Document:

Exhibit
4.27

 

CLINICAL
TRIAL AGREEMENT

 

THIS
Agreement is entered into on October 7,2011 by and between Prana Biotechnology Limited
(“Sponsor”), a corporation established under the laws of Australia, with offices located at Level 2, 369 Royal
Parade, Parkville VIC 3052, Australia and the University of Rochester
(“Institution”), a not-for-profit educational institution established under the laws
of New York State, with business offices located at 5th Floor Hylan Building, RC Box 270140, Rochester, NY 14627.

 

RECITALS

Whereas,
Sponsor desires Institution to study the safety and efficacy of PBT2 (“Study Drug”) and Institution is willing to perform
a clinical study of the Study Drug; and

 

Whereas,
the Study (as defined below) is of mutual interest and benefit to Sponsor and Institution,
and will further the Institution’s instructional and research objectives in a manner
consistent with its status as a not-for-profit tax-exempt educational institution;

 

Now
therefore, in consideration of the promises and mutual covenants herein contained, Sponsor and Institution hereby agree
as follows:

 

	1.	STATEMENT OF WORK. The Institution shall
exercise reasonable efforts to carry out the clinical trial research study set forth in the research protocol developed by Sponsor
dated           , 2011 and entitled “A randomised, double-blind, placebo-
controlled study to assess the safety and tolerability, and efficacy of PBT2 in patients with mild to moderate Huntington disease”
(the “Study”), which is attached hereto as Attachment A (the “Protocol”) and hereby incorporated into
this Agreement by reference. An allocation of tasks to be undertaken by the Sponsor and Institution in the conduct of the Study
is described in Exhibit A (“the Scope of Work”) is attached hereto and is incorporated into this Agreement by reference.
The Study shall be conducted under the direction of Elise Kayson as Principal Investigator in accordance with
this Agreement.
	 	 
	 	In
the event of any inconsistency between this Agreement and the Protocol, the terms of this Agreement shall govern. Changes in the
Protocol may be made only through prior written agreement between the Sponsor and the Institution.
	 	 
	2.	PERIOD OF PERFORMANCE. The Period of Performance under
this Agreement shall be from the effective date of this Agreement through the end of
the Study, unless extended by amendment of this Agreement or terminated in accordance
with Article 14. The Study is deemed completed upon receipt by Institution of final
payment. The Study may not begin, and no patient shall be enrolled, until approval
of the Study is received from the Institution’s Institutional Review Board (“IRB”).

 

 

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	3.	PAYMENT.
	 	 
		(a) Sponsor
shall reimburse the Institution for all direct and indirect costs incurred by Institution in accordance with the budget
attached hereto as Attachment B and incorporated herein by reference (the “Budget”). The parties estimate that
the payments provided for in the Budget will be sufficient to support the Study, but Institution may submit to Sponsor a
revised budget requesting additional funds in the event that costs may reasonably be projected to exceed the Budget. Except
as otherwise provided in this Agreement, Sponsor will not be required to make any payment in excess of the Budget without
Sponsor’s prior written approval.
	 	 
	 	The parties
estimate that the costs set forth in the Budget are adequate to support the Study, but if certain patient care costs are expected
to be covered by insurance or another third party payor and such costs are denied, Sponsor agrees to reimburse Institution for
the patient care costs not covered by insurance or third party payors.
	 	 
	 	Regardless
of whether it is included in the Budget, the Sponsor understands and agrees that it is responsible for paying the Institution’s
nonrefundable Institutional Review Board fee, and shall pay such fee within thirty (30) days of the date of invoice except as otherwise
provided in the Budget.
	 	 
	 	(b)
Sponsor shall make payments to Institution in accordance with the payment schedule set forth in Attachment B and incorporated
herein. Checks shall be made payable to the University of Rochester and sent to:

 

		University of Rochester
	 	Center for Human Experimental Therapeutics
	 	265 Crittenden Blvd
	 	CU 420694
	 	Rochester, NY 14642-0694
	 	ATTN: Patric Donaghue

  

		(c) For purposes of identification, each payment shall include the title of the
                                                                               project and the name of the Principal Investigator.

 

	4.	SUPPLIES. Sponsor will provide Institution, at no charge, with a
sufficient quantity of the Study Drug to conduct the Study, as well as any other compounds, materials, equipment, and information,
which the Protocol or Scope of Work specifies as being provided by the Sponsor, or which Sponsor deems necessary to conduct the
Study. All such Study Drug, compounds, materials, and equipment remain the sole property of Sponsor, unless otherwise designated.
	 	 
	5.	INVESTIGATOR’S AND SPONSOR’S ASSURANCE.

 

	 	(a) The Study shall be conducted in
accordance with the Study Protocol, Sponsor’s written instructions and all laws and regulations applicable to the performance
of the Study. In the event that Sponsor’s written instructions are inconsistent with the
Protocol, the Protocol approved by the IRB shall take precedence.

 

 

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		(b) Any amendments to the Protocol will be upon mutual consent of the parties and be
submitted to the Institution’s IRB for approval.
	 	 
		(c) Institution, Principal Investigator and
         Sponsor shall comply with all applicable international standards and federal,
         state and local laws, regulations and guidelines including, but not limited to,
         the Federal Food, Drug and Cosmetic Act, as amended (the “Act”) and regulations promulgated thereunder and the
         United States Food and Drug Administration (“FDA”) regulations
         governing the protection of human subjects and regulations governing clinical
         investigators, the Helsinki Declaration, and all current applicable ICH Harmonised Tripartite Guidelines.
	 	 
	 	(d) Sponsor acknowledges that the responsibility to comply with and perform the provisions of
                                           21 C.F.R. 312 subpart D and/or 21 C.F.R. 812 Subpart C (Responsibility of Sponsors) rests with the Sponsor as required by
                                           FDA.
	 	 
	 	(e) Institution
certifies that neither Institution nor any person employed or engaged by Institution
in the conduct of the Study has been debarred pursuant to Sections 306(a) or (b)
of the Act and that no debarred person will in the future be employed or engaged
by Institution in connection with conduct of the Study. Institution further certifies
that it will notify Sponsor immediately in the event of any debarment or threat
of debarment of any person employed or engaged by Institution in the conduct of the Study occurring during the period
of this Agreement.
	 	 
	 	(f) In
connection with research studies, Institution may collect “Protected Health Information”
(“PHI”) as defined in 45 C.F.R. Section 164.501 or medical information on
a patient as defined under New York State Public Health Law. Institution shall obtain
a patient authorization/informed consent from study subjects to allow Institution
to disclose the PHI and medical information to Sponsor. Sponsor shall use the
PHI or medical information in accordance with the patient authorization/informed consent.
If either party de-identifies PHI in accordance with the standards set forth in 45
C.F.R. Section 164.514, either party may use and disclose the de-identified information as permitted by law.
	 	 
	6.	PRINCIPAL INVESTIGATOR
	 	 
	 	(a) The
Institution has authorised the Principal Investigator as the person responsible on a day-to-day
basis for the conduct of the Study. The Principal Investigator does not have authority
on behalf of the Institution to amend this Agreement or the Protocol.
	 	 
	 	(b)
If the Principal Investigator leaves the Institution or otherwise ceases to be available then the Institution must consult
with the Sponsor and use reasonable endeavours to nominate as soon as practicable
a replacement reasonably acceptable to both Parties.
	 	 
	 	(c) If the Principal Investigator fails
to carry out those obligations specified in this s.6 the Institution will use reasonable
efforts to find another Principal Investigator to perform those obligations and rectify
and make good any breach. The Institution will ensure that any Personnel
who assist in the conduct of the Study are informed of and agree to abide by all terms of this Agreement relevant to the
activities they perform.

 

 

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	7.	NOTICES. Any
                                                                          notices related to this Agreement or required herein shall be in writing and delivered by first class mail, postage prepaid,
                                                                          or by facsimile to the parties as follows:

 

		INSTITUTION
	 	Gunta
J, Liders,
	 	Associate
VP for Research Administration
	 	University
of Rochester
	 	Office
of Research & Project Administration
	 	5th
Floor Hylan Bldg.
	 	Rochester,
NY 14627
	 	Phone: (585)275-4031
	 	FAX:
(585) 275-9492
	 	 
	 	SPONSOR
	 	Dianne
Angus
	 	Chief
Operating Officer
	 	Level
2, 369 Royal Parade
	 	Parkville
VIC 3052
	 	Australia
	 	Phone: +61 (0)3 93494906
	 	FAX: +61
(0)3 9348 0377

 

	8.	INDEPENDENT CONTRACTOR. The
Institution is an independent contractor and not an agent, joint venturer, or partner of Sponsor.
	 	 
	9.	INDEPENDENT RESEARCH. Nothing in this Agreement shall be construed to limit the
freedom of the Principal Investigator and/or Institution, its employees and agents, whether
paid under this Agreement or not, to engage in similar inquiries made independently under other grants, contracts or agreements
with parties other than Sponsor.
	 	 
	10.	CONFIDENTIAL INFORMATION. All
information whether disclosed orally or in writing pertaining to the Study and clearly
identified as confidential, shall be deemed as confidential (“Confidential Information”) and shall not be used by the
other party other than for purposes of this Agreement. Each party agrees to treat Confidential Information received from the other
party with at least the same degree of care with which it would treat its own Confidential Information of a similar nature and
further agrees not to disclose such Confidential Information to a third party without
prior written consent of the other party, for a period of seven (7) years following disclosure.
The foregoing obligations of non-disclosure do not apply to Confidential Information which: 

 

 

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	 	(a) is
in the public domain at the time of disclosure or becomes publicly available through no fault of the recipient;
	 	(b) was
known to the other party prior to disclosure;
	 	(c) was
received from a third party not under an obligation of confidence to Sponsor;
	 	(d) is
developed by the recipient without reference to the Confidential Information; or
	 	(e) is
required to be disclosed by law.

 

	 	In addition,
no Confidential Information involving individual patient data or medical records may be disclosed by either party at any time without
appropriate patient authorization or consent as required by law.
	 	 
	11.	 DATA OWNERSHIP and INTELLECTUAL
PROPERTY.
	 	
	 	(a) Sponsor
shall retain ownership of all completed case report forms and data generated as a result of the Study. Institution and the
Huntington Study Group shall have the right to maintain a copy of all Study data for educational, auditing, archival, patient
care and/or research purposes and to use Study results for publication purposes as outlined in Article 11. All patient
medical records being original records of work completed under this Agreement including, laboratory records and reports,
scans, films and information pre-existing in Institution’s databases shall be and remain Institution’s property.
	 	 
