EXHIBIT 10.3

 

 

[***]

Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

SPONSORED RESEARCH AGREEMENT NO. UTA13-001113

This Sponsored Research Agreement (“Agreement”) is made between The University
of Texas at Austin, Austin, Texas (“University”), an institution of higher
education created by the Constitution and law of the State of Texas under The
University of Texas System (“System”) and Aeglea Development Company, Inc.,
AERase, Inc., AEMase, Inc., AECase, Inc., AE4ase, Inc., AE5ase, Inc., and
AE6ase, Inc., all Delaware C corporations with their principal place of business
at 815 A Brazos St., #101, Austin TX 78701 (each a “Sponsor Entity” and
collectively, “Sponsor”).  Aeglea Development Company, Inc. may be referred to
herein as the “Funding Sponsor” or “Sponsor Entity” as appropriate.

RECITALS

A.

Sponsor desires that University perform certain research work hereinafter
described and is willing to advance funds to sponsor such research;

B.

Sponsor desires to obtain certain rights to patents and technology developed
during the course of such research with a view to profitable commercialization
of such patents and technology for the Sponsor’s benefit; and

C.

University is willing to perform such research and to grant rights to such
patents and technology;

NOW THEREFORE, in consideration of the mutual covenants and promises herein
contained, the University and Sponsor agree as follows:

1.EFFECTIVE DATE

This Agreement shall be effective as of December 1, 2013 (the “Effective Date”).

2.RESEARCH PROGRAM

2.1University will use reasonable efforts to conduct the Research Program
described in Attachment A (“Research Program”), and will furnish the facilities
necessary to carry out said Research Program.  The Research Program will be
under the direction of Professor George Georgiou (“Principal Investigator”), or
(his or her) successor as mutually agreed to by the parties and will be
conducted by the Principal Investigator at the University.  University agrees to
use reasonable efforts to perform the Research Program in a manner consistent
with its status as an institution of higher education.  University shall perform
the Research Program in accordance with (i) established University policies and
procedures, including, but not limited to, policies and procedures applicable to
research involving human subjects, human tissues or organs, laboratory animals,
and hazardous agents and materials, and (ii) all applicable federal, state, and
local laws, rules, regulations and guidelines.

2.2The Research Program shall be performed during the period from the Effective
Date for a period of 12 month periods thereafter (the “Research Term”).  Funding
Sponsor shall have the option of extending the Research Program under mutually
agreeable support terms.

***Confidential Treatment Requested.

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2.3Sponsor understands that University’s primary mission is education and
advancement of knowledge, and consequently the Research Program will be designed
to carry out that mission.  The manner of performance of the Research Program
shall be determined solely by the Principal Investigator.  University does not
guarantee specific results, and the Research Program will be conducted only on a
reasonable efforts basis.

2.4University will keep accurate financial and scientific records relating to
the Research Program and will make such records available to Sponsor or its
authorized representative throughout the Term of the Agreement during normal
business hours upon reasonable notice.

2.5Sponsor understands that University may be involved in similar research on
behalf of itself and others.  University shall be free to continue such research
provided that it is conducted separately from the Research Program hereinafter
defined, and Sponsor shall not gain any rights via this Agreement to such other
research.

2.6University does not guarantee that any patent rights will result from the
Research Program, that the scope of any patent rights obtained will cover
Sponsor’s commercial interests, or that any such patent rights will be free of
dominance by other patents, including those based upon inventions made by other
inventors in The University of Texas System independent of the Research Program.

3.COMPENSATION

3.1Sponsor obligations under this Article 3 shall be limited to Funding Sponsor.

3.2As consideration for the performance by University of its obligations under
this Agreement, Funding Sponsor will pay the University an amount equal to its
reasonable, documented expenditures and reasonable overhead (such overhead to
not exceed the rate set forth in University’s indirect rate agreement with the
U.S. Federal Government) in conducting the Research Program subject to a maximum
expenditure limitation of $386,252, provided that in any and all events, the
amounts charged by University shall not, without Funding Sponsor’s prior written
consent, exceed the amount.  Payments shall be made as follows (subject to the
possible later return of funds if uncommitted and unexpended, under Section
3.3):

(a)Upon execution of all parties to the Agreement: $193,126;

(b)$96,563 by March 31, 2014; and

(c)$96,563 by June 30, 2014

Payments should be made within 30 days of the receipt of an undisputed invoice
sent via mail and email and payable to The University of Texas at Austin, make
reference to the Principal Investigator, Agreement number and title of the
Research Program funded under this Agreement, and submitted to the address in
Article 3.5.

3.3University shall maintain all Research Program funds in a separate account
and shall expend such funds for wages, supplies, equipment, travel, and other
operational expenses in connection with the Research Program.  It is understood
that funds of the Research Program which are not used in a particular quarter
may be used in subsequent quarters, and that the Principal Investigator may
transfer funds within the budget as needed without Funding Sponsor’s approval,
as long as such transfers do not effect a change in the scope of work of the
Research Program.  It is also understood that subject to Section 10.4,
uncommitted and unexpended funds remaining at the termination of the Agreement
shall be returned to

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Funding Sponsor within ninety (90) days of the effective date of termination;
provided, however, that the parties agree that in order to minimize
administrative close-out expenses, if funds remaining upon termination or
expiration of the Agreement equal $250.00 or less, such funds shall be retained
by the University and disposed of in accordance with University policy.

3.4University shall retain title to all equipment purchased and/or fabricated by
it with funds provided by Funding Sponsor under this Agreement.

3.5

Checks shall be made payable to University and sent to:

The University of Texas at Austin

Office of Accounting  SPAA

P.O.  Box 7159

Austin, Texas 78713-7159

(512) 471-6231

Tax ID #: 746000203

Invoices shall be mailed and emailed to Funding Sponsor at:

Aeglea Development Company

815-A Brazos, Ste_#101

Austin TX 78701

Attn: David G.  Lowe

Phone: [phone]

Fax: (866) 873-2149

E-mail: [email[

 

4.CONSULTATION AND REPORTS

4.1Sponsor’s designated representative (“Designated Representative”) for
consultation and communications with the Principal Investigator shall be  David
G.  Lowe or such other person as Sponsor may from time to time designate in
writing to University and the Principal Investigator.

4.2During the term of the Agreement, Sponsor’s representatives may consult
informally with University’s representatives regarding the project, both
personally and by telephone.  Access to work carried on in University
laboratories in the course of these investigations shall be entirely under the
control of University personnel but shall be made available on a reasonable
basis.

4.3The Principal Investigator will make up to one oral report(s) monthly and
quarterly written reports accompanied by a presentation describing the results
and accomplishments obtained and plans going forward.  Changes or amendments to
the Research Program if any, will be discussed at the quarterly meeting and
described in a written amendment to the Research Program as requested by
Sponsor’s Designated Representative.  The Principal Investigator shall also
submit a comprehensive final report within ninety (90) days of termination of
the Agreement which shall consist of a report of all activities undertaken and
accomplishments achieved through the Research.

5.PUBLICITY

Neither party shall make reference to the other in a press release or any other
written statement in connection with work performed under this Agreement, if it
is intended for use in the public media, except as required by the Texas Public
Information Act or other law or regulation.  University, however, shall have the
right to acknowledge Sponsor’s support of the investigations under this
Agreement in scientific or academic publications and other scientific or
academic communications, without Sponsor’s prior approval.  In any statements,
the scope and nature of participation shall be described accurately and
appropriately.

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6.PUBLICATION AND ACADEMIC RIGHTS; CONFIDENTIALITY

6.1University and the Principal Investigator have the right to publish or
otherwise publicly disclose information gained in the course of this Agreement,
except for Sponsor’s Confidential Information.  In order to avoid loss of patent
rights as a result of premature public disclosure of patentable information,
University will submit (a) any prepublication materials and (b) a copy of any
materials to be publicly disclosed to Sponsor for review and comment thirty (30)
days in advance of its planned submission for publication or public disclosure
to the extent possible, but in the case of any requests under the Texas Public
Information Act, prior to release of any information to the requestor.  Funding
Sponsor may request in writing, and University shall agree to, (i) the deletion
of any Confidential Information provided by Sponsor, and (iii) a delay of such
proposed publication or public disclosure for an additional period, not to
exceed sixty (60) days, in order to protect the potential patentability of any
technology described therein.  Funding Sponsor shall be entitled to receive in
any such publication or public disclosure an acknowledgment of its sponsorship
of the Research Program.  University shall have final authority to determine the
scope and content of any publications or disclosures provided that in no event
shall any publication or disclosure include Sponsor’s Confidential Information.

6.2It is anticipated that inventions or discoveries arising from the Research
Program (“Inventions”) shall be discussed with Funding Sponsor concurrently with
their reduction to practice by the Principal Investigator.  It is understood
that the University investigators may discuss the research being performed under
this Agreement with other University investigators but shall not reveal
Confidential Information to such investigators unless such investigators have
signed a nondisclosure agreement.

