Document:

Exhibit 4.3

 

GENTIUM
S.p.A.

2007 STOCK OPTION PLAN

 

(AS AMENDED THROUGH MAY 9, 2011)

 

    	 

    	 

    

 

TABLE OF CONTENTS

 

	SECTION 1.	PURPOSE	1
	 	 	 
	SECTION 2.	DEFINITIONS	1
	 	 	 
	(a)	“ADS”	1
	 	 	 
	(b)	“Affiliate”	1
	 	 	 
	(c)	“Award”	1
	 	 	 
	(d)	“Award Agreement”	1
	 	 	 
	(e)	“Board”	1
	 	 	 
	(f)	“Change In Control”	2
	 	 	 
	(g)	“Code”	2
	 	 	 
	(h)	“Committee”	2
	 	 	 
	(i)	“Company”	2
	 	 	 
	(j)	“Consultant”	2
	 	 	 
	(k)	“Corporate Transaction”	2
	 	 	 
	(l)	“Covered Employee”	3
	 	 	 
	(m)	“Director”	3
	 	 	 
	(n)	“Disability”	3
	 	 	 
	(o)	“Employee”	3
	 	 	 
	(p)	“Exchange Act”	3
	 	 	 
	(q)	“Exercise Price”	3
	 	 	 
	(r)	“Fair Market Value”	3
	 	 	 
	(s)	“Grant”	4
	 	 	 
	(t)	“Incentive Stock Option” or “ISO”	4
	 	 	 
	(u)	“Key Employee”	4
	 	 	 
	(v)	“Non-Employee Director”	4
	 	 	 
	(w)	“Non-Employee Independent Director”	4
	 	 	 
	(x)	“Nonstatutory Stock Option” or “NSO”	4
	 	 	 
	(y)	“Option”	4
	 	 	 
	(z)	“Optionee”	4
	 	 	 
	(aa)	“Parent”	5
	 	 	 
	(bb)	“Participant”	5
	 	 	 
	(cc)	“Plan”	5
	 	 	 
	(dd)	“Securities Act”	5

 

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	(ee)	“Service”	5
	 	 	 
	(ff)	“Share”	5
	 	 	 
	(gg)	“Stock Option Agreement”	5
	 	 	 
	(hh)	“Subsidiary”	5
	 	 	 
	(ii)	“10-Percent Shareholder”	5
	 	 	 
	SECTION 3.	ADMINISTRATION	5
	 	 	 
	(a)	Administration by Board	5
	 	 	 
	(b)	Powers of Board	5
	 	 	 
	(c)	Delegation to Committee	6
	 	 	 
	(d)	Effect of Board’s Decision	6
	 	 	 
	(e)	Indemnification	7
	 	 	 
	SECTION 4.	ELIGIBILITY	7
	 	 	 
	(a)	General Rules	7
	 	 	 
	(b)	Incentive Stock Options	7
	 	 	 
	(c)	Non-Employee Director Options	7
	 	 	 
	SECTION 5.	SHARES SUBJECT TO PLAN	8
	 	 	 
	(a)	Basic Limitation	8
	 	 	 
	(b)	Additional Shares	8
	 	 	 
	SECTION 6.	TERMS AND CONDITIONS OF OPTIONS	8
	 	 	 
	(a)	Stock Option Agreement	8
	 	 	 
	(b)	Number of Shares	8
	 	 	 
	(c)	Exercise Price	9
	 	 	 
	(d)	Exercisability and Term	9
	 	 	 
	(e)	Modifications or Assumption of Options	9
	 	 	 
	(f)	Transferability of Options	9
	 	 	 
	(g)	Restrictions on Transfer	9
	 	 	 
	(h)	Incentive Stock Option $100,000 Limitation	10
	 	 	 
	SECTION 7.	PROTECTION AGAINST DILUTION	10
	 	 	 
	(a)	Adjustments	10
	 	 	 
	(b)	Participant Rights	10
	 	 	 
	SECTION 8.	EFFECT OF A CORPORATE TRANSACTION	10
	 	 	 
	(a)	Merger or Reorganization	10

 

    	-ii-

    	 

    

 

	(b)	Acceleration	10
	 	 	 
	SECTION 9.	LIMITATIONS ON RIGHTS	11
	 	 	 
	(a)	Retention Rights	11
	 	 	 
	(b)	Shareholders’ Rights	11
	 	 	 
	(c)	Regulatory Requirements	11
	 	 	 
	SECTION 10.	WITHHOLDING TAXES	11
	 	 	 
	(a)	Withholding Obligations	11
	 	 	 
	SECTION 11.	DURATION AND AMENDMENTS	11
	 	 	 
	(a)	Term of the Plan	11
	 	 	 
	(b)	Right to Amend, Suspend or Terminate the Plan	11
	 	 	 
	(c)	Right to Amend Award	11
	 	 	 
	SECTION 12.	EXECUTION	12

 

    	-iii-

    	 

    

 

GENTIUM
S.p.A.

2007 STOCK OPTION PLAN

(AS AMENDED THROUGH MAY 9, 2011)

 

	SECTION 1.	PURPOSE.

 

This Gentium S.p.A. 2007 Stock
Option Plan (the “Plan”) was originally adopted by the Board on March 26, 2007, subject to approval by the Company’s
shareholders (which was obtained). The Plan has been amended by action of the Board pursuant to Section 11(b) herein, including
increasing the number of authorized Shares for issuance under the Plan to 3,200,000, which capital increase was approved by the
Company’s shareholders on May 9, 2011. The purpose of the Plan is to promote the long-term success of the Company and the
creation of shareholder value by offering Key Employees an opportunity to acquire a proprietary interest in the success of the
Company, or to increase such interest, and to encourage such selected persons to continue to provide services to the Company and
to attract new individuals with outstanding qualifications.

