Exhibit 10.1
                               AMENDMENT AGREEMENT

                  AMENDMENT AGREEMENT (this "Agreement"), dated October 28, 2005
and  effective  as of  October  6, 2005  (the  "Effective  Date"),  by and among
Hemispherx  Biopharma,  Inc., a Delaware  corporation (the "Company"),  Portside
Growth and Opportunity  Fund  ("Portside") and Leonardo,  L.P.  ("Leonardo" and,
together with Portside, each, a "Buyer" and, collectively, the "Buyers").

                  WHEREAS:

A. The  Company  and the  Buyers  are  parties  to (i) that  certain  Securities
Purchase  Agreement,  dated as of October  29,  2003 (the  "October  2003 SPA"),
pursuant to which,  among  other  things,  the  Company  issued to the Buyers 6%
Senior Secured  Convertible  Debentures due October 31, 2005 of the Company (the
"October 2003  Debentures"),  which are convertible into shares of the Company's
common  stock,  par value $0.001 per share (the "Common  Stock"),  and (ii) that
certain  Securities  Purchase  Agreement,  dated as of  January  26,  2004  (the
"January 2004 SPA"),  pursuant to which,  among other things, the Company issued
to the Buyers 6% Senior Secured  Convertible  Debentures due January 31, 2006 of
the Company (the "January 2004  Debentures")  and  additional 6% Senior  Secured
Convertible  Debentures  due January 31,  2006 of the Company  (the  "Additional
Debentures" and,  together with the October 2003 Debentures and the January 2004
Debentures,  the  "Debentures")  pursuant to the exercise of certain  Additional
Investment Rights (as defined in the January 2004 SPA).

B.  Contemporaneously  with the  execution and delivery of the January 2004 SPA,
the Company and the Buyers entered into a Registration  Rights Agreement,  dated
as of January 26, 2004 (the "Registration Rights Agreement"),  pursuant to which
the Company agreed to provide  certain  registration  rights to the Buyers under
the  Securities  Act  of  1933,  as  amended,  and  the  rules  and  regulations
promulgated thereunder (the "1933 Act"), and applicable state securities laws.

C. The  Company and the Buyers  desire to enter into this  Agreement  to,  among
other things, (i) extend the Maturity Date (as defined in the Debentures) of the
Debentures to June 30, 2007,  (ii) amend the definition of  Installment  Date in
the  Debentures to extend the date on which  Installment  Amounts (as defined in
the Debentures) are required to be paid, (iii) increase the interest rate of the
Debentures  to 7% per annum and (iv)  provide for the  issuance to the Buyers of
warrants (the  "Warrants")  to purchase an aggregate of 225,000 shares of Common
Stock (as may be adjusted  pursuant to the terms of the  Warrants,  the "Warrant
Shares").


D. The parties hereto desire that the Warrant Shares and the Interest Shares (as
defined in the Debentures) be covered by the terms set forth in the Registration
Rights Agreement.

E. Capitalized terms used herein and not otherwise defined herein shall have the
respective meanings ascribed to them in the Debentures.






                  NOW, THEREFORE, in consideration of the foregoing recitals and
the mutual  promises  hereinafter  set forth,  the Company and the Buyers hereby
agree as follows:

1.       Amendment of Debentures.
         -----------------------

(a) Maturity  Date;  Installment  Amount;  Installment  Date. The Debentures are
hereby  amended  to extend  the  Maturity  Date  thereof  to June 30,  2007.  In
addition,  the definition of "Installment Amount" in the January 2004 Debentures
and the  Additional  Debentures is hereby  amended by replacing the reference to
"January 31, 2006" with "June 30, 2007." The definition of "Installment Date" in
the January 2004  Debentures  is hereby  amended by replacing  the  reference to
"July 26, 2005" with "July 1, 2006," and the definition of "Installment Date" in
the Additional  Debentures is hereby amended by replacing the reference to "July
26, 2005" with "January 1, 2007."


(b) Interest  Rate.  The  Debentures are hereby amended to increase the interest
rate set forth in the Debentures  from 6% per annum to 7% per annum effective as
of the  Effective  Date,  and on and after the  Effective  Date  interest on the
Debentures shall accrue at the rate of 7% per annum.

(c)  Registration  Rights  Agreement.  All  references in the  Debentures to the
Registration  Rights  Agreement,  the  Registration  Statement  and  Registrable
Securities  shall be deemed to include the  Registration  Rights  Agreement,  as
modified by Section 2(b) below, the Registration  Statement to be filed pursuant
to Section 2(b) below and the definition of Registrable  Securities set forth in
Section 2(b) below, respectively.

(d) Further  Amendments.  The Debentures are further  amended as provided in the
forms of Debentures attached hereto as Exhibits A, B and C.
                                       -------------------

2.       OTHER TRANSACTION DOCUMENTS.
         ---------------------------

(a) Warrant.  As of the Effective  Date,  the Company shall issue and deliver to
(i) Portside a Warrant to purchase  107,104  Warrant  Shares and (ii) Leonardo a
Warrant to purchase  117,896 Warrant  Shares.  The Warrants issued to the Buyers
shall be in the form of Exhibit C attached  hereto.  The issuance by the Company
of the Warrants  and the Warrant  Shares is exempt from  registration  under the
1933 Act.

