing and selling the affected products, incur significant damage awards, including punitive damages, or be required to seek third-party licenses that may not be available on commercially acceptable terms, if at all |
| 26 _________________________________________________________________ Although Roche has an extensive patent estate covering the composition of matter, methods of treatment and manufacture of CellCept, it is possible that a third party may be issued a patent covering some aspect of CellCept or its use |
| If this happens, we and Roche may be restricted from developing and commercializing CellCept for autoimmune indications |
| If a third party brings an infringement claim against us based solely upon the development or promotion of CellCept in autoimmune indications, Roche has the right under our agreement to deduct 50prca of its cost in defending such action, plus any amounts paid in settlement or in a judgment against Roche or Aspreva, from the calculation of CeIlCeptapstas net sales prior to determining our share of such sales |
| Roche is obligated to indemnify us if the infringing activity relates to the development and commercialization of CellCept in both transplant and non-transplant indications |
| If we or our collaborators are unable to adequately protect or enforce our intellectual property, our competitive position could be impaired |
| Our commercial success depends in part on our ability to: • obtain patents or rights to patents and maintain their validity; • protect our trade secrets; and • effectively enforce our proprietary rights or patents against infringers |
| Patent applications may not result in patents being issued |
| As a result, we may face unanticipated competition, or conclude that, without patent rights, the risk of bringing products to the market is too great |
| Even if we or our collaborators are issued patents covering our products we cannot predict with certainty whether we or our collaborators will be able to ultimately enforce our patents or proprietary rights |
| Any patents that we own or license may be challenged, invalidated or circumvented and may not provide us with protection against competitors |
| We or our collaborators may be forced to engage in costly and time-consuming litigation in order to protect our intellectual property rights |
| In addition, our collaborators may choose not to enforce or maintain their intellectual property rights, and we may be forced to incur substantial additional costs to maintain or enforce such rights |
| Patent rights may not provide us with adequate proprietary protection or competitive advantages against competitors with similar products or technologies |
| The laws of certain foreign countries do not protect our intellectual property rights to the same extent as do the laws of the United States |
| In addition to patents, we rely on trade secrets and proprietary know-how |
| We seek protection, in part, through confidentiality and non-disclosure agreements |
| These agreements may not provide meaningful protection of our technology or adequate remedies in the event of unauthorized use or disclosure of confidential and proprietary information and, in any event, others may develop independently, or obtain access to, the same or similar information |
| Our failure or inability to protect our trade secrets and proprietary know-how could impair our competitive position |
| Our stock price is volatile and purchasers of our common shares could incur substantial losses |
| Since our initial public offering on March 4, 2005 and through February 15, 2006 our common shares have traded on the NASDAQ National Market between dlra11dtta18 and dlra27dtta90 per share |
| The stock market in general and the market for biopharmaceutical and biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies |
| The price for our common shares may be influenced by many factors, including: • our ability to develop and obtain regulatory approval for CellCept and any future products in our targeted indications; • our ability to establish marketing and sales capabilities and the costs of launching CellCept and any future products for our targeted indications; • market acceptance of CellCept and any future products for our targeted indications; • developments concerning our collaboration with Roche; • our success in establishing additional collaborations; • regulatory developments in the United States, Canada and other countries; • developments or disputes concerning patents or other proprietary rights; • public concern over CellCept or any future products; • litigation; 27 _________________________________________________________________ • the departure of key personnel; • future sales of our common shares; • variations in our financial results or those of companies that are perceived to be similar to us; • investors’ perceptions of us; and • general economic, industry and market conditions |
| If there are substantial sales of our common shares, our stock price could decline |
| If our existing shareholders sell a large number of our common shares or the public market perceives that existing shareholders might sell our common shares, the market price of our common shares could decline significantly |
| Our executive officers, directors and major shareholders continue to have substantial control over us and will maintain the ability to control all matters submitted to shareholders for approval |
| As of December 31, 2005, our directors and executive officers, together with their affiliates, beneficially owned the majority of our outstanding common shares, including shares subject to outstanding stock options and warrants |