 

The Plan seeks to achieve this
purpose by providing for Awards in the form of Options (which may constitute Incentive Stock Options or Nonstatutory Stock Options).

 

The Plan shall be governed by,
and construed in accordance with, the laws of the Republic of Italy. Capitalized terms shall have the meaning provided in Section
2 of the Plan unless otherwise provided in this Plan or the applicable Award Agreement, or other applicable agreement.

 

	SECTION 2.	DEFINITIONS.

 

(a)          “ADS”
means American Depositary Shares issued pursuant to the Deposit Agreement dated June 15, 2005 between the Company and Bank
of New York, each ADS representing one Share.

 

(b)          “Affiliate”
means any entity other than a Subsidiary, if the Company and/or one or more Subsidiaries own not less than 50% of such entity.
For purposes of determining an individual’s “Service,” this definition shall include any entity other than a
Subsidiary, if the Company, a Parent and/or one or more Subsidiaries own not less than 50% of such entity.

 

(c)          “Award”
means any Grant of an Option.

 

(d)          “Award
Agreement” means a written agreement between the Company and a Participant evidencing the terms and conditions of a
Grant of an individual Award. Each Award Agreement shall be subject to the terms and conditions of the Plan.

 

(e)          “Board”
means the Board of Directors of the Company, as constituted from time to time.

 

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(f)          “Change
In Control” except as may otherwise be provided in an Award Agreement or other applicable
agreement, means the occurrence of any of the following:

 

(i)          The
consummation of a merger or consolidation of the Company with or into another entity or any other corporate reorganization, if
more than 50% of the combined voting power of the continuing or surviving entity’s securities outstanding immediately after
such merger, consolidation or other reorganization is owned by persons who were not shareholders of the Company immediately prior
to such merger, consolidation or other reorganization;

 

(ii)         The
sale, transfer or other disposition of all or substantially all of the Company’s assets;

 

(iii)        Any
transaction as a result of which any person becomes the beneficiary, owner and/or “beneficial owner” (as defined in
Rule 13d-3 under the Exchange Act), directly or indirectly, of securities of the Company representing at least 20% of the total
voting power represented by the Company’s then outstanding voting securities. For purposes of this Paragraph (iii),
the term “person” shall indicate any person and/or entity except for:

 

(A)         A
trustee or other fiduciary holding securities under an employee benefit plan of the Company or a subsidiary of the Company;

 

(B)         A
corporation owned directly or indirectly by the shareholders of the Company in substantially the same proportions as their ownership
of Shares; and

 

(C)         The
Company; or

 

(iv)         A
complete liquidation or dissolution of the Company.

 

(g)          “Code”
means the United States Internal Revenue Code of 1986, as amended.

 

(h)          “Committee”
means a committee consisting of one or more members of the Board that is appointed by the Board
(as described in Section 3) to administer the Plan.

 

(i)          “Company”
means Gentium S.p.A., a stock corporation organized under the laws of the Republic of Italy.

 

(j)          “Consultant”
means an individual who performs bona fide services to the Company,
a Parent, a Subsidiary or an Affiliate other than as an Employee or Director or Non-Employee Director.

 

(k)          “Corporate
Transaction” means the occurrence, in a single transaction or
in a series of related transactions, of any one or more of the following events:

 

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(i)          a
sale or other disposition of all or substantially all, as determined by the Board in its discretion, of the consolidated
assets of the Company and its Subsidiaries;

 

(ii)         a
merger, consolidation or similar transaction following which the Company is not the surviving corporation; or

 

(iii)        a
merger, consolidation or similar transaction following which the Company is the surviving corporation but the outstanding shares
thereof immediately preceding the merger, consolidation or similar transaction are converted or exchanged by virtue of the merger,
consolidation or similar transaction into other property, whether in the form of securities, cash or otherwise.

 

(l)          “Covered
Employee” means each of the chief executive officer and the 4 (four)
other highest compensated officers of the Company.

 

(m)         “Director”
means a member of the Board who is also an Employee.

 

(n)          “Disability”
means that the Key Employee is unable to engage in any substantial gainful
activity by reason of any medically determinable physical or mental impairment which can be expected to result in death or which
has lasted or can be expected to last for a continuous period of not less than 12 months.

 

(o)          “Employee”
means any individual who is an employee of the Company, a Parent, a Subsidiary
or an Affiliate. Mere service as a Director or payment of a director’s fee by the Company or an Affiliate shall not be sufficient
to constitute “employment” by the Company or an Affiliate.

 

(p)          “Exchange
Act” means the United States Securities Exchange Act of 1934, as amended.

 

(q)          “Exercise
Price” means, the amount for which a Share may be purchased upon exercise
of such Option, as specified in the applicable Stock Option Agreement.

 

(r)          “Fair
Market Value” means the market price of Shares, determined by the
Committee as follows:

 

(i)          If
ADSs were traded on a stock exchange on the date in question, then the Fair Market Value shall be equal to the closing price reported
by the applicable composite transactions report for such date;

 

(ii)         If
the ADSs were traded over-the-counter on the date in question and were classified as a national market issue or small cap issue,
then the Fair Market Value shall be equal to the closing price quoted by the NASDAQ system for such date;

 

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(iii)        If
the ADSs were traded over-the-counter on the date in question but were not classified as a national market issue, then the Fair
Market Value shall be equal to the mean between the last reported representative bid and asked prices quoted by the applicable
trading market for such date; and

 

(iv)         If
none of the foregoing provisions is applicable, then the Fair Market Value shall be determined by the Committee in good faith on
such basis as it deems appropriate.

 

Whenever possible, the determination
of Fair Market Value by the Committee shall be based on the prices reported in the Wall Street Journal. Such determination
shall be conclusive and binding on all persons.

 

(s)          “Grant”
means any grant of an Award under the Plan.

 

(t)          “Incentive
Stock Option” or “ISO” means an incentive stock option
described in Code section 422(b).

 

(u)          “Key
Employee” means an Employee, Director, Non-Employee Director or Consultant
who has been selected by the Committee to receive an Award under the Plan.

 

(v)          “Non-Employee
Director” means a member of the Board who is not an Employee.

 

(w)          “Non-Employee
Independent Director” means a Non-Employee Director who:

 

(i)          is
not a current Employee, is not a former Employee who received compensation for prior services in the current year, and has not
been an officer of the Company;

 

(ii)         did
not directly or indirectly receive more than $60,000 in remuneration from the Company during the current year, other than director
fees; and

 

(iii)        did
not receive more than $60,000 in remuneration from the Company during the prior year, other than director fees.

 

(x)          “Nonstatutory
Stock Option” or “NSO” means a stock option that is not
an ISO.

 

(y)          “Option”
means an ISO or NSO granted under the Plan entitling the Optionee to purchase
Shares.

 

(z)          
“Optionee” means an individual, estate or other entity
that holds an Option.

 

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(aa)         “Parent”
means a “parent corporation,” whether now or hereafter existing,
as defined in section 424(e) of the Code.

 

(bb)         “Participant”
means an individual or estate or other entity that holds an Award.

 

(cc)         “Plan”
means this Gentium S.p.A. 2007 Stock Option Plan as it may be amended from
time to time.

 

(dd)         “Securities
Act” means the United States Securities Act of 1933, as amended.

 

(ee)         “Service”
means service as an Employee, Director, Non-Employee Director or Consultant.
A change in the capacity in which the Participant renders service to the Company or an Affiliate as an Employee, Consultant, Director
or Non-Employee Director or a change in the entity for which the Participant renders such service, provided that there is no interruption
or termination of the Participant’s service with the Company or an Affiliate, shall not terminate a Participant’s
Service. For example, a change in status from an Employee of the Company to a Consultant of an Affiliate or a Director shall not
constitute an interruption of Service.

 

(ff)         “Share”
means one ordinary share of the Company.

 

(gg)         “Stock
Option Agreement” means the agreement described in Section 6
evidencing each Grant of an Option.

 

(hh)         “Subsidiary”
means a “subsidiary corporation,” whether now or hereafter existing,
as defined in section 424(f) of the Code.

 

(ii)         “10-Percent
Shareholder” means an individual who owns more than ten percent (10%)
of the total combined voting power of all classes of outstanding stock of the Company, its Parent or any of its Subsidiaries.
In determining stock ownership, the attribution rules of section 424(d) of the Code shall be applied.

 

	SECTION 3.	ADMINISTRATION.

 

(a)          Administration
by Board. The Board shall administer the Plan unless and until the Board
delegates administration to a Committee, as provided in Section 3(c).

 

(b)          Powers
of Board. The Board shall have the power, subject to, and within the limitations
of, the express provisions of the Plan:

 

(i)          to
determine from time to time which of the persons eligible under the Plan shall be granted Awards; when and how each Award shall
be granted; the provisions of each Award granted (which need not be identical), including the time or times when a person shall
be permitted to receive Shares pursuant to an Award; and the number of Shares with respect to which an Award shall be granted to
each such person;

 

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(ii)         to
construe and interpret the Plan, and Awards granted under it, and to establish, amend and revoke rules and regulations for its
administration. The Board, in the exercise of this power, may correct any defect, omission or inconsistency in the Plan or in any
Award Agreement, in a manner and to the extent it shall deem necessary or expedient to make the Plan fully effective;

 

(iii)        to
amend the Plan or an Award as provided in Section 11;

 

(iv)         to
terminate or suspend the Plan as provided in Section 11; and

 

(v)          generally,
to exercise such powers and to perform such acts as the Board deems necessary or expedient to promote the best interests of the
Company which are not in conflict with the provisions of the Plan.

 

(c)          Delegation
to Committee.

 

(i)          The
Board may delegate administration of the Plan to a Committee or Committees of the Board, and the term “Committee” shall
apply to persons to whom such authority has been delegated. If administration is delegated to a Committee, the Committee shall
have, in connection with the administration of the Plan, the powers theretofore possessed by the Board (and references in this
Plan to the Board shall thereafter be to the Committee), subject, however, to such resolutions, not inconsistent with the provisions
of the Plan, as may be adopted from time to time by the Board. The Board may abolish the Committee at any time and revest in the
Board the administration of the Plan.

 

(ii)         With
respect to Awards granted to any Covered Employee, the Committee shall consist of those individuals who are outside Non-Employee
Independent Directors.

 

The Board may also appoint one
or more separate committees of the Board, each composed of directors of the Company who need not to be outside Non-Employee Independent
Directors.

 

Notwithstanding
the foregoing, the Board shall constitute the Committee and shall administer the Plan with respect to all Awards granted to Non-Employee
Directors.

 

(d)          Effect
of Board’s Decision. All determinations, interpretations and constructions
made by the Board are not subject to review by any person and shall be final, binding and conclusive on all persons pursuant to
the relevant Italian law provisions.

