Document:

Exhibit 10.46

 

First Amendment to the
License Agreement Between The Regents of the University of California and 

General Fiber, Inc. UC Agreement Control No. 2006-04-0026

 

This First Amendment ("First Amendment"),
dated November 08, 2005 (the "Effective Date"), is made by and between The Regents of the University of California ("The
Regents") and General Fiber, Inc. ("Licensee").

 

RECITALS 

 

WHEREAS, The Regents has entered into
an existing Exclusive License Agreement with Licensee, dated July 11, 2005, relating to various inventions entitled, "Estriol
for the treatment of autoimmune diseases & the use of estriol and other estranges, estrogens and estrogen receptor active compositions
in the treatment of psoriasis & other autoimmune diseases" (UCLA Case No. 1998-531 & UCLA Case No. 2004-101) developed
at The Regents (the "License Agreement");

 

WHEREAS, Licensee desires
to amend and clarify the License Agreement with The Regents;

 

NOW THEREFORE, in consideration of the
foregoing premises and the mutual promises, covenants, and agreements hereinafter set forth, all parties to this First Amendment
mutually agree to amend the License Agreement as follows:

 

1. Paraqraph 1.1 ("Regents' Patent Rights")
is deleted and replaced with the following, which is amended to include "UC Case No. 2006-154" and UC Case
No. 2006-155" in the parenthetical in the paragraph:

 

1.1 "Regents' Patent Rights"
means The Regents interest in any of the patent applications listed in Appendix A attached to this Agreement and assigned to The
Regents (UCLA Case No. 1998-531, UCLA Case No. 2004-101, UCLA Case No. 2006.. 154
and UCLA Case No. 2006-155); any continuing applications thereof including divisions; but excluding continuations-in-part except
to the extent of claims entirel'y supported in the specification
and entitled to the priority date of the parent application; any patents issuing on these applications including reissues and reexaminations;
and any corresponding foreign patents or patent applications; all of which will be automatically incorporated in and added to Appendix
A and made a part of this Agreement. 

 

2. Appendix A ("Regents' Patent Rights")
is deleted and replaced with the following, which is amended to include the patent applications filed under UC Case No. 2006-154
and UC Case No. 2006-155.

 

APPENDIX A REGENTS' PATENT
RIGHTS

 

                       
Patent No. 6,936,599, which was based on U.S. Patent Application No. 10/131,834 entitled "Estriol Therapy for
Multiple Sclerosis and Other Autoimmune Diseases," Wed April 24, 2002, which was based on Provisional Application No. 60/286,842
filed 4125/01 (UCLA Case Nos. 1998-531-1,2) by Dr. Rhonda

 

                       
Voskuhl, and assigned to The Regents.

 

                       
S. Patent Application No. 10/984,364 entitled "The Use of Estriol and Other Estranes, Estrogen and Estrogen
Receptor Active Compositions in the Treatment of Psoriasis ... ," filed November 8,2004, (UCLA Case No. 2004-101-3) by Drs.
Rhonda R. Voskuhl, Gerald D. Weinstein and Jenny E. Murase and assigned to The Regents.

 

    	 

    	 

    

 

European Patent Application
No. 02729034.5 based on PCT/US02/13407 (UCLA Case No. 1998-531-2), filed April 25, 2002 entitled "Estriol Therapy for
Multiple Sclerosis and Other Autoimmune Diseases" by Dr. Rhonda R. Voskuhl.

 

Provisional Patent Application
entitled "Method of treating post-partum diseases with estrogens, estranges, estriol, or estrogen receptor composition",
filed September 26, 2005 (UCLA Case No.2006154), invented by Dr. Rhonda Voskuhl and assigned to The Regents.

 

Provisional
Patent Application entitled "Method of treating of preventing a neurodegenerative disease with estrogens, estranges, estriol,
or estrogen receptor composition", filed September 26, 2005 (UCLA ~ase No.2006-155), invented by Dr.
Rhonda Voskuhl and assigned to The Regents. 

