LIGAND PHARMACEUTICALS INC - LGND Quarterly Report (10-Q) ITEM 2. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL ...

The following is an excerpt from a 10-Q SEC Filing, filed by LIGAND PHARMACEUTICALS INC on 5/7/2004.

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ITEM 2. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

Caution: This discussion and analysis may contain predictions, estimates and other forward-looking statements that involve a number of risks and uncertainties, including those discussed at "Risks and Uncertainties". This outlook represents our current judgment on the future direction of our business. Such risks and uncertainties could cause actual results to differ materially from any future performance suggested. We undertake no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date of this quarterly report. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Our trademarks, trade names and service marks referenced herein include Ligand®, AVINZA®, ONTAK®, Panretin® and Targretin®. Each other trademark, trade name or service mark appearing in this quarterly report belongs to its owner.

Overview

We discover, develop and market drugs that address patients' critical unmet medical needs in the areas of cancer, pain, men's and women's health or hormone-related health issues, skin diseases, osteoporosis, blood disorders and metabolic, cardiovascular and inflammatory diseases. Our drug discovery and development programs are based on our proprietary gene transcription technology, primarily related to Intracellular Receptors, also known as IRs, a type of sensor or switch inside cells that turns genes on and off, and Signal Transducers and Activators of Transcription, also known as STATs, which are another type of gene switch.

We currently market five products in the United States: AVINZA®, for the relief of chronic, moderate to severe pain; ONTAK®, for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (or CTCL); Targretin® capsules, for the treatment of CTCL in patients who are refractory to at least one prior systemic therapy; Targretin® gel, for the topical treatment of cutaneous lesions in patients with early stage CTCL; and Panretin® gel, for the treatment of Kaposi's sarcoma in AIDS patients. In Europe, we have marketing authorizations for Panretin® gel and Targretin® capsules and are currently marketing these products under arrangements with local distributors. In April 2003, we withdrew our ONZAR™ (ONTAK® in the U.S.) marketing authorization application in Europe for our first generation product. It was our assessment that the cost of the additional clinical and technical information requested by the European Agency for the Evaluation of Medicinal Products (or EMEA) for the first generation product would be better spent on acceleration of the second generation ONTAK® development. We expect to resubmit the ONZAR™ application with the second generation product in 2005.

In February 2003, we entered into an agreement for the co-promotion of AVINZA® with Organon Pharmaceuticals USA Inc. (or Organon). Under the terms of the agreement, Organon committed to specified numbers of primary and secondary product calls delivered to high prescribing physicians and hospitals beginning in March 2003. In exchange, we pay Organon a percentage of AVINZA® net sales based on the following schedule:

Annual Net Sales of AVINZA % of Incremental Net Sales Paid to -------------------------- Organon by Ligand $0-35 million (2003 only) 0% (2003 only) $0-150 million 30% $150-300 million 40% $300-425 million 50% >$425 million 45%

During the first quarter of 2004, we incurred co-promotion expense of $6.7 million, with no such expenses recognized in the same period during 2003. Additionally, both companies agreed to share equally all costs for AVINZA® advertising and promotion, medical affairs and clinical trials. Each company is responsible for its own sales force costs and other expenses. The initial term of the co-promotion agreement is 10 years. Organon has the option any time prior to January 1, 2008 to extend the agreement to 2017 by making a $75.0 million payment to us.

We are currently involved in the research phase of research and development collaborations with Eli Lilly and Company (or Lilly) and TAP Pharmaceutical Products Inc. (or TAP). Collaborations in the development phase are being pursued by GlaxoSmithKline, Lilly, Organon, Pfizer, TAP and Wyeth. We receive funding during the research phase of the arrangements and milestone and royalty payments as products are developed and marketed by our corporate partners. In addition, in connection with some of these collaborations, we received non-refundable up-front payments. As of March 31, 2004, we had deferred revenue of $0.2 million resulting from an up-front payment received under our collaboration agreement with TAP. This amount is being amortized as revenue over the service period of the agreement which runs from June 2001 to June 2004.

We have been unprofitable since our inception on an annual basis. We achieved quarterly net income for the first time in our corporate history during the fourth quarter of fiscal 2003. To consistently be profitable, we must successfully develop, clinically test, market and sell our products. Even if we consistently achieve profitability, we cannot predict the level of that profitability or whether we will be able to sustain profitability. We expect that our operating results will fluctuate from period to period as a result of differences in the timing of revenues earned from product sales, expenses incurred, collaborative arrangements and other sources. Some of these fluctuations may be significant.

Recent Developments

In March 2004, Ligand and Organon announced plans to increase sales calls to primary care physicians and the long-term care and hospice market segments. We plan to achieve this through the hiring of an additional 36 Ligand specialty sales representatives that will call on top decile primary care physicians, starting in the second quarter of 2004, in a mirrored activity to Organon's sales representatives. The long-term care and hospice efforts will be achieved through an additional focus of the Organon hospital sales force and a specific call plan on key long-term care and hospice physicians and pain treatment staff, also starting in the second quarter of 2004.

Results of Operations

Total revenues for the first quarter of 2004 were $36.6 million compared to $23.1 million for the first quarter of 2003. Loss from operations for the first quarter of 2004 was $10.3 million compared to $12.6 million for the 2003 period. Net loss for the first quarter of 2004 was $13.1 million, or $.18 per share, compared to net loss of $20.3 million, or $.29 per share, for the first quarter of 2003.

Product Sales

Net product sales for the first quarter of 2004 were $34.1 million compared to $18.9 million for the first quarter of 2003. A comparison of sales by product is as follows (in thousands):

Quarter Ended March 31,
2004 2003
AVINZA® $ 22,436 $ 6,648 ONTAK® 7,308 7,131 Targretin ® capsules 3,506 3,596 Targretin® gel and Panretin® gel 886 1,553 Total net product sales $ 34,136 $ 18,928

The increase in sales of AVINZA® is due to higher prescriptions as a result of the increased level of marketing and sales activity under our co-promotion agreement with Organon which started in March 2003. As a result of the co-promotion arrangement, AVINZA® is now promoted by approximately 800 sales representatives compared to approximately 50 representatives in the first quarter of 2003 prior to co-promotion. Sales in the first quarter of 2004 also benefited from a price increase of 9.9% effective January 1, 2004. AVINZA® sales for the quarter were negatively impacted, however, by wholesaler purchases in the fourth quarter of 2003 in advance of the announced price increase. In addition AVINZA® sales were negatively impacted by a higher level of Medicaid prescriptions in states where 1) AVINZA® recently obtained preferred formulary status relative to competing products and 2) in states where AVINZA® recently came onto the state formulary but not in a preferred position. As a result, the provision for rebates in the first quarter of 2004 was increased by approximately $2.5 million and $0.5 million, respectively. AVINZA® sales in the first quarter of 2004 were also negatively impacted by approximately $1.0 million related to higher than estimated product returns from development stage batches with shorter than normal expiry dates.

