Pursuant to the Agreement, ARx shall provide:

· formulation, chemistry, manufacturing and control (“CMC”) support and documentation,

· clinical unit production and

· mixing, coating, slitting, manufacturing and testing

Pursuant to the future CSA, ARx shall provide:

· commercial supply

With respect to the Agreement, Cynapsus shall provide:

· final release of all Product manufactured by ARx,

· fulfillment of clinical requirements,

· analytical method development, validation, testing, and stability studies,

· management of patent filings with respect to Cynapsus-Owned Patents (as defined below); and,

· fulfillment of regulatory requirements, correspondence and documentation provided in support of Product filing

The items listed above with respect to the Agreement are defined as the “Responsibilities”.

Specific program activities and associated Responsibilities will be defined in mutually agreed upon Work Plans (“WP”), a template WP being attached to the Agreement as Exhibit B. In each WP, Cynapsus and ARx shall agree upon project scope, specifications, deliverables, price and timelines for the Responsibilities.

Each Party shall execute their respective Responsibilities according to the WP, associated deliverables, and in accordance with applicable laws and regulatory requirements.

ARx shall be the sole partner for formulation and process development activities for the Product during the term of the Agreement, unless otherwise agreed to by Parties in writing.

Unless otherwise agreed by the Parties in a WP, if either Party reasonably believes that it cannot meet its obligations under a WP, it shall provide the other Party written notice of such inability as soon as it determines that it cannot meet such obligations. Failure to provide such notice shall be considered a material breach of the Agreement.

In consideration of meeting the deliverable for the performance of the Responsibilities with respect to an individual WP, ARx will invoice Cynapsus in accordance with the deliverable specified in the WP and the terms and conditions specified in this Agreement.

IV. Term and

Termination

The initial term of the Agreement shall begin on the effective date and continue for 5 years. Thereafter the Agreement shall automatically renew for successive one (1) year periods.

The following Sections shall survive the termination of this Agreement: V. Future Commercial Supply, VI. Intellectual Property, XI. Indemnification XII. Insurance and XIII: Assignment.

Convenience. At any time, a Party may terminate this Agreement effective upon one hundred and eighty (180) days prior written notice to the other Party.

Material Breach. Either Party may terminate this Agreement effective upon sixty (60) days prior written notice to the other Party, if the other Party commits a material breach of this Agreement and fails to cure such breach by the end of such sixty (60) day period.

Bankruptcy, etc. Either Party may terminate this Agreement effective upon written notice to the other Party, if the other Party becomes insolvent or admits in writing its inability to pay its debts as they become due, files a petition for bankruptcy, makes an assignment for the benefit of its creditors or has a receiver, trustee or other court officer appointed for its properties or assets.

Consequences. Unless otherwise agreed to, upon termination of this Agreement in accordance with this Article IV, ARx will be reimbursed for all costs reasonably incurred to the date notice of termination, such reimbursement not to exceed the total estimated WP price specified in the relevant WP. At the same time, the Parties may also agree upon other matters with respect to the termination of the Agreement.

The Parties anticipate entering into a CSA with respect to the United States of America (“Territory”), prior to Product filing with respect to U.S. Food and Drug Administration (“FDA”). The CSA shall contain the following material provisions and other terms and conditions typically included in commercial supply agreements with respect to pharmaceutical products.

ARx shall be the majority supplier of Product during the term of the CSA in the Territory, unless otherwise agreed to by the Parties in writing. Majority Supply shall be defined as [*****] % of demand or higher (“Majority Supply”).

As required by good commercial and supply practice, Cynapsus shall qualify a secondary supplier of the Product for contingency purposes (“Contingency Supplier”) in the Territory that shall be acceptable to ARx, acting reasonably. To enable the Contingency Supplier to successfully produce the Product, Cynapsus may request ARx’s technical transfer assistance for a mutually agreed upon cost. Continuing services provided by ARx to the Contingency Supplier with respect to the supply of the Product in the Territory shall be further defined in the CSA.

ARx shall have an option to provide to Cynapsus services in the Territory with respect to [*****] in connection with the Product (“Additional Services”), provided that (a) ARx has the regulatory authority and commercial capability to provide such Additional Services, in the opinion of Cynapsus, acting reasonably, and (b) the Additional Services that are offered are offered to Cynapsus on financial terms and conditions no less favorable than any other third party from which Cynapsus shall have solicited competing bids. In the event that ARx shall satisfy the conditions set out in the preceding sentence, the Parties shall negotiate in good faith such agreement(s) on commercially reasonable terms with respect to the Additional Services similar to those terms set forth in the CSA, to the extent relevant.

