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Exhibit 10.1

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SECOND AMENDED AND RESTATED
STRATEGIC ADVISORY SERVICES AGREEMENT
(“SUMMARY PAGE”)

This Second Amended and Restated Strategic Advisory Services Agreement is
entered into and made effective as of January 9, 2020, and amends and restates
the Strategic Advisory Service Agreement dated January 15, 2018, as amended on
March 22, 2019, by and between B. Lynne Parshall and Ionis Pharmaceuticals, Inc.
(“Ionis”).

Date of Strategic Advisory Services Agreement: (“Agreement”)
 
January 15, 2018 (“Effective Date”).  Effective Date of Second Amendment and
Restatement January 9, 2020.
     
Name of Strategic Advisor:
 
B. Lynne Parshall (hereinafter “Strategic Advisor”).
     
Scope of Strategic Advisory Services:
 
As set forth on Schedule A attached hereto.
     
Duration of Strategic Advisory Services (the “Strategic Advisory Period”):
 
Until termination by Ionis or Strategic Advisor in accordance with Section 8 of
Exhibit A below.
     
Consideration for Strategic Advisory Services:
 
As set forth on Schedule B attached hereto.
     
Time Provided by Strategic Advisor:
 
As set forth on Schedule A attached hereto.

In addition to such compensation, Ionis will reimburse Strategic Advisor for
Ionis approved travel and other out-of-pocket costs reasonably incurred in the
course of performing Strategic Advisory Services under this Agreement as further
described on Schedule B attached hereto.

Strategic Advisor agrees to provide Ionis with Strategic Advisory Services on
the terms described above and according to the additional terms attached hereto
as Exhibit A.  In this Agreement references to Ionis, including but not limited
to Sections 3-6 of Exhibit A, will include Ionis’ affiliate companies where
applicable.

 
Strategic Advisor
 
Ionis Pharmaceuticals, Inc.
By (Signature):
/s/ B. Lynne Parshall
 
/s/ Brett Monia
       
Date:
January 9, 2020
 
January 9, 2020
Printed Name:
B. Lynne Parshall
 
Brett Monia

Social Security or Employer Tax ID Number to be provided separately via W-9 form
or foreign equivalent.

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EXHIBIT A

TERMS OF STRATEGIC ADVISORY AGREEMENT

1.
Engagement of Services

Strategic Advisor is retained to perform certain services, as needed and
requested by Ionis, which services are specifically described on Schedule A
attached hereto (“Strategic Advisory Services”).  Strategic Advisor will perform
such Strategic Advisory Services to the best of Strategic Advisor’s talent and
ability.

2.
Compensation

As full and complete compensation for Strategic Advisory Services and for the
discharge of all of Strategic Advisor’s obligations hereunder, Ionis will pay
Strategic Advisor at the rate set forth on Schedule B attached hereto. Strategic
Advisor will invoice Ionis on a quarterly basis for Strategic Advisor fees and
reimbursable expenses, and Ionis, upon its approval, will pay all undisputed
fees and expenses within 30 days after Ionis’ receipt of the invoice.

3.
Independent Contractor

Strategic Advisor is an independent contractor and not an employee of Ionis. 
Strategic Advisor has no authority to obligate Ionis by contract or otherwise. 
Strategic Advisor will not be eligible for any employee benefits.  Taxes will be
the sole responsibility of Strategic Advisor.

4.
Additional Activities

(a)
Strategic Advisor agrees that during the Strategic Advisory Period and for one
year thereafter, Strategic Advisor will not attempt to induce any employee or
employees of Ionis to terminate their employment with, or otherwise cease their
relationship with Ionis.

(b)
Strategic Advisor acknowledges that Ionis has developed, through an extensive
acquisition process, valuable information regarding actual or prospective
partners, licensors, licensees, clients, customers and accounts of Ionis (“Trade
Secret Information”). Strategic Advisor acknowledges that Strategic Advisor’s
use of such Trade Secret Information after the termination of the Strategic
Advisory Period would cause Ionis irreparable harm. Therefore, Strategic Advisor
also agrees that Strategic Advisor will not utilize any Trade Secret Information
to solicit the business relationship or patronage of any of the actual or
prospective partners, licensors, licensees, clients, customers or accounts of
Ionis.

(c)
The restrictions set forth in this Section 4 are considered by the parties to be
reasonable for the purposes of protecting Ionis’ business.  However, if any such
restriction is found by a court of competent jurisdiction to be unenforceable
because it extends for too long a period of time or over too great a range of
activities or in too broad a geographic area, it will be interpreted to extend
only over the maximum period of time, range of activities or geographic areas as
to which it may be enforceable.

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5.
Confidential Information

(a)
Ionis possesses confidential information that has been created, discovered,
developed by, or otherwise become known to Ionis (including, without limitation,
information created, discovered, developed or made known by Strategic Advisor
arising from the Strategic Advisory Services).

(i)
All such information is hereinafter referred to as “Confidential Information.” 
By way of illustration, but not limitation, Confidential Information includes: 
(A) inventions, developments, designs, improvements, trade secrets, ideas,
formulas, source and object codes, programs, other works of authorship,
organisms, plasmids, expression vectors, know-how, processes, cell lines,
discoveries, techniques, data and documentation systems (hereinafter
collectively referred to as “Inventions”); and (B) information regarding plans
for research, development, new products, clinical data, pre-clinical product
data, clinical trial patient data, marketing and selling, business plans,
budgets and unpublished financial statements, licenses, prices and costs, as
well as information regarding the skills and compensation of employees of Ionis.

(ii)
All Confidential Information will be the sole property of Ionis and its assigns,
and Ionis and its assigns will be the sole owner of all patents, copyrights and
other rights in connection with such Confidential Information.  At all times,
both during the term of this Agreement and for five years after its termination,
Strategic Advisor will keep in confidence and trust all Confidential Information
and will not use, disclose, lecture upon or publish any Confidential Information
or anything related to such information without Ionis’ prior written consent. 
Any permitted disclosures will be made in strict compliance with the Ionis
publication and presentation clearance policy.

(b)
Strategic Advisor also understands that Ionis has received and in the future,
will receive valuable information from third parties that is confidential or
proprietary (“Third-Party Information”) subject to a duty on the part of Ionis
to maintain the confidentiality of such information and to use it only for
certain limited purposes.  During the term of this Agreement and for five years
thereafter, Strategic Advisor will hold Third-Party Information in the strictest
confidence and will not disclose or use Third-Party Information except as
permitted by the agreement between Ionis and such third party, unless expressly
authorized to act otherwise by an officer of Ionis in writing.  Any permitted
disclosures will be made in strict compliance with Ionis publication and
presentation clearance policy.

(c)
The obligations of Section 5 will not apply to information that Strategic
Advisor can establish by written records: (i) was known by Strategic Advisor
prior to the receipt of Confidential Information; (ii) was disclosed to
Strategic Advisor by a third party having the right to do so; (iii) was, or
subsequently became, in the public domain through no fault of Strategic Advisor,
its officers, directors, affiliates employees or agents; (iv) was independently
developed by Strategic Advisor without use of Confidential Information; or (v)
was disclosed by Strategic Advisor pursuant to any judicial, governmental or
stock exchange request, requirement or order, so long as Strategic Advisor
provided Ionis with sufficient prior notice in order to allow Ionis to contest
such request, requirement or order.

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6.
Inventions

In the course of performing Strategic Advisory Services for Ionis, Strategic
Advisor may develop new ideas or Inventions or make other contributions of value
to Ionis.

(a)
Strategic Advisor hereby assigns to Ionis Strategic Advisor’s entire right,
title and interest in and to any and all Inventions (and all patent rights,
copyrights, and all other rights in connection therewith, hereinafter referred
to as “Proprietary Rights”) whether or not patentable or registrable under
patent, copyright or similar statutes, made or conceived of or reduced to
practice or learned by Strategic Advisor, either alone or jointly with others,
as a result of performing Strategic Advisory Services hereunder.  All Inventions
assigned to Ionis pursuant to this section will be known as “Company
Inventions”.  Strategic Advisor agrees that all Proprietary Rights and Company
Inventions are Ionis’ sole property.  Strategic Advisor agrees, upon request, to
execute, verify and deliver assignments of such Proprietary Rights to Ionis or
its designee.  Strategic Advisor understands that, to the extent this Agreement
will be construed in accordance with the laws of any state which precludes a
requirement in an agreement to assign certain classes of inventions made by an
individual acting as a Strategic Advisor, this section will be interpreted not
to apply to any inventions that a court rules and/or Ionis agrees falls within
such classes.

(b)
Strategic Advisor further agrees to assist Ionis in every proper way to obtain,
from time to time, and to enforce United States and foreign Proprietary Rights
relating to Company Inventions in any and all countries.  To that end Strategic
Advisor will execute, verify and deliver such documents and perform such other
acts (including appearances as a witness) as Ionis may reasonably request for
use in applying for, obtaining, sustaining and enforcing such Proprietary Rights
relating to Company Inventions.  Strategic Advisor’s obligation to assist Ionis
in obtaining and enforcing Proprietary Rights relating to Company Inventions in
any and all countries will continue beyond the termination of this Agreement,
but Ionis will compensate Strategic Advisor at a reasonable rate after such
termination for the time actually spent by Strategic Advisor at Ionis’ request
in connection with such assistance.  If Ionis is unable, after reasonable
effort, to secure Strategic Advisor’s signature on any document needed to apply
for or prosecute any Proprietary Rights relating to a Company Invention,
Strategic Advisor hereby irrevocably designates and appoints Ionis and its duly
authorized officers and agents as  her agent and attorney in fact, to act for
and on Strategic Advisor’s behalf to execute, verify and file any such
applications and to do all other lawfully permitted acts to further the
prosecution and issuance of any such Proprietary Rights with the same legal
force and effect as if executed by Strategic Advisor.

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(d)
During the term of this Agreement, Strategic Advisor will promptly disclose to
Ionis, or any persons designated by it, fully and in writing and will hold in
trust for the sole right and benefit of Ionis any and all Company Inventions,
whether or not patentable or protectable by copyright.  At the time of each such
disclosure, Strategic Advisor will advise Ionis in writing of any Inventions
that Strategic Advisor believes are not subject to the assignment provisions of
Section 6(a) above, and Strategic Advisor will at that time provide to Ionis in
writing all evidence necessary to substantiate that belief.  Strategic Advisor
will not be obligated to disclose information received by Strategic Advisor from
others under a contract of confidentiality.  In addition, after termination of
this Agreement, Strategic Advisor will disclose to Ionis all patent applications
filed by Strategic Advisor relating to any Company Inventions or relating to any
work performed by Strategic Advisor on behalf of Ionis.

7.
Previous Strategic Advisory Relationships

Strategic Advisor represents that Strategic Advisor’s performance of Strategic
Advisory Services, as well as Strategic Advisor’s performance of the rest of
Strategic Advisor’s obligations under the terms of this Agreement, will not
breach any agreement to keep in confidence any proprietary information acquired
by Strategic Advisor in confidence or in trust from another entity prior to the
date of this Agreement.  Strategic Advisor agrees not to bring to Ionis or to
use in the performance of Strategic Advisory Services for Ionis any materials or
documents of a present or former employer or client of Strategic Advisor, or any
materials or documents obtained by Strategic Advisor under a confidentiality
agreement imposed by reason of another of Strategic Advisor’s Strategic Advisory
relationships, unless such materials or documents are generally available to the
public or Strategic Advisor has authorization from such present or former
employer or client for the possession and unrestricted use of such materials.

8.
Termination; Survival

(a)         The term of this Agreement will begin on January 15, 2018 and will
end when terminated by either Ionis or Strategic Advisor.  Ionis may terminate
this Agreement at any time for any reason by providing Strategic Advisor at
least 120 days advance written notice.  Strategic Advisor may terminate this
Agreement at any time for any reason by providing Ionis at least 120 days
advance written notice; provided, once Strategic Advisor delivers such a
termination notice, Ionis may elect to accelerate the effective date of such
termination.  Upon any termination, Ionis will pay Strategic Advisor for any
Strategic Advisory Services appropriately rendered and for any out of pocket
expenses reasonably incurred on behalf of Ionis, up to and including the
termination date.

(b)          Sections 9 and 10, the last sentence of the paragraph of Schedule B
entitled “Ionis Stock Awards” and the last paragraph of Schedule B will survive
termination of this Agreement.  In addition, upon expiration or termination of
this Agreement, each party will be released from all obligations and liabilities
to the other occurring or arising after the date of such expiration or
termination, except that any termination or expiration of this Agreement will
not relieve Strategic Advisor of Strategic Advisor’s obligations under Sections
4, 5, 6, 7, 9, 10 and 11 hereof, nor will any such expiration or termination
relieve Strategic Advisor or Ionis from any liability arising from any breach of
this Agreement.  Upon expiration or termination of this Agreement for any reason
whatsoever, Strategic Advisor will promptly surrender and deliver to Ionis any
and all notes, business records, memoranda, specifications, devices, formulas,
molecules, cells, storage media, including calculations, sequences, data and
other materials of any nature pertaining to Strategic Advisory Services for
Ionis, as well as any documents or data of any description (or any reproduction
of any documents or data) containing or pertaining to any Trade Secret
Information, Ionis’ Confidential Information or Third Party Information.

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9.
Arbitration

(a)
Ionis and Strategic Advisor agree to resolve by arbitration all disputes, claims
or controversies (“Claims”), past, present or future, whether or not arising out
of this Agreement or its termination, that Ionis may have against Strategic
Advisor or that Strategic Advisor may have against any of the following (i)
Ionis; (ii) Ionis officers, directors; employees or agents; (iii) Ionis’
subsidiary or affiliated entities, joint ventures, or joint employers; (iv)
Ionis’ benefit plans or the plans’ sponsors, fiduciaries, administrators,
affiliates and agents; and/or (v) all successors and assigns of any of the
foregoing.  The Claims covered by this Agreement include all disputes that Ionis
or Strategic Advisor could otherwise pursue in state or federal court including,
but not limited to, Claims based on any state, federal, or local statute,
regulation or ordinance (including Claims for discrimination, retaliation,
harassment, unpaid wages or violation of state or federal wage and hour laws),
as well as common law Claims (including Claims for breach of contract, breach of
the implied covenant of good faith and fair dealing, wrongful discharge,
defamation, misrepresentation, fraud, or infliction of emotional distress). 
Ionis and Strategic Advisor anticipates that this Section 9 provides the
benefits of a speedy, less formal, impartial, final and binding dispute
resolution procedure.

(b)
To the maximum extent permitted by law, Strategic Advisor hereby waives any
right to bring on behalf of persons other than Strategic Advisor, or to
otherwise participate with other persons in, any class, collective or
representative action (i.e. a type of lawsuit in which one or several persons
sue on behalf of a larger group of persons).

(c)
The arbitration will be conducted by a single neutral arbitrator in accordance
with the then-current Commercial Arbitration and Mediation Procedures of the
American Arbitration Association (“AAA”).  The arbitration will take place in
San Diego, California.  Ionis will pay the arbitrator’s fee and will bear all
administrative charges by AAA.  All parties will be entitled to engage in
reasonable pre-hearing discovery to obtain information to prosecute or defend
the asserted claims.  Any disputes between the parties regarding the nature or
scope of discovery will be decided by the arbitrator.  The arbitrator will hear
and issue a written ruling upon any dispositive motions brought by either party,
including but not limited to, motions for summary judgment or summary
adjudication of issues.  After the hearing, the arbitrator will issue a written
decision setting forth the award, if any, and explaining the basis therefore. 
The arbitrator will have the power to award any type of relief that would be
available in court.  The arbitrator’s award will be final and binding upon the
parties and may be entered as a judgment in any court of competent
jurisdiction.  If there is conflict in the arbitration procedures set forth in
this Agreement and the AAA rules specified above, the AAA rules will control. 
Notwithstanding the foregoing, and regardless of what is provided by the AAA
rules, the arbitrator will not have authority or jurisdiction to consolidate
claims of different individuals or entities into one proceeding, nor will the
arbitrator have authority or jurisdiction to hear the arbitration as a class
action.  As noted above, Strategic Advisor has agreed to waive any right to
bring any class, collective or representative action.  To the extent that the
class, collective or representative action waiver described above is not
enforceable, the issue of whether to certify any alleged or putative class for a
class action proceeding must be decided by a court of competent jurisdiction. 
The arbitrator will not have authority or jurisdiction to decide class
certification, collective or representative action issues.  Until any class
certification, collective, or representative action issues are decided by the
court, all arbitration proceedings will be stayed, and the arbitrator will take
no action with respect to the matter.  However, once any issues regarding class
certification, collective, or representative action have been decided by the
court, the arbitrator will have authority to decide the substantive claims.

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10.
Indemnification

(a)
Ionis will indemnify, defend and hold Strategic Advisor harmless against any and
all losses, costs, expenses and damages (including reasonable attorney’s fees)
(“Loss(es)”) incurred as a result of any third party claims, suits, actions,
demands or proceedings resulting or arising  from the performance of Strategic
Advisory Services as specifically directed by Ionis in accordance with the
Agreement to the extent such Loss(es) are not the result of Strategic Advisor’s
gross negligence, intentional misconduct or material breach of this Agreement.

(b)
Ionis’ agreement to indemnify, defend and hold  Strategic Advisor harmless is
conditioned upon the Strategic Advisor (i) providing written notice to Ionis of
any claim, demand or action arising out of the indemnified activities within
thirty (30) days after Strategic Advisor has knowledge of such claim, demand or
action, provided that the failure to so notify Ionis shall not relieve Ionis of
its obligations hereunder except to the extent such failure shall have actually
materially prejudiced Ionis; (ii) permitting Ionis to assume full responsibility
to investigate, prepare for and defend against any such claim or demand; (iii)
assisting Ionis, at Ionis’ reasonable expense, in the investigation of,
preparation of and defense of any such claim or demand; (iv) undertaking
reasonable steps to mitigate any loss, damage or expense with respect to the
applicable claim or demand; and (v) not settling such claim or demand without
Ionis’ prior written consent.

(c)
Ionis will endeavor to include Strategic Advisor as a covered attorney on its
insurance policy for attorneys who advise Ionis.

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11.
Miscellaneous

(a)
The rights and liabilities of the parties hereto will bind and inure to the
benefit of their respective successors, heirs, executors and administrators, as
the case may be; provided that, as Ionis has specifically contracted for
Strategic Advisor’s services, Strategic Advisor may not assign or delegate
Strategic Advisor’s obligations under this Agreement either in whole or in part
without Ionis’ prior written consent.

(b)
Because Strategic Advisor’s services are personal and unique and because
Strategic Advisor has access to and become acquainted with Ionis’ Confidential
Information, the parties agree that in the event of a threatened or actual
material breach of this Agreement by Strategic Advisor injunctive relief would
be appropriate.  As such, Ionis has the right to enforce this Agreement and any
of its provisions by injunction, specific performance or other equitable relief
without prejudice to any other rights and remedies that Ionis may have for a
breach of this Agreement.

(c)
This Agreement will be governed by and construed according to the laws of the
State of California as such laws are applied to contracts entered into and
performed entirely within such State.  If any provision of this Agreement is
held to be or becomes invalid, illegal or unenforceable, such provision will be
validly reformed to approximate as nearly as possible the intent of the parties
and the remainder of this Agreement will not be affected thereby and will remain
valid and enforceable to the greatest extent permitted by law.

(d)
This Agreement, and all other documents mentioned herein, constitute the final,
exclusive and complete understanding and agreement of the parties hereto and
supersedes all prior understandings and agreements.  Any waiver, modification or
amendment of any provision of this Agreement will be effective only if in
writing and signed by the parties hereto.

(e)
Any notices required or permitted hereunder will be given to the appropriate
party at the address specified on the Summary Page or at such other address as
the party will specify in writing.  Such notice will be deemed given upon
personal delivery to the appropriate address, or by facsimile transmission
(receipt verified and with confirmation copy followed by another permitted
method), sent by express courier service, or, if sent by certified or registered
mail, three (3) days after the date of mailing.

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SCHEDULE  A

Strategic Advisory Services

Ionis Board of Directors
You will serve on the Ionis board of directors as a nonemployee director until
your resignation or removal in accordance with Ionis’ corporate charter.  You
will serve on the Agenda committee of the Board, and Ionis will periodically
evaluate your ability to serve on other Board committees to the extent permitted
by applicable SEC and Nasdaq rules. You will participate in other Board
Committee meetings as requested as a non-member.

Akcea
Your services to Akcea will be handled by a separate agreement between you and
Akcea.  Any services you provide Akcea will not count towards hours worked under
this Agreement.

Strategic Neurology/Rare Disease Subsidiary Board of Directors
When Ionis forms a strategic neurological/rare disease focused  subsidiary, you
will serve on the board of directors of such subsidiary as a non employee
director on the same terms as other non employee directors until your
resignation or removal in accordance with the subsidiary’s corporate charter.

Additional Strategic Advisory Services

You will provide Ionis strategic advice regarding Ionis’ business, including but
not limited to the following:

For calendar year 2020, you will provide approximately seventy-three full days
of strategic advice.  For each year following 2020, you and Ionis will mutually
agree on the approximate number of business days each month you will provide
strategic advice during such year.  You will make yourself generally available
for conference calls and in person meetings Ionis invites you to attend.  You
will travel to locations as reasonably requested by Ionis, including to Ionis,
Akcea, Ionis’ partners, or other locations where Ionis is conducting corporate
development activities (e.g. JP Morgan conference or strategic off-site
meetings).  You and Ionis expect that, you will participate in Ionis’
development management committee (DMC) meetings, Ionis’ affiliate’s and Biogen
joint steering committee meetings, and when requested, Ionis’ strategic
management meetings.  As requested by Ionis, you will facilitate Ionis’
strategic partnerships and help develop Ionis’ subsidiaries’ and affiliates’
senior management teams.  You will work with the Executive Chairman, CEO and
others on strategic planning and direction for the Company.  You will
participate in major corporate communication initiatives, including
business/financial messaging.  You will participate in structuring and
negotiating as requested new strategic alliances.  Your advisory services may
include providing Ionis legal advice.

You and Ionis will reasonably coordinate to have you present on site for board
of directors meetings, and a few days before and/or after such meetings to
perform strategic advisory services.  The time you spend preparing for or
attending board of directors or board committee meetings for Ionis or any
subsidiary will not count towards your commitment to perform additional
strategic advisory services outlined above.

While you are providing such services, Ionis will make an appropriate level of
administrative and technical personnel available to facilitate your performance
of Advisory Services at no cost to you, including, without limitation IT support
and access to Ionis’ electronic calendar and IT systems that are necessary to
perform your duties.

Schedule A
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SCHEDULE  B

Compensation for Strategic Advisory Services

Ionis Board of Directors
For your service on the Ionis board of directors, you will receive the same
compensation as Ionis provides its other nonemployee directors.  You will
receive the same annual equity awards as Ionis’ other nonemployee directors. 
You will also be eligible for any benefits (including any applicable health
benefits) Ionis provides to its nonemployee directors.

Strategic Neurology/Rare Disease Subsidiary Board of Directors
For your service on the board of directors of Ionis’ strategic neurological/rare
disease subsidiary (if formed), you will receive the same compensation
(including equity awards) as such subsidiary provides its other nonemployee
/outside directors.

Additional Strategic Advisory Services
For your other strategic advisory services, starting in the fiscal year ending
in 2020, Ionis will pay you as follows:

•
$300,000 for services rendered through December 31, 2020 to be paid in equal
quarterly installments; provided, however, that if you provide more than
seventy-three full days of service during the aforementioned period, then
payment for days above seventy-three will be $5,000 per day to be paid at the
end of 2020.

•
You will not be eligible for an Ionis performance bonus.

•
Ionis will evaluate its needs and your availability at the end of 2020.

Ionis Stock Awards
Since you transitioned seamlessly from an Ionis employee to a nonemployee
director, the stock options and RSUs you received for your previous service as
an Ionis employee will continue to vest so long as your Continuous Service (as
defined in the applicable equity plan) continues.  Once you are no longer
serving on the Ionis board and no longer providing strategic advisory services,
to the extent permitted by the terms of the applicable stock option agreement,
your vested stock options will not terminate until the earlier of 18 months
following your retirement or the expiration of the original term of such stock
option.

For Ionis-directed travel and lodging Ionis will reimburse you for such travel,
lodging and related expenses or reasonable rate equivalents for lodging, car and
meals you provide.  All such reimbursements will be in accordance with Ionis’
travel policy and you will provide Ionis reasonably acceptable supporting
documentation.

For the 18 months following the end of your Ionis board of directors services,
if you are eligible for continued health coverage under COBRA, Ionis will pay
your COBRA premium payments sufficient to continue your coverage at your then
current level, or if COBRA is not available, Ionis will pay you an amount equal
to the cost of comparable replacement coverage.

Schedule B

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