The increase in ONTAK® sales in the first quarter of 2004 compared to the first quarter of 2003 reflects a 9.0% price increase effective January 1, 2004 and increasing use (impacted in part by expanded clinical data) in cutaneous T-cell lymphoma (or CTCL), chronic lymphocytic leukemia (or CLL), non-Hodgkins lymphoma (or NHL) and graft-versus-host disease (or GVHD). Sales of Targretin® capsules also benefited from a 7.0% price increase effective January 1, 2004 while prescriptions for the first quarter of 2004 were consistent with the first quarter of 2003. Sales of both ONTAK®and Targretin® capsules, however, were negatively impacted by increased chargebacks and rebates reflecting changes in our patient mix and evolving reimbursement rates. We continue to study recently enacted changes to the 2004 Centers of Medicare and Medicaid Services reimbursement rates for ONTAK® and Section 641 of the Medicare Prescription Drug Improvement and Modernization Act relating to anti-cancer drugs for Targretin®. We continue to expect improved patient access for Targretin® capsules but increased challenges for a small sub-segment of our ONTAK®/Medicare patients in 2004 and 2005.

Our product sales for any individual quarter can be influenced by a number of factors including changes in demand for a particular product, the level and nature of promotional activity, the timing of announced price increases, wholesaler inventory practices and the level of prescriptions subject to rebates and chargebacks. According to IMS Health National Prescription Audit (or IMS NPA) data, AVINZA®ended the first quarter of 2004 with a market share of prescriptions in the sustained-release opioid market of 4.0% compared to less than 1.0% in the first quarter of 2003. We expect that AVINZA® prescription market share will continue to increase as a result of a higher level of sales and marketing activity compared to 2003. We also expect that the expansion of the Ligand and Organon AVINZA® sales forces and sales efforts discussed under the "Recent Developments" section above will have a further positive impact on AVINZA® sales and prescriptions. Overall demand for ONTAK® measured by unit shipments from wholesalers to end users, increased 20% for the 2004 period compared to the prior year. We expect that total product sales will continue to increase in 2004 due primarily to higher sales of AVINZA®, which will further benefit from our co-promotion arrangement with Organon. We also continue to expect that demand for and sales of ONTAK® will increase as further data is obtained from ongoing expanded-use clinical trials and the initiation of new expanded-use trials. The level and timing of any such increases, however, are influenced by a number of factors outside our control, including the accrual of patients and overall progress of clinical trials that are managed by third parties.

Excluding AVINZA®, our products are small-volume specialty pharmaceutical products that address the needs of cancer patients in relatively small niche markets with substantial geographical fluctuations in demand. To ensure patient access to our drugs, we maintain broad distribution capabilities with inventories held at approximately 150 locations throughout the United States. Furthermore, the purchasing and stocking patterns of our wholesaler customers are influenced by a number of factors that vary with each product. These factors include, but are not limited to, overall level of demand, periodic promotions, required minimum shipping quantities and wholesaler competitive initiatives. As a result, the level of product in the distribution channel may average from two to six months' worth of projected inventory usage. If any or all of our major distributors decide to substantially reduce the inventory they carry in a given period, our sales for that period could be substantially lower than historical levels.

Collaborative Research and Development and Other Revenues

Collaborative research and development and other revenues for the quarter ended March 31, 2004 were $2.5 million compared to $4.2 million for the quarter ended March 31, 2003. A comparison of collaborative research and development and other revenues is as follows (in thousands):

Quarter Ended March 31,
2004 2003
Collaborative research and development $ 2,398 $ 4,117 Other 78 78 $ 2,476 $ 4,195

Collaborative research and development revenue includes reimbursement for ongoing research activities, earned development milestones and recognition of prior years' up-front fees previously deferred in accordance with Staff Accounting Bulletin ("SAB") No. 101, Revenue Recognition in Financial Statements.

The decrease in ongoing research activities reimbursement revenue in 2004 compared to the corresponding quarter in 2003 is due to lower funding from our research arrangement with Lilly, which contributed $1.1 million to revenue in the first quarter of 2004 compared to $1.4 million in the first quarter of 2003. The initial research term of the Lilly collaboration was extended for one year effective November 2003 at a lower level of ongoing research funding. Additionally, the decrease is due to the contractually agreed lower level of research activity and funding under our collaboration arrangement with TAP, which contributed $0.8 million to revenue in the first quarter of 2004 compared to $1.3 million in the first quarter of 2003. Revenue for the first quarter of 2003 includes a $1.1 million milestone earned from Lilly. There were no development milestones earned in the first quarter of 2004.

Gross Margin

Gross margin on product sales was 74.2% for the first quarter of 2004 compared to 65.0% for the first quarter of 2003. The increase in the margin in 2004 is due to the relative increase of sales of AVINZA® compared to 2003. AVINZA®, which represented 66% of net product sales in 2004 compared to 35% in the prior year quarter, has significantly better margins than ONTAK® for which we pay third party royalties totaling 28.0% of product sales. For both AVINZA® and ONTAK® we have capitalized license, royalty and technology rights recorded in connection with the acquisition of the rights to those products. These rights are amortized to cost of products sold on a straight-line basis over 15 years. Given the fixed level of amortization of the capitalized AVINZA® license and royalty rights and the ONTAK® acquired technology, we expect the AVINZA® and ONTAK® gross margin percentages to continue to increase as sales of AVINZA® and ONTAK® increase.

Research and Development Expenses

Research and development expenses were $16.9 million in the first quarter of 2004 compared to $16.6 million for the first quarter of 2003.

Quarter Ended March 31,

Research 2004 2003 Research performed under collaboration agreements $ 1,992 $ 2,914 Internal research programs 3,746 2,861 Total research 5,738 5,775

Development
New product development 8,405 8,762 Existing product support (1) 2,709 2,103 Total development 11,114 10,865

Total research and development $ 16,852 $ 16,640

(1) Includes costs incurred to comply with U.S. post-marketing regulatory commitments.

