Document:

Exhibit 4.2

 

EXECUTION VERSION

 

FIRST Supplemental
Indenture

 

between

 

PROTALIX
BIOTHERAPEUTICS, INC., as Issuer,

AND
EACH OF THE GUARANTORS PARTY HERETO,

 

and

 

The
Bank of New York Mellon Trust CoMPANY, N.A., as Trustee,

 

and

 

wilmington
savings fund society, fsb, as Collateral Agent

 

Dated as of July 24, 2017

to the Indenture, dated as of December 7,
2016,

relating to 7.50% Senior Secured Convertible Notes due
2021

  

     

     

    

 

FIRST Supplemental
Indenture

 

FIRST SUPPLEMENTAL INDENTURE, dated as of
July 24, 2017 (this “First Supplemental Indenture”), between PROTALIX BIOTHERAPEUTICS, INC., a Delaware corporation
(the “Company”), as issuer, the Guarantors party hereto, and The Bank of New York Mellon Trust Company, N.A.,
as Trustee, registrar, paying agent and conversion agent, and Wilmington Savings Fund Society, FSB, as the Collateral Agent, under
an Indenture, dated as of December 7, 2016, by and among the Company, each of the guarantors party thereto, Wilmington Savings
Fund Society, FSB, as collateral agent, and the Trustee (the “Base Indenture”). All capitalized terms used in
this First Supplemental Indenture and not otherwise defined herein have the meanings given to the terms in the Base Indenture.

 

WHEREAS, on December 7, 2016, the Company
duly authorized the creation of an issue of $62,686,000 aggregate principal amount of the Company’s 7.50% Senior Secured
Convertible Notes due 2021 (the “Notes”) pursuant to the Base Indenture;

 

WHEREAS, the Company wishes to issue Additional
Notes in the aggregate principal amount of $10,000,000, and for that purpose, to enter into this First Supplemental Indenture to
the Base Indenture, the form and substance of such Notes and the terms, provisions and conditions thereof, to be set forth as provided
in the Base Indenture and this First Supplemental Indenture;

 

WHEREAS, Sections 2.01, 9.01, 9.03, 9.04
and 9.05 of the Base Indenture provide that the Company may enter into this Supplemental Indenture to issue the Additional Notes
as permitted by Section 2.01(b) therein;

 

WHEREAS, the Additional Notes will have
the same terms and conditions and form the same series as the Notes, except as set forth herein and except that the Additional
Notes will have a separate CUSIP, and therefore will not be fungible with the Notes, pursuant to Section 2.01 of the Base Indenture;

 

WHEREAS, the Security Documents will inure
to the benefit of the holder of the Additional Notes;

 

WHEREAS, the Trustee is authorized to execute
and deliver this First Supplemental Indenture;

 

WHEREAS, the Company has requested and hereby
requests that the Trustee join with the Company in the execution and delivery of this First Supplemental Indenture and the Company
has provided the Trustee with a Board Resolution authorizing the execution of and approving this First Supplemental Indenture;
and

 

WHEREAS, all requirements necessary to make
this First Supplemental Indenture a valid instrument in accordance with its terms and to make the Additional Notes, when executed
by the Company and authenticated and delivered by the Trustee, the valid obligations of the Company, have been performed, and the
execution and delivery of this First Supplemental Indenture have been duly authorized in all respects.

 

     

     

    

 

NOW, THEREFORE, in consideration of the
foregoing and for other good and valuable consideration, the receipt of which is hereby acknowledged, the Company and the Trustee
mutually covenant and agree for the benefit of holders of the Additional Notes as follows:

 

SECTION 1.1           Designation
and Principal Amount.

 

The Additional Notes issued hereby are:
(i) 7.50% Secured Convertible Senior Notes due 2021 having the same terms and attributes provided for in the Base Indenture except
as set forth in Section 1.2 herein; and (ii) limited in aggregate principal amount to no more than $10,000,000, which amount shall
be as set forth in one or more written orders of the Company for the authentication and delivery of the Notes pursuant to Section 2.05
of the Base Indenture.