 

3. Section 6.3

 

Under Section 6.3 of the
License Agreement, the list of diligence items shall be expanded to include the following:

 

Section 6.3e: Licensee
will, within eighteen months from the Effective Date of this Amendment, conduct preclinical or clinical studies with one or more
of the compounds whQse utility is claimed in the patent application described in Appendix A above to test efficacy in at least
one disease other than multiple sclerosis,.

 

The remainder of the due
diligence obligations shall remain in place for the patent applications under Appendix A.

 

4. In consideration for
this Amendment, Licensee will pay to The Regents a two thousand dollar ($2,000) amendment fee within thirty (30) days of the Effective
Date of this First Amendment.

 

IN WITNESS WHEREOF, the
parties have executed this First Amendment to the License Agreement by their duly authorized representatives for good and valuable
consideration.

 

	GENERAL FIBER, INC 	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

	 	 
	By: /s/ Nicholas Stergis	By: /s/ Claire T . Wake, Ph.D.
	Name: Nicholas Stergis	Name: Claire T . Wake, Ph.D.
	Title: Chief Operating Officer	Title: Assistant Director, Licensing
	 	Office of Intellectual Property Administration

 

    	2Exhibit 10.47

 

Second Amendment to the License Agreement
Between the Regents of the University of California and 

General Fiber, Inc. License Agreement Control No. 2006-04-0026 Effective
January 3, 2007 

 

This Second Amendment (the “Second Amendment”) dated
January 3, 2007 is made by and between The Regents of the University of California and General Fiber,
Inc.

 

RECITALS

 

WHEREAS, The Regents has entered into an Exclusive License with
dated July 11, 2005, and a First Amendment to the License November 8. 2005 to various inventions entitled, "Estriol for the
treatment of autoimmune diseases & the use of estnol and other and f'ci-rr.rrpn actlVe in the treatment of & other autoimmune
diseases" 1998-531 & UCLA Case No. 2004-1 at The Regents (the "License Agreement’)

 

WHEREAS, Licensee desires to amend and the License with The

 

NOW THEREFORE, in consideration of the foregoing premises and
the mutual promises, covenants, and agreements hereinafter set forth, all parties to this Second Amendment mutually agree to amend
the License Agreement as follows:

 

1  In Paragraph 1.1 ("Regents' Patent Rights"), any reference to "UC Case No. 2004101-3" 1S amended to
exclude this case number (UC Case No. 2004-JOl-3). The remainder of the case numbers shall remain as part of the license.

 

2  Appendix
A Patent is hereby amended to remove any reference to UC Case No. 2004-101 and LLS. Patent Application No.1 entitled. "The
Use of Estriol and Other Estranes. Estrogen and Estrogen Active Compositions in the treatment of Psoriasis:, filed November 8,
2004, invented by Drs. Rhonda Voskuhl, Gerald D. Weinstein and Jenny E. Murase and to the

 

The remainder of the patents listed on A will remain of the
license.

 

3. Under Section 6.3
of the License Agreement, section 6.3e shall be deleted.

 

4. In consideration for this Second Amendment, Licensee will
pay to the a two thousand dollar ($2,000) amendment fee within thirty (30) of the Effective Date of this amendment.

 

IN WITNESS WHEREOF, the parties have executed this Second Amendment
to the License by their duly authorized for and valuable consideration.

 

 

	GENERAL FIBER, INC. 	  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
	 	 
	By: /s/ Nicholas Stergis            	By: /s/ Emily W. Loughran             
	Name: Nicholas Stergis	Name: Emily W. Loughran
	Title: Chief Operating Officer	Title: Director of LicensingExhibit 10.48

 

THIRD AMENDMENT TO EXCLUSIVE LICENSE
AGREEMENT

 

UC Agreement Control No. 2006-04-0026

 

This third amendment ("Third Amendment")
to the Exclusive License Agreement ("Agreement"), effective August 29, 2007 is made by and between The Regents of the
University of California, a California corporation ("The Regents"), and Putney Drug Corp, a Delaware company ("Licensee").

