T H E N E W F R O N T I E R O F I M M U N O - O N C O L O G Y

NYC Oncology InvestorNovember 12-13, 2019

2

Safe Harbor

Forward Looking StatementsThis presentation may contain forward-looking statements that are based on our current expectations, estimates and projections about our industry as well as management's beliefs and assumptions. Words such as "anticipates," "expects," "intends," "plans," "believes," "seeks,” "estimates," "may," "will," and variations of these words or similar expressions are intended to identify forward-looking statements. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding, which may not be available; our limited operating history; the unpredictable nature of our early stage development efforts for marketable drugs; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; potential delays in enrollment of patients which could affect the receipt of necessary regulatory approvals; potential delays in regulatory approval, which would impact the ability to commercialize our product candidates and affect our ability to generate revenue; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; ability to attract and retain key executives, and other factors.

These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Therefore actual results could differ materially and adversely from those expressed in any forward-looking statements as a result of various factors, While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

The PIONYR Opportunity

• Myeloid TuningTM therapies to enhance anti-tumor immunity as single agents and in combination• Deep myeloid biology expertise; integrated capabilities from target discovery to clinical trials• Advancing a pipeline of highly differentiated antibodies and mechanisms for a range of solid cancers • Compelling pre-clinical efficacy and safety data for two First in Class programs • Planning two INDs and Phase 1 trials in 2020

9 12 18 21 24 27 30

Dosed Dosed Dosed Dosed

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TME Target Discovery Platform 2 INDs in 2020 with differentiated Development Candidates

Myeloid TuningTM Target Pipeline

PY314

PY159TAMs1

TANs2

MDSCs3

1. Tumor Associated Macrophages, 2. Tumor Associated Neutrophils, 3. Myeloid Derived Suppressor Cells, 4. Dendritic Cells

DCs4

Confidential 3

4

Cells other than T-cells can also regulate the anti-tumor immune response

Effective in only a small subset of patients; Other drivers of immunosuppression in TME

Innovating Beyond Conventional IO Targets

Current Approaches

Matthew Krummel PIONYR FOUNDER

Professor, UCSF

YERVOY (ipi)Allison, Krummel et al

UC BerkeleyNobel winning research

Limitations

StimulatoryT Cell targets

Checkpoint Inhibitors

PIONYR:“MyeloidTuning”

Krummel et al. UCSF

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Targeting Myeloid Cell Populations Provides Rich Immuno-oncology Opportunities

Inhibitory myeloid cells• Tumor-associated

macrophages (TAMs)

Stimulatory myeloid cells• Dendritic cells (DC)

• Inhibitory myeloid cells can “crowd out” stimulatory myeloid cells

TUMOR

CD4TH1

Treg

CD8

B

NK

CD4TH2

Neutrophils/gMDSC

Mast

Patrollingmonocytes

Conv. Mono.mMDSC

TAMs

DC

Adapted from Cancer Growth and Metastasis, 2014, 7:9

• IO is currently dominated by lymphocyte targets

• Targeting TME-associated myeloid cells offers a new IO frontier

Krummel lab. Cancer Cell 2014, 26:638Intervital imaging of genetically engineered mice

Myeloid TuningTM

Myeloid TuningChanging the function and/or composition of myeloid cells within the tumor microenvironment in order to generate effective anti-tumor immunity

Tumor-associated

suppressive

myeloid cells

(TAMs, TANs, MD

SC)

Tumor-associated proinflammatory myeloid cells

Tumor growth

Tumor destruction

Confidential 6

PY314PY159

Front. Immunol. 2019, 10:1611

Tumor destruction

Tumor growth

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PIONYR’s Myeloid Tuning in Perspective:Mechanisms to Activate Anti-tumor Immunity

Direct activation of adaptive and innate anti-tumor immune cells

Examples: • Interferons• Interleukins• Vaccines• TNFSFR agonists

• anti-CD40• anti-CD137

Reverse dysfunctional adaptive anti-tumor immune cells

Examples (Check-point Inhibitors) • anti-CTLA4• anti-PD-1• anti-PD-L1• anti-LAG3• Etc• Etc

Disable suppressive myeloid cells to unleash anti-tumor immunity• Highly selective deletion of TME

myeloid suppressive cells

• “Hotwiring” suppressive myeloid cells to stimulatory state

Pushing the accelerator Releasing the brakes Pionyr: Turbocharge the engine

PY314

PY159

Example:

Example:

• TLR agonists• CAR-Ts• CD3 bi-

specifics

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Targeting CPI-resistance is a High Unmet NeedMultiple Mechanisms Prevent CPIs From Achieving Higher Response Rates

Indication ORR (%) No Response (%)Melanoma 33.7 66.3

NSCLC 19.2 80.8RCC 25.0 75.0

Bladder 14.8 85.2Gastric 30.0 70.0

Pancreatic 17.0 83.3

A majority of cancer patients do not respond to CPI therapies

Presented by Timothy Chan at the 2018 ASCO Annual Meeting

Mechanisms of CPI resistance

• Immune suppressive cellso Inhibitory Myeloid cells (eg, TAMs) – PIONYR focuso Inhibitory Lymphoid cells (eg, Tregs)

• Impaired tumor antigen processing/presentationo Stimulatory Myeloid cells (eg, DC) PIONYR focus

• Alternate immune checkpoints (eg, LAG3, TIM3)• Lack of sufficient or suitable neo-antigens• Impaired intratumor immune infiltration (eg, CD8+ CTLs)• Impaired IFNg signaling• Metabolic/inflammatory mediators (eg, IDO, A2AR)• Severe T cell exhaustion• T cell epigenetic changes (eg, histone deacetylase)

Adapted from BJC 2018, 118:9

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The Ratio of Stimulatory to Inhibitory Myeloid Cells Correlates with Patient Survival

Ø Patients with relatively low numbers of inhibitory myeloid cells control their disease better

Ø Myeloid Tuning increases the ratio of stimulatory to inhibitory myeloid cells

Stimulatory/Inhibitory Myeloid Cell Ratio in Metastatic Melanoma

Ratio Low

Ratio High

p = 0.00495OS

Sin

ce M

etas

tasi

s

Time (Months)

Myeloid ratio was measured using signature genes (underlying data from Bogunovic et al. 2009, 106:20429)

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Advancing a Pipeline of First-in-Class IO Programs

Drug Candidate (Target) Target Validation mAb Generation and Optimization IND-enabling

Activities IND

PY314 (TREM2)

PY159 (TREM1)

Discovery Engine

Q3 2020

Q3 2020

Surgical “Deletion” of immunosuppressive M2-like TAMs

“Reprogrammer” of suppressive M2-like TAMs, TANs and MDSCs

PY265 (undisclosed)

PY359 (undisclosed)

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PY314 Deletes TREM2+ TAMs and Converts CPI Resistance to Sensitivity• Tumor-associated macrophages (TAMs) are likely a major resistance mechanism to Checkpoint Inhibitors

• TREM2 is a highly specific TAM cell surface marker

• Depleting TAMs removes multiple mechanisms that subvert anti-tumor immunity and promote tumor growth

• Preclinical models show strong anti-tumor activity of anti-TREM2 + anti-PD-1 in anti-PD-1-resistant tumors

• Patients with high TREM2 expression have poor survival probability

• PY314 has wide therapeutic window; is well tolerated in GLP non-human primate (NHP) study

• PY314 biomarker assays have been established

• Highly favorable Pre-IND meeting with FDA

• Expression data suggests PY314 will have broad solid tumor application; especially gastric and ovarian

“Surgical” Deletion of a Specific Subset of TAMs Eliminates Multiple Pro-tumor, Immuno-suppressive Mechanisms

12 Adapted from Nature Reviews Cancer. 2016, 16:447

“M2-like” macrophages promote:

Production of arginase, IL-10, PD-L1, NO, and TGFb

Secretion of EGF, IL-6, and TNF

Production of cysteine cathepsins, MMPs, and EGF

Production of VEGFA, Sema4D, and IL-8

IMMUNOSUPPRESSION

TUMOR CELL PROLIFERATION

TUMOR CELL INVASION

ANGIOGENESIS

• Increased CD8+ T cells• Increased NKp46+ NK cells• Increased MHCIIHigh TAMs (“M1-like”)

Removal of “M2-like” macrophages with PY314 promotes anti-tumor immunity:

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PY314m Enhances the TME Immune Landscape

PY314m therapy decreases tumors

PY314m therapy increases CD8+ and NKp46+ NK cells

PY314m therapy decreases M2-like TAMs and increases M1-like TAMs

EMT6 tumor PD study

Dosing: isotype control or PY314m

(anti-TREM2) (30 mg/kg)

2 doses 5 d apart; tumors harvested 2 d

post second dose

TAMs

M2-like M1-likeCD8+T cells

NKp46+NK cells

Contr

ol

PY31

4mCo

ntrol

PY31

4m

Contr

ol

PY31

4m

Contr

ol

PY31

4m

Contr

ol

PY31

4m

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PY314m Has Single Agent Anti-Tumor Activity in the EMT6 Mammary Tumor Model

Isotype (20 mpk)

Anti-PD-1 (5 mpk)

Anti-PY314m (15 mpk)

Anti-PY314m (15 mpk)+ anti-PD-1 (5 mpk)

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pe

Anti-

PD-1

15 m

g/kg

Ant

i-TRE

M2

15 m

pk A

nti-T

REM2

+Ant

i-PD-

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Isotyp

e

Anti-P

D-1

(30%

CR)

PY31

4m

(40%

CR)

PY31

4m

+ anti

-PD-

1

(40%

CR)

• 10 mice per group • Dosing initiated when

tumors reached ~70 mm3• EMT6: mouse mammary

tumor

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• 10 mice per group • Dosing initiated when tumors reached

~100 mm3• CT26: mouse colon carcinoma

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PY314m (10 mpk)

PY314m (10 mpk)+ anti-PD-1 (5 mpk)

CR: 20% (range 20-60%)

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PY314m anti-tumor activity was observed in 7/8 syngeneic models tested to date as monotherapy and/or in combination with anti-PD-1

PY314m Plus Anti-PD-1 Inhibits Tumor Growth in the Anti-PD-1 Resistant CT26 Colon Tumor Model

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PY314m Plus Anti-PD-1 Induces Immune Memory

BALB/c mice that were tumor-free from previous studies after PY314m + anti-PD-1 treatment were re-challenged with CT26 tumor cells

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Rechallenge (N=4)

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TREM2 Expression is Higher in Diverse Cancers, and Inversely Correlates With Patient SurvivalTREM2 expression in

gastric cancer

Healthytissue

Gastriccancertissue

TREM2 expression levels in colorectal cancer inversely correlate

with patient survival probability

TREM2High

TREM2Low

Time (months)

Sur

viva

l pro

babi

lity

n=37n=413

n=192

Log2

TR

EM

2 ex

pres

sion

TREM2 expression inverse correlation with patient survival also seen in:• Hepatocellular Carcinoma (HCC)

• Renal Cell Carcinoma (RCC)

High TREM2 RNA expression also seen in:• Ovarian

• NSCLC

• Breast Cancer

• HNSCC

• Melanoma

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PY314 IND is On Track for early July 20202018 2019 2020

A S O N D J F M A M J J A S O N D J F M A M J J A S O N D

CMC

Research

Toxicology

Bioanalytics

Regulatory

Clinical

CLDProcess Dev

MCB GMP Production

Rodent Pilot ToxGLP Tox

GLP TCR

GMP F/F

GMP Stability

Pre-INDIND Prep

INDProtocol Concept Development CRO Engagement

Finalize Protocol Invest Brochure

Label

FPI

Tox Material

Dose Ranging PK/PDBiomarker Assay Implementation

MOA

NHP Pilot Tox

Biomarker/Translation

PK/ADA Assay Development and Tech Transfer

Pre-IND Prep

Clinical Protocol Development

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PY159 Reprograms TREM1+ Suppressive Myeloid Cells into Stimulatory Myeloid Cells• Reprogramming TAMs from immune suppressive to immune stimulatory can unleash anti-tumor immunity

• TREM1 is expressed by immuno-suppressive TAMs, myeloid-derived suppressive cells (MDSCs), and tumor-associate neutrophils (TANs)

• Anti-TREM1 mAb, PY159, induces production of cytokines and immuno-stimulatory cell surface proteins on myeloid cells that can recruit lymphocytes and enhance antigen presentation

• Preclinical models demonstrate strong anti-tumor activity of PY159

• Patients with high TREM1 expression have poor survival probability

• The anti-mouseTREM1 mAb is well tolerated in mice; single and multi dose in pilot NHP is well-tolerated

• PY159 biomarker assays are being established

• Expression data suggest PY159 will have broad application

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PY159’s MOA: Reprogramming of Suppressive Myeloid Cells