 

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(e)          Indemnification.
Each member of the Committee, or of the Board, shall be indemnified and held harmless by the Company against and from (i) any
loss, cost, liability, or expense that may be imposed upon or reasonably incurred by him or her in connection with or resulting
from any claim, action, suit, or proceeding to which he or she may be a party or in which he or she may be involved by reason
of any action taken or failure to act under the Plan or any Award Agreement, and (ii) from any and all amounts paid by him
or her in settlement thereof, with the Company’s approval, or paid by him or her in satisfaction of any judgment in any
such claim, action, suit, or proceeding against him or her, provided he or she shall give the Company an opportunity, at its own
expense, to handle and defend the same before he or she undertakes to handle and defend it on his or her own behalf, except for
the case of fraud or gross negligence. The foregoing right of indemnification shall not be exclusive of any other rights of indemnification
to which such persons may be entitled under the Company’s Certificate of Incorporation or Bylaws, by contract, as
a matter of law, or otherwise, or under any power that the Company may have to indemnify them or hold them harmless.

 

	SECTION 4.	ELIGIBILITY.

 

(a)          General
Rules. Only Employees, Directors, Non-Employee Directors and Consultants shall be eligible for
designation as Key Employees by the Committee.

 

(b)          Incentive
Stock Options. A Key Employee who is a 10-Percent Shareholder shall not be eligible for the
grant of an ISO unless the requirements set forth in Sections 6(c) and 6(d) with respect to ISOs.

 

(c)          Non-Employee
Director Options. Non-Employee Directors shall also be eligible to receive Options as described
in this Section 4(c).

 

(i)          Each
Non-Employee Director shall be eligible to be granted an NSO to purchase a number of Shares (and upon such terms consistent with
the Plan) as determined by the Board and, if required by applicable law, approved by the Company’s shareholders (subject
to adjustment under Section 7(a)) as a result of his or her initial election to the Board as a Non-Employee Director.

 

(ii)         Upon
the conclusion of each regular annual meeting of the Company’s shareholders following his or her initial election, each eligible
Non-Employee Director who is re-elected as a Non-Employee Director shall be eligible to receive an NSO to purchase a number of
Shares (and upon such terms consistent with the Plan) as determined by the Board and, if required by applicable law, approved by
the Company’s shareholders (subject to adjustment under Section 7(a)).

 

(iii)        All
NSOs granted to Non-Employee Directors under this Section 4(c) shall vest and become exercisable provided the individual is serving
as a Non-Employee Director of the Company as of the vesting date as follows: one-twelfth of the total Shares subject to the NSO
(rounded to nearest whole number) on each monthly anniversary of the date of grant.

 

(iv)         All
NSOs granted to Non-Employee Directors under this Section 4(c) shall become exercisable in full in the event of Change in Control
with respect to the Company.

 

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(v)          The
Exercise Price under all NSOs granted to a Non-Employee Director under this Section 4(c) shall be equal to one hundred percent
(100%) of the Fair Market Value of a Share on the date of grant, but in no event at the date of exercise less than (a) Euro 3.02
per Share if the NSO is granted before April 30, 2010, (b) Euro 1.94 per Share if the NSO is granted before May 9, 2011 (and after
April 30, 2010), or (c) Euro 2.12 per Share if the NSO is granted on or after May 9, 2011.

 

(vi)         All
NSOs granted to a Non-Employee Director under this Section 4(c) shall terminate on the earlier of:

 

(A)         March
26, 2022; or

 

(B)         The
date ninety (90) days after the termination of such Non-Employee Director’s Service for any reason.

 

	SECTION 5.	SHARES SUBJECT TO PLAN.

 

(a)          Basic
Limitation. Subject to the provisions of Section 7(a), the stock issuable under the Plan shall
be authorized but unissued Shares or treasury Shares (the latter, within the limits set forth under Italian law). The aggregate
number of Shares reserved for Awards under the Plan shall not exceed 3,200,000 Shares.

 

(b)          Additional
Shares. If Awards are forfeited or terminate for any other reason before being exercised, then
the Shares underlying such Awards shall again become available for Awards under the Plan.

 

	SECTION 6.	TERMS AND CONDITIONS OF OPTIONS.

 

(a)          Stock
Option Agreement. Each Grant of an Option under the Plan shall be evidenced by a Stock Option
Agreement between the Optionee and the Company. Such Option shall be subject to all applicable terms and conditions of the Plan
and may be subject to any other terms and conditions that are not inconsistent with the Plan and that the Committee deems appropriate
for inclusion in a Stock Option Agreement. The provisions of the various Stock Option Agreements entered into under the Plan need
not be identical. A Stock Option Agreement may provide that new Options will be granted automatically to the Optionee when he
or she exercises the prior Options. The Stock Option Agreement shall also specify whether the Option is an ISO or an NSO.

 

(b)          Number
of Shares. Each Stock Option Agreement shall specify the number of Shares that are subject to
the Option and shall provide for the adjustment of such number in accordance with Section 7(a).

 

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(c)          Exercise
Price. An Option’s Exercise Price shall be established by the Board or the Committee and
set forth in a Stock Option Agreement. The Exercise Price of an ISO shall not be less than the higher of (i) 100% of the Fair
Market Value (110% for 10-Percent Shareholders) of a Share on the date of Grant, or (ii) an amount corresponding, as of the date
of exercise, to Euro 3.02 per Share if the ISO is granted before April 30, 2010, or Euro 1.94 per Share if the ISO is granted
before May 9, 2011 (and after April 30, 2010), or Euro 2.12 if the ISO is granted on or after May 9, 2011. The Exercise Price
of an NSO shall not be less than the higher of (i) 100% of the Fair Market Value of a Share on the date of Grant, or (ii) an amount
corresponding, as of the date of exercise, to Euro 3.02 per Share if the NSO is granted before April 30, 2010, or Euro 1.94 per
Share if the NSO is granted before May 9, 2011 (and after April 30, 2010), or Euro 2.12 if the NSO is granted on or after May
9, 2011. All Exercise Prices must be paid in cash in compliance with the relevant Italian law provisions.