6.3In conjunction with the Research Program, Sponsor may wish to disclose
certain of its confidential and/or proprietary information (“Confidential
Information”) to University during the term of this Agreement.  Confidential
Information will be transmitted in writing and clearly marked “Confidential,”
“Proprietary,” or similarly, or if disclosed orally will be reduced to writing
by Disclosing Party, clearly marked “Confidential,” “Proprietary,” or similarly,
and transmitted to the Contact Person of Receiving Party within thirty (30) days
after oral disclosure.  No license under or title to any invention, patent,
trademark, trade name or other intellectual property or other rights or
interests in the Confidential Information now or hereafter owned by or
controlled by any Party is granted either expressly, by implication, estoppel or
otherwise by the Agreement.  All Confidential Information is provided “AS IS”
and without warranty, express or implied, of any kind.

University will use Confidential Information solely for the purpose of
conducting the Research Program, and shall use reasonable efforts to prevent the
disclosure of Confidential Information to third parties during the term of this
Agreement and for a period of five (5) years after its expiration or
termination.  If required, University may disclose Confidential Information to a
governmental authority or by order of a court of competent jurisdiction,
provided that such disclosure is subject to all applicable governmental or
judicial protection available for like information and reasonable advance notice
is given to Funding Sponsor.  University’s obligations with respect to
Confidential Information shall not apply to information that (a) is already in
University’s possession at the time of disclosure; (b) is or later becomes part
of the public domain through no fault of University; (c) is received on a
non-confidential basis from a third party having no obligations of
confidentiality or nonuse to University’s; or (d) independently developed by
University.  Notwithstanding the foregoing, University may retain one archival
copy of the Confidential Information received in a secure location to be used
solely to determine its obligations under the Agreement.

The Parties agree that, in the event of breach or threatened breach or intended
breach of the Agreement, each Party, in addition to any other rights and
remedies available to it at law or in equity, may seek injunctive or equitable
relief without the necessity of posting bond or proving that it has no adequate
remedy at law.

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7.PATENTS, COPYRIGHTS AND TECHNOLOGY RIGHTS

7.1Title to Inventions conceived and reduced to practice solely by University
shall reside in University (“University Inventions”).  Title to all Inventions
conceived and reduced to practice solely by Sponsor shall reside in Sponsor
(“Sponsor Inventions”).  Title to all inventions and discoveries conceived and
reduced to practice jointly by Sponsor and University shall reside jointly in
Sponsor and University (“Joint Inventions”).  University hereby grants to
Sponsor an exclusive first option to negotiate a royalty- bearing exclusive
license for any invention or discovery that is conceived or reduced to practice
during the term of this Agreement directly resulting from the performance of
research hereunder to the extent that University is able to do so under
applicable law.  It is contemplated that, in the majority of instances, Sponsor
will be asked to determine whether it will exercise its option prior to the
filing of the first patent application.  University reserves for itself a
royalty-free, irrevocable license to make and use such University Inventions and
Joint Inventions for its own research and educational purposes, but not for
commercial purposes during the option period.  If a University Invention or
Joint Invention arises from the Research Program, the Principal Investigator
shall promptly submit an invention disclosure
(http://www.otc.utexas.edu/InventorForms.jsp) to University’s Office of
Technology Commercialization (“OTC”).  University will provide to Sponsor a full
copy of such disclosure promptly after such disclosure is received by
OTC.  Sponsor may review (and University shall provide to Sponsor) any and all
patentability and freedom to operate opinions that have been commissioned by the
University.  A Sponsor Entity shall then have ninety (90) days from receipt of
such disclosure of any University Invention or Joint Invention to notify
University of its desire to enter into such a license agreement, and a
non-binding term sheet and thereafter a license agreement shall be negotiated in
good faith within a period not to exceed six (6) months (“License Option
Period”) from the applicable Sponsor Entity’s notification to University of its
desire to enter into a license agreement, or such period of time as the parties
shall mutually agree in writing.  The parties agree to negotiate, in good faith,
a license agreement with terms and conditions substantially similar to existing
license agreements between the parties, to the extent allowed by current law,
University policy, and reasonable updates to financial terms.  During the
License Option Period, University agrees that it will not offer its rights in
University Inventions or Joint Inventions to any third party or negotiate with
third parties with respect to those rights.  If the parties fail to enter into a
license agreement within the License Option Period under the provisions of this
Section 7.1, University rights in University Inventions and Joint Inventions
shall be disposed of in accordance with University policies with no further
obligations to Sponsor.

7.2“Background Intellectual Property” (“BIP”) means intellectual property and
the legal rights therein (including, but not limited to, inventions, patent
applications, patents, copyrights, and any information embodying proprietary
data such as technical data and computer software) of University developed or
created by Principal Investigator(s) before the Effective Date of the Research
Program and necessary for the full exercise of all intellectual property which
is related to the Research Program.  University BIP is listed in Attachment B of
this Agreement.  The Parties agree that nothing in this Agreement grants either
Party any rights to any background intellectual property of the other Party
created before the Effective Date of the Agreement.

7.3The applicable Sponsor Entity has the right to elect to have patent
applications filed on any University Invention or Joint Invention, and if it
does so, then such Sponsor Entity shall reimburse University for all documented,
out-of-pocket patent expenses incurred by University, including those for
patentability opinions, within thirty (30) days of such Sponsor Entity’s receipt
of an invoice from University.  Such patent expenses shall include, but not be
limited to, the cost of any prior activities investigating patentability of said
invention before exercise of the option, such as search and opinion for
patentability, that may have been performed by University pursuant to its
arrival at a judgment of commercially exploitable status.  Following expiration
of the License Option Period, and in the event that University grants a license
to any University Inventions to a third party (the “Third Party License”),

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University shall pay to the applicable Sponsor Entity its reasonable costs
incurred in connection with the preparation, filing, prosecution and maintenance
of the licensed University Inventions or Joint Inventions paid under the Third
Party License with the following priority for payment: i) in one full payment
from the fees reimbursed to University by a third party under the executed
license; or if necessary, ii) on a quarterly basis, a royalty (the “Third Party
Royalty”) equal to one hundred percent (100%) of University’s net licensing
revenue attributable to the Third Party License (including license fees,
royalties, revenue sharing, milestone payments and other monetary payments)
until such time as University has paid to such Sponsor Entity aggregate Third
Party Royalties equal to such Sponsor Entity’s reasonable costs incurred in
connection with the preparation, filing, prosecution and maintenance of the
licensed University Inventions.

7.4At its discretion, University may allow the applicable Sponsor Entity to
instruct Prosecution Counsel directly for University Inventions and Joint
Inventions, provided, that prior written approval is obtained and the
Prosecution Counsel remains counsel to the University with an appropriate
contract (and shall not jointly represent such Sponsor Entity unless requested
by such Sponsor Entity and approved by University, not to be unreasonably
denied, and an appropriate engagement letter and conflict waiver are in
effect).  If such Sponsor Entity wishes to instruct Prosecution Counsel directly
or change Prosecution Counsel, such Sponsor Entity may request to do so by
following the University’s procedures for such.  Subject to the terms herein
University reserves in its sole discretion the ability to change Prosecution
Counsel and to approve or disapprove any requested changes by such Sponsor
Entity.  The Parties agree that they share a common legal interest to get valid
enforceable patents in strategically important countries and that both Parties
will maintain as privileged all information received pursuant to this Section
7.  Each Party agrees to cooperate fully in the preparation, filing, and
prosecution of any patent and any joint patent, as described herein.  Such
cooperation includes without limitation executing all papers and instruments, or
requiring its representatives to execute such papers and instruments, so as to
effectuate the ownership of such intellectual property rights.

7.5Notwithstanding anything to the contrary set forth herein, , University
hereby grants to Sponsor a perpetual, irrevocable, worldwide, non-exclusive,
royalty free right and license, with the right to sublicense to third parties
through multiple tiers, to use the Data and Results for any and all
purposes.  Data and Results mean all data, information and results arising from
the Research Program that are included in the Research Program deliverables but
are not inventions and discoveries for which a patent invention disclosure is
made.

8.LIABILITY

8.1Sponsor agrees to defend (and subject to the statutory duties of the Texas
State Attorney General to defend University, if applicable),indemnify and hold
harmless System, University, their Regents, officers, agents and employees from
any liability, loss or damage they may suffer as a result of third party claims,
demands, costs or judgments against them arising out of the activities to be
carried out pursuant to the obligations of this Agreement, including but not
limited to the use by Sponsor of the results obtained from the activities
performed by University under this Agreement; provided, however, that the
following is excluded from Sponsor’s obligation to defend, indemnify and hold
harmless:

(a)the negligent failure of University to substantially comply with any
applicable FDA or other governmental requirements; or

(b)the negligence or willful malfeasance of any Regent, officer, agent or
employee of University or System

8.2To the extent authorized by the constitution and laws of the State of Texas,
University agrees to defend, indemnify and hold harmless Sponsor, its officers,
agents and employees from any

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liability, loss or damage they may suffer as a result of third party claims,
demands, costs or judgments against them arising out of (i) the negligence or
willful malfeasance of any Regent, officer, agent or employee of University or
System or (ii) breach of this Agreement by any Regent, officer, agent or
employee of University or System, provided, however, that University shall not
be obligated to hold harmless any Sponsor Indemnitee from claims arising out of
the negligence or willful malfeasance of Sponsor.

