Puma Biotechnology Inc · NASDAQ:PBYI
Puma Biotechnology — Investor Presentation (January 2023)
87 slides from Puma Biotechnology's investor presentation, Jan 9, 2023
Slide 1: Puma Biotechnology Corporate Presentation
Puma Biotechnology Corporate Presentation January 2023
Slide 2: Forward-Looking Safe-Harbor Statement
Forward-Looking Safe-Harbor Statement This presentation contains forward-looking statements, including statements regarding commercialization of NERLYNX® and the potential indications and development of our drug candidates. All forward-looking statements involve risks and uncertainties that could ca
Slide 3: Product Pipeline
Product Pipeline Phase lll Registration Approval Neratinib: Tyrosine kinase inhibitor HER2+ Breast Cancer ExteNET (Phase Ill HER2+ EBC*) Extended adjuvant Neratinib monotherapy CONTROL $< Metastatic Monotherapy or combo therapy Metastatic w/ brain mets Monotherapy or combo therapy HER2-mutant Solid
Slide 4: Specialty Pharmacy Network (SP)
Specialty Pharmacy Network (SP) Acaria Heal | Accredo macy and Distributor Network CVS | ONCO 360 Optum / Diplomat | Biologics Specialty Distributor Network (SD) McKesson ASD/Oncology Supply Cardinal Health DMS Pharmaceutical Group Inc. Hub Services PumaPatientl y nis Patients Sites of Care Academic
Slide 5: ~$54 Million net NERLYNX revenue in Q3'22
~$54 Million net NERLYNX revenue in Q3’22 Quarterly Net Revenue (in $MM) 61.4 587 cog 528 538 53.5 54.3 ; aa6 499 49.3 50.0 51.0 51.3 45.6 40.7 36.0 204 64 | 1798F 63T_ go8 got 403% 903% 9019 903 9039903? 3 qn gu Popp" ywIO™’ gy 70 oe oe ‘on™ ‘x 070 370 a7 on eae os oe oo. oo. oe +2)
Slide 6: 3,323 Ex-factory bottles were sold in Q4'22
3,323 Ex-factory bottles were sold in Q4’22* Bottles Sold (SP + SD) by Quarter 5,538 are 4936 4791 ggoe *2%5 4,452 4,035 3,817 3,728 3.611 3,585 3,454 3,247 9,354 3,200 3,197 3:323 2,947 2,680 2,137 675 | ‘a oe a0 ‘on ® 10 xro® 2 01? 37s 20? 7 ae 370 ‘a7 ‘os 0. ‘328 Rg oy Poy Includes Commercial SP
Slide 7: Patients started at a reduced dose
22 started at a reduced dose* ** % of Patients starting at reduced dose 67.9% 65.4% 59.4% 615% 54.9% 42.4% 37.7% 38.7% go.o% 31.0% 329% 19.0% i 11.0% a Aa 2.0% 2.0% 3.0% 4.0% oe ae Foss oo eae = = if a 3720 ‘on ™ on™ oo ‘a, oo ‘2 92 370 on™ ‘on™ oo, 3? “Reduced dose defined as fewer than 6 pills per
Slide 8: World Partnerships — Timelines
World Partnerships — Timelines Regi Regulat pprovals Commercial Launches + 2019 —Ext. Adi. in Australia, Singapore SR) = F : = Singapore Australia / SE Asia Specialised + 2020 — Ext. Adj. in Brunei, Malaysia, New Zealand {G9 9994 - Malaysia Therapeutics + Q22022 — Ext. Adi. in the Philippines : se 8
Slide 9: Early stage HER2+ breast cancer patient population
@ Approximately 28,300 patients (US) with early stage HER2+ breast cancer treated with adjuvant treatment @ Approximately 6,000 patients (US) with HR positive early stage HER2+ breast cancer and no pathological complete response to neoadjuvant treatment (high risk disease) @ Approximately 37,000 pat
Slide 10: TBCRC 022: Phase II Trial of HKI-272 (Neratinib) in Brain Metastases
