Exhibit 10.1

 

CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT IS
BOTH (I) NOT MATERIAL AND (II) WOULD LIKELY CAUSE COMPETITIVE HARM TO ORAMED
PHARMACEUTICALS INC. IF PUBLICLY DISCLOSED. OMISSIONS ARE DENOTED IN BRACKETS
WITH ASTERISKS THROUGHOUT THIS EXHIBIT.

 

CLINICAL RESEARCH ORGANIZATION SERVICES AGREEMENT

 

By and Between

 

Oramed Ltd.

 

and

 

Integrium, LLC

 

Effective Date: January 15, 2020

 

 

 

Integrium, LLC.   Confidential

 

CRO Agreement

 

EFFECTIVE DATE: January 15, 2020

 

Name and Address of the Contact for Integrium, LLC

 

Name: Jessica Coutu     Title: Sr. V.P. of Clinical Operations     Address: 100
East Hanover Avenue, Suite 401   Cedar Knolls, NJ 07927     Telephone: (908)
357-2010     Cell Phone: (908) 458-3058     e-mail: jessica.coutu@integrium.com
    Name and Address of the Contact for Oramed Ltd.     Name: Dr. Miriam Kidron
    Title: Chief Medical and Technology Officer     Address: Hi-Tech Park 2/4
Givat-Ram,   P.O. Box 39098   Jerusalem, 91390, Israel     Telephone: 972 2
566001     Facsimile: 972 2 566004     e-mail: miriam@oramed.com

 

 

 

Integrium, LLC.   Confidential

 

INDEX

 

1. Term 1       2. Scope of Work 1       3. Conditions of Work/Sponsor
Responsibilities 1       4. Compensation 2       5. Representations of CRO 3    
  6. Confidentiality 4       7. Conflicts of Interest 5       8. Independent
Contractor 6       9. Tax Reporting and Payment 6       10. Ownership,
Disclosure and Transfer of Developments and Study Data 7       11. Relationship
with Investigators 8       12. Indemnification 9       13. Limitation of
Liability 10       14. Insurance 11       15. Termination 11       16. Personnel
Recruitment 12       17. Equal Opportunity / Affirmative Action         18.
Miscellaneous Provision 12

 

Exhibit 1 Protocol Exhibit 2 Study Specifications: Assumptions, Timeline and
Task Ownership Matrix Exhibit 3 Study Budget Exhibit 4 Payment Schedule Exhibit
5 Transfer of Obligations

 

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Oramed Ltd. (“Sponsor”), an Israeli company, with principal offices at Hi-Tech
Park 2/4 Givat-Ram, P.O. Box 39098, Jerusalem, 91390, Israel and Integrium, LLC,
(“Integrium”), a California limited liability company, located at 14351 Myford
Road, Suite A, Tustin, California, 92780, hereby agree as follows:

 

1.Term

 

1.1The term of this Agreement shall be for the period beginning January 15, 2020
and ending upon the satisfactory performance of all the Services (as defined
herein) unless terminated sooner as provided herein. The initial term of this
Agreement was for the period beginning as of January 15, 2020 and ending on
April 24, 2020 (the “Initial Term”) during which Start-up activities for the
Project were initiated. This Agreement now represents the study in its entirety.
Any previous payments for the ORA-D-013 Start-up are incorporated and reconciled
herein and represented in the payment schedule.

 

2.Scope of Work

 

2.1Sponsor is conducting a Study pursuant to Protocol No. ORA-D-013-1,
(“Protocol”) entitled “A Double-Blinded, Placebo-controlled, Double Dummy,
Multi-center Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of
ORMD-0801 in Subjects with Type 2 Diabetes Mellitus with Inadequate Glycemic
Control on One, Two or Three Oral Glucose-lowering Agents” (the “Study”).

 

2.2Integrium shall perform services (“Services”) as required for the execution
of the Protocol according to the Study Specifications (Study Assumptions,
Timeline and Task Ownership Matrix), Exhibit 2, attached hereto and made fully a
part hereof. The designation of personnel to perform the services, shall be
within Integrium’s discretion, but Sponsor reserves the right, at its sole
discretion, to reject any personnel so designated by Integrium, and require
replacement of such personnel. Prior to performing the Services under this
Agreement, Integrium will inform Sponsor of the identity of the personnel
designated and Integrium shall make reasonable efforts to assure that the
personnel designated to perform the Services shall not be changed until the
Services are completed; provided, however, that where any such personnel ceases
to be employed by Integrium, Integrium shall promptly notify Sponsor of such
cessation and use its best efforts to locate replacement personnel acceptable to
Sponsor.

 

3.Conditions of Work/Sponsor Responsibilities

 

3.1In order for Integrium to perform the Services properly and timely, unless
otherwise agreed in writing, Sponsor shall provide Integrium with those
materials and take those actions as described in the Study Specifications, set
out in Exhibit 2 attached hereto and made a part hereof. In addition, Sponsor
shall cause all Sponsor contracted designees to (i) reasonably cooperate with
Integrium, and (ii) perform their services and supply to Integrium their study
materials and deliverables in a timely manner. Any failure under this Section
3.1 shall not constitute a breach of this Agreement by Sponsor but may require
changes in the budget/compensation and/or timelines for the Services in
accordance with Section 4.3.

 

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3.2Sponsor and/or its representatives may, during the Term, visit Integrium’s
facilities (and those of Integrium’s approved contractors) at reasonable times
and with reasonable frequency during normal business hours to (i) observe the
progress of the Study at Integrium’s facilities and all Study sites (it being
clarified that Integrium shall ensure that Sponsor has such rights viz-a-viz
each Study site), (ii) monitor the accuracy and completeness of the Services,
including, but not limited to, quality control and assurance, and/or (iii)
review the responsibilities and/or performance obligations of Integrium
personnel. Integrium will assist Sponsor in scheduling such visits and will make
records and any other relevant information available to Sponsor and/or its
representatives.

 

3.3Both Sponsor and Integrium enter into the Agreement for the express purpose
of transferring from Sponsor to Integrium the responsibilities and obligations
of a Sponsor to conduct, coordinate, manage, and/or develop the Study in
accordance with United States Food and Drug Administration (“FDA”) regulations
set forth in 21 CFR Section 312, Subpart D, as such may be amended from time to
time. Accordingly, if Sponsor is transferring to Integrium the responsibility
for various regulatory responsibilities under the U.S. laws and regulations as
set forth in Exhibit 5 (sample form), a Transfer of Regulatory Obligations Form
will be completed. Any regulatory responsibilities not specifically stated as
transferred to Integrium shall remain the regulatory responsibility of Sponsor.
Sponsor shall file the Transfer of Regulatory Obligations with the FDA or as
otherwise required by law or regulation. If an amendment to this Agreement
affects the scope of regulatory obligations that have been transferred to
Integrium, Integrium and Sponsor shall execute a corresponding amendment. Such
amendment shall be filed by Sponsor with the appropriate government bodies.

 

4.Compensation

 

4.1In consideration for Integrium’s satisfactory performance of any and all of
the Services, Sponsor shall pay Integrium a fee in the amount and on the terms
specified in Exhibit 3 (the “Study Budget and Payment Schedule”) attached hereto
and made fully a part hereof. All fees will be invoiced by Integrium and Sponsor
shall pay each invoice within thirty (30) days of receipt. If any portion of an
invoice is disputed, then Sponsor shall pay the undisputed amounts as provided
above and the parties will use good faith efforts to reconcile the disputed
amount as soon as practicable. If any undisputed invoice is not paid within
forty-five (45) days Sponsor will be considered in material breach. If the
breach is not cured within ten (10) days of written notice thereof provided by
Integrium, Integrium will suspend all activity until the breach is cured. If any
breach extends beyond forty-five (45) days Integrium will terminate this
Agreement. Any 3rd Party Vendor late fee charges resulting from Sponsor delays
in providing payment to Integrium will be passed on to Sponsor.

 

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4.2Any statement or invoice for services or expenses shall be stated with
sufficient specificity for Sponsor to be able to determine the services
performed, the work done, the related charges, and summary of pass through
expenses.

 

4.3Any material change in the Services, or the Assumptions set out in Exhibit 2
(including, but not limited to, changes in an agreed starting date or suspension
of the Study by the Sponsor) may require changes in the budget/compensation
and/or timelines and shall require a written amendment to this Agreement. Each
amendment shall detail the changes to the Services, Conditions, Compensation,
Timeline or other matter. Sponsor agrees that it will not unreasonably withhold
approval of an amendment even if it involves a fixed price contract if the
proposed changes in compensation or timelines result from, among other
appropriate reasons, changes in the assumptions upon which current compensation
or timelines were based. Integrium shall not implement any change in the Project
scope without Sponsor’s prior written approval. Integrium reserves the right to
postpone effecting material changes in the Project’s scope until such time as
the parties agree to and execute the corresponding Change Order.

 

5.Representations of CRO

 

5.1Integrium represents that it has the requisite facilities, equipment, and
personnel with the requisite expertise, experience and skill, to render the
desired Services, and it shall render the Services, in a timely, competent and
efficient manner. Integrium further represents that the Services to be provided
pursuant to this Agreement will represent Integrium’s best efforts and will be
of the highest professional standards and quality. Integrium further represents
that it shall abide by all laws, rules and regulations including, but not
limited to, GCP Guidelines issued by the FDA that apply to the performance of
the Services at the time they are provided, including applicable requirements
regarding equal employment opportunity and, when on Sponsor’s premises,
Integrium’s employees shall comply with Sponsor’s policies with respect to
conduct of visitors.

 

5.2Integrium certifies that neither Integrium nor any person employed by
Integrium has been debarred under Section 335a of Title 22 of the United States
Code, and that no debarred person will in future be employed or utilized to
perform any Services. Integrium certifies that, to the best of its knowledge, no
person performing any Services, including any investigator, has a conviction
which could lead to debarment under Section 335a. Furthermore, Integrium agrees
to notify Sponsor immediately of any action toward conviction or debarment of
any person performing any Services. Integrium understands that Sponsor shall
have the right to terminate this Agreement immediately upon receipt of notice
that any employee or agent of Integrium has been debarred or is subject to any
action toward conviction or debarment.

 

5.3Integrium shall maintain accurate and complete records specifically relating
to the Services provided hereunder in accordance with generally accepted
accounting principles and practices, consistently applied. To the extent that
such records may be relevant in Sponsor’s reasonable opinion in determining
whether Integrium is complying with its obligations pursuant to this Agreement,
Sponsor, or Sponsor’s authorized representative, may audit such records during
Integrium’s normal working hours and at Sponsor’s expense, upon providing five
(5) working days’ written notice to Integrium. Integrium shall retain such
records for a period of three (3) years from the date of final payment by
Sponsor pursuant to the Agreement.

 

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5.4Integrium represents and warrants that in any and all contracts between
Integrium and a third party with respect to the performance by such third party
of clinical trials or tests and services associated with any such clinical
trials or tests (a “Third Party Contractor”), and in which Integrium acts as an
agent or general contractor for Sponsor and to which such contract Sponsor is
not a party, Integrium will include a third party beneficiary provision naming
Sponsor as the third party beneficiary under such agreement. Notwithstanding
anything to the contrary in this Agreement, prior to entering into any contract
or arrangement with any Third Party Contractor or with any subcontractor with
respect to the performance by such subcontractor of any of Integrium’s
obligations under this Agreement, Integrium shall notify Sponsor thereof and be
required to obtain the written consent of Sponsor to any such contract or
arrangement (such consent not to be unreasonably withheld, delayed or
conditioned).

 

6.Confidentiality

 

6.1It is understood by the parties hereto that during the performance of the
Services, Integrium may receive from Sponsor, or otherwise acquire, certain
Confidential, Proprietary, and/or Trade Secret Information which is the property
of Sponsor (“Confidential Information”). Confidential Information shall include
without limitation the Investigator’s brochure, the Protocol, the data recorded
during the Study and data, formulae and information on the Study drug. For
purposes of this Agreement, Confidential Information shall be understood to
include all written or electronically transferred information received from
Sponsor by Integrium, and unless expressly described in this section 6.1 such
written material shall be marked “Confidential.” Confidential Information which
is disclosed orally shall be deemed confidential if it is confirmed to be
confidential by a writing provided to Integrium by Sponsor within a reasonable
amount of time following oral disclosure or if such information is known or
reasonably should be known by Integrium to be deemed to be Confidential
Information (even without such written confirmation). Integrium hereby warrants
and affirms that it shall neither use nor disclose Confidential Information for
any purpose other than as is specifically allowed by this Agreement.

 

6.2Integrium shall disclose Confidential Information only to such of its
employees or third parties (approved by Sponsor in writing) as may reasonably be
required to assist Integrium in the performance of this Agreement and who have
agreed to be bound by confidentiality and non-use terms and conditions similar
to those in this Agreement. In the event of such disclosure, Integrium shall
advise its employees, of the confidential nature of the information and shall
instruct them to take all necessary and reasonable precautions to prevent the
unauthorized use or disclosure thereof at least consistent with those
precautions undertaken by Integrium hereunder.

 

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6.3Upon the expiration or termination of this Agreement, Integrium shall either
destroy or return to Sponsor all tangible and electronic forms of Confidential
Information, including any and all copies and/or derivatives of Confidential
Information made by Integrium (or Integrium’s employees or agents), as well as
any writings, drawings, specifications, manuals or other printed material made
by Integrium (or Integrium’s employees or agents) and based on, or derived from,
Confidential Information; provided, however, that Integrium shall retain all
information it is required by law to retain. Such information shall be retained
for the amount of time required by law using the same amount of care and
diligence to protect Sponsor’s information as it uses to protect its own
confidential information but in any case not less than reasonable care and
diligence.

 

6.4The foregoing obligations shall not apply to Confidential Information to the
extent that it: (a) is or becomes generally available to the public other than
as a result of a disclosure by the receiving party; (b) becomes available to the
receiving party on a non-confidential basis from a source which is not
prohibited from disclosing such information; (c) was developed independently of
any disclosure by the disclosing party or was known to the receiving party prior
to its receipt from the disclosing party, as shown by contemporaneous written
evidence; or (d) is required by law or regulation to be disclosed (in which case
notice of such disclosure shall be given promptly to Sponsor and Integrium shall
reasonably cooperate with Sponsor in seeking to obtain assurances that any such
information will be treated confidentially).

 

6.5Integrium shall not disclose, or otherwise make public, the terms of this
Agreement, except as may be necessary to secure enforcement of the terms of this
Agreement or in response to a lawful subpoena or to comply with applicable
regulations.

 

6.6All of Integrium’s obligations set forth in this Article 6, including the
obligations of confidentiality and non-use, shall continue through the term of
this Agreement and shall survive for a period of ten (10) years following the
expiration or termination of this Agreement.

 

7.Conflicts of Interest

 

7.1Integrium hereby warrants and represents that it has advised Sponsor, prior
to the date of signing of this Agreement, of any relationship with any third
parties, including competitors of Sponsor, which would prevent Integrium from
performing the Services contemplated by this Agreement in accordance with the
legal and ethical standards set out herein or as otherwise mandated by
applicable law.

 

7.2Integrium undertakes to advise Sponsor of any such relationships that might
arise during the Term of this Agreement. In the event such a relationship
arises, the parties will discuss in good faith options to minimize or eliminate
possible effects of such conflicts of interest.

 

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8.Independent Contractor

 

8.1The parties hereto agree that Integrium is being retained and shall perform
as an “Independent Contractor”. Neither Integrium nor any of its employees
performing Service’s, shall be employees of Sponsor, it being understood and
agreed that Integrium is an independent contractor for all purposes and at all
times. All matters of compensation and benefits and terms of employment for
Integrium’s employees shall be solely a matter between Integrium and its
employees. Nothing contained herein shall be deemed or construed to create
between the parties hereto a partnership or joint venture or employment
relationship. No party shall have the authority to act on behalf of any other
party, or to commit any other party in any manner or cause whatsoever or to use
any other party’s name in any way not expressly authorized by this Agreement. No
party shall be liable for any act, omission, representation, obligation or debt
of any other party, even if informed of such act, omission, representation,
obligation or debt.

 

8.2It is further understood that all Integrium services will be performed in
accordance with Integrium’s SOPs; provided, however, that in the event that the
performance of such services according to such SOPs conflict with the terms of
this Agreement, performance of such services shall follow the terms of this
Agreement.

 

8.3Integrium acknowledges and agrees that its employees are not eligible to
participate in any benefits programs offered by Sponsor to its employees, or in
any pension plans, profit sharing plans, insurance plans (including but not
limited to, worker’s compensation insurance), or any other employee benefit or
perquisite plans offered from time to time by Sponsor to its employees or to
receive Sponsor stock directly from Sponsor or its officers, directors, or
employees.

 

8.4Nothing contained in this Agreement shall be construed as making the parties
joint venturers or as granting to either party the authority to bind or contract
any obligations in the name of or on the account of the other party or to make
any representations, guarantees or warranties on behalf of the other party
except to the extent such authority is expressly provided in writing and agreed
by the parties.

 

9.Tax Reporting and Payment

 

9.1Integrium acknowledges and agrees that it shall be solely responsible for
paying the appropriate amount of all federal, state and local taxes with respect
to all compensation paid to Integrium pursuant to this Agreement, and that
Sponsor shall have no responsibility whatsoever for withholding or paying any
such taxes for or on behalf of Integrium.

 

9.2Integrium further agrees to indemnify and hold Sponsor harmless from and
against any and all damages, losses, expenses, or penalties arising from or in
connection with any claim brought by any federal, state or local taxing
authority with regard to Integrium’s failure to pay required taxes or failure to
file required forms with regard to compensation paid to Integrium by Sponsor
pursuant to this Agreement.

 

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10.Ownership, Disclosure and Transfer of Developments and Study Data

 

10.1Sponsor acknowledges that Integrium possesses certain computer technical
expertise, software and methodologies for administration of clinical trials,
data collection, data management and statistical analyses methods which have
been independently developed by Integrium without the benefit of any information
provided by Sponsor. Sponsor and Integrium agree that any computer software
programs, methodologies or other formulae or analyses or methodologies developed
by Integrium in the administration and the conduct of clinical trials used by
Integrium under or during the term of this Agreement are the product of
Integrium’s technical expertise possessed and developed by Integrium prior to
the date of this Agreement and remain the sole property of Integrium and Sponsor
agrees that such technology is commercially valuable to Integrium and Sponsor
agrees not to disclose such technology to any other party without Integrium’s
prior written consent.

 

10.2All written materials and other works which may be subject to copyright and
all patentable and un-patentable inventions, discoveries, data, and ideas
(including but not limited to any computer software) which are made, conceived
or reduced to practice or written by Integrium or Integrium’s employees or third
party contractors authorized by Integrium pursuant to the terms hereof and which
are based upon or arise from the Services performed by Integrium specifically
for Sponsor (“Developments”) shall become Sponsor’s exclusive property, and may
be used by Sponsor as Sponsor deems appropriate in its sole discretion without
any obligation of any nature (including financial, reporting, accounting or
otherwise) to Integrium. Integrium, by signing this Agreement, expressly agrees
to Sponsor’s ownership of all Developments, and represents and warrants that it
has appropriate provisions in its agreements with third party contractors
approved to provide services hereunder that would enable Integrium to meet the
obligations set out in this Article 10.

 

10.3Integrium agrees to hold all Developments in strict confidence in accordance
with Article 6 of this Agreement.

 

10.4Integrium shall disclose promptly to Sponsor each Development and, upon
Sponsor’s request and at Sponsor’s expense, Integrium shall assist Sponsor, or
its designees, in filing patent or copyright applications in any country in the
world. Each copyrightable work, to the extent permitted by law, shall be
considered a work made for hire and the authorship and copyright of the work
shall be in Sponsor’s name and, if not so considered, Integrium hereby assigns
to Sponsor all of Integrium’s rights, title, and interests in such works, and
agrees to the waiver of all moral rights therein - to the extent that same may
exist. Integrium shall execute or cause to be executed by the inventor(s) or a
duly authorized agent of Integrium, as the case may be, all papers and do all
things which may be necessary or advisable, in the opinion of Sponsor, to
prosecute such applications and to vest in Sponsor, or its designee, all the
right, title and interest in and to the Developments.

 

10.5To avoid doubt, Integrium acknowledges and agrees that Sponsor and its
licensors retain all right, title and interest in and to the Confidential
Information, the Investigator’s brochure, the Protocol, and all rights and
information underlying and related to the Study drug, and that no license
(whether express or implied) to any of the foregoing is granted to Integrium
under this Agreement.

 

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10.6Upon the expiration or termination of this Agreement, Integrium shall
transfer to Sponsor all Developments including any and all copies and/or
derivatives hereof, made by Integrium (or Integrium employees) as well as any
writings, drawings, specifications, manuals or other printed material made by
Integrium (or Integrium employees or contractors), to the extent such
Development is not already transferred prior to expiration or termination.
Notwithstanding the reason for expiration or termination of this Agreement,
Integrium shall under no circumstances be entitled to retain Confidential
Information.

 

10.7All data developed relating to the Study shall be the sole and exclusive
property of Sponsor, and Sponsor may use all data relating to the Study for any
lawful purpose, including but not limited to submission to the FDA or other
regulatory agencies. All agreements with Investigators and/or Trial Sites shall
provide for the foregoing rights of Sponsor.

 

10.8Sponsor’s authorised representative(s) and, to the extent permitted by law,
regulatory authorities may, during regular business hours, arrange in advance
with Integrium and/or the respective Principal Investigator(s) and/or Trial
Site(s) to inspect all data and work products relating to the respective Study
and to examine Integrium’s facilities required for performance of this
Agreement.

 

11.Relationship with Investigators and Third Party Contractors

 

11.1If this Agreement requires Integrium to contract with investigators or
investigative sites (collectively, “Investigators”), then any such contract
shall be in a form mutually acceptable to Integrium and Sponsor. If an
Investigator requests any material changes to such form effecting Sponsor’s
rights, Integrium shall submit the proposed change to Sponsor, and Sponsor shall
promptly review, comment on and/or approve such proposed change(s). The parties
acknowledge and agree that Investigators shall not be considered the employees,
agents, or subcontractors of Integrium or Sponsor, and that Investigators shall
exercise their own independent medical judgement. Integrium’s responsibilities
with respect to Investigators shall be limited to those responsibilities
specifically set forth in this Agreement and any amendments hereto.

 

11.2It is hereby agreed that Exhibit 3 (the “Study Budget and Payment Schedule”)
represents the entire consideration that will be paid by Sponsor to Integrium on
behalf of the Study, and that the Sponsor will not pay directly or indirectly to
any third party, including Investigators, and/or any other third party vendors
(IRBs, labs, meeting planners, subcontracting CROs, IVRS, etc.), any amount that
is not included in Exhibit 3. Sponsor acknowledges that Integrium shall not be
responsible for any Study timeline delays as a result of site enrollment delays
due to lack of payment or late payment from Sponsor. Integrium warrants that all
up-front and advance payment or any monies made by Sponsor to Integrium will be
allocated only to the Sponsor study specified on the invoice and will not be
used for any other purposes. Integrium will provide Sponsor with a monthly
pass-through reconciliation report indicating the status of these funds.
Notwithstanding anything contained herein to the contrary, Sponsor agrees to
indemnify and hold Integrium harmless for any and all claims from any sites and
3rd Party Vendors for unpaid invoices submitted to Sponsor.

 

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11.3Sponsor agrees that, although Integrium will assume responsibility for
disbursing fees and/or expenses to Investigators, and Third Party Contractors,
Integrium is not liable for payment to Investigators and Third Party Contractors
until Sponsor has pre-paid Integrium in advance for these fees and expenses.
Upon contract execution of this Agreement, Sponsor agrees to provide the
start-up and vendor advance requirements in accordance with Exhibit 4, Payment
Schedule.

 

11.4Reserved

 

11.5Sponsor acknowledges and agrees that Integrium will not be responsible for
delays in a Study or Project to the extent that such delays are caused by
Sponsor’s failure to make adequate pre-payment for Investigators’ services.
Sponsor further acknowledges and agrees that payments for
Investigator’s/vendors’ services are pass-through payments at actual costs to
Third Party Contractors and are separate from payments for Integrium’s Services.
Sponsor agrees that it will not withhold Investigator payments except to the
extent that it has reasonable questions about the services performed by a
particular Investigator.

 

12.Indemnification

 

12.1Sponsor hereby agrees to indemnify, defend, and hold Integrium, and its
respective agents, servants, employees, officers, and directors (“Integrium
Indemnities”) harmless from and against any and all losses, costs, damages,
expenses, claims, actions, liability, and/or suits (including court costs and
reasonable attorney fees) (“Liabilities”) suffered or incurred by Integrium or
any of the foregoing as a result of personal injury to or death of a participant
in any Study, and such personal injury or death arises from or is, by
unappealable judgment or binding settlement between the parties, attributed to:
(a) a claim of product liability or claim arising from the design, production,
manufacture, or instructions for use of any Study Product; (b) a claim of strict
liability in tort; (c) the design of the Study; and (d) Sponsor’s negligence
with respect to performance of its obligations under this Agreement; provided,
however, that if a claim with respect to the matters set forth in this Section
12.1 hereof arises in whole or in part from Integrium’s negligence or
intentional misconduct or fraud, then the amount of Claim that Sponsor shall
indemnify Integrium pursuant to this Section 12.1 shall be reduced by an amount
in proportion to the percentage of Integrium’s responsibilities for such Claim
as determined by a court of competent jurisdiction in a final and non-appealable
decision or in a binding settlement between the parties. Under no circumstances
shall Integrium be liable for any Third Party Contractor’s (i) adherence to the
Study Protocol, (ii) adherence to project specifications or the Study timeline,
(iii) breach of contract, (iv) the negligence or willful misconduct, or (v) any
infringement, misappropriation or violation by Third Party Contractors of any
right of any other party.

 

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12.2Integrium hereby agrees to indemnify, defend, and hold Sponsor and its
respective affiliates, employees, directors, agents, approved subcontractors and
consultants (“Sponsor Indemnitees”) harmless from and against any and all
Liabilities suffered or incurred by and Sponsor Indemnitee arising out of (a)
any Integrium Indemnitee’s error, omission, gross negligence or willful
misconduct, or (b) any breach of any covenant or warranty, or the inaccuracy of
any representation of Integrium in this Agreement, or (c) Integrium’s failure to
comply with the terms of this Agreement.

 

12.3Integrium Indemnitees agree: (a) to promptly notify Sponsor of any such
Liability or Liabilities; (b) to cooperate fully in the handling of such
Liability or Liabilities and, in the event of litigation, to attend hearings and
trials and assist in securing and giving evidence, and obtaining the attendance
of necessary and proper witnesses, and (c) to Sponsor’s control of the defense
and settlement, with Integrium’s consent which shall not be unreasonably
withheld, of all Liability or Liabilities by Sponsor. Sponsor will reimburse
Integrium for all reasonable expenses incurred at Sponsor’s request in
connection with this Section 12.2 (b) except to the extent and in the proportion
that Integrium is responsible under 12.1 Sponsor shall carry out the management
and defense of such claims or suits at their own expense.

 

12.4In the event that a patient participating in a Study suffers an illness or
injury that the Investigator(s) and Sponsor determine to be directly associated
with Study participation, and for which Sponsor would be obligated to indemnify
Integrium under section 12.1, then – provided such illness or injury is not
excluded by Sponsor’s insurance policy -Sponsor shall pay all medical and
hospital expenses directly associated with the medical treatment of such adverse
reaction which are in excess of that portion covered by the patient’s own
insurance. In the event diagnostic procedures are required to determine the
etiology of the patient’s symptoms, Sponsor shall pay the reasonable expense of
such diagnostic workup without regard to the final diagnosis, but up to the
amount covered by the Sponsor’s insurance policy and in accordance with its
terms.

 

13.Limitation of Liability; Damages

 

13.1Except in the case of gross negligence, willful misconduct, fraud or
non-adherence to the Protocol, neither Integrium, nor its affiliates, nor any of
its or their respective directors, officers, employees or agents shall have any
liability of any type (including, but not limited, to contract, negligence, and
tort liability), for any special, incidental, indirect or consequential damages,
including, but not limited to the loss of opportunity, loss of use, or loss of
revenue or profit, in connection with or arising out of this Agreement, or any
service order, even if such damages may have been foreseeable to Integrium. In
addition, except in the case of gross negligence, willful misconduct, fraud or
non-adherence to the Protocol, in no event shall the collective, aggregate
liability (including, but not limited to, contract, negligence and tort
liability) of Integrium and its affiliates and its and their respective
directors, officers, employees and agents under this Agreement or any service
order hereunder exceed the CRO Service Fees Grand Total amount set out in the
Study Budget.

 

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13.2For Failure to Perform. In the event that the Services provided hereunder
(or any portion thereof) do not meet the specifications or other performance
criteria agreed to by Integrium and Sponsor in writing, then Integrium will, at
Sponsor’s option, promptly (i) re-perform such Services at Integrium’s cost, or
(ii) refund to Sponsor all amounts paid by Sponsor to Integrium in connection
with such Services.

 

13.3Except in the case of gross negligence, willful misconduct or fraud, neither
Sponsor, nor its affiliates, nor any of its or their respective directors,
officers, employees or agents shall have any liability of any type (including,
but not limited, to contract, negligence, and tort liability), for any special,
incidental, indirect or consequential damages, including, but not limited to the
loss of opportunity, loss of use, or loss of revenue or profit, in connection
with or arising out of this Agreement, or any service order, even if such
damages may have been foreseeable to Sponsor.

 

14.Insurance

 

14.1Each party will maintain, for the duration of this Agreement, insurance in
an amount reasonably adequate to cover its obligations under this Agreement and
any and all Service Orders then in effect, and, upon request, each party will
provide to the other party a certificate of insurance showing that such
insurance is in place.

 

14.2Sponsor will supply Integrium with the Clinical Trial Insurance Certificate
for each Study covered under a Service Order prior to commencement of subject
screening for each Service Order. Integrium will not be responsible for
enrollment delays due to Sponsor’s delay in providing said Certificate.

 

15.Termination

 

15.1In the event that a party hereto shall commit a material breach of this
Agreement, the other party hereto shall have the right to terminate this
Agreement immediately unless the breaching party can cure its breach and provide
full performance within thirty (30) days of notice to it that a material breach
has been declared. Upon termination of this Agreement, the non-breaching party
shall have no further obligation to the breaching party, other than for Sponsor
to pay for Services performed by Integrium as of the date of such termination
and any rights and duties which the parties expressly stated herein as surviving
termination.

 

15.2Sponsor may terminate this Agreement at any time by giving Integrium thirty
(30) days written notice of such termination. If Sponsor should terminate
pursuant to this Article 15.2, Sponsor will pay for all Service units performed
up to the point of termination in accordance with the Budget, as well as costs
reasonably incurred for the Services and which Integrium is unable to cancel
(for the avoidance of doubt, Sponsor shall be responsible for any and all 3rd
Party Vendor cancellation fees due upon Study cancellation), and all
administrative costs incurred in the conduct of this Agreement up to the point
of termination for those Services which are necessary to be performed for
patient safety, government requirement compliance and/or expressly requested by
Sponsor; provided, however, that no amounts shall be required to be paid which
are in excess of the corresponding amounts set forth for such activities in this
Agreement. Integrium shall use its best efforts to minimize the costs incurred
following its receipt of notice of such termination.

 

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15.3Either party may terminate this Agreement upon receipt of written notice to
the other party and regard the other party as in breach of this Agreement, if
the other party becomes insolvent, makes a general assignment for the benefit of
creditors, files a voluntary petition of bankruptcy, suffers or permits the
appointment of a voluntary petition of bankruptcy, suffers or permits the
appointment of a receiver for its business or assets, or becomes subject to any
proceeding under any bankruptcy or insolvency law, whether domestic or foreign,
or has wound up or liquidated, voluntary or otherwise. In the event that any of
the above events occur, that party shall immediately notify the other, in
writing, of its occurrence.

 

15.4Upon receipt of notice of termination of this Agreement by either party: (i)
Integrium will, as soon as reasonably practicable discontinue providing the
applicable Services, except to the extent reasonably required to safely close
out a Study or to transfer the remaining Services to another Service Provider
selected by Sponsor, and (ii) Integrium will terminate or, if requested by
Sponsor, assign existing 3rd Party obligations to the extent cancelable or
assignable, as applicable. Any amounts paid by Sponsor which exceed the amounts
owed to Integrium as of expiration or termination of this Agreement shall be
refunded to Sponsor within thirty (30) days after expiration or termination. Any
amounts owed by Sponsor, including 3rd Party Vendor cancellation fees, shall be
paid to Integrium within thirty (30) days after expiration or termination.

 

16.Personnel Recruitment

 

16.1Neither Sponsor nor Integrium will solicit or make offers of employment to
or enter into consultant relationships with employees or consultants of the
other party if such person was involved, directly or indirectly, in the
performance of this Agreement, at any time during the term of this Agreement;
provided, however, that nothing contained herein will prevent a party from
hiring any such employee or consultant who responds to a general hiring program
conducted in the ordinary course of business or who approaches such party on a
wholly unsolicited basis.

 

17.Reserved

 

18.Miscellaneous Provision

 

18.1Assignment. This Agreement may not be assigned by either party without the
prior written consent of the other party, except that either of the parties may
assign this Agreement to a successor in connection with the merger,
consolidation or sale of all or substantially all of its assets. No assignment
whether consensual or permissive shall relieve either party of its
responsibility for performance of its obligations under this Agreement.

 

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18.2Complete Agreement. This Agreement, together with its exhibits and Change
Orders then in effect, supersedes all prior Agreements and understandings
between the parties related to the subject matter of this Agreement.

 

18.3Waiver. No waiver by Sponsor with respect to any breach or default or of any
right or remedy, and no course of dealing by Sponsor shall be deemed to
constitute a continuing waiver of any other breach or default or of any other
right or remedy, unless such waiver be expressed in writing, signed by Sponsor.
No payment made by Sponsor shall be considered as acceptance of satisfactory
performance of the Services, or as in any way relieving Integrium from its full
responsibility pursuant to this Agreement.

 

18.4Amendment. This Agreement may not be altered, changed or amended except in
writing signed by each of the parties hereto.

 

18.5Survival. The provisions of this Agreement dealing with confidentiality,
independent contractor, ownership of developments, indemnification, limitations
of liability, termination, governing law and survival shall survive the
expiration and/or termination of this Agreement.

 

18.6Severability. In the event that any provision of this Agreement is held
illegal or invalid for any reason, such provision shall not affect the remaining
parts of this Agreement, but this Agreement shall be construed and enforced as
if that illegal and invalid provision had never been inserted herein.

 

18.7Extraordinary Relief. In the event of the actual or threatened breach by
Integrium of any of the terms of the Articles 6, 7, and 11 hereof, Sponsor shall
have the right to specific performance and injunctive relief. The remedies in
this paragraph are in addition to all other remedies and rights available at law
or in equity.

 

18.8Force Majeure. Performance of this Agreement by each party shall be pursued
with due diligence in all requirements hereof; however, neither party shall be
liable for any loss or damage for delay or nonperformance due to causes not
reasonably within its control. In the event of any delay resulting from such
causes, the time for performance and payment hereunder shall be extended for a
period of time necessary to overcome the effect of such delays. In the event of
any delay or nonperformance caused by such uncontrollable forces, the party
affected shall promptly notify the other in writing of the nature, cause, date
of commencement thereof, and the anticipated extent of such delay, and shall
indicate whether it is anticipated that the completion date of the Agreement
would be affected thereby.

 

18.9Captions and Headings. The captions, numbering and headings in this
Agreement are for convenience and reference only, and they shall in no way be
held to explain, modify, or construe the meaning of the terms of this Agreement.

 

18.10Counterpart Originals. This Agreement may be executed in any number of
counterparts, each of which, when executed, shall be deemed to be an original
and all of which together shall constitute one and the same document.

 

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18.11Governing Law. It is understood and agreed that this Agreement shall be
governed by the laws of the State of Delaware in all respects of validity,
construction and performance without regard to its conflict of laws rules.

 

18.12Arbitration. Any controversy or claim arising out of or relating to this
Agreement, or the breach thereof, may be submitted to binding arbitration under
the auspices of, and in accordance with, the then existing rules of JAMS, in a
forum selected by the party to whom a request for arbitration is directed.
Notwithstanding the foregoing, either party may seek injunctive or equitable
relief from any court of competent jurisdiction.

 

18.13Notices. Except as otherwise provided, all communications and notices
concerning payments required under this Agreement shall be mailed by certified
mail, return receipt requested postage prepaid, or sent by Federal Express or
telecopy to the addresses set forth below, or to such other addresses as the
parties from time to time specify in writing

 

If to Integrium for contractual matters:

 

Integrium, LLC

100 East Hanover Ave., Suite 401

Cedar Knolls, NJ 07927

Attn: Jessica Coutu, Sr. VP Clinical Operations

 

If to Integrium for financial matters:

 

Integrium, LLC

14351 Myford Road, Suite A

Tustin, CA 92780

Attn: David Hyman, Financial Controller

 

If to Sponsor: Oramed Ltd.

Hi-Tech Park 2/5 Givat-Ram

P.O. Box 39098

Jerusalem 91390, Israel

Attn: Dr. Miram Kidron

 

(Remainder of Page Intentionally Left Blank)

 

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IN WITNESS WHEREOF, the parties hereto have executed, or have caused their duly
authorized representatives to execute, this Agreement as of its initial
effective date.

 

For and on behalf of   For and on behalf of     Integrium, LLC   Oramed Ltd.    
            /s/ Jessica Coutu   /s/ Nadav Kidron   /s/ Josh Hexter By: Jessica
Coutu   By: Nadav Kidron   Josh Hexter Title:  Sr. Vice President,
Clinical Operations   Title: CEO   COO               Date: September 2, 2020  
Date: September 2, 2020    

 

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Integrium/ Oramed

 

Exhibit 1

 

Protocol Number: ORA-D-013-1

Version: 1

Date: 29 JUL 2020

 

 

 

 

 

 

 

 

(Remainder of Page Intentionally Left Blank)

 

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Integrium/Oramed

 

Exhibit 2

 

Study Specifications

 

 

 

 

 

 

 

(Remainder of Page Intentionally Left Blank)

 

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Project Identifiers   Sponsor Company Oramed Ltd. Protocol Number ORA-D-013-1
Protocol Title A Double-Blinded, Placebo-controlled, Double Dummy, Multi-center
Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of ORMD-0801 in
Subjects with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on One,
Two or Three Oral Glucose-lowering Agents Investigational Product(s) ORMD-0801
Indication Type 2 Diabetes Mellitus Therapeutic Area Metabolic Study Phase III
Sponsor Country Israel Country Locations US     Study Assumptions   Subjects   #
Subjects Screened 1250 % Screen Failure Rate 46% # Screen Failures 575 #
Subjects Entering Treatment Phase 675 % Early Termination Rate 25% # Early
Terminations 169 # Subjects Complete 506 Sites   # Sites Identified 80 Total
Sites 75 # Central IRB Sites 73 # Local IRB Sites 2 Enrollment   # Screened/site
16.67 # Screened/site/week 0.43 # Randomized/site 9.00 # Randomization Rate (per
site/ month) 1.00 Third Party Vendors   Meeting Planner 1 Central IRB 1 Central
Lab 1 CGM/Glucometer Vendor 1 - Contracted by Sponsor Product Packaging &
Distribution 1 - Contracted by Sponsor IWRS 1 - Contracted by Sponsor

 

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Project Meetings # Meetings Assumptions Investigators’ Webcast Meeting 3 Assumes
three 3-hour Investigators’ WebEx meetings Launch Meeting 1 Assumes 6-hour
launch Meeting Sponsor Team Teleconferences 81 Assumes calls will be every other
week for the duration of the study Internal Team Teleconferences 6 Monthly for
the first months CRA Training Teleconferences 1 Assumes a 3-hour CRA training
teleconference. CRA Teleconferences 12 Assumes monthly from FPFV to Database
Lock     Monitoring Assumptions   # CRAs 12 # Pre-Study Selection Visits 56 #
Initiation Visits 75 # In Person Site Initiation Visits 70 # Remote Site
Initiation Visits 5 # Interim Monitoring Visits   Monitoring Interval (Maximum -
weeks) Assumed every 6-8 weeks dependent upon enrollment # Interim Monitoring
Visits/site 12 # Additional Days on-site/site 1 # 1-day Interim Monitoring
Visits 900 # Additional Days 75 # Close-out Visits 75     Safety Assumptions  
SAE rate (%) 6% Estimated # SAEs 40     Data Management   CRF pgs per randomized
patient 115 Unique CRFs/Subject 53 Standard 24 Non-Standard 29 Non-Unique
CRFs/Subject 62 Standard 53 Non-Standard 9 CRF pgs per early term 86 CRF pgs per
screen failure 29 Total CRF Pages 89399 Complete subjects 58190 Early Terms
14534

 

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Screen Failures 16675 Total DM Datasets 20 Total Edit Checks 300 Estimated #
Total Queries 17880 Estimated # Queries/Patient (1/5 pages) 26.49 Manual Coding
  # Medical History/Subject 2 # ConMeds/Subject 2 # AEs/Subject 2 Data Transfers
  # Sponsor Transfers 2   test,  final #  Lab Transfers 23   test, monthly,
final # Central CGM Reader Transfers 9   test, quarterly, final # IWRS Transfers
2   prior to primary lock and final lock     Statistical Analysis The following
assumptions are estimates. The total number of TLGs will be defined upon the
finalization of the Statistical Analysis Plan. An amendment to the budget will
be issued at that time, if applicable. # SAS Datasets 22 Estimated Tables   #
Standard and Non-Standard Repeat 70 # Non-Standard Unique 0 Estimated Listings  
# Standard and Non-Standard Repeat 40 # Non-Standard Unique 0 Estimated Graphs  
# Standard and Non-Standard Repeat 20 # Non-Standard Unique 0 Exploratory Output
  # Exploratory Tables 0 # Exploratory Listings 0 # Exploratory Graphs 0 pK
Parameters 0 Post-hoc Analysis 200 EDC - ClinPlus   Number of Screens   Unique
Screens 53 Redundant Screens 62 Site Patient Activity Duration (Months) 13.1
Enrollment Duration (Months) 9 Server Activity Duration (Months) 15 Usage
Fee/Help Desk Fees           Product Usage Fee/Month $2,800 Integrium Archiving
Pricing   CD/DVD per site $100 Clinical Study Report The budget is based on one
draft and one final version of the CSR, assuming there will be no hyperlinking.
If hyperlinking and/or additional versions of the CSR are requested, they will
be provided at the study hourly rate for the actual additional hours.

