Jefferies Global Healthcare ConferenceJune 6, 2019

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Kyn Therapeutics Executive Summary

Clinical-stage, patient-directed immuno-oncology pipeline in difficult to treat cancers

• Programs with robust patient selection/enrichment strategies• Rapid to clinical POC opportunities

Significant milestones expected over next year• Lead program with 2 clinical POC opportunities• Two additional programs filing INDs

Building a leading translational science-driven oncology R&D company

• Experienced team with biologics/small-molecule experience• Well funded from Series A and Celgene collaboration• Expanding pipeline through internal programs and in-licensing• IPO pending positive clinical POC and favorable market conditions

Top Tier Partners

$49M Series A

Strategic collaboration on AHR and Kynase,

$80M upfront + equity

Strong Leadership Team and Advisors

Mark Manfredi, Ph.D.Chief Executive Officer

Michelle Zhang, Ph.D.VP Translational

Karen McGovern, Ph.D.VP Discovery Biology

Jim NolanVP CMC

Alfredo Castro, Ph.D.SVP Chem & Preclin.

Jeff Ecsedy, Ph.D.Chief Scientific Officer

Maude Tessier, Ph.D.VP BD

Jason Sager, M.D.Chief Medical Officer

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Doug CarlsonChief Financial Officer

Senior Management

George Prendergast, Ph.D.Advisor

Andrew Mellor, Ph.D.Advisor

Jedd Wolchok, M.D., Ph.D.Collaborator

Francisco Quintana, Ph.D.Advisor

• IDO/TDO• Lankenau Institute

• IDO/TDO• Univ. Newcastle

• AHR• Harvard Medical

School

• IO Clinical Development

• MSKCC

Pawel Kalinski, M.D., Ph.D.Advisor

• PGE2/EP4• Translational• Roswell Park

Advisors/Collaborators

Experienced Board of Directors/Investor

David Bonita, M.D.OrbiMed

Jean Francois Formela, M.D.Atlas Venture

Ian Dukes, Ph.D.OrbiMed

George Georgiou, Ph.D.UT Austin

Mark Manfredi, Ph.D.Kyn Therapeutics

• Private Equity Partner• BOD member on many

preclinical/clinical biotechs

• Partner• BOD member on

private/public biotechs

• Venture Partner• Previously at Merck,

Amgen, GSK

• Academic founder• Founder of 2 other biotechs• Protein engineer and

immunologist

• CEO of Kyn Therapeutics• Previously at Raze

Therapeutics, Takeda Oncology, Atlas Venture

Ron RenaudChairman of Board

• Banking/analyst• Former CEO Idenix• Current CEO Translate Bio

(NASDAQ: TBIO)

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Atsushi Nagahisa, Ph.D.AskAt

• Co-founder AskAt• Previously at Pfizer,

ReQualia, DNA partners

Pioneering the Next Frontier in Cancer Immunotherapy

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Our mission is bringing breakthrough therapies to patients with cancer, particularly those who do not benefit from current treatments like checkpoint inhibitors

Our Central Thesis

• Combinations with meaningful benefit, especially in resistance setting, will inherently target multiple mechanisms of immunosuppression

• Focus on modulating pathways that stimulate the innate and adaptive immune system

• Leverage years of preclinical and clinical research to explore full potential of immuno-metabolic targets

• Core interest in fundamental immuno-metabolites likely to be effective across multiple tumor types, in resistance setting, and active in combos beyond IO

Our Approach

Kyn Development Stage Pipeline

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COX2/PGE2/EP4 pathway Associated

Poor Survival in CRC and NSCLC

Development strategy to reach rapid POC in checkpoint resistance setting

ARY-007 is the right molecule

ARY-007: EP4 InhibitorRapid POC opportunity in Oncology

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EP4 is the right target

• Ongoing Ph1b/2 studies in combo with pembrolizumab in microsatellite stable (MSS) CRC and in PD-1/PDL-1 refractory NSCLCo MSS CRC inherently resistant to anti-PD-1

therapieso NSCLC study in patients who have progressed on

PD-1 or PD-L1 therapy• Retrospective patient selection biomarkers for

possible prospective Ph2 selection

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Pathway is linked to cancer initiation and progression ↑ COX-2, PGE2 and EP4 expression associated with decreased OS, therapeutic and preventive precedent

in a number of cancers, in particular in CRC and NSCLC

Sheehan KM, JAMA 282:1254-57 (1999)