 

SECTION 1.2           Form
of Additional Notes

 

The Additional Notes and
the Trustee’s certificate of authentication to be endorsed thereon shall be substantially in the form of Exhibit A to the
Base Indenture. The terms and provisions contained in the form of Additional Notes shall constitute, and are hereby expressly made,
a part of the Indenture as supplemented by this First Supplemental Indenture.

 

SECTION 1.3           Issuance
of Notes to Constitute Same Series.

 

The Additional Notes issued hereunder shall,
in accordance with Section 2.01(b) of the Base Indenture, constitute and be deemed to be the same series as the Notes and have
the same terms and conditions in all respects as the Notes, except (a) the Issue Date (which shall be July 25, 2017), (b) the Last
Original Issue Date (which shall be July 25, 2017); (c) the issue price and (d) a separate CUSIP 74365A AH4.

 

SECTION 1.4           Ratification
of Indenture.

 

(a)          The
Base Indenture, as supplemented by this First Supplemental Indenture, is in all respects ratified and confirmed, and this First
Supplemental Indenture shall be deemed part of the Base Indenture in the manner and to the extent herein and therein provided.

 

(b)          Each
party hereto hereby acknowledges and agrees that before and after giving effect to this First Supplemental Indenture all terms,
conditions, provisions and covenants in the Security Documents shall remain unaltered and in full force and effect, except as expressly
modified or waived hereby. Each party hereto hereby confirms and agrees that to the extent any Security Document purports to grant,
assign or pledge to the Collateral Agent or any other Person a security interest or Lien on any Collateral as security for the
obligations secured by the Security Documents, such grant, assignment or pledge is hereby ratified and confirmed in all respects.
Each party hereto hereby confirms and agrees that the obligations secured by any Security Documents (i) shall include the obligations
incurred in connection with the issuance of the Additional Notes, (ii) shall continue in full force and effect and (iii) are hereby
ratified and confirmed in all respects.

 

     

     

    

 

SECTION 1.5           Governing
Law.

 

This First Supplemental Indenture and each
Note shall be deemed to be a contract made under the internal laws of the State of New York, and for all purposes shall be construed
in accordance with laws of said State.

 

SECTION 1.6           Separability.

 

In case any one or more of the provisions
contained in this First Supplemental Indenture or in the Notes shall for any reason be held invalid, illegal or unenforceable in
any respect, such invalidity, illegality or unenforceability shall not affect any other provisions of this First Supplemental Indenture
or of the Notes, but this First Supplemental Indenture and the Notes shall be construed as if such invalid or illegal or unenforceable
provision had never been contained herein or therein.

 

SECTION 1.7           Counterparts.

 

This First Supplemental Indenture may be
executed in any number of counterparts each of which shall be an original; but such counterparts shall together constitute but
one and the same instrument. The exchange of copies of this Indenture and of signature pages by facsimile or PDF transmission shall
constitute effective execution and delivery of this Indenture as to the parties hereto and may be used in lieu of the original
Indenture for all purposes. Signatures of the parties hereto transmitted by facsimile or PDF shall be deemed to be their original
signatures for all purposes.

 

SECTION 1.8           Effect
of Headings. The Section headings in this First Supplemental Indenture are for convenience only and shall not affect the construction
hereof.

 

SECTION 1.9           Responsibility
for Recitals, Etc. The recitals and statements in this First Supplemental Indenture and in the Additional Notes (except in
the Trustee's certificate of authentication) shall be taken as the statements of the Company, and the Trustee assumes no responsibility
for the correctness thereof. The Trustee makes no representations as to the validity, adequacy or sufficiency of this First Supplemental
Indenture or of the Additional Notes. The Trustee shall not be accountable for the use or application by the Company of the Additional
Notes or of the proceeds thereof.

 

SECTION 1.10         TIA
Controls. If any provision of this First Supplemental Indenture limits, qualifies or conflicts with another provision which
is required to be included in this First Supplemental Indenture by the TIA, the provision required by the TIA shall control.