TBCRC 022: Phase II Trial of HKI-272 (Neratinib) for Patients with HER2+ Breast Cancer and Brain Metastases Progressive | brain mets Craniotomy candidates Progressive brain mets: 3a: No prior lapatinib 3b: Prior lapatinib 4a: Untreated CNS disease; no prior T-DM1 4b: Progressive CNS disease; no prio
Slide 11: % reduction in volume of CNS lesions
% reduction in volume of CNS lesions al CRC-022 Cohort 3a CNS Response Best Volumetric Response (n=31)* 100 80 60 40 20 ° -2' 3S -4 S -60 -80 -100
Slide 12: Cohort Response
022 Cohort 4 Response* 3 Cohort4A} Cohort4B eee | i H j Cohort4c i TT Best Response Unconfirmed PR
Slide 13: Included as a Treatment Option by NCCN Guidelines
Included as a Treatment Option for ancer CNS Metastases By NCCN® Guidelines’ uidelines updated Mai Category 2A: Category 2B: Neratinib + Capecitabine Neratinib + Paclitaxel TBCRC 022? NEfERT-T?4 A Phase II Trial of Neratinib and Randomized, Multi-Center, International Capecitabine for Patients with
Slide 14: Basket Trial: Study Design
EGFR exont8- Neratinib monotherapy Neratinil monotherapy — Neratinib: Paclitaxel istologicaly confirmed cancers for which nocurativetherapy exists * Documented EGFR exon 18, HER2 or HERA mutation + ECOGstatusof0to2 © RECIST11 evaluable disease (measurable or non-measurable disease): if RECIST non-me
Slide 15: SUMMIT Breast Cancer Cohort
SUMMIT Breast Cancer Cohort
Slide 16: Change in tumor size and characteristics
Change in tumor size (target lesion) and characteristics* Non-randomized Randomized Randomized Randomized HR HR HRe BRE Prin COKAtG Ploy CDKA/ Prior CDKA/oi Prior CDKAl eg Best overall response mR PR $0 100 HER? mutation category : a [BB Kinase domain hotspot IB Kinase domain hotspot; non-hotspot Hi
Slide 17: SUMMIT (PUMA-NER-5201) Basket Trial EGFR exon lung cancer cohort update
SUMMIT (PUMA-NER-5201) Basket Trial EGFR exon 18 lung cancer cohort update
Slide 18: Lung Cancer Cohort Receiving Neratinib
ing Cancer Cohort Receiving Neratinib in, Best Response and Best Change in Tumor* 100: EGER mutation mG19X 1IG719X and S7681 I G719X and S7681 and T790M 60 719 and E709K ME709x IBE709_T710delinsD ‘Not evaluable Prior TKI Osimertinib Afatini Gefitinib Erlotinib Erlotinib and Osimertinib Afatinib and
Slide 19: ALISERTIB Breast Cancer and Small-Cell Lung Cancer
ALISERTIB Breast Cancer and Small-Cell Lung Cancer
Slide 20: Alisertib (MLN 8237)
Alisertib (MLN 8237) Orally Bioavailable Drug Class: Benzazepine Aurora Kinase A (AURKA) inhibitor + Single-agent and combinational clinical activity in solid tumors including hormone receptor-positive breast cancer (HR+ MBC), triple negative breast cancer (TNBC), small cell lung cancer (SCLC), and
Slide 21: Synthetic Lethality of AURKA and Rb1
Synthetic Lethality of AURKA and Rb1 Cancers with a hypersensitive spindle assembly checkpoint (SAC) depend on AURKA for mitotic exit and survival’ a... RBI MYC \ JZ ‘Tubulin inhibitors une > (MAD2L1, BUB1B) Low AURKA High AURKA, Kinase activity kinase activity Mitotic arres [a Mitotic ext apor Loss
Slide 22: AURKA and c-Myc Co-regulate Each Other
AURKA and c-Myc Co-regulate Each Other Nuclear AURKA exerts kinase-independent functions by acting as a transcription factor x \ « AURKA and c-Myc transcriptionally upregulate each other, tumor development suggesting the existence of a positive feedback loop + c-Myc upregulates Cyclin D2, CDK4, and
