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Filed Pursuant to Rule 424(b)(5)
Registration No. 333-109015

The information in this prospectus is not complete and may be changed. A registration statement relating to these securities has been filed with the Securities and Exchange Commission and has been declared effective. This preliminary prospectus supplement and the accompanying prospectus are not an offer to sell these securities and we are not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

SUBJECT TO COMPLETION, DATED OCTOBER 29, 2003

PROSPECTUS SUPPLEMENT
(To Prospectus Dated October 9, 2003)

GRAPHIC

7,500,000 Shares

AVI BioPharma, Inc.

Common Stock

        This is a public offering of 7,500,000 shares of our common stock. All of the shares of common stock offered pursuant to this prospectus supplement are being offered by us.

        Our common stock is quoted on the Nasdaq National Market under the symbol "AVII". The last reported sale price of the common stock on October 28, 2003 was $5.08 per share.

        Investing in our common stock involves risks. See "Risk Factors" beginning on page 2 of the accompanying prospectus and "Forward-Looking Information" on page S-1 of this prospectus supplement.

        Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the accuracy or adequacy of this prospectus supplement or the accompanying prospectus. Any representation to the contrary is a criminal offense.

 
   Per Share
   Total
Public Offering Price   $              $           
Underwriting Discount   $              $           
Proceeds, Before Expenses, to AVI BioPharma   $              $           

        The underwriters expect to deliver the shares of common stock to purchasers on or about                        , 2003. The underwriters have an option to purchase up to an additional 1,125,000 shares of common stock to cover over-allotments.

  Legg Mason Wood Walker  
  Incorporated  

 
Jefferies & Company, Inc.
 

 
First Albany Corporation
 

                       , 2003

        You should only rely on the information contained in, or incorporated by reference in, this prospectus supplement and the accompanying prospectus. We have not, and the underwriters have not, authorized anyone to provide you with different information and if anyone provides you with different or additional information, you should not rely on it. We are not making an offer of these securities in any state where the offer of these securities is not permitted. You should not assume that the information contained in this prospectus supplement, the accompanying prospectus and the documents incorporated by reference is accurate as of any date other than the dates of the specific information.

TABLE OF CONTENTS

Prospectus Supplement

 
   Page
About this Prospectus Supplement   S-1
Forward-Looking Information   S-1
Prospectus Supplement Summary   S-3
Use of Proceeds   S-9
Price Range of Common Stock   S-9
Capitalization   S-10
Dilution   S-11
Underwriting   S-12
Legal Matters   S-14

Prospectus

 
   Page

 
 
 
About this Prospectus   i 
AVI BioPharma   1
The Securities We May Offer   1
Risk Factors   2
Forward-Looking Information   11
Use of Proceeds   11
Description of Capital Stock   11
Description of Warrants   16
Legal Ownership of Securities   17
Plan of Distribution   18
Legal Matters   20
Experts   20
Where You Can Find More Information   20

        Unless we have indicated, or the context otherwise requires, references in this prospectus supplement to "AVI BioPharma," "we," "us," or similar terms, are to AVI BioPharma, Inc.

i


ABOUT THIS PROSPECTUS SUPPLEMENT

        We are providing this information to you about this offering of common stock in two parts. The first part is this prospectus supplement, which provides the specific details regarding the offering. The second part is the accompanying base prospectus, which provides general information. Generally, when we refer to this "prospectus," we are referring to both documents combined. Some of the information in the base prospectus may not apply to this offering.

        You should also read and consider the information in the documents that we have referred you to in "Where You Can Find More Information" on page 20 of the accompanying prospectus. The information incorporated by reference is considered to be part of this prospectus supplement, and information that we file later with the SEC will automatically update and supersede this information, except for any information updated or superseded by information contained directly in the prospectus or this prospectus supplement.

        If information in this prospectus supplement is inconsistent with the accompanying prospectus, you should rely on this prospectus supplement.


FORWARD-LOOKING INFORMATION

        This prospectus supplement and the accompanying prospectus and the information incorporated by reference herein and therein contain forward-looking statements regarding our plans, expectations, estimates and beliefs. Such statements are "forward-looking statements" for purposes of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Our actual results could differ materially from those discussed in, or implied by, these forward-looking statements. Forward-looking statements are identified by words such as "believe," "anticipate," "expect," "intend," "plan," "will," "may," and other similar expressions. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements are based on current expectations and are not guarantees of future performance. We caution you not to place undue reliance on these statements, which speak only as of the date on which the statement was made. Forward-looking statements in this prospectus supplement and the accompanying prospectus include, but are not necessarily limited to, those relating to:

        Forward-looking statements are subject to risks and uncertainties, certain of which are beyond our control. Actual results could differ materially from those anticipated as a result of the factors described in "Risk Factors" in the accompanying prospectus and detailed in our other Securities and Exchange Commission (SEC) filings, including among others:

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        Because of these risks and uncertainties, the forward-looking events and circumstances discussed in this prospectus supplement and the accompanying prospectus or incorporated by reference might not transpire. Except for our ongoing obligations to disclose material information as required by the federal securities laws, we undertake no obligation to release publicly any revisions to any forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. All of the above factors are difficult to predict, contain uncertainties that may materially affect our actual results and may be beyond our control. New factors emerge from time to time, and it is not possible for our management to predict all of such factors or to assess the effect of each factor on our business.

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PROSPECTUS SUPPLEMENT SUMMARY

        The following information supplements, and should be read together with, the information contained or incorporated by reference in other parts of this prospectus supplement and in the accompanying prospectus. This summary highlights selected information from this prospectus supplement and the accompanying prospectus to help you understand our business. Because the following is only a summary, it does not contain all of the information that may be important to you. You should carefully read this prospectus supplement and the accompanying prospectus before deciding whether to invest in our common stock. You should pay special attention to the "Risk Factors" section beginning on page 2 of the accompanying prospectus to determine whether an investment in our common stock is appropriate for you.


Business Overview

        We are a biopharmaceutical company developing therapeutic products based on two distinct core technologies, our third-generation NEUGENE® antisense program and our AVICINE® cancer vaccine. Our principal products in development target life-threatening diseases, including cardiovascular disease, infectious disease and cancer. Currently approved drugs or other therapies for these diseases often prove to be ineffective or produce undesirable side effects. Our pre-clinical and clinical studies indicate that our two core technologies may produce drugs that we believe offer more effective treatment options and produce significantly fewer side effects than currently approved products. A patent estate including 107 issued patents and 110 pending patent applications protects our technologies. Our lead product candidates, Resten-NG® and AVICINE, will each target a market estimated to exceed $1 billion worldwide.

        We have developed third-generation antisense technology that we believe produces drugs that may be more stable, specific, efficacious, and cost effective than other gene-targeting technologies including second-generation antisense, ribozyme, and siRNA compounds. In eleven clinical trials involving over 220 patients, we have not observed a single drug-related adverse event. Our NEUGENE drugs are distinguished by a novel backbone chemistry that replaces the natural or modified backbones of competing technologies with a synthetic backbone that has been designed to improve pharmaceutical parameters.

        NEUGENE drugs are synthetic polymers that block the function of selected genetic sequences involved in disease processes. Targeting specific genetic sequences provides for greater selectivity than that available through conventional drugs. NEUGENE drugs have the potential to provide safe and effective treatment for a wide range of human diseases.

        We have completed pre-clinical studies using our NEUGENE drugs in the treatment of cardiovascular disease, infectious disease, cancer and polycystic kidney disease (PKD), and in regulating drug metabolism. We filed our first antisense Investigational New Drug application (IND) with the FDA for Resten-NG for cardiovascular restenosis in 1999 and have substantially completed both Phase I and Phase II clinical trials. We have completed three Phase I trials in our drug metabolism program and two Phase Ib trials in our cancer and polycystic kidney disease programs. We have filed an IND, and we began a Phase Ib trial in 2003 for our NEUGENE antisense drug for West Nile virus infection.

        AVICINE, a therapeutic cancer vaccine, represents our most advanced product opportunity, having substantially completed six human clinical trials including multi-center Phase II trials for colorectal cancer and pancreatic cancer. Cancer vaccines operate under the rationale that immunization stimulates an immune response that is effective in combating an existing cancer. AVICINE stimulates an immune response against a hormone that is expressed on most cancers and is believed to promote the growth and spread of cancer. This hormone, human chorionic gonadotropin (hCG), is normally responsible for stimulating fetal development during pregnancy, but is also associated with all major types of cancer, including colon, pancreatic, prostate, lung and breast.

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        Based on our AVICINE clinical trials involving over 225 patients with advanced stages of cancer, we believe that this vaccine has a very modest toxicity profile compared to most other cancer therapies and is capable of producing a specific immune response in most patients. Further, the patients who mounted an immune response to vaccination appeared to derive a survival benefit. We intend to investigate further the use of AVICINE alone and in combination with other approved therapies in additional Phase II and Phase III trials for pancreatic cancer.


Clinical Development Programs

        Our therapeutic products are based on NEUGENE antisense technology with initial applications in cardiovascular disease, infectious disease, cancer, drug metabolism and polycystic kidney disease, and our AVICINE cancer vaccine with applications in cancer. We currently have products at various stages of clinical development as summarized below. We will not have marketable products until our drug candidates complete all required clinical trials and receive FDA approval in the United States or approval by regulatory agencies outside of the United States.

Product Candidate
   Type
   Pre-Clinical
   Phase I/Ib
   Phase II
   Phase III
Cardiovascular Disease                    
  Restenosis: Resten-NG   NEUGENE Drug   Completed   Completed   Completed   Planned
  Restenosis: Resten-NG microbubbles   NEUGENE Drug   Completed   Completed   In-progress    
  CABG: AVI-4126   NEUGENE Drug   In-progress   Planned        
  Cholesterol lowering   NEUGENE Drug   In-progress   Planned        
Infectious Disease (Viral targets)                    
  West Nile: AVI-4020   NEUGENE Drug   Completed   In-progress   Planned    
  Hepatitis C: AVI-4020   NEUGENE Drug   In-progress   Planned        
  SARS: AVI-4179   NEUGENE Drug   In-progress   Planned        
  Norovirus   NEUGENE Drug   In-progress            
Cancer                    
  Pancreatic: AVICINE   Cancer Vaccine   Completed   Completed   Completed   Planned
  Colorectal: AVICINE   Cancer Vaccine   Completed   Completed   Completed*    
  Lymphoma: Oncomyc-NG™   NEUGENE Drug   Completed   Completed   Planned    
  Lung: Oncomyc-NG   NEUGENE Drug   Completed   Planned   Planned    
  Prostate   NEUGENE Drug   In-progress   Planned   Planned    
Drug Metabolism                    
  Cytochrome P450: AVI-4557   NEUGENE Drug   Completed   Complete   In-progress    
Genetic Disorders                    
  PKD: AVI-4126   NEUGENE Drug   Completed   Complete   Planned    

        In this table, "Planned" refers to trials that are being designed although a protocol may not be complete; "In-progress" refers to studies or trials that have actively begun but are not yet complete; and "Completed" refers to studies in which the clinical trial or study has ended, the data has substantially been collected and validated, and a full study report is either in progress or complete.