Overall, spending for research expenses remained relatively constant in the first quarter of 2004 compared to the first quarter of 2003, with increases in expenses for internal research programs offset by decreases in expenses for research performed under collaboration agreements. The decrease in expenses for research performed under collaboration agreements was due primarily to a lower contractual level of research funding under our agreement with TAP in the first quarter of 2004 compared to the first quarter of 2003. The decrease is also attributable to a lower level of research funding agreed to with Lilly in connection with the November 2003 extension of our collaboration agreement through November 2004.

Spending for development expenses remained relatively constant in the first quarter of 2004 compared to the first quarter of 2003, with increases in expenses for existing product support offset by a slight decrease in expenses for new product development. The increase in expenses for existing product support was attributable to expenses incurred in connection with the development of an alternate source of supply for AVINZA®. Expenses for our non-small cell lung cancer (or NSCLC) Phase III clinical trials for Targretin® capsules remained relatively constant in the first quarter of 2004 compared to the first quarter of 2003.

We expect development expenses to continue to increase in 2004 related to AVINZA®post-marketing regulatory commitments, increased activity on the development of our ONTAK® second generation product, expanded ONTAK® trials for indications other than CTCL, ongoing expenses on the Phase III clinical trials for Targretin® capsules in NSCLC, and initiation of additional clinical trials for Targretin® capsules in second/third line NSCLC and Targretin® gel in hand dermatitis.

A summary of our significant internal research and development programs is as follows:

Program Disease/Indication Development Phase AVINZA® Chronic, moderate-to-severe pain Marketed in U.S.

Phase IIIB/IV ONTAK® CTCL Marketed in U.S.
CLL Phase II Peripheral T-cell lymphoma Phase II B-cell NHL Phase II Psoriasis (severe) Phase II NSCLC third line Phase II Targretin®capsules CTCL Marketed in U.S.
NSCLC first-line Phase III NSCLC third-line monotherapy Phase II NSCLC second/third line Phase II Advanced breast cancer Phase II Psoriasis (moderate to severe) Phase II Renal cell cancer Phase II Targretin® gel CTCL Marketed in U.S.
Hand dermatitis (eczema) Phase II Psoriasis Phase II Panretin® gel KS Marketed in U.S. LGD1550 (RAR agonist) Advanced cancers Phase II Acne Pre-clinical Psoriasis Pre-clinical LGD1331 (Androgen Prostate cancer, hirsutism, Pre-clinical antagonist) acne, androgenetic alopecia LGD5552 (Glucocorticoid Inflammation, cancer Pre-clinical agonists)

We do not provide forward-looking estimates of costs and time to complete ongoing research and development projects, as such estimates would involve a high degree of uncertainty. We currently estimate our total research and development expenditures over the next three years to range between $250 million and $325 million. Uncertainties include, but are not limited to, our ability to predict the outcome of complex research, our ability to predict the results of clinical studies, requirements placed upon us by regulatory authorities such as the FDA and the EMEA, our ability to predict the decisions of our collaborative partners, our ability to fund research and development programs, competition from other entities of which we may become aware in future periods, predictions of market potential from products that may be derived from our research and development efforts, and our ability to recruit and retain personnel or third-party research organizations with the necessary knowledge and skills to perform certain research and development. Refer to the "Risks and Uncertainties" section for additional discussion of the uncertainties surrounding our research and development initiatives.

Selling, General and Administrative Expenses

Selling, general and administrative expenses were $14.5 million for the first quarter of 2004 compared to $12.4 million for the first quarter of 2003. The increase in 2004 is primarily due to costs associated with additional Ligand sales representatives hired to promote AVINZA® and higher advertising and promotion expenses for AVINZA®. Additionally, marketing expenses increased in 2004 in conjunction with our increased emphasis on physician-attended product information and advisory meetings for AVINZA®. Selling, general and administrative expenses are expected to continue to increase in 2004 as a result of increased selling and marketing activities for AVINZA®which is now promoted on a broader scale and by a significantly larger sales force as a result of our co-promotion agreement with Organon and due to the planned hiring of an additional 36 pain specialist sales representatives as further discussed under "Recent Developments". Under the co-promotion agreement, we and Organon share equally all costs for AVINZA®advertising and promotion, medical affairs and clinical trials.

Co-promotion Expense

Co-promotion expense payable to Organon amounted to $6.7 million in 2004 in connection with net sales of AVINZA® of $22.4 million. As further discussed under "Overview", we are required to pay Organon, under the terms of our co-promotion agreement, 30% of net AVINZA® sales up to $150.0 million. We expect this expense to continue to increase in 2004 as sales of AVINZA® increase.

Other Expenses, Net

Interest expense increased to $3.1 million for the first quarter of 2004 compared to $2.7 million for the first quarter of 2003. The increase in interest expense is due primarily to interest expense related to a note payable consolidated in connection with the adoption of FIN 46(R) effective December 31, 2003 as more fully discussed under "Leases and Off Balance Sheet Arrangements" below.

Other expenses, net were $.01 million for the first quarter of 2004 and $5.3 million for the first quarter of 2003. The decrease in the net expense for the three months ended March 31, 2004 is due to the March 2003 write-off of a $5.0 million one-time payment made in July 2002 to X-Ceptor Therapeutics, Inc. (or X-Ceptor) to extend Ligand's right to acquire the outstanding stock of X-Ceptor not already held by Ligand. In March 2003, we informed X-Ceptor that we would not exercise the purchase right.

Liquidity and Capital Resources

We have financed our operations through private and public offerings of our equity securities, collaborative research and development and other revenues, issuance of convertible notes, product sales, capital and operating lease transactions, accounts receivable factoring and equipment financing arrangements and investment income.

At March 31, 2004, working capital was $67.6 million compared to working capital of $76.1 million at December 31, 2003. Cash, cash equivalents, short-term investments, and restricted investments totaled $98.8 million at March 31, 2004 compared to $100.7 million at December 31, 2003. We primarily invest our excess cash in United States government and investment grade corporate debt securities.

During the second quarter of 2003, we entered into a one-year accounts receivable factoring arrangement. We pay commissions to the finance company based on the gross receivables sold, subject to a minimum annual commission. Additionally, we pay interest on the net outstanding balance of the uncollected factored accounts receivable. During the first quarter of 2004, cash in the amount of $24.0 million was received through the factoring arrangement. We plan to extend the factoring agreement, if available, when it comes up for renewal in the second quarter of 2004.