Slide 23: Clinical Experience in Small-Cell Lung Cancer
Clinical Experience in Small-Cell Lung Cancer
Slide 24: Phase Study of Alisertib Monotherapy in Solid Tumors - SCLC
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - SCLC Cohorts Study design: Pts had to have undergone < 2 previous cytotoxic regimens, not including adjuvant or neoadjuvant treatments Alisertib administration: orally in 21-day cycles at 50 mg twice daily for 7 days followed by a break of 14
Slide 25: Alisertib Monotherapy SCLC Response
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - SCLC Cohorts 10 (21%; 95% Cl 10-35) of 48 patients had an objective response; all responders achieved a partial response Bl Chemotherapy-sensitive relapse Il Refractory or chemotherapy- resistant relapse Change in target lesion size and best r
Slide 26: Alisertib Monotherapy SCLC Adverse Events
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - SCLC Cohorts All-cause adverse eventsin safety evaluable SCLC cohort (n=60) Any adverse event Neutropenia Fatigue ‘Anaemia Alopecia Diarthoea Nausea Levkopenia ‘Stomatitis Decreased appetite Vomiting Thrombocytopenia Somnolence Dyspnoea Consti
Slide 27: Grade 3-4 AEs: alisertib vs lurbinectedin
Grade 3-4 AEs Present in 2 10% of SCLC Patients - alisertib monotherapy compared to lurbinectedin monotherapy Pee eee EE Ee ee eee Neutropenia 27 (45%) 22 (37%) 75 (71%) 48 (46%) Anemia 19 (32%) 10 (17%) 100 (95%) 9 (9%) Leukopenia 12 (20%) 8 (13%) 83 (79%) 30 (29%) Thrombocytopenia 11 (18%) 6 (10%)
Slide 28: Paclitaxel plus Alisertib vs Paclitaxel as Second-Line SCLC: Primary Analysis
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Primary Analysis Study design: + Patients with relapsed or refractory SCLC stratified by relapse type (sensitive vs resistant or refractory) + Randomized 1:1 to alisertib + paclitaxel or placebo + p
Slide 29: Second-Line SCLC: c-Myc Biomarker Analysis
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Correlative Biomarker Analysis Improved PFS observed among patients positive versus negative for c-Myc expression PFS in patients positive for c-Myc expression Median PFS 4.64 mo w/ paclitaxel + ali
Slide 30: Second-Line SCLC: Cell Cycle Gene Biomarker Analysis
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Correlative Biomarker Analysis Improved outcomes among pts with genetic alternations in cell cycle genes CDK6, RBL1, RBL2, and RB1 (collectively referred to as “mutant”) | ‘Survival probability ‘Sun
Slide 31: Second-Line SCLC: Safety
Randomized Phase 2 Study of Paclitaxel plus Alisertib vs Paclitaxel plus Placebo as Second-Line SCLC: Safety Cause) or at Least 10% (Drug-Related) of Patients Overall (Any Grade) in Either Arm, Respectively, with the Corresponding Grade 3 or higher AEs (Safety Population), and All Drug-Related Fatal
Slide 32: Clinical Studies of Alisertib in Breast Cancer
Clinical Studies of Alisertib in Breast Cancer
Slide 33: Alisertib Monotherapy in Solid Tumors - Breast Cancer Cohorts
