Aptevo Therapeutics

A Leading Bispecific Antibody Company

NASDAQ: APVO

March 2020

2

This presentation includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.Any statements, other than statements of historical fact, including our financial guidance, product portfolio, product sales,capabilities and any other statements containing the words “believes”, “expects”, “anticipates”, “intends”, “plans”, “forecasts”,“estimates” and similar expressions in conjunction with, among other things, discussions of financial performance or financialcondition, growth strategy, product sales, manufacturing capabilities, product development, regulatory approvals or expendituresare forward-looking statements. These forward-looking statements are based on our current intentions, beliefs and expectationsregarding future events. We cannot guarantee that any forward-looking statement will be accurate. Investors should realize that ifunderlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially fromour expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement. Any forward-looking statement speaks only as of the date of this presentation, and, except as required by law, we do not undertake to updateany forward-looking statement to reflect new information, events or circumstances.

There are a number of important factors that could cause Aptevo's actual results to differ materially from those indicated by suchforward-looking statements, including possible negative effects on Aptevo’s business operations, assets or financial results as aresult of the separation; a deterioration in the business or prospects of Aptevo; adverse developments in Aptevo’s customer-baseor markets; our ability to enter into and maintain selective collaboration and partnership arrangements; the timing of and our abilityto achieve milestones in collaboration and partnership contracts; our ability and the ability of our contractors and suppliers tomaintain compliance with cGMP and other regulatory obligations; the results of regulatory inspections; the rate and degree ofmarket acceptance and clinical utility of our products; the success of our ongoing and planned development programs; the timingof and our ability to obtain and maintain regulatory approvals for our product candidates; and our commercialization, marketingand manufacturing capabilities and strategy and changes in regulatory, social and political conditions. Additional risks and factorsthat may affect results are set forth in our filings with the Securities and Exchange Commission, including Aptevo’s most recentAnnual Report on Form 10-K, as filed on March 18, 2019, and its subsequent reports on Form 10-Q and current reports on Form8-K.

The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in anyforward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our periodicreports filed with the SEC, when evaluating our forward-looking statements.

Aptevo™, ADAPTIR and any and all Aptevo Therapeutics Inc. brand, product, service, and feature names, logos, and slogans aretrademarks or registered trademarks of Aptevo Therapeutics Inc. or its subsidiaries in the United States or other countries. Allrights reserved.

Forward-Looking Statements

3

AGENDA

Leadership in Bispecific Antibody Development

▪ Aptevo Today

▪ ADAPTIR – A Differentiated Bispecific Platform

▪ Summary

4

• Clinical-stage immunotherapy company

• Robust bispecific antibody platform technology (ADAPTIR™)

▪ Flexible; ability to generate multiple unique MOAs

▪ Potential best-in-class candidate attributes

• Broad clinical/preclinical portfolio- multiple novel candidates in development

▪ APVO436 – AML and MDS (r/r and first-line therapy)

▪ ALG.APV-527 – multiple solid tumors

▪ APVO603 – multiple solid tumors

• Market cap: ~$20M

• Cash and Investments: ~$30.4M (9/30/19 proforma)

Aptevo at a Glance (NASDAQ: APVO)

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Experienced Leadership Team

Senior Management

Marvin White – President & CEOFormer Emergent Director; Former CFO, St. Vincent’s

Health; Former Exec. Director & CFO, Lilly USA

Jeff Lamothe – SVP, CFOFormer Emergent VP, Finance; Former CFO, Cangene

Corporation

Randy Maddux – SVP, Chief Manufacturing

Officer Former VP, Global Mfg & Supply, GSK;

Former VP, Mfg Ops & Quality, Human Genome Sciences

Dr. Scott Stromatt – CMO*Former Emergent SVP, CMO; Former CMO, Trubion

Dr. Jane Gross – SVP, CSOFormer Emergent VP, Research/Non-Clinical Development;

Former VP Immunology Research ZymoGenetics Inc.