8.3Both parties agree that upon receipt of a notice of claim or action arising
out of the activities to be carried out pursuant to the Research Program, the
party receiving such notice will notify the other party promptly.

9.INDEPENDENT CONTRACTOR

For the purpose of this Agreement and all services to be provided hereunder, the
parties shall be, and shall be deemed to be, independent contractors and not
agents or employees of the other party.  Neither party shall have authority to
make any statements, representations or commitments of any kind, or to take any
action which shall be binding on the other party, except as may be expressly
provided for herein or authorized in writing.

10.TERM AND TERMINATION

10.1This Agreement shall commence on the Effective Date and extend until the end
of the Research Term, unless sooner terminated in accordance with the provisions
of this Article 10.

10.2This Agreement may be terminated by Sponsor for its convenience upon sixty
(60) days prior written notice to University.

10.3 In the event that either party shall be in default of its material
obligations under this Agreement and shall fail to remedy such default within
sixty (60) days after receipt of written notice thereof, this Agreement may be
terminated at the option of the party not in default upon expiration of the
sixty (60) day period.

10.4This Agreement shall terminate automatically and immediately if Sponsor
becomes bankrupt or insolvent and/or enters receivership or trusteeship, whether
by voluntary act of Sponsor or otherwise.

10.5Termination or cancellation of this Agreement shall not affect the rights
and obligations of the parties accrued prior to termination.  Upon termination,
(i) Sponsor shall pay University for all reasonable expenses incurred or
committed to be expended due pursuant to Section 3 hereof as of the effective
termination date, including salaries for appointees for the remainder of their
appointment and (ii) University shall return to Sponsor or destroy any
Confidential Information in its possession or control, subject to University’s
right to keep an archival copy pursuant to Section 6.3.

10.6Any provisions of this Agreement which by their nature extend beyond
termination shall survive such termination including, without limitation,
Sections 6 and 7.

10.7This Agreement will terminate with respect to any individual Sponsor Entity
at such time as it is no longer a wholly owned subsidiary of Aeglea
BioTherapeutics Holdings LLC and upon such a termination the respective Sponsor
Entity shall be removed as a party to this Agreement.  Sponsor will provide
prompt written notice of the same to University.

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11.ATTACHMENTS

Attachments A and B are incorporated and made a part of this Agreement for all
purposes.  

12.USE OF HUMAN SUBJECTS (if applicable)

12.1University will conduct all research in accordance with Federal Wide
Assurance #2030, written protocol, applicable law, and University’s ethical
standards.  In the event a research participant has a research related injury
neither University nor the Sponsor are responsible for any resulting medical
care.

12.2If the Sponsor is responsible for monitoring research, then the Sponsor must
alert University’s Institutional Review Board (“IRB”) when research findings:

(a)Affect the safety of the participants

(b)Affect the willingness of research participants to continue participation

(c)Influence the conduct of the study

(d)Alter the IRB’s approval for the study

12.3In the event research findings indicate that current and past participants
are at increased risk that was not anticipated at the time of the study design,
the Principal Investigator, in accordance with both University IRB Policy and
Procedures and the informed consent agreement, will immediately inform research
participants of risk alteration.

13.GENERAL

13.1Neither Party can assign its rights under this Agreement without the prior
written consent of the other Party, which consent will not be unreasonably
withheld.  Notwithstanding the foregoing, no such consent shall be needed for a
assignment by any Sponsor Entity to another Sponsor Entity of part or all of the
assigning Sponsor Entity’s interest.  After a Party has received a written
request for consent to assign, the receiving Party will respond in writing
within thirty (30) days.  If the receiving Party does not respond in writing
within thirty (30) days, that Party’s silence will be deemed to mean that the
receiving Party consents to the assignment.  Any assignment made without the
written or deemed consent of the non-assigning Party will be null and
void.  Subject to the approval of University, which may not be unreasonably
withheld, Sponsor is permitted to assign this Agreement in connection with a
merger or a sale or transfer of substantially all of its assets; provided,
however, that such assignee shall have expressly assumed all of the obligations
and liabilities of Sponsor under this Agreement, and provided, further that,
University may assign its right to receive payments hereunder.

13.2This Agreement constitutes the entire and only agreement between the parties
relating to the Research Program, and all prior negotiations, representations,
agreements and understandings are superseded hereby.  No agreements altering or
supplementing the terms hereof may be made except by means of a written document
signed by the duly authorized representatives of University and Funding
Sponsor.  Terms and conditions which may be set forth (front, reverse, attached
or incorporated) in any purchase order issued by Sponsor in connection with this
Agreement shall not apply, except for informational billing purposes; i.e.,
reference to purchase order number, address for submission of invoices, or other
invoicing items of a similar informational nature.

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13.3Any notice required by this Agreement by Articles 7, 8 or 10 shall be given
prepaid, first class, certified mail, return receipt requested, addressed in the
case of University to:

The University of Texas System, O.G.C.
201 West 7th Street
Austin, Texas 78701
Attention: Intellectual Property Section
Phone: (512) 499-4462
FAX: (512) 499-4523

Vice President for Research
The University of Texas at Austin
P.O. Box 7996, Mail Code G1400
Austin, Texas 78713
Attention: Technology Licensing Specialist
Phone: (512) 471-2995
FAX: (512) 475-6894

or in the case of the Sponsor to:

Aeglea Development Company, Inc.
815-A Brazos St., #101
Austin TX 78701
Attn: David G. Lowe
Phone: [phone]
FAX: (866) 873-2149
E-Mail: [email]

or at such other addresses as may be given from time to time in accordance with
the terms of this notice provision.

Notices and other communications regarding the day-to-day administration and
operations of this Agreement shall be mailed (or otherwise delivered), addressed
in the case of University to:

The University of Texas at Austin
Office of Industry Engagement
North Office Building-A, Suite 5.2
Post Office Box 7727, MC A9300
Austin, Texas 78712-1736
Attention: Bill Catlett, Director
Phone: (512) 471-3866
FAX: (512) 471-7839
E-mail: industry@austin.utexas.edu

with a copy to:

Dr. George Georgiou
The University of Texas at Austin
Department of Chemical Engineering
Austin, Texas 78712

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Phone: [phone]
E-Mail: [email]

or in the case of Sponsor to:

Aeglea Development Company, Inc.
815-A Brazos St., #101
Austin TX 78701
Attn: David G. Lowe
Phone: [phone]
FAX: (866) 873-2149
E-Mail: [email]

13.4This Agreement shall be governed by, construed, and enforced in accordance
with the internal laws of the State of Texas.

13.5Each Party acknowledges that this Agreement and the performance thereof are
subject to compliance with any and all applicable United States laws,
regulations, or orders, including those that may relate to the export of
technical data, and each Party agrees to comply with all such laws, regulations
and orders, including, if applicable, all requirements of the International
Traffic in Arms Regulations and/or the Export Administration Act, as may be
amended.  Sponsor further agrees that if the export laws are applicable, it will
not disclose or re-export any technical data under this Agreement to any
countries for which the United States government requires an export license or
other supporting documentation at the time of export or transfer, unless Sponsor
has obtained prior written authorization from the U.S. Office of Export Control
or other authority responsible for such matters.

13.6If any provision contained in this Agreement is held invalid, unenforceable
or contrary to laws then the validity of the remaining provisions of this
Agreement shall remain in full force.  In such instance, Parties shall use their
best efforts to replace the invalid provision(s) with legally valid provisions
having an economic effect as close as possible to the original intent of
Parties,

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IN WITNESS WHEREOF, the parties have caused this Agreement to be executed by
their duly authorized representatives.

THE UNIVERSITY OF TEXAS AT AUSTINAEGLEA DEVELOPMENT COMPANY, INC.

/s/ Ty Helpinstill/s/ David G. Lowe

By:  Ty HelpinstillBy:  David G. Lowe

Title:  Assoc. Dir, Office of Industry EngagementTitle:  CEO

Date:  19 December 2013Date:  12/24/13

AERASE, INC.AEMASE, INC.

/s/ David G. Lowe/s/ David G. Lowe

By:  David G. LoweBy:  David G. Lowe

Title:  CEOTitle:  CEO

Date:  12/24/13Date:  12/24/13

AECASE, INC.AE4ASE, INC.

/s/ David G. Lowe/s/ David G. Lowe

By:  David G. LoweBy:  David G. Lowe

Title:  CEOTitle:  CEO

Date:  12/24/13Date:  12/24/13

AE5ASE INC.AE6ASE; INC.

/s/ David G. Lowe/s/ David G. Lowe

By:  David G. LoweBy:  David G. Lowe

Title:  CEOTitle:  CEO

Date:  12/24/13Date:  12/24/13

 

 

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ATTACHMENT A — RESEARCH PROGRAM

Aeglea LLC will sponsor research in the laboratory of Professor George Georgiou,
Depts of Chemical Engineering, Biomedical Engineering and Molecular Biosciences
on the engineering, optimization and initial animal validation of human enzyme
therapeutics for the following purposes:

Specific Aim 1.  The systemic depletion of amino acids for cancer therapy, as
elaborated below.