 

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Project Timeline                         Project Activity  Date  Month #   Week
#  Study Start Date  January 15, 2020   0.0    0.0  Create Site Feasibility
Questionnaire  January 17, 2020   0.1    0.3  Draft Protocol Date  April 27,
2020   3.4    14.7  Identify 75 sites  May 25, 2020   4.3    18.7  Final
Protocol Date  June 29, 2020   5.5    23.7  Submission of Protocol to FDA  May
4, 2020   3.6    15.7  Pre-study Visits Complete  July 23, 2020   6.3    27.1 
Response from FDA  June 24, 2020   5.3    23.0  Submission of Revised Protocol
to FDA  July 31, 2020   6.5    28.3  Response from FDA  September 29, 2020 
 8.5    36.9  Initial Paper Representation of eCRF  August 14, 2020   7.0  
 30.3  Final Paper Representation of eCRF  August 21, 2020   7.2    31.3 
Programming of Database Complete  October 5, 2020   8.7    37.7 
UAT/Pre-production Audit of Database Complete  October 19, 2020   9.1    39.7 
Investigators’ Webcast Meeting  October 19, 2020   9.1    39.7  Drug Available
at Sites  November 2, 2020   9.6    41.7  First Patient Screened  November 3,
2020   9.6    41.9  First Patient Randomized to 26w Treatment Phase  November
24, 2020   10.3    44.9  First Patient Enters 26w Extension Phase  May 25, 2021 
 16.3    70.9  First Patient Last Visit  December 7, 2021   22.8    98.9  Last
Patient Screened  August 3, 2021   18.6    80.9  Last Patient Randomized to 26w
Treatment Phase  August 24, 2021   19.3    83.9  Last Patient Completes 26w
Treatment Phase  February 22, 2022   25.3    109.9  Last IMV 26w Treatment
Phase  March 22, 2022   26.2    113.9  Primary Database Lock  May 17, 2022 
 28.1    121.9  Last Patient Enters 26w Extension Phase  February 22, 2022 
 25.3    109.9  Last Patient Last Visit  September 6, 2022   31.8    137.9  Last
IMV  October 4, 2022   32.7    141.9  Final Database Lock  November 29, 2022 
 34.5    149.9  Draft Final TLGs  December 6, 2022   34.8    150.9  Final TLGs 
December 20, 2022   35.2    152.9  Draft CSR  January 17, 2023   36.1    156.9 
Final CSR  February 14, 2023   37.1    160.9  CRO End Date  February 24, 2023 
 37.4    162.4  Total Project Duration (Months)  37.4                         
   Months   Weeks    Phase  Start-up  9.6   14.3    I  Enrollment  9.0   39.1  
 II  Treatment  13.1   57.0    III  LPLV-DBL  2.8   12.0    IV  DBL-CRO End 
2.9   12.4    V     37.4   134.8      

 

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Integrium/Oramed

 

EXHIBIT 3

 

Study Budget

 

   STUDY START-UP  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 1  Project
Management (Start Up)  [**]  9.6  Month  [**] 2  Develop/Finalize Project
Management Plan  [**]  1  Plan  [**] 3  Project Launch Webcast Meeting/Training 
[**]  1  Meeting  [**] 4  Study Materials Management  [**]  75  Site  [**] 5 
Source Documentation Development  [**]  1  Total  [**] 6  Site Identification 
[**]  81  Site  [**] 7  Pre-study Site Evaluation Visit  [**]  56  Visit  [**]
8  Develop/Finalize CRA Monitoring Plan  [**]  2  Plan  [**]    Data Management
Plan (“DMP”)  [**]  1  Total  [**] 9  Regulatory Document Collection - Start Up 
[**]  75  Site  [**] 10  Investigator Budget/Contract Negotiations  [**]  75 
Site  [**] 11  Webcast Investigators’ Meeting/Preparation  [**]  3  Meeting 
[**] 12  CRA Training Teleconference  [**]  1  Telecon  [**] 13  Clinical System
Set-Up Configuration & Maintenance  [**]  81  Site  [**]    STUDY START-UP FEES
TOTAL            [**]    EDC STUDY START-UP  UNIT COST  UNITS  MEASURE OF UNIT 
TOTAL 14  eCRF Development  [**]  1  Total  [**] 15  eCRF Completion
Instructions  [**]  1  Total  [**] 16  Edits Specifications and Programming 
[**]  1  Total  [**] 17  Validate/Test Data Entry Screens (UAT)  [**]  1  Total 
[**] 18  Annotate CRF  [**]  1  Total  [**] 19  Clinical Database
Development-SDTM Dataset Creation/Documentation  [**]  1  Total  [**] 20 
Database Design/Validation Specifications  [**]  1  Database  [**] 21  EDC
Kick-Off Meeting  [**]  1  Meeting  [**] 22  Set-up Standard Data Entry Screens 
[**]  1  Total  [**] 23  Training Session  [**]  1  Study  [**] 24  Project
Manage all aspects of EDC start-up  [**]  1  Start-up  [**] 25  Create
Enrollment Screen  [**]  1  Total  [**] 26  Data Export Programming  [**]  20 
Dataset  [**] 27  Register users/maintain passwords for life of study (per user
(4 per site; 6 for sponsor))  [**]  306  Per User  [**]    EDC START-UP FEES
TOTAL           [**]

 

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   CLINICAL MONITORING  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 28  Project
Management (enrollment phase)  [**]  9.0  Month  [**] 29  Project Management
(treatment phase)  [**]  13.1  Month  [**] 30  Project Management Study (LPLV to
DBL)  [**]  2.8  Month  [**] 31  Project Management Study (DBL - CRO end)  [**] 
2.9  Month  [**] 32  Sponsor Team Teleconferences  [**]  81  Telecon  [**] 33 
Internal Team Teleconferences  [**]  6  Telecon  [**] 34  CRA Teleconferences 
[**]  24  Telecon  [**] 35  Trial Master File  [**]  76  Site  [**] 36 
Regulatory Document Maintenance  [**]  1950  Site*Month  [**] 37  Reg. Doc.
Collection - Protocol Amendments  [**]  75  Amendment  [**] 38  Site Initiation
Visits  [**]  75  Site  [**] 39  Remote Site Initiation Visits  [**]  5  Visit 
[**] 40  Site Management, Patient Review, Query Resolution  [**]  1950 
Site*Month  [**] 41  Interim Monitoring Visits - One Day  [**]  900  Visit  [**]
42  Interim Monitoring Visits – Add’l Day On-site  [**]  75  Day  [**] 43 
Close-out Visits  [**]  75  Visit  [**] 44  Site Grant Administration  [**] 
1725  Site*Month  [**]    CLINICAL MONITORING/LOGISTICS SERVICES SUBTOTAL       
   [**]    MEDICAL/SAE MANAGEMENT  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 45 
Medical Management  [**]  25  Month  [**] 46  Create Safety Plan  [**]  1  Plan 
[**] 47  Review Protocol Deviation Log  [**]  25  Month  [**] 48  Tracking
Protocol Waivers  [**]  25  Month  [**] 49  Lab Alert/Patient Review  [**]  25 
Month  [**] 50  Monthly Review of AE Data Listings  [**]  25  Month  [**] 51 
Create Safety Database  [**]  2  Database  [**] 52  SAE Management  [**]  40 
SAE  [**]    MEDICAL/SAE MANAGEMENT SERVICES SUBTOTAL           [**]    DATA
MANAGEMENT  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 53  Data Entry Activities 
[**]  89,399  CRF Pg  [**] 54  Generate/Track/Resolve Queries  [**]  17,880 
Query  [**] 55  Data Cleaning/Manual Listing Review  [**]  675  Patient  [**]
56  Import Other Data  [**]  34  Transfer  [**] 57  Export Data to Sponsor 
[**]  2  Transfer  [**] 58  Manual Coding  [**]  4,050  Manual Code  [**] 59 
Archive Study Records, Database  [**]  1  Database  [**] 60  Data Base Lock
Activities  [**]  2  Total  [**]    DATA MANAGEMENT FEES SUBTOTAL           [**]

 

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   EDC SYSTEM MAINTAINANCE  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 61  Coding
System Set-up [WHO/MEDRA]  [**]  1  User  [**] 62  Third Party Data
Integrations  [**]  39  Transfer  [**] 63  SAS Platform (months)  [**]  37 
Month  [**] 64  Ongoing Support Project Management  [**]  15  Month  [**] 65 
CRF Export Programming (Site Archives, Submission eCRFs)  [**]  1  Total  [**]
66  Provide End of Study Archives to All Sites; 2 Copies to Sponsor  [**]  1 
Total  [**]    EDC SYSTEM SET-UP AND MAINTAINANCE SUBTOTAL           [**]   
BIOSTATISTICAL ANALYSIS  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 67  Draft &
Final Statistical Analysis Plan (SAP)  [**]  1  SAP  [**] 68  Analysis DataSets 
[**]  22  Dataset  [**] 69  Create/Document ADaM (Submission Ready) Datasets 
[**]  22  Dataset  [**] 70  Statistical Programming Deliverables (TLGs)  [**] 
130  T/L/G  [**] 71  Generate/QC TLFs  [**]  152  Appendix  [**] 72  Output
Review/Dry Runs  [**]  3  Dry Run  [**] 73  Post-hoc Analysis Hours  [**]  200 
Hour  [**] 74  Annual IND Listings  [**]  2  Annual IND  [**]    BIOSTATISTICAL
ANALYSIS SUBTOTAL           [**]    MEDICAL WRITING  UNIT COST  UNITS  MEASURE
OF UNIT  TOTAL 75  Finalize Protocol  [**]  1  Protocol  [**] 76 
Develop/Finalize  ICF  [**]  1  Total  [**] 77  Final CSR  [**]  1  Total  [**]
   MEDICAL WRITNG SUBTOTAL           [**]    CRO SERVICE FEES GRAND TOTAL       
   [**]    PASS THROUGH COSTS  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 1 
Pre-study Site Evaluation Visit  [**]  56  Visit  [**] 2a  Site Initiation
Visit  [**]  70  Visit  [**] 2b  Remote Site Initiation Visits  [**]  5  Visit 
[**] 3a  Interim Monitoring Visits - One Day  [**]  900  Visit  [**] 3b  Interim
Monitoring Visits – Add’l Day On-site  [**]  75  Day  [**] 4  Close-out Visits 
[**]  75  Visit  [**] 5  WebEx Investigators’ Meeting Planner  [**]  1  Meeting 
[**] 6  Investigator Grants             6a  # Patients Completed  [**]  506 
Patient  [**] 6b  # Screen Failures  [**]  575  Patient  [**] 6c  # Early
Terminations  [**]  169  Patient  [**]

