Loxo Oncology — Corporate Update (June 2017)
32 slides from Loxo Oncology's corporate update, Jun 5, 2017
Slide 1: Forward Looking Statements
Forward Looking Statements This presentation and the accompanying oral presentation contain “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anti
Slide 2: Pipeline of Highly Selective Drug Candidates for Genetically Defined Cancers
Pipeline of Highly Selective Drug Candidates for Genetically Defined Cancers 3 Program Indication Stage of Development Eligible US patients/yr1 Preclinical Phase 1 Phase 2 Marketed Key Milestones Larotrectinib (LOXO-101) TRK fusion cancers Will form the basis of NDA expected to be filed in late 2017
Slide 3: Agenda
Agenda Review of larotrectinib data presented at ASCO Dr. David Hyman, MSKCC Dr. Alex Drilon, MSKCC Dr. Theodore Laetsch, UT Southwestern Ongoing larotrectinib development activities LOXO-195 LOXO-292 Upcoming milestones / Q&A 4
Slide 4: Agenda
I Agenda + Review of larotrectinib data presented at ASCO — Dr. David Hyman, MSKCC — Dr. Alex Drilon, MSKCC — Dr. Theodore Laetsch, UT Southwestern * Ongoing larotrectinib development activities + LOXO-195 + LOXO-292 + Upcoming milestones / Q&A
Slide 5: The efficacy of larotrectinib in adult and pediatric TRK fusion cancers
The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers Hyman DM,’ Laetsch TW, ? Kummar S,> DuBois SG, Farago AF,° Pappo AS,° Demetri GD,” El-Deiry WS,* Lassen UN,? Dowlati A,}° Brose MS," Boni V,? Turpin B,!3 Nagas
Slide 6: Larotrectinib TRKA/B/C
Larotrectinib TRKA/B/C * Larotrectinib is the first and only selective pan- TRK inhibitor in clinical development + Highly potent against TRKA, TRKB, TRKC — 5-11 nM [Cop in cellular assays + Highly selective * Development timeline — March 2015: 1* TRK-fusion patient treated — July 2016: breakthrough
Slide 7: Larotrectinib TRK fusion development program
Larotrectinib TRK fusion development program ‘Adult phase | * Age 218 years * Advanced solid tumors Sg n=12 phase Il ‘basket’ trial * Age 212 years * TRK fusion positive NAVIGATE: adult/adolescent * Advanced solid tumors Data cut-off: April 14, 2017 ASCO ANNU; MEETING ‘17 #ASCO17 an Hy N=55 TRK fusi
Slide 8: Patient demographics
Patient demographics Gender, n (%) Male 29153) Female 26 (47) Median age (range), years 45.0 (0.3-76.0) Age group, n (%) <2 years 6 (11) 2-6 years 5 (9) 6-15 years 1(2) 15-39 years 12 (22) 240 years 31655), ECOG PS, n(%) o 27 (49) 1 22 (40) 2 6 (11) No. of prior systemic chemotherapies, n (%) o1 30
Slide 9: Diversity of cancers treated - unique types
Diversity of cancers treated - 17 unique types Breast Appendix 2% Pancreatic _ Infantile Peripheral nerve 2°, 2% \myofibromatosis 2% sheath tumor 4% Salivary gland 22% Sarcoma, NOS 4% Myopericytoma . 4% Cholangiocarcinoma Infantile fibrosarcoma (IFS) 3% Spindle cell sarcoma 5% Gist 5% Melanoma T% Th
Slide 10: Clinical activity of larotrectinib in patients with TRK fusion cancers
Clinical activity of larotrectinib in patients with TRK fusion cancers Enrolled patients with confirmatory response All enrolled data available (n=5S0) patients (n=55)* Objective response rate 76% 78% (95% ci) (62-87%) (65-88%) Partial response 64% 65%" Complete response 12% 13%* Stable disease 12%
Slide 11: Efficacy of larotrectinib in TRK fusion cancers