Specific Aim 2.  Enzyme replacement for the treatment of patients having inborn
metabolic defects, primarily but not limited to diseases stemming from mutations
impacting physiological enzymatic function.

It is anticipated that during the 2013-2014 fiscal year, the work to be carried
out at the Georgiou lab will focus primarily, but not exclusively on Specific
Aim 1.  During this period the Georgiou lab will seek to focus on the
engineering and optimization of the following enzymes:

 

1.1

[***]

 

1.2

[***]

 

1.3

[***]

 

1.4

[***]

Studies to be performed under 1.1-1.4 may include:

 

a)

Engineering enzymes having high catalytic proficiency (kcat/Km) and substrate
specificity, as required for human therapeutic purposes.

 

b)

High thermodynamic stability in vitro and in physiological fluids, namely in
human serum

 

c)

Formulation of the enzymes from 1.1-1.4 for prolonged circulation half-life by
conjugation or polyethylene glycol or similar means.

 

d)

Development of lab scale processes for the preparative production of these
enzymes at scale.

 

e)

In vitro studies to evaluate the effect of the engineered enzymes from 1.1-1.4
on cancer cell lines and, if available on primary tumor cells.

 

f)

Evaluation of the efficacy of the enzymes from 1.1-1.4 above in xenograft tumor
mouse models, as applicable.

 

g)

Mechanistic studies as might be required to support Investigative New Drug
applications (IND) to the FDA specifically addressing the impact of enzymes from
1.1-1.4 on cell cycle arrest, autophagy and apoptotic death of cancer cells.

***Confidential Treatment Requested.

--------------------------------------------------------------------------------

Background IP * and party owning or controlling that BIP

Restrictions on BIP**

(If restrictions exist, describe nature of restrictions and third party that
holds the rights thereto.) (If no restrictions exist, state “none”)

Owned by The University of Texas at Austin:

Engineering of L-Cysteine/L-Cystine degrading enzymes for therapeutic purposes

Improvement on UTSB 741 “Engineered human methionine gamma lyase enzymes and
pharmacological preparations thereof

 

Exclusively licensed by Sponsor:

PLA number PM1400601 (6337 GEO)
BIP: 61/871,727 (provisional patent application number)

PLA number PM4011501 (6314 GEO)
BIP: 61/871,768 (provisional patent application number)

 

* “Background IP” means any and all patents or patent applications for
inventions, discoveries or technology developed prior to the date hereof which
necessarily would be infringed by the making, use or sale of a product the
making, use or sale of which would also infringe a claim of a patent or patent
application for any invention, discovery or technology reasonably expected to
result from the performance of the Research Program.  If the BIP is applicable
to multiple items, components, or processes identify both the BIP and each such
item, component, or process.

**Restrictions on BIP may include licenses granted by the owner of the BIP or
industrial sponsorship arrangements that allow the sponsor rights to review
publications or to negotiate a license.  Indicate whether development was funded
either exclusively or partially by a government or non-government source, and
list the source.  Enter any reason that owner’s ability to grant licenses in the
BIP could be restricted.  Identify basis of restriction (e.g., rights from a
pre-existing agreement, rights in data generated under another contract, limited
purpose rights under this or a prior contract, or specifically negotiated
licenses).

Printed Name:George Georgiou

Title:Professor

Signature/s/ George Georgiou

DateDecember 6, 2013

 

13

--------------------------------------------------------------------------------

 

ATTACHMENT B
SPONSORED RESEARCH AGREEMENT UTA13-001113

Identification of Background IP and Restrictions on its Use, Release,
or Disclosure

University’s Principal Investigator asserts that the following identifies the
Background IP (BIP) developed by University researchers performing under the
Research Program and restrictions that exist on the rights of the entity owning
or controlling the BIP to use, release, or disclose the BIP.

Controlled by George Georgiou and exclusively licensed by Sponsor:

“Amnase formulations and methods”

Serial No. 13/380,776

United States

Serial No. PCT/US2010/040205

International

Serial No. 61/221,396

United States

Serial No. 10800270.0 (Publication No. EP2449102)

European Patent Office

Serial No. 12111085.9

Hong Kong

Serial No. 2012-:517824

Japan

Serial No. 2,766,039

Canada

“Engineered Enzymes with Methionine-Gamma-Lyase Enzymes and Pharmacological
Preparations Thereof”

Serial No. 61/301,368

United States

Serial No. 13/020,268

United States

Serial No. PCT/US2011/023606

International

Serial No. 2011212885

Australia

Serial No. 2,788,689

Canada

Serial No. 201180013307.X

China

Serial No. 11740355

European Patent Office

Serial No. 2012-552084

Japan

Serial No. 10-2012-7023176

Republic of Korea .

“Compositions of Engineered Human Arginases and Methods for Treatine Cancer”

Serial No. 12/610,685

United States

Serial No. 61/110,218

United States

Serial No. PCT/US2009/062969

International

Serial No. 09824219.1
(Publication No. EP2350273)

European Patent Office

Serial No. 12100429.7

Hong Kong

Serial No. 2,742,497

Canada

Serial No. 2011-534855
(Publication No. JP2012507301)

Japan

 

14

--------------------------------------------------------------------------------

 

Amendment 1
To Sponsored Research Agreement UTA13-001113 (“Agreement”)
Between
The University of Texas at Austin (“UT”)
And
Aeglea Development Company, Inc., AERase, Inc., AEMase, Inc., AECase, Inc.,
AE4ase,  Inc., AE5ase, Inc., and AE6ase, Inc. (each a “Sponsor Entity” and
collectively, “Sponsor”)

The purpose of this Amendment:

To extend the period of performance and increase the limitation of funding to
perform additional research.

This Sponsored Research Agreement is modified by mutual agreement of the Parties
as follows:

1.

Attachment A, Statement of Work, is appended with the Statement of Work included
with this Amendment 1 as Attachment A-1, attached hereto.

2.

Section 2.2 is hereby replaced with the following: “The Research Program shall
be performed during the period from the Effective Date through and including
January 15, 2016 (the “Research Term”).  Funding Sponsor shall have the option
of extending the Research Program under mutually agreeable support terms.

3.

Section 3.2, first paragraph and payment schedule, are hereby replaced with the
following: “As consideration for the performance by University of its
obligations under this Agreement, Funding Sponsor will pay the University an
amount equal to its reasonable, documented expenditures and reasonable overhead
(such overhead to not exceed the rate set forth in University’s indirect rate
agreement with the U.S. Federal Government) in conducting the Research Program
subject to a maximum expenditure limitation of $761,252, an increase of $375,000
over the currently funded amount of $386,252, provided that in any and all
events, the amounts charged by University shall not, without Funding Sponsor’s
prior written consent, exceed the amount of the maximum expenditure
limitation.  Funding Sponsor has paid University $386,252 as consideration for
its performance under the Research Program as described in Attachment
A.  Payments under the following Attachment A-1 shall be made as follows
(subject to the possible later return of funds if uncommitted and unexpended,
under Section 3.3):

a)Upon execution of all parties to the Agreement: $93,750;
b)$93,750 by March 31, 2015; and
c)$93,750 by June 30, 2015
d)$93,750 by Sept 30, 2015”

Effective Date of the Sponsored Research Agreement:December 1, 2013
Effective Date of Amendment:January 15, 2015

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 1

The University of Texas at Austin15Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

All other terms and conditions of this Sponsored Research Agreement remain
unchanged.

 

THE UNIVERSITY OF TEXAS AT AUSTIN

 

 

 

/s/ Ty Helpinstill

By: Ty Helpinstill

Title: Assoc Dir, Office of Industry Engagement

Date: 28 October 2014

 

AEGLEA DEVELOPMENT COMPANY, INC.

 

 

 

/s/ David G. Lowe

By: David G Lowe

Title: CEO

Date: 11/13/14

AERASE, INC.

 

 

/s/ David G. Lowe

By: David G Lowe

Title: CEO

Date: 11/13/14

 

AEMASE, INC.

 

 

/s/ David G. Lowe

By: David G Lowe

Title: CEO

Date: 11/13/14

AECASE, INC.

 

 

/s/ David G. Lowe

By: David G Lowe

Title: CEO

Date: 11/13/14

 

AE4ASE, INC.

 

 

/s/ David G. Lowe

By: David G Lowe

Title: CEO

Date: 11/13/14

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 1

The University of Texas at Austin16Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

AE5ASE, INC.

 

 

/s/ David G. Lowe

By: David G Lowe

Title: CEO

Date: 11/13/14

 

AE6ASE, INC.

 

 

/s/ David G. Lowe

By: David G Lowe

Title: CEO

Date: 11/13/14

 

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 1

The University of Texas at Austin17Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

Attachment A-1, Statement of Work

Aeglea LLC will sponsor research in the laboratory of Professor George Georgiou,
Departments of Chemical Engineering, Biomedical Engineering and Molecular
Biosciences on the engineering, optimization and initial animal validation of
human enzyme therapeutics for the following purposes:

Specific Aim 1.  The systemic depletion of amino acids for cancer therapy.