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - Breast Cancer Cohorts Study design: + Pts had to have undergone < 2 previous cytotoxic regimens, not including adjuvant or neoadjuvant treatments + Alisertib administered orally in 21-day cycles at 50 mg twice daily for 7 days followed by a br
Slide 34: Alisertib Monotherapy Breast Cancer Response
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - Breast Cancer Cohorts 9 / 49 patients (18%; 95% Cl 9-32) had an objective response; all responders achieved a partial response Wi Triple negative Gi HR positive/HER2-negative TB HER?-positive/any HR Change in target lesion size and best respon
Slide 35: Alisertib Monotherapy Breast Cancer Adverse Events
Phase 2 Study of Alisertib Monotherapy in Solid Tumors - Breast Cancer Cohorts All-cause adverse eventsin safety evaluable breast cancer cohort (n=53) Table adapted from Matichar B Lancet Oncol 2015, Data are number of pations with AE (%) for AES of any grade in atleast 10% of patients vera NAS not
Slide 36: Randomized Trial of Alisertib + Fulvestrant vs Alisertib in HR+ Breast Cancer
Phase 2 Randomized Trial of Alisertib + Fulvestrant vs Alisertib in Advanced HR+ Breast Cancer Inclusion Criteria Pa + Post-menopausal women + Histologically-proven ER+ (>10% expression) and HER2 negative + No more than two prior chemotherapy regimens + Prior treatment with fulvestrant in the metast
Slide 37: Alisertib + Fulvestrant vs Alisertib: Safety
Phase 2 Randomized Trial of Alisertib + Fulvestrant vs Alisertib in Advanced HR+ Breast Cancer Reason for Alisertib* Alisertib + Fulvestrant Treatment (n=45) (n=45) Discontinuation Disease progression Alisertib + Fulvestrant (n=45) G3 G4 Hematologic Adverse Events Anemia Intolerability Patient Refus
Slide 38: Paclitaxel + Alisertib vs Paclitaxel: ER+/HER2- MBC Efficacy
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Efficacy in ER+/HER2-MBC Cohort Study design: 1.0 PFS in ER+/HER2-ITT Median PFS: 10.2 (3.8-15.7) mo for paclitaxel + alisertib vs 7.1 (3.8-10.6) mo with paclitaxel HR = 0.56, 95% Cl: 0.37-0.84, p=.005 Patients with ER+/HER2- o
Slide 39: Efficacy in Patients Pretreated with Palbociclib
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Efficacy in ER+/HER2-MBC Cohort Pretreated with Palbociclib Efficacy in patients pretreated with palbociclib (n=30) ¢ Median PFS: 13.9 (5.6-15.6) mo (14 pts) w/ paclitaxel + alisertib vs 5.6 (3.0-10.6) mo (16 pts) w/ paclitaxel
Slide 40: Rb1 Loss and c-Myc Upregulation Correlate with Palbociclib Resistance
Rb1 Loss and c-Myc Upregulation Correlate with Palbociclib Resistance Both RB1 loss and MYC upregulation were observed in palbociclib-resistant HR+ breast cancer cell lines, supporting a role for alisertib in this setting RB1 Loss C-Myc Upregulation MCF7 MCF7-PR Tegave control P Negatwe MCF7-PR Vs M
Slide 41: Summary of Alisertib Efficacy in Metastatic Breast Cancer
Summary of Alisertib Efficacy in Metastatic Breast Cancer Regimen (N) Median PFS Regimen (N) Median PFS (mo, 95% Cl) (mo, 95% Cl) NA HR+/HER2- _ alisertib 50 mg BID" 26 7.9 (4.2-12.2) NA Melichar B Lancet ‘Oncol 2015 ER+/HER2- _ alisertib 50 mg BID? 45 5.6 (3.9-9.3) alisertib 50 mg BID? + 45 5.1 (3.
