Document:

Exhibit 4.3

 EXHIBIT 4.3 
  

COLUMBIA BANCORP 
  
 7168 Columbia Gateway Drive 
 Columbia, Maryland 21046 
  
                     , 20     
  
 Incentive Stock Option Agreement 
  
 [Name] 
 [Address] 
  
 Dear                     : 
  
 The Administrator of the Columbia Bancorp 1997 Stock Option Plan (the “Plan”) takes pleasure in extending to you an option (the
“Option”) to purchase shares of Common Stock of Columbia Bancorp (the “Common Stock”) pursuant to the Plan. The Option shall be subject to the following terms and conditions: 
  
 (1) Incentive Stock
Option.    The Option is intended to qualify as an incentive stock option within the meaning of Section 422 of the Internal Revenue Code of 1986, as amended or replaced (the “Code”), to the fullest extent
permitted within the limit set forth under Section 422(d) of the Code. The tax treatment under Code Section 421 for incentive stock options may not be applicable to a transfer of the Shares (as defined in Paragraph (2) hereof) to you if the Option
or the Shares do not satisfy the requirements of: (i) Code Section 421(b) (denying Code Section 421 tax treatment upon a disposition of the Shares within two (2) years from the Date of Grant or one (1) year after the transfer of Shares to you); (ii)
Code Section 422(a)(2) (denying such tax treatment if you have not been an employee continuously from the Date of Grant up to at least three (3) months before the date of exercise, except in the case of disability or death); or (iii) Code Section
422(b) (other requirements for incentive stock options). 
  
 (2) Number of Shares.    The Option covers              shares of Common Stock (the “Shares”). 

 
 (3) Option Price. The exercise price per share of
Common Stock covered by the Option shall be $             (“Exercise Price Per Share”; hereinafter “Exercise Price” means the exercise price with
respect to all Shares acquired pursuant to each exercise of the Option). 

 (4) Exercise of Option.    [For Options of 200 Shares or
Less:    Except as provided in Section 5(c) of the Plan, this Option may not be exercised during the first year after the Date of Grant, as defined in Paragraph (6) hereof. Unless terminated earlier pursuant to other
provisions hereof, this Option shall become exercisable in full after one year after the Date of Grant.] [For Options of More than 200 Shares:    Except as provided in Section 5(c) of the Plan, this Option (A) may not be
exercised during the first year after the Date of Grant, and (B) unless terminated earlier pursuant to other provisions hereof, the Option may be exercised to acquire up to: (i) twenty-five percent (25%) of the Shares after one year after the Date
of Grant; (ii) fifty percent (50%) after two years; (iii) seventy-five percent (75%) after three years; and (iv) one hundred percent (100%) after four years. 
  

(5) Termination of Employment.    This Option, to the extent it is not then exercisable, shall terminate
when your employment with Columbia Bancorp (the “Company”) and all Subsidiaries terminates. Except as provided in Paragraphs (5)(A) and (5)(B) hereof, the Option, to the extent it is exercisable but has not been exercised (the
“Unexercised Option”), shall also terminate when your employment with the Company and its Subsidiaries terminates. 
  
 (A) Retirement or Voluntary Resignation.    If you terminate employment with the Company and its Subsidiaries
due to (i) Retirement, as defined hereinafter, or (ii) voluntary resignation with the consent of the Board of Directors of the Company or a Subsidiary, the Unexercised Option may be exercised until the expiration of three (3) months after the date
your employment terminates. “Retirement” means a retirement from employment with the Company and its Subsidiaries either on or after the first day of the month coinciding with or next following your sixty-fifth (65th) birthday.

  
 (B) Death or
Disability.    If you terminate employment with the Company and its Subsidiaries due to (i) death or (ii) Disability, as defined hereinafter, the Unexercised Option may be exercised (in the case of death, by your executor,
personal representative, or the person to whom the Unexercised Option shall have been transferred by will or the laws of descent and distribution, as the case may be) until the expiration of one (1) year after the date of your termination of
employment. If you die during the three (3) month post-termination exercise period provided to you under Paragraph 5(A) above, the Unexercised Option may be exercised by your executor, personal representative, or the person to whom the Unexercised
Option shall have been transferred by will or the laws of descent and distribution, as the case may be, until the expiration of one (1) year after the date of your death. “Disability” means a permanent mental or physical disability
due to accident or illness that renders you unable to perform every duty of your occupation with the Company and the Subsidiaries for a period of at least one hundred eighty (180) days, provided that you establish such disability to the satisfaction
of the Administrator. Evidence of such Disability shall include the certificate of a competent licensed physician selected by you and 

  

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approved by the Administrator which confirms that you have a Disability as defined herein. 
  
 (6) Term of Option.    This
Option is effective as of the date the Administrator approved the Option,                     , 20     (the
“Date of Grant”). Notwithstanding anything herein to the contrary, this Option may not be exercised, in whole or in part, after ten (10) years from the Date of Grant (i.e., after
                    , 20    ). 
  
 (7) Manner of Exercise.    You or any person exercising the Option may do so only
by delivering written notice thereof to the Administrator. Such notice shall be in such form as the Administrator may require at its sole discretion. 
  
 (A) Payment of Exercise Price.    Full payment for the Exercise Price shall be made at or prior to the time
that the Option, or any part thereof, is exercised (or, in the discretion of the Administrator, at such later time as the certificates for such Shares are delivered). Such payment shall be made: (i) by cash or certified check; (ii) by tender (via
delivery or attestation to the Company of other shares of Common Stock of the Company which have a Fair Market Value on the date of tender equal to the Exercise Price, provided that such shares have been owned by you for a period of at least six
months free of any substantial risk of forfeiture or were purchased on the open market without assistance, direct or indirect, from the Company; or (iii) by a broker-assisted cashless exercise in accordance with Regulation T of the Board of
Governors of the Federal Reserve System and other applicable laws through a brokerage firm pre-approved by the Administrator. 
  