Specific Aim 2.  Enzyme replacement for the treatment of patients having inborn
metabolic defects, primarily but not limited to diseases stemming from mutations
impacting physiological enzymatic function.

It is anticipated that during the 2014-2015 fiscal year most of the work to be
carried out at the Georgiou lab will focus primarily, but not exclusively on
Specific Aim 1.  During this period the Georgiou lab will seek to focus on the
engineering and optimization of the following enzymes:

 

1.1.

[***]

 

1.2.

[***]

 

1.3.

[***]

 

1.4.

[***]:

 

a)

Engineering enzymes having high catalytic proficiency (kcat/Km) and substrate
specificity, as required for human therapeutic purposes.

 

b)

High thermodynamic stability in vitro and in physiological fluids, namely in
human serum

 

c)

Formulation of the enzymes from 1.1-1.4 for prolonged circulation half-life by
conjugation or polyethylene glycol or similar means.

 

d)

Development of lab scale processes for the preparative production of these
enzymes at scale.

 

e)

In vitro studies to evaluate the effect of the engineered enzymes from 1.1-1.4
on cancer cell lines and, if available on primary tumor cells.

 

f)

Evaluation of the efficacy of the enzymes from 1.1-1.4 above in xenograft tumor
mouse models, as applicable.

 

g)

Mechanistic studies as might be required to support Investigative New Drug
applications (IND) to the FDA specifically addressing the impact of enzymes from
1.1-1.4 on cell cycle arrest, autophagy and apoptotic death of cancer cells.

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 1

The University of Texas at Austin18Agreement No. UTA13-001113

 

***Confidential Treatment Requested.

--------------------------------------------------------------------------------

 

Amendment 01
To Sponsored Research Agreement UTA13-001113 (“Agreement”)

This Amendment to the Sponsored Research Agreement (“Agreement”) is made between
The University of Texas at Austin, Austin, Texas (“University”), an institution
of higher education created by the Constitution and law of the State of Texas
under The University of Texas System (“System”) and Aeglea Development Company,
Inc., AERase, Inc., AEMase, Inc., AECase, Inc., AE4ase, Inc., AE5ase, Inc., and
AE6ase, Inc., all Delaware C corporations with their principal place of business
at 815 A Brazos St., #101, Austin TX 78701 (each a “Sponsor Entity” and
collectively, “Sponsor”). Aeglea Development Company, Inc. may be referred to
herein as the “Funding Sponsor” or “Sponsor Entity” as appropriate.

The purpose of this Amendment:

Sponsor and University desire to amend the terms of the Agreement to extend the
performance period at no cost as set forth below.

This Agreement is modified by mutual agreement of the Parties as follows:

1. Article 2. Research Program, paragraph 2.2 is hereby amended to read:

The Research Program shall be performed during the period from the Effective
Date through and including January 15, 2015. Funding Sponsor shall have the
option of extending the Research Program under mutually agreeable support terms.

All other terms and conditions of this Agreement remain unchanged.

IN WITNESS WHEREOF, the parties have caused this Amendment to be executed by
their duly authorized representatives.

THE UNIVERSITY OF TEXAS AT AUSTINAEGLEA DEVELOPMENT COMPANY, INC.

/s/ Ty Helpinstill/s/ David G. Lowe

By:  Ty HelpinstillBy:  David G. Lowe

Title:  Assoc. Dir, Office of Industry EngagementTitle:  CEO

Date:  24 September 2014Date:  9/23/14

AERASE, INC.AEMASE, INC.

/s/ David G. Lowe/s/ David G. Lowe

By:  David G. LoweBy:  David G. Lowe

Title:  CEOTitle:  CEO

Date:  9/23/14Date:  9/23/14

 

--------------------------------------------------------------------------------

 

AECASE, INC.AE4ASE, INC.

/s/ David G. Lowe/s/ David G. Lowe

By:  David G. LoweBy:  David G. Lowe

Title:  CEOTitle:  CEO

Date:  9/23/14Date:  9/23/14

AE5ASE INC.AE6ASE; INC.

/s/ David G. Lowe/s/ David G. Lowe

By:  David G. LoweBy:  David G. Lowe

Title:  CEOTitle:  CEO

Date:  9/23/14Date:  9/23/14

 

 

--------------------------------------------------------------------------------

 

Amendment 3
To Sponsored Research Agreement UTA13-001113 (“Agreement”)
Between
The University of Texas at Austin (“UT”)
And
Aeglea Development Company, Inc., AERase, Inc., AEMase, Inc., AECase, Inc.,
AE4ase,
Inc., AE5ase, Inc., and AE6ase, Inc. (each a “Sponsor Entity” and collectively,
“Sponsor”)

The purpose of this Amendment:

To correct the numeration of the prior amendment and increase the limitation of
funding to perform additional research, and restructure payment terms,

This Sponsored Research Agreement is modified by mutual agreement of the Parties
as
follows:

1.

“Amendment 1” executed between the parties on November 13, 2014, is restated as
and shall hereafter be known as “Amendment 2.”

2.

Attachment A, Research Program, is appended with the statement of work included
with this Amendment 3 as Attachment A-2, attached hereto.

3.

Section 2.2 is hereby replaced with the following: “The Research Program shall
be performed during the period from the Effective Dale through and including
August 31, 2016 (the “Research Term”). Funding Sponsor shall have the option of
extending the Research Program under mutually agreeable support terms.

4.

Section 3.2, first paragraph and the payment schedule, are hereby replaced with
the following: “As consideration for the performance by University of its
obligations under this Agreement, Funding Sponsor will pay the University an
amount equal to its reasonable, documented expenditures and reasonable overhead
(such overhead to not exceed the rate set forth in University’s indirect rate
agreement with the U.S. Federal Government) in conducting the Research Program
subject to a maximum expenditure limitation of $1,323,752, an increase of
$562,500 over the currently funded amount of $761,252, provided that in any and
all events, the amounts charged by University shall not, without Funding
Sponsor’s prior written consent, exceed the amount of the maximum expenditure
limitation. Payments shall be made as follows (subject to the possible later
return of funds if uncommitted and unexpended, under Section 3.3):

 

a)

$573,752 - PAID TO DATE (consisting of $386,252 under the initial Agreement and
$187,500 under Amendment 2)

 

b)

$375,000 due upon execution of this Amendment, which shall include the $93,750
previously due June 30, 2015 under Amendment 2, invoice issued on June 29, 2015

 

c)

$187,500 due on January 31, 2016, invoice to be issued by December 31, 2015

 

d)

$187,500 due on April 30, 2016, invoice to be issued by March 31, 2016

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 3
The University of Texas at AustinPage 1 of 5Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

5.

Section 3.5 is hereby amended to change the Sponsor contact information for
University invoices to: accounting@aegleabio.com, and for questions: Jo O’Keefe,
512-900-3662, (Alternate contacts: April Duley, aduley@aegleabio.com,
512-900-3826, and Charles York, cyork@aegleabio.com, 512-394-4188)

All other terms and conditions of this Sponsored Research Agreement remain
unchanged.

THE UNIVERSITY OF TEXAS AT AUSTIN

/s/ Ty Helpinstill
By: Ty Helpinstill
Title: Assoc Dir, Office of Industry Engagement
Date: 3 Aug 2015

AEGLEA DEVELOPMENT COMPANY, INC.

/s/ Charles York
By: Charles York
Title: Sr. Vice President of Finance + Accounting
Date: 10 Aug 2015

AERASE, INC.

/s/ Charles York
By: Charles York
Title: Sr. Vice President of Finance + Accounting
Date: 10 Aug 2015

AEMASE, INC.

/s/ Charles York
By: Charles York
Title: Sr. Vice President of Finance + Accounting
Date: 10 Aug 2015

AECASE, INC.

/s/ Charles York
By: Charles York
Title: Sr. Vice President of Finance + Accounting
Date: 10 Aug 2015

AE4ASE, INC.

/s/ Charles York
By: Charles York
Title: Sr. Vice President of Finance + Accounting
Date: 10 Aug 2015

AE5ASE, INC.

/s/ Charles York
By: Charles York
Title: Sr. Vice President of Finance + Accounting
Date: 10 Aug 2015

AE6ASE, INC.

/s/ Charles York
By: Charles York
Title: Sr. Vice President of Finance + Accounting
Date: 10 Aug 2015

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 3
The University of Texas at AustinPage 2 of 5Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

Attachment A-2
Statement of Work

Aeglea LLC will sponsor research in the laboratory of Professor George Georgiou,
Departments of Chemical Engineering, Biomedical Engineering and Molecular
Biosciences on the engineering, optimization and initial animal validation of
human enzyme therapeutics for the following purposes:

Specific Aim 1. The systemic depletion of amino acids for cancer therapy.

Specific Aim 2. Enzyme replacement for the treatment of patients having inborn
metabolic defects, primarily but not limited to diseases stemming from mutations
impacting physiological enzymatic function.

During the 2014-2015 fiscal year the Georgiou lab has been focusing on Specific
Aim 1; the engineering and optimization of the following enzymes:

 

1.1.