Slide 42: Study-related Neutropenia in Metastatic Breast Cancer
Study-related Neutropenia in Metastatic Breast Cancer - Alisertib compared to other agents All-grade Neutropenia (%) Grade 3/4 Neutropenia (%) Febrile Neutropenia (%) Alisertib monotherapy 50 mg BID' Alisertib monotherapy 50 mg BID? Alisertib 50 mg BID + fulvestrant? Alisertib 40 mg BID + paclitaxel
Slide 43: Overview of Alisertib Clinical Development Plan
Overview of Alisertib Clinical Development Plan Target Patient Population(s) | Rationale for Selected Indication | Potential Biomarker-defined Subgroups HR+/HER2- metastatic breast « Prior Clinical Data cancer (MBC) « Puma experience in breast cancer « c-Mycamplification Small Cell Lung Cancer + Pri
Slide 44: Expected Milestones
— Expected Milestones Publication of the biomarker studies from the randomized trial of alisertib plus fulvestrant versus alisertib alone in hormone receptor-positive, HER2-negative breast cancer (H1 2023) Biomarker data from the randomized trial of alisertib plus paclitaxel versus paclitaxel alone
Slide 45: Management Team
ed Management Team Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder Chief Executive Officer, President, Founder, Cougar Biotechnology Jeff Ludwig Chief Commercial Officer Eli Lilly, Astellas, Amgen Maximo F. Nougues Chief Financial Officer Getinge AB, Boston Scientific, The Clo
Slide 46: Board of Directors
Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder, Puma Biotechnology, Inc. Alessandra Cesano, MD, PhD Chief Medical Officer, ESSA Pharmaceuticals; NanoString; Cleave Biosciences; Nodality; Amgen; Biogen; SmithKline Allison Dorval CFO, Verve Therapeutics; Former CFO Voyager Ther
Slide 47: Puma Biotechnology — Financial
chnology — Financial Currently trading on NASDAQ: PBY1 Cash, cash equivalents and marketable securities at September 30, 2022: $78 million Net loss in Q3 2022: $0.4 million Cash earned in Q3 2022: $17.4 million Private placements: — March 2022: 3,584,228 shares issued to Alan Auerbach and Athyrium C
Slide 48: Investment highlights
NERLYNX® — first HER2-directed drug approved by FDA for extended adjuvant treatment of early-stage HER2+ breast cancer in patients who have received prior trastuzumab NERLYNX® — first HER2-directed tyrosine kinase inhibitor approved in both early stage and metastatic HER2+ breast cancer Retain full
Slide 49: Puma Biotechnology
Puma Biotechnology Corporate Presentation January 2023
Slide 50: Appendix
Puma Biotechnology Appendix January 2023
Slide 51: CONTROL Study Design
CONTROL Study Design Phase 2 trial to characterize the incidence and severity of diarrhea in patients with HER2+ early breast cancer treated with neratinib and loperamide prophylaxis + an investigational agent 1 year of therapy n nw hechet e's SS ee + Received up to 1 year of adjuvant trastuzumab *
Slide 52: CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea Loperamide prophylaxis reduces incidence and severity of diarrhea CONTROL' Neratinib dose Budesonide Colestipol Colestipol + escalation + Loperamide loperamide prn loperamide pn pm (n=104) (n=60)? (Gs Treatment-emergem diarrhea incidence, n (
Slide 53: Phase III Trial — Third-Line HER2+ MBC (NALA)
