Exhibit 10.20(ii)

AMENDING AGREEMENT

This Amending Agreement is made effective the 1st day of April, 2015 (the
“Effective Date”).

BETWEEN:

THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO

(the “University”)

- and -

PROTAGENIC THERAPEUTICS CANADA (2006), INC,

PROTAGENIC THERAPEUTICS INC.

(the “Sponsor”)

(Individually a “Party” and collectively the “Parties”)

WHEREAS the Parties entered into a Technology License Agreement effective
July 21, 2005, as amended, (collectively, the “License Agreement”)

AND WHEREAS the Parties under said License Agreement entered into a Sponsored
Research greement effective April 1st, 2014 (the “Research Agreement”) for the
performance of a research project entitled “Teneurin C-terminal Associated
Peptide (TCAP)-mediated stress attenuation in vertebrates: Establishing the role
of organismal and intracellular energy and glucose regulation and metabolism”
(the “Project”);

AND WHEREAS the parties now wish to amend the Research Agreement by reference
herein;

NOW THEREFORE the Parties hereby agree as follows:

 

1. Definitions. Except as otherwise defined herein, any capitalized terms used
in this Amending Agreement shall have the meanings prescribed by the Research
Agreement.

 

2. Amendments.

 

  a. Section 5.1 is hereby deleted in its entirety and replaced with the
following:

5.1 Term. This Agreement will enter into force as of the Effective Date and will
terminate on 31 March 2016 (“Term”) unless sooner terminated in accordance with
Article 5.2, or upon the written agreement of the Parties.

 

  b. Appendix “A” Description of the Project, is hereby amended to include
“Appendix A-1” attached hereto.

 

  c. Appendix “B” Project Budget is hereby amended to include “Appendix B-1”
attached herto.

 

1

--------------------------------------------------------------------------------

3. Counterparts. This amending agreement may be executed by signatures delivered
by facsimile transmission or delivered electronically in optically scanned form;
and/or it may be simultaneously executed by the parties in multiple
counterparts, each of which will be considered to be an original instrument, and
all of which taken together, where each party has executed at least one
counterpart, will constitute one and the same instrument.

 

4. General. The provisions herein shall supersede and replace all conflicting
provisions and subject matter otherwise contained in the Research Agreement, and
in the event of any contradiction or conflict between the Research Agreement and
this Amending Agreement, this Amending Agreement shall prevail and govern the
contractual relations and all other obligations and rights between the Parties
hereto. All other terms of the Research Agreement shall remain unchanged and in
full force and effect. This Amending Agreement shall be governed by, and
interpreted and enforced in accordance with the laws in force in the Province of
Ontario and the federal laws of Canada applicable therein.

IN WITNESS WHEREOF by signature of their respective authorized officers, the
parties agree to be bound by the terms of this Amending Agreement.

 

THE GOVERNING COUNCIL OF

THE UNIVERSITY OF TORONTO

   

PROTAGENIC THERAPEUTICS CANADA (2006), INC.

PROTAGENIC THERAPEUTICS, INC.

 

/s/ P. Lino DeFacendis

     

/s/ Robert Ziroyan

NAME:   P. Lino DeFacendis     NAME:   Robert Ziroyan TITLE:   Director,
Partnerships     TITLE:   President and Chief Operating Officer DATE:   Sept.
28, 2015     DATE:   September 23, 2015

Acknowledgement:

I, the Principal Investigator, having read this Agreement, hereby agree to act
in accordance with all the terms and conditions herein and applicable University
policies, and further agree to ensure that all University participants are
informed of their obligations under such terms and conditions.

 

 

/s/ David Lovejoy

NAME:   David Lovejoy DATE:   September 29, 2015

 

2

--------------------------------------------------------------------------------

Appendix “A-1”

Description of the Project

April 2015 – March 2016

Prepared by David A. Lovejoy, August 2015

Project 2015-1: Effect of TCAP on Glucose Regulation and Type II Diabetes

2015-1-A: TCAP actions of Glucose in the brain

This project was designed to establish proof of principal that TCAP could
regulate glucose action in the brain. This was a 5-year project to establish
both in vitro and in vivo mechanisms of how TCAP acts to increase glucose
transmission in the brain and how it affects organismal glucose, insulin and
glucagon levels.

2015-1-A1: Brain Glucose Completion: Following from studies with Molecular
Imagining, Inc in 2014, this project was aimed at finalizing completing the
blood biochemistry and hematology studies. [complete]

2015-1-A2: Brain Glucose, Mechanism: Further studies were aimed at establishing
the signal transduction mechanism of TCAP in the cell line models used for the
glucose study. Further studies were aimed at establishing that TCAP-1 had a
distinct action on intracellular calcium flux.[complete]

2015-1-B: TCAP actions of glucose in the muscle

Following from the original observation that TCAP-1 could affect glucose
regulation in muscle, further studies were performed to establish an in vivo
action in muscle.

2015-1-B1: In vivo proof of concept: SC administered rats showed significantly
improved muscle tension and recovery from exertion. [complete]

2015-1-B2: Immunohistochemistry: Tissues collected from the animals in the above
study will be assessed for water and glycogen accumulation, and fiber type. This
study has already established that water is significantly increased in affected
muscle. Previous studies have established that TCAP acts in part through
dystroglycan actions which have been implicated with aquaporin regulation.
Aquaporin-4 is the dominant water transporter in muscle and studies are
currently underway to establish how this protein is regulated. [partially
complete. Expected completion Oct, 2015]

2015-1-B3: Pathology. Muscle tissue will be assessed for damage. Sectioning has
been completed. Final pathology assessment expected to be completed Sept-Oct
2015) [in progress]

2015-1-B4: Ion Regulation. In vivo studies indicated that the increased recovery
from muscle fatigue is likely due to increased calcium and possibly sodium and
or potassium flux. This will be assessed using differentiated C2C12 cells. The
model and methods have been developed. Studies are currently underway to assess
these ion fluxes [expected completion Oct-Nov, 2015]

2015-1-B5: Wound Healing. Based on the findings of the pathological studies, to
be performed, as well as novel studies indicating increased growth of the C2C12
myocyte model, and previous studies indicating a role of TCAP in cell
protection, studies are planned to assess proof of principal for wound healing.
This is expected to begin Jan 2016. Should this prove successful, this will
generate new IP and a new research project. [completion expected May 2016]

2015-1-B6: Long term studies: To date, the actions of TCAP with respect to
glucose regulation in brain and muscle have been performed with acute
administration. This study will include both the actions of TCAP with respect to
type II diabetes and muscle action in a single study. [to begin Autumn 2015,
results expected Jan-Feb 2016]

--------------------------------------------------------------------------------

Project 2015-2 Structure Function Studies

This project is designed to assess the binding affinity, signal transduction
mechanisms of the key TCAP peptides and their truncated analogues with the goal
to produce novel variants and to protect the key amino acid motifs for patent
applications.

2015-2-A Bioactivity

This component focuses on the signal transduction mechanisms of the endogenous
TCAP peptides

2015-2-A1: Calcium Flux. Calcium flux will be measured electrophysiologically
using various pharmacological agonists and antagonists of endoplasmic reticulum,
mitochondrial and plasma membrane channels. To date, studies for mouse TCAP-1
have been completed. Mouse TCAP-3, and human TCAP-1 are expected in the next
month. [completion Jan-Mar 2016]

2015-2-A2: Potassium. Plasma membrane potassium channels will be measured using
patch-clamping electrophysiology methods. Studies have begun. [Completion
Jan-Mar 2016]

2015-2-A3: IP3, DAG. This signal transduction system is associated with the
receptors (latrophilins). Mouse TCAP-1 has been assessed in five different cell
lines. Further studies, currently in progress will assess the actions of the
other key endogenous peptides [Completion expected Nov-Dec 2015]

2015-2-A4: MEK, ERK: This signal transduction system is associated with the
dystroglycans which associate with the latrophilins. Mouse TCAP-1 has been
assessed in three different cell lines. Further studies, currently in progress
will assess the actions of the other key endogenous peptides [Completion
expected Nov-Dec 2015]