| These shareholders, acting together, can exercise significant influence over all matters requiring shareholder approval, including the election of directors and any amendment of our notice of articles or articles |
| This concentration of ownership could also have the effect of delaying or preventing a change in our control |
| Our articles, our shareholder rights plan and certain Canadian laws could delay or deter a change of control |
| Our authorized preferred capital stock is available for issuance from time to time at the discretion of our board of directors, without shareholder approval |
| Our articles grant our board of directors the authority, subject to the corporate law of British Columbia, to determine or alter the special rights and restrictions granted to or imposed on any wholly unissued series of preferred shares, and such rights may be superior to those of our common shares |
| Also, pursuant to our shareholder rights plan, anyone who seeks to acquire 20prca or more of our outstanding common shares is required to make a bid complying with specific provisions of the plan |
| Limitations on the ability to acquire and hold our common shares may be imposed by the Competition Act (Canada) |
| This legislation permits the Commissioner of Competition of Canada to review any acquisition of a significant interest in us |
| This legislation grants the Commissioner jurisdiction to challenge such an acquisition before the Canadian Competition Tribunal if the Commissioner believes that it would, or would be likely to, result in a substantial lessening or prevention of competition in any market in Canada |
| The Investment Canada Act (Canada) subjects an acquisition of control of a company by a non-Canadian to government review if the value of our assets as calculated pursuant to the legislation exceeds a threshold amount |
| A reviewable acquisition may not proceed unless the relevant minister is satisfied that the investment is likely to be a net benefit to Canada |
| Any of the foregoing could prevent or delay a change of control and may deprive or limit strategic opportunities for our shareholders to sell their shares |
| We may be a passive foreign investment company for US tax purposes which may negatively affect US investors |
| For US federal income taxation purposes, we will be a passive foreign investment company, or PFIC, if in any taxable year either: (a) 75prca or more of our gross income consists of passive income; or (b) 50prca or more of the value of our assets is attributable to assets that produce, or are held for the production of, passive income |
| If we meet either test, our shares held by a US person in that year will be PFIC shares for that year and all subsequent years in which they are held by that person |
| Because in the past our gross income consisted mostly of interest, we have been a PFIC in prior taxable years |
| Gain realized by a US investor from the sale of PFIC shares is taxed as ordinary income, as opposed to capital gain, and subject to an interest charge unless the US person has timely made a certain tax election |
| The PFIC rules are extremely complex |
| A US person is encouraged to consult his or her US tax advisor before making an investment in our shares |
| As a foreign private issuer, we are subject to different US securities laws and rules than a domestic US issuer, which may limit the information publicly available to our shareholders |
| As a foreign private issuer we are not required to comply with all the periodic disclosure requirements of the Securities Exchange Act of 1934 and therefore there may be less publicly available information about Aspreva than if we were a US domestic issuer |
| In addition, our officers, directors, and principal shareholders are exempt from the reporting and "e short-swing "e profit recovery provisions of Section 16 of the Securities Exchange Act of 1934 and the rules thereunder |
| However, under Canadian provincial securities laws, our officers, directors and principal shareholders are required to file reports in electronic format through the System for Electronic Disclosure by Insiders, or SEDI, disclosing changes in beneficial ownership of, or control or direction over, our common shares and other securities |
| Our shareholders can access such reports at www |
| 28 _________________________________________________________________ You may be unable to enforce actions against us, or certain of our directors and officers, under US federal securities laws |
| We are a corporation organized under the laws of British Columbia, Canada |
| A majority of our directors and officers reside principally in Canada |
| Because all or a substantial portion of our assets and the assets of these persons are located outside the US, it may not be possible for you to effect service of process within the United States upon us or those persons |
| Furthermore it may not be possible for you to enforce against us or them in the United States, judgments obtained in US courts based upon the civil liability provisions of the US federal securities laws or other laws of the US There is doubt as to the enforceability, in original actions in Canadian courts, of liabilities based upon the US federal securities laws and as to the enforceability in Canadian courts of judgments of US courts obtained in actions based upon the civil liability provisions of the US federal securities laws |
| Therefore, it may not be possible to enforce those actions against us or certain of our directors and officers |