Exhibit 10.3

SPECIFIC TERMS IN THIS EXHIBIT HAVE BEEN REDACTED BECAUSE CONFIDENTIAL TREATMENT
FOR THOSE TERMS HAS BEEN REQUESTED. THE REDACTED MATERIAL HAS BEEN SEPARATELY
FILED WITH THE SECURITIES AND EXCHANGE COMMISSION, AND THE TERMS HAVE BEEN
MARKED AT THE APPROPRIATE PLACE WITH THREE ASTERISKS [***]

21 May 2018

From:
F-star Gamma Limited (“Gamma”)
Eddeva B920
Babraham Research Campus
Cambridge CB22 3AT
 
 
 
F-star Biotechnology Limited (“Ltd”)
Eddeva B920
Babraham Research Campus
Cambridge CB22 3AT
 
 
 
F-star Biotechnologische Forschungs-und Entwicklungsges.m.b.h (“GmbH”)
C/O – F-start Biotechnology Limited
Eddeva B920
Babraham Research Campus
Cambridge CB22 3AT
 
 
To:
Denali Therapeutics Inc. (“Denali”)
201 Gateway Boulevard
South San Francisco
CA, United States
Attention: Ryan Watts, CEO

Re:
Exercise of Buy-out Option pursuant to the Collaboration Agreements

Dear Ryan,

As you know, since 2016 Denali and F-star have developed a collaborative and
productive business relationship. As Denali prepares to execute the Buy-out
Option Agreement (as defined in the LCA) pursuant to Section 7.1 of the LCA the
Parties have discussed the progress of the Denali Fcabs and have agreed various
clarifications and some amendments to the LCA and the Gamma IP Licence.

These clarifications and amendments reflect the precise Fcab development path
and timings which has arisen since the original agreements were signed. 

CONFIDENTIAL
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[F-star Letterhead]

Capitalized terms used in this letter agreement (the “Letter”) but not defined
herein have the meanings set forth in the LCA.
“F-star Parties”
means Gamma, GmbH and Ltd
“Gamma IP License”

means the Amended and Restated Gamma IP License Agreement between Ltd and Gamma
dated 24 August 2016.
“LCA”
means the License and Collaboration Agreement between Denali, Gamma, GmbH and
Ltd dated 24 August 2016
“Second Accepted Fcab Target
means the Target listed as the Second Fcab Target in the table set out in
paragraph 1.2.1 of this letter or any Target which replaces such Target
following a substitution pursuant to paragraph 1.2.3 of this letter.
“Third Accepted Fcab Target
means the Target listed as the Third Fcab Target in the table set out in
paragraph 1.2.1 of this letter or any Target which replaces such Target
following a substitution pursuant to paragraph 1.2.3 of this letter.

Based on our recent discussions, Denali and the F-star Parties have agreed as
follows. This Letter shall be effective upon signature by all of the parties
with a signature line provided below, effective as of the date of the last such
signature (the “Letter Effective Date”).
1.1
Exclusivity Fees. The Parties have agreed that no Denali Fcab Delivery Notice
has been received by Gamma as of the Letter Effective Date and as such, the
requirement that Denali make payments to Gamma pursuant to Section 9.4 or
Section 9.5 of the License Agreement has not arisen as of the Letter Effective
Date and that, provided Denali acquires the shares of Gamma pursuant to the
Buy-Out Option Agreement by 1 September 2018, shall not arise during the process
of the Buy-Out Option exercise.

1.2
Target Nomination and Fcab Selection.

1.2.1
Target Selection. Upon the Letter Effective Date, the following target shall be
the second Accepted Fcab Target:

 
Second Accepted Fcab Target
Target
[***]
Entrez Gene ID
[***]
HUGO ID
[***]
Common Synonyms
[***]

CONFIDENTIAL
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*** Certain information in this agreement has been omitted and filed separately
with the Securities and Exchange Commission. [***] indicates that text has been
omitted and is the subject of a confidential treatment request

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At any time after the Letter Effective Date (but not later than [***] and
subject to Section 1.2.5 of this Letter), Denali shall have the right to
nominate the third Accepted Fcab Target using the same gatekeeping process as
set out in Article 3 of the Gamma IP Licence. For clarity, Denali is paying the
selection payment for the third Accepted Fcab Target in advance pursuant to
Section 1.2.2 of this Letter, so no additional selection payment shall be due
upon Denali’s nomination (or subsequent clearance) of the third Accepted Fcab
Target. For clarity, after the nomination (and clearance) of the third Accepted
Fcab Target, the substitution right under Section 1.2.3 shall apply to the third
Accepted Fcab Target in accordance with the terms of Section 1.2.3.
1.2.2
Target Selection payment payable to Ltd. Denali and the F-star Parties hereby
agree that (i) [***] Denali shall pay to Ltd the sum of six million dollars
($6,000,000) within [***] hereof; and (ii) the provisions of Section 9.3 of the
LCA shall no longer apply.