2015-2-A5: cAMP, PKA. Previous studies established that mouse TCAP-1 and 3
activate this signal transduction system, and reports in the literature indicate
the receptor can be associated with this system. Additional homologues will be
investigated. [Completion Early 2016]

2015-2-A6: Glucose ATP. Previous studies have established that mouse TCAP-1
increases glucose transport in the cells resulting in increased mitochondrial
ATP activity. Further studies on the actions of mitochondria will establish the
role of TCAPs on mitochondrial activity. Methods are currently be evaluated
[completion early 2016]

2015-2-B Receptor Binding

Both the full-length and functional domains of the receptor will be
over-expressed in cell lines and the binding ability of TCAP variants will be
assessed.

2015-2-B1 Full length latrophilin: Currently several methods have been employed
to express the full length receptor. Data indicates increased co-localization of
tagged TCAP with the receptor. The sensitivity of this method will be improved.
[completion: Dec 2015]

2015-2-B2: Hormone binding domain: The latrophilins possess a conserved hormone
binding domain. This region has been transgenetically over expressed in cell
lines and shown to bind with the putative mature endogenous mouse TCAP-1 (1-41)
but not the prohormone confirming that the synthetic form of TCAP-1 binds to the
latrophilin receptor. [Completed]

2015-2-C: Analogue Development

To date, several truncated variants of TCAP-1 have been developed. This study is
designed to assess the efficacy of each analogue and design novel sequences with
the goal of developing a shorter and more efficacious synthetic form

2015-2-C1: Human TCAP-1. Synthesis is completed. Evalution of the sequence
currently in progress.

2015-2-C2: Mouse TCAP-3. Synthesis is completed. Bioactivity testing to being
Oct 2015

--------------------------------------------------------------------------------

2015-2-C3: Human TCAP-3. Sequence defined. Synthesis is expected to being early
2016.

2015-2-C4: Truncated analogues. First set of truncated variants synthesized.
Partial activity assessed for the mouse TCAP-1 (9-37) variant.

Project 2015-3: TCAP and infertility

Previous studies have established that TCAP-1 has a regulatory action of sex
steroids and gonadal morphology in mice. However, the studies were equivocal in
that it was not clear whether TCAP-1 had a direct action on the gonads (i.e.
gonadotropin-independent) or were acting at the level of GnRH production,
release and synthesis at the hypothalamic level. Moreover, in both male and
female tissues TCAP-1 and teneurin immunoreactivity was highly expressed
indicating a number of physiological roles.

2015-3-A: Male Reproduction

These studies are designed to establish the mechanism by which TCAP-1 regulates
reproductive function.

2015-3-A1: In vivo, LH, T: This study was a follow up to a previous study
showing that TCAP-1 could regulate testosterone production in mice. In this
study the regimen was changed to reflect current efficacy studies of TCAP and
blood was sampled to determine if testosterone and LH was regulated in a
pulsatile manner. Testosterone studies have been completed. LH studies are
currently in progress. [Completion Dec 2015]

2015-3-A2: In vitro LH, T: An in vitro model has been developed to examine the
molecular and cellular actions of TCAP in leydig and sertoli cells. Currently,
the signal transduction and cellular expression of key molecular components have
been completed. LH measurements will begin within the next two months.

2015-3-A3: Sperm motility, ex vivo: Based on previous studies, TCAP-1 is not
expected to have an appreciable effect on sperm motility in normal animals.
Models are currently being assessed for an appropriate in vivo model. Studies
are expected to being in 2016.

2015-3-A4: Sperm motility, in vivo: Based on previous studies, TCAP-1 is not
expected to have an appreciable effect on sperm motility in normal animals.
Models are currently being assessed for an appropriate in vivo model. Studies
are expected to being in 2016.

2015-3-B: Female Reproduction

These studies are designed to complete previous studies on the expression of
TCAP-1, teneurin, dystroglycan and latrophilin expression in the female
reproductive tract.