TREM1PY159

Anti-tumor immune cell

recruitment and activation

• T cells• NK cells • DC• Macrophages

TREM1

+TREM1+Pro-tumor

myeloid

suppressor cells

PY159-mediated

TREM1 cross-linking

TREM1

Reprogramming

towards anti-tumor

myeloid cells

TREM1

Secretion of pro-inflammatory

cytokines, and induction of

co-stimulatory molecules

TREM1+

Anti-tumor

myeloid

stimulatory cells

Tumor

destruction

21

aa

PY159 Promotes Anti-tumor Activity via Selective Secretion of Immune-enhancing Cytokines

Figure adapted from: https://www.biooncology.com/pathways.html

Immune Desert

Immune Excluded

Inflamed

Treatment Strategies

• Generate/Release/Deliver Antigens

• Enhance Antigen Presentation and T Cell Priming

• Redirect and Engage T Cells

Treatment Strategies• Recruit T cells to Tumor

• Address Stromal Barrier

• Redirected and Engage T Cells

Treatment Strategies• Invigorate T Cells

• Redirect And Engage T Cells

PY159

PY159-induced factors Function

IFN-g, IL-1a, IL-12, TNFSF9, CXCL9, CXCL10, CCL17

T cell recruitment and activation

IFN-g, CXCL1,CXCL5, CXCL11,

CXCL15, CCL4, CSF1

Myeloid cell recruitment and activation

IFN-g, CXCL10, TNFSF9

Enhance antigen presentation

IFN-g, CXCL10, IL-12, CCL4

NK cell activation

IFN-g, CXCL9, CXCL10 Required for anti-PD-1 efficacy

TNFSF10, FasL, GzmA, GzmB Direct tumor cell killing

PY159 can target Immune Excluded and Immune Desert TMEs

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• 10 mice per group• Dosing initiated when tumors

reached ~100 mm3• MC38: murine colon carcinoma • CT26: murine colon carcinoma

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PY159m has Significant Efficacy as Single Agent in MC38, and as Combo in CT26 Models

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MC38 mono-therapy CT26 combo-therapy

Isotype (20 mpk)

Anti PD-1 (5 mpk)

PY159m (15 mpk)

PY159m (15 mpk)+ anti PD-1 (5 mpk)

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me

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ControlControl + anti-PD-1Afuc PI-9067 + ControlAfuc-PI-9067 + anti-PD-1

CR: 20% (range 20-40%)

PY159m anti-tumor activity seen in 5/6 syngeneic models tested to date as monotherapy and/or in combination with anti-PD-1

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PY159m Induces Immune Memory

BALB/c mice that were tumor-free from previous studies after anti-PY159m + anti-PD-1 treatment were re-challenged with CT26 tumor cells

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Historical CT26

Reimplant CT26 (N=6)

Historical CT26 (N=6)

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Historical CT26

Reimplant CT26 (N=6)

Naive CT26 (N=6)

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CD4CD8

NK

B

Plasma

TAM

Monocyte(mMDSC)

Treg

pDC

Cell populations TREM2 TREM1

tSNE plots of single cell sequencing results from CD45+ immune infiltrate sorted from human ovarian tumor dissociated cells(neutrophils are not included in the analysis)

TREM2 + TREM1

TREM1 is Predominantly Expressed on Human Tumor Associated Monocytes (mMDSC)

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+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

+ + +++

+ +

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ + ++++ +++++ + +

p = 0.02

0.00

0.25

0.50

0.75

1.00

0 50 100 150 200Time

Surv

ival p

roba

bilit

y

Strata + +trem1median=TREM1hi trem1median=TREM1low

TREM1 Expression is Higher in Diverse Cancers, and Inversely Correlates With Patient Survival

TREM1 expression in colorectal cancer

TREM1 expression levels in gastric cancer inversely correlate with

patient survival probability

TREM1High

TREM1Low

Time (months)

Sur

viva

l pro

babi

lity

n=192

TREM1 expression inverse correlation with patient survival also seen in:• Breast cancer