1.2.3
Substitution of Accepted Fcab Target. In addition to Denali’s and Gamma’s rights
to [***] pursuant to [***] and [***] Gamma shall have the right to substitute
(i) the Second Accepted Fcab Target [***] and (ii) the Third Accepted Fcab
Target [***] on the following terms:

(a)
Such substitution may not take place after Denali has given a written request to
Ltd to [***] without the prior written consent of Ltd.

(b)
Such substitution shall be made using the same process as set out in Article 3
of the Gamma IP Licence except that the Fcab Target Nomination Notice shall name
the Accepted Fcab Target being deselected by Gamma and the proposed Accepted
Fcab Target being selected by Gamma. Such Fcab Target shall be subject to the
same gatekeeping process as set out in Article 3 of the Gamma IP Licence.

(c)
On the receipt of the Gatekeeper Notice indicating that the proposed Accepted
Fcab Target is not on the Unavailable Target List such proposed Accepted Fcab
Target shall become an Accepted Fcab Target in place of the Second or Third (as
the case may be) Accepted Fcab Target and the Accepted Fcab Target that was
deselected shall cease to be an Accepted Fcab Target.

(d)
The Fcab Target Nomination Notice for the substitution of the Second or Third
(as the case may be) Accepted Fcab Target according to this paragraph 1.2.3 of
this Letter shall be received by Ltd: (i) in respect of the Second Accepted Fcab
Target (as set out in the table above), before [***]; and (ii) in respect of the
Third Accepted Fcab Target (as set out in the table above), before [***]. Any
Fcab Target Nomination Notice received after the relevant date shall be invalid.

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*** Certain information in this agreement has been omitted and filed separately
with the Securities and Exchange Commission. [***] indicates that text has been
omitted and is the subject of a confidential treatment request

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(e)
For the avoidance of doubt, Denali shall not be entitled to substitute the TfR
Accepted Fcab Target.

1.2.4
The Parties shall commence work on the preparation of an Fcab Discovery Plan in
respect of the Second Accepted Fcab Target [***] following the [***] and the
Parties shall commence work under such Fcab Discovery Plan on the written
request of Denali. In the event that Denali has not requested Ltd to commence
work under such Fcab Discovery Plan by [***] in respect of the Second Accepted
Fcab Target, such Target would cease to be an Accepted Fcab Target and all of
Denali’s rights and obligations under the LCA or the Gamma IP Licence in respect
of the Second Accepted Fcab Target shall cease from such date and none of the
F-star Parties shall have any obligation to Denali in respect of it.

1.2.5
The Parties shall commence work on the preparation of an Fcab Discovery Plan in
respect of the Third Accepted Fcab Target on the written request of Denali. In
the event that Denali has not requested Ltd to commence work under an Fcab
Discovery Plan by [***] in respect of the Third Accepted Fcab Target, such
Target would cease to be an Accepted Fcab Target and all of Denali’s rights and
obligations under the LCA or the Gamma IP Licence in respect of the Third
Accepted Fcab Target shall cease from such date and none of the F-star Parties
shall have any obligation to Denali in respect of it.

1.3
Continuation of the Milestone Payments in respect of the LCA. The Parties to
this letter agree that:

1.3.1
The obligation to make payments under Section 9.6 and 9.11 of the LCA shall be
deleted from the LCA, and for clarity nothing is therefore owed under Sections
7.5.1 or 7.5.2 of the Gamma IP License with respect to the payments under
Section 1.3.2 below.

1.3.2
Denali shall pay to Ltd, on an Accepted Fcab Target basis, the following
one-time (per Accepted Fcab Target), [***],[***] milestone payments within [***]
days after:

(a)
Fcab Delivery: (a) [***] if the Fcab Delivery was in the circumstances described
in Section 4.3.1 of the LCA or (b) [***] if the Fcab Delivery was deemed
achieved in the circumstances described in Section 4.3.2 of the LCA;

(b)
the first initiation of GMP manufacture of a Licensed Product with respect to
such Accepted Fcab Target: (i) [***], and (ii) in the case Denali had only paid
[***] under Section 1.3.2(a) above for the applicable Fcab Delivery, then an
additional [***]; provided that this additional payment under clause (ii) shall
only be due one (1) time with respect to a particular Fcab.

CONFIDENTIAL
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*** Certain information in this agreement has been omitted and filed separately
with the Securities and Exchange Commission. [***] indicates that text has been
omitted and is the subject of a confidential treatment request

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[F-star Letterhead]

1.3.3
Denali Fcab Payment Reductions. In the event that for a given Accepted Fcab
Target, (i) the Proposed Fcab provided by Ltd to Denali fails to meet the Fcab
Delivery Criteria for that Accepted Fcab Target (or Ltd was otherwise unable to
provide to Denali a Proposed Fcab during the [***] period after Denali has
transferred to Ltd all reagents and assays for Ltd to conduct the antigen
validation (e.g. conclusion of Step 1, Antigens of Schedule 1.5.1 of the LCA for
the TfR Fcab Discovery Plan or [***]) under the applicable Fcab Discovery Plan);
(ii) Denali has provided to Ltd the Denali Fcab Notice with respect to a Denali
Fcab for such Accepted Fcab Target; provided that solely for purposes of this
Section 1.3.3 of this Letter the parties agree that this Letter will serve as
the Denali Fcab Notice for TfR; and (iii) Ltd does not provide to Denali an Fcab
against that Accepted Fcab Target which meets the relevant Fcab Delivery
Criteria within the later of (a) [***] after Denali has transferred to F-star
all reagents and assays for F-star to conduct the antigen validation (e.g.
conclusion of Step 1, Antigens of Schedule 1.5.1 of the LCA for the TfR Fcab
Discovery Plan or [***]) under the applicable Fcab Discovery Plan, and (b) [***]
after the date Denali provides to Licensor the Denali Fcab Notice (the “Fcab
Disclosure Period”); then all of the payments set out in paragraph 1.3.2 above
in respect of the relevant Fcab and any such payment in respect of a mAb2
incorporating such Fcab shall be reduced by [***] such that the amount payable
is [***]. The Parties agree that the Fcab Disclosure Period for TfR Accepted
Fcab Target shall expire upon [***]. If the Proposed Fcab for an Accepted Fcab
Target failed to meet the Fcab Delivery Criteria, and Ltd subsequently provides
to Denali during the Fcab Disclosure Period another Licensor Fcab for validation
testing, then Denali shall only be obligated to conduct [***] additional
validation experiment(s) for such additional Licensor Fcab, and if such
additional Licensor Fcab does not meet the Fcab Delivery Criteria, then Licensor
shall be responsible to reimburse Denali for its costs to conduct such
additional validation experiment(s) in respect of [***] Licensor Fcab only. In
addition, Ltd shall be entitled (but not obliged) to conduct, at its own cost,
[***] validation experiment(s) for [***] Licensor Fcab in addition to the [***]
Licensor Fcabs that are subject to the validation experiments carried out by
Denali, provided such validation experiment(s) is carried out within the Fcab
Disclosure Period. The above reduction shall not apply:

(a)
if Ltd delivers the sequence of an Fcab against such Accepted Fcab Target which
within such period meets or subsequently is found to meet the Fcab Delivery
Criteria prior to expiration of the Fcab Disclosure Period for such Accepted
Fcab Target, and, upon the date of Fcab Delivery of such an Fcab, Denali shall
pay to Ltd the difference between the amounts that were paid in respect of the
Denali Fcab and the amounts that would have been paid if Denali had selected a
Licensor Fcab. For clarity, if at the time the milestone payment due under
Section 1.3.2(b) of this Letter becomes due with respect to an Accepted Fcab
Target, Ltd has not yet delivered to Denali a Proposed

CONFIDENTIAL
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*** Certain information in this agreement has been omitted and filed separately
with the Securities and Exchange Commission. [***] indicates that text has been
omitted and is the subject of a confidential treatment request

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[F-star Letterhead]