	 	(b) If
biological materials will be used or obtained in the performance of the Study, Sponsor agrees to reimburse Institution for
the cost of shipping such biological materials to Sponsor. The term “biological materials” shall include the
materials derived from subjects enrolled in the Study and used pursuant to the approved Protocol, including, but not limited
to, blood, bone marrow, urine, sera and other human tissue or fluids. At no time shall any biological materials be used by
Sponsor for any purpose other than as described in the Protocol or transferred to any third party without Institution’s prior
written consent, Upon completion or termination of the Study, all unused biological materials shall be destroyed as required
under any law or regulation or stored as permitted by the Protocol and applicable law and regulation.
	 	 
	 	(c) Institution
understands and acknowledges that the Study Drug that is being provided to Institution for the purpose of conducting this
Study is the property of Sponsor and/or that the Study Drug is subject to certain intellectual property rights owned by or
licensed to Sponsor. This Agreement shall not be deemed or construed to convey or transfer any rights with respect to the
Study Drug or with respect to any of such existing intellectual property rights to Institution except insofar as necessary to
permit Institution to conduct the Study which is the subject of this Agreement.
	 	 
	 	(d) For
all purposes herein, “Invention” shall mean any discovery, improvement, concept or idea which arises out of work
performed pursuant to the Study and which involve the use of the Sponsor’s drug. Inventions shall be the sole and exclusive
property of Sponsor. Institution will disclose promptly to Sponsor any and all Inventions,
patentable or not, arising out of the work pursuant to the Study and complete
any paperwork necessary to vest title in such Invention in the Sponsor.

 

 

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	12.	PUBLICATION. Sponsor acknowledges
that Institution is dedicated to the generation of new knowledge and information and to
its public dissemination. Institution acknowledges that Sponsor is a company dedicated
to understanding the basis of neurodegenerative disease and considers publication
of clinical and preclinical findings with its therapeutics to be critical to its mission and to the benefit
of the community. Therefore, Institution shall have the right to publish material
resulting from or related to the Study and the Sponsor and Institution will collaborate on the preparation of any proposed publication
or presentation of such material The Institution shall furnish Sponsor with a copy of any proposed written publication or presentation
of such material at least thirty (30) days prior to the submission for publication
or presentation. Sponsor may review the publication or presentation to see if it
contains patentable subject matter or other Sponsor-owned confidential information
that needs protection. Institution will, upon written request from Sponsor within
the thirty (30) day review period, delay the publication or presentation for a maximum of an additional sixty (60) days to allow
Sponsor or Institution to file a patent application or to remove the confidential
information. Such Sponsor required modification will not result in withholding any
study results from academic publication.
	 	 
	 	If
this is a multicenter Study, Principal Investigator understands that it is the intention of the Sponsor that a multicenter publication
will be prepared and published. Principal Investigator understands and agrees not
to publish the results of Institution’s participation in the Study until after the
completion of the Study at all participating sites and the review, analysis and write-up
of the Study results. Should a multicenter publication not be prepared for submission
within 12 months after the Study is completed (e.g. the data is locked) at all participating
sites, Principal Investigator may publish and present the individual Study results
as stated in the preceding paragraph. If Sponsor elects to publish the results from Institution’s participation, Sponsor agrees
to provide Institution with a copy of the proposed publication at least thirty (30) days prior to publication and agrees to acknowledge
Institution’s participation in the Study as appropriate for peer review publications.
	 	 
	13.	 SITE ACCESS. Either Sponsor or FDA, as required by FDA regulations, shall have reasonable
access to Principal Investigator and other project personnel, project facilities, drug
records, subject records, case reports, and other records directly related to this
Study, subject to applicable laws and regulations, during regular business hours and
with reasonable prior notice. Any audits by Sponsor (other than “for cause” audits)
shall require Sponsor to reimburse Institution or any site for the time and effort required for such audits.
	 	 
	 	If
there is an FDA audit or investigation, Institution agrees to provide Sponsor with prompt
notice of the audit or investigation and Sponsor may be present during such audit
but Sponsor agrees not to alter or interfere with any documentation or practice of
Institution. Institution shall be free to respond to any FDA inquiries and will provide
Sponsor with a copy of any final response or documentation to the FDA regarding the
Study. Sponsor agrees to reimburse Institution for the reasonable costs incurred by
Study personnel in responding to an FDA audit or investigation.

 

 

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	14.	PUBLICITY. Neither party shall
use the name of the other in connection with any products, promotion, or advertising related to this Study without the prior written
permission of the other party. The foregoing shall not, however, preclude any legally required
disclosure, reports generated in the normal course of business, or acknowledgement
of sponsorship as required by an academic organization.
	 	 
	15.	TERMINATION.

 

		(a)	Either the Sponsor or the Institution may
                                                         terminate this Agreement with 30 days prior written notice or such shorter time
                                                         period as is reasonably required in the circumstances for any reason, or if the other party:

 

	 	(i)	 is in breach of any obligations under the Agreement or the Protocol (including
without just cause to meet a timeframe) and fails to remedy such breach where it is capable of remedy within 30 days of a
written notice from the terminating party specifying the breach and requiring its
remedy; or
	 	 	 
	 	(ii)	 is declared insolvent or has an administrator or receiver appointed over all or any
part of its assets or ceases or threatens to cease to carry on its business.

 

		(b)	In addition to clause 15(a), a party may terminate this
                                                                                                     Agreement immediately by written notice to the other party if it believes on
                                                                                                     reasonable grounds that:

 

	 	(i)
	continuing the Study poses an unacceptable risk to the rights, interests, safety or well-being of Study Subjects; and
	 	 	 
	 	(ii)	 terminating this Agreement is the most appropriate way to respond to that risk.

 

		(c)	The Sponsor may terminate this Agreement with 30 days prior written notice to the
Institution.
	 	 	 
	 	(d)	In
the event of termination:

 

	 	(i)	 the Institution must promptly initiate all appropriate action to close the Study and, subject to any applicable retention requirements
imposed by law .
	 	 	 
	 	(ii)	 the Institution must take all appropriate action to close out the Study Site in a timely manner.
	 	 	 
	 	(iii)	 the Sponsor will cooperate with the Institution to ensure that Study Subjects who
may be affected by termination receive adequate medical care. This may include the
provision of Investigational Product in certain circumstances at the Sponsor’s expense.

 

 

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	 	(ii)	 The Institution shall be reimbursed for the reasonable costs of bringing this Study
to termination incurred prior to termination and for non-cancellable commitments outstanding at that date. The Sponsor shall receive
a refund of any amounts paid prior to such termination in excess of amounts earned
by the Institution as of the date of termination or notification of the decision to
terminate, whichever is later. If a subject discontinues his or her participation or
if the Study is discontinued for any reason, the Institution shall be held harmless
and Sponsor shall pay Institution on a prorated basis for such subjects or as otherwise set forth in payment schedule. If
Sponsor discontinues the Study for any reason, Sponsor shall reimburse Institution and all
sites that Institution has subcontracted with, for all expenses incurred up until that time, including all time and effort expended
and all non-cancelable commitments even if not included in the payment schedule.

 

	 	All
provisions of this Agreement that by their terms require performance by one or both
parties following expiration or termination of tin’s Agreement shall survive such expiration
or termination. Such provisions shall include, but not be limited to, Articles, 3, 5, 6,7,10,11,12,13,16,17,18,19 and 20.
	 	 
	16.	INDEMNIFICATION.
	 	 
	 	(a)
Sponsor shall indemnify, defend and hold harmless the Institution and its agents, representatives,
trustees, officers and employees (“Indemnitees”) from and against any liability,
damages, loss, expense, claims or costs that may be made or instituted against any of them (including the reasonable attorneys’
fees and other costs and expenses of defense), by reason of personal injury (including
but not limited to death) or property damage which arises out of or is connected with
the performance of the Study or use of the Study results or data; provided, however,
that Sponsor shall not be liable for any loss or damage resulting from an Indemnitee’s
(a) failure to adhere to the material terms of the Protocol; (b) breach of any applicable
FDA or other government law or regulation; and/or (c) negligent act or omission or
intentional misconduct of any of the indemnitee’s. Institution agrees to reasonably
cooperate in the defense of any such action or claim.
	 	 
	 	(c)
Institution will promptly notify Sponsor of any such claim and will cooperate with Sponsor
in the defense of the claim. Sponsor agrees, at its own expense, to provide attorneys
reasonably acceptable to Institution to defend against any claim with respect to which
Sponsor has agreed to provide indemnification hereunder. The Sponsor agrees not to
settle any claim against the Institution with an admission of liability against the
Institution without the Institution’s prior written consent. This indemnity shall not
be deemed excess coverage to any insurance or self-insurance Institution may have covering a claim.

 

 

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	 	(c) Sponsor
agrees to reimburse Institution for the cost of reasonable and customary medical treatment of any illness or injury sustained by
a Study subject as a result of injuries or adverse reactions caused by the Study drug or for injuries caused by the administration
of the Study drug or adverse reactions directly related to the study or properly performed procedures in accordance with the Protocol,
except to the extent that such costs are covered by subject’s insurance or other third party coverage. Notwithstanding the foregoing,
Sponsor’s obligations under this paragraph shall not apply to the extent that any such cost or illness or injury is attributable
to (i) the failure of Institution or Principal Investigator or other Institution personnel involved in the Study to adhere to the
terms of the Study Protocol or to comply with applicable laws or regulations; (ii) any negligent act or omission or intentional
misconduct of Institution, Principal Investigator or other Institution personnel involved in the Study; or (iii) the natural progress
of the Study subject’s underlying disease.
	 	 
	 	The provisions of this clause shall survive
termination of this Agreement.
	 	 