[***]

 

1.2.

[***]

 

1.3.

[***]

 

1.4.

[***]

 

It is anticipated that during the 2015-2016 fiscal year most of the work to be
carried out at the Georgiou lab will focus primarily on Specific Aim 1 but also
Specific Aim 2. During this period the Georgiou lab will seek to focus on the
engineering and optimization of the following enzyme programs:

1.1. [***]

1.2. [***]

1.3. [***]

2.1. Specific Aim 1

2.2. Specific Aim 2

2.4. Specific Aim 3

 

Studies to be performed under 1.1-2.4 may include:

 

•

Recombination (DNA shuffling) and screening of variants identified from pfunkel
library:

 

-

[***]

 

-

[***]

 

-

[***]

•

Biophysical studies aimed at [***]

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 3
The University of Texas at AustinPage 3 of 5Agreement No. UTA13-001113

 

***Confidential Treatment Requested.

--------------------------------------------------------------------------------

 

 

-

Excipients: survey of buffer, pH, excipient conditions for effect on activity,
aggregation etc.

 

-

Preliminary stress tests

•

Develop assays for transsulfuration enzyme expression

•

Proof of concept experiments in triple negative breast cancer

 

 

1.2 [***] program

•

[***]

 

 

1.3. [***]

•

1.3.1 Proof of concept studies for immune-oncology studies.

•

[***]

•

1.3.2. [***]

•

1.3.3. [***]

•

1.3.4 [***]

 

 

2. SRA expansion

The purpose of the SRA expansion is to further support activities outlined in
the initial 2015-2016 scope of work and to provide expanded research for:

 

a)

the treatment of patients having inborn metabolic defects, primarily but not
limited to diseases stemming from mutations impacting physiological enzymatic
function

 

b)

the treatment of patients with solid or hematologic malignancies

Specific Aim 1: [***]

Specific Aim 2: [***]

Specific Aim 3. [***]

 

 

2.1 Specific Aim 1:

Recombination (DNA shuffling) and screening of variants identified from a
scanning saturation library of [***]

 

-

[***]

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 3
The University of Texas at AustinPage 4 of 5Agreement No. UTA13-001113

 

***Confidential Treatment Requested.

--------------------------------------------------------------------------------

 

 

-

Tertiary screening for expression, kinetics and stability (purified protein)

•

Biophysical studies of selected variants

•

[***]

•

PD study in mice to evaluate Cystine & Cysteine levels following single dose
administration

 

 

2.2 Specific Aim 2:

•

Method development to support analysis of [***] in animal models (see below)

•

Evaluation of [***]

•

[***]

•

[***]

 

 

2.3 Specific Aim 3:

•

[***]

•

[***]

•

Other scaffold TBD

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 3
The University of Texas at AustinPage 5 of 5Agreement No. UTA13-001113

 

***Confidential Treatment Requested.

--------------------------------------------------------------------------------

 

Amendment 4
To Sponsored Research Agreement UTA13-001113 (“Agreement”)
Between
The University of Texas at Austin (“UT”)
And
Aeglea BioTherapeutics, Inc., Aeglea Development Company, Inc., AERase, Inc.,
AEMase,
Inc., AECase, Inc., AE4ase, Inc., AE5ase, Inc., and AE6ase, Inc. (each a
“Sponsor Entity”
and collectively, “Sponsor”)

The purpose of this Amendment:

To name a new sponsor entity and to change the designated Funding Sponsor under
the Agreement.

This Sponsored Research Agreement is modified by mutual agreement of the parties
as
follows:

 

1.

Aeglea BioTherapeutics, Inc. is hereby added to the Agreement as a new Sponsor
Entity.

 

2.

All rights and obligations of Funding Sponsor referred to in the Agreement are
hereby assigned from Aeglea Development Company, Inc. to Aeglea BioTherapeutics,
Inc., who is designated as the new Funding Sponsor under the Agreement.

 

3.

Section 13.3 is hereby amended to change Sponsor contact information to:

Aeglea BioTherapeutics, Inc.
901 S. MoPac Expressway, Suite 250
Barton Oaks Plaza One
Austin, TX 78746
Attn: Charles N. York II
Phone: [phone]
E-Mail: [email]

All other terms and conditions of this Sponsored Research Agreement remain
unchanged.

THE UNIVERSITY OF TEXAS AT AUSTINAEGLEA DEVELOPMENT COMPANY,
INC.

/s/ Bill Catlett/s/ Charles York
By:  Bill CatlettBy:  Charles N. York II
Title:  Director, Office of Industry EngagementTitle:  Chief Financial Officer

Date:   05 NOV 15Date:   04 NOV 2015

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 4

The University of Texas at AustinPage 1 of 2Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

AERASE, INC.AEMASE, INC.

/s/ Charles York/s/ Charles York
By:  Charles N. York IIBy:  Charles N. York II
Title:  Chief Financial OfficerTitle:  Chief Financial Officer

Date:   04 NOV 2015Date:   04 NOV 2015

AECASE, INC.AE4ASE, INC.

/s/ Charles York/s/ Charles York
By:  Charles N. York IIBy:  Charles N. York II
Title:  Chief Financial OfficerTitle:  Chief Financial Officer

Date:   04 NOV 2015Date:   04 NOV 2015

AE5ASE, INC.AE6ASE, INC.

/s/ Charles York/s/ Charles York
By:  Charles N. York IIBy:  Charles N. York II
Title:  Chief Financial OfficerTitle:  Chief Financial Officer

Date:   04 NOV 2015Date:   04 NOV 2015

AEGLEA BIOTHERAPEUTICS, INC.

/s/ Charles York
By:  Charles N. York II
Title:  Chief Financial Officer

Date:   04 NOV 2015

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 4

The University of Texas at AustinPage 2 of 2Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

Amendment 5
To Sponsored Research Agreement UTA13-001113 (“Agreement”)
Between
The University of Texas at Austin (“UT”)
And
Aeglea BioTherapeutics, Inc., Aeglea Development Company, Inc., AERase, Inc.,
AEMase,
Inc., AECase, Inc., AE4ase, Inc., AE5ase, Inc., and AE6ase, Inc. (each a
“Sponsor Entity”
and collectively, “Sponsor”)

The purpose of this Amendment:

To increase the limitation of funding in order to purchase equipment to be used
to perform the research.

This Sponsored Research Agreement is modified by mutual agreement of the parties
as follows:

 

1.

Attachment A, Research Program, is appended with the listing of equipment to be
purchased and used to perform the Research Program, and included with this
Amendment 5 as Attachment A-3, attached hereto.

 

 

2.

Section 3.2, first paragraph and the payment schedule, are hereby replaced with
the following: “As consideration for the performance by University of its
obligations under this Agreement, Funding Sponsor will pay the University an
amount equal to its reasonable, documented expenditures and reasonable overhead
(such overhead to not exceed the rate set forth in University’s indirect rate
agreement with the U.S. Federal Government) in conducting the Research Program
subject to a maximum expenditure limitation of $1,406,211, an increase of
$82,459 over the currently funded amount of $1,323,752, provided that in any and
all events, the amounts charged by University shall not, without Funding
Sponsor’s prior written consent, exceed the amount of the maximum expenditure
limitation. Payments shall be made as follows (subject to the possible later
return of funds if uncommitted and unexpended, under Section 3.3):

 

a)$948,752 — PAID TO DATE

b)$187,500 due on January 31, 2016, invoice issued on January 5, 2016

c)$82,459 due upon execution of this Amendment and within fourteen (14) days of
receipt

of an undisputed invoice sent via email to the address in Article 3.5

d)$187,500 due on April 30, 2016, invoice to be issued by March 3 I , 2016

All other terms and conditions of this Sponsored Research Agreement remain
unchanged.

[Signature Page Follows]

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 5

The University of Texas at AustinPage 1 of 9Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

THE UNIVERSITY OF TEXAS AT AUSTIN

AEGLEA DEVELOPMENT COMPANY, INC.

/s/ Ty Helpinstill

/s/ Charles York

By: Ty Helpinstill, Assoc. Director

By: Charles N. York II

Title:  Office of Industry Engagement

Title:  Chief Financial Officer

Date:6 Jan 2016

Date:07 Jan 2016

 

 

AERASE, INC.

AEMASE, INC.

/s/ Charles York

/s/ Charles York

By: Charles N. York II

By: Charles N. York II

Title:  Chief Financial Officer

Title:  Chief Financial Officer

Date:07 Jan 2016

Date:07 Jan 2016

 

 

AECASE, INC.

AE4ASE, INC.

/s/ Charles York

/s/ Charles York

By: Charles N. York II

By: Charles N. York II

Title:  Chief Financial Officer

Title:  Chief Financial Officer

Date:07 Jan 2016

Date:07 Jan 2016

 

 

AE5ASE, INC.

AE6ASE, INC.

/s/ Charles York

/s/ Charles York

By: Charles N. York II

By: Charles N. York II

Title:  Chief Financial Officer

Title:  Chief Financial Officer

Date:07 Jan 2016

Date:07 Jan 2016

 

 

AEGLEA BIOTHERAPEUTICS, INC.