Operating Activities

Operating activities used cash of $3.6 million for the three months ended March 31, 2004 compared to $9.7 million for the three months ended March 31, 2003. Operating cash flow in 2004 compared to the prior year period reflects increased product sales of AVINZA® and ONTAK®. Additionally, due to our factoring arrangement, net accounts receivable decreased $2.9 million from March 31, 2003 to March 31, 2004, increasing cash flow. The factoring arrangement has served to accelerate collection of accounts receivable, including $24.0 million received under the arrangement for the quarter ended March 31, 2004. Operating cash was negatively impacted, however, by higher selling and marketing expenses for AVINZA®.

Non-cash expenses for the quarter ended March 31, 2004 decreased $5.1 million compared to the quarter ended March 31, 2003. This decrease was due to the write-off of the X-Ceptor purchase right in March 2003. Net decreases in operating assets generated an additional $8.1 million during the quarter ended March 31, 2004 compared to the quarter ended March 31, 2003. This was due primarily to the receipt of cash through our factoring arrangement. Additionally, net increases in operating liabilities over the quarter ended March 31, 2004 generated $2.8 million more than over the prior year period. This was primarily due to the payment of co-promotion expense to Organon related to fourth quarter 2003 sales of AVINZA®.

Investing Activities

Investing activities provided cash of $6.4 million for the quarter ended March 31, 2004, and used cash of $3.4 million for the quarter ended March 31, 2003. Cash provided in 2004 reflects proceeds of $8.4 million from the sale of short-term investments net of purchases of short-term investments. The use of cash in 2004 reflects $1.1 million for the exercise of an option to buy out future payments due on future sales of lasofoxifene, a product under development by Pfizer, and $1.0 million for capital purchases. Cash used in the first quarter of 2003 reflects net proceeds of $0.9 million from the sale of short-term investments, offset by a $4.1 million payment to Elan in connection with the November 2002 restructuring of the AVINZA® license and supply agreement.

Financing Activities

Financing activities provided cash of $3.7 million and used cash of $16.3 million for the quarters ended March 31, 2004 and 2003, respectively. Cash provided by financing activities in the first quarter of 2004 includes net proceeds of $2.5 million from the exercise of employee stock options, and $1.1 million from equipment financing arrangements. The use of cash in the first quarter of 2003 reflects the $15.9 million repurchase of approximately 2.2 million shares of our outstanding common stock held by an affiliate of Elan in connection with a November 2002 share repurchase agreement.

Certain of our property and equipment is pledged as collateral under various equipment financing arrangements. As of March 31, 2004, $6.0 million was outstanding under such arrangements with $2.4 million classified as current. Our equipment financing arrangements have terms of 3 to 5 years with interest ranging from 4.73% to 10.66%.

Liquidity

We expect operating cash flows to continue to benefit in 2004 from increased product sales driven by AVINZA®. Operating cash will be negatively impacted, however, by higher development expenses to fund clinical trials of our existing products in new indications including Phase III registration trials for Targretin® capsules in non-small cell lung cancer, higher selling and marketing expenses on AVINZA®, and by the payment of our co-promotion fee to our partner Organon. Additionally, we are required to pay interest of approximately $4.7 million in May 2004 and November 2004 on the $155.3 million in 6% convertible subordinated notes issued in November 2002.

We believe our available cash, cash equivalents, short-term investments and existing sources of funding will be sufficient to satisfy our anticipated operating and capital requirements through at least the next 12 months. Our future operating and capital requirements will depend on many factors, including: the effectiveness of our commercial activities; the scope and results of preclinical testing and clinical trials; the pace of scientific progress in our research and development programs; the magnitude of these programs; the time and costs involved in obtaining regulatory approvals; the costs involved in preparing, filing, prosecuting, maintaining and enforcing patent claims; competing technological and market developments; the efforts of our collaborators; the ability to establish additional collaborations or changes in existing collaborations; and the cost of production.

Leases and Off Balance Sheet Arrangements

We lease our office and research facilities under operating leases that generally require us to pay taxes, insurance, maintenance and minimum lease payments. Some of our leases have options to renew. An operating lease for one of our two corporate office buildings is commonly referred to as a "synthetic lease". Prior to the issuance of Financial Accounting Standards Board (or FASB) Interpretation No. 46, as revised (or "FIN 46(R)"), Consolidation of Variable Interest Entities, an interpretation of Accounting Research Bulletin No. 51, synthetic leases represented a form of off-balance sheet financing which allowed us to treat the lease as an operating lease for accounting purposes and as a financing lease for tax purposes. We implemented FIN 46(R) effective December 31, 2003 and as a result, consolidated the entity from which we lease the subject office building.

As of March 31, 2004, we are not involved in any off-balance sheet arrangements.

Contractual Obligations

As of March 31, 2004, future minimum payments due under our contractual obligations are as follows (in thousands):

Payments Due by Period Less than 1 After 5 Total year 1-3 years 4-5 years years
Capital lease obligations $ 5,957 $ 2,397 $ 2,916 $ 644 $ - Operating lease obligations 19,740 1,812 3,698 3,415 10,815 Loan payable to bank (1) 12,381 303 675 11,403 - 6% Convertible Subordinated
Notes 155,250 - - 155,250 - Other long-term liabilities
(2) 3,516 124 2,840 - 552 Total contractual
obligations $ 196,844 $ 4,636 $ 10,129 $ 170,712 $ 11,367

(1) In connection with the implementation of FIN 46(R), we consolidated the entity from which we lease one of our corporate office buildings. The loan payable to bank represents the loan secured by the office building.
(2) Other long-term liabilities include merger contingencies, a liability under a royalty financing arrangement and a non-controlling interest in a variable interest entity. Deferred revenues are excluded because they have no effect on future liquidity.

As of March 31, 2004, we have net open purchase orders (defined as total open purchase orders at quarter end less any accruals or invoices charged to or amounts paid against such purchase orders) totaling approximately $16.2 million. During 2004, we also plan to spend approximately $4.0 to $5.0 million on capital expenditures.

Under the terms of our AVINZA® license and supply agreement with Elan, we are committed to purchase an annual minimum number of batches of AVINZA® from Elan through 2005 estimated at approximately $9.2 million per year.

In March 2004, we entered into a five-year manufacturing and packaging agreement with Cardinal Health PTS, LLC ("Cardinal") under which Cardinal will manufacture AVINZA® at its Winchester, Kentucky facility. Under the terms of the agreement, we committed to certain minimum annual purchases ranging from approximately $1.6 million to $2.3 million. In addition, if regulatory approval for the manufacture of AVINZA® at the Kentucky facility has not been obtained within 30 months of the agreement's effective date, we will pay Cardinal $50,000 per month until such approval is obtained or through the initial term of the contract. The technology transfer and regulatory approval is expected to be complete in 2005 after which commercial product manufacturing may commence.