 (B) Withholding Taxes.    In the event any federal, state or local income and employment taxes required to be
withheld with respect to the Option (e.g., upon a loss of tax treatment under Code Section 421), you shall pay to the Company, or make provision satisfactory to the Administrator for payment of such taxes no later than the date of the event creating
the tax liability. The Company may, to the extent permitted by law, deduct any such tax obligations from any payment of any kind otherwise due to you. In the event that payment to the Company of such tax obligations is made in shares of Common
Stock, such shares shall be valued at Fair Market Value on the applicable date for such purposes. 
  
 (8) Right As Stockholder.    You will have no rights as a stockholder solely because of the grant or exercise
of the Option before the certificates for the Shares as to which the Option has been exercised is issued to you by the Company. 
  
 (9) Option Non-Assignable and Non-Transferable.    The Option and all rights granted hereunder, including the
right to surrender the Option, is not assignable or transferable other than by will or the laws of descent and 

  

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distribution and, during your lifetime, is exercisable only by you or your guardian or legal representative. 
  
 (10) Restricted Stock.    You
will receive Shares restricted in terms of transferability, as will be indicated in a legend printed on the stock certificate in the event that there is not an effective registration statement with respect to such Shares at the time of their issue.

  
 (11) Terms of
Plan.    The Option is granted under and subject to the provisions applicable to incentive stock options under the Plan, a copy of which is attached hereto and made a part hereof. Unless stated otherwise herein, capitalized
terms herein shall have the same meaning as defined in the Plan. 
  
 (12) Notices.    Any notice required or permitted to be given to the Administrator shall be sufficient if in writing and hand delivered, or sent by registered or certified mail, to:

  
 Personnel, Compensation and Stock Option
Committee 
 Columbia Bancorp 
 7168 Columbia Gateway Drive 
 Columbia, Maryland 21046 
  
 Such notice shall be deemed given as of the date of delivery or, if delivery
is made by mail, as of the date shown on the postmark on the receipt for registration or certification. 
  
 (13) Non-Guarantee of Employment.    Nothing in the Plan or in this Incentive Stock Option Agreement shall
confer any right on an individual to continue in the employ of the Company or any Subsidiary or shall interfere in any way with the right of the Company or a Subsidiary to terminate such employment at any time with or without cause or notice and
whether or not such discharge results in the Option becoming unexercisable. 
  
 (14) Binding Effect.    The covenants and agreements of this Incentive Stock Option Agreement contained herein shall be binding upon, and inure to the benefit of, the heirs, legal
representatives, successors, and assigns of the respective parties hereto. 
  
 (15) Entire Agreement.    Except as provided in Paragraph (11) hereof, this Incentive Stock Option Agreement contains the entire agreement between the Company and you with respect to the
subject matter contained herein. Any oral or written agreements, representations, warranties, written inducements, or other communications made prior to the execution of this Incentive Stock Option Agreement shall be void and ineffective for all
purposes. 
  
 (16) Governing
Law.    The validity, construction and effect of this Incentive Stock Option Agreement, and of any rules, regulations, determinations 

  

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or decisions made by the Administrator relating thereto, and the rights of any and all persons having or claiming to have any interest hereunder, shall be
determined exclusively in accordance with applicable federal laws and the laws of the State of Maryland, without regard to its conflict of laws principles. 
  
 (17) Amendment.    This Incentive Stock Option Agreement may be amended from time to time by the Administrator
in its discretion; provided, however, that it may not be amended in a manner that would have a materially adverse effect on the Option as determined in the discretion of the Administrator, except as provided in the Plan or in a written document
signed by you and the Company. 
  
 {Signatures appear on next
page} 
  

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 The copy of the Option enclosed should be signed by you, dated, and returned to the Company prior to
                    , 20     to acknowledge your receipt of the Option and your approval of each of the terms and
conditions hereof. If the Option has not been accepted and approved by you in writing by such date, it shall terminate. 
  

					
	 Very truly yours,
  
 ADMINISTRATOR, COLUMBIA BANCORP
 1997 STOCK OPTION PLAN

		
	By:	 	  

	 Print Name:
	 	  

	 Title:
	 	  

  

			
	Accepted and Approved:
	
	  

	 Print Name:
	 	  

							
	 Dated:
	 	  

	 	, 20	 	  

  
  

 6AMENDED & RESTATED GENESOFT PHARMACEUTICALS 1998 STOCK OPTION ISSUANCE PLAN

 Exhibit 4.1 
  

AMENDED AND RESTATED 
 GENESOFT
PHARMACEUTICALS, INC. 
 1998 STOCK OPTION/STOCK ISSUANCE PLAN 
  
 (as amended on September 29, 1998, August 11, 1999, April 18, 2000, May 16, 2001, December 3, 2002 and December 9, 2002)

  
 ARTICLE ONE 
  
 GENERAL PROVISIONS 
  

	 	I.	PURPOSE OF THE PLAN 

  
 This Amended and Restated 1998 Stock Option/Stock Issuance Plan (the “Plan”) is intended to promote the interests of GeneSoft Pharmaceuticals,
Inc., a Delaware corporation, by providing eligible persons in the Corporation’s employ or service with the opportunity to acquire a proprietary interest, or otherwise increase their proprietary interest, in the Corporation as an incentive for
them to continue in such employ or service. 
  
 Capitalized terms
herein shall have the meanings assigned to such terms in the attached Appendix. 
  