 

/s/ Charles York

 

By: Charles N. York II

 

Title:  Chief Financial Officer

 

Date:07 Jan 2016

 

 

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 5

The University of Texas at AustinPage 2 of 9Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

Attachment A-3: Equipment

[***] [Redacted Seven Pages]

 

Sponsor: AegleaPI: George GeorgiouSRA Amendment No. 5

The University of Texas at AustinPage 3 of 9Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

Amendment 6
To Sponsored Research Agreement UTA13-001113 (“Agreement”)
Between
The University of Texas at Austin (“UT”)
And
Aeglea BioTherapeutics, Inc., Aeglea Development Company, Inc., AERase, Inc.,
AEMase,
Inc., AECase, Inc., AE4ase, Inc., AE5ase, Inc., and AE6ase, Inc. (each a
“Sponsor Entity”
and collectively, “Sponsor”)

 

The purpose of this Amendment:

To extend the term of the Research Program, increase the limitation of funding
under the Agreement to continue the research, and provide for title transfer of
certain equipment to Sponsor.

This Sponsored Research Agreement is modified by mutual agreement of the parties
as
follows:

1.

Attachment A, Research Program, is appended with the statement of work included
with this Amendment 6 as Attachment A-4, attached hereto.

2.

Section 2.2 is hereby replaced with the following:  “The Research Program shall
be performed during the period from the Effective Date through and including
August 31, 2017 (the “Research Term”).  Funding Sponsor shall have the option of
extending the Research Program under mutually agreeable support terms.”

3.

Section 3.2, first paragraph and the payment schedule, are hereby replaced with
the following:

As consideration for the performance by University of its obligations under this
Agreement, Funding Sponsor will pay the University an amount equal to its
reasonable, documented expenditures and reasonable overhead (such overhead to
not exceed the rate set forth in University’s indirect rate agreement with the
U.S. Federal Government) in conducting the Research Program subject to a maximum
expenditure limitation of $2,156,211, an increase of $750,000 over the currently
funded amount of $1,406,211, provided that in any and all events, the amounts
charged by University shall not, without Funding Sponsor’s prior written
consent, exceed the amount of the maximum expenditure limitation. Sponsor has
paid University $1,406,211 as consideration for its performance under the
Project as described in Attachments A, A-1, A-2, and A-3. Upcoming payments are
intended to cover performance by University under the Project as described in
Attachment A-4, and shall be made as follows (subject to the possible later
return of funds if uncommitted and unexpended, under Section 3.3):

Payment Due Date

Invoice Due Date

Payment Amount

Within 30 days of Funding Sponsor’s receipt of invoice

Upon execution of this Amendment

$187,500

December 1, 2016

November 1, 2016

$187,500

Sponsor:  Aeglea

PI:  George Georgiou

SRA Amendment No. 6

The University of Texas at Austin

Page 1 of 5

Agreement No. UTA13-001113

 

--------------------------------------------------------------------------------

 

March 1, 2017

February 1, 2017

$187,500

June 1, 2017

May 1, 2017

$187,500

 

Total:

$750,000

 

4.

Section 3.4 is hereby replaced with the following:

3.4University shall retain title to all equipment purchased and/or fabricated by
it with funds provided by Funding Sponsor under this Agreement, except that
Sponsor shall retain title and all rights, interest and risks of ownership to
the equipment listed hereunder as Attachment C (“HPLC Equipment”), which was
purchased by University on March 10, 2016, and delivered to University on April
11, 2016, with funds provided by Funding Sponsor under Amendment 5.

(i)Sponsor agrees to loan the HPLC Equipment to University for a period
beginning March 10, 2016, until the termination of this Agreement (“Loan
Period”). Subject to terms, conditions and restrictions in this Agreement,
Sponsor hereby grants to University, at no charge, a limited, nonexclusive,
nontransferable license to use the HPLC Equipment in the Principal
Investigator’s lab only during the Loan Period and specifically for the Research
Program. ALL RIGHTS NOT EXPRESSLY GRANTED HEREUNDER ARE RESERVED TO SPONSOR.

(ii)Sponsor agrees to arrange with the Principal Investigator’s lab for the HPLC
Equipment to be removed at the end of the project using a vendor of Sponsor’s
choice upon the expiration of the Loan Period. Such recovery shall be at
Sponsor’s expense. In the event Sponsor does not recover said HPLC Equipment
within 60 days of the termination of this Agreement, University shall provide
written notice to Sponsor regarding such recovery and title to the HPLC
Equipment will vest in University with no compensation owed to Sponsor if
Sponsor has not recovered such HPLC Equipment from University within 30 days of
Sponsor’s receipt of such written notice.

(iii)University and Sponsor hereby agree that there will be no rental rate or
deposit for the described Equipment. The loan is free of any financial
obligation by the University.

(iv)Sponsor acknowledges that the HPLC Equipment will be insured by University,
at Sponsor’s expense, and University will be liable for any theft, loss or
damage to the HPLC Equipment resulting from use contrary to written handling or
operating instructions supplied by Sponsor or the manufacturer. University shall
provide prompt written notice to Sponsor in the event of any theft, loss or
damage to the HPLC Equipment. University’s sole responsibility will be limited
to exercising reasonable care of and providing reasonable security for the HPLC
Equipment on University premises.

(v)University will be responsible for obtaining all expendable supplies required
in the operation of equipment, to be paid for with funds provided by Funding
Sponsor.

(vi)Normal wear and tear to the HPLC Equipment will not be considered damage or
loss reimbursable by insurance or otherwise. Further, University will also not
be responsible for any repair and modification of the HPLC Equipment that is
caused by normal wear and tear, or machinery defect.

Sponsor:  Aeglea

PI:  George Georgiou

SRA Amendment No. 6

The University of Texas at Austin

Page 2 of 5

Agreement No. UTA13-001113

 

--------------------------------------------------------------------------------

 

(vii)If the loan of the HPLC Equipment under this Agreement requires the
presence on University’s premises of Sponsor’s employees, agents, suppliers or
permitted subcontractors (if any), Sponsor agrees to maintain, at Sponsor’s sole
expense, and to cause its agents, suppliers and permitted subcontractors (if
any) to maintain, at their sole expense, the following insurance coverages in at
least the amounts specified:

(a)Workers Compensation: Statutory Limits

(b)Employer’s Liability: $1,000,000 per accident and employee

(c)Commercial General Liability (including contractual liability): $1,000,000
per occurrence

(d)Auto Liability: $1,000,000 combined single limit

(e)All other insurance required by state or federal law

All policies (except Workers’ Compensation) shall name University as an
additional insured. A waiver of subrogation in favor of University and thirty
(30) day notice of cancellation is required on all policies. Certificates of
insurance verifying the foregoing requirements shall be provided to University
within thirty (30) days of the execution of this Amendment or thirty (30) days
before any planned presence of Sponsor or its agents on University’s presence as
required by the HPLC Equipment loan. If a policy contains deductible provisions,
Sponsor shall be responsible for payment of the deductible amount for any
claim(s) or the pursuit of any claim(s) or asserted claim(s) against University,
its agents, employees or representatives.

Verification of insurance coverage shall be forwarded to:

[***]
The University of Texas at Austin
Department of Chemical Engineering
1 University Station C0400
Austin, TX 78712
[***]

(viii)UNIVERSITY ACKNOWLEDGES THAT THE HPLC EQUIPMENT IS PROVIDED “AS IS” AND
WITHOUT WARRANTY OF ANY KIND. SPONSOR MAKES NO WARRANTIES HEREUNDER, EXPRESS,
IMPLIED, STATUTORY OR OTHERWISE REGARDING THE HPLC EQUIPMENT, AND SPONSOR
SPECIFICALLY DISCLAIMS THE IMPLIED WARRANTIES OF MERCHANTABILITY,
NON-INFRINGEMENT AND FITNESS FOR A PARTICULAR PURPOSE.

(ix)Without prejudice to any of the foregoing, to the extent authorized by the
laws and Constitution of the State of Texas, Sponsor will not be liable for
special, indirect, consequential, incidental or exemplary damages arising out of
or alleged to arise out of the use of the HPLC Equipment (collectively,
“Damages”). The foregoing exclusions and limitations shall apply to all Damages
(a) however caused or alleged to be caused, (b) even if Sponsor has been advised
of the possibility of such Damages, (c) whether grounded in warranty,
negligence, tort, strict liability, breach of contract, civil liability or other
cause of action or claim, (d) regardless of whether claimed in the form of an
allegation, demand, suit, action or other proceeding, and (e) notwithstanding
any failure of essential purpose of any limited remedy.

***Confidential Treatment Requested.

 

(x)The intellectual property and publication provisions of this Agreement shall
govern the rights for intellectual property and publication resulting from the
use of the HPLC Equipment hereunder.

Sponsor:  Aeglea

PI:  George Georgiou

SRA Amendment No. 6

The University of Texas at Austin

Page 3 of 5

Agreement No. UTA13-001113

 

--------------------------------------------------------------------------------

 

(xi)Neither Party will make any press releases, public statements, or
advertisement referring to the loan of the HPLC Equipment for publication,
advertisement or any other purpose without the prior written approval of the
other Party.