Critical Accounting Policies

Certain of our accounting policies require the application of management judgment in making estimates and assumptions that affect the amounts reported in the consolidated financial statements and disclosures made in the accompanying notes. Those estimates and assumptions are based on historical experience and various other factors deemed to be applicable and reasonable under the circumstances. The use of judgment in determining such estimates and assumptions is by nature, subject to a degree of uncertainty. Accordingly, actual results could differ from the estimates made. Management believes there have been no material changes during the quarter ended March 31, 2004 to the critical accounting policies reported in the Management's Discussion and Analysis section of our annual report on Form 10-K for the year ended December 31, 2003.

New Accounting Pronouncements

In January 2003, the FASB issued FASB Interpretation No. 46 ("FIN 46"), Consolidation of Variable Interest Entities, an Interpretation of ARB No. 51 which was subsequently revised prior to implementation in December 2003. The revised interpretation, known as "FIN 46(R), requires the consolidation of certain variable interest entities ("VIEs") by the primary beneficiary of the entity if the equity investment at risk is not sufficient to permit the entity to finance its activities without additional subordinated financial support from other parties, or if the equity investors lack the characteristics of a controlling financial interest. We implemented FIN 46(R) on December 31, 2003, and consolidated the entity from which we lease one of our two corporate office buildings as of that date, as we determined that this entity was a VIE, as defined by FIN 46(R), and that we would absorb a majority of its expected losses, if any, as defined by the Interpretation.

In May 2003, the FASB issued SFAS No. 150, Accounting for Certain Financial Instruments with Characteristics of both Liabilities and Equity. SFAS No. 150 establishes standards for how an issuer classifies and measures certain financial instruments with the characteristics of both liability and equity, and requires that such financial instruments be reported as liabilities. The provisions of SFAS No. 150 are effective for instruments entered into or modified after May 31, 2003, and pre-existing instruments after June 15, 2003. The Company does not have any financial instruments covered by the Statement.

Risks and Uncertainties

The following is a summary description of some of the many risks we face in our business. You should carefully review these risks in evaluating our business, including the businesses of our subsidiaries. You should also consider the other information described in this report.

RISKS RELATED TO US AND OUR BUSINESS

Our product development and commercialization involves a number of uncertainties, and we may never generate sufficient revenues from the sale of products to become profitable.

We were founded in 1987. We have incurred significant losses since our inception. At March 31, 2004, our accumulated deficit was approximately $669 million. We began receiving revenues from the sale of pharmaceutical products in 1999. We achieved quarterly net income for the first time in our corporate history during the fourth quarter of fiscal 2003. To consistently be profitable, we must successfully develop, clinically test, market and sell our products. Even if we consistently achieve profitability, we cannot predict the level of that profitability or whether we will be able to sustain profitability. We expect that our operating results will fluctuate from period to period as a result of differences in when we incur expenses and receive revenues from product sales, collaborative arrangements and other sources. Some of these fluctuations may be significant.

Most of our products in development will require extensive additional development, including preclinical testing and human studies, as well as regulatory approvals, before we can market them. We cannot predict if or when any of the products we are developing or those being co-developed with our partners will be approved for marketing. There are many reasons that we or our collaborative partners may fail in our efforts to develop our other potential products, including the possibility that:

º preclinical testing or human studies may show that our potential products are ineffective or cause harmful side effects;
º the products may fail to receive necessary regulatory approvals from the FDA or foreign authorities in a timely manner, or at all;
º the products, if approved, may not be produced in commercial quantities or at reasonable costs;
º the products, once approved, may not achieve commercial acceptance;
º regulatory or governmental authorities may apply restrictions to our products, which could adversely affect their commercial success; or
º the proprietary rights of other parties may prevent us or our partners from marketing the products.

We are building marketing and sales capabilities in the United States and Europe which is an expensive and time-consuming process and may increase our operating losses.

Developing the sales force to market and sell products is a difficult, expensive and time-consuming process. We have developed a US sales force of about 95 people and plan to add an additional 36 sales representatives in the second and third quarters of 2004. We also rely on third-party distributors to distribute our products. The distributors are responsible for providing many marketing support services, including customer service, order entry, shipping and billing and customer reimbursement assistance. In Europe, we currently rely on other companies to distribute and market our products. We have entered into agreements for the marketing and distribution of our products in territories such as the United Kingdom, Germany, France, Spain, Portugal, Greece, Italy and Central and South America and have established a subsidiary, Ligand Pharmaceuticals International, Inc., with a branch in London, England, to coordinate our European marketing and operations. Our reliance on these third parties means our results may suffer if any of them are unsuccessful or fail to perform as expected. We may not be able to continue to expand our sales and marketing capabilities sufficiently to successfully commercialize our products in the territories where they receive marketing approval. With respect to our co-promotion or licensing arrangements, for example our co-promotion agreement for AVINZA®, any revenues we receive will depend substantially on the marketing and sales efforts of others, which may or may not be successful.

Our small number of products means our results are vulnerable to setbacks with respect to any one product.

We currently have only five products approved for marketing and a handful of other products/indications that have made significant progress through development. Because these numbers are small, especially the number of marketed products, any significant setback with respect to any one of them could significantly impair our operating results and/or reduce the market prices for our securities. Setbacks could include problems with shipping, distribution, manufacturing, product safety, marketing, government licenses and approvals, intellectual property rights and physician or patient acceptance of the product.

Sales of our specialty pharmaceutical products may significantly fluctuate each period based on the nature of our products, our promotional activities and wholesaler purchasing and stocking patterns.

Excluding AVINZA®, our products are small-volume specialty pharmaceutical products that address the needs of cancer patients in relatively small niche markets with substantial geographical fluctuations in demand. To ensure patient access to our drugs, we maintain broad distribution capabilities with inventories held at approximately 150 locations throughout the United States. Furthermore, the purchasing and stocking patterns of our wholesaler customers are influenced by a number of factors that vary with each product, including but not limited to overall level of demand, periodic promotions, required minimum shipping quantities and wholesaler competitive initiatives. As a result, the overall level of product in the distribution channel may average from two to six months' worth of projected inventory usage. If any or all of our major distributors decide to substantially reduce the inventory they carry in a given period, our sales for that period could be substantially lower than historical levels.