Shawnte Mitchell – SVP, Gen’l CounselFormer Emergent VP, Associate General Counsel

Board of Directors

Marvin WhiteFormer Emergent Director; Former CFO, St. Vincent’s

Health; Former Exec. Director & CFO, Lilly USA

Fuad El-HibriFounder, Executive Chairman, Emergent BioSolutions

Daniel Abdun-NabiFormer President & CEO, COO, Emergent BioSolutions,

Former General Counsel, IGEN International, Inc.

Grady Grant, IIIVice President of Sales, Tissue Tech Limited; Former Reckitt

Benckiser Group; Eli Lilly & Co.

Zsolt Harsanyi, Ph.D.N-Gene Research Labs; Exponential Biotherapies;

Porton Int’l

Barbara Lopez KunzDIA; Battelle; Thermo Fisher Scientific; ICI/Uniqema

John Niederhuber, M.D.Inova Translational Medicine Institute; National Cancer

Institute; Johns Hopkins University

Deep R&D, Manufacturing, Commercial and Financial Expertise and Experience

*Dr. Stromatt is a consultant to the company

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• Sold off-strategy hemophilia B asset to Medexus (Feb 2020) for

estimated proceeds in excess of $100M

– Simplified Aptevo investment thesis and value proposition

– Transformed Aptevo into a ‘pure play’ biotech company

– Streamlined focus on novel bispecific antibody technology platform

(ADAPTIR™)

– Strengthened Aptevo’s financial position

▪ Provided non-dilutive upfront cash to fund the organization

▪ Repaid all debt

▪ Established royalty stream (15 years)

▪ Established milestone payments (up to $11 million)

▪ Extended current cash runway into Q4 2020

– Increases focus on important upcoming valuation catalysts

▪ APVO436 poised to make important progress in 2020

▪ Currently evaluating clinically-relevant dosing levels (cohorts 5-8)

IXINITY Divestiture

The New Aptevo - A Pure Play Biotech Company

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Our Strategy

1

2

3

Develop and advance novel immuno-oncology ADAPTIR

product candidates

Expand collaborations and partnerships

Maximize non-dilutive funding sources

to support future capital requirements

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Product/Candidate

TargetTechnology

Potential

Indications

Pre-

Clinical

Clinical Development Stage

Marketed Milestones/Highlights

Phase I Phase II Phase III

APVO436

CD3/CD123

Redirected T-Cell

CytotoxicityAML/MDS (R/R) Phase 1/1b study ongoing

APVO436

CD3/CD123

Redirected T-Cell

Cytotoxicity

AML front-line

setting

Selected for inclusion in

groundbreaking ‘BEAT

AML® Master Clinical Trial’

spearheaded by LLS

ALG.APV-527*

4-1BB/5T4

T-Cell Co-

stimulation

Multiple Solid

Tumors

Seeking partnership for

clinical development.

Preclinical package ready

for filing of CTA

APVO603

4-1BB/OX40

Dual T-Cell

Co-stimulation

Multiple Solid

Tumors

Unique asset for use in

multiple solid tumors;

Advancing lead candidate

Multiple ADAPTIR

Candidates

ADAPTIR

Bispecific RTCC

and New MOA

Hematologic and

Solid Tumors

Advancing new candidates

that modulate the immune

system

• Partnered with Alligator Bioscience

• Redirected T-Cell Cytotoxicity Based on Targeting CD3

ADAPTIR PIPELINE

Robust and Diversified Product Portfolio

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AGENDA

Leadership in Bispecific Antibody Development

▪ Aptevo Today

▪ ADAPTIR – A Differentiated Bispecific Platform

▪ Summary

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• Bispecific Antibodies

– Blyncytocyto® (blinatumomab) first approved bispecific

– Increasing number of bispecifics in clinical development

– ASH 2019 data showed compelling complete responses

with bispecific technologies in several indications

– Potential for equal or better efficacy; simpler delivery and

manufacturing than CAR-T therapies

• ADAPTIR platform advancing multiple bispecifics

in preclinical and clinical development

– Multiple mechanisms of action

– Clear advantages over other platform technologies

Bispecific Antibodies

The Next Wave of Targeted Immunotherapies

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MODULAR AND FLEXIBLE▪ Monospecific and bispecific formats▪ Flexible design supports reproducible generation of