Increased COX-2 expression associated with poor prognosis in CRC

35 estimates from 32 studies were used in the meta-analysis of OTC NSAIDs and colon cancerHarris RE Inflammopharmacology 2009, 17(2):55-67

Kaplan-Meier survival estimates by COX-2 epithelial staining in CRC tumors

COX-2 blockade in the chemoprevention of colon cancer

Zhou et al, PLOS One 11(3):e0151939 (2016)

Forest plot of ORR, meta-analysis of 9 randomized clinical trials

COX-2 inhibitors increased ORR in advanced NSCLC

Prognostic, Therapeutic and Preventive Relevance of PGE2 Pathway in Cancer

AAT-008 combo with anti-PD1 in CT-26

Beneficial Combination Activity with anti-PD-1 in CT-26Need for durable pathway inhibition for benefit

TreatmentPeriod

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Increased complete responses with combination

• Tumor re-inoculation challenge in CR animals demonstrated induction of memory

• Similar beneficial combination activity observed with anti-CTLA4 in 4T-1 model (data not shown)

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ARY-007 – Ongoing Phase 1b in MicroSatellite Stable (MSS) CRCPost-2nd Line Chemotherapy

Pre-dose• Blood• Urine• Tumor biopsy• Archived tumor

Steady–State (Days 5-8):• 2nd Tumor biopsy

for Cohort 1 participants

• Blood

End of Cycle 1 to End of Cycle 3:• Blood• 2nd Tumor biopsy for Cohort 2

participants

Anytime:• 3rd Tumor biopsy in

participants with PR

ARY-007 + pembrolizumabARY-007

1 week SA run-in

15 patients

10 patientsARY-007 + pembrolizumab

Cohort 1

Cohort 2

ARY-007 dosed at 300 mg BID with no dose-escalationPembrolizumab dosed at 200 mg IV Q3WClinicalTrials.gov Identifier: NCT03658772

• Tumor immune cells• Peripheral immune cells• Chemokine / cytokine

Pharmacodynamics

• Tumor immune cells• PD-L1• COX-2• EP4• Tumor mutational burden• PGEM

Patient selection (retrospective)

Robust biomarker strategy

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ARY-007 – Ongoing Phase 1b/2 in Post-PD1/PDL1 NSCLCIn Patients who Have Progressed While on PD-1

ARY-007 + pembrolizumabPost-PD1/L1

(≥ 12 weeks of prior treatment

with anti-PD1/L1, followed by

progression while being treated with

anti-PD1/L1)

Pre-dose• Blood• Urine• Archived tumor (if available)• Tumor Biopsy (10 Patients)

End of Cycle 1 to End of Cycle 3• Tumor biopsy (for the

10 participants in the biopsy subgroup)

• Blood per SoE

Anytime for participants in biopsy subgroup:• 3rd Tumor biopsy in

participants with PR

25 patients

ARY-007 dosed at 300 mg BID with no dose-escalationPembrolizumab dosed at 200 mg IV Q3WClinicalTrials.gov Identifier: NCT03696212

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Targeting Diseases with High Unmet Medical Need

82,450

14,550

CRC

MSS MSI

Estimated Market Size (new cases per year in the U.S.)

Current Treatment Paradigm

• ORR in MSS CRC is 0% (0/18), SD at week 12 is 11% (2/18) with single agent pembrolizumab

• 1st / 2nd line chemo is SOC• Checkpoint inhibitors only active in MSI-H CRC• Microsatellite instability (MSI) is a unique

molecular alteration and hyper-mutable phenotype, present in 15% of CRC

• Microsatellite stable (MSS) is 85% of CRC

• Among 121 Treatment Past resist-defined disease Progression (TPP) subjects treated with anti-PD-1 therapy, PR rate was 8.3%

• 1st line becoming chemo + pembrolizumab • Estimated ~30% 5 year survival in Pembro treated

patients - assume 70% PD1 refractory NSCLC

High market penetration and premium pricing may be achievable if ARY-007 (in combo with pembrolizumab) shows response rate ≥ 20% in MSS CRC or PD1/PDL1 refractory NSCLC