 

(d)          Exercisability
and Term. Each Stock Option Agreement shall specify the date when all or any installment of
the Option is to become exercisable. The Stock Option Agreement shall also specify the term of the Option; provided that the term
of an ISO shall in no event end after March 26, 2022. No Option can be
exercised after the expiration date provided in the applicable Stock Option Agreement. A Stock Option Agreement may provide for
accelerated exercisability in the event of the Optionee’s death, Disability or retirement or other events and may provide
for expiration prior to the end of its term in the event of the termination of the Optionee’s Service. A Stock Option Agreement
may permit an Optionee to exercise an Option before it is vested, subject to the Company’s right of repurchase over any
Shares acquired under the unvested portion of the Option (an “early exercise”), which right of repurchase shall (i)
lapse at the same rate the Option would have vested had there been no early exercise and (ii) be exercised by the Company only
within the strict limits and in compliance with the provisions of the Italian Civil Code. In no event shall the Company be required
to issue fractional Shares upon the exercise of an Option.

 

(e)          Modifications
or Assumption of Options. Within the limitations of the Plan, the Board or the Committee may
modify, extend or assume outstanding stock options or may accept the cancellation of outstanding stock options (whether granted
by the Company or by another issuer) in return for the grant of new Options for the same or a different number of Shares and at
the same or a different Exercise Price. The foregoing notwithstanding, no modification of an Option shall, without the consent
of the Optionee, alter or impair his or her rights or obligations under such Option.

 

(f)          Transferability
of Options. Except as otherwise provided in the applicable Stock Option Agreement and then
only to the extent permitted by applicable law, no Option shall be transferable by the Optionee other than by will or by the laws
of descent and distribution. Except as otherwise provided in the applicable Stock Option Agreement, an Option may be exercised
during the lifetime of the Optionee only or by the guardian or legal representative of the Optionee. No Option or interest therein
may be assigned, pledged or hypothecated by the Optionee during his or her lifetime, whether by operation of law or otherwise,
or be made subject to execution, attachment or similar process.

 

(g)          Restrictions
on Transfer. Any Shares issued upon exercise of an Option shall be subject to such rights of
repurchase, rights of first refusal and other transfer restrictions as the Committee may determine. Such restrictions shall apply
in addition to any restrictions that may apply to holders of Shares generally and shall also comply to the extent necessary with
applicable law.

 

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(h)          Incentive
Stock Option $100,000 Limitation. To the extent that the aggregate Fair Market Value (determined
at the time of grant) of the Shares with respect to which ISOs are exercisable for the first time by any Optionee during any calendar
year (under all plans of the Company and its Affiliates) exceeds one hundred thousand dollars ($100,000), the Options or portions
thereof which exceed such limit (according to the order in which they were granted) shall be treated as NSOs.

 

	SECTION 7.	PROTECTION AGAINST DILUTION.

 

(a)          Adjustments.
In the event of a subdivision of the outstanding Shares, a declaration of a dividend payable
in Shares, a declaration of a dividend payable in a form other than Shares in an amount that has a material effect on the price
of Shares, a combination or consolidation of the outstanding Shares (by reclassification or otherwise) into a lesser number of
Shares, a recapitalization, reorganization, merger, liquidation, spin-off or a similar occurrence (all without the receipt of
consideration), the Board or the Committee shall make such adjustments as it, in its reasonable discretion, deems appropriate
in order to prevent the dilution or enlargement of rights hereunder in one or more of:

 

(i)          the
number of Shares subject to automatic Grants under Section 4(c) and the number of Shares available for future Awards under Section
5(a);

 

(ii)         the
number of Shares covered by each outstanding Award; or

 

(iii)        the
Exercise Price under each outstanding Option.

 

(b)          Participant
Rights. Except as provided in this Section 7, a recipient of an Award shall have no rights by
reason of any issue by the Company of stock of any class or securities convertible into stock of any class, any subdivision or
consolidation of shares of stock of any class, the payment of any stock dividend or any other increase or decrease in the number
of shares of stock of any class.

 

	SECTION 8.	EFFECT OF A CORPORATE TRANSACTION.

 

(a)          Merger
or Reorganization. In the event that the Company is a party to a Corporate Transaction, outstanding
Awards shall be subject to the terms and conditions of the agreement memorializing such Corporate Transaction. Such agreement
may provide, without limitation, for the assumption or substitution of outstanding Awards by the surviving corporation or its
parent, for their continuation by the Company (if the Company is a surviving corporation), for accelerated vesting or for their
cancellation with or without consideration.

 

(b)          Acceleration.
The Committee may determine, at the time of granting an Award, or thereafter, that such Award
shall become fully exercisable as to all Shares subject to such Award in the event that a Change in Control occurs with respect
to the Company.

 

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	SECTION 9.	LIMITATIONS ON RIGHTS.

 

(a)          Retention
Rights. Neither the Plan nor any Award granted under the Plan shall be deemed to give any individual
a right to remain an Employee, Consultant or Director of the Company. The Company reserves the right to terminate the Service
of any person at any time, and for any reason, subject to applicable laws, the Company’s Certificate of
Incorporation and Bylaws and a written employment agreement (if any).

 

(b)          Shareholders’
Rights. A Participant shall have no dividend rights, voting rights or other rights as a stockholder
with respect to any Shares covered by his or her Award prior to the issuance of a stock certificate, or similar means of representations
of the Shares, for such Shares. No adjustment shall be made for cash dividends or other rights for which the record date is prior
to the date when such certificate is issued, except as expressly provided in Section 7.

 

(c)          Regulatory
Requirements. Any other provision of the Plan notwithstanding, the obligation of the Company
to issue Shares under the Plan shall be subject to all applicable laws, rules and regulations and such approval by any regulatory
body as may be required. The Company reserves the right to restrict, in whole or in part, the delivery of Shares pursuant to any
Award prior to the satisfaction of all legal requirements relating to the issuance of such Shares, to their registration, qualification
or listing or to an exemption from registration, qualification or listing.