bispecifics with potent activity

MULTIPLE MECHANISMS OF ACTION▪ Redirected T-Cell Cytotoxicity (RTCC)▪ Tumor target co-stimulation of immune receptors▪ Dual receptor targeting that stimulates or inhibits

immune responses

EXCELLENT MANUFACTURING PROPERTIES▪ Single gene facilitates ease of CHO cell production▪ Antibody backbone increases stability▪ Standard manufacturing process with high yields and

purity

ANTIBODY-LIKE HALF LIFE▪ Half-life up to 12 days in rodents

ADAPTIR – A Differentiated Bispecific

Antibody Platform Technology

IgG Fc

Protein Domain 2

Protein Domain 1

Linker

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Engineer scFv from Human or

Mouse hybridoma

Isolate Human scFv

From Phage library

ADAPTIR

Built on A Modular Antibody Platform

Utilize Binding Domains from Multiple Sources

Engineer ADAPTIR Candidates with Different Structures and for Different MOA

scFv

IgG Fc

Linker

Engineered Ligands and Cell-

Surface Receptors

scFv 1

scFv 2

Bispecific

Engineered Ligands and Cell-

Surface Receptors

scFv 1 scFv 1 scFv 2

Multi-Specific

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• ADAPTIR bispecifics are based on a robust technology platform with advantages over other platforms

– Antibody-like manufacturing and half-life

– Ease of transfer and manufacturing at CMOs

– Bivalent binding enables avidity tuning to spare normal tissue expression of tumor antigen and improve biodistribution

• ADAPTIR T-cell engagers use a proprietary anti-CD3

– Demonstrated potent killing in vitro and in vivo (preclinical models)

– Reduced cytokine release in preclinical studies may improve tolerability in a clinical setting

• ADAPTIR bispecifics have been built to achieve several biological mechanisms:

– Tumor-targeted CD3 agonism for redirected T cell killing

– Tumor-targeted TNFR agonism, which may have improved biodistribution and potency in solid tumors

– Targeted cytokines to stimulate or inhibit the immune system

ADAPTIR Summary

A Powerful and Flexible Platform

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Current ADAPTIR Bispecific Pipeline With

Different Mechanisms of Action

APVO436

Anti-CD3

Anti-CD123

• CD3 x CD123 Engager• Currently in Ph 1, AML• Silenced Fc• Long serum half-life• ~1.5 g/L CHO expression• Low cytokine release

ALG.APV-527

Anti-5T4

Anti-4-1BB

• Activates tumor-specific T cells• For multiple solid tumors• Silenced Fc• Co-developing with Alligator

Bioscience

APVO603

Anti-OX40

Anti-4-1BB

• Activates tumor-specific T cells via 4-1BB and OX40

• For multiple tumors• Silenced Fc• Synergistic activation of T

cells demonstrated

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APVO436CD123 x CD3

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APVO436 – A Novel Immunotherapy for AML

CANDIDATE

OPPORTUNITY

FUNCTION/MOA

POTENTIAL

INDICATIONS

DEVELOPMENT

STAGE

PARTNERSHIP

STATUS

• ADAPTIR (CD123 x CD3) T cell engager

• Preclinical studies showed key differentiation from another

bispecific format*

• CD123 - compelling target for AML due to its overexpression on

leukemic stem cells and AML blasts; Designed to engage T cells

via binding to CD3 to specifically kill tumor cells expressing CD123

• AML, MDS, ALL, hairy cell leukemia, myelodysplastic syndrome

• Strong unmet need for safe and effective new therapies

• Phase 1 study dose escalation in R/R AML and MDS ongoing

• Orphan drug designation granted

• Selected for inclusion in groundbreaking BEAT AML Master

Clinical Trial; evaluating APVO436 in front-line AML setting

• Wholly-owned by Aptevo

aCD3 scFv

aCD123 scFv

*Aptevo-generated version of Macrogenics’ CD123 x CD3 dual-affinity re-targeting (D.A.R.T) molecule, MGD006

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• AML: 21,000 new cases/year in U.S. / 10,500 deaths/year in U.S.

– Average age 67 years / 5-year survival 26%

• MDS: 10,000 – 20,000 new cases/year in U.S.

– 1 in 3 patients with MDS will progress to have AML

• Front-line treatment is chemotherapy

– Standard therapy = “7+3”; cytarabine and daunorubicin for induction over 1-2 mos

– Consolidation therapy for 2 mos (radiation, stem cell transplant)

• Strong unmet need for novel therapies that improve outcomes and survival

– Elderly, newly diagnosed, high-risk, relapsed/refractory patients

• CD123 broadly expressed in AML blasts and on leukemic stem cells

– Numerous novel targeted agents in development but they only impact AML subsets

AML / MDS Opportunity*

*Source: Global Data 2018, Decision Resources 2015, Seer.cancer.gov, EvaluatePharma, Pharmaetrack, American Cancer Society;

Myelodysplastic Syndromes, Cancer Network, Jorge E. Cortes, MD, June 2007

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Unique T-Cell Engagers

• Demonstrated ability to build several T-cell engager bispecificswith highly potent in vitro and in vivo activity

• Novel anti-CD3 selected for desired properties

– Based on unique CD3 binding domain; distinct from most CD3 binding domains used by other T-cell engagers

• Unique properties of ADAPTIR T-cell engager platform demonstrated

– Bivalent binding enables avidity tuning to spare normal tissue expression of tumor antigen

– Efficient tumor cell lysis with reduced cytokine release (in vitro)

– Long half-life (~12.5 days in rodents and ~4.5 days in cynos for CD123xCD3) to enable once weekly dosing

– Excellent stability and manufacturability

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ADAPTIR T-Cell Engager Induced Comparable T-cell

Cytotoxicity Compared to Another Bispecific Format*

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e C

ell

Co

un

ts

A P V O 4 3 6

A p te v o -M G D 0 0 6

T R I1 4 9 (N e g .) C o n tro l

*Aptevo-generated version of Macrogenics’ CD123 x CD3 dual-affinity re-targeting (D.A.R.T) molecule, MGD006

*Statement evaluated with ADAPTIR CD3-based bispecifics only

AACR 2018 Poster: APVO436, a Bispecific anti-CD123 x anti-CD3 ADAPTIR Molecule for Redirected T-cell Cytotoxicity, Induces

Potent T-cell Activation, Proliferation and Cytotoxicity with Limited Cytokine Release

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• Cytokines measured after 20 hr stimulation of T cells with ADAPTIR and

tumor cells

ADAPTIR T-Cell Engager Candidates Induced Lower

Levels of Cytokines than Another Bispecific Format*

ADAPTIR bispecifics generated lower levels of cytokines when tumor antigen present

compared to another bispecific format targeting the same tumor antigen in in vitro studies*

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pg

/mL

DART

ADAPTIR

Tumor TargetT cell activation

cytokine release

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/mL

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pg

/mL

AACR 2018 Poster: APVO436, a Bispecific anti-CD123 x anti-CD3 ADAPTIR Molecule for Redirected T-cell Cytotoxicity, Induces Potent T-

cell Activation, Proliferation and Cytotoxicity with Limited Cytokine Release

* Aptevo-generated version of Macrogenics’ CD123 x CD3 dual-affinity re-targeting (D.A.R.T) molecule, MGD006

* Statement evaluated with ADAPTIR CD3-based bispecifics only

Cytokines measured after 20 hr stimulation of T cells with ADAPTIR and tumor cells

21

APVO436 Key Differentiation From Other

Bispecifics Targeting CD123 and CD3

APVO436 – Key Competitor Differentiation

Novel structure• Supports traditional antibody-like manufacturing

processes

• Single gene construct and CHO production cell line

Improved half-life• ~12.5 days (in rodents); 4.5 days (NHPs)

• Enables potential for improved dosing regime in clinic

Potential for

reduced cytokine

release

• Robust data set shows lower levels of cytokine release

versus competitor molecule (Macrogenics)

• Comparable tumor lysis and T-cell activation to

competitor molecule (Macrogenics)

• Potential for superior safety profile and broader

therapeutic window

AACR 2018 Poster: APVO436, a Bispecific anti-CD123 x anti-CD3 ADAPTIR Molecule for Redirected T-cell Cytotoxicity, Induces Potent

T-cell Activation, Proliferation and Cytotoxicity with Limited Cytokine Release

Aptevo-generated version of Macrogenics’ CD123 x CD3 dual-affinity re-targeting (D.A.R.T.) molecule, MGD006

22

In AML patient samples APVO436:

• Induced rapid activation and proliferation of endogenous T cells

• Showed robust responses to APVO436 with low endogenous T cell numbers

• Showed a progressive reduction of CD123+ cells over 96-hour culture period

APVO436 Induced Endogenous T-cell Proliferation and

Depletion of CD123+ Cells in AML Patient Samples

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ell

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un

t

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1 0 0

1 2 0

C o n c e n tra t io n (p M )

A P V O 4 3 6

N e g . C o n tro l

% L

ive

CD

12

3+

Ce

lls

AML Subject Samples

CD123+ Cell DepletionT-cell Proliferation

AACR 2018 Poster: APVO436, a Bispecific anti-CD123 x anti-CD3 ADAPTIR Molecule for Redirected T-cell Cytotoxicity, Induces Potent T-

cell Activation, Proliferation and Cytotoxicity with Limited Cytokine Release

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• Treatment of previously established MOLM-13 tumors

in mice with APVO436 resulted in rapid reduction in

skeletal tumor burden

Therapeutic Delivery Model: APVO436 Eliminated

Skeletal Tumor Burden in Mice with Established Tumors

R e m a in in g T u m o r B u rd e n in

N o n -S k e le ta l L o c a tio n

0 4 8 1 2 1 6

1 0 6

1 0 7

1 0 8

1 0 9

1 0 1 0

D a y s p o s t tu m o r c e lls e n g ra ftm e n t

Bio

lum

ine

sc

en

ce

To

tal

Flu

x [

p/s

]

M O L M -1 3 o n ly

V e h ic le c o n tro l

3 g A P V O 436

• NSG mice implanted IV with MOLM-13 cells on Day 0

• T cells implanted on Day 4

• Drug delivered after tumors are established

3 g APVO436

Molm-13

only

CONTROL

APVO436

*Model artifact – tumor expansion after 8 days due to loss of human T cells

and sequestration of tumor cells in ovaries

*

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Phase 1/1b Open-Label, Dose-Escalation Clinical Trial

ObjectiveEvaluate safety, pharmacokinetics, pharmacodynamics

Determine recommended dose for Phase 1b

Primary

Endpoints

Phase 1: Incidence of dose-limiting toxicities occurring during

Cycle 1 of each dose cohort

Phase 1b: Assess clinical activity (Overall Response Rate)

Study

Design

Phase 1: Determine maximum tolerated dose and recommended

dose for Phase 1b

Phase 1b: Assess clinical activity at recommended dose

Administration APVO intravenous (IV) dosing weekly for six 28-day cycles

Subjects Phase 1: up to 60 patients; Phase 1b: up to 48 patients

Status

Dose escalation ongoing; beginning cohort 6

19 patients enrolled and treated to date (cohorts 1-5)

No evidence of drug-induced anti-drug antibodies (ADA) to date

1 DLT in 1/6 patients in cohort 4; no DLTs in cohort 5

APVO436 Clinical Development Program

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• Groundbreaking national clinical trial