5.

Article 11 of this Agreement is hereby replaced with the following:
“Attachments A, B and C are incorporated and made a part of this Agreement for
all purposes.”

All other terms and conditions of this Sponsored Research Agreement remain
unchanged.

[Signature Page Follows]

 

 

Sponsor:  Aeglea

PI:  George Georgiou

SRA Amendment No. 6

The University of Texas at Austin

Page 4 of 5

Agreement No. UTA13-001113

 

--------------------------------------------------------------------------------

 

THE UNIVERSITY OF TEXAS AT AUSTIN

AEGLEA DEVELOPMENT COMPANY,
INC.

/s/ Ty Helpinstill

/s/ Charles N. York II

By: Ty Helpinstill, Associate Director
Title:  Office of Industry Engagement

By: Charles N. York II
Title:  Chief Financial Officer

Date:

4 August 2016

Date:

03 Aug 2016

 

AERASE, INC.

AEMASE, INC.

/s/ Charles N. York II

/s/ Charles N. York II

By: Charles N. York II
Title:  Chief Financial Officer

By: Charles N. York II
Title:  Chief Financial Officer

Date:

03 Aug 2016

Date:

03 Aug 2016

 

AECASE, INC.

AE4ASE, INC.

/s/ Charles N. York II

/s/ Charles N. York II

By: Charles N. York II
Title:  Chief Financial Officer

By: Charles N. York II
Title:  Chief Financial Officer

Date:

03 Aug 2016

Date:

03 Aug 2016

 

AE5ASE, INC.

AE6ASE, INC.

/s/ Charles N. York II.

/s/ Charles N. York II

By: Charles N. York II
Title:  Chief Financial Officer

By: Charles N. York II
Title:  Chief Financial Officer

Date:

03 Aug 2016

Date:

03 Aug 2016

 

AEGLEA BIOTHERAPEUTICS, INC.

 

/s/ Charles N. York II

 

By: Charles N. York II
Title:  Chief Financial Officer

 

Date:

05 Aug 2016

 

 

 

 

Sponsor:  Aeglea

PI:  George Georgiou

SRA Amendment No. 6

The University of Texas at Austin

Page 5 of 5

Agreement No. UTA13-001113

 

--------------------------------------------------------------------------------

 

Attachment A-4
Statement of Work

Aeglea BioTherapeutics, Inc. will sponsor research in the laboratory of
Professor George Georgiou, Departments of Chemical Engineering, Biomedical
Engineering and Molecular Biosciences on the engineering, optimization and
initial animal validation of human enzyme therapeutics for the following
purposes:

Specific Aim 1. The systemic depletion of amino acids for cancer therapy.

Specific Aim 2. Enzyme replacement for the treatment of patients having inborn
metabolic defects, primarily but not limited to diseases stemming from mutations
impacting physiological enzymatic function.

It is anticipated that during the 2016-2017 fiscal the Georgiou lab will seek to
focus on the engineering and optimization of the following enzyme programs:

1.1.

[***]

1.2.

[***]

1.3.

[***]

2.1.

[***]

2.2

[***]

Studies to be performed under 1.1-2.2 will include:

1.1 [***]

Recombination (DNA shuffling) and analysis of enzyme variants identified
following screening of a variety of libraries.

[***]

Biophysical studies aimed at [***]

[***]

 

-

Preliminary stress tests

1.2. [***]

 

1.3. [***]

 

2.1. [***]

 

2.2. [***]

 

Sponsor:  Aeglea

PI:  George Georgiou

SRA Amendment No. 6

The University of Texas at Austin

Page 6 of 5

Agreement No. UTA13-001113

 

***Confidential Treatment Requested.

--------------------------------------------------------------------------------

 

Attachment C

[***]

 

***Confidential Treatment Requested.

--------------------------------------------------------------------------------

 

Amendment 7

To Sponsored Research Agreement UTA13-001113 (“Agreement”)

Between

The University of Texas at Austin (“UT”)

And

Aeglea BioTherapeutics, Inc., Aeglea Development Company, Inc., AERase, Inc.,
AEMase, Inc., AECase, Inc., AE4ase, Inc., AE5ase, Inc., and AE6ase, Inc. (each a
“Sponsor Entity” and collectively, “Sponsor”)

 

 

The purpose of this Amendment, effective as of August 31, 2017:

 

 

To extend the term of the Research Program and increase the limitation of
funding under the Agreement to continue the research.  

 

 

This Sponsored Research Agreement is modified by mutual agreement of the parties
as follows:

 

 

 

1.

Attachment A, Research Program, is appended with the statement of work included
with this Amendment 7 as Attachment A-5, attached hereto.

 

 

2.

Section 2.2 is hereby replaced with the following: “The Research Program shall
be performed during the period from the Effective Date through and including
August 31, 2018 (the “Research Term”).  Funding Sponsor shall have the option of
extending the Research Program under mutually agreeable support terms.”

 

 

3.

Section 3.2, first paragraph and the payment schedule, are hereby replaced with
the following:  

 

As consideration for the performance by University of its obligations under this
Agreement, Funding Sponsor will pay the University an amount equal to its
reasonable, documented expenditures and reasonable overhead (such overhead to
not exceed the rate set forth in University’s indirect rate agreement with the
U.S. Federal Government) in conducting the Research Program subject to a maximum
expenditure limitation of $2,531,211, an increase of $375,000 over the currently
funded amount of $2,156,211, provided that in any and all events, the amounts
charged by University shall not, without Funding Sponsor’s prior written
consent, exceed the amount of the maximum expenditure limitation.  Sponsor has
paid University $2,156,211 as consideration for its performance under the
Project as described in Attachments A, A-1, A-2, A-3 and A-4.  Upcoming payments
are intended to cover performance by University under the Project as described
in Attachment A-5, and shall be made as follows (subject to the possible later
return of funds if uncommitted and unexpended, under Section 3.3):  

 

 

 

 

Sponsor: AegleaPI: George Georgiou SRA Amendment No. 7

The University of Texas at AustinPage 1 of 4Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

 

Payment Due Date

 

 

Invoice Due Date

 

Payment Amount

 

 

Within 30 days of Funding Sponsor’s receipt of invoice

 

 

Upon execution of this Amendment

 

 

 

$187,500

 

January 1, 2018

 

December 1, 2017

 

$187,500

 

 

 

 

 

                                          Total:

 

$375,000

 

 

 

 

 

All other terms and conditions of this Sponsored Research Agreement remain
unchanged.

 

[Signature Page Follows]

 

Sponsor: AegleaPI: George Georgiou SRA Amendment No. 7

The University of Texas at AustinPage 2 of 4Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

THE UNIVERSITY OF TEXAS AT AUSTINAEGLEA DEVELOPMENT COMPANY,

INC.

 

 

/s/ Ty Helpinstill/s/ Charles N. York II

By:Ty Helpinstill, Associate DirectorBy: Charles N. York II

Title:  Office of Industry EngagementTitle: Chief Financial Officer

Date: 17 OCTOBER 2017Date: 12 • OCT • 2017

 

 

AERASE, INC.AEMASE, INC.

 

 

/s/ Charles N. York II/s/ Charles N. York II

By: Charles N. York IIBy: Charles N. York II

Title: Chief Financial OfficerTitle: Chief Financial Officer

Date: 12 • OCT • 2017Date: 12 • OCT • 2017

 

 

 

AECASE, INC. AE4ASE, INC.

 

 

/s/ Charles N. York II/s/ Charles N. York II

By: Charles N. York IIBy: Charles N. York II

Title: Chief Financial OfficerTitle: Chief Financial Officer

Date: 12 • OCT • 2017Date: 12 • OCT • 2017

 

 

AE5ASE, INC.AE6ASE, INC.

 

 

/s/ Charles N. York II/s/ Charles N. York II

By: Charles N. York IIBy: Charles N. York II

Title: Chief Financial OfficerTitle: Chief Financial Officer

 

 

Date: 12 • OCT • 2017Date: 12 • OCT • 2017

 

 

AEGLEA BIOTHERAPEUTICS, INC.

 

/s/ Charles N. York II

By: Charles N. York II

Title: Chief Financial Officer

 

Date: 12 • OCT • 2017

 

Sponsor: AegleaPI: George Georgiou SRA Amendment No. 7

The University of Texas at AustinPage 3 of 4Agreement No. UTA13-001113

--------------------------------------------------------------------------------

 

Attachment A-5

Statement of Work

 

Sponsor will sponsor research in the laboratory of Professor George Georgiou,
Departments of Chemical Engineering, Biomedical Engineering and Molecular
Biosciences on the engineering, optimization and initial validation in animal
models of human enzyme therapeutics for the following purposes:

 

Specific Aim 1. [***]

 

Specific Aim 2. [***]

 

Specific Aim 3. [***]

 

Specific Aim 4. [***]

 

The completion of these Specific Aims will require the following work:

 

[***]

Sponsor: AegleaPI: George Georgiou SRA Amendment No. 7

The University of Texas at AustinPage 4 of 4Agreement No. UTA13-001113

 

***Confidential Treatment Requested.