Document:

Document

Exhibit 10.3

TERRA INCOME FUND 6, INC.
550 Fifth Avenue, 6th Floor New York, New York 10036
September 27, 2022 

  Eagle Point Credit Management LLC, as Agent
and each Lender signatory hereto 600 Steamboat Road, Suite 202
Greenwich, CT 06830 Ladies and Gentlemen:
Reference is made to (i) the Credit Agreement, dated as of April 9, 2021 (including all annexes, exhibits and schedules thereto, the “Existing Credit Agreement” and as amended hereby and as may be amended, restated, amended and restated, replaced, supplemented, or otherwise modified from time to time, the “Credit Agreement”), among Terra Income Fund 6, Inc., a Maryland corporation (the “Initial Borrower”), certain funds and accounts managed by Eagle Point Credit Management LLC (“Eagle Point”), as lenders (in such capacity, collectively, the “Lenders”) and Eagle Point as the administrative agent and collateral agent for the Lenders (in such capacity, the “ Agent”), (ii) the Form S-4 Registration Statement of Terra Property Trust, Inc., as filed with the Securities and Exchange Commission on June 24, 2022 (as amended on July 13, 2022, the “TPT S-4”) and (iii) the Proxy Statement/Prospectus, as filed by the Initial Borrower with the Securities and Exchange Commission and mailed to stockholders of the Initial Borrower on dated July 25, 2022 (the “Proxy Statement”). Capitalized terms used herein without definition shall have the meanings set forth in the Credit Agreement.

The Initial Borrower has entered into the Agreement and Plan of Merger, dated as of May 2, 2022 (the “Merger Agreement”), by and among Terra Property Trust, Inc., a Maryland corporation (“TPT”), the Initial Borrower, Terra Merger Sub, LLC, a Delaware limited liability company and a wholly owned subsidiary of TPT (“ Ultimate Borrower”), Terra Income Advisors, LLC, a Delaware limited liability company, and Terra REIT Advisors, LLC, a Delaware limited liability company. Pursuant to the Merger Agreement, and subject to the satisfaction of the closing conditions set forth therein, the Initial Borrower will merge with and into the Ultimate Borrower (the “Merger”), with the Ultimate Borrower continuing as the surviving entity of the Merger. A copy of the Merger Agreement is attached to the TPT S-4, which describes in further detail the transactions contemplated by the Merger Agreement. The Proxy Statement notified the stockholders of the Initial Borrower that, among other things, the Initial Borrower’s board of directors, based on the recommendation of an independent special committee, has approved the Merger.

1.    Waiver and Consent.

The Initial Borrower hereby requests that the Agent and Lenders agree to (i) waive their rights pursuant to Section 2(d)(ii) of the Credit Agreement to receive an offer to repay
			
	

the Loans and all other Obligations under the Credit Agreement in full as of the date of the Merger, and (ii) waive Section 6(m) (Transactions with Affiliates) of the Credit Agreement, solely to the extent the Merger and the related transactions would constitute a breach thereof and for no other purpose (such request by the Initial Borrower under clauses (i) and (ii), collectively, the “Requested Waiver”).

Subject to the satisfaction of the conditions set forth in Section 5 below, the Agent and the undersigned Lenders, constituting all of the Lenders under the Credit Agreement, hereby (A) agree to the Requested Waiver and (B) notwithstanding any other terms or provisions set forth in the Credit Agreement or any other Transaction Document, consent to the Merger and the assumption and assignment by the Ultimate Borrower of all obligations, covenants and agreements of the Initial Borrower under the Credit Agreement and the other Transaction Documents.
2.    Notice Regarding Status as a BDC and REIT.

In connection with the transactions contemplated by the Merger Agreement, the Initial Borrower intends to withdraw its election to be treated as a business development company under the Investment Company Act, as more fully described in the TPT S-4 (the “BDC Election Withdrawal”). The Initial Borrower hereby notifies the Agent in accordance with Section 5(i) (Compliance with Investment Company Act) of the Credit Agreement that the Initial Borrower will approve the BDC Election Withdrawal prior to the consummation of the Merger, and at such time the Initial Borrower will no longer be regulated as a BDC under the Investment Company Act. The Agent hereby acknowledges receipt of the forgoing notice and waives the twenty (20) day notice period for such notice as set forth in Section 5(i) (Compliance with Investment Company Act) of the Existing Credit Agreement.

In addition, the Initial Borrower hereby notifies the Agent in accordance with Section 5(q) (Maintenance of REIT Status) of the Credit Agreement that, upon consummation of the Merger, the Ultimate Borrower will notqualify for taxation as a REIT and, accordingly, a REIT Status Termination Date will have occurred. The Agent hereby acknowledges receipt of the forgoing notice and waives the twenty (20) day notice period for such notice as set forth in Section 5(q) (Maintenance of REIT Status) of the Credit Agreement. For the avoidance of doubt, prior the effectiveness of the Merger, the Initial Borrower will, and after the effectiveness of the Merger, the Ultimate Borrower will, at all times during the term of the Credit Agreement maintain a pass-through tax status.

3.    Amendment.

On the Effective Date, Initial Borrower, the Agent and the Lenders, constituting all of the Lenders under the Credit Agreement, hereby agree that the Existing Credit Agreement shall be amended to:

(a)    delete the defined term “Scheduled Maturity Date” in its entirety and insert the following in lieu thereof:
			
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“Scheduled Maturity Date” means July 1, 2023, or if such day is not a Business Day, the immediately preceding Business Day.

(b)    (i) delete the definition of “Make Whole Premium” in its entirety, and (ii) delete Section 2(c) (Optional Prepayments of Loans) of the Credit Agreement in its entirety and insert the following in lieu thereof:

(c)    Optional Prepayments of Loans. The Borrower may voluntarily prepay any Loan, in whole or in part, together with all accrued but unpaid interest thereon, by irrevocable written notice to the Agent not later than 2:00 p.m. (New York time) at least thirty (30) days (but not more than sixty (60) days) prior to the proposed date of prepayment. Any such prepayment of a Loan shall be in a principal amount of at least $500,000 and an integral multiple of $100,000 in excess of such amount (or, if less, the entire principal amount thereof then outstanding). Prepayments in whole pursuant to this Section 2(c) shall not, in and of themselves, constitute a termination of this Agreement by the Borrower.

(c)    insert the parenthetical phrase “(or similar governing body)” immediately following each instance of the phrase “board of directors” in the Credit Agreement.

4.    Borrower Assignment and Assumption.

The Initial Borrower and the Ultimate Borrower hereby acknowledge and agree that concurrently with the effectiveness of the Merger, (a) the Initial Borrower will be merged within and into the Ultimate Borrower and the separate corporate existence of the Initial Borrower will thereupon cease, (b) the Ultimate Borrower, by operation of law and pursuant to the terms of the Merger Agreement, will be the surviving entity of the Merger and will unconditionally and irrevocably assume, and be deemed to have assumed, the due and punctual performance and observance of each term, covenant and condition applicable to the Initial Borrower as set forth in the Credit Agreement, as amended hereby, and the other Transaction Documents, (c) the validity and enforceability of all Liens and security interests heretofore granted, pursuant to and in connection with the Transaction Documents to the Agent, on behalf and for the benefit of the Lenders, as collateral security for the Obligations under the Transaction Documents (including, without limitation, after giving effect to this letter agreement) are ratified and reaffirmed by the Ultimate Borrower in accordance with their respective terms from and after the effectiveness of the Merger, and
(d)    all Liens and security interests, and all Collateral heretofore pledged as security for such Obligations, shall continue to be and remain Collateral for such Obligations from and after the effectiveness of the Merger, and (e) each reference to the “Borrower” and a “Grantor”, as applicable, in the Credit Agreement and the other Transaction Documents will be deemed to refer to the Ultimate Borrower.

The Ultimate Borrower hereby confirms and agrees that from and after the effectiveness of the Merger, the Credit Agreement, as amended by this letter agreement, and the other Transaction Documents are and will continue to be in full force and effect in accordance with their respective terms, are ratified and confirmed by the Ultimate
			
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Borrower in all respects, and constitute the legal, valid and binding obligations of the Ultimate Borrower, duly executed and enforceable against the Ultimate Borrower in all respects, subject to Debtor Relief Laws and general equity principles.

5.    Conditions to Effectiveness.

The effectiveness of this letter agreement, including the amendments set forth in Section 3 above, is subject to reasonable satisfaction, or waiver by the Agent, of the following conditions on or before the closing of the Merger (such date, the “Effective Date”):
(a)    the Agent shall have received (i) duly executed counterparts of this letter agreement by each party hereto, (ii) a customary secretary’s certificate of the Ultimate Borrower in substantially the same form as the secretary’s certificate delivered by the Initial Borrower to the Agent on the Closing Date, which shall include, for the avoidance of doubt, resolutions authorizing the Ultimate Borrower to enter into this letter agreement and consummate the assignment and assumption set forth in Section 4 above, (iii) a UCC- 3 financing statement amendment with respect to change in the debtor from the Initial Borrower to the Ultimate Borrower, and (iv) an opinion of Alston & Bird LLP to the effect that the borrower assignment and assumption pursuant to Section 4 above has been duly authorized by the Ultimate Borrower and is enforceable in accordance with its terms;

(b)    the Initial Borrower shall have paid (or caused to be paid) to the Agent (i) an amendment fee equal to $62,500 and (ii) all actual, reasonable and documented (in summary form) costs and expenses of the Agent incurred in connection with this letter agreement pursuant to Section 9(e)(ii) of the Credit Agreement and invoiced prior to the Effective Date; and

(c)    each of the representations and warranties contained in Section 6 below shall be true and correct in all material respects on and as of the Effective Date.

6.    Representations and Warranties.

The Initial Borrower represents and warrants to the Agent and each Lender that, as of the date of this letter agreement:
(a)    the representations and warranties of the Initial Borrower contained in Section 4 of the Existing Credit Agreement and the other Transaction Documents are true and correct in all material respects on and as of such date (except (x) to the extent any representation or warranty relates to an earlier date in which case such representation or warranty is true and correct in all material respects as of such earlier date and (y) any representation or warranty which is subject to any materiality qualifier shall be true and correct in all respects);

(b)    the Initial Borrower has taken all necessary action to authorize the execution, delivery and performance of this letter agreement and each of the other Transaction Documents to which it is a party;
			
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(c)    this letter agreement is the legally valid and binding obligation of the Initial Borrower, enforceable against each of the Initial Borrower in accordance with its terms, subject to Debtor Relief Laws and to general equity principles, and

(d)    as of the Effective Date after giving effect to this letter agreement, no Default or Event of Default has occurred and is continuing or would result from the transactions contemplated by this letter agreement.

7.    Reaffirmation of Obligations; Security Interests.

The Initial Borrower hereby (a) acknowledges and reaffirms its obligations owing to the Agent and each Lender under the Credit Agreement and each other Transaction Document to which it is a party, and (b) agrees that the Credit Agreement, the Security Agreement and each of the Transaction Documents to which it is a party is and shall remain in full force and effect and confirms that all Liens granted, conveyed or assigned to the Agent by the Initial Borrower pursuant to any Transaction Document to which it is a party remain in full force and effect, are not released or reduced, and continue to secure full payment and performance of the Obligations. The Initial Borrower hereby (i) further ratifies and reaffirms the validity and enforceability of all Liens and security interests heretofore granted, pursuant to and in connection with the Transaction Documents to the Agent, on behalf and for the benefit of the Lenders, as collateral security for the Obligations under the Transaction Documents (including, without limitation, after giving effect to this letter agreement) in accordance with their respective terms, and (ii) acknowledges that all Liens and security interests, and all Collateral heretofore pledged as security for such Obligations, continue to be and remain Collateral for such Obligations from and after the date hereof (including, without limitation, after giving effect to this letter agreement).

8.    Miscellaneous.

Except as expressly set forth herein, the execution, delivery and performance of this letter agreement shall not constitute a waiver of any provision of, or operate as a waiver of any right, power or remedy of the Agent or any Lender under the Credit Agreement or any of the other Transaction Documents. On and after the Effective Date, each reference in the Credit Agreement to “this Agreement”, “hereunder”, “hereof”, “herein” or words of like import referring to the Credit Agreement, and each reference in the other Transaction Documents to the “Credit Agreement”, “thereunder”, “thereof” or words of like import referring to the Credit Agreement shall mean and be a reference to the Credit Agreement as amended by this letter agreement. To the extent that any of the terms and conditions in any of the Transaction Documents shall contradict or be in conflict with any of the terms or conditions of the Credit Agreement after giving effect to this letter agreement, such terms and conditions are hereby deemed modified or amended accordingly to reflect the terms and conditions of the Credit Agreement as modified or amended hereby.

This letter agreement shall constitute a “Transaction Document” for all purposes under the Credit Agreement and the other Transaction Documents. Sections 9(o) (Counterparts; Integration), 9(q) (Severability), 9(r) (Governing Law), 9(s) (Jurisdiction)
			
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and 9(t) (Waiver of Jury Trial) of the Credit Agreement are hereby incorporated herein by reference mutatis mutandis.

[Remainder of Page Intentionally Blank]
			
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Please confirm your agreement to the foregoing by signing and returning this letter agreement to us.

Very truly yours,

TERRA INCOME FUND 6, INC., as the Initial Borrower

By:/s/ Gregory M. Pinkus     Name: Gregory M. Pinkus
Title: Chief Financial Officer

Acknowledged and agreed:

TERRA MERGER SUB, LLC, as the Ultimate Borrower

By:/s/ Gregory M. Pinkus     Name: Gregory M. Pinkus
Title: Chief Financial Officer

  Acknowledged and agreed by the Agent and each of 
  the Lenders:
  EAGLE POINT CREDIT MANAGEMENT,
  as the Agent

  By: /s/ Taylor Pine                                                
  Name: Taylor Pine
  Title: Director

			
	Terra/EP - Consent Letter and Amendment

EAGLE POINT DIF DELAWARE I LLC, as a
Lender

By: Eagle Point Credit Management LLC, its investment advisor

By:/s/ Taylor Pine    
Name: Taylor Pine Title: Director

EP DIF CAYMAN I LP, as a Lender

By: Eagle Point Credit Management LLC, its investment advisor

By:/s/ Taylor Pine    
Name: Taylor Pine Title: Director

WILTON REINSURANCE COMPANY, as a
Lender

By: Eagle Point Credit Management LLC, its investment advisor

By:/s/ Taylor Pine    
Name: Taylor Pine Title: Director
			
	Terra/EP - Consent Letter and Amendment

 WILCAC LIFE INSURANCE COMPANY, as a
  Lender

  By: Eagle Point Credit Management LLC, its  
    investment advisor

By:/s/ Taylor Pine    
Name: Taylor Pine Title: Director

  BLUECROSS BLUESHIELD OF TENNESSEE
  INC., as a Lender

  By: Eagle Point Credit Management LLC, its 
     investment advisor

By:/s/ Taylor Pine    
Name: Taylor Pine Title: Director

  PCT PARTNERS LLC, as a Lender

  By: Eagle Point Credit Management LLC, its  
    investment advisor

By:/s/ Taylor Pine    
Name: Taylor Pine Title: Director

Terra/EP - Consent' Letter and AmendmentExhibit 10.1

 

APPENDIX TO THE AGREEMENT DATE JULY 07, 2019

 

Signed at October 23, 2022

 

	Between:	Rambam Med-Tech Ltd Reg. no. 514496587
	 	By Roee Atlas – CEO 
	 	(So Called: “Med- Tech”) 
	 	 
	AND Between:	Raphael Pharmaceutical Ltd Reg. no. 516054400
	 	By Shlomo Pilo –CEO  
	 	(So Called: “Raphael”)

 

WHEREAS, the parties signed research agreement
on July 7, 2019 (So called: “the Primary Agreement”); 

 

WHEREAS, Med-Tech had signed on December
31, 2020 an appendix to the Primary Agreement in which its extent the primary agreement for an extra of four years in terms & conditions
as will set up between the parties;

 

WHEREAS, the parties will set up, herein,
the terms & conditions for the extension of two years out of the four in this appendix;

 

WHEREAS, the description plan & the
objectives of the new research development will be set forth herein;

 

Now, THEREFORE, in consideration of the
promises & mutual covenants set forth herein, the parties agrees as follows:

 

		A.	Description of the Research Development:

 

Development of a novel patentable formulation
based on combination of purified cannabinoid and Cannabinoid Receptor’s antagonist to treat rheumatoid
diseases

 

		B.	Research plan:

 

Scientific background

 

Rheumatoid diseases are characterized by progressive
chronic inflammation of the musculoskeletal system afflicting primarily the joints but can lead to systemic comorbidities like pulmonary
diseases or vasculitis. Chronic inflammation results in cartilage and bone damage, which in the course of deterioration can lead to disability
of the affected patient (Smolen, Aletaha, & McInnes, 2016).