	 	II.	STRUCTURE OF THE PLAN 

  
 A. The Plan shall be divided into two (2) separate equity programs: 
  
 (i) the Option Grant Program under which eligible persons may, at the discretion of the Plan Administrator,
be granted options to purchase shares of Common Stock, and 
  
 (ii) the Stock Issuance Program under which eligible persons may, at the discretion of the Plan Administrator, be issued shares of Common Stock directly, either through the immediate purchase of such shares or as a
bonus for services rendered the Corporation (or any Parent or Subsidiary). 
  
 B. The provisions of Articles One and Four shall apply to both equity programs under the Plan and shall accordingly govern the interests of all persons under the Plan. 
  

	 	III.	ADMINISTRATION OF THE PLAN 

  
 A. The Plan shall be administered by the Board. However, any or all administrative functions otherwise exercisable by the Board may be delegated to the
Committee. Members of the Committee shall serve for such period of time as the Board may determine and shall be subject to removal by the Board at any time. The Board may also at any time terminate the functions of the Committee and reassume all
powers and authority previously delegated to the Committee. 

 B. The Plan Administrator shall have full power and authority (subject to the provisions of the Plan) to
establish such rules and regulations as it may deem appropriate for proper administration of the Plan and to make such determinations under, and issue such interpretations of, the Plan and any outstanding options or stock issuances thereunder as it
may deem necessary or advisable. Decisions of the Plan Administrator shall be final and binding on all parties who have an interest in the Plan or any option or stock issuance thereunder. 
  

	 	IV.	ELIGIBILITY 

  
 A. The persons eligible to participate in the Plan are as follows: 
  
 (i) Employees, 
  
 (ii) non-employee members of the Board or the non-employee members of the board of directors of any Parent or Subsidiary, and 

 
 (iii) consultants and other independent advisors who
provide services to the Corporation (or any Parent or Subsidiary). 
  
 B. The Plan Administrator shall have full authority to determine, (i) with respect to the grants made under the Option Grant Program, which eligible persons are to receive the option grants, the time or times when those grants are to be
made, the number of shares to be covered by each such grant, the status of the granted option as either an Incentive Option or a Non-Statutory Option, the time or times when each option is to become exercisable, the vesting schedule (if any)
applicable to the option shares and the maximum term for which the option is to remain outstanding, and (ii) with respect to stock issuances made under the Stock Issuance Program, which eligible persons are to receive such stock issuances, the time
or times when those issuances are to be made, the number of shares to be issued to each Participant, the vesting schedule (if any) applicable to the issued shares and the consideration to be paid by the Participant for such shares. 
  
 C. The Plan Administrator shall have the absolute discretion either to grant
options in accordance with the Option Grant Program or to effect stock issuances in accordance with the Stock Issuance Program. 
  

	 	V.	STOCK SUBJECT TO THE PLAN 

  
 A. The stock issuable under the Plan shall be shares of authorized but unissued or reacquired Common Stock. The maximum number of shares of Common Stock
which maybe issued over the term of the Plan shall not exceed Four Million Eleven Thousand Eight Hundred Fourteen (4,011,8141) shares. 

	1	Number reflects initial share reserve of 1,000,000 approved by the Board of Directors on June
30, 1998, 710,000-share increase approved by the Board of Directors on September 29, 1998, 1,000,000-share increase approved by the Board of Directors on August 11, 1999, 2,000,000-share increase approved by the Board of Directors on April 18, 2000,
500,000-share increase approved by the Board of Directors on May 16, 2001, 6,051,162-share increase approved by the Board of Directors on December 3, 2002, and a 1-for-2.807 stock split approved by the Board of Directors on December 9, 2002.

  

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 B. Shares of Common Stock subject to outstanding options shall be available for subsequent issuance under
the Plan to the extent (i) the options expire or terminate for any reason prior to exercise in full or (ii) the options are cancelled in accordance with the cancellation-regrant provisions of Article Two. Unvested shares issued under the Plan and
subsequently repurchased by the Corporation, at the option exercise or direct issue price paid per share, pursuant to the Corporation’s repurchase rights under the Plan shall be added back to the number of shares of Common Stock reserved for
issuance under the Plan and shall accordingly be available for reissuance through one or more subsequent option grants or direct stock issuances under the Plan. 
  

C. Should any change be made to the Common Stock by reason of any stock split, stock dividend, recapitalization, combination of shares, exchange of
shares or other change affecting the outstanding Common Stock as a class without the Corporation’s receipt of consideration, appropriate adjustments shall be made to (i) the maximum number and/or class of securities issuable under the Plan and
(ii) the number and/or class of securities and the exercise price per share in effect under each outstanding option in order to prevent the dilution or enlargement of benefits thereunder. The adjustments determined by the Plan Administrator shall be
final, binding and conclusive. In no event shall any such adjustments be made in connection with the conversion of one or more outstanding shares of the Corporation’s preferred stock into shares of Common Stock. 
  

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 ARTICLE TWO 
  
 OPTION GRANT PROGRAM 

	 	I.	OPTION TERMS 

  
 Each option shall be evidenced by one or more documents in the form approved by the Plan Administrator; provided, however, that each such document
shall comply with the terms specified below. Each document evidencing an Incentive Option shall, in addition, be subject to the provisions of the Plan applicable to such options. 
  
 A. Exercise Price. 
  
 1. The exercise price per share shall be fixed by the Plan Administrator in accordance with the following provisions:

  
 (i) The exercise price per share shall not be
less than eighty-five percent (85%) of the Fair Market Value per share of Common Stock on the option grant date. 
  
 (ii) If the person to whom the option is granted is a 10% Stockholder, then the exercise price per share shall not be less than one
hundred ten percent (110%) of the Fair Market Value per share of Common Stock on the option grant date. 
  