In the event that ARx shall obtain required regulatory approvals to manufacture the Product in one or more markets outside of the Territory and Cynapsus shall have decided to enter one or more such markets outside of the Territory, ARx shall be invited by Cynapsus to bid for the right to supply the Product in such market(s). Notwithstanding the above, Cynapsus shall retain the sole discretion to select one or more suppliers of the Product in markets outside of the Territory.

In consideration for the clarification of the intellectual property rights described in Section VI, Cynapsus, its successors and assigns shall pay to ARx [*****] % of the invoiced cost incurred by Cynapsus with respect to the manufacture of the Product, less the costs of the related active pharmaceutical ingredient and packaging, in the Territory by Contingency Supplier, or any other party outside of the Territory.

For as long as the CSA remains in force and the terms of this Article V are satisfied, ARx will not manufacture any apomorphine sublingual thin film generic Product applications in the Territory. Any additional exclusivity terms will be negotiated as part of the CSA.

All rights, title, and interest to intellectual property, know how, trade secrets and data related to the Product are herein assigned and will be assigned as follows:

(a) ARx shall assign and herein assigns to Cynapsus all rights, title, and interest to U.S. Patent Nos. 8,414,922 and 8,846,074 and their U.S. and foreign counterparts (“Cynapsus – Owned Patents”). A confirmatory assignment assigning ARx’s rights to Cynapsus – Owned Patents is attached to the Agreement as Exhibit C.

(b) Cynapsus shall and herein grants ARx a non-exclusive, royalty- free, license to Cynapsus-Owned Patents in all fields, other than apomorphine sublingual thin film generic Product applications.

(c) Cynapsus owns all Product-related formulation and process know how, trade secrets and data generated pursuant to the Agreement /WPs (“Agreement-IP”).

(d) Cynapsus shall and herein grants ARx an exclusive, royalty-free, license to Agreement IP, in all fields, in respect of other products and formulations. As contemplated in V. Future Commercial Supply, ARx shall facilitate the transfer of the Agreement IP to the Contingent Supplier.

(f) Product Filings: solely owned by Cynapsus.

Both Parties represent and warrant to the other that it has the experience, capability and resources to fulfill the Responsibilities and that the Responsibilities shall be performed in a workmanlike manner with professional diligence and skill and in conformance with applicable specifications or requirements as set forth in the Agreement or the WP(s).

Both Parties represent and warrant to the other that the execution, delivery and performance of this Agreement have been authorized by all necessary corporate action, do not conflict with or result in a material breach of the articles of incorporation or by-laws of such Party or any material agreement by which such Party is bound, or any law, regulation or decree of any governmental entity or court that has jurisdiction over such Party.

Both Parties represent and warrant to the other that it is not now nor has in the past been suspended, debarred, disqualified, restricted or excluded or proposed for suspension, debarment, disqualification, restriction or exclusion under applicable laws. Neither Party has never been convicted of a felony under U.S. federal law for conduct relating to the development or approval of a drug product and/or relating to a drug product; and representatives who perform Responsibilities under this Agreement on behalf of the Parties are not now nor have in the past been suspended, debarred, disqualified, restricted or excluded or proposed for suspension, debarment, disqualification, restriction or exclusion under applicable laws.

Both Parties warrant that it and its representatives shall comply with all applicable laws during the term of and in the performance of the Agreement, and that both Parties’ actions in establishing and performing the Agreement have been and will be consistent with ethical business practices and without the influence of any association with any respective employee, officer or director that would amount to a conflict of interest.

Both Parties represent that it is not a party to any existing agreement that would prevent it from entering into and performing this Agreement or any WP.

Both Parties will not enter into any other agreement that is in conflict with its obligations under the Agreement.