        * A Phase III trial in colorectal cancer is not anticipated. We have selected pancreatic cancer for a Phase III trial due to considerations of cost, timeline and study design.


Overview

        Cardiovascular Disease Program. Resten-NG is a NEUGENE antisense drug for treating cardiovascular restenosis, or the re-narrowing of a coronary artery following balloon angioplasty. Resten-NG targets a key regulatory gene involved in the disease process. A global nonexclusive license has been granted to Medtronic, Inc. for our antisense compounds deployed on stents or certain other devices for treating restenosis. At the September 2003 Transcatheter Cardiovascular Therapeutics conference, we announced interim Phase II clinical trial data showing that Resten-NG delivered via catheter during balloon angioplasty procedures resulted in an approximate 80% reduction in the restenosis rate. At the April 2003 American College of Cardiology meeting, results from two independent studies were presented that additionally demonstrate the potential of treating cardiovascular restenosis by delivering Resten-NG systemically using our proprietary microbubble

S-4

delivery technology, possibly lessening the need to use special drug delivery catheters or drug-coated stents. We have initiated a Phase II clinical trial with Resten-NG coupled with our microbubble delivery technology at the University of Nebraska Medical Center. We are planning a Phase III trial to be initiated in the first quarter 2004 in Europe for Resten-NG delivered on a stent platform to meet the regulatory requirements for a CE Mark, constituting marketing approval for the European Union.

        Infectious Disease Program. Our infectious disease program is currently focusing on single-stranded RNA viruses using our proprietary NEUGENE antisense agents targeting West Nile virus, Hepatitis C virus, Norovirus and the SARS coronavirus, and also targeting many of the viruses included on the Domestic Homeland Security list of bioterrorism viruses. In May 2003, we filed an application with the FDA to obtain Orphan Drug designation for our West Nile NEUGENE drug candidate, AVI-4020, and submitted an IND the following month. Phase Ib clinical trials in West Nile virus are currently underway. Our NEUGENE drug candidate AVI-4179, designed to combat the SARS coronavirus, has been evaluated at the National Institutes of Health and the World Health Organization laboratories and found to be efficacious in laboratory pre-clinical studies. We have filed for Orphan Drug designation for our SARS coronavirus drug candidate.

        Cancer Program. We have completed a Phase Ib clinical trial with our NEUGENE drug candidate AVI-4126, which demonstrated the effectiveness of systemic delivery into solid tumor tissues for both breast and prostate cancer patients. AVI-4126 targets the oncogene c-myc. Over-expression of c-myc has been described in many types of cancers. We plan to conduct a multiple dosing study with AVI-4126 early in 2004 and a Phase Ib clinical trial in Lymphoma later in 2004. In January 2003, we received a $250,000 grant from the National Cancer Institute to target prostate cancer. We plan to initiate a Phase Ib clinical study with an additional NEUGENE antisense agent in 2004 in prostate cancer.

        In June 2000, we reported Phase II data demonstrating that AVICINE provided a survival benefit to patients with late-stage colorectal cancer who responded to the vaccine. Moreover, patients that had a strong antibody response to the vaccine had nearly twice the median survival of patients that had a weak antibody response or patients treated with chemotherapeutic drugs from published studies. These results were presented in May 2001 at the American Society of Clinical Oncology (ASCO) meeting and published in July 2002 in Cancer Research, a publication of the American Association for Cancer Research.

        In December 2001, we reported Phase II data demonstrating that AVICINE provided a survival benefit to patients with pancreatic cancer. In this study, patients were treated with AVICINE alone, or with AVICINE in combination with the chemotherapeutic agent Gemzar®. A one-year survival rate of 30% was reported for patients treated with AVICINE plus Gemzar, which is approximately double the survival rate for either treatment alone. In May 2002, we presented complete survival data from the Phase II pancreatic cancer study at the ASCO meeting. This data confirmed and extended the positive results reported previously in our Phase II study in colorectal cancer. We plan to begin a Phase III clinical program with AVICINE for treating pancreatic cancer by the first half of 2004. SuperGen, Inc. (SuperGen) is an exclusive partner with us in the development and commercialization of AVICINE in the United States.

        Drug Metabolism Program. We have successfully completed clinical trials demonstrating that our NEUGENE antisense drug improved the pharmacokinetic profile of two different test drugs by down-regulating the liver enzyme that is critical to the body's processing of many drugs. Two clinical studies completed in late 2002 showed that AVI-4557 down-regulated cytochrome P450 3a4, which resulted in an improved pharmacokinetic profile of the test drug. In September 2003, we initiated an oral dosing study with this agent to evaluate the oral route of administration for our antisense compounds. This study is currently ongoing. Additional Phase II trials will be designed after establishing strategic relationships with pharmaceutical co-development partners.

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        Polycystic Kidney Disease Program. We completed a Phase Ib clinical trial in 2002 to evaluate the safety and pharmacokinetics of three doses of AVI-4126 in patients with polycystic kidney disease and with varying degrees of compromised kidney function. Results of the study showed an excellent safety profile and no adverse effect on kidney function. We have designed a Phase II clinical study in the early onset form of PKD that is usually lethal for children. This form of PKD is very similar genetically to the pre-clinical PKD models that we have used to produce efficacy data for our antisense drug. We expect to initiate this trial in the second half of 2004.


Our Strategy

        Our strategy is to:

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The Offering

Common stock offered by us   7,500,000 shares

Common stock to be outstanding after the offering
 
38,705,559 shares

Use of proceeds
 
We intend to use the net proceeds from this offering to fund clinical trials for our lead product candidates, to fund the advancement of our pre-clinical programs and for other research and development and general corporate purposes.

Over-allotment option
 
We have granted the underwriters an option to purchase an additional 1,125,000 shares of common stock solely to cover over-allotments.

Risk factors
 
See "Risk Factors" beginning on page 2 of the accompanying prospectus and "Forward-Looking Information" on page S-1 of this prospectus supplement for a discussion of material risks that prospective purchasers of our common stock should consider.

Nasdaq National Market Symbol
 
AVII

        The number of shares of common stock to be outstanding after the offering is based on the number of shares outstanding as of October 28, 2003, and does not include up to 1,125,000 shares of common stock issuable upon exercise of the underwriters' over-allotment option. As of that date, we had 31,205,559 shares of common stock outstanding, which does not include:

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Summary Financial Data

        The tables below set forth summary financial data for the years ended December 31, 2000, 2001 and 2002 and for the six months ended June 30, 2002 and 2003. The summary financial data for the years ended December 31, 2000 through December 31, 2002 are derived from our audited financial statements for those periods. We derived the summary financial data as of June 30, 2003 and for the six months ended June 30, 2002 and 2003 from our unaudited financial statements. The unaudited financial statement data includes, in our opinion, all adjustments that are necessary for a fair presentation of our financial position and results of operations for these periods. Operating results for the six months ended June 30, 2003 are not necessarily indicative of the results that may be expected for the fiscal year ending December 31, 2003.

        This information is only a summary. You should read it in conjunction with our historical financial statements and related notes contained in our annual reports, quarterly reports and other information on file with the SEC. For more details on how you can obtain our SEC reports and other information, you should read the section entitled, "Where You Can Find More Information," beginning on page 20 of the accompanying prospectus. The adjusted balance sheet data give effect to the sale of common stock in this offering, at an assumed offering price of $5.08 per share, after deducting the estimated underwriting discounts and commissions and estimated offering expenses.

Income statement data
(in thousands, except per share data)

 
   Year Ended December 31,
   Six Months Ended
June 30,
  
 
   2000
   2001
   2002
   2002
   2003
  
 
    
    
    
   (unaudited)

  
Total revenues   $ 1,297   $ 706   $ 837   $ 435   $ 420  
Total operating expenses   $ 11,539   $ 16,109   $ 26,178   $ 16,253   $ 7,456  
Net loss   $ (9,240 ) $ (26,925 ) $ (29,359 ) $ (18,314 ) $ (6,917 )
Net loss per share, basic and diluted   $ (0.49 ) $ (1.20 ) $ (1.14 ) $ (0.74 ) $ (0.25 )
Shares used in computing basic and diluted net loss per share     18,725     22,399     25,692     24,906     27,982  

Balance sheet data
(in thousands)

 
   June 30, 2003
  
 
   Actual
   As Adjusted
  
 
   (unaudited)

  
Cash, cash equivalents and short-term investments   $ 30,340   $ 65,909  
Working capital   $ 29,481   $ 65,050  
Total assets   $ 39,624   $ 75,193  
Long-term obligations, less current portion   $ —   $ —  
Accumulated deficit   $ (123,495 ) $ (123,495 )
Total stockholders' equity   $ 38,328   $ 73,897  

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USE OF PROCEEDS

        We expect to receive approximately $35.6 million in net proceeds from the sale of 7,500,000 shares of common stock in this offering (or approximately $40.9 million if the underwriters exercise their option to purchase additional shares in full), after deducting estimated underwriting discounts and commissions and offering expenses payable by us. These amounts are based on an assumed offering price to the public of $5.08 per share.

        We intend to use the net proceeds from this offering to fund clinical trials for our lead product candidates, to fund the advancement of our pre-clinical programs and for other research and development and general corporate purposes. We may also use a portion of the net proceeds to acquire or invest in businesses, products and technologies that are complementary to our own, although we are not currently planning or negotiating any such transactions. We have not identified the amounts we plan to spend on each of these areas or the timing of such expenditures, and we will have significant discretion in the use of any net proceeds. The amounts and timing of our actual expenditures for each purpose may vary significantly depending upon numerous factors, including the status of our research and product development efforts, regulatory approvals, competition, and economic or other conditions.