33,270

77,630

NSCLC

PD1 sensitive PD1 refractory

• ONO-4578 / BMS-986310• Oral, selective EP4

receptor antagonist

• Ongoing Ph 1/2 • Solid tumors (Japan)• Single agent and nivolumab dose

finding / safety study

• BMS licensed ONO-4578 in Dec 2017• Ph 1 study may be ongoing in Tokyo, Japan (started 2017)• BMS initiated 280 solid tumor-patient Phase 1/2 study

alone and in combination with nivolumab (started Sept 2018)

• E7046 / AN0025• Oral, selective EP4

receptor antagonist

• Completed single agent Ph I

• Combo ongoing / planned

• Adlai Nortye licensed E7046 in Jan 2018• Eisai Ph1 monotx data – POM demonstrated• Saturated PK above 500 mg• Adlai Nortye initiated solid tumor trial in Jan 2019 in

combo with pembrolizumab

• Solid tumors• Preoperative P1b

radiation/chemo combination in rectal cancer enrolling

Company ProgramStage ofDevelopment Indication Additional information

Competitive Landscape – EP4 Inhibitor Clinical Stage Programs

• ARY-007• Oral, selective EP4

receptor antagonist

• Ongoing Ph Ib/2 • Anti-PD-1 combo in MSS CRC and PD1 refractory NSCLC

• Safety, PK, efficacy and biomarker endpoints

• Ongoing clinical studies with pembrolizumab supplied by Merck

• Safely dosed in ~1000 humans in non-oncology interventional setting

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e.g. kynurenine

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KYN-175: AHR AntagonistIndustry Leading Program in IND-Enabling Studies

Combo with Chemo (Doxil)Combo with anti-PD1Achieved target profile including but not limited toSingle agent and combination efficacy with anti-

PD1 and with chemo in multiple syngeneic models

Well tolerated in DC-enabling 14-day rat toxicity study

IND filing target: Q4 2019

Biomarker Driven Clinical Development for KYN-175Enabling Patient Selection/Enrichment Strategy

IDO TDO

Selecting Tumor Indication

• AHR dependent gene signature• Kynurenine tumor IHC• RNAscope - pathway gene expression

in TME• IDO / TDO tumor expression analysis

and IHC• Nuclear AHR localization

AHR Activation

Potential PD Biomarkers

• Plasma kynurenine• Modified gene expression /

signatures of AHR inhibition• Tumor & peripheral immune

cell, chemo/cytokine phenotyping

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Kyn Proprietary AHR Activation Gene Signature

Low signature

High signature

Indication 1 Indication 2

Novel AHR Signature Expression Correlates with Survival

Low signature

High signature

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KYN-412: Human Engineered Kynurenine Degrading Enzyme Program IND-enabling stage program that Inhibits pathway in a manner IDO selective inhibition cannot

Q1W I.v. human dosing

Well tolerated in DC-enabling rat tox study Superior to epacadostat in efficacy and immune stimulation

Durable depletion of kynurenine in mouse and cyno PD studies: superior to epacadostat

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Achieved development candidate target profile including but not limited to

IDO TDO

Kynurenine

Immunosuppression

Kynase

Co-expression IDO/TDO (mRNA/Protein)

IND filing target: Q1 2020

Kyn Continued Value Creation to 2022

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Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q41H Q1 Q2 Q3 Q42H2019

Development Candidates for AHR and Kynase

2018 2020 2021 2022

Clinical trial initiation for ARY-007 MSS CRC study

Clinical trial initiation for ARY-007 NSCLC study

Celgene strategic collaborationFor AHR and Kynase

IND filing for AHR

POC clinical data for ARY-007 MSS CRC study

Pipeline expansion (in-license and/or internal)

POC clinical data for ARY-007 NSCLC study

POC clinical data for AHR

Potential IPO

ARY-007 Phase 2 randomized study initiation

ARY-007 Phase 2 randomized study data

POM data for AHR

POM data for Kynase

POC: Proof-of-Concept; POM: Proof-of-Mechanism

Completed milestones

POC clinical data for Kynase

IND filing for Kynase