• Pancreatic cancer

High TREM1 mRNA expression seen in:• NSCLC

• HNSCC

• Ovarian

• Stomach

• Bladder

Log2

TR

EM1

expr

essi

on

Healthytissue

Colorectalcancertissue

0

2

4

6

N Tnorm

TREM

1

n=41 n=282

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PY159 IND is On Track

2018 2019 2020A S O N D J F M A M J J A S O N D J F M A M J J A S O N D

CMC

Research

Toxicology

Bioanalytics

Regulatory

Clinical

CLDProcess Dev

MCB GMP Production

GLP Tox

GLP TCR

GMP F/F

GMP Stability

Pre-INDPre-IND Prep IND Prep

INDProtocol Concept Development

Clinical Protocol Development

CRO Engagement

Finalize Protocol Invest Brochure

Label

FPI

Tox Material

Dose Ranging PK/PD

Biomarker/Translation Biomarker Assay Implementation

PK/ADA Assay Development and Tech Transfer

NHP Pilot Tox

27

PY314 Clinical Hypotheses

• The presence of TREM2 positive cells in tumor infiltrates is a mechanism of both primary and acquired resistance to CPI therapies

• Patients with tumors that have higher levels of TREM2 positive inhibitory myeloid cells are more likely to respond to PY314 mono-therapy or CPI combination therapy

• PY314 therapy:o Convert CPI resistance to responseo Convert CPI stable disease to responseo Augment primary CPI response-better RR, longer PFS or OS

• Demonstration of objective tumor responses in patients with prior CPI resistance will be used for both assets as initial POC in order to de-risk clinical development in the smallest number of patients

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First-in-Human Trials Strategy: Efficient and Cost-Effective Path to PoC • Clinical indication selection ongoing

o IHC screening for target in TMAso Acquisition of tissue samples from CPI resistant patientso Thought leader consultation

• Establish single agent safety and in combination with approved CPIo Dose finding in subjects with a histologic diagnosis from 4-5 groups where TREM1 or TREM2 is

implicated in resistance selected for clinical progression on or after CPI based therapy

• Expansion Cohorts enriched for subjects with tumors that are target positive on contemporaneous biopsy by IHC obtained for study enrollmento IHC diagnostic LDT developed at PIONYR to be utilized for the patient selection

• If threshold RR achieved in a given tumor type, increase that expansion cohort size and plan phase II/III trialso Seek “breakthrough therapy” (BT) designation and/or determine if there is a path to Accelerated Approval

in specific indications

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Level 1 + CPI

Level 2 + CPIPY314Level 2

PY314Level 3

PY314Level 1

PY314Level 4

Level 4 + CPI

Timeline

Expansion cohorts of one or more dose

levels may start once safety declared

3 +3 design for initial dose escalation

6 months 12 months

First-in-Human Trial Strategy:Simultaneous Determination of Single Agent and CPI Combo Safety

18 months

Level 3 + CPI

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Experienced Team, Strong Syndicate R&D Leadership with deep IO expertise

Steven James PRESIDENT AND CEO

Michel Streuli, Ph.D. SVP, CHIEF SCIENTIFIC OFFICER

Leonard Reyno, M.D. SVP, CHIEF MEDICAL OFFICER

Monte Montgomery SVP, CHIEF FINANCIAL OFFICER

Alicia Levey, Ph.D. SVP, CHIEF BUSINESS OFFICER

Kevin Baker, Ph.D. SVP, PRECLINICAL & PROJECT MANAGEMENT

Evan Greger VP, CMC AND PROCESS DEVELOPMENT

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PIONYR’s Pipeline Provides Strategic Optionality

Myeloid Tuning

Self-develop products

$$$

RegionalLicensing

Deals$$

M&A$$$

Target Discovery

Deals$$

Co-Dev/ Co-Mktng

Deals$$$

IPO$$$

1Q 2020:Ø Pharma dealØ Series C financingØ 3rd Dev Candidate

3Q 2020:Ø PY314 INDØ PY159 IND

4Q 2020:Ø FPI PY314 and PY159

Key PIONYR Messages• Myeloid TuningTM through selective depletion and reprogramming of myeloid suppressive cells is a differentiated and orthogonal approach to tumor immunotherapy

• PY314 and PY159 are first-in-class therapies with the potential for mono or combo therapy across multiple tumor types, including those that are CPI resistant

• PIONYR will have 2 clinical programs in 2020 and potential for 2 additional DCs

• PIONYR’s discovery engine yields novel targets for oncology and other myeloid relevant indications

PY314 PY159

DCs for Targets PI-114 & 115

CD4CD8

NK

B

Plasma

TAM

Monocyte(m M DS C)

Treg

pDC