 

	SECTION 10.	WITHHOLDING TAXES.

 

(a)          Withholding
Obligations. The Company will be entitled to make any applicable withholding or deduction on
account of any taxes or social security contributions due on benefits derived from the Plan pursuant to applicable law. A Participant
shall make arrangements satisfactory to the Company for the satisfaction of such tax or social security obligations that arise
in connection with his or her Award. The Company shall not be required to issue any Shares or make any cash payment under the
Plan until such obligations are fully satisfied.

 

	SECTION 11.	DURATION AND AMENDMENTS.

 

(a)          Term
of the Plan. The Plan shall terminate on March 26, 2022 or on any earlier date pursuant to Section
11(b) of the Plan.

 

(b)          Right
to Amend, Suspend or Terminate the Plan. The Board may amend, suspend or terminate the Plan
at any time and for any reason. The suspension or termination of the Plan, or any amendment thereof, shall not affect any Award
previously granted under the Plan. No Awards shall be granted under the Plan after the Plan’s suspension or termination.
An amendment of the Plan shall be subject to the approval of the Company’s shareholders only to the extent required by applicable
laws, regulations or rules.

 

(c)          Right
to Amend Award. The Board at any time, and from time to time, may amend the terms of any one
or more Awards; provided, however, that the rights under any Award shall not be impaired by any such amendment unless (i) the
Company requests the consent of the Participant and (ii) the Participant consents in writing.

 

    	11

    	 

    

 

	SECTION 12.	EXECUTION.

 

To record the adoption
of the Plan by the Board, the Company has caused its duly authorized officer to execute this Plan on behalf of the Company.

 

	 	Gentium S.p.A.
	 	 
	 	 
	 	Khalid Islam
	 	Chief Executive Officer

 

    	12Exhibit 4.21

 

Lease agreement for real property not
for use as dwelling

 

(the “Agreement”)

 

between

 

FinSirton S.p.A. with a company capital
of 479,928.00 euro and registered office in Villa Guardia, Piazza XX Settembre n. 2, companies' register, VAT number and tax identification
number 02827580131; represented here by its accountant Angelo Aredi Butti, born in Como on 5/10/1967, domiciled for this office
at the company, who declares that is acting here as Sole Director, being vested with all necessary powers (and hereinafter referred
to as the “Lessor”);

 

- on the one hand -

and

 

Gentium S.p.A. with a company capital of
14,969,150 euro and registered office in Villa Guardia, Piazza XX Settembre n. 2, companies' register, VAT number and tax identification
number 02098100130; represented here by Dr. Khalid Islam born in London on 08/11/1955, domiciled for this office at the company,
who declares that is acting here as Legal Representative of the company, being vested with all necessary powers as conferred to
him at the Board of Directors' meeting of 9th May 2011 (and hereinafter referred to as the “Lessee”);

 

- on the other hand -

 

(hereinafter referred individually also,
in the singular, as the “Party”, and together as the “Parties”)

 

Recitals

 

		(A)	the Lessor is the owner and may fully dispose of a building complex located in Villa Guardia (CO),
Piazza XX Settembre n. 2, Sezione Civello, registered in the town land registry at sheet 5 number 1089, sub plot 702 with cadastral
rentable value of 96,230 euro, of which some parcels - described and identified in green in the annexes “A” to this
Agreement (hereinafter referred to as, the “Leased Unit”) form the subject matter of this lease agreement;

 

		(B)	on 1 January 2005 the Parties signed a lease agreement regarding certain areas of the real property
complex, for which notice of cancellation has been given in accordance with the law and with the agreement;

 

		(C)	on 1 January 2007 the Parties signed another lease agreement, subsequently amended by the supplementary
instrument of 1 July 2009, regarding further parcels of the building complex included in the Leased Units (jointly with the previously
mentioned lease agreement annex (B), the “Previous Leases”);

 

		(D)	during the currency of the Previous Leases, the “Lessee carried out some works, with the
prior consent of the Lessor and in accordance with articles 1592 and 1593 of the civil code, (i.e. electrical plant, smoke
detectors, air conditioning/heating, doors, sanitary fixtures, flooring and awnings) that concerned the first and second floors
of building L of the building complex (the “Works Carried out”);

 

		(E)	on the basis of the agreements made between the Parties, what was due to the Lessee for the Works
Carried out, which was agreed as being 320,000 (three hundred and twenty thousand) euro, of which 140,000 (one hundred and forty
thousand) euro have already been paid by the setting off of rental due from Gentium for calendar year 2011, and, as regards the
balance of 180,000 (one hundred and eighty thousand) euro, shall be taken into account when calculating the rental as established
in 6.1 and therefore will no longer be due on the signing of this instrument;

 

		(F)	in the light of all the above, the Parties intend to stipulate a new lease agreement running from
1/1/2012 regarding the Leased Units after the termination of the lease Agreement of 1 January 2007, as subsequently amended;

 

     

     

    

Exhibit 4.21

 

 

Given all of the above, the Parties agree
as follows:

 

		1.	Recitals and annexes

 

		1.1	The recitals and the annexes to the Agreement form an integral and substantial part of the same.

 

		2.	Subject matter of the agreement

 

		2.1	The Parties agree to terminate the lease agreement of 1 January 2007, as amended with addendum
of 1 July 2009, with no payments due to or from the other Party, with the aforesaid lease therefore deemed ended and of no effect
between the parties as from 31 December 2011.

 

		2.2	With this Agreement, the Lessor grants a lease to the Lessee, who accepts, for the Leased Units,
in the condition of fact and of law as found at the date of the signing of this Agreement (hereinafter referred to as, the “
Starting Date”).