 2. The exercise price shall become immediately due upon exercise of the option and shall, subject to the provisions of Section I of Article Four and the
documents evidencing the option, be payable in cash or check made payable to the Corporation. Should the Common Stock be registered under Section 12 of the 1934 Act at the time the option is exercised, then the exercise price may also be paid as
follows: 
  
 (i) in shares of Common Stock held
for the requisite period necessary to avoid a charge to the Corporation’s earnings for financial reporting purposes and valued at Fair Market Value on the Exercise Date, or 
  
 (ii) to the extent the option is exercised for vested shares, through a special sale and remittance
procedure pursuant to which the Optionee shall concurrently provide irrevocable instructions (A) to a Corporation-designated brokerage firm to effect the immediate sale of the purchased shares and remit to the Corporation, out of the sale proceeds
available on the settlement date, sufficient funds to cover the aggregate exercise price payable for the purchased shares plus all applicable Federal, state and local income and employment taxes required to be withheld by the Corporation by reason
of such exercise and (B) to the Corporation to deliver the certificates for the purchased shares directly to such brokerage firm in order to complete the sale. 
  

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 Except to the extent such sale and remittance procedure is utilized, payment of the exercise price for
the purchased shares must be made on the Exercise Date. 
  
 B.
Exercise and Term of Options. Each option shall be exercisable at such time or times, during such period and for such number of shares as shall be determined by the Plan Administrator and set forth in the documents evidencing the
option grant. However, no option shall have a term in excess of ten (10) years measured from the option grant date. 
  
 C. Effect of Termination of Service. 
  
 1. The following provisions shall govern the exercise of any options held by the Optionee at the time of cessation of Service or death: 
  
 (i) Should the Optionee cease to remain in Service for any
reason other than death, Disability or Misconduct, then the Optionee shall have a period of three (3) months following the date of such cessation of Service during which to exercise each outstanding option held by such Optionee. 
  
 (ii) Should Optionee’s Service terminate by reason of
Disability, then the Optionee shall have a period of twelve (12) months following the date of such cessation of Service during which to exercise each outstanding option held by such Optionee. 
  
 (iii) If the Optionee dies while holding an outstanding
option, then the personal representative of his or her estate or the person or persons to whom the option is transferred pursuant to the Optionee’s will or the laws of inheritance shall have a twelve (12)-month period following the date of the
Optionee’s death to exercise such option. 
  
 (iv) Under no circumstances, however, shall any such option be exercisable after the specified expiration of the option term. 
  
 (v) During the applicable post-Service exercise period, the option may not be exercised in the aggregate for more than the number of
vested shares for which the option is exercisable on the date of the Optionee’s cessation of Service. Upon the expiration of the applicable exercise period or (if earlier) upon the expiration of the option term, the option shall terminate and
cease to be outstanding for any vested shares for which the option has not been exercised. However, the option shall, immediately upon the Optionee’s cessation of Service, terminate and cease to be outstanding with respect to any and all option
shares for which the option is not otherwise at the time exercisable or in which the Optionee is not otherwise at that time vested. 
  
 (vi) Should Optionee’s Service be terminated for Misconduct, then all outstanding options held by the Optionee shall terminate
immediately and cease to remain outstanding. 
  

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 2. The Plan Administrator shall have the discretion, exercisable either at the time an option is granted
or at any time while the option remains outstanding, to: 
  
 (i) extend the period of time for which the option is to remain exercisable following Optionee’s cessation of Service or death from the limited period otherwise in effect for that option to such greater period of
time as the Plan Administrator shall deem appropriate, but in no event beyond the expiration of the option term, and/or 
  
 (ii) permit the option to be exercised, during the applicable post-Service exercise period, not only with respect to the number of vested
shares of Common Stock for which such option is exercisable at the time of the Optionee’s cessation of Service but also with respect to one or more additional installments in which the Optionee would have vested under the option had the
Optionee continued in Service. 
  
 D. Stockholder
Rights. The holder of an option shall have no stockholder rights with respect to the shares subject to the option until such person shall have exercised the option, paid the exercise price and become the recordholder of the purchased
shares. 
  
 E. Unvested Shares. The Plan
Administrator shall have the discretion to grant options which are exercisable for unvested shares of Common Stock. Should the Optionee cease Service while holding such unvested shares, the Corporation shall have the right to repurchase, at the
exercise price paid per share, any or all of those unvested shares. The terms upon which such repurchase right shall be exercisable (including the period and procedure for exercise and the appropriate vesting schedule for the purchased shares) shall
be established by the Plan Administrator and set forth in the document evidencing such repurchase right. The Plan Administrator may not impose a vesting schedule upon any option grant or the shares of Common Stock subject to that option which is
more restrictive than twenty percent (20%) per year vesting, with the initial vesting to occur not later than one (1) year after the option grant date. However, such limitation shall not be applicable to any option grants made to individuals who are
officers of the Corporation, non-employee Board members or independent consultants. 
  
 F. First Refusal Rights. Until such time as the Common Stock is first registered under Section 12 of the 1934 Act, the Corporation shall have the right of first refusal with respect to any proposed
disposition by the Optionee (or any successor in interest) of any shares of Common Stock issued under the Plan. Such right of first refusal shall be exercisable in accordance with the terms established by the Plan Administrator and set forth in the
document evidencing such right. 
  
 G. Limited
Transferability of Options. During the lifetime of the Optionee, Incentive Options and Non-Statutory Options shall be exercisable only by the Optionee and shall not be assignable or transferable other than by will or by the laws of descent
and distribution following the Optionee’s death. 
  