Phase Ill Trial — Third-Line HER2+ MBC (NALA) Study Design m@ 3rd- orlater-line therapy for patients with HER2+ mBC = Patients with asymptomatic CNS metastatic disease are eligible ™ Obtained SPA from FDA and review by EMA in February 2013 HER2+ mBC # Received 22 prior lines of Follow-up A (Survival
Slide 54: NALA Study Results: Progression-Free Survival
Phase Ill Trial — Third-Line HER2+ MBC (NALA): Study Results PFS probability ° a H Centrally Confirmed PFS (co-primary endpoint) Hazard ratio Log-rank (95% Cl) p-value — Neratinib + Capecitabine 0.76 (0.63-0.93) 0.0059 — Lapatinib + Capecitabine TH i———4 No. at risk: N+C 307 L+C 314 T 1 T T 3 6 9 12
Slide 55: NALA Study Results: Restricted Means PFS
Phase Ill Trial — Third-Line HER2+ MBC (NALA): Study Results Prespecified restricted means analysis — PFS PFS probability ° a H Mean PFS (months) p-value — Neratinib + Capecitabine 88 0.0003 — Lapatinib + Capecitabine 66 Restriction: 24 months 044 03 ‘7 024 a 12.2 months, | 017 ee . wl —— a 0 T T T
Slide 56: NALA Study Results: Overall Survival
Phase Ill Trial — Third-Line HER2+ MBC (NALA): Study Results OS (co-primary endpoint) Mean OS Hazard ratio —Log-rank (months) (95% Cl) p-value —Neratinib + Capecitabine 24.0 0.88 (0.72-1.07) 0.2086 —Lapatinib +Capecitabine 22.2 Restriction: 48 months 0.25 ~ ‘4.7 months | 017 . 0 T T T T T T T T T T
Slide 57: NALA Study Results: CNS Metastases Intervention
Phase Ill Trial — Third-Line HER2+ MBC (NALA): Study Results Time to intervention for CNS metastases 1007 Neratinib +Capecitabine —_Lapatinib + Capecitabine 90-4 Intervention (n=55/307) (n=75/314) Radiation therapy 11% 15% bala Surgery/procedure 2% 3% 70-4 Anticancer medication 1% 1% Overall cumulat
Slide 58: Third-Line HER2+ MBC Market Size
Third-Line HER2+ MBC Market Size m Approximately 6,400 patients (US) with third-line HER2+ metastatic breast cancer and 4,700 patients (US) with fourth-line HER2+ metastatic breast cancer’ ‘Roche epidemiology slides 09/18
Slide 59: FB-10 — Phase I/II Trial of Kadcyla + Neratinib
FB-10 — Phase I/II Trial of Kadcyla (T-DM1) + Neratinib HER2+ MBC Must have received prior anti-HER2-based therapy with pertuzumab for mBC No prior T-DM1 or HER2 TKI allowed Neratinib Dose level 1: 120 mg/d Dose level 2: 160 mg/d Dose level 3: 200 mg/d Dose level 4: 240 mg/d T-DM1 3.6 mg/kg IV d1 Q3
Slide 60: FB-10 Response by Dose and Days on Treatment
Dose mg/d 240 240 200 200 200 200 200 160 160 160 160 160 160 160 160 120 120 120 120 120 FB-10 — Phase I/II Trial of Kadcyla (T-DM1) + Neratinib T “Off TX, AE/withdrawn + On treatment ORR (CR/PR): 12 of 20 (60%) cR PR sD PD 200 300 400 Days on Treatment 500 700 60
Slide 61: Characteristics of HER2-mutant breast cancer
Characteristics of HER2-mutant breast cancer*® SESS EEET: oT * 2% Primary breast cancers * Predominantly in hormone Occur across multiple domains * 2-4% MBC receptor-positive (luminal-A) of the protein (KD, ECD, TMD) and HER2-negative tumors * Most common variants: * 8% ER+ MBC * Upto 15% in metasta
Slide 62: Current SUMMIT breast cancer cohorts
Current SUMMIT breast cancer cohorts + Added inclusion criteria for HR+ cohort to reflect current standard of care: prior CDK4/6 inhibitor therapy HER2-mutant MBC MBC cohort Treatment assignment HR+/HER2-negative MBC ine —_ [ee ae] Non-randomized Neratinib + Fulvestrant + Trastuzumab HR+/HER2-negati