(b) Registration  Rights  Agreement.  The Company shall file with the Securities
and Exchange Commission a Registration Statement on Form S-3 covering the resale
of at least 135% of the number of Warrant  Shares and Interest  Shares as of the
trading day  immediately  preceding the date of the filing of such  Registration
Statement.  The  calculation  of the number of shares to be registered  shall be
made without regard to any limitations on the exercise of the Warrants, and such
calculation  shall assume that the Warrants are then  exercisable into shares of
Common Stock and the maximum  number of Interest  Shares  under the  Debentures,
assuming the respective initial outstanding  principal amounts of the Debentures
remain outstanding through June 30, 2007, assuming no conversions or redemptions
of the Debentures  prior to June 30, 2007, and taking into account the amendment
to the interest rate of the Debentures effected hereby, are issuable at the then
prevailing Warrant Exercise Price (as defined in the Warrants) or Interest Share
Conversion Rate (as defined in the applicable  Debentures),  as applicable.  The
registration for resale of the Warrant Shares and the Interest  Shares,  and all
rights,  remedies and obligations of the Company and the Buyers related thereto,
shall be  governed  in all  respects  by the  terms of the  Registration  Rights
Agreement;  provided,  that, to effectuate this  provision,  the following terms
defined  in the  Registration  Rights  Agreement  shall  be  deemed  to have the
following meanings:

(i) "Warrants" and "Warrant Shares" shall have the meanings given to those terms
in this Agreement;

(ii) "Convertible Debentures" shall mean the Debentures;

(iii) "Closing Date" shall mean the Effective Date;

(iv)  "Registrable  Securities"  shall mean the (i) the Warrant Shares issued or
issuable  upon  exercise of all of the  Warrants,  (ii) the Interest  Shares (as
defined in the  Convertible  Debentures)  issued or issuable on the  Convertible
Debentures and (iii) any shares of capital stock issued or issuable with respect
to the Warrant  Shares or the  Interest  Shares as a result of any stock  split,
stock  dividend,  recapitalization,  exchange  or  similar  event or  otherwise,
without  regard to any  limitations  on the exercise of the Warrants;  provided,
however,  that shares of Common  Stock which are  Registrable  Securities  shall
cease to be Registrable  Securities (A) upon any sale pursuant to a Registration
Statement,  Rule 144  under  the 1933  Act or upon any sale in any  manner  to a
person  or entity  which,  by virtue  of  Section 9 of the  Registration  Rights
Agreement,  is not entitled to the rights  provided in the  Registration  Rights
Agreement  or (B) at such time as all such shares may be sold under Rule 144(k);
and

(v) "Filing  Deadline"  shall mean the date that is 60 days after the  Effective
Date.

3.       REPRESENTATIONS AND WARRANTIES

(a) Buyer Bring Down.  Each Buyer hereby  represents and warrants to the Company
with respect to only itself as set forth in Section 2 of the January 2004 SPA as
to this Agreement,  the Registration Rights Agreement, The Warrants, the Warrant
Shares and the Interest  Shares as if such  representations  and warranties were
made as of the Effective Date and set forth in their entirety in this Agreement.
References in such Section 2 to the  Securities  shall be deemed to refer to the
Warrants, the Warrant Shares and the Interest Shares.

(b) Company Bring Down. The Company hereby represents and warrants to each Buyer
as set forth in  Sections  3(b) and 3(e) and the first  and third  sentences  of
Section  3(d) of the January  2004 SPA as to this  Agreement,  the  Registration
Rights Agreement, the Warrants, the Warrant Shares and the Interest Shares as if
such  representations  and warranties were made as of the Effective Date and set
forth in their  entirety in this  Agreement.  References in such Sections to (i)
the  Transactions  Documents  shall be  deemed to refer to this  Agreement,  the
Warrants and the Registration  Rights Agreement and (ii) the Securities shall be
deemed to refer to the Warrants, the Warrant Shares and the Interest Shares.

4.       CONDITIONS TO ComPANY'S OBLIGATIONs hereunder.

     The  obligations of the Company to each Buyer  hereunder are subject to the
satisfaction of each of the following conditions, provided that these conditions
are for the Company's  sole benefit and may be waived by the Company at any time
in its sole  discretion  by  providing  each  Buyer with  prior  written  notice
thereof:

(a) Such Buyer shall have executed this  Agreement and delivered the same to the
Company.

(b)      Such Buyer shall have delivered to the Company its original Debentures.

(c) The  representations  and  warranties  of such Buyer in Section  3(a) hereof
shall be true and correct in all respects as of the Effective Date.

5.       CONDITIONS TO Buyer's OBLIGATIONs hereunder.

     The obligations of each Buyer hereunder are subject to the  satisfaction of
each of the following  conditions,  provided that these  conditions are for such
Buyer's  sole  benefit  and may be waived by such  Buyer at any time in its sole
discretion by providing the Company with prior written notice thereof:

(a) The Company  shall have  executed  this  Agreement and delivered the same to
such Buyer.