 

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   PASS THROUGH COSTS  UNIT COST  UNITS  MEASURE OF UNIT  TOTAL 6d  # Rescue
Visits  [**]  34  Visit  [**] 6e  # Unscheduled visits  [**]  34  Visit  [**] 7 
Site: Advertising/Patient Recruitment  [**]  75  Site  [**] 8  Site: Archive
Fees  [**]  75  Site  [**] 9  Site: Database Review Fee  [**]  75  Site  [**]
10  Site: Start-up Costs  [**]  75  Site  [**] 11  Site: Regulatory Fee  [**] 
0  Site  [**] 12  Site: Pharmacy Start-up Fee  [**]  75  Site  [**] 13  Site:
IRB Fees  [**]  2  Total  [**] 14a  Central IRB - Protocol Submission  [**]  1 
Protocol  [**] 14b  Central IRB - Site Submissions  [**]  73  Protocol  [**]
14c  Central IRB annual renewal  [**]  73  Amend.  [**] 14d  Central IRB - Site
Specific Translations  [**]  20  Site  [**] 14e  Central IRB annual renewal 
[**]  73  Site  [**] 14f  Central IRB Closeout Fee  [**]  73  Site  [**] 14g 
Central IRB - Advertising Approval  [**]  73  Site  [**] 15  Estimated Central
Laboratory Fees  [**]  1  Total  [**] 16  Estimated IWRS Fees  [**]  0  Total 
[**] 17  Estimated CGM/Glucometer Fees  [**]  0  Total  [**] 18  EDC Platform
Product Usage  [**]  28  Total  [**] 19  EDC Coding System Integration Fee
[WHO/MEDRA]  [**]  1  Total  [**] 20  End of study archive CDs to sites; 2 to
Sponsor  [**]  77  Total  [**] 21  Regulatory Binders  [**]  76  Binder  [**]
22  Copying/ Printing  [**]  1  Total  [**] 23  Postal & Shipping Fees  [**]  1 
Total  [**]    PASS-THROUGH COSTS TOTAL           [**]    PROJECT’S OVER-ALL
TOTAL COST           $ 21,589,332.07

 

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Integrium, LLC.   Confidential

 

Integrium/Oramed

 

EXHIBIT 4

 

Study Payment Schedule

 

Payment Schedule              Monthly Management Fees  Month   $ Amount  
Verification of Milestone Completion/Deliverables Project Management Fees 
January 2020   [**]   Paid (ORA-D-013 Start-up) Project Management Fees 
February 2020   [**]   Paid (ORA-D-013 Start-up) Project Management Fees  March
2020   [**]   Paid (ORA-D-013 Start-up) Project Management Fees  April 2020 
 [**]   Paid (ORA-D-013 Start-up) Project Management Fees  May 2020   [**]  
Invoiced Monthly Project Management Fees  June 2020   [**]   Invoiced Monthly
Project Management Fees  July 2020   [**]   Invoiced Monthly Project Management
Fees  August 2020   [**]   Invoiced Monthly Project Management Fees  September
2020   [**]   Invoiced Monthly Project Management Fees  October 2020   [**]  
Invoiced Monthly Project Management Fees  November 2020   [**]   Invoiced
Monthly Project Management Fees  December 2020   [**]   Invoiced Monthly Project
Management Fees  January 2021   [**]   Invoiced Monthly Project Management Fees 
February 2021   [**]   Invoiced Monthly Project Management Fees  March 2021 
 [**]   Invoiced Monthly Project Management Fees  April 2021   [**]   Invoiced
Monthly Project Management Fees  May 2021   [**]   Invoiced Monthly Project
Management Fees  June 2021   [**]   Invoiced Monthly Project Management Fees 
July 2021   [**]   Invoiced Monthly Project Management Fees  August 2021 
 [**]   Invoiced Monthly Project Management Fees  September 2021   [**]  
Invoiced Monthly Project Management Fees  October 2021   [**]   Invoiced Monthly
Project Management Fees  November 2021   [**]   Invoiced Monthly Project
Management Fees  December 2021   [**]   Invoiced Monthly Project Management
Fees  January 2022   [**]   Invoiced Monthly Project Management Fees  February
2022   [**]   Invoiced Monthly Project Management Fees  March 2022   [**]  
Invoiced Monthly Project Management Fees  April 2022   [**]   Invoiced Monthly
Project Management Fees  May 2022   [**]   Invoiced Monthly Project Management
Fees  June 2022   [**]   Invoiced Monthly Project Management Fees  July 2022 
 [**]   Invoiced Monthly Project Management Fees  August 2022   [**]   Invoiced
Monthly Project Management Fees  September 2022   [**]   Invoiced Monthly
Project Management Fees  October 2022   [**]   Invoiced Monthly Project
Management Fees  November 2022   [**]   Invoiced Monthly Project Management
Fees  December 2022   [**]   Invoiced Monthly Project Management Fees  January
2023   [**]   Invoiced Monthly Project Management Fees  February 2023   [**]  
Invoiced Monthly Total Monthly Management Fees:   [**]    

 

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Integrium, LLC.   Confidential

 

Monthly Service Fees  Date  % Total Service Budget   % Milestone Service
Budget   $ Amount   Verification of Milestone Completion/Deliverables Contract
Execution  8/31/2020   5.00%   10.13%   [**]   Contract Execution EDC System
Complete  10/19/2020   0.50%   1.01%   [**]   UAT complete 1st Subject
Randomized  11/24/2020   2.50%   5.07%   [**]   Enrollment log 25% Subjects
Randomized  1/26/2021   4.38%   8.87%   [**]   Enrollment log 50% Subjects
Randomized  3/30/2021   4.38%   8.87%   [**]   Enrollment log 75% Subjects
Randomized  6/1/2021   4.38%   8.87%   [**]   Enrollment log 100% Subjects
Randomized  8/24/2021   4.38%   8.87%   [**]   Enrollment log 1st Subject Last
Visit  12/7/2021   3.13%   6.33%   [**]   Enrollment log 25% Subjects Last
Visit  2/8/2022   3.13%   6.33%   [**]   Enrollment log 50% Subjects Last Visit 
4/12/2022   3.13%   6.33%   [**]   Enrollment log Primary Database Lock 
5/17/2022   4.38%   8.87%   [**]   Database Lock 75% Subjects Last Visit 
6/14/2022   3.13%   6.33%   [**]   Enrollment log 100% Subjects Last Visit 
9/6/2022   3.13%   6.33%   [**]   Enrollment log Final Database Lock 
11/29/2022   3.13%   6.33%   [**]   Database Lock Draft Final TLGs  12/6/2022 
 0.29%   0.58%   [**]   Draft Final TLGs Final CSR  12/20/2022   0.44%   0.89% 
 [**]   Draft Final TLGs Total Milestone Based Services:      49.39%   100.00% 
 [**]    

 

Unit Based Payments:
Actual Units Invoiced Monthly  % Total Services Budget   # Units   Unit Cost   $
Amount   Verification of Milestone Completion/Deliverables SAE Management 
 1.22%   40    [**]    [**]   Invoiced monthly as occurred Total Unit Based
Services:    [**]                              Total Services:    [**]    

 

Pass-through expenses  $ Amount   Verification of Milestone
Completion/Deliverables Monitoring Visit Travel Expenses   [**]   Invoiced as
Actuals Monthly Investigator Grants   [**]   Invoiced and Paid in Advance of
Payment to Vendor Site Start-up Costs   [**]   Invoiced and Paid in Advance of
Payment to Sites Site Pharmacy Start-up Costs   [**]   Invoiced and Paid in
Advance of Payment to Sites Site Advertising   [**]   Invoiced as Actuals
Monthly Site Archiving Fees   [**]   Invoiced as Actuals Monthly Central IRB
Fees   [**]   Invoiced as Actuals Monthly Meeting Planner   [**]   Invoiced and
Paid in Advance of Payment to Vendor Central Lab Vendor   [**]   Invoiced and
Paid in Advance of Payment to Vendor EDC Platform Fees    [**]   Invoiced as
Actuals Monthly Copying/Printing/Supplies/Other   [**]   Invoiced as Actuals
Monthly Postal & Shipping Fees   [**]   Invoiced as Actuals Monthly Total
Pass-through Budget:   [**]               Grand Total Budget:  $21,589,332.07  
 

 

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Integrium, LLC.   Confidential

 

Pass Through Advance Payment Schedule

 

    Contract Execution     TBD     Study Total  

Investigators’ Meeting Planner:

80% invoiced start-up payment

20% paid upon final reconciliation

   [**]    [**]    [**] 

Site Start-up Costs:

[**]/site x 75 sites

   [**]    [**]    [**] 

Site Grant Payments:  

Advance Payment = [**]/site X 65 sites

   [**]    [**]    [**] 

Site Pharmacy Start-up Costs:  

[**]/site X 75 sites

   [**]    [**]    [**] 

Central Lab Vendor:

Start-up payment

   [**]    [**]    [**]  Pass-Through Advance Payment   [**]    [**]    [**] 

 

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Integrium, LLC.   Confidential

 

EXHIBIT 5

 

Transfer of Regulatory Obligations

 

TRANSFER OF US FDA REGULATORY OBLIGATIONS FOR INVESTIGATIONAL PHARMACEUTICAL AND
BIOLOGIC PRODUCTS UNDER AN INVESTIGATIONAL NEW DRUG (IND) APPLICATION (21 CFR
312.52 and ICH E6)

 

   

 

Study Drug: ORMD-0801

IND #:      

Protocol Title: A Double-Blinded, Placebo-controlled, Double Dummy, Multi-center
Randomized, Phase 3 Study to Evaluate the Efficacy and Safety of ORMD-0801 in
Subjects with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on One,
Two or Three Oral Glucose-lowering Agents.