ARx: While this agreement is in place and for 2 years after the sale of the last ARx produced Product, except to the extent that it is proximately caused by the gross negligence, or intentional misconduct in the performance of its obligations under the Agreement by Cynapsus, ARx shall defend, indemnify and hold harmless Cynapsus and its officers, directors, employees, successors and assigns from and against any liabilities, claims, suits, actions, loss, damage, cost or expense (including reasonable attorneys’ fees and expenses) (“Loss”) arising from any third party claim, demand, assessment, action, suit or proceeding (“Claim”) arising from personal injury and/or death and/or loss of and/or damage to property as a result of ARx’s gross negligence or intentional misconduct in the performance of its obligations under the Agreement; provided, however, that ARx’s liability hereunder shall not exceed [*****] and, provided further, that ARx shall not provide an indemnity for infringement of any patent, copyright, trademark, trade secret or other intellectual property rights.

Cynapsus: While this Agreement is in place and for 2 years after the sale of the last Product sold by Cynapsus, except to the extent that it is proximately caused by the gross negligence, or intentional misconduct in the performance of its obligations under the Agreement by ARx, Cynapsus shall defend, indemnify and hold harmless ARx and its officers, directors, employees, successors and assigns from and against any Loss relating to the Product or arising from the performance of its obligations under this Agreement. For greater certainty, the obligations of Cynapsus under this paragraph do extend to defending, indemnifying and holding harmless ARx and its officers, directors, employees, successors and assigns from and against any Loss or any Claim related to any infringing by ARx of a 3^rd party patent related to its method of making Cynpasus’ Product. 

While this Agreement is in place and for 2 years after the expiration date of the last unit of Product sold by Cynapsus, Cynapsus shall maintain in full force and effect the following insurance coverage: (i) products liability; (ii) contractual liability; and (iii) clinical trials insurance (including coverage for any negligence on the part of Cynapsus in the conduct of any clinical trials as well as for any defects or negligence in the design of the clinical trial process). Insurance coverage for each of the foregoing subsections (i), (ii) and (iii) shall be in the minimum amount of [*****] per occurrence with an annual aggregate amount of [*****]. ARx shall be named as an additional insured and the policy/ies shall be endorsed to provide that Cynapsus has assumed the liability set forth above. The policy/ies shall also provide for at least 30 days’ notice to ARx of cancellation or nonrenewal. Cynapsus will provide ARx with a copy of a certificate of insurance related to such policy/ies upon execution of the Agreement.

While this Agreement is in place and for 2 years after the expiration date of the last unit of Product manufactured by ARx, ARx shall maintain in full force and effect the following insurance coverage for products liability. Insurance coverage for the foregoing shall be in the minimum amount of [*****] per occurrence with an annual aggregate amount of [*****]. The policy/ies shall also provide for at least 30 days’ notice to Cynapsus of cancellation or nonrenewal. ARx will provide Cynapsus with a copy of a certificate of insurance related to such policy/ies upon execution of the Agreement. 

Cynapsus may assign its rights and obligations under the Agreement, with written notice to ARx, provided that the terms and conditions of this Agreement shall be binding upon any assignee.

ARx may not assign its rights and obligations under the Agreement, unless given written consent by Cynapsus.

The terms of this Agreement shall be binding upon its successors and assigns. 

The terms of the Agreement and WPs related hereto constitute the entire agreement between the Parties and will supersede the terms of the current agreement/agreements between ARx and Cynapsus, including WPs, whether oral or written, except for the CDA noted above. 

Apomorphine Hydrochloride Loading (mg)

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

Test 

Appearance

[*****]

[*****]

[*****]

[*****]

[*****]

Specified Degradation Products

Unspecified Degradation Product

Total Impurities

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

[*****]

Objective: 

Materials: 

Activities:

Testing:

Mix: 

Batch Size: 

Deliverables: 

Invoicing:

Objective:

Materials:

Activities:

Testing:

Mix: 

Batch Size: 

Mix: 

Deliverables:

Invoicing:

Objective:

Materials:

Activities:

Testing:

Mix:

Batch Size:

Mix:

Deliverables:

Invoicing:

Documentation:
GMP Batch Record
Data Summary 

U.S.S.N. 13/445,656,

Granted as US Pat. No. 8,414,922

U.S.S.N. 13/858,638

Granted as US Pat. No. 8,846,074

U.S.S.N. 14/478,975

Filed 09/05/14

SUBLINGUAL FILMS

Corresponding international applications

based upon PCT/US2011/65665,

Filed 12/16/11

PCT Publication No.  WO/2012/083269