(b) The Company  shall have  executed and delivered to such Buyer the Warrant to
be issued to it hereunder.

(c) The Company  shall have  executed and  delivered  to such Buyer  replacement
Debentures,  which shall be identical  in all respects to such Buyer's  original
Debentures,  but shall incorporate the amendments to the Debentures  effected by
Section 1 hereof.

(d) The  Board of  Directors  of the  Company  shall  have  adopted  resolutions
consistent with the transactions contemplated hereby.

(e) Within  fifteen  business days after the Effective  Date,  the Company shall
have  delivered  to the  Company's  transfer  agent a  letter  stating  that the
Irrevocable  Transfer Agent Instructions dated January 26, 2004 shall also apply
to the Warrant Shares and the Interest Shares issuable under the Debentures.

(f) The  representations  and  warranties  of the Company in Section 3(b) hereof
shall be true and correct in all respects as of the Effective Date.

6.       MISCELLANEOUS.

(a)  Expenses.  Each party  hereto  shall bear its  respective  costs,  fees and
expenses in  connection  with the  negotiation,  execution  and delivery of this
Agreement and any and all documents executed in connection herewith.

(b)  Counterparts.  This  Agreement  may be  executed  in two or more  identical
counterparts,  all of which shall be considered  one and the same  agreement and
shall  become  effective  when  counterparts  have been signed by each party and
delivered to the other  parties;  provided that a facsimile  signature  shall be
considered  due execution  and shall be binding upon the signatory  thereto with
the same force and effect as if the signature were an original,  not a facsimile
signature.

(c) Headings.  The headings of this  Agreement are for  convenience of reference
and shall not form part of, or affect the interpretation of, this Agreement.

(d)  Severability.  If any  provision  of this  Agreement  shall be  invalid  or
unenforceable in any jurisdiction, such invalidity or unenforceability shall not
affect the validity or enforceability of the remainder of this Agreement in that
jurisdiction  or the  validity  or  enforceability  of  any  provision  of  this
Agreement in any other jurisdiction.

(e) No Third Party Beneficiaries.  This Agreement is intended for the benefit of
the parties hereto and their respective permitted successors and assigns, and is
not for the benefit of, nor may any  provision  hereof be enforced by, any other
Person.  This  Agreement  may not be assigned  by the Company  without the prior
written consent of the Buyers.

(f) Further Assurances. Each party shall do and perform, or cause to be done and
performed,  all such further acts and things,  and shall execute and deliver all
such other  agreements,  certificates,  instruments and documents,  as any other
party may reasonably request in order to carry out the intent and accomplish the
purposes of this Agreement and the consummation of the transactions contemplated
hereby.

(g) No Strict  Construction.  The language used in this Agreement will be deemed
to be the language chosen by the parties to express their mutual intent,  and no
rules of strict construction will be applied against any party.

(h)  Filing of Form 8-K.  At or before  8:30 a.m.,  New York City  time,  on the
business day following the date of execution  hereof,  the Company shall file an
amendment  to its  Current  Report on Form 8-K  (originally  filed on October 7,
2005) with the Securities and Exchange  Commission  describing the terms of this
Agreement and including  this  Agreement as an exhibit to such Current Report on
Form 8-K amendment.

(i) Debentures in Full Force and Effect.  Except to the extent modified  hereby,
the terms of the  Debentures  shall remain  unchanged and continue in full force
and effect.

(j) Amendments; Waivers. No provision of this Agreement may be amended or waived
except by a written instrument signed by all of the parties hereto.

(k) Governing Law. This Agreement  shall be governed by the laws of the State of
New York, without regard to its conflicts of laws principles.

(l) Independent Obligations. The obligations of each Buyer hereunder are several
and not joint with the obligations of the other Buyer,  and no provision of this
Agreement is intended to confer any obligations on one Buyer vis-a-vis the other
Buyer.  Nothing  contained  herein,  and no action  taken by any Buyer  pursuant
hereto,  shall  be  deemed  to  constitute  the  Buyers  as  a  partnership,  an
association,  a  joint  venture  or any  other  kind  of  entity,  or  create  a
presumption  that the Buyers are in any way acting in concert or as a group with
respect to such obligations or the transactions contemplated herein.

                            [Signature Page Follows]










                  IN WITNESS  WHEREOF,  each Buyer and the  Company  have caused
their respective  signature page to this Agreement to be duly executed as of the
date first written above.



                           COMPANY:

                           HEMISPHERX BIOPHARMA, INC.



                       By: s/
                           ---------------------------
                           Name:
                           Title:










                  IN WITNESS  WHEREOF,  each Buyer and the  Company  have caused
their respective  signature page to this Agreement to be duly executed as of the
date first written above

                       BUYER:

                       PORTSIDE GROWTH & OPPORTUNITY FUND



                   By: s/
                       -----------------------------------
                       Name:
                       Title:








         IN  WITNESS  WHEREOF,  each Buyer and the  Company  have  caused  their
respective  signature  page to this Agreement to be duly executed as of the date
first written above.



                       BUYER:

                       LEONARDO, L.P.



                   By: s/
                       -----------------------------------
                       Name:
                       Title: