Exhibit 10.2

 

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SIXTH AMENDMENT TO THE LICENSE AGREEMENT
UC Control No. 2006-04-0026

 

THIS SIXTH AMENDMENT (the “Sixth Amendment”), dated July 8, 2015, (the “Sixth
Amendment Effective Date”), is made by and between THE REGENTS OF THE UNIVERSITY
OF CALIFORNIA (“The Regents”), a California corporation having its statewide
administrative offices at 1111 Franklin Street, 12th Floor, Oakland, California
94607-5200, acting through the offices of The University of California, Los
Angeles, located at 11000 Kinross Avenue, Suite #200, Los Angeles, CA 90095-1406
(the “Institution”), and PUTNEY DRUG CORP. (“Licensee”), having a principal
place of business at 617 Detroit Street, Suite 100, Ann Arbor, MI 48104, and
amends the Exclusive License Agreement, dated June 11, 2005, between Licensee
and The Regents with UC Agreement Control No. 2006-04-0026 (the “Original
License Agreement”) and subsequent amendments thereto (collectively, the
“License Agreement”) in accordance with the terms and conditions of this Sixth
Amendment. The Regents and Licensee may be referred to herein individually as a
“Party”, and collectively as the “Parties”.

 

RECITALS

 

WHEREAS, Institution’s employee Rhonda Voskhul, M.D. (“Investigator”) and her
laboratory have conducted and are conducting other research and development
relating to Estriol, and The Regents and Licensee are parties to that certain
Clinical Trial Agreement dated April 29, 2010 relating to the conduct of certain
clinical trials of Estriol by Investigator (the “CTA”), and certain additional
intellectual property relating to the subject matter of the License Agreement
has been created at Institution;

 

WHEREAS, issues have arisen concerning certain of the Parties’ respective rights
and obligations under the License Agreement and the CTA and the Parties wish to
expand their relationship to cover such additional intellectual property and to
resolve such issues, including by amending the License Agreement to provide for,
inter alia, expanded intellectual property rights to Licensee and enhanced
economic consideration to The Regents as provided in the terms and conditions
set forth below, and by amending certain terms of the CTA; and

 

WHEREAS, in connection therewith, the Parties have entered into an amendment to
the CTA (the “CTA Amendment”) and a Release Agreement, each of even date
herewith;

 

NOW, THEREFORE, in consideration of the foregoing premises and the mutual
promises, terms and conditions contained in this Agreement, the sufficiency of
which is hereby acknowledged, the Parties agree as follows:

 

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1.Definitions.

 

(a)Capitalized terms used herein and not otherwise defined shall have the
meaning ascribed in the License Agreement.

 

(b)Article 1 of the License Agreement is hereby amended to add the following
definitions:

 

1.12             “Additional Patent Rights” means all Patent Rights, other than
the Regents’ Patent Rights, that are Controlled by The Regents during the term
of the License Agreement that satisfy all of the following criteria: (a) the
practice, manufacture, use or sale of the invention in such Patent Right is
covered or claimed by a claim in The Regents Patent Rights; (b) the invention
arose from Investigator’s Laboratory Work; (c) the invention was conceived of
and reduced to practice (solely or jointly with others) prior to the Effective
Date or on or after the Effective Date but prior to the 24-month anniversary of
the Sixth Amendment Effective Date; (d) covers the use of Compounds in the Field
of Use.

 

1.13             “Compound” means Estriol, and shall specifically exclude any
other E3-receptor targeted molecules.

 

1.14             “Control” means, with respect to any intellectual property
right (including, without limitation, know-how), that a Party owns or has a
license to such intellectual property right and has the ability to grant to the
other Party access, a license, or a sublicense (as applicable) to the foregoing
on the terms and conditions set forth in this Agreement without violating the
terms of any then-existing agreement with a third party, without violating any
law or regulation, and without incurring any additional financial obligation.