 

		3.	Use

 

		3.1	The Parties agree that for the whole duration of this Agreement, the Leased Units shall be used
as commercial premises, offices, laboratories and depots, without such activities involving direct contact with the public. The
Lessee may consequently not, without giving good reason, use the Leased Units for any other purposes without the prior written
consent of with Lessor, which may not however be unreasonably withheld. Any refusal by the Lessor must be made with suitable stated
reasons.

 

		4.	The State of the Leased Units

 

		4.1	The Lessee declares he is fully aware and of and accepts the present state of fact and of law of
the Leased Units.

 

		4.2	The Lessee furthermore acknowledges that the conditions of fact and of law of the Leased Units
satisfy the use requirements as provided for in article 3.

 

		5.	Term

 

		5.1	The duration of this Agreement is agreed as being for 6 (six) years, running from 1 January 2012
and ending on 31 December 2017 (hereinafter referred to as the “First Expiry Date”).

 

		5.2	On the First Expiry Date, this Agreement will be automatically renewed at the same terms and conditions,
save that agreed in 6.3 of this Agreement for a further period of 6 (six) years and save the withdrawal of the Lessee notified
to the Lessor by registered letter sent with at least 12 (twelve) months’ notice before First Expiry Date.

 

		5.3	The Lessor waives as of now any right to refuse the first renewal of this Agreement for the reasons
given in article 29 of law n. 392 of 27 July 1978.

 

		5.4	At the end of the first renewal period of 6 (six) years, this Agreement will be automatically renewed
at the same terms and conditions, for a further period of six years and hence as follows; such renewals will not take place if
the Lessor or if the Lessee gives notice to the other Party of his desire to cancel the Agreement by registered letter sent with
notice of at least 12 (twelve) months before the corresponding expiry date.

 

		5.5	In accordance with and pursuant to article 27, paragraph VII) 5, of law n. 392 of 27 July 1978,
the Lessor grants to the Lessee the right to withdraw at any time from this Agreement on giving notice to the aforesaid Lessor
by means of registered letter, at least 12 (twelve) months before the date the withdrawal will be executed.

 

     

     

    

Exhibit 4.21

 

		6.	Rental rates

 

		6.1	By virtue of the agreements made and in the light of what is referred to in recitals C, D and E
of this Agreement, the Parties agree that for the first six years the annual rental shall be 185,000.00 euro plus VAT.

 

		6.2	Running from the start of the second year of the term of the lease and for each year subsequent,
at the specific request of the Lessor the rental shall be updated annually by 75% of the percentage change in the consumer price
index for working families and employees as ascertained by ISTAT (national statistics office) (and hereinafter referred to as the
“ISTAT index)”) in the previous year as published in the Official Journal of Italy.

 

		6.3	From the 7th (seventh) year of the duration of the Agreement, the annual rental due from the Lessee
shall be 215,000.00 euro plus VAT.

 

		6.4	The Rental shall be paid in quarterly prepaid amounts as above by the 15th day of the months of
January, April, July and October of each year (hereinafter referred to as, individually the “Instalment” and
together as the “Instalments”), by means of bank transfer on the current account that will be indicated in the
invoice.

 

		7.	Secondary Charges

 

		7.1	From the Starting Date, the Lessee will sustain and pay directly the expenses, the costs, the costs
and/or charges of any kind, in any way regarding to or connected with the Leased Units and their use (hereinafter referred to as,
the “Secondary Charges), with the exception of that which is provided for in article 7.3 below.

 

		7.2	By way only of example, included among the Secondary Charges are the costs, expenses and charges
connected with the telephone, water supply, electricity and gas, heating and air conditioning, local waste disposal charges and
similar charges (hereinafter referred to as, the “Utilities”), leaving aside the Party to in whose name the
Utilities are made. If the Utilities are in the name of the Lessor, this latter shall pay these and shall have the right tot receive
from the Lessee a corresponding reimbursement, on providing suitable supporting documents.

 

		7.3	The parties agree that the condominium co-owners' ordinary expenses regarding the maintenance of
lifts, extinguishers, green areas and snow clearance will be shared as follows: lifts and hoists by the lessor, extinguishers by
the lessor, except for in the porter's lodge, for which the lessor shall be responsible, with the green areas and snow clearance
lessor being borne one third part by the lessee.

 

		7.4	The Lessee shall insure the Leased Units against fire as well as damage suffered at the hands of
customers, up to a suitable upper limit, including also damages to neighbours.

 

		8.	Maintenance of the Leased Units - Modifications, Additions and Improvements

 

		8.1	The Lessee declares he has examined the premises and all the plant and systems and that he has
found them to be in a state of maintenance in accordance with article 1575 of the Italian civil code.

 

		8.2	Repairs that are part of ordinary maintenance of the Leased Units, and any other regarding all
plant of exclusive appurtenance to the Leased Units shall be borne by the Lessee pursuant to articles 1576 and 1609 of the civil
code.

 

		8.3	The Lessee must ask the consent of the lessor to perform works of extraordinary maintenance and
restoration that he deems useful and necessary for the carrying out of his business after obtaining the prior authorisation of
the competent authorities, for whose authorisation he undertakes to bear all relative costs, none excluded, with no possibility
of acting for restitution or the indemnities under article 1592 c.c. The Lessee undertakes to give copies of the technical documents
illustrating the various proposed works before these are submitted to the local authorities. Without prejudice to the above, the
Parties agree that the lessor will bear the costs of extraordinary maintenance regarding the structure of the Leased Units.