 

[Signature Page Follows]

 

     

     

    

 

IN WITNESS WHEREOF, the parties hereto have
caused this First Supplemental Indenture to be duly executed by their authorized respective officers as of the day and year first
above written.

 

	 	PROTALIX BIOTHERAPEUTICS, INC., as Issuer
	 	 	 
	 	By:	/s/ Moshe Manor
	 	 	Name:   Moshe Manor
	 	 	Title: President and Chief Executive Officer
	 	 	 
	 	THE BANK OF NEW YORK MELLON TRUST COMPANY, N.A., as Trustee
	 	 	 
	 	By:	/s/ Leslie Lockhart
	 	 	Name:  Leslie Lockhart
	 	 	Title:   Vice President

 

	PROTALIX LTD., as Guarantor	 
	 	 	 
	By:	/s/ Moshe Manor	 
	 	Name:   Moshe Manor	 
	 	Title: President and Chief Executive Officer	 
	 	 	 
	PROTALIX B.V., as Guarantor	 
	 	 	 
	By:	/s/ Moshe Manor	 
	 	Name:   Moshe Manor	 
	 	Title: Managing Director	 

 

     

     

    

 

IN WITNESS WHEREOF, the undersigned, being
duly authorized, has executed this Indenture as of the day and year first before written.

 

Wilmington Savings Fund Society, FSB, as Collateral Agent

 

	By: 	/s/ Geoffrey J. Lewis	 
	Name: Geoffrey J. Lewis	 
	Title: Vice PresidentExhibit 4.4

 

FORM OF FACE OF NOTE

 

THIS SECURITY IS A GLOBAL NOTE WITHIN THE MEANING OF THE
INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE
EXCHANGED IN WHOLE OR IN PART FOR A SECURITY REGISTERED, AND NO TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED,
IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE
INDENTURE.

 

THIS NOTE WILL BE ISSUED WITH ORIGINAL ISSUE DISCOUNT.
TO OBTAIN THE “ISSUE PRICE”, “ISSUE DATE”, “YIELD TO MATURITY”, “COMPARABLE YIELD”
AND “PROJECTED PAYMENT” SCHEDULE FOR THE NOTES REQUIRED PURSUANT TO SECTION 1.1275-3(B) OF THE TREASURY REGULATIONS,
CONTACT THE SENIOR DIRECTOR, FINANCE OF PROTALIX BIOTHERAPEUTICS, INC. AT THE ADDRESS SET FORTH IN SECTION 12.08 OF THE INDENTURE.

 

 

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Protalix BioTherapeutics, Inc.

 

4.50% Convertible Senior Notes due 2022

 

No.: 1

 

CUSIP: 74365AAG6

 

Principal

		Amount:	$8.55 million as revised by the Schedule of Increases and Decreases in the Global Note attached hereto

 

Protalix BioTherapeutics, Inc., a Delaware corporation (the
“Company”), promises to pay to Cede & Co. or registered assigns the principal amount of eight million five
hundred and fifty five thousand dollars as revised by the Schedule of Increases and Decreases in the Global Note attached hereto,
on February 15, 2022 (the “Maturity Date”).

 

Interest Payment Dates: February 15 and August 15.

Regular Record Dates: February 1 and August 1.

Additional provisions of this Security are set forth on the
other side of this Note.

 

 

IN WITNESS WHEREOF, Protalix BioTherapeutics, Inc. has caused
this instrument to be signed manually or by facsimile by one of its duly authorized Officers.

 

	 	Protalix BioTherapeutics, Inc.
	 	By:	/s/ Yossi Maimon
	 	Name: Yossi Maimon
	 	Title: Chief Financial Officer

 

This is one of the Notes referred to in the within-mentioned
Indenture.

Dated:

 

	 	The Bank of New York Mellon Trust Company, N.A., as Trustee
	 	By:	/s/ Leslie Lockhart
	 	 	Authorized Signatory

 

 

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FORM OF REVERSE OF NOTE

 

Protalix BioTherapeutics, Inc.