	17.	INSURANCE, (a) Sponsor shall, at its sole cost and expense, procure and maintain comprehensive liability, clinical trial
and product liability insurance in amounts not less than $3,000,000 per incident <and $9,000,000 annual aggregate>. Such liability
insurance shall include Institution and its trustees, directors, employees and agents as additional insured’s with respect to this
Agreement. If Sponsor’s insurance is written on a claims made basis as opposed to an occurrence basis, Sponsor shall purchase tail
coverage and/or a retrospective coverage provision to provide continuation and uninterruption of coverage of all claims. Sponsor’s
insurance will be primary coverage with respect to its indemnification obligations hereunder and Institution’s insurance or self-insurance
will be excess and noncontributory. Upon request, Sponsor shall provide Institution with written evidence of such insurance prior
to commencement of the Study. Sponsor shall provide Institution with written notice at least fifteen (15) days prior to the cancellation,
non-renewal or material change in such insurance; if Sponsor does not obtain replacement insurance providing comparable coverage
within such fifteen (15) day period, Institution shall have the right to terminate this Agreement effective at the end of such
fifteen (15) day period without notice of any additional waiting periods.
	 	 
	 	(b) Institution
shall maintain Worker’s Compensation insurance or other coverage on its employees as required by New York law and will
self-insure or maintain insurance covering its liability under this Agreement.
	 	 
	 	(c)Sponsor
and Institution hereby waive any rights of subrogation.
	 	 
	18.	COMPLIANCE WITH HIPAA. It is understood and agreed that Institution, as a covered entity under the Health Insurance Portability
and Accountability Act of 1996 (“HIPAA”), may not use or disclose protected health information (“PHI”),
as defined in HIPAA and its implementing regulations, for purposes other than treatment, payment, or health care operations without
first obtaining authorization from the individual
concerned. Institution agrees to obtain authorization from individuals enrolled in
the Study which permits disclosure to and use of PHI by Sponsor for purposes of conducting
and overseeing the trial. Sponsor agrees that it shall not disclose PHI to any person
or entity except as permitted by the HIPAA authorization.

 

 

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	19.	COMMUNICATION
                                                         CONCERNING CERTAIN EVENTS AFFECTING RESEARCH SUBJECTS.
                                                         Sponsor acknowledges that Institution has a human research protection
                                                         program that complies with the standards of the Association for the
                                                         Accreditation of Human Research Protection Programs (AHRPP). In furtherance of Institution’s compliance with AHRPP
                                                         standards, Sponsor agrees:
	 	 
	(a)	to
promptly notify the Principal Investigator and/or the IRB of any finding or study results
indicating (i) any non-compliance with the Protocol or applicable laws that could
impact the safety or welfare of participating subjects, (ii) of any serious adverse events that have been reported to the FDA
or other governmental agency in relation to the Study at Institution or any other
site, (iii) unanticipated problems in the Study at Institution or at any other site that could reasonably relate to risks to participating
subjects and could reasonably affect subjects’ willingness to continue to participate
in the Study or in the IRB’s continuing approval of the Study; and
	 	 
	(b)	to develop a plan of communication
to subjects with the Principal Investigator if and when the circumstances set forth
in paragraph (a)(iii) above occur.
	 	 
	20.	NO WARRANTIES. THE INSTITUTION
MAKES NO WARRANTIES, EXPRESS, OR IMPLIED, CONCERNING ANY MATTER WHATSOEVER, INCLUDING WITHOUT
LIMITATION, THE RESULTS OF THIS STUDY OR THE OWNERSHIP, MERCHANTABILITY, OR FITNESS
FOR A PARTICULAR PURPOSE OF SUCH RESULTS. The Institution shall not be liable for any
indirect, consequential, or other damages suffered by Sponsor or any other entity or individual including, but not limited
to, damages arising from loss of data or delay or termination of the Study or from the use
of the results of the Study or any invention or product resulting from the Study.
	 	 
	21.	NO WAIVER. The waiver of any
breach or default hereunder by either party shall not operate or be construed as a
waiver of any repetition of such breach or default or of any other breach or default.
	 	 
	22.	DISPUTES. Except in the case of an urgent interlocutory
injunction if a dispute arises out of or relates to this Agreement, or breach thereof,
the parties agree first to try in good faith to settle the dispute by negotiation within 28 days of a party notifying the other
party in writing of the dispute. If the dispute is not resolved within the initial 28 days,
the dispute will be referred to mediation. If the dispute is not settled at mediation
within a further 28 days (or such other period as the parties agree in writing) the
parties will be free to pursue their claims before the courts of the state of New York. .
	 	 
	23.	ENTIRE AGREEMENT. This Agreement describes the entire
agreement between the parties concerning the subject matter hereof and supersedes all prior
or contemporaneous
agreements, representations or understandings, written or oral. This Agreement controls over any inconsistent agreement
between Sponsor and Principal Investigator, and may not be amended, changed or modified except in a writing signed by both parties
hereto.

 

 

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	24.	ASSIGNMENT. Neither party may assign this Agreement without the prior
written consent of the other party; provided, however, that Sponsor may assign this Agreement to a successor in ownership of at
least 51% of its assets, provided that such successor expressly assumes, in writing, the obligation
to perform in accordance with the terms and conditions of this Agreement. Any attempt by either party to assign this Agreement
without such consent shall be void.
	 	 
	25.	SEVERABILITY. If any provision of this Agreement shall be or become
invalid under any provision of federal, state or local law, or by a court of competent jurisdiction,
such invalidity shall have no effect on the validity or enforceability of the remaining provisions of this Agreement, and
they shall continue in full force and effect. If such deletion substantially alters the basis
of this Agreement, the parties will negotiate in good faith to amend the Agreement to give effect to the original intent of the
parties.
	 	 
	26.	GOVERNING LAW. This Agreement shall be interpreted in accordance
with, and governed by, the laws of the State of New York, without regard to its conflict of
laws rules, and irrespective of the domicile or residence of the parties or of the location of any property affected hereby.
The venue for any action to interpret or enforce this Agreement shall be in Monroe County, New York.

 

IN
WITNESS WHEREOF, the parties hereto have executed this Agreement in duplicate by proper persons thereunto duly authorized.

 

	SPONSOR	 	UNIVERSITY OF ROCHESTER
	 	 	 	 	 
	By:		 	By:	
	Name: 	Dianne Angus	 	Name: 	Cheryl K. Williams
	Title:	Chief Operating Officer	 	Title:	Assistant Director. Office of Research and Project Administration
	 	 	 	 	 
	Date:	10/10/2011	 	Date:	10/7/2011

 

 

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Read and Acknowledged:

I have read the foregoing and, while
not a party to this Agreement, I understand and agree to comply with the obligations of the Principal Investigator as stated
herein.

 

	By:		 
	PRINCIPAL INVESTIGATOR	 
	Name: 	Elise Kayson	 
	 	 	 
	Date:	07 October 2011	 

 

 

12Exhibit 4.28

 

Clinical Research
Support Agreement

 

Parties

 

Prana Biotechnology Ltd ACN
080 699 065 of Level 2, 369 Royal Parade, Parkville Victoria 3052 (Prana)

 

The General Hospital Corporation
d/b/a Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, United States of America (MGH)

 

Introduction

 

	A.	Prana is a biotechnology company that undertakes neurological research by exploring the mechanisms of action and potential of its Metal Protein Attenuating Compounds (MPACs) to treat neurodegenerative conditions such as Alzheimer’s Disease, Huntington’s Disease, and Parkinson’s Disease. PBT2 is Prana’s lead proprietary MPAC for preclinical and clinical studies in Alzheimer’s Disease and Huntington’s Disease (HD). Prior studies have shown that PBT2 can rescue the HD phenotype in a fragment mouse model, R6/2 of HD and that PBT2 can confer neuroprotective and cognitive benefits.
	 	 	 
	B.	Prana is conducting a Phase IIa clinical study using PBT2-203 entitled “Reach 2HD” in the United Stated of America and Australia (the “Clinical Trial”).
	 	 	 
	C.	MGH has agreed to provide services that include (without limitation):
	 	 	 
	 	(a)	Analysis of biomarkers from biological samples taken from subjects enrolled in the Clinical Trial; and
	 	 	 
	 	(b)	Undertaking neuroimaging of selected subjects from the Clinical Trial.
	 	 	 
	D.	Prana has agreed to engage MGH to perform the Services (defined below) and MGH has accepted the engagement on the terms and conditions contained in this Agreement.

 

Agreement

 

 

	1.	Definitions and Interpretation
	 	 
	1.1	Definitions
	 	 
	 	Clinical Trial has the meaning given in Recital B above.
	 	 
	 	Confidential Information means information of any kind that is obtained by Receiving Party (as defined below) from Disclosing Party (as defined below), which, is identified as confidential and proprietary at the time of disclosure and includes (without limitation) Prana Confidential Information, when the Disclosing Party is Prana and the Receiving Party is MGH
	 	 
	 	Prana Confidential Information means current and future products and compounds (including
    PBT2) and all clinical structures, characterizations, preclinical and clinical data (including investigative brochures
    and toxicology data), information, papers, materials, records, documents, and data concerning Prana and its research projects
    including the clinical trial protocol PBT2-203, results, data, plans and strategies,
    products and compounds, trade secrets, know how, technology, business, operations, commercial and financial dealings that are
    or have been disclosed to or obtained by MGH on or after the date of this Agreement or is otherwise obtained by MGH in
    the performance of the Services.

 

    

	 

    	 

    

	 	Intellectual Property Rights means any and all intellectual, industrial, and commercial property rights throughout the world including rights and interests in respect of or in connection with designs, inventions (including patents), copyright (including future copyright and rights in the nature of or analogous to copyright), trade marks and service marks, trade names, database rights, Confidential Information, know-how and trade secrets, whether or not now existing and whether or not registered or registrable and includes applications for and any right to apply for the registration of such rights and includes all renewals and extensions.
	 	 	 
	 	Key Personnel has the meaning provided in clause 9.1. Steven Hersch, M.D., Ph.D. shall be designated as the principal investigator (“Principal Investigator”).
	 	 	 
	 	Results means all data and results, inventions, discoveries, information, processes, procedures, methodologies, techniques, concepts, ideas, compounds, materials, items or things created, developed, discovered, modified, improved or adapted by Prana relating to the use of PBT2 or arising from the implementation of protocol PBT2-203 and also means all inventions, discoveries, information, processes, procedures, methodologies, techniques, concepts, ideas, compounds, materials, items or things created, developed, discovered, modified, improved or adapted (“Innovations”) by MGH during, or as a direct consequence of, the performance of Services provided to Prana under this Agreement but specifically excluding where such Innovation relates to either:
	 	 	 
	 	(a)	modifications, improvements or adaptations made to any Biomarker Assay as described in Schedule 2, whilst MGH is providing the Services; or
	 	 	 
	 	(b)	modifications, improvements or adaptations made to any Imaging Marker or Imaging methodology, whilst MGH is providing the Services.
	 	 	 
