Exhibit 10.11


 


AMENDMENT NO. 2


TO SECOND AMENDED AND RESTATED
RESEARCH AND LICENSE


AGREEMENT


 


This
amendment no. 2 to the Second Amended and Restated Research and License Agreement (this “Amendment”) is
entered into as of April 30, 2014 (the “Amendment Effective Date”), by and between Ramot at Tel Aviv
University Ltd., a company organized under the laws of Israel with offices at Tel Aviv University, Tel Aviv, Israel (“Ramot”)
and Brainstorm Cell Therapeutics Ltd., a limited liability company incorporated under the laws of Israel with offices at 12 Bazel
Street, Petach Tikva, Israel 49170 (the “Company”).


 


WHEREAS,
Ramot and Brainstorm Cell Therapeutics Inc. executed a Second Amended and Restated Research and License Agreement dated July 26,
2007, as amended on December 24, 2009 which was assigned from Brainstorm Cell Therapeutics Inc. to the Company on December 20,
2011 (the “Agreement”); and


 


WHEREAS, the
Company and Ramot wish to have the TAU Team perform additional research under the Agreement as set forth herein.


 


NOW, THEREFORE,
the parties hereto, intending to be legally bound, hereby agree as follows:


 


		1.	Definitions.



 


All terms used
in this Amendment with an initial capital letter shall have the meanings ascribed to them in the Agreement, unless otherwised specified
herein.


 


		2.	New Research Period.



 


Although
the parties agreed that the Research Period ended on July 11, 2007, the parties wish to conduct additional research commencing
on the Amendment Effective Date, for a period of 6 months (the “New Research Period”).


 


		3.	New Research Plan.



 


The new Research
Plan is attached hereto as Exhibit A.


 


		4.	New Research Funding.



 


The Company
shall fund the new Research performed during the New Research Period in the total amount of $25,000 plus value added tax, which
shall be paid to Ramot as follows:


		-	$12,500 plus value added tax within 10 days of the Amendment Effective Date.



		-	$12,500 plus value added tax within 60 days of the Amendment Effective Date.



 




    	 	 	 



     


    

  


		5.	Principal Investigator.



 


For the purposes of Section 2
of the Agreement, the “Principal Investigator” shall be “Dr. Daniel Offen, or such other proncipal investigator
who may replace him pursuant to Section 2.”


 


		6.	General.



 


Except for the terms revised herein,
all other terms and conditions of the Agreement shall continue to apply and shall remain in full force and effect.


 


IN WITNESS HEREOF, the parties
have caused this Amendment to be executed by their duly authorized representatives as of the date first written above.


 





	Ramot at Tel Aviv University, Ltd.	 	Brainstorm Cell Therapeutics Ltd.
	 	 	 	 	 
	By:	/s/ Shlomo Nimrodi	 	By:	/s/ Liat Sossover
	Name:	Shlomo Nimrodi	 	Name:	Liat Sossover
	Title:	CEO	 	Title:	CFO
	By:	/s/ Avi Nataneli	 	
         

         

	Name:	Avi Nataneli	 
	Title:	Chief Financial Officer	 




  




    	 	 	 



     


    

  


Dani Offen PhD


 


Neurotrophic factors secreting cells
for the treatment of Autism Spectrum Disorders (ASD)


 


Rationale for the study


 


In the Neuroscience Laboratory,
FMRC (Tel Aviv Uni.) we have vast experience using mesenchymal stem cells (MSCs) transplantation as a tool for treating brain diseases.
In the current project, we plan to further explore this therapeutic strategy towards a clinical tool for the treatment of ASD by
transplantation of MSC-NTF cells (Brainstorm protocol) to the brain through intraventricular transplantation in animal models relevant
to autism.


 


In a translational perspective,
this technology will be presented as a novel therapy for ASD. Importantly, our preliminary study involved transplantation into
the brain ventricles, which may be translatable to intrathecal transplantation in ASD patients.


 


Scientific background


 


Autism
is a debilitating neuropsychiatric developmental condition affecting 1% of the population. Current available treatments
offer no cure for patients affected with ASD. The mainstay of treatment includes behavioral interventions and the use of
psychiatric medications to control symptoms often associated with ASD, such as aggression and agitation. Therefore, ASD research
is focused on the search for novel therapeutic approaches.


 


To date, few studies have reported
beneficial pharmacological interventions in ASD animal models which were described to improve some aspects of disease but not all
the behavior features.


 


The difficulty of finding therapeutic
agents capable of reducing the three symptoms (repetitive, cognitive and social behavior) emphasizes the beneficial potential of
MSC implantation, since our preliminary experiments showed that MSCs-treated mice demonstrated improved function in all criteria
tested. Mechanistically, stem cell based regenerative approaches have the potential to enhance repair to an ill-developing
brain and perhaps be more effective in presenting a cure rather than pharmacological control of symptoms. Our previous studies
have shown that MSCs transplantation indeed enhance the brain regenerative capacity (neurogenesis), a process that is known to
be induced by the neurotrophic factors we plan to deliver in this study.


 


Preliminary results


 


In a proof of concept study, we
have shown that transplantation of MSCs diminishes core autistic symptoms in a mouse model relevant to autism (the BTBR mice) as
manifested by the reduction of repetitive and stereotypical behavior (Figure 1) and improved cognitive flexibility (Figure 2) and
social behavior (Figure 3). The behavioral effect of the cell therapy was accompanied by a significant increase in brain derived
neurotrophic (BDNF) levels in the hippocampus of mice. Also, there was a significant enhancement of neurogenesis in the hippocampus
of stem cells-treated mice.


 


Study aim: To evaluate the effect of transplantation
of NTF-MSC compared to MSC on autistic behaviors of the BTBR mouse model of ASD


 


Specific aims:


 


		•	To evaluate transplantation outcome as observed in various behavioral tests representing core autistic behaviors including
(1) repetitive behavior (2) social behavior (3) cognitive flexibility (2 months).



		•	To evaluate the regenerative effect of transplantation on the brain as observed by measurements of neurotrophic factors levels
in situ (one month).



 




    	 	 	 



     


    

  


Dani Often PhD


 


We will include three treatment
groups:


(1)intraventricular transplantation
sham surgery (n=15)


(2)intraventricular transplantation
human MSCs transplantation (n=15)


(3)intraventricular transplantation
human MSC-NTFCs transplantation (n=15)


The cells will be provided by Brainstorm. ELISA tests
will be performed in collaboration with Brainstorm.


 


Budget: $25,000


 


The costs include BTBR mice (45), cell transplantation,
animal maintenance, behavioral tests, tissue analysis and Ramot overheads (35%)


  


	 	 	 
	 	 	 
	Figure. 1. MSCs transplantation reduce the repetitive behaviors (total duration of digging and self-grooming).	 	Figure. 2. Effect of MSCs transplantation on cognitive rigidity (time of reversal learning after the platform was moved to the other arm).


  


 


 


Figure. 3. MSCs
transplantation improve sociability (sniffing durations in cage contained a stranger mouse).