Our drug development programs will require substantial additional future funding which could hurt our operational and financial condition.

Our drug development programs require substantial additional capital to successfully complete them, arising from costs to:

º conduct research, preclinical testing and human studies;
º establish pilot scale and commercial scale manufacturing processes and facilities; and
º establish and develop quality control, regulatory, marketing, sales and administrative capabilities to support these programs.

Our future operating and capital needs will depend on many factors, including:

º the pace of scientific progress in our research and development programs and the magnitude of these programs;
º the scope and results of preclinical testing and human studies;
º the time and costs involved in obtaining regulatory approvals;
º the time and costs involved in preparing, filing, prosecuting, maintaining and enforcing patent claims;
º competing technological and market developments;
º our ability to establish additional collaborations;
º changes in our existing collaborations;
º the cost of manufacturing scale-up; and
º the effectiveness of our commercialization activities.

We currently estimate our research and development expenditures over the next 3 years to range between $250 million and $325 million. However, we base our outlook regarding the need for funds on many uncertain variables. Such uncertainties include regulatory approvals, the timing of events outside our direct control such as product launches by partners and the success of such product launches, negotiations with potential strategic partners and other factors. Any of these uncertain events can significantly change our cash requirements as they determine such one-time events as the receipt of major milestones and other payments.

While we expect to fund our research and development activities from cash generated from internal operations to the extent possible, if we are unable to do so we may need to complete additional equity or debt financings or seek other external means of financing. If additional funds are required to support our operations and we are unable to obtain them on terms favorable to us, we may be required to cease or reduce further development or commercialization of our products, to sell some or all of our technology or assets or to merge with another entity.

Some of our key technologies have not been used to produce marketed products and may not be capable of producing such products.

To date, we have dedicated most of our resources to the research and development of potential drugs based upon our expertise in our IR and STAT technologies. Even though there are marketed drugs that act through IRs, some aspects of our IR technologies have not been used to produce marketed products. In addition, we are not aware of any drugs that have been developed and successfully commercialized that interact directly with STATs. Much remains to be learned about the location and function of IRs and STATs. If we are unable to apply our IR and STAT technologies to the development of our potential products, we will not be successful in developing new products.

We may require additional money to run our business and may be required to raise this money on terms which are not favorable or which reduce our stock price.

We have incurred losses since our inception and may not generate positive cash flow to fund our operations for one or more years. As a result, we may need to complete additional equity or debt financings to fund our operations. Our inability to obtain additional financing could adversely affect our business. Financings may not be available at all or on favorable terms. In addition, these financings, if completed, still may not meet our capital needs and could result in substantial dilution to our stockholders. For instance, in April 2002 and September 2003 we issued an aggregate of 7.7 million shares of our common stock in a private placement. In addition, in November 2002 we issued in a private placement $155.3 million in aggregate principal amount of our 6% convertible subordinated notes due 2007, which could be converted into 25,149,025 shares of our common stock.

If adequate funds are not available, we may be required to delay, reduce the scope of or eliminate one or more of our research or drug development programs, or our marketing and sales initiatives. Alternatively, we may be forced to attempt to continue development by entering into arrangements with collaborative partners or others that require us to relinquish some or all of our rights to technologies or drug candidates that we would not otherwise relinquish.

Our products face significant regulatory hurdles prior to marketing which could delay or prevent sales. Even after approval, government regulation of our business is extensive.

Before we obtain the approvals necessary to sell any of our potential products, we must show through preclinical studies and human testing that each product is safe and effective. We and our partners have a number of products moving toward or currently in clinical trials, the most significant of which are our Phase III trials for Targretin® capsules in non-small cell lung cancer and three Phase III trials by our partners involving bazedoxifene and lasofoxifene. Failure to show any product's safety and effectiveness would delay or prevent regulatory approval of the product and could adversely affect our business. The clinical trials process is complex and uncertain. The results of preclinical studies and initial clinical trials may not necessarily predict the results from later large-scale clinical trials. In addition, clinical trials may not demonstrate a product's safety and effectiveness to the satisfaction of the regulatory authorities. A number of companies have suffered significant setbacks in advanced clinical trials or in seeking regulatory approvals, despite promising results in earlier trials. The FDA may also require additional clinical trials after regulatory approvals are received, which could be expensive and time-consuming, and failure to successfully conduct those trials could jeopardize continued commercialization.

The rate at which we complete our clinical trials depends on many factors, including our ability to obtain adequate supplies of the products to be tested and patient enrollment. Patient enrollment is a function of many factors, including the size of the patient population, the proximity of patients to clinical sites and the eligibility criteria for the trial. For example, each of our Phase III Targretin® clinical trials involves approximately 600 patients and required significant time and investment to complete enrollments. Delays in patient enrollment for our other trials may result in increased costs and longer development times. In addition, our collaborative partners have rights to control product development and clinical programs for products developed under the collaborations. As a result, these collaborators may conduct these programs more slowly or in a different manner than we had expected. Even if clinical trials are completed, we or our collaborative partners still may not apply for FDA approval in a timely manner or the FDA still may not grant approval.

In addition, the manufacturing and marketing of approved products is subject to extensive government regulation, including by the FDA, DEA and state and other territorial authorities. The FDA administers processes to assure that marketed products are safe, effective, consistently of uniform, high quality and marketed only for approved indications. For example, while our products are prescribed legally by some physicians for unapproved uses, we may not market our products for such uses. Failure to comply with applicable regulatory requirements can result in sanctions up to the suspension of regulatory approval as well as civil and criminal sanctions.

We face substantial competition which may limit our revenues.

Some of the drugs that we are developing and marketing will compete with existing treatments. In addition, several companies are developing new drugs that target the same diseases that we are targeting and are taking IR-related and STAT-related approaches to drug development. The principal products competing with our products targeted at the cutaneous t-cell lymphoma market are Supergen/Abbott's Nipent and interferon, which is marketed by a number of companies, including Schering-Plough's Intron A. Products that compete with AVINZA® include Purdue Pharma L.P.'s OxyContin and MS Contin, Janssen Pharmaceutica Products, L.P.'s Duragesic, aai Pharma's Oramorph SR, Faulding's Kadian, and generic sustained release morphine sulfate and oxycodone. Many of our existing or potential competitors, particularly large drug companies, have greater financial, technical and human resources than us and may be better equipped to develop, manufacture and market products. Many of these companies also have extensive experience in preclinical testing and human clinical trials, obtaining FDA and other regulatory approvals and manufacturing and marketing pharmaceutical products. In addition, academic institutions, governmental agencies and other public and private research organizations are developing products that may compete with the products we are developing. These institutions are becoming more aware of the commercial value of their findings and are seeking patent protection and licensing arrangements to collect payments for the use of their technologies. These institutions also may market competitive products on their own or through joint ventures and will compete with us in recruiting highly qualified scientific personnel.