Fcab that meets the Fcab Delivery Criteria for that Accepted Fcab Target, and
Denali did not select a Licensor Fcab or Joint Fcab for such Accepted Fcab
Target for the development of mAb2 (as evidenced by initiation of GMP
manufacture as described in clause (b) below), then the milestone payable under
Section 1.3.2(b) by Denali shall be reduced by [***] such that the amount
payable is [***], subject to Denali paying to Ltd the difference thereof if Ltd
delivers a Fcab during the Fcab Disclosure Period that meets the Fcab Delivery
Criteria as provided above in this clause (a);
(b)
if, notwithstanding that the Fcab against such Accepted Fcab Target delivered by
Ltd did not meet the relevant Fcab Delivery Criteria, Denali nevertheless
selects a Licensor Fcab or Joint Fcab for the development of mAb2 as evidenced
by initiation of GMP manufacture for a Licensed Product that incorporates such
Licensor Fcab or Joint Fcab; or

(c)
in respect of any mAb2 which contains a Licensor Fcab or a Joint Fcab.

Notwithstanding the final paragraph of this letter or the provisions of Section
13.11 of the Gamma IP Licence, this paragraph 1.3 shall (in addition to the
F-star Parties) be for the benefit of and enforceable by the Shareholders of
Gamma.

1.4
Technical Development.

1.4.1
Following the Letter Effective Date, the definition of the Technical Development
Term in the LCA shall be deleted and replaced by the following: “ “Technical
Development Term” means the Term”

1.4.2
Following the Letter Effective Date, the definition of the Technical Development
Term in the Gamma IP Licence shall be deleted and replaced by the following: “
“Technical Development Term” means the Term”

1.4.3
In addition to Gamma’s obligations under Section 4.3 of the Gamma IP Licence,
Gamma shall, and shall procure that Denali shall, within [***] following the end
of each [***] during the Technical Development Term, provide to Ltd (i) [***]
and (ii) a [***] during such [***] and the [***]. Gamma’s obligations under this
Section 1.4.3, including its obligations under Section 4.3 of the Gamma IP
License, shall expire upon [***] (as defined in the Gamma IP License).

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*** Certain information in this agreement has been omitted and filed separately
with the Securities and Exchange Commission. [***] indicates that text has been
omitted and is the subject of a confidential treatment request

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[F-star Letterhead]

1.5
Diligence. Without limiting Sections 4.2, 4.3, and 4.7 of the LCA, in respect of
the second and third Accepted Fcab Targets, following Denali’s written request
to Ltd to [***], Denali shall [***] to [***] transfer to Gamma [***] and perform
[***] and [***]. In addition, Denali shall [***] transfer to Gamma [***] in
connection with and as necessary for [***].

1.6
Gamma IP License. The parties acknowledge that the first sentence of Section
13.3.2 of the Gamma IP License shall not apply to Denali’s acquisition of Gamma,
such that following the Completion (as defined in the Buy-Out Option Agreement),
Denali shall be an Affiliate of Gamma for purposes of the Gamma IP License.

1.7
Disclosure Notice. The Parties acknowledge that concurrently with the execution
of this Letter Denali is providing a Disclosure Notice pursuant to the Buy-Out
Option Agreement.

Please confirm your agreement to the foregoing by countersigning this Letter
below and returning a signed copy to me.

This Letter may be executed in any number of counterparts, each of which when
executed shall constitute a duplicate original, but all the counterparts
together shall constitute the one agreement.

The provisions of Section 7.10, 7.11 and 7.12 of the Gamma IP Licence shall
apply to any payments to be made pursuant to this Letter on the basis that the
reference to Party therein, for the purposes of this letter only, [***].

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*** Certain information in this agreement has been omitted and filed separately
with the Securities and Exchange Commission. [***] indicates that text has been
omitted and is the subject of a confidential treatment request

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This Letter, including any non-contractual disputes or claims, shall be governed
by and construed in accordance with the laws of England and Wales and the
provisions of Article 13 of the Gamma IP Licence shall apply to it.

Yours sincerely,

…/s/ John Haurum……………………………………
Name: John Haurum, CEO
For and on behalf of F-STAR GAMMA LIMITED

…/s/ John Haurum……………………………………
Name:
For and on behalf of F-STAR BIOTECHNOLOGY LIMITED

…/s/ John Haurum……………………………………
Name:
For and on behalf of
F-STAR BIOTECHNOLOGISCHE FORSCHUNGS-UND ENTWICKLUNGSGES.M.B.H

Acknowledged and agreed by:

…/s/ Ryan Watts……………………………………
Name: Ryan Watts, CEO
For and on behalf of
DENALI THERAPEUTICS INC.

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