Efficacy of larotrectinib in TRK fusion cancers 50: Maximum change in tumor size (18) were recanted
Slide 12: Efficacy regardless of age
Efficacy regardless of age Maximum change in tur siz (6) “PletodTR she fesse mation TRE GAR) tbe or ey *Paboge CR OD Note: One patent not shown here. Pater experenced circa progression and no post baseline tumor measurements were recorded ASCO ANNU. LOX 2
Slide 13: Efficacy regardless of tumor type
Efficacy regardless of tumor type Maximum change in tur siz (6) 50 40. Ey 2» 10 ° 40 eT 0 40: 50 0 10 0 0 100: ASI “Patent had TRKsohent fot resistance mutaton (NTRK3 GE23R) at baseline de lo prot heap. "Patogc CR Note: One patent nt shown here. Patent experenced clinica progression and no post-base
Slide 14: Efficacy regardless of NTRK gene
Efficacy regardless of NTRK gene 0 ma TRKt a BENTRK xo NTRS mo z 0 § 4 5 2 : LL § i “Patent had TRKsohent fot resistance mutaton (NTRK3 GEZ3R) at baseline defo ror heropy. *Patagic CR Note One patent not shown here Patent experenced cincal pogrssen and no post baseline tumor measurements wer recorde
Slide 15: Efficacy regardless of fusion partner
Efficacy regardless of fusion partner 22 Maximum change in tumor size (16) NTRKIMNILUNA IETPM3 IMTPR MECTRC POEAOIP MM RF28P2 IM SOSTMt IMPPL MMTRIMES NTRI2 [ll STRN NTRS METS Ml TPMs “Patent ha TRK solvent ont resistance mutation NTRKS GE23R) at basene due to por herapy: *Pathlogic OR Note: One pat
Slide 16: Duration of larotrectinib therapy
Duration of larotrectinib therapy 93% of responding patients and 75% of all patients remain on treatment or underwent surgery with curative intent - = = — Saal = = — | Treatment ater progression = J i Tresimer ater sugey i > Treatment onging = é © Time to frst response e gf © Surgery ? + PahaegccR H
Slide 17: Adverse events
Adverse events Treatment-emergent AEs (%)* ‘Treatment-related AEs (%) Gadei | Gade2 | Gnde3 | Gndea [Tor Greses | Gredea [Tota Faia : : cea 2 7 7 ——a i = 0 Nausea 20 5 2 - 26 2 = 18 Anemia 8 9 9 oa 26 3 _ 10 Torting ise = — = = ro Increased AST 16 4 3 = 23 1 > 18 Constpation 7% 2 i = @ = = i Cough 1
Slide 18: Baseline
Baseline see ASCO ANNI MEETING ‘17 Sees ree oe OX) Cycle 4 #ASCOIT Hyman, LBA2501 4S5F NSCLC & paraneoplastic hypertrophic osteoarthropathy Prior therapy: platinum/pemetrexed Larotrectinib ongoing in month 8, resolution of paraneoplastic symptoms
Slide 19: ETV6-NTRK3 secretory breast cancer patient
ETV6-NTRK3 secretory breast cancer patient Baseline Day6 Day 20 14F, prior therapy: 4 lines of chemotherapy and repeated resections Treated with larotrectinib under expanded access ETING "17 | $ASCOTTZ Courtesy of N. Shukla, Memorial Sloan Kettering
Slide 20: ETV6-NTRK3 infantile fibrosarcoma patient
ETV6-NTRK3 infantile fibrosarcoma patient Baseline Cycle 3 Fromm ASCO ANN Sers ant EETING q7 #ASCOIT jyman, LBA2604 xe) 2F infantile fibrosarcoma 2 cycles of vincristine/ actinomycin- D/ cyclophosphamide > progression > leg amputation was only alternative option 4.cycles larotrectinib > referred for
Slide 21: LOXO-195 to Address TRK Acquired Resistance
LOXO-195 to Address TRK Acquired Resistance LOXO-195 Treatment Resistance 2 Tumor type Fusion mutation £ 3 Colorectal TPM3-NTRK1 —_TRKAG595R Fe g Colorectal LMNA-NTRK1 TRKA G595R. 8 sete TPR-NTRKL —_TRKAGSSSR Sercomat —TPM3-NTRK1 _‘TRKA G595R TRKC G623R TRKA FS891" + a GNAS 0227H ot g TRK solvent fr