Slide 63: HR+ non-randomized N+F+T: Efficacy findings
HR+ non-randomized N+F+T w prior CDK4/6i: Efficacy findings Objective response (confirmed CR/PR)?, n (%) 12 (46.2) CR 0 PR 12 (46.2) Best overall response 15 (67.7) (confirmed or unconfirmed PR or CR), n (%) Median DOR®, months (95% Cl) 14.4 (6.4-NE) Clinical benefits, n (%) 15 (57.7) Median PFS, mo
Slide 64: HR+ randomized cohorts: Efficacy findings
HR+ randomized cohorts: Efficacy findings Neratinib appears to be critical for inhibition of HER2 mutations Characteristics (N+F+T, n=7) (F#T,n=7) Objective response (confirmed CR/PR)?, n (%) 2 (28.6) 0 0 CR 414.3) 0 0 PR 414.3) 0 0 Best overall response 3 (42.9 ie) (¢) (confirmed or unconfirmed PR
Slide 65: TNBC cohort: baseline characteristics and efficacy
TNBC cohort: baseline characteristics and efficacy ECOG performance status, n (%) cancer regimens (range) 0 9 (50.0) 1 9 (50.0) Histological type, n (%) Lobular 3 (16.7) Ductal 7 (38.9) Mixed Ductal and Lobular 0 Other 8 (44.4) Median number of prior anti- 3.5 (1-7) Objective response (confirmed CR/
Slide 66: SUMMIT Cervical Cancer Cohort
SUMMIT Cervical Cancer Cohort
Slide 67: Characteristics of HER2-Mutant Cervical Cancer
Characteristics of HER2-Mutant Cervical Cancer ae ™@ 5% metastatic cervical cancers m May be negatively prognostic for survival @ Enriched in adenocarcinomas m High occurrence in HPV+ tumors ics Most common HER2™t is S310 extracellular domain hotspot mutation Usually exclusive to HER2 amplifications
Slide 68: Neratinib Monotherapy Results Published in Gynecologic Oncology
Neratinib Monotherapy Results Published in Gynecologic Best change from baseline (%) 100 = 100 OOSOOBDDOO00O8 OOOOOOS8OI Ol ooo0o0sgoo000000 Oncology Best response Histology PIK3CA.co-mutation KRASco-mutation ‘TP53.co-mutation HER2-mutation category D Non-hotspot ECD and KO hotspot I Extracollar dom
Slide 69: Neratinib Monotherapy Results Published in Gynecologic Oncology
Neratinib Monotherapy Results Published in Gynecologic Oncology s310F s30F SOF, veant Tras: Rer0a s310F Rerea or e600 s310F onsze so10y stor > @ Key O Complete response (PET) @ Partial response (RECIST) @ Stable disease (RECIST) @ Progressive disease (RECIST) 6 12 18 24 30 36 42 Time (months) Gyneco
Slide 70: Historical Response Rates of Afatinib in NSCLC Patients
Historical Response Rates of Afatinib in NSCLC Patients With EGFR Exon 18 Mutations (G719X) Table 3. Response Rates With Afatinib in Patients With NSCLC Harboring Uncommon Mutations Mutation Type CR, n(%) PR, n(%) SD, n(%) PD,n(%) DCR, n (%) ORR,n (%) DoR, Mo (95% Cl) EGFR TKI-naive patients Major u
Slide 71: Alisertib Mechanism of Action
Alisertib Mechanism of Action Alisertib ® Inhibits Aurora Kinase A (AURKA), a _ serine/threonine protein kinase and transcription Mitotic entry delay factor ® Leads to: ais wo —_ slgrment/ spina \ bipolarity defects — Disruption of mitotic spindle apparatus assembly — Disruption of chromosome segreg
Slide 72: Aurora Kinase A and Epithelial to Mesenchymal Transition