Third-party reimbursement and health care reform policies may reduce our future sales.

Sales of prescription drugs depend significantly on access to the formularies, or lists of approved prescription drugs, of third-party payers such as government and private insurance plans, as well as the availability of reimbursement to the consumer from these third party payers. These third party payers frequently require drug companies to provide predetermined discounts from list prices, and they are increasingly challenging the prices charged for medical products and services. Our current and potential products may not be considered cost-effective, may not be added to formularies and reimbursement to the consumer may not be available or sufficient to allow us to sell our products on a competitive basis. For example, we have current and recurring discussions with insurers regarding formulary access, discounts and reimbursement rates for our drugs, including AVINZA®. We may not be able to negotiate favorable reimbursement rates and formulary status for our products or may have to pay significant discounts to obtain favorable rates and access. Only one of our products, ONTAK®, is currently eligible to be reimbursed by Medicare. Recently enacted changes by Medicare to the hospital outpatient payment reimbursement system may adversely affect reimbursement rates for ONTAK®.

In addition, the efforts of governments and third-party payers to contain or reduce the cost of health care will continue to affect the business and financial condition of drug companies such as us. A number of legislative and regulatory proposals to change the health care system have been discussed in recent years, including price caps and controls for pharmaceuticals. These proposals could reduce and/or cap the prices for our products or reduce government reimbursement rates for products such as ONTAK®. In addition, an increasing emphasis on managed care in the United States has and will continue to increase pressure on drug pricing. We cannot predict whether legislative or regulatory proposals will be adopted or what effect those proposals or managed care efforts may have on our business. The announcement and/or adoption of such proposals or efforts could adversely affect our profit margins and business.

We rely heavily on collaborative relationships and termination of any of these programs could reduce the financial resources available to us, including research funding and milestone payments.

Our strategy for developing and commercializing many of our potential products, including products aimed at larger markets, includes entering into collaborations with corporate partners, licensors, licensees and others. These collaborations provide us with funding and research and development resources for potential products for the treatment or control of metabolic diseases, hematopoiesis, women's health disorders, inflammation, cardiovascular disease, cancer and skin disease, and osteoporosis. These agreements also give our collaborative partners significant discretion when deciding whether or not to pursue any development program. Our collaborations may not continue or be successful.

In addition, our collaborators may develop drugs, either alone or with others, that compete with the types of drugs they currently are developing with us. This would result in less support and increased competition for our programs. If products are approved for marketing under our collaborative programs, any revenues we receive will depend on the manufacturing, marketing and sales efforts of our collaborators, who generally retain commercialization rights under the collaborative agreements. Our current collaborators also generally have the right to terminate their collaborations under specified circumstances. If any of our collaborative partners breach or terminate their agreements with us or otherwise fail to conduct their collaborative activities successfully, our product development under these agreements will be delayed or terminated.

We may have disputes in the future with our collaborators, including disputes concerning which of us owns the rights to any technology developed. For instance, we were involved in litigation with Pfizer, which we settled in April 1996, concerning our right to milestones and royalties based on the development and commercialization of droloxifene. These and other possible disagreements between us and our collaborators could delay our ability and the ability of our collaborators to achieve milestones or our receipt of other payments. In addition, any disagreements could delay, interrupt or terminate the collaborative research, development and commercialization of certain potential products, or could result in litigation or arbitration. The occurrence of any of these problems could be time-consuming and expensive and could adversely affect our business.

Challenges to or failure to secure patents and other proprietary rights may significantly hurt our business.

Our success will depend on our ability and the ability of our licensors to obtain and maintain patents and proprietary rights for our potential products and to avoid infringing the proprietary rights of others, both in the United States and in foreign countries. Patents may not be issued from any of these applications currently on file, or, if issued, may not provide sufficient protection. In addition, disputes with licensors under our license agreements may arise which could result in additional financial liability or loss of important technology and potential products and related revenue, if any.

Our patent position, like that of many pharmaceutical companies, is uncertain and involves complex legal and technical questions for which important legal principles are unresolved. We may not develop or obtain rights to products or processes that are patentable. Even if we do obtain patents, they may not adequately protect the technology we own or have licensed. In addition, others may challenge, seek to invalidate, infringe or circumvent any patents we own or license, and rights we receive under those patents may not provide competitive advantages to us. Further, the manufacture, use or sale of our products may infringe the patent rights of others.

Several drug companies and research and academic institutions have developed technologies, filed patent applications or received patents for technologies that may be related to our business. Others have filed patent applications and received patents that conflict with patents or patent applications we have licensed for our use, either by claiming the same methods or compounds or by claiming methods or compounds that could dominate those licensed to us. In addition, we may not be aware of all patents or patent applications that may impact our ability to make, use or sell any of our potential products. For example, US patent applications may be kept confidential while pending in the Patent and Trademark Office and patent applications filed in foreign countries are often first published six months or more after filing. Any conflicts resulting from the patent rights of others could significantly reduce the coverage of our patents and limit our ability to obtain meaningful patent protection. While we routinely receive communications or have conversations with the owners of other patents, none of these third parties have

directly threatened an action or claim against us. If other companies obtain patents with conflicting claims, we may be required to obtain licenses to those patents or to develop or obtain alternative technology. We may not be able to obtain any such licenses on acceptable terms, or at all. Any failure to obtain such licenses could delay or prevent us from pursuing the development or commercialization of our potential products.

We have had and will continue to have discussions with our current and potential collaborators regarding the scope and validity of our patents and other proprietary rights. If a collaborator or other party successfully establishes that our patent rights are invalid, we may not be able to continue our existing collaborations beyond their expiration. Any determination that our patent rights are invalid also could encourage our collaborators to terminate their agreements where contractually permitted. Such a determination could also adversely affect our ability to enter into new collaborations.

We may also need to initiate litigation, which could be time-consuming and expensive, to enforce our proprietary rights or to determine the scope and validity of others' rights. If litigation results, a court may find our patents or those of our licensors invalid or may find that we have infringed on a competitor's rights. If any of our competitors have filed patent applications in the United States which claim technology we also have invented, the Patent and Trademark Office may require us to participate in expensive interference proceedings to determine who has the right to a patent for the technology.