 

1.15             “Development Costs” means fully-burdened costs and expenses
incurred by or on account of Licensee and its Affiliates in conducting
development activities that are directed to or useful for obtaining or
maintaining marketing approval(s) of a Licensed Product, including: all
non-clinical, preclinical and clinical activities, testing and studies of such
Licensed Product (including IND-enabling Studies and translational research);
manufacturing development, process and formulation development; toxicology,
pharmacokinetic, pharmacodynamic, drug-drug interaction, safety, tolerability
and pharmacological studies; distribution of such Licensed Product for use in
clinical trials (including placebos and comparators); data and statistical
analyses; assay development; instrument design and development; protocol design
and development; quality assurance and control; report writing; and the
preparation, filing and prosecution of any regulatory filings and applications
for marketing approval for Licensed Product; development activities directed to
label expansion (including prescribing information) and/or obtaining marketing
approval for one or more additional indications or patient populations following
initial marketing approval; development activities conducted after receipt of
marketing approval which were a condition for the receipt of such marketing
approval (including Phase IV studies); and all regulatory activities related to
any of the foregoing.

 

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1.16             “Development Partner” means an entity to which Licensee (or its
Affiliate) has granted, as contemplated in the provisions of Section 7 of this
Sixth Amendment, a Sublicense to develop and commercialize Licensed Products in
at least the United States or Europe, provided that such entity (together with
its affiliates) has, at the time such Sublicense is granted, at least one
hundred million dollars ($100,000,000) in annual sales in the pharmaceutical
industry. A Development Partner must be an independent Third Party that is not
an Affiliate of Licensee or its Affiliates and enters into an arms-length
Sublicense.

 

1.17             “Estriol” means the compound having the structure set forth in
Exhibit B.

 

1.20             “Estriol Product” means any Compound and any pharmaceutical
composition or preparation (in any and all formulations and dosage forms)
containing a Compound.

 

1.21             “IND” means an investigational new drug application, clinical
study application, clinical trial exemption, or similar application or
submission for approval to conduct human clinical investigations filed with or
submitted to a Regulatory Authority in conformance with the requirements of such
Regulatory Authority, including any such application filed with the FDA pursuant
to 21 CFR Part 312.

 

1.22             “Investigator’s Laboratory Work” means any work performed by or
on behalf of Investigator or by a person working in Investigator’s laboratories
or research facilities or under Investigator’s direction, in each case, to the
extent relating or applicable to the Field of Use. Investigator’s Laboratory
Work shall expressly exclude any human clinical trial work or patient work.

 

1.23             “Joint Venture” shall mean a contractual relationship between a
third party and Licensee or its Affiliate or Sublicensee, under which the third
party and such party markets and commercializes the Licensed Product or Licensed
Method in collaboration with Licensee, or its Affiliate or such Sublicensee, as
applicable.

 

1.24             “Know-How” means any and all data, results, technology and
other information of any type, in any tangible form, that is located by the
University of California Office of Intellectual Property after a reasonable
investigation.

 

1.25             “Licensed Know-How” means all non-privileged Know-How that
meets all of the following criteria: (a) is Controlled by The Regents, (b) was
generated or developed as part of the Investigator’s Laboratory Work prior to
the Effective Date or after the Effective Date but prior to the date 24 months
after the Sixth Amendment Effective Date; and (c) is reasonably necessary for
development, use, manufacture or sale of any Licensed Product or Licensed Method
in the Field of Use, or, in the case of Licensed Know-How created after the
Effective Date, “in the Field of Use” shall be replaced with “ in the Compound
in the Field of Use. “

 

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1.26             “Patent Rights” means (a) patents and patent applications
(which for the purposes of the License Agreement shall be deemed to include
certificates of invention and applications for certificates of invention), (b)
any and all divisionals, continuations, continuations-in-part but only to the
extent of claims entirely supported in the specification and entitled to the
priority date of the parent application to such CIP, reissues, renewals,
substitutions, registrations, re-examinations, revalidations, extensions,
supplementary protection certificates and the like of any such patents and
patent applications, and (c) any and all foreign equivalents of any of the
foregoing.