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 H. Withholding. The Corporation’s obligation to deliver shares of Common Stock upon
the exercise of any options granted under the Plan shall be subject to the satisfaction of all applicable Federal, state and local income and employment tax withholding requirements. 
  

	 	II.	INCENTIVE OPTIONS 

  
 The terms specified below shall be applicable to all Incentive Options. Except as modified by the provisions of this Section II, all the provisions of
Articles One, Two and Four shall be applicable to Incentive Options. Options which are specifically designated as Non-Statutory Options shall not be subject to the terms of this Section II. 
  
 A. Eligibility. Incentive Options may only be granted to
Employees. 
  
 B. Exercise Price. The exercise price
per share shall not be less than one hundred percent (100%) of the Fair Market Value per share of Common Stock on the option grant date. 
  
 C. Dollar Limitation. The aggregate Fair Market Value of the shares of Common Stock (determined as of the respective date or dates of grant)
for which one or more options granted to any Employee under the Plan (or any other option plan of the Corporation or any Parent or Subsidiary) may for the first time become exercisable as Incentive Options during any one (1) calendar year shall not
exceed the sum of One Hundred Thousand Dollars ($100,000). To the extent the Employee holds two (2) or more such options which become exercisable for the first time in the same calendar year, the foregoing limitation on the exercisability of such
options as Incentive Options shall be applied on the basis of the order in which such options are granted. 
  
 D. 10% Stockholder. If any Employee to whom an Incentive Option is granted is a 10% Stockholder, then the option term shall not exceed five
(5) years measured from the option grant date. 
  

	 	III.	CORPORATE TRANSACTION 

  
 A. The shares subject to each option outstanding under the Plan at the time of a Corporate Transaction shall automatically vest in full so that each such
option shall, immediately prior to the effective date of the Corporate Transaction, become fully exercisable for all of the shares of Common Stock at the time subject to that option and may be exercised for any or all of those shares as fully-vested
shares of Common Stock. However, the shares subject to an outstanding option shall not vest on such an accelerated basis if and to the extent: (i) such option is assumed by the successor corporation (or parent thereof) in the Corporate
Transaction and any repurchase rights of the Corporation with respect to the unvested option shares are concurrently assigned to such successor corporation (or parent thereof) or (ii) such option is to be replaced with a cash incentive program of
the successor corporation which preserves the spread existing on the unvested option shares at the time of the Corporate Transaction and provides for subsequent payout in accordance with the same vesting schedule applicable to those unvested option
shares or (iii) the acceleration of such option is subject to other limitations imposed by the Plan Administrator at the time of the option grant. 
  

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 B. All outstanding repurchase rights shall also terminate automatically, and the shares of Common Stock
subject to those terminated rights shall immediately vest in full, in the event of any Corporate Transaction, except to the extent: (i) those repurchase rights are assigned to the successor corporation (or parent thereof) in connection with such
Corporate Transaction or (ii) such accelerated vesting is precluded by other limitations imposed by the Plan Administrator at the time the repurchase right is issued. 
  
 C. Immediately following the consummation of the Corporate Transaction, all outstanding options shall terminate and cease to
be outstanding, except to the extent assumed by the successor corporation (or parent thereof). 
  
 D. Each option which is assumed in connection with a Corporate Transaction shall be appropriately adjusted, immediately after such Corporate Transaction,
to apply to the number and class of securities which would have been issuable to the Optionee in consummation of such Corporate Transaction, had the option been exercised immediately prior to such Corporate Transaction. Appropriate adjustments shall
also be made to (i) the number and class of securities available for issuance under the Plan following the consummation of such Corporate Transaction and (ii) the exercise price payable per share under each outstanding option, provided the
aggregate exercise price payable for such securities shall remain the same. 
  
 E. The Plan Administrator shall have the discretion, exercisable either at the time the option is granted or at any time while the option remains outstanding, to structure one or more options so that those options
shall automatically accelerate and vest in full (and any repurchase rights of the Corporation with respect to the unvested shares subject to those options shall immediately terminate) upon the occurrence of a Corporate Transaction, whether or not
those options are to be assumed in the Corporate Transaction. 
  
 F. The Plan Administrator shall also have full power and authority, exercisable either at the time the option is granted or at any time while the option remains outstanding, to structure such option so that the shares subject to that option
will automatically vest on an accelerated basis should the Optionee’s Service terminate by reason of an Involuntary Termination within a designated period (not to exceed eighteen (18) months) following the effective date of any Corporate
Transaction in which the option is assumed and the repurchase rights applicable to those shares do not otherwise terminate. Any option so accelerated shall remain exercisable for the fully-vested option shares until the expiration or sooner
termination of the option term. In addition, the Plan Administrator may provide that one or more of the Corporation’s outstanding repurchase rights with respect to shares held by the Optionee at the time of such Involuntary Termination shall
immediately terminate on an accelerated basis, and the shares subject to those terminated rights shall accordingly vest at that time. 
  
 G. The portion of any Incentive Option accelerated in connection with a Corporate Transaction shall remain exercisable as an Incentive Option only to the
extent the applicable One Hundred Thousand Dollar limitation is not exceeded. To the extent such dollar limitation is exceeded, the accelerated portion of such option shall be exercisable as a Non-Statutory Option under the Federal tax laws.

  

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 H. The grant of options under the Plan shall in no way affect the right of the Corporation to adjust,
reclassify, reorganize or otherwise change its capital or business structure hereto, merge, consolidate, dissolve, liquidate or sell or transfer all or any part of its business or assets. 
  

	 	IV.	CANCELLATION AND REGRANT OF OPTIONS 

  
 The Plan Administrator shall have the authority to effect, at any time and from time to time, with the consent of the affected option holders, the
cancellation of any or all outstanding options under the Plan and to grant in substitution therefor new options covering the same or different number of shares of Common Stock but with an exercise price per share based on the Fair Market Value per
share of Common Stock on the new option grant date. 
  

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 ARTICLE THREE 
  
 STOCK ISSUANCE PROGRAM 
  

	 	I.	STOCK ISSUANCE TERMS 

  
 Shares of Common Stock may be issued under the Stock Issuance Program through direct and immediate issuances without any intervening option grants. Each
such stock issuance shall be evidenced by a Stock Issuance Agreement which complies with the terms specified below. 
  

	 	A.	Purchase Price. 

  
 1. The purchase price per share shall be fixed by the Plan Administrator but shall not be less than eighty-five percent (85%) of the Fair Market Value
per share of Common Stock on the issue date. However, the purchase price per share of Common Stock issued to a 10% Stockholder shall not be less than one hundred percent (100%) of such Fair Market Value. 
  
 2. Subject to the provisions of Section I of Article Four, shares of Common
Stock may be issued under the Stock Issuance Program for any of the following items of consideration which the Plan Administrator may deem appropriate in each individual instance: 
  
 (i) cash or check made payable to the Corporation, or 
  
 (ii) past services rendered to the Corporation (or any
Parent or Subsidiary). 
  

	 	B.	Vesting Provisions. 

  
 1. Shares of Common Stock issued under the Stock Issuance Program may, in the discretion of the Plan Administrator, be fully and immediately vested upon
issuance or may vest in one or more installments over the Participant’s period of Service or upon attainment of specified performance objectives. However, the Plan Administrator may not impose a vesting schedule upon any stock issuance effected
under the Stock Issuance Program which is more restrictive than twenty percent (20%) per year vesting, with initial vesting to occur not later than one (1) year after the issuance date. Such limitation shall not apply to any Common Stock issuances
made to the officers of the Corporation, non-employee Board members or independent consultants. 
  
 2. Any new, substituted or additional securities or other property (including money paid other than as a regular cash dividend) which the Participant may
have the right to receive with respect to the Participant’s unvested shares of Common Stock by reason of any stock dividend, stock split, recapitalization, combination of shares, exchange of shares or other change affecting the outstanding
Common Stock as a class without the Corporation’s receipt of consideration shall be issued subject to (i) the same vesting requirements applicable to 
  

 10 

 the Participant’s unvested shares of Common Stock and (ii) such escrow arrangements as the Plan Administrator shall
deem appropriate. 
  
 3. The Participant shall have full
stockholder rights with respect to any shares of Common Stock issued to the Participant under the Stock Issuance Program, whether or not the Participant’s interest in those shares is vested. Accordingly, the Participant shall have the right to
vote such shares and to receive any regular cash dividends paid on such shares. 
  
 4. Should the Participant cease to remain in Service while holding one or more unvested shares of Common Stock issued under the Stock Issuance Program or should the performance objectives not be attained with respect
to one or more such unvested shares of Common Stock, then those shares shall be immediately surrendered to the Corporation for cancellation, and the Participant shall have no further stockholder rights with respect to those shares. To the extent the
surrendered shares were previously issued to the Participant for consideration paid in cash or cash equivalent (including the Participant’s purchase-money indebtedness), the Corporation shall repay to the Participant the cash consideration paid
for the surrendered shares and shall cancel the unpaid principal balance of any outstanding purchase-money note of the Participant attributable to such surrendered shares. 
  
 5. The Plan Administrator may in its discretion waive the surrender and cancellation of one or more unvested shares of
Common Stock (or other assets attributable thereto) which would otherwise occur upon the non-completion of the vesting schedule applicable to those shares. Such waiver shall result in the immediate vesting of the Participant’s interest in the
shares of Common Stock as to which the waiver applies. Such waiver may be effected at any time, whether before or after the Participant’s cessation of Service or the attainment or non-attainment of the applicable performance objectives.

  
 C. First Refusal Rights. Until such time as the Common
Stock is first registered under Section 12 of the 1934 Act, the Corporation shall have the right of first refusal with respect to any proposed disposition by the Participant (or any successor in interest) of any shares of Common Stock issued under
the Stock Issuance Program. Such right of first refusal shall be exercisable in accordance with the terms established by the Plan Administrator and set forth in the document evidencing such right. 
  

	 	II.	CORPORATE TRANSACTION 

  
 A. Upon the occurrence of a Corporate Transaction, all outstanding repurchase rights under the Stock Issuance Program shall terminate automatically, and
the shares of Common Stock subject to those terminated rights shall immediately vest in full, except to the extent: (i) those repurchase rights are assigned to the successor corporation (or parent thereof) in connection with such Corporate
Transaction or (ii) such accelerated vesting is precluded by other limitations imposed by the Plan Administrator at the time the repurchase right is issued. 
  
 B. The Plan Administrator shall have the discretionary authority, exercisable either at the time the unvested shares are issued or any time while the
Corporation’s repurchase rights with respect to those shares remain outstanding, to provide that those rights shall 
  

 11 

 automatically terminate on an accelerated basis, and the shares of Common Stock subject to those terminated rights shall
immediately vest, in the event the Participant’s Service should subsequently terminate by reason of an Involuntary Termination within a designated period (not to exceed eighteen (18) months) following the effective date of any Corporate
Transaction in which those repurchase rights are assigned to the successor corporation (or parent thereof). 
  

	 	III.	SHARE ESCROW/LEGENDS 

  
 Unvested shares may, in the Plan Administrator’s discretion, be held in escrow by the Corporation until the Participant’s interest in such
shares vests or may be issued directly to the Participant with restrictive legends on the certificates evidencing those unvested shares. 
  