Aurora Kinase A and Epithelial to Mesenchymal Transition Aurora Kinase A overexpression Epithelial cells V tERo isertil +CD24 Alisertib +ERa. ¥CD24 4HER-2/Neu Mesenchymal cells AURKA promotes epithelial to mesenchymal transition in breast cancer cells AURKA overexpression leads to the transition fro
Slide 73: Prognostic Implications of High Aurora Kinase A Expression
Prognostic Implications of High Aurora Kinase A Expression lh AURKA expression is correlated with worse overall survival in multiple sol tumor types Hazard Ratio Hazard Ratio Study/Subgroup _LogHazardRatio SE__Weight_1V,Random, 95% Cl IV, Random, 95% Cl Tung_cancer 1 ‘Ogawa 2008 10716 04907 30% — 29
Slide 74: Alisertib in Breast Cancer Cell Lines
Alisertib in Breast Cancer Cell Lines Alisertib inhibits proliferation and induces G2/M cell cycle arrest, apoptosis, and autophagy Alisertib induces G2/M cell cycle arrest CFT cols (HR+, HERZ.) Number MOA-MB-231 colts |" (TNBC) ALS (uM) Channel (Pt) Alisertib inhibits CDK1 and Cyclin B1 and induces
Slide 75: RB1-mutant Cell Lines are Sensitive to Alisertib
RB1-mutant Cell Lines are Sensitive to Alisertib Alisertib inhibits Rb1 deficient small-cell lung cancer cell line models to a much greater degree than wild- type Cell viability (%) 125 100 75 10% 10° 10° 10! Alisertib (uM) HCC827 H1650 H1975 H446 H82 RB | RB* Alisertib inhibits RB1-mutant TNBC cell
Slide 76: Alisertib in c-MYC-amplified Cancer Models
Alisertib in c-MYC-amplified Cancer Models c-Myc, AURKA, and p-AURKA protein levels trend together in a panel of thyroid cancer cell lines CFs & ete pays mm Alisertib inhibits tumor growth in xenograft models of bed thyroid cancer with high c-Myc expression, but not low c- Myc expression 8505C cells
Slide 77: Paclitaxel + Alisertib vs Paclitaxel: TNBC Cohort Efficacy
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Efficacy in TNBC Cohort PFS in TNBC ITT 107477 | Median PFS 9.6 (6.1-22.6) mo w/ q paclitaxel + alisertib vs 5.7 (2.9-8.2) mo wos4q bn w/ paclitaxel 2 1 HR = 0.35, 95% Cl: 0.14-0.89, p=0.022 2 '- > 3 vs Median OS: 16 (9.6-34.0)
Slide 78: Safety for ER+/HER2- MBC & TNBC Cohorts
Phase 2 Randomized Study of Paclitaxel + Alisertib vs Paclitaxel Alone - Safety for ER+/HER2-MBC & TNBC (both cohorts combined) Table 3. Treatment-Related Toxic Effects in Both Cohorts Patients, No. (%) Paclitaxel plus alisertib (n = 66) Paclitaxel (n = 70) Reported term Grade 1 Grade 2 Grade 3 Grad
Slide 79: Clinical Milestones
Clinical Milestones * Biomarker data from Phase 2 randomized trial of alisertib plus fulvestrant vs alisertib alone in hormone receptor-positive, HER2-negative advanced breast cancer (H1 2023) * Biomarker data from Phase 2 randomized trial of paclitaxel plus alisertib vs paclitaxel alone in patients
Slide 80: Treatment Landscape
Treatment Landscape
Slide 81: HR-positive HER2-negative Breast Cancer in US
Slide 82: Proposed Schema of Management of HR+/HER2- MBC
Slide 83: Small Cell Lung Cancer Market in US
Slide 84: Limited Agents Currently Under P2/3 Development for SCLC
Slide 85: Licensing Agreement Terms
Slide 86: Intellectual Property for NERLYNX
Slide 87: Intellectual Property on EGFR T790M Mutations
Puma Biotechnology — Investor Presentation (January 2023) on 6ix