 

1.27             “Sales-Based Payments” means all payments received by Licensee
from a Sublicensee based on sales of Licensed Product or Licensed Methods, which
expressly includes royalties, sales-based milestone payments, and profit-sharing
payments.

 

1.28             “Sixth Amendment” means that certain Sixth Amendment to the
License Agreement, dated as of July 7, 2015.

 

1.29             “Sublicense” means the grant by Licensee of sublicense rights
under the License to a Sublicensee between Licensee and such Sublicensee, and
the applicable terms of the agreement between Licensee and such Sublicensee
relating so such sublicensing.

 

(c)The Parties hereby agree that Article 1 of the License Agreement is hereby
amended as follows:

 

(i)In Section 1.2 (“Licensed Product”) and Section 1.3 (“Licensed Method”), all
references to “The Regents’ Patent Rights” are replaced by the phrase “The
Regents’ Patent Rights and/or the Additional Patent Rights”.

 

(ii)Section 1.4 is replaced in its entirety with the following:

 

“Field of Use” means the use of Licensed Products for the treatment, prevention
or palliation of any autoimmune disease, condition or indication, including,
without limitation, multiple sclerosis.

 

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(iii)Section 1.5 is replaced in its entirety with the following:

 

“Affiliate” means, with respect to Licensee, any entity that directly or
indirectly controls, is controlled by or is under common control with Licensee.
An entity shall be deemed to control another entity if such entity possesses the
power to direct or cause the direction of the management, business and policies
of such entity, whether through the ownership of 50% or more of the voting
securities of such entity, by contract or otherwise.

 

(iv)Section 1.10 is replaced in its entirety with the following:

 

“Sublicensing Income” mean all consideration received by Licensee from a
Development Partner or other Sublicensee based on the grant of Sublicense rights
(including rights to any of The Regents data, including clinical data licensed
under the CTA) to such Development Partner or other Sublicensee, including in
kind consideration, development milestone payments, Sales-Based Payments,
upfront license payment, and other license fee payments for such Sublicense
grant, but expressly excluding the following: cash reimbursements or advances
for actual future research or development costs, amounts received in connection
with the sale or issuance of equity or convertible debt issued as part of an
investment (to the extent at fair market value), bona fide loans and
reimbursement of patent expenses.

 

2.Amendment to License Rights; Additional Licenses; Access to Know-How

 

(a)Section 2.1 of the License Agreement is hereby amended to replace the Section
in its entirety with the following:

 

2.1             Subject to the limitations in this Agreement, The Regents hereby
grants to Licensee the exclusive license (the “License”) under the Regents’
Patent Rights and the Additional Patent Rights, in all jurisdictions where The
Regents’ Patent Rights or Additional Patent Rights exist, to make, have made,
use, sell, offer for sale and import Licensed Products and to practice Licensed
Methods in the Field of Use to the extent permitted by law. Notwithstanding the
foregoing, all rights granted in this Agreement as to Additional Patent Rights
shall be limited solely to the use of Compound in the Field of Use.

 

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(b)Section 3.1 of the License Agreement is hereby amended to replace the Section
in its entirety with the following:

 

3.1         The Regents also grants to Licensee the rights to issue exclusive or
nonexclusive sublicenses through multiple tiers (“Sublicenses”) to third parties
under the License (including as amended in Section 2(a) of the Sixth Amendment)
and under the rights granted to Licensee in Section 2(c) of the Sixth Amendment
(which are themselves non-exclusive), to research, develop, make, have made,
use, sell, offer for sale, import or export Licensed Products and to practice
Licensed Methods. To the extent applicable, sublicenses must include all of the
rights of and obligations to the Regents (and, if applicable, the U.S.
Government under 35 U.S.C. ss 2012) contained in the License Agreement, except
that the payment obligations of the Sublicensee may be different from Sections 4
and 5, and the diligence obligation may be different for a Development Partner
pursuant to Section 5(b) of the Sixth Amendment.

 

(c)The Regents hereby grant to Licensee a non-exclusive (to the extent permitted
by law) license, including the right to sublicense through multiple tiers in
accordance with Section 3.1 of License Agreement, as amended hereby, under the
Licensed Know-How to research, develop, make, have made, use, sell, offer for
sale, import and export Licensed Products worldwide in the Field of Use.