	 	Services means the scope of work (“SOW”) for Prana set out in Schedule 2.
	 	 	 	 

	1.2	Interpretation
	 	 
	 	In this Agreement, headings are for convenience only and do not affect the interpretation of this agreement and, unless the context otherwise requires:

 

	 	(a)	words importing the singular include the plural and vice versa;
	 	 	 
	 	(b)	words importing a gender include any gender;
	 	 	 
	 	(c)	other parts of speech and grammatical forms of a word or phrase defined in this agreement have a corresponding meaning;
	 	 	 
	 	(d)	an expression importing a natural person includes any company, partnership, joint venture, association, corporation or other body corporate and vice versa;
	 	 	 
	 	(e)	“including” and similar expressions are not words of limitation;
	 	 	 
	 	(f)	a reference to a party in a document includes that party’s successors and permitted assigns;

 

    	 

    	 

    
 

	 	(g)	a reference to a statute, regulation, proclamation, ordinance, or by-law includes all statutes, regulations, proclamations, ordinances, or by-laws varying, consolidating or replacing it, and a reference to a statute includes all regulations, proclamations, ordinance and by-laws issued under that statute;
	 	 	 
	 	(h)	a reference to a document or agreement includes all amendments or supplements to, or replacements or novation of, that document or agreement;
	 	 	 
	 	(i)	a reference to a month, is a reference to a calendar month; and
	 	 	 
	 	(j)	no provision of this agreement will be construed adversely to a party solely on the ground that the party was responsible for the preparation of this agreement or that provision.

 

	2.	Term
    and Engagement
	 	 	 
	2.1	Term
	 	 	 
	 	This Agreement will commence on 1 April, 2012 and will continue until 31 March, 2014, unless otherwise terminated in accordance with Clause 13.
	 	 	 
	2.2	Engagement
	 	 	 
	 	Prana engages MGH to provide the Services to Prana and MGH agrees to provide the Services on the terms and conditions contained in this Agreement.
	 	 	 
	2.3	Status of MGH
	 	 	 
	 	Prana and the MGH are independent contracting parties and MGH is not an employee or agent of Prana.
	 	 	 
	3.	Duties and obligations
	 	 	 
	3.1	Duties and obligations
	 	 	 
	 	MGH must:
	 	 	 
	 	(a)	act in good faith in all dealings with or on behalf of Prana;
	 	 	 
	 	(a)	comply with all lawful policies and procedures of Prana applicable to this Agreement and the Services to be provided hereunder, as amended from time to time; to the extent such policies and procedures are not in conflict with MGH’s policies and procedures and are communicated to MGH;
	 	 	 
	 	(b)	keep Prana fully informed of all matters concerning the performance of the Services;
	 	 	 
	 	(c)	provide such reports as may be required by the Chief Operating Officer in relation to the Services performed and any consequent outcomes and results;

 

    	 

    	 

    

 

	 	(d)	properly and carefully produce consistently high levels of accuracy and expertise in performing the Services;
	 	 	 
	 	(e)	in providing the Services, act in full compliance with all laws including (without limitation) all applicable national, state, and local laws, and in particular in compliance with the applicable standards of Good Laboratory Practice (“GLP”) and Good Clinical Practice (“GCP”) in the conduct of the Services;
	 	 	 
	 	(f)	perform the Services and ensure that its employees, servants, agents, subcontractors, or nominees assigned to perform or provide the Services under this Agreement perform the Services with reasonable skill, care, and diligence and in accordance with the professional standards that could be expected of a provider of GLP and GCP research services;
	 	 	 
	 	(g)	devote such time and attention to the performance of the Services as may be required to fully discharge MGH’s obligations under this Agreement in a timely manner;
	 	 	 
	 	(h)	secure any necessary licenses, certificates, and permits required to perform the Services;
	 	 	 
	 	(i)	ensure that the Services are performed under the supervision of the relevant Key Personnel;
	 	 	 
	 	(j)	perform the Services in strict accordance with the SOW as it has been reviewed and approved by the Institution’s Institutional Review Board (“IRB”), and any subsequent IRB-approved amendments thereto; and
	 	 	 
	 	(k)	begin the Services only after IRB approval has been obtained.

 

	3.2	Additional Obligations
	 	 	 
	 	In providing the Services performing its obligations under this Agreement, MGH must at all times and must ensure that its employees and agents:
	 	 	 
	 	(a)	act in accordance with the instructions, guidelines, or procedures specified by Prana to MGH from time to time;
	 	 	 
	 	(b)	control, coordinate, supervise, direct and complete all activities necessary to complete the Services; and
	 	 	 
	 	(c)	must work with and provide all reasonable assistance (provided it does not impact the delivery of Services) to any third party engaged by Prana including (without limitation) any third party specified in Schedule 1, to provide services set out in Schedule 1 (if any) to Prana relating to or associated with the Services or other Prana projects and activities relating to or associated with the Services. Where such assistance requires material work effort from the MGH that has not been contemplated within the scope of the Services, the parties will negotiate in good faith an amendment to the scope of the Services in respect of such assistance.

  

    	 

    	 

    

 

	3.3	Material Transfer Agreement
	 	 	 
	 	(a)	During the course of the Services, Prana will provide MGH with human biological samples (“Human Biological Samples”), which means “any human biological materials,” that were collected, or will be collected in accordance with appropriate patient informed consent procedures of Prana or its clinical trial collaborators in effect at the time of collection and approved by the Institutional Review Board (“IRB”) or equivalent regulatory entity having jurisdiction, or other materials or information, regardless of route of transfer, which Prana provides for use in the provision of the Service, or to be tested or in relation to which an analytical method is required to be developed and/or validated, as MGH and Prana determine to be necessary for the conduct of the Services. The Human Biological Samples will be provided to MGH de-identified, as defined in § 164.514, Final Standards for Privacy of Individually Identifiable Health Information (the “Privacy Rule”) under HIPAA. However, to the extent that the de-identified information nevertheless could be used to identify an individual at a later time, MGH hereby agrees to treat such information as protected health information (“PHI”) as defined in § 164.501, Privacy Rule. Upon termination of this Agreement, all unused Human Biological Samples and any information, including Confidential information, provided by Prana shall be promptly returned to Prana at Prana’s cost and expense, or, at Prana’s option, destroyed with the destruction certified in writing.

 

	 	(b)	MGH: (i) shall use the Human Biological Samples only to perform the Services described in Schedule 2; (ii) shall not chemically, physically, or otherwise modify the Human Biological Samples, except if specifically required by the Services; and (iii) shall handle, store, and ship or dispose of the Human Biological Samples in compliance with all applicable local, state, and federal laws, rule, and regulations including, but not limited to, those governing hazardous substances.
	 	 	 
	 	(c)	Prana represents and warrants that the Human Biological Samples provided to MGH for use in the provision of the Services

 

	 	(i)	were obtained in material compliance with all applicable laws, regulations, and any generally accepted ethical guidelines regarding the collection, storage, transfer, subsequent use, and disposal of such Human Biological Samples; and
	 	 	 
	 	(ii)	that, if applicable, informed consent with respect to the Human Biological Sample has been obtained which
included statements informing the donor that the Human Biological Sample may be used for research purposes, and that does
not exclude the Services to be performed under this Agreement.

 

	4.	Remuneration
	 	 	 
	4.1	Payment
	 	 	 
	 	(a)	Prana will pay the MGH the fees as set out in Schedule 2.
	 	 	 
	 	(b)	The MGH will provide invoices each month for the Services.
	 	 	 
	 	(c)	if GST is imposed on any taxable supply made under or in accordance with this Agreement, then the amount payable for that supply is increased by the amount of the GST.
	 	 	 
	 	(d)	Prana is not responsible for payment of any annual leave, sick leave, long service leave, superannuation contributions, insurances, workers’ compensation or Workcover levies.

 

    	 

    	 

    
 

	 	(e)	Checks shall be made payable to The General Hospital Corporation, Federal Tax ID No.: 04-2697983, shall reference the name of the Principal Investigator, the Protocol number, if any, and the Research Management agreement number #2012A050671, and shall be forwarded to:

 

	 	Massachusetts General Hospital
	 	Research Finance
	 	c/o Bank of America, N.A.
	 	P.O. Box 414876
	 	Boston, MA 02241-4876
	 	USA

 

	 	(f)	IRB fees. Prana shall pay a non-refundable, non-overhead-bearing fee of Three Thousand Five Hundred Dollars ($3,500) to MGH to cover its IRB’s costs for reviewing the initial Services. A non-overhead-bearing fee of One Thousand Dollars ($1,000) will be charged to Prana for continuing annual reviews. MGH shall invoice Prana for the initial fee upon execution of this Agreement and annually for any continuing annual reviews.

 

	5.	Expenses
	 	 
	5.1	Expenses
	 	 
	 	Prana will pay directly for travel expenses for various expenses related to meetings in accordance with this Agreement (such as meetings with regulatory bodies or presenting the Results at various professional meetings). In the event that Prana does not pay for such travel expenses directly, Prana shall provide a budget for and will reimburse MGH for these expenses, such as travel, lodging and/or meal expenses, plus overhead. Consistent with Prana’s policies and applicable laws and regulations, Prana may provide meals for the purpose of facilitating the presentations/discussions and exchange of information at these meetings. Any expense claims shall be confirmed by receipts.
	 	 
	6.	Confidentiality
	 	 
	 	It is anticpated that in the performance of the Services, the parties may need to disclose to each other information that is considered confidential. The rights and obligations of the parties with respect to such information are as follows.
	 	 
	6.1	Disclosing Party” shall mean a party that discloses Confidential Information (as defined in herein) under this Agreement. “Receiving Party” shall mean a party that receives Confidential Information under this Agreement.
	 	 
	6.3	Period of Restriction. For a period of seven (7) years after the Effective Date of this Agreement and indefinitely with respect to any individually identifiable health information, institutional billing information and institutional financial information disclosed by MGH to Prana, Receiving Party agrees to use reasonable efforts, no less than the protection given its own confidential information, to use Confidential Information received from Disclosing Party and accepted by Receiving Party only in accordance with this Clause 6.
	 	 