 

BACKGROUND

 

	 	A. 	The Regents and Licensee are parties to the Agreement, dated as of July II, 2005. 
	 	B. 	The Agreement was amended on November
8, 2005 ("First Amendment") and on January 3, 2007 ("Second Amendment");

 

The parties agree as follows:

 

I. Amend Paragraph I.l ("Regents'
Patent Rights") to include UC Case No. 2007

 

561.

 

2. In consideration for adding
UC Case No. 2007-561 to the Agreement, a milestone payment in the new Paragraph 4.5, which reads as follows, is added to the Agreement:

 

4.5 Licensee will pay The Regents,
in either cash or publicly traded equity, twenty thousand dollars ($20,000) upon issuance of the first US patent claiming priority
to the provisional filing (SN 60/933,030).

 

IN WITNESS WHEREOF, the parties have executed
this Third Amendment to the Agreement by their duly authorized representatives for good and valuable consideration.

 

	PUTNEY DRUG CORP. 	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
	 	 
	By: /s/ Steve Kanzer            	By: /s/ Emily Waldron Loughran             
	Name: Steve Kanzer	Name: Emily Waldron Loughran
	Title: President 	Title: Director of Licensing
	 	 
	Dated: August 30, 2007	Dated: September 4, 2007Exhibit 10.49

 

FOURTH AMENDMENT TO EXCLUSIVE LICENSE
AGREEMENT

UC Agreement Control No. 2006-04-0026

 

This fourth amendment (“Fourth
Amendment”) to the Exclusive License Agreement (“Agreement”), effective December 31, 2012 is made
by and between the Regents of the University of California, a California corporation (“The Regents”), and Putney
Drug Corp., a Delaware company (“Licensee”).

 

BACKGROUND

 

		A.	The Regents and Licensee are parties to the Agreement, dated as of July 11, 2005.

 

		B.	The Agreement was amended on November 8, 2005 (“First Amendment”), on January
3, 2007 (“Second Amendment”) and on August 29, 2007 (“Third Amendment”);

 

The parties agree as follows:

 

		1.	Amend paragraph 1.4 to read as follows: “1.4 The ‘Field of Use’ means
human therapeutics for the treatment of autoimmune diseases, including multiple sclerosis.”

 

		2.	Amend paragraph 4.3 to increase the annual maintenance fee from “$5,000” to “$10,000”.

 

		3.	Amend paragraph 4.2 by adding a new subparagraph 4.2c to read “seven hundred fifty thousand
dollars ($750,000) upon the first achievement of fifty million dollars ($50,000,000) in annual sales while covered by a validly
issued U.S. patent.”

 

		4.	Amend paragraph 6.3c to replace “Within eight years of the Effective Date of this Agreement,
initiate Phase III clinical trials” with “Within 3 years from the successful completion of the ongoing clinical trial
of estriol for relapsing-remitting multiple sclerosis being conducted by Dr. Rhonda Voskuhl as principal investigator, initiate
a Phase III clinical Trial”.

 

		5.	Amend paragraph 6.3d to replace “fourteen (14) years” with “seventeen (17) years”.

 

IN WITNESS WHEREOF, the parties have executed
this Fourth Amendment to the Agreement by their duly authorized representatives for good and valuable consideration.

 

	PUTNEY DRUG CORP.	 	THE REGENTS OF THE UNIVERSITY OF
	 	 	 	CALIFORNIA
	 	 	 	 	 
	By:	/s/ Jeff Riley	 	By:	/s/ Emily Waldron Loughran
	 	(signature)	 	 	(signature)
	Name: 	Jeff Riley	 	Name: 	Emily Waldron Loughran
	Title:	CEO	 	Title:	Director of Licensing
	Date:	3/15/2013	 	Date:	3/25/2013

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