 12 

 ARTICLE FOUR 
  
 MISCELLANEOUS 
  

	 	I.	FINANCING 

  
 The Plan Administrator may permit any Optionee or Participant to pay the option exercise price under the Option Grant Program or the purchase price for
shares issued under the Stock Issuance Program by delivering a full-recourse, interest bearing promissory note payable in one or more installments and secured by the purchased shares. The terms of any such promissory note (including the interest
rate and the terms of repayment) shall be established by the Plan Administrator in its sole discretion. In no event may the maximum credit available to the Optionee or Participant exceed the sum of (i) the aggregate option exercise price or purchase
price payable for the purchased shares (less the par value of those shares) plus (ii) any Federal, state and local income and employment tax liability incurred by the Optionee or the Participant in connection with the option exercise or share
purchase. 
  

	 	II.	EFFECTIVE DATE AND TERM OF PLAN 

  
 A. The Plan shall become effective when adopted by the Board, but no option granted under the Plan may be exercised, and no shares shall be issued under
the Plan, until the Plan is approved by the Corporation’s stockholders. If such stockholder approval is not obtained within twelve (12) months after the date of the Board’s adoption of the Plan, then all options previously granted under
the Plan shall terminate and cease to be outstanding, and no further options shall be granted and no shares shall be issued under the Plan. Subject to such limitation, the Plan Administrator may grant options and issue shares under the Plan at any
time after the effective date of the Plan and before the date fixed herein for termination of the Plan. 
  
 B. The Plan shall terminate upon the earliest of (i) the expiration of the ten (10)-year period measured from the date the Plan is adopted by the
Board, (ii) the date on which all shares available for issuance under the Plan shall have been issued as vested shares or (iii) the termination of all outstanding options in connection with a Corporate Transaction. All options and unvested stock
issuances outstanding at the time of a clause (i) termination event shall continue to have full force and effect in accordance with the provisions of the documents evidencing those options or issuances. 
  

	 	III.	AMENDMENT OF THE PLAN 

  
 A. The Board shall have complete and exclusive power and authority to amend or modify the Plan in any or all respects. However, no such amendment or
modification shall adversely affect the rights and obligations with respect to options or unvested stock issuances at the time outstanding under the Plan unless the Optionee or the Participant consents to such amendment or modification. In addition,
certain amendments may require stockholder approval pursuant to applicable laws and regulations. 
  
 B. Options may be granted under the Option Grant Program and shares may be issued under the Stock Issuance Program which are in each instance in excess of
the number of shares of Common Stock then available for issuance under the Plan, provided any excess 
  

 13 

 shares actually issued under those programs shall be held in escrow until there is obtained stockholder approval of an
amendment sufficiently increasing the number of shares of Common Stock available for issuance under the Plan. If such stockholder approval is not obtained within twelve (12) months after the date the first such excess grants or issuances are made,
then (i) any unexercised options granted on the basis of such excess shares shall terminate and cease to be outstanding and (ii) the Corporation shall promptly refund to the Optionees and the Participants the exercise or purchase price paid for any
excess shares issued under the Plan and held in escrow, together with interest (at the applicable Short Term Federal Rate) for the period the shares were held in escrow, and such shares shall thereupon be automatically cancelled and cease to be
outstanding. 
  

	 	IV.	USE OF PROCEEDS 

  
 Any cash proceeds received by the Corporation from the sale of shares of Common Stock under the Plan shall be used for general corporate purposes.

  

	 	V.	WITHHOLDING 

  
 The Corporation’s obligation to deliver shares of Common Stock upon the exercise of any options or upon the issuance or vesting of any shares issued
under the Plan shall be subject to the satisfaction of all applicable Federal, state and local income and employment tax withholding requirements. 
  

	 	VI.	REGULATORY APPROVALS 

  
 The implementation of the Plan, the granting of any options under the Plan and the issuance of any shares of Common Stock (i) upon the exercise of any
option or (ii) under the Stock Issuance Program shall be subject to the Corporation’s procurement of all approvals and permits required by regulatory authorities having jurisdiction over the Plan, the options granted under it and the shares of
Common Stock issued pursuant to it. 
  

	 	VII.	NO EMPLOYMENT OR SERVICE RIGHTS 

  
 Nothing in the Plan shall confer upon the Optionee or the Participant any right to continue in Service for any period of specific duration or interfere
with or otherwise restrict in any way the rights of the Corporation (or any Parent or Subsidiary employing or retaining such person) or of the Optionee or the Participant, which rights are hereby expressly reserved by each, to terminate such
person’s Service at any time for any reason, with or without cause. 
  

	 	VIII.	FINANCIAL REPORTS 

  
 The Corporation shall deliver a balance sheet and an income statement at least annually to each individual holding an outstanding option under the Plan,
unless such individual is a key Employee whose duties in connection with the Corporation (or any Parent or Subsidiary) assure such individual access to equivalent information. 
  

 14 

 APPENDIX 
  

The following definitions shall be in effect under the Plan: 
  

A. Board shall mean the Corporation’s Board of Directors. 
  
 B. Code shall mean the Internal Revenue Code of 1986, as amended. 
  
 C. Committee shall mean a committee of two (2) or more Board
members appointed by the Board to exercise one or more administrative functions under the Plan. 
  
 D. Common Stock shall mean the Corporation’s common stock. 
  
 E. Corporate Transaction shall mean either of the following stockholder-approved transactions to which the
Corporation is a party: 
  
 (i) a merger or
consolidation in which securities possessing more than fifty percent (50%) of the total combined voting power of the Corporation’s outstanding securities are transferred to a person or persons different from the persons holding those securities
immediately prior to such transaction, or 
  
 (ii) the sale, transfer or other disposition of all or substantially all of the Corporation’s assets in complete liquidation or dissolution of the Corporation. 
  