 

(d)Sections 2.2 and 2.3 of the License Agreement shall apply to the licenses
granted in subsections (b) and (c) above in the same manner as to the License.

 

(e)Promptly after the Sixth Amendment Effective Date, The Regents shall use
reasonable efforts to disclose and provide to Licensee all Licensed Know-How.
Promptly after new Licensed Know-How is identified, The Regents shall disclose
and provide to Licensee such new Licensed Know-How.

 

3.Right of First Negotiation to Expand the Field of Use. The Regents shall
negotiate reasonably and in good faith with Licensee for up to 12 months from
the Sixth Amendment Effective Date on the terms for the expansion of the Field
of Use to include uses of Licensed Products to treat, palliate or prevent
diseases, conditions or indications outside the existing Field of Use. If
Licensee has signed a term sheet with a Development Partner for a Sublicense
during this period, then The Regents also agrees to negotiate reasonably and in
good faith with such potential Development Partner for such an expansion of the
Field of Use for an additional period of negotiation extending until the date 90
days after the execution of a definitive Sublicense agreement with the
Development Partner. The Regents agrees that the terms of any such expansion of
the Field of Use will be commercially reasonable.

 

4.Terms Regarding Commitment To Find A Development Partner

 

(a)The diligence obligations in Sections 6 of the License Agreement shall remain
in full effect and force, except as otherwise expressly stated in this Sixth
Amendment. Notwithstanding the foregoing, The Regents hereby agree that the
obligations in subsection 6.3a and 6.3b of the License Agreement have been met
or that The Regents waive compliance with such obligations.

 

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(b)The Parties, subject to the other provisions of this Article 4, agree that
the mutual goal is for Licensee either (i) to obtain a Sublicense agreement with
a Development Partner within twelve (12) months of the Sixth Amendment Effective
Date, which Sublicense would include a commitment by the Development Partner to
sponsor an appropriate phase clinical trial of an Estriol Product in the Field
of Use (assuming prior clinical data supports initiation of such trial and there
is no regulatory or clinical guidance or other delay outside of the control of
Licensee and its Development Partner); or (ii) to continue the clinical
development of a Licensed Product, using commercially reasonable, diligent
efforts (which may include sublicensing Licensed Product to a third party at
some later stage of development).

 

(c)Licensee shall use commercially reasonable efforts to seek and enter into a
Sublicense agreement with a Development Partner in the Field of Use, within
twelve (12) months of the Sixth Amendment Effective Date and on commercially
reasonable terms. Such sublicensing activities will be conducted in consultation
with The Regents, as follows: Licensee shall provide regular updates on such
partnering efforts to The Regents and use reasonable efforts to permit The
Regents to attend (via a mutually-agreeable designee) one or more material
meetings with a prospective partner where the Parties agree such participation
would be helpful to the partnering process. The Regents agree to provide
reasonable technical and other cooperation in connection with such partnering
efforts, at its expense, to the extent The Regents agrees to participate in a
meeting.

 

(d)Prior to signing any Sublicense agreement for Estriol with a Development
Partner, Licensee shall confer with The Regents regarding the main provisions of
such arrangement and shall consider The Regents’ reasonable comments and
suggestions in good faith. If The Regents reasonably disputes that a proposed
partnering arrangement is appropriate, then if requested in writing by The
Regents, each party shall designate a senior representative and such
representatives shall meet within ten (10) business days of such request to
discuss reasonably and seek to resolve the issue. Notwithstanding the foregoing,
following such meeting, Licensee shall have the right in its reasonable
discretion to determine whether to enter into such agreement with such
Development Partner.

 

(e)If Licensee does not enter into a Sublicense agreement with a Development
Partner within the 12 month period contemplated in subsection (b) and (c) above,
then Licensee nonetheless will continue to retain its exclusive License rights
with respect to the Licensed Products in the Field of Use (and the rights
subsequently to enter into Sublicense agreements, including with Development
Partners). Licensee will remain subject to its obligations under the License,
and its diligence obligations as described above in subsection (b), in Section 5
below, and in Section 6 of the License Agreement.