 

Rheumatoid diseases have a great individual and
societal burden. Pain and musculoskeletal deficits lead to a progressive decline in physical activity and quality of life and carry the
risk of cumulative comorbidity. Medical costs for treatment as well as the reduction in work capacity and the decreased societal participation
of patients with RA have a major socioeconomic effect on society (Cross et al., 2014).

 

     

     

    

 

Therapy
of rheumatoid diseases is challenging not only because of the progressive nature of the disease but also because of the side effects
of the current treatments available (Nawaz, Ali, Rehman, & Aslam, 2020). Moreover, available treatment options cannot reverse rheumatoid
diseases. Thus, therapy efforts are followed in two directions: i) preventive medicine (starting treatment before clinical manifestation)
and ii) development of new drugs that treat rheumatoid diseases. Three classes of drugs are available today; i) disease-modifying anti-rheumatic
drugs (DMARDs), which target TNF, the IL-6 receptor and stimulate the depletion of T and B cells diminishing the progression
of the structural damage (Singh et al., 2016; Smolen et al., 2014), ii) non-steroidal anti-inflammatory drugs (NSAIDS), which improve
the physical function by reducing pain and stiffness but do not modify the disease (Nawaz et al., 2020) and iii) glucocorticosteroids,
which have a rapid symptomatic and disease-modifying effect (Kirwan, 1995).

 

Prolonged use of glucocorticoids and DMARDs has
serious long-term adverse effect (Szostak, Machaj, Rosik, & Pawlik, 2020; Yasir, Goyal, Bansal, & Sonthalia, 2020). Moreover,
biological DMARDs have an increased risk of serious infections by tuberculosis and herpes zoster virus as well as the risk to develop
melanoma (Ramiro et al., 2014). This exemplifies the need for novel treatment approaches and safe therapeutics. One of them might be the
usage of medical cannabis taking advantage of its pain-reducing and immune-modulating features.

 

Cannabis and cannabinoids

 

Cannabis is the most widely used illicit drug
in the world. It is not a single substance but refers to a compilation of > 550 different chemical constituents accumulated in
the cannabis plant, among them ≈ 150 psychoactive and non-psychoactive cannabinoids and > 400 non-cannabinoids. The
cannabis plant belongs to the family Cannabaceae. Two different forms are distinguished; cannabis with high levels of the psychoactive
tetrahydrocannabinoids (THC) is referred to as marijuana and cannabis with high levels of non-psychoactive cannabinoids and low levels
of THC is referred to as hemp (Baron, 2015). Two main THC compounds are pharmacologically active, 8-THC and 9-THC.
The main non-psychoactive but pharmacologically active cannabinoids are cannabinol (CBN), cannabidiol (CBD) or cannabigerol (CBG) (Figure
1) as well as non-cannabinoids like flavonoids, terpenes and fatty acids (Andre, Hausman, & Guerriero, 2016; Gould, 2015).

 

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Figure 1: Cannabinoids in the cannabis plant

 

List and number of phytocannabinoids found in the
cannabis plant.

 

Cannabis and cannabinoids occur in several forms; as they occur in
the cannabis plant or as isolates and synthetic or semi-synthetic produced substances.

 

Natural cannabinoids

 

Medical cannabis is available as the whole plant
in the form of dried flowers or as extracts thereof. Drying and heating allows gradual decarboxylation of the cannabinoid acid precursors
into the proper neutral forms, i.e. cannabidiol acid (CBDA) converts to cannabidiol (CBD) or tetrahydrocannabinol acid (THCA) converts
to tetrahydrocannabinol (THC) (de Meijer et al., 2003). Physiologic effects of non-cannabinoids that are also found in the leaves and
flowers are not yet entirely known (Sarzi-Puttini, Batticciotto, et al., 2019).