Slide 22: Path to Regulatory Filings
Path to Regulatory Filings Clinical Independent radiology review to be conducted 2H 2017 NDA filing will utilize a later data cut-off date relative to ASCO data Trials continue to enroll as mechanism of expanded access CMC scale-up and stability testing ongoing Dictates the expiration date of the co
Slide 23: Larotrectinib Diagnostics Strategy
Larotrectinib Diagnostics Strategy Multiple diagnostic relationships are likely Focused on immunohistochemistry (IHC) and next-generation sequencing (NGS) IHC Collaboration announced with Roche Ventana Loxo/Ventana are creating pan-TRK test 8,500+ installed base of Ventana instruments worldwide NGS
Slide 24: Larotrectinib Diagnostics Strategy
EEE Ee Larotrectinib Diagnostics Strategy + Multiple diagnostic relationships are likely + Focused on immunohistochemistry (IHC) and next-generation sequencing (NGS) + IHC AY, ° — Collaboration announced with Roche Ventana ye VENTANA — Loxo/Ventana are creating pan-TRK test — 8,500+ installed base o
Slide 25: LOXO-195: Structurally Distinct, Similarly Selective
LOXO-195: Structurally Distinct, Similarly Selective 26 LOXO-195 Larotrectinib TRKB TRKB TRKA TRKA
Slide 26: LOXO-195 Clinical Development
LOXO-195 Clinical Development Clinical proof-of-concept established in Cancer Discovery publication First 2 emergency use patients with PRs 1 additional emergency use patient (unpublished) with limited duration of treatment amidst clinical deterioration 3 remaining larotrectinib RECIST progressions:
Slide 27: LOXO-195 Clinical Development
LOXO-195 Clinical Development + Clinical proof-of-concept established in Cancer Discovery publication — First 2 emergency use patients with PRs — 1 additional emergency use patient (unpublished) with limited duration of treatment amidst clinical deterioration — 3 remaining larotrectinib RECIST progr
Slide 28: LOXO-292 Phase 1 Trial Design
LOXO-292 Phase 1 Trial Design 29 Advanced RET-altered solid tumor Any prior TKIs that inhibit RET ~ 30 patients MTD/ recommended expansion dose 5. Advanced RET-altered solid tumor, any of: Disease not measurable Other RET-altered tumors RET mutation-neg. MTC Any prior TKIs that inhibit RET ~ 15 pati
Slide 29: LOXO-292 Clinical Development
LOXO-292 Clinical Development First patient enrolled in Phase 1 clinical trial in May 2017 Early human pharmacokinetic data is in line with preclinical predictions Opportunity for patient enrichment in Phase 1 Growing target awareness Detection technology is relatively straightforward Expect single
Slide 30: Milestones and Capitalization
Milestones and Capitalization 31 FINANCIAL* NASDAQ: LOXO Shares Outstanding*: 26.2M basic, 3.0M options ($17.63 weighted avg strike price) Cash, cash equivalents, and investments*: $244.3M * As of Q1 2017 10-Q PROGRAM UPDATE DEC 2016 GUIDANCE STATUS Larotrectinib (LOXO-101, TRK) Complete enrollment
Slide 31: Milestones and Capitalization
Milestones and Capitalization DEC 2016 PROGRAM UPDATE GUIDANCE Complete enrollment for primary efficacy analysis dataset Early 2017 Present Phase 1/2 pediatric clinical data Mid-2017 PUTA ULI Present interim data for integrated TRK fusion NDA database (local a (LOXO-101, [ERIE] TRK) ‘Announce final
Slide 32: Q&A