 

(f)Licensee shall use reasonable efforts to provide that Investigator shall have
the first right to be a “co-Principal Investigator” on any future Estriol
clinical trial sponsored by Licensee or its Development Partner.

 

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5.Diligence.

 

(a)The License Agreement is hereby amended to replace Section 6.3(c) of the
License Agreement in its entirety with the following:

 

6.3(c)    Within 25 months of the Effective Date of Sixth Amendment, initiate
Phase III clinical trials for a Licensed Product in the Field of Use.

 

(b)If Licensee sublicenses all or substantially all of its rights in the
Licensed Products to a Development Partner at least in the United States and/or
Europe within twelve (12) months of the Sixth Amendment Effective Date, then the
diligence obligations in Section 6.3 of the Licensee Agreement shall be
automatically amended and adjusted as follows:

 

(i)Section 6.3(c) of the License Agreement shall be replaced with the following:

 

(A) Within twenty-four (24) months of delivery to Licensee of all the patient
name-redacted MRI image and electronic data created under the Study under the
CTA, as required under Section 3.1 of the CTA, as amended by the CTA Amendment,
complete all clinical trials requested by the FDA to be completed prior to
initiating Phase III clinical trials of a Licensed Product within the Field of
Use; and

 

(B) Within six (6) months of completing the trials covered in (A) above,
initiate a phase III clinical trial of a Licensed Product within the Field of
Use;

 

(ii)The time frames set forth in Section 6.3(c) will be subject to reasonable
extensions for any delays caused by regulatory issues outside of the Development
Partner’s control. To the extent a first Phase III trial of a Licensed Product
within the Field of Use commences later than 40 months from Effective Date of
this Sixth Amendment, the Development Partner must pay $100,000 to The Regents
for every 6 months of additional delay beyond such date.

 

(c)Subsections (a) and (b) do not in any way alter the diligence obligations of
Section 6.3(d) of the License Agreement.

 

6.Royalties. Section 5.1 of the License Agreement is hereby amended in its
entirety to read:

 

5.1         Licensee must pay to The Regents for sales by Licensee or its
Affiliates the an earned royalty of 7% of Net Sales on Licensed Products or
Licensed Methods

 

For clarity, the Licensee does not owe The Regents any royalty payments under
this Section 5.1 for sales of Licensed Products or Licensed Methods by any
Sublicensee (such sales are covered under the obligations in Sections 3.2 of the
License Agreement, and Section 8 of this Sixth Amendment).

 

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7.Milestone Payments. Section 4.2 of the License Agreement is hereby amended in
its entirety to read as follows:

 

4.2         Upon each of the following milestone events first being achieved by
Licensee or its Affiliates, Licensee shall make the corresponding one-time
payments to The Regents within thirty (30) days of such achievement:

 

(a)Two million dollars ($2,000,000) upon the dosing of the first patient in the
first Phase III clinical trial of a Licensed Product.

 

(b)Three million dollars ($3,000,000) upon the filing of an NDA with the U.S.
Food and Drug Administration for a Licensed Product which is covered by a
validly issued U.S. patent.

 

(c)One million five hundred thousand dollars ($1,500,000) upon the approval by
the U.S. Food and Drug Administration of an NDA for a Licensed Product which is
covered by a validly issued U.S. patent.

 

(d)One million five hundred thousand dollars ($1,500,000) upon the achievement
of fifty million dollars ($50,000,000) in annual Net Sales for a Licensed
Product which is covered by a validly issued U.S. patent.

 

(e)Three million dollars ($3,000,000) upon the achievement of one hundred
million dollars ($100,000,000) in annual Net Sales for a Licensed Product which
is covered by a validly issued U.S. patent.

 

If Licensee sublicenses all or substantially all of its rights in the Licensed
Products in at least in the United States to a Development Partner, then the
above milestones shall not be owed and need not be paid.