	6.4	Use of Confidential Information. Receiving Party agrees to use or reproduce Disclosing Party’s Confidential Information solely for the purposes of performing the Services, obtaining any required review of the Services or their conduct, or ensuring proper medical treatment of any patient or subject. Receiving Party agrees to (a) take all reasonable and necessary precautions to maintain the secrecy and prevent the disclosure of the Confidential Information; (b) make Confidential Information available only to those personnel and agents at Receiving Party and those consultants and vendors who require access to it in the performance of the Services and to inform them of the confidential nature of such information; (c) keep all Confidential Information secret and confidential, except to the extent that Receiving Party is required by law to disclose it; and (d) not disclose any Confidential Information without first obtaining the prior written consent of Disclosing Party.

 

    	 

    	 

    

 

	6.5	Release of Confidential Information. Except as provided herein, Receiving Party agrees to keep all Confidential Information confidential unless Disclosing Party gives specific written consent for release.
	 	 	 
	6.6	Notice of Unauthorized Disclosure. Receiving Party shall notify, and shall require any recipient to notify, Disclosing Party of any disclosure not authorized hereunder of which it becomes aware. In such situations, Receiving Party shall take and shall require each such recipient to take reasonable steps to prevent any further disclosure or unauthorized use.
	 	 	 
	6.7	Exclusions. No Receiving Party shall be required to treat any information as Confidential Information under this Agreement in the event:
	 	 	 
	 	(a)	the information was already in the public domain at the time of its provision to Receiving Party;
	 	 	 
	 	(b)	the information was independently discovered by Receiving Party after the date of this Agreement without the aid, application or use of the Confidential Information;
	 	 	 
	 	(c)	it was known to Receiving Party prior to the date of disclosure or becomes known to Receiving Party thereafter from a third party having an apparent bona fide right to disclose the information;
	 	 	 
	 	(d)	it is disclosed by Receiving Party in accordance with the terms of Disclosing Party’s prior written approval; or
	 	 	 
	 	(e)	Receiving Party is obligated to produce it pursuant to a requirement of applicable law or an order of a court of competent jurisdiction or a facially valid administrative, Congressional, or other subpoena, provided that the Receiving Party, subject to the requirement or order or subpoena (A) promptly notifies Disclosing Party and (B) cooperates reasonably with Disclosing Party’s efforts to contest or limit the scope of such disclosure.
	 	 	 
	6.8	Each party reserves the right, in its sole discretion and without prior notice to any other party, to disclose its own Confidential Information to any third party for any purpose.
	 	 	 
	6.9	Return of Confidential Information. Prana may at any time by notice in writing to the MGH request the destruction or return of all Confidential Information in the Contractors possession, power or control and the MGH must immediately comply with such request, provided that MGH may retain one (1) copy of Confidential Information in its confidential files to demonstrate compliance with this Agreement.

 

	7.	Intellectual
    Property and Indemnities
	 	 
	7.1	Acknowledgment
	 	 
	 	The parties acknowledge and agree that:

 

    	 

    	 

    

 

	 	(a)	MGH-owned Intellectual Property Rights in existence at the time of the Effective Date of this Agreement remain the property of the MGH (“MGH Material”). Prana acknowledges that it does not own any Intellectual Property Rights in the MGH Material.
	 	 	 
	 	(b)	Prana-owned Intellectual Property Rights in existence at the time of the Effective Date of this Agreement remain the property of Prana (“Prana Material”). MGH acknowledges that it does not own any Intellectual Property Rights in the Prana Material.
	 	 	 
	 	(c)	all Results, as defined above, and all Intellectual Property Rights directly related to the Results will vest in and be solely owned by Prana (“Prana Developed Material”).
	 	 	 
	 	Each party hereby grants the other a royalty free, irrevocable worldwide, non-exclusive license to use, install, and test their respectively owned Material in the manner necessary to perform their obligations under this Agreement.

 

	7.2	Assignment of Results and Intellectual Property Rights
	 	 	 
	 	Should any right, title, or interest in or to the Results or Confidential Information (or any part thereof) and the Intellectual Property Rights in them that are directly related to the performance of the Services be or become owned by MGH (by operation of law or otherwise), then MGH must immediately assign all such right, title, or interest to Prana. If required by Prana, MGH must do all things and execute all documents which Prana determines are reasonably necessary to give effect to this assignment.
	 	 	 
	7.3	Further Assistance
	 	 	 
	 	MGH will give Prana all assistance and advice as reasonably may be required by Prana from time to time, in relation to:
	 	 	 
	 	(a)	the prosecution of any patents arising from the Results; or
	 	 	 
	 	(b)	the enforcement or defense of the Results and the Intellectual Property Rights in and to them.
	 	 	 
	 	Prana will give MGH all assistance and advice as may be required from time to time in relation to the enforcement or defense of any Intellectual Property Rights created and owned by MGH under this Agreement.
	 	 	 
	7.4	Intellectual Property Rights Warranty
	 	 	 
	 	MGH represents and certifies that to the best of its knowledge and belief all information and materials supplied to Prana for the use in the provision of Services:
	 	 	 
	 	(a)	do not infringe the Intellectual Property Rights of any person;
	 	 	 
	 	(b)	do not compromise MGH’s ability to provide the Services requested of Prana.
	 	 	 
	 	Prana warrants that to the best of its knowledge and belief all information and materials supplied to Prana for the use in the provision of Services do not infringe the Intellectual Property Rights of any person.

 

    	 

    	 

    

 

	7.5	Use of Intellectual Property Rights
	 	 	 
	 	MGH is not prevented from using any ideas, concepts, expression, know-how, skills and experience possessed by it before or developed or learned by it during the course of performing its obligations under this Agreement and remembered by its employees, servants, or agents without needing to refer to any written Confidential Information, provided that such use does not infringe any Intellectual Property Rights in the:
	 	 	 
	 	(a)	Prana Material; or
	 	 	 
	 	(b)	Prana Developed Material,
	 	 	 
	 	or otherwise would or could result in the disclosure of any of Prana’s Confidential Information (provided that nothing in the foregoing will prevent MGH from using and disclosing any MGH Material or MGH Developed Material as permitted under this agreement as long as any Confidential Information of Prana that was formerly incorporated in such MGH Material (if any) is removed).
	 	 	 
	7.6	Indemnities
	 	 	 
	 	MGH indemnifies and shall defend and hold harmless, Prana, its affiliates and its and their directors, officers, employees, agents, and subcontractors, and their respective successors, heirs, and assigns (“the Prana Parties”) against any actions, suits, claims, demands, proceedings, losses, damages, compensation, sums of money, costs (including solicitor/attorney and client costs), charges and expenses (“the Losses”) to the extent such Losses arise from any third party claim, action, lawsuit, or other proceeding which is attributable to any negligent or wilful act or omission or any breach of this Agreement on the part of MGH or any of its agents, employees, representatives or subcontractors except to the extent such Losses are determined to have resulted from:
	 	 	 
	 	(a)	a failure by the Prana Parties to adhere to the terms of this agreement;
	 	 	 
	 	(b)	negligence, recklessness, or wilful misconduct on the part of the Prana Parties; or
	 	 	 
	 	(c)	a breach of any applicable law or regulation by the Prana Parties.
	 	 	 
	 	Prana indemnifies and shall defend and hold harmless MGH, its affiliates and its and their directors, officers, medical and professional staff, employees, agents, and subcontractors, and their respective successors, heirs, and assigns (“the MGH Parties”) against any actions, suits, claims, demands, proceedings, losses, damages, compensation, sums of money, costs (including reasonable solicitor/attorney and client costs), charges and expenses (“the Losses”) incurred by the MGH Parties in respect of or relating to the Services or a Clinical Trial subject under this Agreement except to the extent such Losses are determined to have resulted from:
	 	 	 
	 	(a)	a failure by the MGH Parties to adhere to the terms of this agreement;
	 	 	 
	 	(b)	negligence, recklessness, or wilful misconduct on the part of the MGH Parties; or
	 	 	 
	 	(c)	a breach of any applicable law or regulation by the MGH Parties.

 

    	 

    	 

    

 

	8.	Subcontractors
	 	 
	8.1	MGH must not subcontract any of its obligations under this Agreement, including the provision of other Services, without Prana’s prior consent, which consent may not be unreasonably withheld. This clause does not prevent MGH from engaging individuals to provide contract labour to it. MGH remains fully responsible for the performance of all work in accordance with this Agreement notwithstanding the engagement of a subcontractor.
	 	 
	9.	Key Personnel
	 	 
	9.1	The parties may designate certain MGH personnel (if any) as “Key Personnel” in Schedule 1 to this Agreement.
	 	 
	9.2	MGH will ensure that all Key Personnel are engaged, throughout the term of the Agreement to carry out the Services.
	 	 
	10.	Right of Review
    of Standard Operating Procedures
	 	 
	 	Upon request of Prana, MGH shall make available its Standard Operating Procedures that comply with Good Laboratory Practice standards (“SOP”), for Prana’s review and comment.
	 	 
	11.	MGH Audits
	 	 
	 	Prana in its sole discretion and at its cost and expense (which shall include MGH personnel time and the cost of responding to any findings of such audits) may conduct audits at MGH’s premises. Audits will be performed in conjunction with MGH by Prana and/or, at Prana’s discretion, by a third party, which shall not be any of MGH’s competitors. MGH will receive reasonable advance notice of at least five (5) working days, of any forthcoming audits including information on what will be audited including the minimally necessary portions of Study subject medical records; such audits shall occur during usual business hours, and subject to MGH’s policies for the protection of confidential patient information. MGH shall provide feedback to Prana’s audit findings or corrective action items not less than the period requested by Prana and failing any period being specified, then thirty (30) working days after the receipt of the audit findings.

 

    	 

    	 

    
 

	12.	Privacy
	 	 	 
	12.1	Obligations for Both Parties
	 	 	 
	 	Each party must comply with all relevant privacy Laws in the USA, in relation to
    providing the Services whether or not the party is an organisation bound by those laws. Each party acknowledges that personal
    information provided by patients under this Agreement is also Confidential Information and is subject to the confidentiality
    obligations under clause 6.
	 	 	 
	12.2	MGH’s Privacy Obligations
	 	 	 
	 	MGH must:
	 	 	 
	 	(a)	collect, store, use, disclose or otherwise deal with any personal information provided by patients under this Agreement, as directed by the Prana or its nominee HSG CTCC, except to the extent that compliance with the direction would cause MGH to breach any relevant privacy laws; and
	 	 	 
	 	(b)	provide all assistance required by Prana to assist Prana in complying with its obligations under any relevant privacy law.
	 	 	 