 

     

     

    

Exhibit 4.21

 

		9.	Access

 

		9.1	On the written request of the Lessor, the Lessee will permit the Lessor and/or person authorised
by the Lessor to have access, during normal office hours, to the Leased Units, to examine their condition; to identify any necessary
repair works; to carry out the inventory of plant and of appurtenances and (ii) carried out any works and/or intervention, in the
event of breach of contract by the Lessee in accordance with the provisions of this Agreement.

 

		10.	Assignment of the Agreement – Sub-letting

 

		10.1	Save the provisions of article 36 of Law number 392 of 27 July 1978, the “Lessee undertakes
not to assign, wholly or in part, this Agreement to third parties without the prior consent of the Lessor.

 

		10.2	The Lessor expressly authorises the “Lessee to sublet the Leased Units to third parties.

 

		11.	Choice of service address – Correspondence

 

		11.1	All correspondence required or permitted under the terms of this Agreement must be in writing and
may be:

 

		11.1.1	delivered personally to the Party concerned;

 

		11.1.2	sent by registered or insured letter with advice of receipt, and sent to the Party concerned at
the address specified here below;

 

		11.1.3	sent by telex or fax with advice of receipt.

 

Correspondence
sent as provided for above shall be deemed validly carried out only when received by the addressee. To this end, the addresses
of the Parties shall be the following, save where changed as provided for in article 11.2 below:

 

For the Lessor:

FinSirton
S.p.A.

To the attention
of its pro tempore legal representative

Piazza XX
Settembre n. 2

Telephone:
031 385 999

Fax: 031
385 333

E-mail: finsirton@finsirton.it

 

For the Lessee:

Gentium S.p.A.

To the attention
of its pro tempore legal representative

Piazza XX
Settembre n. 2

Telephone:
031 385 111

Fax: 031
385 426

E-mail: gentium@gentium.it

 

		11.2	The Parties may from time to time and at any time indicate a different address, informing the other
Party in writing with notice of at least 15 (fifteen) working days.

 

12.Mediation
provisions and competent court

 

		12.1	Any dispute arising from this Agreement or in some way connected to it – including disputes
regarding its interpretation, its validity, its execution and its termination – for which an attempt at mediation is a mandatory
requirement under the provisions of article 5 of legislative decree D.Lgs. 28/2010 or other current and applicable provision, shall
preliminarily be submitted to intermediation in accordance with the procedures provided for in law, before the Arbitration Chamber
of Como at the Chamber of Commerce of Como, mediation department.

 

     

     

    

Exhibit 4.21

 

		12.2	If the dispute cannot be resolved by mediation, or if the attempt at mediation is not mandatory,
the Parties agree that the dispute shall be put to the exclusive and inderogable jurisdiction of the Court of Como.

 

		13.	GENERAL PROVISIONS

 

		13.1	Any article, paragraph, sub-section or other provision of this Agreement that is or that becomes
illegal, null or void, (i) shall in no way prejudice the effectiveness of the other provisions of this Agreement and (ii) shall
be replaced by provisions that reflect the actual intentions of the Parties. In the event of the total or partial nullity of any
of the clauses of this Agreement, the Parties agree to negotiate in good faith new fully valid clauses to replace these where the
new clauses have substantially the same effect, having regard to the aims and the subject matter of this Agreement.

 

		13.2	Any change to this Agreement and/or its Annexes shall be valid and binding only where made in writing
and signed by the Party who is required to abide by it.

 

		13.3	Any tolerance, of a Party, of conduct by the other Party or by a third party, that is in infringement
of the provisions of this Agreement does not amount to waiver of any rights arising under the breached provisions, nor to the right
to require exact performance of all the terms and conditions provided for herein.

 

		13.4	The personal data supplied by each Party to the other Party are protected by legislative decree
number 196 of 30 June 2003, which inter alia protects all persons with respect to the use of their personal details and, therefore,
such data shall be used exclusively for the purposes of performing the Agreement.

 

		13.5	The parties mutually authorise each other to provide notifications required by the law, including
those that have to be submitted to the competent governmental authorities.

 

		13.6	Each Party undertakes to sign, to accept, to deliver, to file, to registered and to publish any
other instrument or document, and to carry out any other action, that may be required by the law or that is rendered necessary
or advisable for the purpose of realising as quickly as possible the aims and intent of this Agreement.

 

		13.7	This Agreement, as well as the rights and duties of the Parties deriving from it, are governed
by Italian law.

 

		13.8	The expenses associated with this Agreement, of the corresponding receipts and releases, the duty
stamps and secondary charges, shall be born in equal parts by the Lessor and the Lessee.

 

		13.9	The registration of the Agreement shall be carried out by the Lessor, within the term of 30 days
from the date of signing of the Agreement, and the corresponding expense shall be borne by the parties in equal parts, i.e. 50%
each.

 

		13.10	The Lessor is in possession of the energy certification filed with the land energy registry at
number 13245-000011/12 on 17/01/2012.

 

		14.	List of Annexes

 

Annex A: Floor plan
of the Leased Units

 

     

     

    

Exhibit 4.21

 

 

Villa Guardia, 18
January 2012

 

 

 

Lessor

 

 

 

 

 

Lessee

 

 

 

 

 

In accordance with and pursuant
to Articles 1341 and 1342 of the civil code the parties hereby declare their specific approval of the following clauses:

3. the
use of the real property and the business conducted therein;

4. the
state of the Leased Units

5. automatic
renewal of the first expiry date;

8. maintenance
of the Leased Units, modifications, additions and improvements;

10. assignment
of the Agreement - Sub-letting;

12. mediation
and competent court

13. replacement
of clauses, good faith, amendments in writing, tolerance of breaches.

 

 

Read, confirmed and
signed.

 

 

Villa Guardia, 18
January 2012

 

Lessor

 

 

 

 

 

 

 

Lessee

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