2015-3-B1: Immunohistochemistry: Normal female mice will be assessed for
dystroglycans and latrophilins in reproductive tissues.

Project 2015-4 Neuroprotection

Based on previous studies, TCAP-1 plays a significant role in the protection of
neuronal cells. These studies will be aimed at delineating the mechanism by
which this occurs.

2015-4-A TCAP variants

Various TCAP peptides will be used to assess different models of cell protection
in neuronal cell lines.

2015-4-A1 In vitro assessment: TCAP will be used to examine ROS and glutamate
actions in hypothalamic, hippocampal and midbrain cell models.

--------------------------------------------------------------------------------

Project 2015-5 Behaviour

Numerous previous studies have indicated a number of actions of TCAP-1 on
behaviour in rodents. Our recent understanding of the mechanisms of TCAP-1 have
allowed us to re-evaluate previous unpublished behavioural studies to develop a
new understanding of TCAP with respect to behaviour. Based on these studies,
further studies are planned to provide a greater understanding of how TCAP
affects behaviour and what could be expected in the clinic.

2015-5-A Learning

To date, no studies have been performed on learning behaviour, per se. Some
studies indicate that TCAP could be affecting motivational behaviours, which
could manifest as a change in learning behaviour. Further tests using
standardized models are planned.

2015-5-A1: Morris water maze: Locational learning has been suggested by previous
in vivo studies indicating that key regions of the hippocampus associated with
direction are modified by TCAP. This study will provide further evidence of
these observations.

2015-5-A2: T-maze: This will be a modification of the previous H-maze test
completed earlier to determine if the effects will be similar.

2015-5-A3: Passive avoidance: This will build on previous studies indicating
that TCAP may influence the avoidance of noxious events.

2015-5-B Depression

Previous studies, particularly the sucrose administration and forced swim test
indicates that TCAP-1 decreases depressive like behaviours. A further test is
suggested to provide confirmation.

2015-5-B1 Tail suspension. This is one of the ‘gold standard’ tests for
depression, and has not been previously performed.

Personnel

Dr. David Hogg: Post Doctoral Fellow: Dr. Hogg is a neurophysiologist with
exception creative problem solving skills. He developed the electrophysiological
methodology for analyzing TCAP variants in vitro and ex vivo. Moreover, he has a
strong understanding of neuroprotection and has the skill set to analyze novel
analogues using a variety of methods. Although his contract ends in February, I
am suggesting that he continues after that.

Andrea D`Aquila: PhD Candidate: Although this student is exceptional and
provided much input into novel intellectual property, she has received a
scholarship and therefore no funding is requested for her.

Tea Pavlovic: PhD Candidate: Tea has taken over Dr. Dhan Chand`s work in the
laboratory. Her work is funding entirely by academic grants until the end of the
year. I have requested additional funding for her to complete the work started
by Dr. Chand in the new year.

Choden Tenjin: PhD Candidate. Choden has reanalyzed all previous CRO associated
behavioural studies and has led to a new synthesis of our understanding of TCAP
associated behaviour. She has been tasked with overseeing all behavioural
studies. Because of her multinational background and ability to speak 7
languages, I have tasked her with overseeing the next set of behavioural studies
to support preclinical studies.

All other students are currently covered by academic grants.

--------------------------------------------------------------------------------

APPENDIX “B-1”

Project Budget

 

Item

   Total, CA$  

Total Direct Costs

   $ 206,437   

Indirect Costs at 15%

   $ 30,966      

 

 

 

Total

   $ 237,403      

 

 

 

Payment schedule:

University of Toronto will submit invoices to Sponsor according to the following
schedule:

 

Date:

   Payment:    CA$  

24-Sep 2015

   1st installment    $ 30,000   

31-Oct 2015

   2nd installment    $ 21,000   

30-Nov 2015

   3rd installment    $ 100,000   

30-Jan 2016

   4th installment    $ 86,403         

 

 

     Total    $ 237,403         

 

 

 

Payment method:

Sponsor will pay via electronic wire transfer or cheque.