	12.3	Prana’s Privacy Obligations
	 	 	 
	 	Prana agrees to collect, use, store, and disclose individually identifiable health information collected or produced as a result of the Services provided under this Agreement only for the purpose of the Study and related studies (that is, other studies of the Study Drug, alone or in combination with other drugs, or other studies that relate to the medical condition or disease area under investigation in the Study), and for the purpose of complying with applicable law, provided that all such uses are disclosed in the IRB-approved informed consent form. Prana may use information that is not identifiable under any applicable U.S. laws for any research and development purpose. Prana will use all reasonable efforts to protect the privacy and security of individually identifiable health information and will require its business partners to do so also. Prana will not contact any Study subjects, unless permitted by the informed consent form. No other provision in this Agreement shall be construed to override the provisions of this Clause 12.3.

 

	13.	Termination
	 	 	 
	13.1	Termination for breach
	 	 	 
	 	Prana may terminate this Agreement at any time by written notice to MGH if MGH:
	 	 	 
	 	(a)	breaches any material term of this Agreement and is unable to, or does not, remedy the breach within thirty (30) business days (or such longer period as may be allowed by Prana as is reasonable in the particular circumstances) of it being brought to MGH’s attention by Prana;
	 	 	 
	 	(b)	commits any act of dishonesty, fraud, wilful disobedience, misbehaviour, or negligent breach of duty (whether or not connected with the performance of the Services for the Company) which may adversely affect Prana;
	 	 	 
	 	(c)	breaches any of its obligations to Prana concerning Confidential Information;

 

    	 

    	 

    

 

	 	(d)	engages in misconduct or acts negligently or incompetently in the performance of the Services; or
	 	 	 
	 	(e)	performs the Services in a manner which, in the reasonable opinion of Prana, is unsatisfactory and inconsistent with the reasonable requirements of Prana.
	 	 	 
	13.2	Termination by MGH
	 	 	 
	 	MGH may terminate this agreement at any time by written notice to Prana, if Prana:
	 	 	 
	 	(a)	breaches any material term of this agreement which is incapable of remedy;
	 	 	 
	 	(b)	breaches any material term of this agreement and is unable to, or does not, remedy the breach within ten (10) business days (or such longer period as may be allowed by MGH as is reasonable in the particular circumstances) of it being brought to Prana’s attention by MGH.
	 	 	 
	13.3	Termination for convenience by Prana
	 	 	 
	 	Prana may terminate this Agreement at any time by giving at least thirty (30) days written notice to MGH.
	 	 	 
	13.4	Termination for protection of Study subjects.
	 	 	 
	 	Either Party may terminate ths Services and this Agreement immediately upon written notice if necessary to protect the health, welfare or safety of any Study subject.
	 	 	 
	14.	Consequences
    of Termination
	 	 	 
	14.1	Consequences of Termination
	 	 	 
	 	If this Agreement is terminated for any reason, then:
	 	 	 
	 	(a)	Prana will pay MGH (if applicable on a pro-rata basis) any Payments and other amounts due to the MGH as at the date of termination;
	 	 	 
	 	(b)	MGH must immediately return to Prana all property owned or leased by the Prana which is in the possession or control of the MGH, including all written or machine readable material, Confidential Information (subject to Clause 6), equipment, computers, software, credit cards, keys, and vehicles;
	 	 	 
	 	(c)	If requested by Prana, MGH will provide a report setting out the status of its work under this Agreement.
	 	 	 
	15.	Publicity
    and use of branding
	 	 	 
	15.1	Academic Publications
	 	 	 
	 	(a)	In the case of any proposed publication or presentation (“Publications”) by MGH on the Results, Prana must be given at least 60 days prior notice for a request for approval of the Publication. Prana reserves its right to review such Publications and either:

 

    	 

    	 

    
 

 

 

	 	(i)	request an appropriate period of delay in publication in order to arrange any necessary intellectual property protection for any part of the Publication; and/or
	 	 	 
	 	(ii)	request amendments or deletions of certain parts of the Publication for the removal of Confidential Information.

 

	 	(b)	All such Publications will properly acknowledge MGH personnel and Prana personnel directly involved in the Clinical Trial.

 

	15.2	Other Publications
	 	 
	 	Except as otherwise required by applicable law, regulations, guidelines, and standards or as a requirement of being a publically listed company neither party may:

 

	 	(a)	make any press release, announcement, or other public notification (excluding the publications referred to in clause 15.1 above) in relation to this Agreement or the Services; nor
	 	 	 
	 	(b)	use or reproduce any trade mark or branding of the other party, use the name of the other party or of any staff member, employee, student, or agent of the other party or any adaptation, acronym or name by which the other party is commonly known, in any advertising, promotional, or sales literature or in any publicity,
	 	 	 
	 	without obtaining the prior written consent of such other party or individual whose name is to be used, which consent may be withheld or provided in such other party’s discretion.

 

	16.	General
	 	 
	16.1	Governing law and jurisdiction

 

	 	(a)	This Agreement shall be governed by and construed and interpreted in accordance with the laws of the Commonwealth of Massachusetts. Each Party agrees to submit to the exclusive jurisdiction of the Superior Court for Suffolk County, Massachusetts, and the United States District Court for the District of Massachusetts with respect to any claim, suit, or action in law or equity arising in any way out of this Agreement or the subject matter hereof.

 

	16.2	Assignment
	 	 
	 	Neither party to this Agreement may assign its obligations hereunder without the prior written consent of the other party.
	 	 
	16.3	Entire Agreement
	 	 
	 	This Agreement constitutes the entire agreement between the parties in relation to its subject matter and supersedes all prior representations, agreements, statements and understandings, whether verbal or in writing.
	 	 
	16.4	Variation
	 	 
	 	This Agreement may only be varied or amended by the agreement of the parties in writing.

 

    	 

    	 

    

 

	16.5	Survival of obligations
	 	 
	 	Clauses 1, 4, 6, 7, 9 and 10.1 will survive the termination of this Agreement.
	 	 
	16.6	Insurance
	 	 
	 	Prana shall, at its sole cost and expense, procure and maintain policies of clinical trial insurance in amounts not less than Three Million Dollars ($3,000,000) per occurrence and Five Million Dollars ($5,000,000) annual aggregate covering its obligations under this Agreement, including contractual liability coverage for its indemnification obligations under Clause 7.6, if any. Prana shall provide MGH at its request with written evidence of such insurance prior to the commencement of the services to be provided under this Agreement. Prana shall provide MGH with written notice at least thirty (30) days prior to the cancellation, non-renewal, or material change, in such insurance; if Prana does not obtain replacement insurance providing comparable coverage within such thirty (30) day period, MGH shall have the right to terminate this Agreement effective at the end of such thirty (30) day period without notice of any additional waiting periods.
	 	 
	16.7	Severability
	 	 
	 	Each clause of this Agreement is a distinct and severable clause and if any clause is deemed illegal, void, or unenforceable, the validity, legality, or enforceability of any other clause of this Agreement will not be affected thereby.
	 	 
	16.8	Priority of Terms
	 	 
	 	In the event of any conflict between the SOW and the provisions of this Agreement, the SOW shall govern with respect to scientific issues, and the provisions of this Agreement shall govern with respect to all other issues.
	 	 
	16.9	Notice
	 	 
	 	Any written notices, reports, correspondences or other communications required under or pertaining to this Agreement shall be given by prepaid, first class, registered or certified mail or by an express/overnight delivery service provided by a commercial carrier, properly addressed as follows:
	 	 
	 	If to MGH:

 

	 	Partners Clinical Research Office
	 	101 Huntington Avenue, 4th Floor
	 	Boston, MA 02199
	 	Attn: Patricia W. Cone, Ph.D., JD

 

	 	If to Prana:

 

	 	Prana Biotechnology Limited
	 	Level 2, 369 Royal Parade,
	 	Parkville, Victoria 3052
	 	Australia
	 	Attn: Dianne Angus

 

    	 

    	 

    

 

Schedule 1 - Agreement Details

 

Third Parties

 

ICON Central Laboratories,
Inc, a Delaware corporation, located at 123 Smith Street, Farmingdale, New York, 11735 United States of America; (“ICON”)
and

 

Huntington Study Group Clinical Trials Coordination Centre (“HSG
CTCC”).

 

Services provided from third parties

 

ICON: Liaising with MGH to deliver biological samples (both tissue
and blood) to MGH

 

HSG CTCC: Prana’s CRO
who handles data capture, project management, monitoring, and auditing of the Clinical Trial.

 

Key Personnel

 

Steven Hersch, MD, Ph.D.

 

Diana
Rosas, MD

 

    	 

    	 

    

 

Schedule 2 - Description of the
Services and Budget

 

MGH Tasks and Budget – PBT2-203
Reach 2HD Project

The following information
describes the essential tasks of the Services, MGH personnel and costs to assist Prana Biotechnology with the Clinical Trial
under protocol PBT2-203.

 

Part A. Biomarkers for Reach2HD

 

Investigator: Steven Hersch
MD, PhD

 

The Reach2HD trial seeks to determine the safety and tolerability
and efficacy of two dose levels of PBT2 in a Stage I or II HD population. Clinical efficacy will be evaluated in terms of cognition,
motor function, global outcomes, functional outcomes and behaviour. Pharmacodynamic responses to PBT2 will be assessed in terms
of plasma and urinary biomarkers and neuroimaging modalities related to HD. Following review of both animal efficacy and toxicology
data, and the results of the previous Phase I and IIa human clinical trials with PBT2, doses of 100 mg and 250 mg once daily were
selected for this study. 100 subjects with stage I or II HD will be enrolled at HSG sites in Australia and the USA and treated
for 6 months with either placebo or one of the two study doses. Blood and urine samples will
be collected from each subject for biomarkers at baseline, week 12, and week 26, according to the schedule of activities.
A subset of subjects will receive neuroimaging studies at MGH at approximately the same time points.