        Pending the use of the net proceeds, we may invest the net proceeds in investment grade, interest-bearing securities.


PRICE RANGE OF COMMON STOCK

        Our common stock has been quoted and traded on the Nasdaq National Market under the symbol "AVII". The following table sets forth, for the periods indicated, the reported high and low closing sales prices per share of our common stock on the Nasdaq National Market:

 
   AVI BioPharma Common Stock
 
   Low
   High
Calendar Year Ended December 31, 2001            
First quarter   $ 3.00   $ 6.88
Second quarter     3.75     9.85
Third quarter     5.86     10.45
Fourth quarter     7.12     11.19

Calendar Year Ended December 31, 2002
 
 
 
 
 
 
First quarter     8.04     12.97
Second quarter     2.69     7.95
Third quarter     2.71     5.34
Fourth quarter     4.60     6.39

Calendar Year Ended December 31, 2003
 
 
 
 
 
 
First quarter     2.04     5.83
Second quarter     3.31     7.05
Third quarter     4.31     6.15
Fourth quarter (through October 28, 2003).     4.78     5.50

        The last reported sale price of our common stock on the Nasdaq National Market on October 28, 2003 was $5.08. As of October 28, 2003, there were approximately 620 stockholders of record of our common stock.

        We have never declared or paid cash dividends on our common stock. We do not intend to declare or pay any cash dividends on our common stock in the foreseeable future. We plan to retain any earnings for use in the operation of our business and to fund future growth.

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CAPITALIZATION

        The following table sets forth as of June 30, 2003:

        This table should be read in conjunction with "Management's Discussion and Analysis of Financial Condition and Results of Operations" appearing in our most recent quarterly and annual reports and the financial statements and the related notes incorporated by reference in the accompanying prospectus.

 
   As of June 30, 2003
  
 
   Actual
   As Adjusted
  
 
   (in thousands, except
share and per share data)

  
Cash, cash equivalents and short-term investments   $ 30,340   $ 65,909  
   
 
 
Long-term debt     —     —  
   
 
 

Stockholders' equity:
 
 
 
 
 
 
 
  Preferred stock, $0.0001 par value; 20,000,000 shares authorized; no shares issued, actual and as adjusted     —     —  
  Common stock, $0.0001 par value; 200,000,000 shares authorized; 31,175,141 shares issued and outstanding, actual; and 38,675,141 shares issued and outstanding, as adjusted     3     4  
  Additional paid-in-capital     160,329     195,897  
  Accumulated other comprehensive income     1,491     1,491  
  Accumulated deficit     (123,495 )   (123,495 )
   
 
 
    Total stockholders' equity     38,328     73,897  
   
 
 
Total capitalization   $ 38,328   $ 73,897  
   
 
 

        The information in the table above does not include:

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DILUTION

        The net tangible book value of our common stock on June 30, 2003 was approximately $36.6 million, or approximately $1.17 per share. Net tangible book value per share is equal to the amount of our total tangible assets, less total liabilities, divided by the aggregate number of shares of common stock outstanding. Dilution in net tangible book value per share represents the difference between the amount per share paid by purchasers of shares of common stock in this offering and the net tangible book value per share of our common stock immediately after this offering. After giving effect to the sale of 7,500,000 shares of common stock in this offering at an assumed public offering price of $5.08 per share, and after deducting estimated underwriting discounts and commissions and offering expenses, our net tangible book value at June 30, 2003 would have been approximately $72.2 million, or approximately $1.87 per share. This represents an immediate dilution of $3.21 per share to new investors purchasing shares of common stock in this offering. The following table illustrates this dilution:

Assumed public offering price per share         $ 5.08
  Net tangible book value per share as of June 30, 2003   $ 1.17      
  Increase per share attributable to new investors     .70      
   
     
Net tangible book value per share as of June 30, 2003 after giving effect to this offering           1.87
         
Dilution per share to new investors         $ 3.21
         

        The foregoing table does not take into account further dilution to new investors that could occur upon the exercise of outstanding options having a per share exercise price less than the per share offering price to the public in this offering. As of June 30, 2003, there were 31,175,141 shares of common stock outstanding, which does not include:


        The above table does not reflect the expected reported loss for our fiscal quarter ended September 30, 2003, which would increase the dilution per share, and does not include up to 1,125,000 shares of common stock issuable upon exercise of the underwriters' over-allotment option.

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UNDERWRITING

        Subject to the terms and conditions stated in the underwriting agreement dated as of the date of this prospectus supplement, each underwriter named below has agreed to purchase, and we have agreed to sell to that underwriter, the number of shares of our common stock set forth opposite that underwriter's name.

Underwriter
   Number
of
Shares
Legg Mason Wood Walker, Incorporated             
Jefferies & Company, Inc.             
First Albany Corporation             
   
  Total             
   

        The underwriting agreement provides that the obligation of the underwriters to purchase the shares included in this offering is subject to approval of legal matters by counsel and to other conditions. The underwriters are obligated to purchase all of the shares (other than those covered by the over-allotment option described below) if they purchase any of the shares.

        The underwriters propose to offer the shares to the public initially at the public offering price set forth on the cover of this prospectus supplement, and to some dealers at that price less a concession not in excess of $            per share. The underwriters may allow, and those dealers may reallow, a discount not in excess of $            per share to other dealers. After the offering, the public offering price, the concession to selected dealers and the reallowance to other dealers may be changed by the underwriter. There can be no assurance that the prices at which our common stock shares will sell in the public market after this offering will not be lower than the price at which they are sold by the underwriters or that an active trading market in the shares will develop and continue after this offering.

        We have granted to the underwriters the option, exercisable for 30 days from the date of this prospectus supplement, to purchase up to 1,125,000 additional shares of common stock at the price set forth on the cover of this prospectus supplement. The underwriters may exercise the option solely for the purpose of covering over-allotments, if any, in connection with the offering. To the extent the option is exercised, each underwriter must purchase a number of additional shares approximately proportionate to that underwriter's initial purchase commitment. If any additional shares are purchased, the underwriters will offer the additional shares on the same terms as those on which the 7,500,000 shares are being offered.

        The following table summarizes the compensation to be paid to the underwriters by us and the proceeds, before expenses, payable to us.

 
   Per
Share
   Without
Over-Allotment
   With
Over-Allotment
Public offering price   $                      $                      $                   
Underwriting discount   $                      $                      $                   
Proceeds, before expenses, to us   $                      $                      $                   

        We estimate that our portion of the total expenses of this offering will be $150,000, excluding underwriters' discounts and commissions.

        We have agreed that, for a period of 60 days from the date of this prospectus supplement, we will not, without the consent of the underwriters, offer, sell, hedge or otherwise dispose of any shares of our common stock or any securities convertible into or exchangeable for our common stock other than sales by us pursuant to stock options plans, exercise of outstanding warrants and stock purchase plan.

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        Additionally, our senior executive officers, Messrs. Burger, Iversen, Mason, Timmins, Webber and Weller, and our outside directors, Messrs. Fara, Ferrara, Hicks, and Rubinfeld, have agreed that, for a period of 90 days from the date of this prospectus supplement, they will not, without the consent of the underwriters, offer, sell, hedge or otherwise dispose of any shares of our common stock or any securities convertible into or exchangeable for our common stock held directly by them other than shares disposed of as bona fide gifts, pledged in a bona fide transaction to a lender or disposed of by a lender in accordance with a bona fide pledge agreement. The underwriters, in their sole discretion, may release any of the securities subject to these lock-up agreements at any time without notice.

        Pursuant to the terms of a registration rights agreement with us, SuperGen (which beneficially owns approximately 8.6% of our common stock) is not permitted to sell, make any short sale, loan, grant any option for the purchase of, or otherwise dispose of any of its shares of our common stock without the prior written consent of the underwriters or us for a period of 90 days from the date of this prospectus supplement, except for a transfer pursuant to an option granted by SuperGen to a third party. SuperGen has waived its rights under the registration rights agreement to request that its common stock be included as part of the offering under this prospectus supplement.

        Our common stock is quoted on the Nasdaq National Market under the symbol "AVII".

        We have been advised by the representatives of the underwriters that, in accordance with Regulation M under the Securities Act, some persons participating in this offering may engage in transactions, including syndicate covering transactions, stabilizing bids or the imposition of penalty bids, that may have the effect of stabilizing or maintaining the market price of the shares at a level above that which might otherwise prevail in the open market.

        A "syndicate covering transaction" is a bid for or the purchase of shares on behalf of the underwriters to reduce a syndicate short position incurred by the underwriters in connection with this offering. The underwriters may create a syndicate short position by making short sales of our shares and may purchase our shares in the open market to cover syndicate short positions created by short sale. Short sales involve the sale by the underwriters of a greater number of shares than they are required to purchase in this offering. Short sales can be either "covered" or "naked." "Covered" short sales are sales made in an amount not greater than the underwriters' over-allotment option to purchase additional shares from us in this offering. "Naked" short sales are sales in excess of the over-allotment option. A naked short position is more likely to be created if the underwriters are concerned that there may be downward pressure on the price of the shares in the open market after pricing that could adversely affect investors who purchase in this offering. If the underwriters create a syndicate short position, they may choose to reduce or "cover" this position by either exercising all or part of the over-allotment option to purchase additional shares from us or by engaging in "syndicate covering transactions." The underwriters may close out any covered short position by either exercising their over-allotment option or purchasing shares in the open market. The underwriters must close out any naked short position by purchasing shares in the open market. In determining the source of shares to close out the covered short position, the underwriters will consider, among other things, the price of shares available for purchase in the open market as compared to the price at which they may purchase shares through the over-allotment option.

        A "stabilizing bid" is a bid for or the purchase of shares on behalf of the underwriters for the purpose of fixing or maintaining the price of our common stock. A "penalty bid" is an arrangement that permits the representatives of the underwriters to reclaim the selling concession from an underwriter or a syndicate member when shares sold by such underwriter or syndicate members are purchased by the representatives in a syndicate covering transaction and, therefore, have not been effectively placed by the underwriter or syndicate member.

        We have been advised by the representatives of the underwriters that these transactions may be effected on the Nasdaq National Market or otherwise and, if commenced, may be discontinued at any

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time. Similar to other purchase activities, these activities may have the effect of raising or maintaining the market price of our common stock or preventing or retarding a decline in the market price of our common stock. As a result, the price of our common stock may be higher than the price that might otherwise exist in the open market.