• Spearheaded by the Leukemia & Lymphoma Society

• Evaluating novel AML immunotherapies

• 800 patients enrolled to date; 16 leading cancer centers

– Memorial Sloan Kettering Cancer Center, The Ohio State University

Comprehensive Cancer Center, Oregon Health and Science University Knight

Cancer Institute, Mayo Clinic

• APVO436 selected for inclusion alongside industry leaders

– Bristol-Myers Squib (formerly Celgene) Alexion Pharmaceuticals, Gilead

Sciences, Takeda Oncology, Agios Pharmaceuticals, Astellas Pharma and

Boehringer Ingelheim as an Industry Participant

• APVO436 to be tested in combination with decitabine in newly diagnosed

AML patients

• Benefits of participation in Beat AML trial:

– Provides access to leading national cancer centers

– Evaluates APVO436 in a front-line AML treatment setting

– Complements ongoing Phase 1/1b study in relapsed/refractory AML

APVO436 Selected for Inclusion in the Leukemia &

Lymphoma Society ‘Beat AML® Master Clinical Trial’

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• A potential best-in-class bispecific T-cell engager targeting CD123 x CD3

– Potent T-cell mediated killing of CD123+ tumors (no killing without target present)

– Reduced cytokines observed in preclinical studies compared to competitor molecule

– Binds to cynomolgus T cells

• Antibody-like half-life in rodents (~12.5 days)

– 4.5 days in NHPs

• Preclinical in vivo proof-of-concept established in multiple xenograft tumor models

• High titer CHO cell clone production levels > 1 g/L

• Good manufacturability attributes

• Phase 1 dose-escalation ongoing in AML and MDS

– No drug-induced ADA observed to date

– No DLTs in cohort 5; 1 DLT in 1/6 patients in cohort 4

– Received orphan drug designation

– Selected for inclusion in groundbreaking ‘Beat AML® Master Clinical Trial’

APVO436 – Summary

27

ALG.APV-5274-1BB X 5T4

28

ALG.APV-527 – Broad Potential

Therapeutic Opportunity in Solid Tumors

CANDIDATE

OPPORTUNITY

FUNCTION/MOA

POTENTIAL

INDICATIONS

DEVELOPMENT

STAGE

PARTNERSHIP

STATUS

• Designed to engage T cells through co-stimulatory

receptor 4-1BB

• Designed to reactivate antigen-primed T cells to specifically kill tumor

cells; Designed to promote CD8 T cell survival and effector function

• Multiple solid tumor indications: breast, cervical, non-small-

cell-lung, prostate, renal, gastric, colorectal and bladder

cancers

• Seeking partnership for clinical development

• Preclinical package ready for CTA filing

• Joint 50/50 ownership & co-development agreement with

Alligator Bioscience

a4-1BB scFv

a5T4 scFv

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• New MOA demonstrates ADAPTIR versatility

• Simultaneously targets

– 4-1BB - costimulatory receptor, member of TNFR super family

– 5T4 tumor antigen

• Promising approach for targeted immunotherapy designed to:

– Target T cells previously activated by tumor antigen

– Exert tumor-localized T cell activation upon 5T4 binding

– Not stimulate all (resting or naive) T cells

• Potential Advantages:

– Improved efficacy and safety (targeted therapy)

– Opportunity to treat multiple solid tumors expressing 5T4 antigen (i.e. NSCLC, renal, pancreas, prostate, breast, ovarian, cervical)

ALG.APV-527 Targeted Immunotherapeutic Bispecific

Antibody Candidate Targeting 4-1BB x 5T4

Activated

T-cell

4-1BB

Tumor

killing

Tumor cell

Expressing 5T4

5T4

30

• In vitro:

– Bound to human and cynomolgus 5T4 and 4-1BB expressing cells and

activated T cells

– Induced 4-1BB reporter activity only when 5T4 targets were present

– Induced CD8+ T cell proliferation and IFN-γ production in the presence of

5T4 antigen

– Induced NK cell activation only in presence of 5T4 targets

• In vivo:

– Localized to 5T4-expressing tumor

– Treatment reduced colon carcinoma HCT116 tumor growth

• Conclusion:

– ALG.APV-527 is a promising therapeutic candidate for 5T4-expressing

solid tumors designed to eliminate the dose-limiting hepatic toxicities of

previous 4-1BB targeting therapies and increase drug concentration in

solid tumors

ALG.APV-527 Preclinical Data

31

5T4-Driven Tumor Localization of

ALG.APV-527 in a B16 Twin Tumor Model

• One B16-wt (5T4-negative) and one B16-5T4 (5T4-

positive) tumor injected SQ (1x105 cells, 100 µL) at each

side of the hind flank/back of C57Bl6 mice

• 100 µg of ALG.APV-527 given twice

• Mice sacrificed 24 h after final treatment

• Levels of ALG.APV-527 bound to cells were assessed by

IHC or flow cytometry using an antibody detecting human

IgG

B16 melanoma twin tumor model ALG.APV-527 localizes to 5T4 positive

but not 5T4 negative tumors

A L G . A P V - 5 2 7 V e h ic le

0

1

2

3

4

% h

IgG

+ b

ind

ing

to

via

ble

CD

45

- t

um

or c

ell

s

B 1 6 - 5 T 4 ( 5 T 4 p o s i t i v e t u m o r )

B 1 6 - w t ( 5 T 4 n e g a t i v e t u m o r )

5T4-neg tumor

5T4-pos tumor

D0 D13 D15 D16

ALG.APV-527

100 g (IP)

B16-wt and B16-5T4

(SQ)

32

ALG.APV-527 Induces Anti-Tumor Effects

and Immunological Memory

• MB49 cells expressing human 5T4 injected SQ into 4-1BB

knock-in mice

• ALG.APV-527 or 4-1BB mAb control (w/ wildtype Fc)

administered twice weekly on day 7 - 24, (8 mice/group)

• Surviving mice that had cleared their primary tumor were re-

challenged with MB49 tumor cells on day 80 with no further

therapy (naïve mice served as controls)

Human 4-1BB knock-in murine cancer model ALG.APV-527 inhibits tumor growth and

promotes immunological memory

0 7 14 21 280

200

400

600

800

1000

1200

Day Post Tumor challenge

Mean T

um

or

Volu

me (

mm

3) PBS

180 ug60 ug20 ug

60ug

ALG.APV-527

monospecific4-1BB mAb

Primary tumor

response

Memory

response

0 7 14 21 280

200

400

600

800

1000

1200

1400

Day Post Tumor challenge

Mean T

um

or

Volu

me (

mm

3)