 

4.50% Convertible Senior Notes due 2022

 

This Note is one of a duly authorized issue of securities of
the Company (herein called the “Notes”) issued under the Indenture dated as of July 25, 2017, between the Company
and the Bank of New York Mellon Trust Company, N.A., herein called the “Trustee,” and reference is hereby made
to the Indenture for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company,
the Trustee and the Holders of the Notes and of the terms upon which the Notes are, and are to be, authenticated and delivered.

 

This Note does not benefit from a sinking fund. This Note shall
be redeemable at the Company’s option in accordance with Section 10 of the Indenture. If the Daily VWAP, for at least 20
Trading Days (whether or not consecutive) during the period of 30 consecutive Trading Days ending on, and including, the Trading
Day immediately preceding the date of the Redemption Notice, equals or exceeds the Trigger Price as specified in Section 10.01(a)
of the Indenture, the Company may redeem for cash all or portions of the Notes at a Redemption Price specified in Section 10.02
of the Indenture, subject to Article X of the Indenture.

 

As provided in and subject to the provisions of the Indenture,
upon the occurrence of a Fundamental Change, the Holder of this Note will have the right, at such Holder’s option, to require
the Company to purchase this Note, or any portion of this Note such that the principal amount of this Note that is not purchased
equals $1,000 or an integral multiple of $1,000, on the Fundamental Change Purchase Date at a price equal to the Fundamental Change
Purchase Price for such Fundamental Change Purchase Date.

 

As provided in and subject to the provisions of the Indenture,
the Holder hereof has the right, at any time prior to the Close of Business on the Business Day immediately preceding the Maturity
Date, to convert this Note or a portion of this Note, such that the principal amount of this Note converted equals $1,000 or an
integral multiple of $1,000, into a number of shares of Common Stock, or cash or a combination thereof, as applicable, determined
in accordance with Article IV of the Indenture and subject to adjustment as set forth therein.

 

As provided in and subject to the provisions of the Indenture,
the Company will make all payments in respect of the Fundamental Change Purchase Price for, the Redemption Price for and the principal
amount of this Note to the Holder that surrenders this Note to the Paying Agent to collect such payments in respect of this Note.
The Company will pay cash amounts in money of the United States that at the time of payment is legal tender for payment of public
and private debts. The Indenture permits, with certain exceptions as therein provided, the amendment thereof and the modification
of the rights and obligations of the Company and the rights of the Holders of the Notes to be effected under the Indenture at any
time by the Company and the Trustee with the consent of the Holders of a majority in principal amount of the Notes at the time
Outstanding.

 

    	 	3	 

     

    

 

The Indenture also contains provisions permitting the Holders
of specified percentages in principal amount of the Notes at the time Outstanding, on behalf of the Holders of all Notes, to waive
compliance by the Company with certain provisions of the Indenture and certain past Defaults under the Indenture and their consequences.
Any such consent or waiver by the Holder of this Note shall be conclusive and binding upon such Holder and upon all future Holders
of this Note and of any Note issued upon the registration of transfer hereof or in exchange herefor or in lieu hereof, whether
or not notation of such consent or waiver is made upon this Note.

As provided in and subject to the provisions of the Indenture,
the Holder of this Note shall not have the right to institute any proceeding with respect to the Indenture, or for the appointment
of a receiver or trustee, or for any other remedy thereunder, unless such Holder shall have previously given the Trustee written
notice of a continuing Event of Default with respect to the Note, the Holders of not less than 25% in principal amount of the Notes
at the time Outstanding shall have made written request to the Trustee to institute proceedings in respect of such Event of Default
as Trustee and offered the Trustee indemnity or security reasonably satisfactory to it, and the Trustee shall have failed to institute
any such proceeding, for 60 days after receipt of such notice, request and offer of indemnity or security, and it shall not have
received from the Holders of a majority in principal amount of Notes at the time Outstanding a direction inconsistent with such
request.