 

8.Sublicensing Income. Sections 3.2 and 3.3 of the License Agreement are hereby
deleted and replaced in their entirety with the following:

 

3.2. Sublicensing Income.

 

(a)Licensee shall pay The Regents the Sublicense Percentage of all Sublicensing
Income received by Licensee or an Affiliate, provided that, once a Sublicensee
begins selling Licensed Products or Licensed Methods, The Regents shall not in
any event receive under this Section 3.2(a) less than an amount equal to five
percent (5%) of Net Sales of such Licensed Products or Licensed Methods sold or
disposed of by such Sublicensee, its Affiliate, Joint Venture or Sublicensee, in
the Field of Use in accordance with Article 5 (Royalties) as if these were
Licensee’s Net Sales (the “Net Sales Floor”).

 

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(b)The “Sublicense Percentage” is 40% commencing as of the Sixth Amendment
Effective Date, and such percentage may be adjusted as provided below. Licensee
represents and warrants that it has not previously granted any Sublicenses that
includes the rights to offer for sale and sell Licensed Products and Licensed
Method. If Licensee, together with its Affiliates, incur Development Costs in
aggregate of fourteen million dollars ($14,000,000) on developing Licensed
Products in the Field of Use following the Sixth Amendment Effective Date (the
“Development Cost Threshold”), then thereafter the Sublicense Percentage will be
reduced as provided in subsection (c) below if Licensee, together with its
Affiliates, incur additional Development Costs prior to granting a Sublicense to
a Development Partner, which Development Costs may include costs expended in
connection with any of the following: (i) clinical trials and other studies and
development work on Licensed Products (including manufacturing and regulatory
activities); and (ii) the analysis of the clinical trial and grey matter data
described in Section 3.2 of the CTA Amendment. Licensee will provide The Regents
with written notice if and when the Development Cost Threshold has been met,
accompanied by such supporting documentation for such costs as The Regents may
reasonably request.

 

(c)Once the Development Cost Threshold has been met, any Development Costs
incurred by Licensee or its Affiliates shall decrease the Sublicense Percentage
by one percentage point for every four million dollars ($4,000,000), or by the
corresponding fraction thereof, of additional Development Costs incurred by
Licensee or its Affiliates, provided that the Sublicense Percentage shall never
decrease below twenty-five percent (25%) (provided that the Net Sales Floor
shall still apply). For example, if the Development Cost Threshold has been met,
and Licensee then incurs Development Costs of twenty million dollars
($20,000,000) in conducting a Phase II study, the Sublicense Percentage will
automatically decrease to thirty-five percent (35%), (provided that the Net
Sales Floor shall still apply). Licenseee shall provide supporting documentation
that The Regents may reasonably request to establish the amount of Development
Costs.

 

(d)To the extent Licensee’s assets associated with the use of Compound in the
Field are transferred to a third party through an asset sale or other similar
procedure other than a Sublicense (an “Asset Transaction”, which expressly
excludes an acquisition of Licensee or its Affiliates), The Regents will receive
the Sublicense Percentage of the compensation Licensee receives in consideration
of the Asset Transaction. To the extent more assets than those related to the
Compound in the Field of Use are transferred in connection with an Asset
Transaction, the Sublicense Percentage shall only apply to consideration
received for the Estriol assets (that is, a reasonable allocation of the total
consideration paid shall be made between the amount of consideration
appropriately allocable to the value of the Estriol assets and the value of the
other assets in the transaction), with any dispute as to such allocation to be
settled by binding arbitration under the complex commercial arbitration rules of
the AAA, with both parties bearing their own costs.

 

3.3.  [Reserved]

 

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9.Effects of Merger/Acquisition. To the extent there is a merger or acquisition
(including by a “change of control” transaction) of Licensee or an Affiliate
that holds the rights to the Licensed Products, then the surviving entity (which
may remain the Licensee, or may be the acquirer) shall pay the amounts set forth
above in Sections 6 and 7 for its development and sale of Licensed Products,
unless and until such rights are sublicensed by a Sublicense, in which case the
sharing of Sublicense Income set forth in Section 8 above shall apply.