 

Pursuant to 21 CFR 312.52 and ICH E6, the following obligation(s) of the
Sponsor, Oramed Ltd. have been transferred to:

 

CRO Name: Integrium, LLC CRO Address: 14351 Myford Road   Tustin, CA 92780

 

              Obligation Assigned to:1 Responsibility   Reference   Integrium  

Oramed

  Third Party Vendor A.   1. Preparation of all or part of an IND application  
312.23 21CFR   N/A   N/A   N/A                             2. Submission of IND
application to FDA, submit all Amendments to FDA       ☐   ☒   ☐                
        B.   Maintain an IND with the following amendments, as necessary:      
                                      1. Preparation of Protocol amendments
(includes new protocols, changes in protocols, adding new investigators)  

312.30 21CFR

  ☐   ☒   ☐                             2. Preparation of Chemistry,
Manufacturing, and Control amendments   312.31 21CFR   ☐   ☒   ☐                
            3. Preparation of Pharmacology and Toxicology amendments   312.31
21CFR   ☐   ☒   ☐                             4. Preparation of Clinical
amendments   312.31 21CFR   ☐   ☒   ☐                             5. 

Safety Reports

(a) Preparation of initial report

(b) Preparation of follow-up reports

(c) Notifications to FDA (phone/fax or written)

(d) Notifications to investigators

  312.32 21CFR  

 

☒

☒

☐

☒

 

 

☐

☐

☐

☐

 

 

☐

☐

☒

☐

                            6. Preparation of Annual Reports   312.33 21CFR   ☐
  ☐   ☒                             7. Preparation of response to request for
information or clinical hold   312.41, 312.42 CFR   ☐   ☒   ☐                  
          8. 

Preparation of letter to withdraw an IND

  312.38 CFR   ☐   ☒   ☐

 

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              Obligation Assigned to:1 Responsibility   Reference   Integrium  
Oramed   Third Party Vendor C.    Preparation and Update Investigative Brochure
 

21 CFR 312.55 (a)

ICH E6 5.12, 7.3

  ☐   ☒                             D.   Selecting investigators and monitors  
21 CFR 312.53   ☒   ☒   ☐                             1. 

Select qualified investigators

(a) Identify qualified investigators/sites

(b) Approve investigators/sites for participation

   
21 CFR 312.53 (a);
ICH E6 5.6.1  

☒

☒

 

☒

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                            2.  Control of drug                       (a) Obtain
required information from investigator (including signed Form FDA 1572, CV)   21
CFR 312.53 (c);
ICH E6 5.14.2, 8.2   ☒   ☐   ☐       (b) Approved investigators for receipt of
drug shipment  

21 CFR 312.53 (b);
ICH E6 5.14.2

  ☒   ☐   ☐       (c) Ship drug to approved investigators  

21 CFR 312.53 (b);
ICH E6 5.14.1, 5.14.4(a)

  ☒   ☐   ☒       (d) Maintain shipment records  

21 CFR 312.57 (a);
ICH E6 5.14.4(b)

  ☒   ☐   ☒                             3. Provide qualified monitors   21 CFR
312.53 (d);
ICH E6 5.18.2   ☒   ☐   ☐                             4.  Informing
investigators                       (a) Review with investigators their
regulatory responsibilities   Guideline for the Monitoring of Clinical
Investigations; ICH E6 5.18.4 (f)(g)   ☒   ☐   ☐       (b) Deliver
investigator’s brochure   21 CFR 312.55 (a);
ICH E6 5.6.2   ☒   ☐   ☐       (c) Inform participating investigators of new
safety information about the study drug   21 CFR 312.55 (b);
ICH E6 5.16.2   ☒   ☐   ☐       (d) Notify participating investigators of all
serious unexpected adverse drug reactions   21 CFR 312.32 (c);
ICH E6 5.17.1   ☒   ☐   ☐                         E.   Review of ongoing
investigations                                             1. Monitoring the
investigation  

21 CFR 312.56

21 CFR 312.56 (a);
ICH E6 5.18.4

  ☒  

☐

  ☐                             2. 

Discontinue investigator participation if not compliant

(a) Notify FDA

(b) Assure disposal or return of investigational drug

  21 CFR 312.56 (b);
ICH E6 5.20  

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☒

☒

 

 

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☐

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                            3. Provide medical expertise to evaluate safety
information   21 CFR 312.56 (c);
ICH E6 5.16.1   ☒   ☐   ☐                             4.  Upon premature
termination or suspension of a trial:   21 CFR 312.56 (d);                  
(a) Notify IRBs or notify investigators of their responsibility to notify IRBs  
ICH E6 5.21   ☒   ☐   ☐       (b) Notify investigators       ☒   ☐   ☐      
(c) Assure disposition of drug from sites to sponsor       ☒   ☐   ☐       (d)
Notify FDA       ☐   ☐   ☒

 

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              Obligation Assigned to:1 Responsibility   Reference   Integrium  
Oramed   Third Party Vendor F.   Trial Data Handling and Reporting              
                             

(a) Manage an independent date safety monitoring committee

(b) Data Management

(c) Statistical plan and/or analysis

(d) Final study report

 

ICH E6 5.5.2

ICH E6 5.5.1

ICH E6 5.5.1

ICH E6 5.5.1

 

NA

☒

☒

☒

 

NA

☐

☐

☒

 

NA

☐

☐

☐

                        G.   Recordkeeping and record retention   21 CFR 312.57
                                      1.  Maintain sponsor records and reports,
other than shipment records (see C.2.d), during the course of the investigation
  21 CFR 312.57 (b), 312.58 (a); ICH E6 5.5.6, 5.5.7, 8   ☒   ☐   ☐    

2. 

 

Archive sponsor records and reports according to applicable regulatory
requirements.  

21 CFR 312.57 (a)(b)(c), 312.58 (a); ICH E6 5.5.8, 5.5.11, 8

 

  ☐   ☒   ☐     3.  Retain reserve samples of the test articles and reference
standards used in bioequivalence or bioavailability studies   21 CFR 312.57 (d);
ICH E6 5.14.5(b)   ☐   ☒   ☐                         H.   Disposition of unused
supply of investigational drug                                           1.  
Assure return of drug from site to sponsor  

21 CFR 312.59; ICH

 

  ☒   ☐   ☒     2.   Conduct final disposition or destruction of drug  

E6 5.14.4 (c)(d), 5.18.4

(c)(iv)(v)

  ☐   ☐   ☒ I.  

Application for FDA approval to export investigational drug

(a) Content

(b) Format

  21 CFR 312.110; 
ICH E6 5.14.2  

☐

☐

 

 

☒

☒

 

 

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☐

 

                        J.  

Obtain investigator financial disclosure information

 

21 CFR 312.53 (c)(4)

                1.   Initial collection prior to study participation       ☒   ☐
  ☐     2.   Responsibility for the one year follow-up financial disclosure
collection shall remain with the Sponsor (one year following the completion of
the study)       ☐   ☒   ☐

 

1If responsibility for an item is shared between Oramed and Integrium, both
boxes will be checked.

 

According to 21 CFR 312.52(b), “A contract research organization that assumes
any obligation of a sponsor shall comply with the specific regulations in this
chapter applicable to this obligation and shall be subject to the same
regulatory action as a sponsor for failure to comply with any obligation assumed
under these regulations.” The assignment of responsibility does not preclude
either the sponsor or the CRO from participating in the requirements of the CFR.

 

Oramed Ltd.

 

    /s/ Miriam Kidron   September 2, 2020     Name:  Miriam Kidron   Date    
Title: CSO     Integrium LLC.                       /s/ Jessica Coutu  
September 2, 2020     Name: Jessica Coutu   Date     Title: Sr. V.P. of Clinical
Operations    

 

 

Page 31