        We have agreed to indemnify the underwriters against certain liabilities, including liabilities under the Securities Act of 1933, or to contribute to payments the underwriters may be required to make because of any of those liabilities.


LEGAL MATTERS

        Certain legal matters with respect to the validity of the securities offered under this prospectus supplement will be passed upon for us by Hurley, Lynch & Re, P.C., Bend, Oregon. Pepper Hamilton LLP, Philadelphia, Pennsylvania, will pass upon certain legal matters relating to this offering for the underwriters.

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PROSPECTUS

AVI BIOPHARMA, INC.

$75,000,000

Common Stock
Preferred Stock
Warrants

        From time to time, we may sell common stock, preferred stock and/or warrants.

        We will provide the specific terms of these securities in one or more supplements to this prospectus. You should read this prospectus and any prospectus supplement carefully before you invest.

        Our common stock is traded on The Nasdaq National Market under the trading symbol "AVII." The applicable prospectus supplement will contain information, where applicable, as to any other listing (if any) on The Nasdaq Stock Market's National Market or any securities exchange of the securities covered by the prospectus supplement.

        THIS PROSPECTUS MAY NOT BE USED TO OFFER OR SELL ANY SECURITIES UNLESS ACCOMPANIED BY A PROSPECTUS SUPPLEMENT.

        The securities may be sold directly by us to investors, through agents designated from time to time or to or through underwriters or dealers. For additional information on the methods of sale, you should refer to the section entitled "Plan of Distribution." If any underwriters are involved in the sale of any securities with respect to which this prospectus is being delivered, the names of such underwriters and any applicable commissions or discounts will be set forth in a prospectus supplement. The net proceeds we expect to receive from such sale will also be set forth in a prospectus supplement.

        NEITHER THE SECURITIES AND EXCHANGE COMMISSION NOR ANY STATE SECURITIES COMMISSION HAS APPROVED OR DISAPPROVED THESE SECURITIES OR DETERMINED IF THIS PROSPECTUS IS TRUTHFUL OR COMPLETE. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.

October 9, 2003


TABLE OF CONTENTS

 
   Page
ABOUT THIS PROSPECTUS   i

AVI BIOPHARMA
 
1

THE SECURITIES WE MAY OFFER
 
1

RISK FACTORS
 
2

FORWARD-LOOKING INFORMATION
 
11

USE OF PROCEEDS
 
11

DESCRIPTION OF CAPITAL STOCK
 
11

DESCRIPTION OF WARRANTS
 
16

LEGAL OWNERSHIP OF SECURITIES
 
17

PLAN OF DISTRIBUTION
 
18

LEGAL MATTERS
 
20

EXPERTS
 
20

WHERE YOU CAN FIND MORE INFORMATION
 
20

        This prospectus is part of a registration statement we filed with the Securities and Exchange Commission. You should rely only on the information we have provided or incorporated by reference in this prospectus or any prospectus supplement. We have not authorized anyone to provide you with information different from that contained in this prospectus. No dealer, salesperson or other person is authorized to give any information or to represent anything not contained in this prospectus. You must not rely on any unauthorized information or representation. This prospectus is an offer to sell only the securities offered hereby, but only under circumstances and in jurisdictions where it is lawful to do so. You should assume that the information in this prospectus or any prospectus supplement is accurate only as of the date on the front of the document and that any information we have incorporated by reference is accurate only as of the date of the document incorporated by reference, regardless of the time of delivery of this prospectus or any sale of a security.


ABOUT THIS PROSPECTUS

        This prospectus is part of a registration statement that we filed with the SEC using a "shelf" registration process. Under this shelf registration process, we may sell common stock, preferred stock and/or warrants in one or more offerings up to a total dollar amount of $75,000,000. This prospectus provides you with a general description of the securities we may offer. Each time we sell common stock, preferred stock and/or warrants, we will provide a prospectus supplement that will contain more specific information, as set forth below under "The Securities We May Offer." We may also add, update or change in the prospectus supplement any of the information contained in this prospectus. This prospectus, together with applicable prospectus supplements, includes all material information relating to this offering. Please carefully read both this prospectus and any prospectus supplement together with the additional information described below under "Where You Can Find More Information."

i



AVI BIOPHARMA

        We are a biopharmaceutical company therapeutic products for the treatment of life-threatening diseases using two technology platforms: NEUGENE® antisense drugs and cancer immunotherapy. Our lead NEUGENE antisense compound is designed to target cancer, cardiovascular restenosis, polycystic kidney disease and other cell proliferation disorders. In addition to targeting specific genes in the body, our antiviral program uses NEUGENE antisense compounds to target single-stranded RNA viruses, including West Nile Virus, SARS, coronavirus, calicivirus, and Hepatitis C. Our lead cancer agent, AVICINE®, is a therapeutic cancer vaccine that has completed Phase II clinical trials in colorectal and pancreatic cancer. We were incorporated in Oregon in 1980 as Antivirals, Inc., and changed our name to AVI BioPharma, Inc. in 1998.

        Our executive offices are currently located at One S.W. Columbia St., Suite 1105, Portland, OR 97258. Our telephone number is (503) 227-0554. Our common stock is listed on the NASDAQ National Market under the symbol "AVII." We maintain a site on the Internet at "www.avibio.com;" however, information found on our website is not part of this prospectus.

        "AVI" and the AVI logo are trademarks of AVI BioPharma, Inc. All other brand names or trademarks appearing in this prospectus are the property of their respective holders.


THE SECURITIES WE MAY OFFER

        We may offer shares of our common stock and preferred stock and/or warrants to purchase any of such securities with a total value of up to $75 million from time to time under this prospectus at prices and on terms to be determined by market conditions at the time of offering. This prospectus provides you with a general description of the securities we may offer. Each time we offer a type or series of securities, we will provide a prospectus supplement that will describe the specific amounts, prices and other important terms of the securities, including, to the extent applicable:

        The prospectus supplement also may add, update or change information contained in this prospectus or in documents we have incorporated by reference.

        THIS PROSPECTUS MAY NOT BE USED TO CONSUMMATE A SALE OF SECURITIES UNLESS IT IS ACCOMPANIED BY A PROSPECTUS SUPPLEMENT.

        We may sell the securities directly to or through agents, underwriters or dealers. We, and our agents or underwriters, reserve the right to accept or reject all or part of any proposed purchase of securities. If we do offer securities through agents or underwriters, we will include in the applicable prospectus supplement:

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        Common Stock.    We may issue shares of our common stock from time to time. Holders of common stock are entitled to one vote per share on all matters submitted to a vote of stockholders. Subject to any preferences of outstanding shares of preferred stock, holders of common stock are entitled to dividends when and if declared by the board of directors.

        Preferred Stock.    We may issue shares of our preferred stock from time to time, in one or more series. Our board of directors shall determine the rights, preferences, privileges and restrictions of the preferred stock, including dividend rights, conversion rights, voting rights, terms of redemption, liquidation preferences, sinking fund terms and the number of shares constituting any series or the designation of any series. Convertible preferred stock will be convertible into our common stock. Conversion may be mandatory or at your option and would be at prescribed conversion rates.

        Warrants.    We may issue warrants for the purchase of common stock and/or preferred stock in one or more series. We may issue warrants independently or together with common and/or preferred stock, and the warrants may be attached to, or separate from, these securities. In this prospectus, we have summarized certain general features of the warrants. We urge you, however, to read the prospectus supplements related to the series of warrants being offered, as well as the warrant agreement that contains the terms of the warrants. The warrant agreement and form of warrant containing the terms of the warrants being offered will be filed as exhibits to the registration statement of which this prospectus is a part or will be incorporated by reference from reports we file with the SEC.

        We will evidence each series of warrants by warrant certificates that we will issue under a separate agreement. We will enter into the warrant agreement with a warrant agent. Each warrant agent will be a bank that we select which has its principal office in the United States and a combined capital and surplus of at least $50,000,000. We will indicate the name and address of the warrant agent in the applicable prospectus supplement relating to a particular series of warrants.


RISK FACTORS

        AN INVESTMENT IN OUR SECURITIES INVOLVES A HIGH DEGREE OF RISK. YOU SHOULD CAREFULLY CONSIDER THE SPECIFIC FACTORS LISTED BELOW, TOGETHER WITH THE CAUTIONARY STATEMENT THAT FOLLOWS THIS SECTION AND THE OTHER INFORMATION INCLUDED IN THIS PROSPECTUS, BEFORE PURCHASING SECURITIES IN THIS OFFERING. If the possibilities described as risks below actually occur, our operating results and financial condition would likely suffer, and the trading price of our Common Stock or, if issued, our Preferred Stock, may fall, causing you to lose some or all of your investment in the shares we are offering.

Risks Related to AVI's Business

Our products are in an early stage of development and may not be determined to be safe or effective.

        We are only in the early stages of clinical development with our NEUGENE antisense pharmaceutical products and mid stage clinical development of our AVICINE products. We have devoted almost all of our time to research and development of our technology and products, protecting our proprietary rights and establishing strategic alliances. Our proposed products are in the pre-clinical or clinical stages of development and will require significant further research, development, clinical testing and regulatory clearances. We have no products available for sale and we do not expect to have any products available for sale for several years. Our proposed products are subject to development risks. These risks include the possibilities that any of the products could be found to be ineffective or toxic, or could fail to receive necessary regulatory clearances. Although we have obtained favorable results in Phase II trials using AVICINE to treat colorectal cancer patients, we may not obtain similar

2


or more favorable results in our planned Phase III clinical trial. We have not received any significant revenues from the sale of products and we may not successfully develop marketable products that will increase sales and provide adequate margins to make us profitable. Third parties may develop superior or equivalent, but less expensive, products.

We have incurred net losses since our inception, and we may not achieve or sustain profitability.

        We incurred a net loss of $26.9 million in 2001 and $29.4 million in 2002, including non-cash write-downs of our investment securities in accordance with SEC accounting rules of $12.5 million in 2001 and $4.5 million in 2002. As of December 31, 2002, our accumulated deficit was $116.6 million and, at June 30, 2003, was $123.5 million. Our losses have resulted principally from expenses incurred in research and development of our technology and products and from selling, general and administrative expenses that we have incurred while building our business infrastructure. We expect to continue to incur significant losses in the future as we continue our research and development efforts and seek to obtain regulatory approval of our products. Our ability to achieve profitability depends on our ability to complete development of our products, obtain regulatory approvals and market our products. It is uncertain when, if ever, we will become profitable.