 

Synthetic and semi-synthetic cannabinoids

 

Many off the shelf products are available, of
which three cannabis products received approval for medicinal use. These are nabiximol which consists of natural THC and CBD extracts,
dronabinol which is plant-derived but chemically modified after extraction and nabilone is synthetically produced (Häuser, Petzke,
& Fitzcharles, 2018; Mücke, Phillips, Radbruch, Petzke, & Häuser, 2018).

 

Nabiximols, better known under the tradename Sativex®,
is a botanical mouth spray that received approval in the UK in 2010 for the alleviation of MS-symptoms like spasticity, pain and overactive
bladder. Its main ingredients are THC and CBD at similar dosage (Häuser et al., 2018; Mücke et al., 2018; Sarzi-Puttini, Batticciotto,
et al., 2019).

 

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Dronabinol (Marinol) contains mainly THC and is
a partial agonist of the cannabinoid receptors CB1 in the nervous system and CB2 in the periphery that activates appetite, mood, cognition,
memory and perception. Dronabinol received FDA-approval for the United States in 1985 for treatment of anorexia in AIDS patients and for
the prevention of chemotherapy-induced nausea and vomiting (CINV). Adverse effects include drowsiness, fatigue, dizziness, conjunctivitis,
paranoia and abnormal thinking and euphoria as well as gastrointestinal problems like nausea, vomiting, abdominal pain and diarrhea (Häuser
et al., 2018; Mücke et al., 2018). Lack of randomized controlled trials (RCTs) makes a recommendation for usage of dronabinol as
a third-line treatment for CINV difficult (Sarzi-Puttini, Batticciotto, et al., 2019). Dronabinol in the form of an oral tablet is known
under the trade name namisol. It has high bioavailability and a long shelf life and is indicated for Multiple Sclerosis (MS), chronic
pain and behavioral disturbances in dement patients (Häuser et al., 2018; Sarzi-Puttini, Batticciotto, et al., 2019).

 

Nabilone with the main ingredient THC is approved
and sold under the brand name Cesamet in Canada, Mexico, the UK and the USA as an anti-emetic and adjunctive analgesic for neuropathic
pain, CINV and treatment for anorexia in AIDS patients. Its main usage today is as adjunct medicine for chronic pain management. However,
ambiguous results from case studies and clinical trials on benefits of nabilone for fibromyalgia and MS were published so that recommendations
for usage cannot be given (Häuser et al., 2018; Reekie, Scott, & Kassiou, 2017; Sarzi-Puttini, Batticciotto, et al., 2019).

 

Signaling pathways and the importance of
cannabinoid receptors for signal transduction

 

Cannabinoids mediate their biological and therapeutic
effects through cannabinoid receptors (Mackie, 2008; Paland et al., 2021; T. H. Smith, Sim-Selley,
& Selley, 2010). At least two members of the G-protein coupled receptor family (GPCRs),
cannabinoid receptors 1 (CB1R) and 2 (CB2R), were identified. G-proteins act as adaptors that link GPCRs to other signaling and
regulatory proteins to operate or modulate intracellular signaling pathways. Other G-protein
coupled receptors such as GPR55 and GPR18 and transient receptor potential channels such as TRPV2, TRPA1, or TRPM8 are involved in cannabinoid
signaling (Rosenbaum, Rasmussen, & Kobilka, 2009).

 

CB1R is highly expressed
on neural cells in the central nervous system (CNS), and is found in particularly high levels in the neocortex, hippocampus, basal ganglia,
cerebellum and brainstem (Marsicano & Kuner, 2008). Low expression levels are observed in the peripheral nervous system. The CB1R
binds the main active ingredient of marijuana, Δ9-THC, and mediates most of the CNS effects of THC (Zimmer, Zimmer, Hohmann,
Herkenham, & Bonner, 1999).

 

CB2R is present at high
levels in cells of the immune system and commonly associated with the regulation of immune function. Furthermore, a functionally relevant
expression of CB2R was also found in the brain (Salort, Álvaro-Bartolomé, & García-Sevilla, 2017). In the CNS,
CB2R expression is associated with inflammation and it is primarily localized to microglia, resident macrophages of the CNS (Palazuelos
et al., 2009).