 

	1.	Sample management for Huntington Assay:
receipt of samples from central laboratory vendor, accounting to verify sample set and missing samples; confirming
quality of samples, setting up and maintaining Freezerworks database for study, logging
samples, generating aliquot labels and logs for delivery to Hersch Lab staff, secure freezer space with temperature monitoring
and alarms for primary and aliquoted samples (effort, supplies):                        $24,000

 

Huntington Assay

Rationale and Background: Huntington’s
disease (HD) is caused by a dominant genetic defect resulting in the cellular expression of the toxic mutant huntingtin protein
(mtHtt)mtHtt misfolds, oligomerizes and becomes insoluble, forming intracellular aggregates which are a
pathologic hallmark of the disease. Most evidence has indicated that toxicity resides in the soluble mtHtt protein
or its cleavage products, which unleash a slow cascade of pathogenic biology leading to gradual neuronal dysfunction and death
(1-11). We (12, 13) have shown that huntingtin coordinates copper (Cu2+) in a redox active manner that promotes the
oligomerization of soluble huntingtin by cross-linking specific N-terminus cysteine residues. This cross-linking promotes accumulation
of Huntington oligomers and promotes toxicity while its prevention enhances the metabolism of mutant huntingtin, reduces accumulation,
and is neuroprotective. We hypothesize that PBT2 could be neuroprotective for HD by preventing huntingtin oligomerization and
promoting its clearance which is suggested by the existing preclinical studies in HD transgenic mice.

 

Together with Weiss et al (14,15) we have described
a cell-based multiplex assay able to measure soluble mtHtt using time-resolved Forster Resonance Energy Transfer (trFRET)
for use in biological and clinical tissues, detecting simultaneously mtHtt and its relative ratio to total huntingtin
(tHtt). In preliminary studies, we have found the assay (Homogeneous trFRET or HTRF) to be sensitive and specific
for soluble mtHtt in tissues and blood from HD mouse models, and in postmortem tissue and blood samples from HD subjects.
We further optimized the assay using human brain lysates from healthy controls and HD subjects, validated it and created a Standard
Operating Procedure (SOP) that complies
with Good Laboratory Practice Standards (GLP). The assay is highly specific, robust and has good technical and biological
reproducibility. Using the GLP’ SOP we detected a significant increase in the mt/tHt
ratio in HD versus control subjects (16). This assay could be an ideal pharmacodynamic
measure of mtHtt for treatments modulating it, as we expect of PBT2.

 

    	 

    	 

    

 

 

Aims. To assess whether
the PBT2 systemic therapy affects the levels of mtHtt and the mt/tHtt ratio, the standard operating
procedure (SOP) in compliance with Good Laboratory Practice (GLP) conditions, previously mentioned, will be used.

The results of this study will help:

	1.	To further investigate the mechanism of action of PBT2 and specifically regarding
    its effect on soluble mtHtt and mt/tHtt.
	2.	If PBT2 affects soluble mtHtt levels and mt/tHtt ratios:
	 	•	Determine the effective PMT2 dose based on mtHtt levels and mt/tHtt ratios and its correlation to the clinical outcome.
	 	•	Determine the predictive value of mtHtt levels and mt/tHtt ratios and its relative added value to other biomarkers evaluated for the disease.

 

Assay Deployment and Technical Key Implementation Steps:

The following steps will be
taken to assess the soluble Htt and mt/tHtt levels in the PBT2 treated and Control HD subjects.

	1.	Assess technical interference of PBT2 with the HTRF assay. PBT2 at different concentrations, including the PBT2 concentration expected to be present in the peripheral blood, will be spiked in our quality control sample set (HD and Control brain lysates), and analyzed in the Soluble Huntingtin HTRF assay, to make sure that the presence of the drug alone does not interfere with the assay.
	2.	Ensure Samples Quality and Traceability:
	 	a.	Samples Quality: Since this is a multi-center clinical research trial it is important to ensure that the blood samples collected at the different clinical sites are processed per the agreed upon protocol, such as to ensure the samples quality and comparability, since preliminary studies done by our collaborators identified a decrease in the measurable human Htt in buffy coat from samples not processed per the protocol. In case there are changes to the protocol, recording the details will help in reconciling discrepancies down the line. Also, the samples need to be shipped on dry ice with prior notification and tracking to maintain samples quality.
	 	b.	Samples derived from the subjects enrolled in the study should be transferred with proper Transfer Documentation.

 

	3.	Testing samples from the PBT2 study in soluble mutant Huntingtin semi-quantitative HTRF assay:
	 	All the buffy coat samples will be tested at 3 two-fold dilutions, starting with a 1:2 dilution of the buffy coats, in parallel to our quality control samples: human HD and Control brain lysates, as described (16). The protein concentration as well as dsDNA content of the buffy coat samples will be evaluated for quality control purposes (16) in the samples.
	 	a.	Some samples, per criteria determined clinically and based on extra samples availability will be initially tested at the baseline time point, to determine the levels of soluble huntingtin in the subjects’ population, to assess if additional optimization of the assay’s conditions and/or samples preparation is necessary and modify the assay protocol, if needed.
	 	b.	Samples from PBT2 treated subjects will be tested occasionally, as needed, but the samples will be collected in addition to the samples collected for the final longitudinal study determining the impact of the drug on soluble Huntingtin levels in the HTRF assay.
	 	c.	A complete set of samples (longitudinal samples) from each subject (Treated and Controls HD patients) will be tested “BLIND” according to our GLP’ SOP (with modifications per 3a-if needed) and as described (16).

 

    	 

    	 

    

 

	4.	The data will be analyzed based on accepted criteria (27) by the Biostatisticians to determine the correlation between the results of the semi-quantitative determinations of the soluble Huntingtin levels in the HTRF assay in the context of the clinical outcome and the additional biomarkers that will be tested to establish the relevance of the soluble mtHtt biomarker as a prognostic marker for PBT2 therapy for HD patients, as outlined in the Specific Aims.

 

Part A Budget (Direct costs) and Time Requirements: 

	Sample Management	 	$	24,000	 
	Sample preparation from frozen EDTA tubes, including dissection, aliquoting, labeling, database entry (effort and supplies):	 	$	12,500	 
	Per subject sample cost for assay: $160, inclusive of personnel, supplies, reagents, sample preparations, replicates, QC assays, primary blinded data analysis and transfer to biostatistics. For 100 patients analyzed at 3 time points	 	$	48,000.	 
	Supervision and analysis: Effort by Dr. Hersch and Dr. Moscovitch-Lopatin to supervise assay, ensure GLP conditions, ongoing optimization of assay conditions, work with study biostatistician on analysis and interpretation	 	$	18,000	 

 

- Part A Direct Costs Total: US$102,500

- Time to completion for transfer of data to
biostatistics: 17 weeks for the longitudinal sets and data analysis, from receipt of the last patient sample.

 

References:

1.A novel gene
containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease
..chromosomes. The Huntington’s Disease Collaborative Research Group. Cell, 1993. 72(6): p. 971-83.

2.Hersch SM, Ferrante
RJ. Neuropathology and pathophysiology of Huntington’s disease. In: Watts RL, Koller WC, editors. Movement disorders. Neurologic
principles and practice.McGraw-Hill; 1997. p. 503-18.

3.Robitaille, Y.,
I. Lopes-Cendes, M. Becher, G. Rouleau, and A.W. Clark, The neuropathology of CAG repeat
diseases: review and update of genetic and molecular features. Brain Pathol, 1997. 7(3): p. 901-26.

4.DiFiglia,
M., E. Sapp, K. Chase, C. Schwarz, A. Meloni, C. Young, E. Martin, J.P. Vonsattel, R. Carraway, S.A. Reeves, and et al., Huntingtin
is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron, 1995.14(5): p. 1075-81.

5.DiFiglia, M.,
E. Sapp, K.O. Chase, S.W. Davies, G.P. Bates, J.P. Vonsattel, and N. Aronin, Aggregation
of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 1997. 277(5334): p. 1990-3.

6.Wellington, C.L.,
R. Singaraja, L. Ellerby, J. Savill, S. Roy, B. Leavitt, E. Cattaneo, A. Hackam, A. Sharp,
N. Thornberry, D.W. Nicholson, D.E. Bredesen, and M.R. Hayden, Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate
formation in neuronal and nonneuronal cells. J BiolChem, 2000. 275(26): p. 19831-8.

7.Bates,
G., Huntingtin aggregation and toxicity in Huntington’s disease. Lancet, 2003. 361(9369): p. 1642-4.

8.Kazantsev,
A., E. Preisinger, A. Dranovsky, D. Goldgaber, and D. Housman, Insoluble detergent-resistant aggregates form between pathological
and nonpathological lengths of polyglutamine in mammalian cells. ProcNatlAcadSci USA, 1999. 96(20): p. 11404-9.

10.Arrasate,
M., S. Mitra, E.S. Schweitzer, M.R. Segal, and S. Finkbeiner, Inclusion body formation reduces
levels of mutant huntingtin and the risk of neuronal death. Nature, 2004. 431 (7010): p. 805-10.

11.Rosas,
H.D., D.H. Salat, S.Y. Lee, A.K. Zaleta, V. Pappu, B. Fischl, D. Greve, N. Hevelone, and S.M. Hersch, Cerebral cortex and
the clinical expression of Huntington’s disease: complexity and heterogeneity. Brain, 2008. 131(Pt 4): p. 1057-68.

12.Fox J, Kama
JA, Lieberman G, Chopra R, Dorsey K, Chopra V, Volitakis I, Cherny RA, Bush Al, Hersch S.
Mechanisms of Copper Ion Mediated Huntington’s Disease Progression. PLoS One, 2007, 3 e334

 

    	 

    	 

    

 

13.Fox
J, Connor T, Stiles M, Kama JA, Chopra R, Dorsey K, Lieberman G, DiFiglia M, Cherny RA, Volitakis I, Berezovska O, Bush Al, Hersch
S. Cysteine oxidation within N-terminal mutant huntingtin promotes oligomerization and delays clearance of soluble protein.
J Biol Chem. 2011 May 20; 286(20): p. 18320-30. Epub 2011 Mar 30.

14.Weiss,
A, D. Abramowski, M. Bibel, R. Bodner, V. Chopra, M. DiFiglia, J. Fox, K. Kegel, C. Klein, S. Grueninger, S. Hersch, D. Housman,
E. Regulier, H.D. Rosas, M. Stefani, S. Zeitlin, G. Bilbe, and P. Paganetti, Single-step detection of mutant huntingtin in animal
and human tissues: A bioassay for Huntington’s disease. Anal Biochem, 2009. 395(1): p. 8-15.