If we fail to attract significant additional capital, we may be unable to continue to successfully develop our products.

        Since we began operations, we have obtained operating funds primarily by selling shares of our common stock and warrants to purchase shares of our common stock. In May 2003, we raised $20.7 million, net of offering costs, by issuing common stock and warrants. Based on our current plans, we believe that current cash balances will be sufficient to meet our operating needs through calendar 2004. However, the actual amount of funds that we will need will be determined by many factors, some of which are beyond our control. These factors include the success of our research and development efforts, the status of our pre-clinical and clinical testing, costs relating to securing regulatory approvals and the costs and timing of obtaining new patent rights, regulatory changes, competition and technological developments in the market. We may need funds sooner than currently anticipated.

        We anticipate that we may need to obtain additional funds in the future. If necessary, potential sources of additional funding include strategic relationships, public or private sales of shares of our common stock or debt or other arrangements. We do not have any committed sources of additional financing at this time. We may not obtain additional funding when we need it on terms that will be acceptable to us or at all. If we raise funds by selling additional shares of our common stock or securities convertible into our common stock, the ownership interest of our existing shareholders will be diluted. If we are unable to obtain financing when needed, our business and future prospects would be materially adversely affected.

If we fail to receive necessary regulatory approvals, we will be unable to commercialize our products.

        All of our products are subject to extensive regulation by the FDA and by comparable agencies in other countries. The FDA and comparable agencies require new pharmaceutical products to undergo lengthy and detailed clinical testing procedures and other costly and time-consuming compliance procedures. AVICINE has completed three Phase I and two Phase II studies and is ready to start a Phase III trial. Our first NEUGENE Antisense drug, Resten-NG®, completed Phase I trials in late 2001 and a Phase II trial in 2002. We initiated two additional Phase 1b studies in 2001 for cancer and polycystic kidney disease and completed three Phase I trials on drug metabolism. Except for clinical trials underway or ready to start, we may not initiate additional trials when predicted or at all, or complete our clinical trials that are started or in a timely fashion. We do not know when or if we will be able to submit our products for regulatory review. Even if we submit a product for regulatory review, there may be delays in obtaining regulatory approvals, or we may not obtain them at all. Sales

3


of our products outside the United States will also be subject to regulatory requirements governing clinical trials and product approval. These requirements vary from country to country and could delay introduction of our products in those countries. We cannot assure you that any of our products will receive marketing approval from the FDA or comparable foreign agencies.

We may fail to compete effectively, particularly against larger, more established pharmaceutical companies, causing our business to suffer.

        The biotechnology industry is highly competitive. We compete with companies in the United States and abroad that are engaged in the development of pharmaceutical technologies and products. They include: biotechnology, pharmaceutical, chemical and other companies; academic and scientific institutions; governmental agencies; and public and private research organizations.

        Many of these companies and many of our other competitors have much greater financial and technical resources and production and marketing capabilities than we do. Our industry is characterized by extensive research and development and rapid technological progress. Competitors may successfully develop and market superior or less expensive products which render our products less valuable or unmarketable.

We have limited operating experience.

        We have engaged solely in the development of pharmaceutical technology. Although some members of our management have experience in biotechnology company operations, we have limited experience in manufacturing or selling pharmaceutical products. We also have only limited experience in negotiating and maintaining strategic relationships, and in conducting clinical trials and other later-stage phases of the regulatory approval process. We may not successfully engage in some or all of these activities.

We have limited manufacturing capability.

        While we believe that we can produce materials for clinical trials and produce products for human use at our recently completed Good Manufacturing Practices, or GMP, manufacturing facility, we may need to, depending on demand, expand our commercial manufacturing capabilities for products in the future if we elect not to or cannot contract with others to manufacture our products. This expansion may occur in stages, each of which would require regulatory approval, and product demand could at times exceed supply capacity. We have not selected a site for any expanded facilities and do not know what the construction cost will be for such facilities and whether we will have the financing needed for such construction. We do not know if or when the FDA will determine that such facilities comply with Good Manufacturing Practices. The projected location and construction of any facilities will depend on regulatory approvals, product development, pharmaceutical partners and capital resources, among other factors. We have not obtained regulatory approvals for any productions facilities for our products, nor can we assure investors that we will be able to do so.

If we lose key personnel or are unable to attract and retain additional, highly skilled personnel required for our activities, our business will suffer.

        Our success will depend to a large extent on the abilities and continued service of several key employees, including Drs. Denis Burger, Patrick Iversen, David Mason and Dwight Weller. We maintain key man life insurance in the amount of $1,000,000 for Dr. Burger and $500,000 for each of Drs. Iversen and Weller. The loss of any of these key employees could significantly delay the achievement of our goals. Competition for qualified personnel in our industry is intense, and our success will depend on our ability to attract and retain highly skilled personnel. To date, we are not aware of any key personnel who plan to retire or otherwise leave AVI in the near future.

4


Asserting, defending and maintaining our intellectual property rights could be difficult and costly, and our failure to do so would harm our ability to compete and the results of our operations.

        Our success will depend on our existing patents and licenses, and our ability to obtain additional patents in the future. We have been issued 74 patents and have filed an additional 110 patent applications in the United States, Canada, Europe, Australia and Japan. We license the composition, manufacturing and use of AVICINE in all fields, except fertility regulation, from The Ohio State University, and we license other patents for certain complementary technologies from others.

        Some of our patents on core technologies expire as early as 2008, including for NEUGENE; however, based on patented improvements and additions to such core patents, we believe our patent protection for those products and other products would extend beyond 2020.

        We cannot assure investors that our pending patent applications will result in patents being issued in the United States or foreign countries. In addition, the patents that have been or will be issued may not afford meaningful protection for our technology and products. Competitors may develop products similar to ours that do not conflict with our patents. Others may challenge our patents and, as a result, our patents could be narrowed or invalidated. The patent position of biotechnology firms generally is highly uncertain, involves complex legal and factual questions, and has recently been the subject of much litigation. No consistent policy has emerged from the United States Patent and Trademark Office, or USPTO, or the courts regarding the breadth of claims allowed or the degree of protection afforded under biotechnology patents. In addition, there is a substantial backlog of biotechnology patent applications at the USPTO and the approval or rejection of patents may take several years.

        Our success will also depend partly on our ability to operate without infringing upon the proprietary rights of others, as well as our ability to prevent others from infringing on our proprietary rights. We may be required at times to take legal action to protect our proprietary rights and, despite our best efforts, we may be sued for infringing on the proprietary rights of others. We have not received any communications or other indications from owners of related patents or others that such persons believe our products or technology may infringe their patents. Patent litigation is costly and, even if we prevail, the cost of such litigation could adversely affect our financial condition. If we do not prevail, in addition to any damages we might have to pay, we could be required to stop the infringing activity or obtain a license. Any required license may not be available to us on acceptable terms, or at all. If we fail to obtain a license, our business might be materially adversely affected.

        To help protect our proprietary rights in unpatented trade secrets, we require our employees, consultants and advisors to execute confidentiality agreements. However, such agreements may not provide us with adequate protection if confidential information is used or disclosed improperly. In addition, in some situations, these agreements may conflict with, or be subject to, the rights of third parties with whom our employees, consultants or advisors have prior employment or consulting relationships. Further, others may independently develop substantially equivalent proprietary information and techniques, or otherwise gain access to our trade secrets.

If our relationships are unsuccessful, our business could be harmed.

        Our strategic relationships with SuperGen, Inc., Medtronic, Inc., Exelixis, Inc. and others are important to our success. The development, improvement and marketing of many of our key therapeutic products are or will be dependent on the efforts of our strategic partners. For example, under the SuperGen relationship, we may fail to achieve clinical and sales milestones; AVICINE may fail to achieve regulatory approval; AVICINE may not be commercially successful; SuperGen may fail to perform its obligations under our agreements, such as failing to devote sufficient resources to marketing AVICINE; and our agreements with SuperGen may be terminated against our will. Similarly, Medtronic may fail to perform its obligations under our nonexclusive agreement, such as failing to devote sufficient resources to development or to market such products. We may also need additional

5


future funding, including for operations, product development and our other activities. We may not receive additional funding from our strategic partners, including SuperGen and Medtronic, under existing agreements. We may not receive any additional payments from SuperGen or Medtronic and those relationships may not be commercially successful. The transactions contemplated by our agreements with strategic partners, including the equity purchases and cash payments, are subject to numerous risks and conditions. The occurrence of any of these events could severely harm our business.

        Our near-term strategy is to co-develop products with strategic partners or to license the marketing rights for our products to pharmaceutical partners after we complete one or more Phase II clinical trials. In this manner, the extensive costs associated with late-stage clinical development and marketing will be shared with, or become the responsibility of, our strategic partners.

        To fully realize the potential of our products, including development, production and marketing, we may need to establish other strategic relationships.

We have limited sales capability and may not be able to successfully commercialize our products.

        We have been engaged solely in the development of pharmaceutical technology. Although some of our management have experience in biotechnology company operations, we have limited experience in manufacturing or selling pharmaceutical products. We also have only limited experience in negotiating and maintaining strategic relationships, and in conducting clinical trials and other later phases of the regulatory approval process. To the extent we rely on strategic partners to fully commercialize our products, we will be dependent on their efforts. We may not successfully engage in any of these activities.

We may be subject to product liability lawsuits and our insurance may not be adequate to cover damages.

        We believe we carry adequate insurance for the product development research we currently conduct. In the future, when we have products available for commercial sale and use, the use of our products will expose us to the risk of product liability claims. Although we intend to obtain product liability insurance coverage, product liability insurance may not continue to be available to us on acceptable terms and our coverage may not be sufficient to cover all claims against us. A product liability claim, even one without merit or for which we have substantial coverage, could result in significant legal defense costs, thereby increasing our expenses, lowering our earnings or, depending on revenues, potentially resulting in additional losses.

Continuing efforts of government and third party payers to contain or reduce the costs of health care may adversely affect our revenues and future profitability.