 

    4

     

    

 

The fact
that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of
the immune system. It has been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental
models. Several studies showed that cannabinoids downregulate cytokine and chemokine production
and, in some models, upregulate T-regulatory cells as a mechanism to suppress inflammatory responses (Berdyshev, 2000; Paland et al.,
2021).

 

Cannabinoids
can inhibit cell proliferation through various mechanisms. They block cell cycle progression at the G1/S phase via CB1R and at
the G2/M phase via CB2R activation by inhibiting Akt and ERK signaling. CB1R activation inhibits the FAK/SRC/RhoA pathway leading to inhibition
of cell migration. Cell migration blockade is also achieved by CB2R activation through the inhibition of COX-2 and ERK signaling, which
is important to suppress inflammatory response (Kisková, Mungenast, Suváková, Jäger, & Thalhammer, 2019).

 

		C.	Research Objectives

 

The overall objective of this study is to identify
a novel cannabinoid based patentable formulation to treat Rheumatoid diseases. Specifically, to
investigate combination of purified cannabinoids with cannabis receptors antagonists to downregulate inflammation related to Rheumatoid
diseases. We propose to base our study on data derived from Dr. Igal Louria-Hayon studies (Helsinki # 0442-20-RMB) on the evaluation of
the immune regulation properties of cannabinoids on the immune system and the data derived from the cannabinoids receptors study (Helsinki
# 0331-20-RMB). We will analyze the activation of cannabinoid receptors on mouse models and will study the role of cannabinoid receptors
antagonists as a potential to develop a novel patentable formulation to treat Rheumatoid Arthritis.

 

Specific
aims:

 

		1.	Identify the potential of purified
specific cannabinoid on Rheumatoid Arthritis in a mouse model

 

		2.	Identify Cannabinoid Receptors
antagonist with a potential to downregulate immune cells activities, in human derived cells and mouse model.

 

		3.	Formulate a combination of
purified cannabinoid and Cannabinoid receptors antagonist which will demonstrate synergistic effect to downregulate inflammation related
to Rheumatoid Arthritis.

 

We suggest that our strategy to combine
purified cannabinoid together with cannabinoid receptor’s antagonists, will allow us to develop a novel formulation for Rheumatoid
Arthritis treatment.

 

    5

     

    

 

		D.	Cost of the New research Development:

 

Raphael will sponsored the new research development
as follows:

 

2 years Budget
(cost including overhead):

 

Pre-Clinical lab research
cost $700,000 USD + V.A.T.

 

Mouse model for systemic
inflammation: 120,000 USD + VAT.

 

Mouse model for Rheumatoid
Arthritis: 140,000 USD + VAT.

 

Total cost: 800,000
+ 160,000 (overhead) + VAT.

 

		●	The
principal investigator is authorized to decide on changes in the budget of each category and the duration of the research in related
to the needs of the study.

 

Payment Schedule:

 

Raphael Pharmaceutical will pay to Rambam MedTech

 

1st payment: 100,000$ + 20,000$
overhead on May 2023 (Mouse Model). 

 

2nd payment: 291,667$ + 58,333$
overhead on December 2023 (Research year I). 

 

3rd payment: 116,667$ + 23,333$
overhead on May 2024 (Mouse Model). 

 

3rd payment: 291,667$+ 58,333$ overhead
$ December 2024 (Research Year II).

 

All payments should be added VAT

 

Payment will be in NIS according to the Bank of
Israel exchange rate on the day of payment.

 

    6

     

    

 

IN WITNESS WHEREOF, each party has caused this
Appendix to be executed by its duly authorized representative as of the effective date: 

 

	Rambam Med-Tech Ltd	 	Raphael Pharmaceutical Ltd 
	 	 	 
	By:	 /s/ Roee Atlas	 	By:	 /s/ Shlomo Pilo
	Name: 	 Roee Atlas	 	Name: 	 Shlomo Pilo
	Title:	 CEO	 	Title:	 CEO 
	Date: 	23.10.22	 	Date:	 24.10.22

 

	Principal Investigator	 
	 	 
	By:	/s/ Igal Louria- Hayon 	 
	Name: 	Igal Louria- Hayon 	 
	Title: 	Scientific Director Medical Cannabis Research and Innovation Center Rambam health care Campus.  	 
	Date:	23.10.2022 	 

 

 

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