15.Weiss A, Grueninger
S, Abramowski D, Giorgio FP, Lopatin MM, Rosas HD, Hersch S and P. Paganetti P. Microtiter
plate quantification of mutant and wild-type huntingtin normalized to cell count. Anal Biochem. 2011. 410(2): p. 304-6.
Epub 2010 Dec 4. PMID: 21134349

16.Moscovitch-Lopatin
M, Andreas Weiss A, Rosas HD, James J. Ritch JJ, Doras G, Kegel KB, DiFiglia M, Kuhn R, Bilbe G, Paganetti P, SM Hersch. Optimization
of an HTRF Assay for the Detection of Soluble Mutant Huntingtin in Human Buffy Coats: A Potential Biomarker in Blood for Huntington
Disease. PLoS Curr. 2010 December 29; 2: RRN1205. doi: 10.1371/currents.RRN1205, PMCID: PMC3015780

 

Part B. Gene Expression markers for Reach2HD

Gene expression markers predictive of either disease progression
or pharmacodynamic response to PBT2 therapy may be used to help assess the beneficial effect of PBT2. We have identified a panel
of promising genes in HD blood cells which strongly correlates with disease progression in brain. One of these genes, H2AFY (a
histone H2A Variant) has recently been established as a marker of huntingtin disease in both HD patients as well as in HD mouse
models and it has also been responsive to neuroprotective therapies (Yu et al, 2011). We have identified additional potential gene
markers of progression as well as genes related to metal homeostasis that change in HD brain and blood that are less well developed
but potentially revealing.

 

Methodology:

Minimizing bias from biospecimen collection and processing.
We will minimize bias from sample processing by collecting, handling and analyzing specimens of cases and controls in parallel,
in a uniform and blinded manner. All blood samples will be collected in PAXgene tubes (Qiagen, Valencia, CA) to preserve
RNA quality. Phlebotomy and transport will be performed in a standardized manner. In addition, all steps of sample processing
will be recorded in detail (e.g. time and clinician performing the phlebotomy, phlebotomy-to-refrigerator interval (< 3 hours),
duration of PAXGene tube storage at 4 degrees (< 5 days), RNA quantity (> 7 μg per subject), purity (Abs 260/280 1.8-2.0),
and quality parameters ( RIN > 7.5)) and statistically examined for influences on the biomarker. It should be noted that rigorous
and established quality standards for each step (shown in brackets above) exist in our lab and samples not meeting these standards
will be excluded.

RNA isolation and quality control: From each subject 5ml
of venous blood will be collected in 2 Paxgene tubes (each receives 2.5 ml of blood) and
immediately incubated at room temperature for 24 hours. The tubes will be then frozen for batch shipping when convenient
(RNA is stable like this for a couple of years, at least). RNA will be extracted from blood samples collected in PAXgene tubes
following the PAXgene procedure including DNase treatment as described previously (Yu et
al, 2011). RNA quality will be determined by spectrophotometry and by using the RNA 6000 NanoChip kit on the Agilent 2100
Bioanalyzer (Agilent Technologies, Palo Alto, CA). Only the high quality RNA with RNA integrity Number > 7.5 will be used for
further analysis.

 

Budget:

	Supervision and analysis: Effort by Dr. Hersch and Dr. Chopra to supervise assay, ongoing optimization of assay conditions, work with study biostatistician on analysis and interpretation	 	$	6,000	 

 

    	 

    	 

    

 

	RNA extractions, RNA QC (600 Paxgene samples, personnel and supplies):	 	$	39,000	 

 

- Part B Direct Costs Total: US$45,000

- Time to completion: RNA extractions,
quantification, and quality analyses will be performed on an ongoing basis as samples are received. The RNA database will be
updated at MGH on a weekly basis for additional samples and transmitted quarterly to the Reach2HD coordination center.
Completion for the entire sample set and transfer of final data base will occur within 3 months from receipt of the last
subject sample. The Reach2HD RNA sample set will be stored in the Hersch lab at MGH in a secure, monitored, temperature
alarmed, -80 freezer.

 

Part C. Imaging Markers for Reach2HD

The development of several of neuroimaging markers at MGH has been
supported by an MGH program project collaborative with the NINDS. In the Reach 2HD study imaging data will be acquired which will
allow us to evaluate several distinct modalities in a group of participants that will be scanned at MGH. With respect to the mechanism
of action and in the context of the improvement that was seen on cognitive measures in the AD study, MGH is proposing a comprehensive
protocol, that will include anatomical measures (both to collect morphometric data but also to co-register with the other scans
to evaluate regional differences), susceptibility weighting (for the iron mapping), diffusion weighted imaging and resting functional
imaging. MGH is planning to collect some data using both the 12 channel and our 32 channel coils, one of the few that currently
exist, which will provide additional signal. The collection of different modalities during the same session in the same group of
subjects is important. It is planned that at least ten to twelve participants will be scanned; it may be possible
to either expand this cohort or plan to scan participants from another site(s). MGH has some experience doing this with
CREST-E.

 

Budget (Direct costs) and
Time:

	The scan costs for one hour of time will come to approximately $1,125 per scan. MGH would scan participants at the start of the study and at the end of their on drug period.
	 
	 	 	$	25,000	 
	 	 	 	 	 
	Data storage and backup;	 	$	5,000	 
	 	 	 	 	 
	Supervision and analysis: Effort by Dr. Rosas and Dr. Chen to optimize the current protocols and to do the SWI analysis (including regional cross-sectional/longitudinal) for the Clinical Trial. MGH will also look at the correlation between these measures and blood biomarkers as well as with clinical measures	 	$	65,000	 

 

- Part C Direct Costs Total:
US$95,000
- Time to completion..........................

 

TOTAL BUDGET; US$242,500 Direct Costs and 25% Indirect Costs
US$60,625 = US$303,125

 

    	 

    	 

    

 

	EXECUTION	 
	 	 
	Date: 19 June 2012	 
	 	 
	Signed on behalf of	 
	Prana Biotechnology Ltd ACN 080 699 065	 
	by its authorised signatory:	 
	 	 
	Dianne Angus	 
	Chief Operating Officer	 
	 	 
		 
	Signature	 
	 19 June 2012	 
	Date 	 
	 	 
	Signed on behalf of	 
	The General Hospital Corporation	 
	by its authorised signatory:	 
	 	 
	Patricia W. Cone, Ph.D., JD	 
	Clinical Research Agreement Associate	 
	Name of Authorised Signatory	 
		 
	Signature	 
	12 June 2012	 
	Date 	 
	 	 
	Read and Acknowledged	 
	 	 
		 
	Steven Hersch, MD	 
	 	 
	 6/7/12	 
	Date 	 

  

    	 

    	 

    

 

Dr. Hersch
CRSA

 

	CRSA:
    Services Agreement for Reach 2HD Clinical Trial
	Part
    A. Biomarkers for Reach2HD
	Sample management for Huntington Assay: receipt of samples from central laboratory vendor, accounting to verify sample set and missing samples; confirming quality of samples, setting up and maintaining Freezerworks database for study, logging samples, generating aliquot labels and logs for delivery to Hersch Lab staff, secure freezer space with temperature monitoring and alarms for primary and aliquoted samples (effort, supplies)	 	$	24,000
	Sample preparation from frozen EDTA tubes, including dissection, aliquoting, labeling, database entry (effort and supplies):	 	$	12,500
	Per subject sample cost for assay: $160, inclusive of personnel, supplies, reagents, sample preparations, replicates, QC assays, primary blinded data analysis and transfer to biostatistics. For 100 patients analyzed at 3 time points	 	$	48,000
	Supervision and analysis: Effort by Dr. Hersch and Dr, Moscovitch-Lopatin to supervise assay, ensure GLP conditions, ongoing optimization of assay conditions, work with study biostatistician on analysis and interpretation	 	$	18,000
	Part A Total Direct Cost	 	$	102,500
	25% Overhead	 	$	25,625
	Part
A Total Cost	 	$	128,125
	Part
    B. Gene Expression markers for Reach2HD
	Supervision and analysis: Effort by Dr. Hersch and Dr. Chopra to supervise assay, ongoing optimization of assay conditions, work with study biostatistician on analysis and interpretation	 	$	6,000
	RNA extractions, RNA QC (600 Paxgene samples, personnel and supplies):	 	$	39,000
	Part B Total Direct Cost	 	$	45,000
	25% Overhead	 	$	11,250
	Part
B Total Cost	 	$	56,250
	Part
    C. Imaging Markers for Reach2HD
	The scan costs for one hour of time will come to approximately $1,125 per scan. MGH would scan participants at the start of the study and at the end of their on drug period.	 	$	25,000
	Data storage and backup:	 	$	5,000
	Supervision and analysis: Effort by Dr. Rosas and Dr. Chen to optimize the current protocols and to do the SWI analysis (including regional cross-sectional/longitudinal) for the Clinical Trial. MGH will also look at the correlation between these measures and blood biomarkers as well as with clinical measures,	 	$	65,000
	Part C Total Direct Cost	 	$	95,000
	25% Overhead	 	$	23,750
	Part C Total Cost	 	$	118,750
	Total
    Direct Cost	 	$	242,500
	25%
    Overhead	 	$	60,625
	Study
    Total Cost	 	$	303,125
	 	 	 	 

	One-Time
    Activities/Start-Up Charges	 	Start-Up
    Costs	 	 
	administration,
    regulatory, protocol review	 	$	4,000	 	 
	Sub-Total
    One-Time Charges	 	$	4,000	 	 
	25% Indirect
    Rate	 	$	1,000	 	 
	Total
    One-Time Charges w/ IDC	 	$	5,000	 	 
	 	 	 	 	 	 
	Invoiceable Activities, Inclusive of 25% IDC	 	 	Invoiceable
    Costs
	IRB
    Fee (no IDC applies)	 	$	3,500	 	one-time fee
	IRB
    Annual Review Fee (no IDC applies)	 	$	1,000	 	per year
	Per
    IRB amendment required, administrative	 	$	500	 	per amendment
	Per
    SAE report	 	$	150	 	per report
	Monitoring
    Visits	 	$	100	 	per hour (one visit per patient; up to 8 hours per visit)
	Travel,
    Accomodation, & Out of Pocket Expenses	 	invoiceable	 	Prana will reimburse the Contractor. These expense claims shall be confirmed by receipts.

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