 

The foregoing shall not apply to any suit instituted by the
Holder of this Note for the enforcement of any payment of the principal hereof, premium, if any, or interest hereon, the Fundamental
Change Purchase Price or the Redemption Price with respect to the amount of cash, the number of shares of Common Stock or the combination
thereof, as the case may be, due upon conversion of this Note or after the respective due dates expressed in the Indenture.

 

No reference herein to the Indenture, and no provision of this
Note or of the Indenture, shall alter or impair the obligation of the Company, which is absolute and unconditional, to pay or deliver,
as the case may be, the principal of (including the Fundamental Change Purchase Price and the Redemption Price), premium, interest
on, the amount of cash, a number of shares of Common Stock or a combination of cash and shares of Common Stock, if any, as the
case may be, due upon conversion of, this Note at the time, place and rate, and in the coin and currency, herein prescribed.

 

As provided in the Indenture and subject to certain limitations
therein set forth, the transfer of this Note is registrable in the Register, upon surrender of this Note for registration of transfer
to the Trustee, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the
Registrar duly executed by, the Holder hereof or its attorney duly authorized in writing, and thereupon a new Note of this series
and of like tenor for the same aggregate principal amount will be issued to the designated transferee.

 

The Notes are issuable only in registered form without coupons
in denominations of $1,000 and integral multiples of $1,000. As provided in the Indenture and subject to certain limitations therein
set forth, the Notes are exchangeable for a like aggregate principal amount of Notes and of like tenor of a different authorized
denomination, as requested by the Holder surrendering the same.

 

    	 	4	 

     

    

 

Subject to the rights of the Holders as of the Regular Record
Date to receive interest on the related Interest Payment Date, prior to due presentment of this Note for registration of transfer,
the Company, the Trustee, the Agents and any of their respective agents may treat the Person in whose name the Note is registered
as the owner hereof for all purposes, whether or not this Note be overdue, and neither the Company, the Trustee, the Agents nor
any agents shall be affected by notice to the contrary.

 

Customary abbreviations may be used in the name of a Holder
or an assignee, such as TEN COM (= tenants in common), TEN ENT (= tenants by the entirety), JT TEN (= joint tenants with rights
of survivorship and not as tenants in common), CUST (= custodian) and U/G/M/A (= Uniform Gift to Minors Act).

 

Upon the issuance of any new Note, the Company may require payment
by the Holder of a sum sufficient to cover any tax or other governmental charge that may be imposed in relation thereto and any
other expenses (including fees and expenses of the Trustee) connected therewith.

All defined terms used in this Note that are defined in the
Indenture shall have the meanings assigned to them in the Indenture. If any provision of this Note limits, qualifies or conflicts
with a provision of the Indenture, such provision of the Indenture shall control.

 

    	 	5	 

     

    

 

[FORM OF NOTICE OF CONVERSION]

 

To: Protalix BioTherapeutics, Inc.

 

The undersigned owner of this Note hereby irrevocably exercises
the option to convert this Note, or a portion hereof (which is such that the principal amount of the portion of this Note that
will not be converted equals $1,000 or an integral multiple of $1,000 in excess thereof) below designated, into a number of shares
of Common Stock or cash or a combination thereof, as applicable, in accordance with the terms of the Indenture referred to in this
Note, and it directs that any cash payable and any shares of Common Stock issuable and deliverable upon conversion, together with
any Notes representing any unconverted principal amount hereof, be paid and/or issued and/or delivered, as the case may be, to
the registered Holder hereof unless a different name is indicated below.

 

If any shares of Common Stock are to be issued in the name of
a Person other than the undersigned, the undersigned will pay all transfer taxes payable with respect to such issuance and transfer
as set forth in the Indenture.