MB49-5T4

MB49

MB49-5T4MB49

Naive

Memoryre-challenge

MB49 / hu5T4 cells

hu4-1BBALG.APV-527

180, 60 or 20 g

7 10 13 17 20 24D0

MB49 cell

re-challenge

80

33

• Designed for 5T4-dependent tumor-directed T-cell activation to overcome

dose-limiting toxicities seen with 4-1BB mAbs

• Optimized in the ADAPTIR format for activity, solubility, stability and

manufacturability properties

• 5T4-dependent T-cell and NK-cell proliferation and activation, 5T4-driven

tumor localization, and anti-tumor efficacy demonstrated

• Limited competition

• Preclinical package ready for CTA filing

• Pursuing partnership for initiation of clinical development

ALG.APV-527 Summary

34

APVO6034-1BB x OX40

35

APVO603 – Dual Agonistic Bispecific Antibody

CANDIDATE

OPPORTUNITY

FUNCTION/MOA

POTENTIAL

INDICATIONS

DEVELOPMENT

STAGE

PARTNERSHIP

STATUS

• Designed to simultaneously target 4-1BB and OX40 both

members of the TNF-receptor family

• Provides synergistic co-stimulation of T cells to potentially amplify

the cytotoxic function of activated T cells and NK cells; may promote

more robust anti-tumor responses

• Multiple solid tumor indications

• Preclinical

• Lead candidate identified

• IND-enabling activities underway

• Wholly-owned by Aptevo

a4-1BB scFv

aOX40 scFv

36

• New ADAPTIR bispecific candidate with novel

mechanism of action targeting both 4-1BB and

OX40

• Designed to activate existing anti-tumor responses

without targeting a specific tumor antigen

• Synergistic activation of T cell and NK cell

responses due to dual targeting of 4-1BB and OX40

only as a bispecific

• Mutated Fc to eliminate FcgR and C1q interactions;

stimulation only when 4-1BB and OX40 are co-

engaged

• Demonstrates versatility of ADAPTIR platform

APVO603: Dual Agonist ADAPTIR Bispecific

Targeting 4-1BB x OX40

Anti-OX40

Fc Region

No effector function

Anti-4-1BB

37

TCR

CD4/8+ T cell

Tumor

Tumor

Activates Multiple Immune Pathways to Increase

Anti-Tumor Response and Reduce Toxicity

Key Advantages:

• Enhances pre-existing anti-tumor responses

• Enhances all effector lymphocyte populations: CD4, CD8 & NK cells

• Potential to limit toxicity seen by 4-1BB monospecific due to lack of Fc

receptor engagement

OX40Upregulation

4-1BBUpregulation

CD4

NK

CD4, CD8 and NK cells cooperate to induce tumor lysis

cytokines

granzymes

Increased number and potency of tumor-specific

cells with effector function

38

• Synergistic activation of CD4, CD8 and NK Cell Proliferation by APVO603

• No proliferation with monospecifics targeting either 4-1BB or OX40 without

cross linking

Potent Synergistic Activity Compared to 4-1BB

or OX40 Monospecific Alone or in Combination

• Cells pre-stimulated with anti-CD3 to upregulate expression of 4-1BB and

OX40

• Proliferation of CD4, CD8 and NK Cell Populations are measured by Flow

Cytometry

0.0

001

0.0

01

0.0

10.1 1

10

100

2 0

3 0

4 0

5 0

6 0

C D 4+

T c e ll p ro life r a t io n

[n M ]

CD

4 %

Pro

life

ra

ted

0

0.0

001

0.0

01

0.0

10.1 1

10

100

1 0

2 0

3 0

4 0

5 0

6 0

C D 8+

T c e ll p ro life r a t io n

[n M ]

CD

8 %

Pro

life

ra

ted

0

0.0

001

0.0

01

0.0

10.1 1

10

100

0

5

1 0

1 5

2 0

2 5

N K c e ll p r o life ra t io n

[n M ]

CD

56

% P

ro

life

ra

ted

a 4 -1 B B -F c -a O X 4 0

a 4 -1 B B -F c

F c -a O X 4 0

a 4 -1 B B -F c + F c -a O X 4 0

0

39

AGENDA

Leadership in Bispecific Antibody Development

▪ Aptevo Today

▪ ADAPTIR – A Differentiated Bispecific Platform

▪ Summary

40

Milestones – Next 12-18 Months

40

Development

• Complete dosing in ongoing

APVO436 Phase 1 clinical trial

• Report ongoing progress in APVO436

Phase 1/1b clinical study as data

become available

• Advance APVO603 towards clinical

development

• Announce new preclinical ADAPTIR

candidate

Operational/Financial

• Continue current and initiate future

partnering discussions around product

candidates and ADAPTIR platform

• Pursue additional non-dilutive funding

opportunities

• Collect quarterly IXINITY deferred

payments (royalties)

41

Why Aptevo?

1

2

3

4

Established leadership and capabilities in protein-based therapies for cancer

Proprietary, versatile, differentiated ADAPTIR technology platform

Broad pipeline of clinical and preclinical bispecific candidates advancing

Wholly-owned portfolio with potential for multiple partnerships