Exhibit 4. 9   

NATIONAL INSTITUTES OF HEALTH

SECOND AMENDMENT TO L-249-2001/0

This is the second amendment (“Second Amendment”) of the agreement by and between the National Institutes of Health (“NIH”) or within the Department of Health and Human Services (“HHS”), and Can-Fite BioPharma, Ltd. having an effective date of January 29, 2003 and having NIH Reference Number L-249-2000/0, as amended by the first amendment to the agreement, having an effective date of August 15,2005, and having NIH reference Number L-249-2000/1 (“First Amendment”) (hereinafter collectively referred to as the “Agreement”). This Second Amendment, having NIH Reference Number L-249-2001/2, is made between the NIH through the Office of Technology Transfer, NIH, having an address at 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804, U.S.A., and Can-Fite BioPharma, Ltd. (“Can-Fite”), having an office at 10 Bareket Street, Kiryat Matalon, P.O.Box 7537, Petach Tikva 49170, Israel, the (“Licensee”). This second Amendment includes, in addition to the amendments made below, 1) a Signature Page and 2) Attachment 1 (Royalty Payment Information).

Whereas, the NIH and the Licensee desire that the Agreement be amended a second time as set forth below in order to accommodate the desire to discontinue or drop Licensed Fields of Use and for modifying Appendix E - Benchmarks and Performance.

NOW, THEREFORE, in consideration of the mutual covenants and promises contained herein, the NIH and the Licensee, intending to be bound, hereby mutually agree to the following:

Appendix E - Benchmarks and Performance shall be deleted in its entirety and be replaced with a new Appendix E - Benchmarks and Performance that shall now read:

APPENDIX E –Benchmarks and Performance

Licensee agrees to the following Benchmarks for its performance under this Agreement and, within thirty (30) days of achieving a Benchmark, shall notify PHS that the Benchmark has been achieved.

Regulatory Benchmarks for the Prime Indications

For the Anti-cancer therapeutic indication (for C1-IB-MECA):

Regulatory Benchmarks for the Non-Prime Indications

SIGNATURES BEGIN ON NEXT PAGE

SECOND AMENDMENT TO L-249-2001/0

SIGNATURE PAGE

In Witness Whereof, the parties have executed this Second Amendment on the dates set forth below. Any communication or notice to be given shall be forwarded to the respective addresses listed below.

For the NIH:

Mailing Address or E-mail Address for Agreement notices and reports:

Chief, Monitoring & Enforcement Branch, DTDT

Office of Technology Transfer

National institutes of Health

6011 Executive Boulevard, Suite 325

Rockville, Maryland 20852-3804 U.S.A.

E-mail: LicenseNotices_Reports@mail.nih.gov

For the Licensee (Upon information and belief, the undersigned expressly certifies or affirms that the contents of any statements of the Licensee made or referred to in this document are truthful and accurate.);

Name: Pnina Fishman

Title: CEO

Mailing Address:

Any false or misleading statements made, presented, or submitted to the Government, including any relevant omissions, under this Agreement and during the course of negotiation of this Agreement are subject to all applicable civil and criminal statutes including Federal statutes 31 U.S.C. §§3801-3812 (civil liability) and 18 U.S.C. § 1001 (criminal liability including fine(s) or imprisonment).

ATTACHMENT 1-ROYALTY PAYMENT OPTIONS

The OTT License Number MUST appear on payments, reports and correspondence.

Automated Clearing Honse (ACH) for payments through U.S. banks only

The NIH encourages its licensees to submit electronic funds transfer payments through the Automated Clearing House (ACH). Submit your ACH payment through the U.S. Treasury web site located at: https://www.pay.gov. Locate the “NIH Agency Form” through the Pay.gov “Agency List”.

Electronic Funds Wire Transfers

The following account information is provided for wire payments. In order to process payment via Electronic Funds Wire Transfer sender MUST supply the following information within the transmission:

Drawn on a U.S. bank account via FEDWIRE should be sent directly to the following account:

Drawn on a foreign bank account should be sent directly to the following account. Payment must be sent in U.S. Dollars (USD) using the following instructions:

Checks

All checks should be made payable to “NIH Patent Licensing”

Checks drawn on a U.S. bank account and sent by US Postal Service should be sent directly to the following address:

National Institutes of Health (NIH)

P.O. Box 979071

St. Louis, MO 63197-9000

Checks drawn on a U.S. bank account and sent by overnight or courier should be sent to the following address:

US Bank

Government Lockbox SL-MO-C2GL

1005 Convention Plaza

St. Louis, MO 63101

Phone: 314-418-4087

Checks drawn on a foreign bank account should be sent directly to the following address:

National Institutes of Health (NIH)

Office of Technology Transfer

Royalties Administration Unit

6011 Executive Boulevard

Suite 325, MSC 7660

Rockville, Maryland 20852