 

Principal amount to be converted (if less than all):

 

$_______

 

Dated: ________

 

	 	 
	 	Signature(s)
	 	(Sign exactly as your name appears on the other side of this Note)
	 	Signature Guarantee
	 	(Signature(s) must be guaranteed by an institution that is a member of one of the following recognized signature Guarantee Programs:
	 	(i) The Securities Transfer Agent Medallion Program (STAMP); (ii) The New York Stock Exchange Medallion Program (MNSP); and (iii) another guarantee program acceptable to the Trustee.)

 

    	 	6	 

     

    

 

Fill in if a check is to be issued, or shares of Common Stock
or Notes are to be registered, otherwise than to or in the name of the registered Holder.

 

	(Name)	 
	 	 
	(Address)	 
	 	 
	Please print name and address	 
	(including zip code)	 
	 	 
	(Social Security or other Taxpayer	 
	Identifying Number)	 
	 	 
	Dated: ________	 

 

 

	 	Signature(s)
	 	(Sign exactly as such Person’s name appears above)
	 	 
	 	Signature Guarantee
	 	(Signature(s) must be guaranteed by an institution which is a member of one of the following recognized signature Guarantee Programs:
	 	(i) The Securities Transfer Agent Medallion Program (STAMP); (ii) The New York Stock Exchange Medallion Program (MNSP); (iii) The Stock Exchange Medallion Program (SEMP); or (iv) another guarantee program acceptable to the Trustee.)

 

    	 	7	 

     

    

 

FORM OF FUNDAMENTAL CHANGE PURCHASE NOTICE

 

The Bank of New York Mellon Trust Company, N.A., as Paying Agent

10161 Centurion Parkway North, 2nd Floor, Jacksonville, Florida 32256

Attention: Corporate Trust

 

The undersigned registered owner of this
Note hereby acknowledges receipt of a notice from Protalix BioTherapeutics, Inc. (the “Company”) as to the occurrence
of a Fundamental Change with respect to the Company and specifying the Fundamental Change Purchase Date and requests and instructs
the Company to pay to the Holder hereof in accordance with the applicable provisions of the Indenture referred to in this Note
(1) the entire principal amount of this Note, or the portion thereof (that is equal to $1,000 principal amount or an integral multiple
of $1,000 in excess thereof) below designated, and (2) if such Fundamental Change Purchase Date does not occur during the period
after a Regular Record Date and on or prior to the corresponding Interest Payment Date, accrued and unpaid interest, if any, thereon
to, but excluding, such Fundamental Change Purchase Date.

 

	Principal amount to be repaid (if less than all): $ ,000

 

	 
	CUSIP/ISIN:	 

 

	Signature Guaranteed
	 
	 
	Participant in a Recognized Signature
	 
	Guarantee Medallion Program
	 	 
	By:	 
	Authorized Signatory

 

    	 	8	 

     

    

 

FORM OF ASSIGNMENT AND TRANSFER

 

For value received, __________ hereby sell(s), assign(s) and
transfer(s) unto __________ (Please insert social security or Taxpayer Identification Number of assignee) the within Note and hereby
irrevocably constitutes and appoints __________ to transfer the said Note on the books of the Company with full power of substitution
in the premises.

 

Dated: __________________

 

________________________

 

________________________

  

Signature(s)

 

(Sign exactly as your name appears on the other side of this
Note)

 

	
        ________________________       

        Signature Guarantee (Signature(s) must be guaranteed by an institution
        which is a member of one of the following recognized signature Guarantee Programs: (i) The Securities Transfer Agent Medallion
        Program (STAMP); (ii) The New York Stock Exchange Medallion Program (MNSP); (iii) The Stock Exchange Medallion Program (SEMP);
        or (iv) another guarantee program acceptable to the Trustee)
	 

 

 

 

    	 	9	 

     

    

 

SCHEDULE OF INCREASES AND DECREASES IN THE
GLOBAL NOTE

Initial Principal Amount of Global Note:

 

	Date	 	Amount of Increase in Principal Amount of Global Note	 	Amount of Decrease in Principal Amount of Global Note	 	Principal Amount of Global Note After Increase or Decrease	 	Notation by Registrar, Note Custodian or authorized signatory of Trustee

 

 

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