 F. Corporation shall mean GeneSoft Pharmaceuticals, Inc., a Delaware corporation, and any successor
corporation to all or substantially all of the assets or voting stock of GeneSoft Pharmaceuticals, Inc. which shall by appropriate action adopt the Plan. 
  
 G. Disability shall mean the inability of the Optionee or the Participant to engage in any substantial gainful activity by reason of any
medically determinable physical or mental impairment and shall be determined by the Plan Administrator on the basis of such medical evidence as the Plan Administrator deems warranted under the circumstances. 
  
 H. Employee shall mean an individual who is in the employ of
the Corporation (or any Parent or Subsidiary), subject to the control and direction of the employer entity as to both the work to be performed and the manner and method of performance. 
  
 I. Exercise Date shall mean the date on which the Corporation shall have received written notice of the option
exercise. 
  
 J. Fair Market Value per share of
Common Stock on any relevant date shall be determined in accordance with the following provisions: 
  
 (i) If the Common Stock is at the time traded on the Nasdaq National Market, then the Fair Market Value shall be the closing price

 per share of Common Stock on the date in question, as such price is reported by the National Association
of Securities Dealers on the Nasdaq National Market. If there is no closing price for the Common Stock on the date in question, then the Fair Market Value shall be the closing price on the last preceding date for which such quotation exists.

  
 (ii) If the Common Stock is at the time
listed on any Stock Exchange, then the Fair Market Value shall be the closing selling price per share of Common Stock on the date in question on the Stock Exchange determined by the Plan Administrator to be the primary market for the Common Stock,
as such price is officially quoted in the composite tape of transactions on such exchange. If there is no closing selling price for the Common Stock on the date in question, then the Fair Market Value shall be the closing selling price on the last
preceding date for which such quotation exists. 
  
 (iii) If the Common Stock is at the time neither listed on any Stock Exchange nor traded on the Nasdaq National Market, then the Fair Market Value shall be determined by the Plan Administrator after taking into account such factors as the
Plan Administrator shall deem appropriate. 
  
 K. Incentive
Option shall mean an option which satisfies the requirements of Code Section 422. 
  
 L. Involuntary Termination shall mean the termination of the Service of any individual which occurs by reason of: 
  

(i) such individual’s involuntary dismissal or discharge by the Corporation for reasons other than Misconduct, or 
  
 (ii) such individual’s voluntary resignation following
(A) a change in his or her position with the Corporation which materially reduces his or her duties and responsibilities or the level of management to which he or she reports, (B) a reduction in his or her level of compensation (including base
salary, fringe benefits and target bonuses under any corporate-performance based bonus or incentive programs) by more than fifteen percent (15%) or (C) a relocation of such individual’s place of employment by more than fifty (50) miles,
provided and only if such change, reduction or relocation is effected without the individual’s consent. 
  
 M. Misconduct shall mean the commission of any act of fraud, embezzlement or dishonesty by the Optionee or Participant, any unauthorized use
or disclosure by such person of confidential information or trade secrets of the Corporation (or any Parent or Subsidiary), or any other intentional misconduct by such person adversely affecting the business or affairs of the Corporation (or any
Parent or Subsidiary) in a material manner. The foregoing definition shall not be deemed to be inclusive of all the acts or omissions which the Corporation (or any Parent or Subsidiary) may consider as grounds for the dismissal or discharge of any

  

 2 

 Optionee, Participant or other person in the Service of the Corporation (or any Parent or Subsidiary). 
  
 N. 1934 Act shall mean the Securities Exchange Act of 1934, as
amended. 
  
 O. Non-Statutory Option shall mean an
option not intended to satisfy the requirements of Code Section 422. 
  
 P. Option Grant Program shall mean the option grant program in effect under the Plan. 
  
 Q. Optionee shall mean any person to whom an option is granted under the Plan. 
  
 R. Parent shall mean any corporation (other than the Corporation) in an unbroken chain of corporations ending
with the Corporation, provided each corporation in the unbroken chain (other than the Corporation) owns, at the time of the determination, stock possessing fifty percent (50%) or more of the total combined voting power of all classes of stock in one
of the other corporations in such chain. 
  
 S.
Participant shall mean any person who is issued shares of Common Stock under the Stock Issuance Program. 
  
 T. Plan shall mean the Corporation’s 1998 Stock Option/Stock Issuance Plan, as set forth in this document. 
  
 U. Plan Administrator shall mean either the Board or the
Committee acting in its capacity as administrator of the Plan. 
  
 V. Service shall mean the provision of services to the Corporation (or any Parent or Subsidiary) by a person in the capacity of an Employee, a non-employee member of the board of directors or a consultant or independent
advisor, except to the extent otherwise specifically provided in the documents evidencing the option grant. 
  
 W. Stock Exchange shall mean either the American Stock Exchange or the New York Stock Exchange. 
  
 X. Stock Issuance Agreement shall mean the agreement entered
into by the Corporation and the Participant at the time of issuance of shares of Common Stock under the Stock Issuance Program. 
  
 Y. Stock Issuance Program shall mean the stock issuance program in effect under the Plan. 
  
 Z. Subsidiary shall mean any corporation (other than the
Corporation) in an unbroken chain of corporations beginning with the Corporation, provided each corporation (other than the last corporation) in the unbroken chain owns, at the time of the determination, stock 
  

 3 

 possessing fifty percent (50%) or more of the total combined voting power of all classes of stock in one of the other
corporations in such chain. 
  
 AA. 10% Stockholder
shall mean the owner of stock (as determined under Code Section 424(d)) possessing more than ten percent (10%) of the total combined voting power of all classes of stock of the Corporation (or any Parent or Subsidiary). 
  

 4

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