Hoffmann-La Roche Inc. has received a US patent, has made patent filings and has issued patents in foreign countries that relate to our Panretin® gel products. While we were unsuccessful in having certain claims of the US patent awarded to Ligand in interference proceedings, we continue to believe that any relevant claims in these Hoffman-La Roche patents in relevant jurisdictions are invalid and that our current commercial activities and plans relating to Panretin® are not covered by these Hoffman-La Roche patents in the US or elsewhere. In addition, we have our own portfolio of issued and pending patents in this area which cover our commercial activities, as well as other uses of 9-cis retinoic acid, in the US, Europe and elsewhere. However, if the claims in these Hoffman-La Roche patents are not invalid and/or unenforceable, they might block the use of Panretin® gel in specified cancers, not currently under active development or commercialization by us.

We have also learned that Novartis AG has filed an opposition to our European patent that covers the principal active ingredient of our ONTAK® drug. We are currently investigating the scope and merits of this opposition. If the opposition is successful, we could lose our ONTAK® patent protection in Europe which could substantially reduce our future ONTAK® sales in that region. We could also incur substantial costs in asserting our rights in this opposition proceeding, as well as in other possible future proceedings in the United States.

We also rely on unpatented trade secrets and know-how to protect and maintain our competitive position. We require our employees, consultants, collaborators and others to sign confidentiality agreements when they begin their relationship with us. These agreements may be breached, and we may not have adequate remedies for any breach. In addition, our competitors may independently discover our trade secrets.

Reliance on third-party manufacturers to supply our products risks supply interruption or contamination and difficulty controlling costs.

We currently have no manufacturing facilities, and we rely on others for clinical or commercial production of our marketed and potential products. In addition, some raw materials necessary for the commercial manufacturing of our products are custom and must be obtained from a specific sole source. Elan manufactures AVINZA® for us, Cambrex manufactures ONTAK® for us and Cardinal Health and Raylo manufacture Targretin® capsules for us. We also recently entered into contracts with Cardinal Health to manufacture and package AVINZA® and with Hollister-Stier for the filling and finishing of ONTAK®. Each of these recent contracts calls for manufacturing and packaging the product at a new facility. Qualification and regulatory approval for these facilities are required prior to starting commercial manufacturing. Any delays or failures of the qualification or approval process could cause inventory problems or product shortages.

To be successful, we will need to ensure continuity of the manufacture of our products, either directly or through others, in commercial quantities, in compliance with regulatory requirements at acceptable cost and in sufficient quantities to meet product growth demands. Any extended or unplanned manufacturing shutdowns, shortfalls or delays could be expensive and could result in inventory and product shortages. If we are unable to reliably manufacture our products our revenues could be adversely affected. In addition, if we are unable to supply products in development, our ability to conduct preclinical testing and human clinical trials will be adversely affected. This in turn could also delay our submission of products for regulatory approval and our initiation of new development programs. In addition, although other companies have manufactured drugs acting through IRs and STATs on a commercial scale, we may not be able to do so at costs or in quantities to make marketable products.

The manufacturing process also may be susceptible to contamination, which could cause the affected manufacturing facility to close until the contamination is identified and fixed. In addition, problems with equipment failure or operator error also could cause delays in filling our customers' orders.

Our business exposes us to product liability risks or our products may need to be recalled, and we may not have sufficient insurance to cover any claims.

Our business exposes us to potential product liability risks. Our products also may need to be recalled to address regulatory issues. A successful product liability claim or series of claims brought against us could result in payment of significant amounts of money and divert management's attention from running the business. Some of the compounds we are investigating may be harmful to humans. For example, retinoids as a class are known to contain compounds which can cause birth defects. We may not be able to maintain our insurance on acceptable terms, or our insurance may not provide adequate protection in the case of a product liability claim. To the extent that product liability insurance, if available, does not cover potential claims, we will be required to self-insure the risks associated with such claims. We believe that we carry reasonably adequate insurance for product liability claims.

We use hazardous materials which requires us to incur substantial costs to comply with environmental regulations.

In connection with our research and development activities, we handle hazardous materials, chemicals and various radioactive compounds. To properly dispose of these hazardous materials in compliance with environmental regulations, we are required to contract with third parties at substantial cost to us. Our annual cost of compliance with these regulations is approximately $600,000. We cannot completely eliminate the risk of accidental contamination or injury from the handling and disposing of hazardous materials, whether by us or by our third-party contractors. In the event of any accident, we could be held liable for any damages that result, which could be significant. We believe that we carry reasonably adequate insurance for toxic tort claims.

Our stock price may be adversely affected by volatility in the markets.

The market prices and trading volumes for our securities, and the securities of emerging companies like us, have historically been highly volatile and have experienced significant fluctuations unrelated to operating performance. For example, in 2003, the intraday sale price of our common stock on the Nasdaq National Market was as high as $16.59 and as low as $3.69. Future announcements concerning us or our competitors as well as other companies in our industry and other public companies may impact the market price of our common stock. These announcements might include:

º the results of research or development testing of ours or our competitors' products;
º technological innovations related to diseases we are studying;
º new commercial products introduced by our competitors;
º government regulation of our industry;
º receipt of regulatory approvals by our competitors;
º our failure to receive regulatory approvals for products under development;
º developments concerning proprietary rights;
º litigation or public concern about the safety of our products; or
º intent to sell or actual sale of our stock held by our corporate partners.

Future sales of our securities may depress the price of our securities.

Sales of substantial amounts of our securities in the public market could seriously harm prevailing market prices for our securities. These sales might make it difficult or impossible for us to sell additional securities when we need to raise capital.

You may not receive a return on your securities other than through the sale of your securities.

We have not paid any cash dividends on our common stock to date. We intend to retain any earnings to support the expansion of our business, and we do not anticipate paying cash dividends on any of our securities in the foreseeable future.

Our shareholder rights plan and charter documents may hinder or prevent change of control transactions.

Our shareholder rights plan and provisions contained in our certificate of incorporation and bylaws may discourage transactions involving an actual or potential change in our ownership. In addition, our board of directors may issue shares of preferred stock without any further action by you. Such issuances may have the effect of delaying or preventing a change in our ownership. If changes in our ownership are discouraged, delayed or prevented, it would be more difficult for our current board of directors to be removed and replaced, even if you or our other stockholders believe that such actions are in the best interests of us and our stockholders.