 

10.Representations, Warranties and Covenants.

 

(a)Reciprocal Representations and Warranties. Each Party represents and warrants
to the other Party that: (i) the License Agreement, as amended hereby, is a
legal and valid obligation binding upon the execution of this Sixth Amendment
and enforceable against it in accordance with its terms and conditions; and (ii)
the execution, delivery and performance of this Sixth Amendment by such Party
has been duly authorized by all necessary corporate action, and the person
executing this Sixth Amendment on behalf of such Party has been duly authorized
to do so by all requisite corporate actions.

 

(b)The Regents’ Representations and Warranties. The Regents represent and
warrant that:

 

(i)The Regents have the right to license the rights to The Regents’ Patent
Rights, the Additional Patent Rights and the Licensed Know-How as provided
herein;

 

(ii)Except as set forth in 2.2 of the License Agreement, and to the extent of
the knowledge of the UCLA Office of Intellectual Property Administration as of
the Effective Date, The Regents have not granted to any Third Party any license
or other right with respect to any portion of The Regents’ Patent Rights, or the
Additional Patent Rights.

 

(iii)Exhibit A contains a true and complete list of the Additional Patent Rights
existing on the Sixth Amendment Effective Date; and

 

(iv)The Regents have obtained a full assignment of ownership from all known
inventors and/or creators of The Regents’ Patent Rights, to the extent of the
knowledge of the UCLA Office of Intellectual Property Administration, and will
make best efforts to do so for the Additional Patent Rights.

 

11.Updates. Within 30-days of the Effective Date of this Sixth Amendment, The
Regents shall provide the following information:

 

(i)Whether The Regents or Institution have been served with or received any
notice of any (A) threatened interference actions or oppositions to any Patent
Rights within The Regents’ Patent Rights or the Additional Patent Rights or (B)
other litigation before any patent office, court, or any other governmental
entity in any jurisdiction in regard to the Regents’ Patent Rights or the
Additional Patent Rights; and

 

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(ii)Whether The Regents or Institution have not been served with any complaint
alleging infringement of a third party’s Patent Rights arising from the practice
of the claims in any of The Regents’ Patent Rights or the Additional Patent
Rights.

 

12.Replacement of Regents’ Patent Rights.

 

(a)Every reference to "Regents’ Patent Rights" in the License Agreement shall be
amended to read as provided in the following: (i) "Regents’ Patent Rights and
Additional Patent Rights" for Recitals, Sections 1.2, 1.3, 2.1 (first instance),
2.3, 5.2, 7.2, 17.4d, 17.4e, (ii) "Regents' Patent Rights or Additional Patent
Rights" for Sections 1.8, 2.1 (second instance), 5.8, 7.1, 7.6, 13.1, 17.4a,
18.1, 29.5.

 

(b)Section 5.3 of the License Agreement is hereby amended to read as follows:
"5.3 Paragraphs 1.1, 1.2, 1.3, 1.4 and 1.12 define Regents' Patent Rights,
Licensed Products, Licensed Methods, the Field of Use and Additional Patent
Rights so that royalties are payable on products covered by pending patent
applications and issued patents. Royalties accrue for the duration of this
Agreement".

 

13.Life of the Agreement. Section 11.1 of the License Agreement is hereby
amended in its entirety to read:

 

11.1      Unless otherwise terminated by operation of law or by acts of the
Parties in accordance with the terms of this Agreement, this Agreement is in
force from the Effective Date recited on page 1 of the License Agreement and
remains in effect for the life payment obligations recited in this Agreement.

 

14.Effectiveness Conditioned. This Sixth Amendment is effective only if (a) it
is fully executed by both Parties and (b) both Parties fully execute the CTA
Amendment and the Release Agreement of equal date with this Sixth Amendment.