        In addition to obtaining regulatory approval, the successful commercialization of our products will depend on our ability to obtain reimbursement for the cost of the product and treatment. Government authorities, private health insurers and other organizations, such as HMOs, are increasingly challenging the prices charged for medical products and services. Also, the trend toward managed health care in the United States, the growth of healthcare organizations, such as HMOs, and legislative proposals to reform healthcare and government insurance programs could significantly influence the purchase of healthcare services and products, resulting in lower prices and reducing demand for our products. The cost containment measures that healthcare providers are instituting and any healthcare reform could affect our ability to sell our products and may have a material adverse effect on our operations. Reimbursement in the United States or foreign countries may not be available for any of our products, any reimbursement granted may be reduced or discontinued, and limits on reimbursement available from third-party payors may reduce the demand for, or the price of, our products. The lack or inadequacy of third-party reimbursements for our products would have a material adverse effect on our operations. Additional legislation or regulation relating to the healthcare industry or third-party

6


coverage and reimbursement may be enacted in the future that adversely affects our products and our business.

If we fail to establish strategic relationships with larger pharmaceutical partners, our business may suffer.

        We do not intend to conduct late-stage human clinical trials ourselves. We anticipate entering into relationships with larger pharmaceutical companies to conduct later stage pharmaceutical trials and to market our products and we also plan to continue to use contract manufacturing for late stage clinical and commercial quantities of our products. We may be unable to enter into corporate partnerships, which could impede our ability to bring our products to market. Any such corporate partnerships, if entered, may not be on favorable terms and may not result in the successful development or marketing of our products. If we are unsuccessful in establishing advantageous clinical testing, manufacturing and marketing relationships, we are not likely to generate significant revenues and become profitable.

We use hazardous substances in our research activities.

        We use organic and inorganic solvents and reagents in our clinical development that are customarily used in pharmaceutical development and synthesis. Some of those solvents and reagents we use, such as methylene chloride, isopropyl alcohol, ethyl acetate and acetone, may be classified as hazardous substances, are flammable and, if exposed to human skin can cause anything from irritation to severe burns. We endeavor to receive, store, use and dispose of such chemicals in compliance with all applicable laws with containment storage facilities and contained handling and disposal safeguards and procedures. We are routinely inspected by federal, state and local governmental and public safety agencies regarding our storage, use and disposal of such chemicals, including the federal Occupational, Safety and Health Agency ("OSHA"), the Oregon Department of Environmental Quality and local fire departments. Based on our limited use of such chemicals, the nature of such chemicals and the safeguards we undertake for storage, use and disposal, we believe we do not have any material exposure for toxic tort liability. While we do not have toxic tort liability insurance at this time, we believe our current insurance coverage is adequate to cover most liabilities that may arise from our use of such substances. If we are wrong in any of our beliefs, we could incur a liability in certain circumstances that would be material to our finances and the value of an investment in our securities.

Risks Related to AVI Common Stock

Our right to issue preferred stock, our classified board of directors and Oregon anti-takeover laws may delay a takeover attempt and prevent or frustrate any attempt to replace or remove the then current management of the company by shareholders.

        Our authorized capital consists of 200,000,000 shares of common stock and 20,000,000 shares of preferred stock. Our board of directors, without any further vote by the shareholders, has the authority to issue preferred shares and to determine the price, preferences, rights and restrictions, including voting and dividend rights, of these shares. The rights of the holders of shares of common stock may be affected by the rights of holders of any preferred shares that our board of directors may issue in the future. For example, our board of directors may allow the issuance of preferred shares with more voting rights, higher dividend payments or more favorable rights upon dissolution, than the shares of common stock or special rights to elect directors.

        In addition, we have a "classified" board of directors, which means that only one-half of our directors are eligible for election each year. Therefore, if shareholders wish to change the composition of our Board of Directors, it could take up to two years to remove a majority of the existing directors or to change all directors. Having a classified board of directors may, in some cases, delay mergers, tender offers or other possible transactions which may be favored by some or a majority of our

7


shareholders and may delay or frustrate action by shareholders to change the then current board of directors and management.

        The Oregon Control Share Act and Business Combination Act may limit parties who acquire a significant amount of voting shares from exercising control over us for specific periods of time. These acts may lengthen the period for a proxy contest or for a person to vote their shares to elect the majority of our Board and change management.

Our stock price is volatile and may fluctuate due to factors beyond our control.

        Historically, the market price of our stock has been highly volatile. The table below shows the volatility of our stock, illustrated by the range of the high and low closing price per share sales prices, over the past two calendar years and calendar year 2003 through September 18, 2003.

 
   AVI COMMON STOCK
 
   LOW
   HIGH
CALENDAR YEAR ENDED DECEMBER 31, 2001            
First quarter   $ 3.00   $ 6.87
Second quarter     3.75     9.85
Third quarter.     5.86     10.45
Fourth quarter.     7.12     11.19

CALENDAR YEAR ENDED DECEMBER 31, 2002
 
 
 
 
 
 
First quarter     8.04     12.97
Second quarter     2.70     7.95
Third quarter.     2.71     5.34
Fourth quarter.     4.60     6.39

CALENDAR YEAR ENDING DECEMBER 31, 2003
 
 
 
 
 
 
First quarter     2.04     5.83
Second quarter     3.31     7.05
Third quarter (through September 18, 2003).     4.31     6.15

        The following types of announcements could have a significant impact on the price of our common stock: positive or negative results of testing and clinical trials by ourselves or competitors; delays in entering into corporate partnerships; technological innovations or commercial product introductions by ourselves or competitors; changes in government regulations; developments concerning proprietary rights, including patents and litigation matters; public concern relating to the commercial value or safety of any of our products; or general stock market conditions.

        Further, the stock market has in recent years experienced and may continue to experience significant price and volume fluctuations. These fluctuations have particularly affected the market prices of equity securities of many biopharmaceutical companies that are not yet profitable. Often, the effect on the price of such securities is unrelated or disproportionate to the operating performance of such companies. These broad market fluctuations may adversely affect the ability of a shareholder to dispose of his or her shares at a price equal to or above the price at which the shares were purchased.

The significant number of our shares of common stock eligible for future sale may cause the price of our common stock to fall.

        As of September 18, 2003, we had outstanding 31,205,412 shares of common stock and all were eligible for sale under Rule 144 or are otherwise freely tradable. The shares being registered hereunder

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will be freely tradable upon issuance and, in the case of warrants or convertible securities, the underlying shares issuable upon conversion or exercise will be freely tradable. In addition:


        Sales of substantial numbers of shares into the public market could lower the market price of our common stock.

        We were unable to obtain Arthur Andersen LLP's consent to incorporate by reference in this shelf registration Arthur Andersen's report on our financial statements for calendar years 2000 and 2001 which Arthur Andersen audited, which could reduce your rights if there were any material misstatements or omissions in such financial statements.

        On May 15, 2002, we dismissed Arthur Andersen as our auditors and retained KPMG LLP. In June 2002, Arthur Andersen was convicted of federal obstruction of justice charges. As a result of Arthur Andersen's conviction, Arthur Andersen is no longer in a position to reissue their audit reports or to provide consents to include financial statements in this prospectus supplement.

        Our financial statements for our two fiscal years ended December 31, 2001 and 2000 were audited by Arthur Andersen LLP ("Prior Financials"). Those Prior Financials were included in our annual report on Form 10-K for the fiscal year ended December 31, 2002, filed with the SEC on March 31, 2003. The Arthur Andersen report, dated February 21, 2002, expressed an unqualified opinion on those financials. The SEC rules relating to the registration of the securities included in this exchange offer require that we include in the registration of such shares the 2002 and 2001 financial statements and the auditor's reports thereon by incorporation of and reference to our annual report on Form 10-K for the year ended December 31, 2002, and that we file a consent of Arthur Andersen to such inclusion of their report. The consent of Arthur Andersen is not available as they are no longer in a position to reissue their reports or provide consents.

        Without Arthur Andersen's consent to such inclusion in the registration of the shares being offered, you may not rely on their audit of the Prior Financials in connection with your decision to exchange shares of eXegenics capital stock for shares of AVI common stock. As a result, your remedies as an investor against Arthur Andersen may be materially reduced or eliminated in the event of a material misstatement or omission in such Prior Financials. Under Section 11 of the Securities Act of 1933, as amended, you would otherwise have certain claims against Arthur Andersen if there were material misstatements or omissions related to Arthur Andersen's audit and opinion included in such Prior Financials. Without such consent, there would not be such liability. Further, there may be similar

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claims and remedies under the antifraud provisions of the 1933 Act, the Securities Exchange Act of 1934 and applicable state securities laws that will also not be available against Arthur Andersen for the audit and material misstatements or omissions, if any, related to such audit without such consent. In giving such consent, Arthur Andersen would normally undertake certain review and updating procedures that could uncover certain material misstatements or omissions, if they existed, in the Prior Financials or require their qualification. The Prior Financials incorporated herein will not have had the benefit of such review process and possible disclosure of any such misstatements, omissions or qualifications. While we are not aware of any material misstatements or omissions or qualifications related to the Prior Financials or Arthur Andersen's audit work, there is no assurance that there are none. If there are any, the value of an investment in our securities could be adversely affected and an investor would not have any recourse against Arthur Andersen if it were otherwise responsible to investors under applicable law for such loss. If there were any, we believe that it is unlikely that damages, if any, could be recovered from Arthur Andersen for any claim against Arthur Andersen.

We do not expect to pay dividends in the foreseeable future.

        We have never paid dividends on our shares of common stock and do not intend to pay dividends in the foreseeable future. Therefore, you should only invest in our common stock with the expectation of realizing a return through capital appreciation on your investment. You should not invest in our common stock if you are seeking dividend income.

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FORWARD-LOOKING INFORMATION

        Certain of the information relating to us contained in or incorporated by reference into this prospectus is forward-looking in nature. All statements included or incorporated by reference into this prospectus or made by your management, other than statements of historical fact regarding us, are forward-looking statements. Examples of forward-looking statements include statements regarding our financing needs, projected costs, future products and services, competitive positions, the effect of FDA regulation, the status and completion of clinical and pre-clinical trials, research and development efforts and plans and objectives of management for future operations. In some cases, you can identify forward-looking statements by terminology, such as "may," "will," "intends," "should," "would," "expects," "plans," "anticipates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other comparable terminology. Any forward-looking statements are qualified in their entirety by reference to the factors discussed throughout this prospectus. These and many other factors could affect our future financial and operating results and could cause actual results to differ materially from expectations based on forward-looking statements made in this document or elsewhere.

        Because the risk factors referred to above, as well as the risk factors incorporated by reference, could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements made by us or on our behalf, you should not place undue reliance on any forward-looking statements. Further, any forward-looking statement speaks only as of the date on which it is made, and we undertake no obligation to update any forward-looking statement to reflect events or circumstances after the date on which the statement is made or to reflect the occurrence of unanticipated events. New factors emerge from time to time, and it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements.


USE OF PROCEEDS

        Except as described in any prospectus supplement, we currently intend to use the net proceeds from the sale of our securities for research and development and general corporate purposes. We may also use a portion of the net proceeds to commercialize our products, or to acquire or invest in businesses, products and technologies that are complementary to our own or provide us with a strategic advantage, although we currently are not planning or negotiating any such transactions. Pending these uses, the net proceeds will be invested in investment-grade, interest-bearing securities.


DESCRIPTION OF CAPITAL STOCK

        Our authorized capital stock consists of 200 million shares of common stock, $.0001 par value, and 20 million shares of preferred stock, $.0001 par value. As of September 18, 2003, there were 31,205,412 shares of common stock outstanding and no shares of preferred stock outstanding.

Common Stock

        The holders of common stock are entitled to one vote for each share held of record on all matters submitted to a vote of the stockholders and do not have cumulative voting rights. Accordingly, holders of a majority of the shares of common stock entitled to vote in any election of directors may elect all of the directors standing for election. Subject to preferences that may be applicable to any outstanding shares of preferred stock, the holders of common stock are entitled to receive ratably such dividends as may be declared by the board of directors out of funds legally available therefor. Upon the liquidation, dissolution or winding up of the Company, holders of our common stock are entitled to share ratably in all assets remaining after payment of liabilities and the liquidation preferences of any outstanding

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shares of preferred stock. Holders of common stock have no preemptive rights and no right to convert their common stock into any other securities. There are no redemption or sinking fund provisions applicable to our common stock. All outstanding shares of common stock are, and all shares of common stock that may be issued under this prospectus will be, fully paid and non-assessable.

Preferred Stock

        Pursuant to our Amended and Restated Articles of Incorporation (as amended), our board of directors has the authority, without further action by the stockholders, to issue up to 20 million shares of preferred stock, in one or more series. Our board shall determine the rights, preferences, privileges and restrictions of the remaining preferred stock, including dividend rights, conversion rights, voting rights, terms of redemption, liquidation preferences, sinking fund terms and the number of shares constituting any series or the designation of any series.

        We will fix the rights, preferences, privileges and restrictions of the preferred stock of each series in the certificate of designation relating to that series. We will incorporate by reference as an exhibit to the registration statement that includes this prospectus or as an exhibit to a current report on Form 8-K, the form of any certificate of designation that describes the terms of the series of preferred stock we are offering before the issuance of the related series of preferred stock. This description will include:

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        If we issue shares of preferred stock under this prospectus, the shares will be fully paid and nonassessable and will not have, or be subject to, any preemptive or similar rights.

        The Oregon Business Corporation Act provides that the holders of preferred stock will have the right to vote separately as a class on any proposal involving fundamental changes in the rights of holders of that preferred stock. This right is in addition to any voting rights that may be provided for in the applicable certificate of designation.

        The issuance of preferred stock could adversely affect the voting power, conversion or other rights of holders of common stock. Preferred stock could be issued quickly with terms calculated to delay or prevent a change in control of our company or make removal of management more difficult. Additionally, the issuance of preferred stock may have the effect of decreasing the market price of common stock.

Registration Rights

        As of the date hereof, holders of rights to acquire approximately 31 million shares of common stock will either acquire shares that are registered upon acquisition and freely tradable or be entitled to require us, at our expense, subject to certain limitations, to file one or more registration statements under the Securities Act with respect to their shares of common stock, when acquired, and we will be required to use our best efforts to effect such registrations and, in some cases, keep such registrations effective until all such shares are sold or registration is no longer required under federal and state securities laws. In certain cases, if we propose to register any of our securities under the Securities Act, either for our own account or for the account of others, certain holders of these shares may be notice of the registration and be entitled to include, at our expense, their shares of common stock in the registration and any related underwriting, provided, among other conditions, that the underwriters may limit the number of shares to be included in the registration, if those shares are not otherwise then registered.

Anti-Takeover Effects of Provisions of Oregon Law and Our Charter Documents.

        Oregon Takeover Statute; Hostile Takovers.    The Oregon Control Share Act ("OCSA") regulates the process by which a person may acquire control of certain Oregon-based corporations without the consent and cooperation of the board of directors. The OCSA provisions restrict a shareholder's ability to vote shares of stock acquired in certain transactions not approved by the board that cause the acquiring person to gain control of a voting position exceeding one-fifth, one-third, or one-half of the votes entitled to be cast in an election of directors. Shares acquired in a control share acquisition have no voting rights except as authorized by a vote of the shareholders. A corporation may opt out of the OCSA by provision in the corporation's articles of incorporation or bylaws. AVI has not opted to take itself outside of the coverage of the OCSA.

        Interested Shareholder Transactions.    Except under certain circumstances, the OBCA prohibits a "business combination" between a corporation and an "interested shareholder" within three years of the shareholder becoming an "interested shareholder." Generally, an "interested shareholder" is a person or group that directly or indirectly controls, or has the right to acquire or control, the voting or disposition of 15% or more of the outstanding voting stock or is an affiliate or associate of the corporation and was the owner of 15% or more of such voting stock at any time within the previous

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three years. A "business combination" is defined broadly to include, among others (i) mergers and sales or other dispositions of 10% or more of the assets of a corporation with or to an interested shareholder, (ii) certain transactions resulting in the issuance or transfer to the interested shareholder of any stock of the corporation or its subsidiaries, (iii) certain transactions which would result in increasing the proportionate share of the stock of a corporation or its subsidiaries owned by the interested shareholder, and (iv) receipt by the interested shareholder of the benefit (except proportionately as a shareholder) of any loans, advances, guarantees, pledges, or other financial benefits.

        A business combination between a corporation and an interested shareholder is prohibited unless (i) prior to the date the person became an interested shareholder, the board of directors approved either the business combination or the transaction which resulted in the person becoming an interested shareholder, (ii) upon consummation of the transaction that resulted in the person becoming an interested shareholder, that person owns at least 85% of the corporation's voting stock outstanding at the time the transaction is commenced (excluding shares owned by persons who are both directors and officers and shares owned by employee stock plans in which participants do not have the right to determine confidentially whether shares will be tendered in a tender or exchange offer), or (iii) the business combination is approved by the board of directors and authorized by the affirmative vote (at an annual or special meeting and not by written consent) of at least 662/3% of the outstanding voting stock not owned by the interested shareholder.

        These restrictions placed on interested shareholders by the OBCA do not apply under certain circumstances, including, but not limited to, the following: (i) if the corporation's original articles of incorporation or certificate of incorporation contains a provision expressly electing not to be governed by the applicable section of the OBCA; or (ii) if the corporation, by action of its shareholders, adopts an amendment to its bylaws, articles of incorporation or certificate of incorporation expressly electing not to be governed by the applicable section of the OBCA, provided that such an amendment is approved by the affirmative vote of not less than a majority of the outstanding shares entitled to vote. Such an amendment, however, generally will not be effective until 12 months after its adoption and will not apply to any business combination with a person who became an interested shareholder at or prior to such adoption. AVI has not elected to take itself outside the coverage of the applicable sections of the OBCA. In addition, the restrictions are not applicable to business combinations proposed between the announcement and the consummation or abandonment of certain transactions, including mergers and tender offers.

        Board Of Directors' Criteria For Evaluating Business Combinations.    Under the OBCA, members of the board of directors of a corporation are authorized to consider certain factors in determining the best interests of the corporation when evaluating any (i) offer of another party to make a tender or exchange offer, (ii) merger or consolidation proposal, or (iii) offer of another party to purchase all or substantially all of the assets of the corporation. These factors include the social, legal and economic effects on employees, customers and suppliers of the corporation and on the communities and geographical areas in which the corporation operates, the economy and the state of the nation, the long-term and short-term interests of the corporation and its shareholders, including the possibility that these interests may be best served by the continued independence of the corporation, and other relevant factors.

        Charter Documents.    Our Amended and Restated Articles of Incorporation (as amended) and bylaws require that any action required or permitted to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders. Additionally, our Amended and Restated Articles of Incorporation or Bylaws:

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        Our board of directors may appoint new directors to fill vacancies or newly created directorships. Oregon law limits who may call a special meeting of stockholders.

        Oregon law and these charter provisions may have the effect of deterring or delaying hostile takeovers or delaying changes in control of our management, which could depress the market price of our common stock.

Transfer Agent and Registrar

        The transfer agent and registrar for our common stock is Mellon Investor Services LLC. Its address is 520 Pike Street, Suite 1220, Seattle, WA 98101and its telephone number is (206) 674-3030.

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DESCRIPTION OF WARRANTS

        The following description, together with the additional information we may include in any applicable prospectus supplements, summarizes the material terms and provisions of the warrants that we may offer under this prospectus and the related warrant agreements and warrant certificates. While the terms summarized below will apply generally to any warrants that we may offer, we will describe the particular terms of any series of warrants in more detail in the applicable prospectus supplement. If we indicate in the prospectus supplement, the terms of any warrants offered under that prospectus supplement may differ from the terms described below. Specific warrant agreements will contain additional important terms and provisions and will be incorporated by reference as an exhibit to the registration statement that includes this prospectus or as an exhibit to a current report on Form 8-K.

General

        We will describe in the applicable prospectus supplement the terms of the series of warrants, including:

        Before exercising their warrants, holders of warrants will not have any of the rights of holders of the securities purchasable upon such exercise, including:

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Exercise of Warrants

        Each warrant will entitle the holder to purchase the securities that we specify in the applicable prospectus supplement at the exercise price that we describe in the applicable prospectus supplement. Unless we otherwise specify in the applicable prospectus supplement, holders of the warrants may exercise the warrants at any time up to 5:00 P.M. New York time on the expiration date that we set forth in the applicable prospectus supplement. After the close of business on the expiration date, unexercised warrants will become void.

        Holders of the warrants may exercise the warrants by delivering the warrant certificate representing the warrants to be exercised together with specified information, and paying the required amount to the warrant agent in immediately available funds, as provided in the applicable prospectus supplement. We will set forth on the reverse side of the warrant certificate and in the applicable prospectus supplement the information that the holder of the warrant will be required to deliver to the warrant agent.

        Upon receipt of the required payment and the warrant certificate properly completed and duly executed at the corporate trust office of the warrant agent or any other office indicated in the applicable prospectus supplement, we will issue and deliver the securities purchasable upon such exercise. If fewer than all of the warrants represented by the warrant certificate are exercised, then we will issue a new warrant certificate for the remaining amount of warrants. If we so indicate in the applicable prospectus supplement, holders of the warrants may surrender securities as all or part of the exercise price for warrants.

Enforceability of Rights by Holders of Warrants

        Each warrant agent will act solely as our agent under the applicable warrant agreement and will not assume any obligation or relationship of agency or trust with any holder of any warrant. A single bank or trust company may act as warrant agent for more than one issue of warrants. A warrant agent will have no duty or responsibility in case of any default by us under the applicable warrant agreement or warrant, including any duty or responsibility to initiate any proceedings at law or otherwise, or to make any demand upon us. Any holder of a warrant may, without the consent of the related warrant agent or the holder of any other warrant, enforce by appropriate legal action its right to exercise, and receive the securities purchasable upon exercise of, its warrants.


LEGAL OWNERSHIP OF SECURITIES

        We can issue securities in registered form. We refer to those persons who have securities registered in their own names on the books that we or any applicable trustee maintain for this purpose as the "holders" of those securities. These persons are the legal holders of the securities. We refer to those persons who, indirectly through others, own beneficial interests in securities that are not registered in their own names, as "indirect holders" of those securities. As we discuss below, indirect holders are not legal holders, and investors in securities issued in book-entry form or in street name will be indirect holders.

Street Name Holders

        Investors may choose to hold their securities in their own names or in "street name." Securities held by an investor in street name would be registered in the name of a bank, broker or other financial

17


institution that the investor chooses, and the investor would hold only a beneficial interest in those securities through an account he or she maintains at that institution.

        For securities held in street name, we will recognize only the intermediary banks, brokers and other financial institutions in whose names the securities are registered as the holders of those securities, and we will make all payments on those securities to them. These institutions pass along the payments they receive to their customers who are the beneficial owners, but only because they agree to do so in their customer agreements or because they are legally required to do so. Investors who hold securities in street name will be indirect holders, not holders, of those securities.

Legal Holders

        Our obligations, as well as the obligations of any applicable trustee and of any third parties employed by us or a trustee, run only to the legal holders of the securities. We do not have obligations to investors who hold securities, in street name or by any other indirect means.

        For example, once we make a payment or give a notice to the holder, we have no further responsibility for the payment or notice even if that holder is required, under agreements with depositary participants or customers or by law, to pass it along to the indirect holders but does not do so. Similarly, we may want to obtain the approval of the holders to amend an indenture, to relieve us of the consequences of a default or of our obligation to comply with a particular provision of the indenture or for other purposes. In such an event, we would seek approval only from the holders, and not the indirect holders, of the securities. Whether and how the holders contact the indirect holders is up to the holders.

Special Considerations For Indirect Holders

        If you hold securities through a bank, broker or other financial institution in street name, you should check with your own institution to find out:


PLAN OF DISTRIBUTION

        We may sell the securities through underwriters or dealers, through agents, or directly to one or more purchasers. The prospectus supplement will describe the terms of the offering of the securities, including:

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        Only underwriters named in the prospectus supplement are underwriters of the securities offered by the prospectus supplement.

        If underwriters are used in the sale, they will acquire the securities for their own account and may resell them from time to time in one or more transactions at a fixed public offering price or at varying prices determined at the time of sale. The obligations of the underwriters to purchase the securities will be subject to the conditions set forth in the applicable underwriting agreement. We may offer the securities to the public through underwriting syndicates represented by managing underwriters or by underwriters without a syndicate. Subject to certain conditions, the underwriters will be obligated to purchase all the securities of the series offered by the prospectus supplement. Any public offering price and any discounts or concessions allowed or reallowed or paid to dealers may change from time to time. We may use underwriters with whom we have a material relationship. We will describe in the prospectus supplement, naming the underwriter, the nature of any such relationship.

        We may sell securities directly or through agents we designate from time to time. We will name any agent involved in the offering and sale of securities and we will describe any commissions we will pay the agent in the prospectus supplement.

        Unless the prospectus supplement states otherwise, our agent will act on a best-efforts basis for the period of its appointment.

        We may authorize agents or underwriters to solicit offers by certain types of institutional investors to purchase securities from us at the public offering price set forth in the prospectus supplement pursuant to delayed delivery contracts providing for payment and delivery on a specified date in the future. We will describe the conditions to these contracts and the commissions we must pay for solicitation of these contracts in the prospectus supplement.

        We may provide agents and underwriters with indemnification against certain civil liabilities, including liabilities under the Securities Act, or contribution with respect to payments that the agents or underwriters may make with respect to such liabilities. Agents and underwriters may engage in transactions with, or perform services for, us in the ordinary course of business.

        All securities we offer, other than common stock, will be new issues of securities with no established trading market. Any underwriters may make a market in these securities, but will not be obligated to do so and may discontinue any market making at any time without notice. We cannot guarantee the liquidity of the trading markets for any securities.

        Any underwriter may engage in over allotment, stabilizing transactions, short covering transactions and penalty bids in accordance with Regulation M under the Exchange Act. Over allotment involves sales in excess of the offering size, which create a short position. Stabilizing transactions permit bids to purchase the underlying security so long as the stabilizing bids do not exceed a specified maximum. Short covering transactions involve purchases of the securities in the open market after the distribution is completed to cover short positions. Penalty bids permit the underwriters to reclaim a selling concession from a dealer when the securities originally sold by the dealer are purchased in a covering transaction to cover short positions. Those activities may cause the price of the securities to be higher than it would otherwise be. If commenced, the underwriters may discontinue any of the activities at any time.

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        Any underwriters who are qualified market makers on the Nasdaq National Market may engage in passive market making transactions in the securities on the Nasdaq National Market in accordance with Rule 103 of Regulation M, during the business day prior to the pricing of the offering, before the commencement of offers or sales of the securities. Passive market makers must comply with applicable volume and price limitations and must be identified as passive market makers. In general, a passive market maker must display its bid at a price not in excess of the highest independent bid for such security; if all independent bids are lowered below the passive market maker's bid, however, the passive market maker's bid must then be lowered when certain purchase limits are exceeded.


LEGAL MATTERS

        The validity of the securities being offered hereby will be passed upon by Hurley, Lynch & Re, P.C., Bend, Oregon.


EXPERTS

        Our financial statements as of December 31, 2002 and for the year then ended, have been incorporated by reference herein and in the registration statement in reliance upon the report of KPMG llp, independent accountants, incorporated by reference herein, and upon the authority of said firm as experts in accounting and auditing.


WHERE YOU CAN FIND MORE INFORMATION

        We are a reporting company and file annual, quarterly and current reports, proxy statements and other information with the SEC. We have filed with the SEC a registration statement on Form S-3 under the Securities Act with respect to the shares of common stock and preferred stock and/or warrants we are offering under this prospectus. This prospectus does not contain all of the information set forth in the registration statement and the exhibits to the registration statement. For further information with respect to us and the securities we are offering under this prospectus, we refer you to the registration statement and the exhibits and schedules filed as a part of the registration statement. You may read and copy the registration statement, as well as our reports, proxy statements and other information, at the SEC's public reference rooms at Room 1024, 450 Fifth Street, N.W., Washington, D.C. 20549, as well as at the SEC's regional offices at 500 West Madison Street, Suite 1400, Chicago, IL 60661 and at 233 Broadway, New York, NY 10279. You can request copies of these documents by writing to the SEC and paying a fee for the copying cost. Please call the SEC at 1-800-SEC-0330 for more information about the operation of the public reference rooms. Our SEC filings are also available at the SEC's web site at "http://www.sec.gov." In addition, you can read and copy our SEC filings at the office of the National Association of Securities Dealers, Inc. at 1735 K Street, N.W., Washington, D.C. 20006.

        The SEC allows us to "incorporate by reference" information that we file with it, which means that we can disclose important information to you by referring you to those documents. The information incorporated by reference is an important part of this prospectus. Information in this prospectus supersedes information incorporated by reference that we filed with the SEC prior to the date of this prospectus, while information that we file later with the SEC will automatically update and supersede this information. We incorporate by reference into this registration statement and prospectus the documents listed below and any future filings we will make with the SEC under Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of the initial registration statement but prior to effectiveness of the registration statement and after the date of this prospectus but prior to the termination of the offering of the securities covered by this prospectus.

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        The following documents filed with the SEC are incorporated by reference in this prospectus:

        We will furnish without charge to you, on written or oral request, a copy of any or all of the documents incorporated by reference, including exhibits to these documents. You should direct any requests for documents to:

AVI BioPharma, Inc.
Investor Relations
One S.W. Columbia
Suite 1105
Portland, OR 97258
Attn: Michael C. Hubbard
(503) 227-0554

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7,500,000 Shares

GRAPHIC

Common Stock

PROSPECTUS SUPPLEMENT

                        , 2003

  Legg Mason Wood Walker  
  Incorporated  

 
Jefferies & Company, Inc.
 

 
First Albany Corporation
 

Neither we nor any of the underwriters have authorized anyone to provide information different from that contained in this prospectus. When you make a decision about whether to invest in our common stock, you should not rely upon any information other than the information in this prospectus. Neither the delivery of this prospectus nor the sale of our common stock means that information contained in this prospectus is correct after the date of this prospectus. This prospectus is not an offer to sell or solicitation of an offer to buy these shares of common stock in any circumstances under which the offer or solicitation is unlawful.



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ABOUT THIS PROSPECTUS SUPPLEMENT
FORWARD-LOOKING INFORMATION
PROSPECTUS SUPPLEMENT SUMMARY
Business Overview
Clinical Development Programs
Overview
Our Strategy
The Offering
Summary Financial Data
USE OF PROCEEDS
PRICE RANGE OF COMMON STOCK
CAPITALIZATION
DILUTION
UNDERWRITING
LEGAL MATTERS
TABLE OF CONTENTS
ABOUT THIS PROSPECTUS
AVI BIOPHARMA
THE SECURITIES WE MAY OFFER
RISK FACTORS
FORWARD-LOOKING INFORMATION
USE OF PROCEEDS
DESCRIPTION OF CAPITAL STOCK
DESCRIPTION OF WARRANTS
LEGAL OWNERSHIP OF SECURITIES
PLAN OF DISTRIBUTION
LEGAL MATTERS
EXPERTS
WHERE YOU CAN FIND MORE INFORMATION