 

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15.General. Except as expressly set forth in this Sixth Amendment, all terms and
conditions of the License Agreement remain in full force and effect. This Sixth
Amendment sets forth and constitutes the entire agreement and understanding
between the Parties with respect to the subject matter hereof and all prior
agreements, understanding, promises and representations, whether written or
oral, with respect thereto. Each Party confirms that it is not relying on any
representations or warranties of the other Party except as specifically set
forth herein. No amendment or modification of this Sixth Amendment will be
binding upon the Parties unless in writing and duly executed by an authorized
representatives of each Party. Any term or condition of this Sixth Amendment may
be waived at any time by the Party that is entitled to the benefit thereof, but
no such waiver will be effective unless set forth in a written instrument duly
executed by or on behalf of the Party waiving such term or condition. The waiver
by either Party hereto of any right hereunder or of claims based on the failure
to perform or a breach by the other Party will not be deemed a waiver of any
other right hereunder or of any other breach or failure by said other Party
whether of a similar nature or otherwise. Each Party acknowledges that it has
been represented by legal counsel with respect to the negotiation and
preparation of this Sixth Amendment and agrees that no provision hereof shall be
strictly construed against either Party, irrespective of which Party is deemed
to have drafted such provision. The captions of this Sixth Amendment are for
convenience of reference only and in no way define, describe, extend or limit
the scope or intent of this Sixth Amendment or the intent of any provision
contained in this Sixth Amendment. The term “including” as used herein means
including, without limiting the generality of any description preceding such
term. This Sixth Amendment may be executed in two or more counterparts, each of
which will be deemed an original, but all of which together will constitute one
and the same instrument. In addition, this Sixth Amendment may be executed by
facsimile or “PDF” and such facsimile or “PDF” signature shall be deemed to be
an original.

 

REMAINDER OF PAGE INTENTIONALLY BLANK.

 

SIGNATURE PAGE FOLLOWS

 

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Execution Version
Confidential

 

In Witness Whereof, the Parties have executed this Sixth Amendment by their
respective authorized representatives as of the date first written above.

 

The Regents Of The University Of California       By: /s/ Emily W Loughran  
Name: Emily W Loughran   Title: Sr. Director of Licensing               Putney
Drug Corp.       By: /s/ Jeffrey Riley   Name: Jeffrey Riley   Title:

CEO, President and Director

 

 

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Execution Version
Confidential

 

Exhibit A

 

Additional Patent Rights
as of the Sixth Amendment Effective Date

 

1)UCLA CASE NO. 2015-280: “Using Estrogens as Treatment to Improve Fatigue in
Multiple Sclerosis and Other Neurodegenerative Diseases”

 

Provisional Patent Application No. 62/067,264 entitled, “Compositions and
Methods for Treating Fatigue”, filed October 22, 2014 (UCLA Case No. 2015-280-1)
by Dr. Rhonda R. Voskuhl, and assigned to The Regents.

 

2)UCLA CASE NO. 2015-282: “Using Estrogens as Treatments to Improve Depression
Mood in Multiple Sclerosis and Other Neurodegenerative Diseases”

 

Provisional Patent Application No. 62/068,162 entitled, “Compositions and
Methods for Treating Depression”, filed October 24, 2014 (UCLA Case No.
2015-282-1) by Dr. Rhonda R. Voskuhl, and assigned to The Regents.

 

3)UCLA CASE NO. 2015-605: “Estriol Blood Level for Maximizing Treatment in MS”

 

Provisional Patent Application No. 62/140,239 entitled, “Methods of Monitoring
Estriol Therapy”, filed October 30, 2014 (UCLA Case No. 2015-605-1) by Dr.
Rhonda R. Voskuhl, and assigned to The Regents.

 

4)UCLA CASE NO. 2015-606-1: “Sparing Gray Matter Atrophy In Ms Patients That Are
Enhancing Lesion Negative”

 

Provisional Patent Application No. 62/140,245 entitled, “Methods of Providing
Neuroprotective Therapy”, filed March 30, 2015 (UCLA Case No. 2015-606-1) by Dr.
Rhonda R. Voskuhl, and assigned to The Regents.

 

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Execution Version
Confidential

 

Exhibit B

 

Estriol

 

[tpg16.jpg]

 

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