Puma Biotechnology Inc · NASDAQ:PBYI

Puma Biotechnology — Technical Presentation (June 2019)

20 slides from Puma Biotechnology's technical presentation, Jun 4, 2019

  1. Slide 1: Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer

    Nera%nib plus capecitabine versus lapa%nib plus capecitabine in pa%ents with HER2-posi%ve metasta%c breast cancer previously treated with ≥2 HER2-directed regimens: Findings from the mul%na%onal, randomized, phase 3 NALA trial Cris%na Saura, Mafalda Oliveira, Yin-Hsun Feng, Ming-Shen Dai, Sara A Hur

  2. Slide 2: Disclosure information – Adam Brufsky

    Disclosure informa%on – Adam Brufsky Consul%ng or Advisory Role Eisai, Myriad Pharmaceu%cals, Merck, Bioarray Therapeu%cs, Puma Biotechnology, Genomic Health, NanoString Technologies, BioTheranos%cs, Lilly, Bayer, Novar%s, Celgene, Agendia, Genentech/Roche, Pfizer Adam Brufsky

  3. Slide 3: Neratinib: An irreversible pan-HER TKI

    Nera%nib: An irreversible pan-HER TKI Aberrant HER activation by: EGFR:EGFR HER2:EGFR HER2:HER3 HER2:HER2 HER2:HER4 • Gene amplification • Receptor overexpression • Somatic mutations HER receptor dimerization Kinase activation • Nera%nib: pan-HER (HER1, 2, and 4) TKI Neratinib PI3K RAS • Breadth of

  4. Slide 4: Clinical experience with neratinib

    Clinical experience with nera%nib • Extended adjuvant: Approved by FDA and EMA based on reduced risk of recurrence of iDFS event with nera%nib vs placebo in ExteNET1 • Neoadjuvant: Higher pCR rates with chemotherapy + nera%nib vs chemotherapy + trastuzumab in pa%ents with HER2+ breast cancer in I-SP

  5. Slide 5: NALA study design

    NALA study design Nera%nib 240 mg/d + Inclusion criteria Capecitabine 1500 mg/m2 14/21 d PD Loperamide (cycle 1)a • Metasta%c breast cancer (MBC) • Centrally confirmed HER2+ disease R Follow-up (1:1) No endocrine therapy permi\ed (survival) • ≥2 lines of HER2-directed therapy for MBC • Asymptoma%c an

  6. Slide 6: Statistical methods

    NALA Sta%s%cal methods Co-primary endpoints of PFS and OS • Conducted under an FDA Special Protocol Assessment • Study posi%ve if either co-primary endpoint met: – p<0.01 for PFS (419 target events required for 85% power) – p<0.04 for OS (378 target events required for 85% power) Planned analyses •

  7. Slide 7: Baseline characteristics

    NALA Baseline characteris%cs Nera%nib + Capecitabine Lapa%nib + Capecitabine (n=307) (n=314) Age <65 years, n (%) 244 (79) 248 (79) Geographic region, n (%) Europe 121 (39) 123 (39) North America 59 (19) 65 (21) Rest of world 127 (41) 126 (40) HR+ (ER+ and/or PR+), n (%) 181 (59) 186 (59) Disease lo

  8. Slide 8: Centrally confirmed PFS (co-primary endpoint)

    NALA Centrally confirmed PFS (co-primary endpoint) 1.0 Hazard ra%o 0.9 (95% CI) Log-rank p-value Nera%nib + Capecitabine 0.8 0.76 (0.63–0.93) 0.0059 Lapa%nib + Capecitabine 0.7 PFS probability 0.6 0.5 47% 0.4 38% 29% 0.3 0.2 16% 0.1 15% 7% 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Time since randomiza%on

  9. Slide 9: Prespecified restricted means analysis – PFS

    NALA Prespecified restricted means analysis – PFS 1.0 Mean PFS 0.9 (months) p-value Nera%nib + Capecitabine 8.8 0.8 0.0003 Lapa%nib + Capecitabine 6.6 0.7 PFS probability 0.6 0.5 Restric%on: 24 months 0.4 0.3 0.2 2.2 months 0.1 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Time since randomiza%on (months) No.

  10. Slide 10: PFS: Forest plot

    NALA PFS: Forest plot Hazard ra%o Events Hazard ra%o Interac%on test Subgroup N (95% CI) N+C vs L+C (95% CI) p-value Overall 621 210 vs 223 0.76 (0.63–0.93) Age group <65 years 492 169 vs 181 0.74 (0.60–0.91) 0.463 ≥65 years 129 41 vs 42 0.83 (0.53–1.28) Race White 355 125 vs 117 0.86 (0.67–1.11) 0.

  11. Slide 11: OS (co-primary endpoint)

    NALA OS (co-primary endpoint) 1.0 Mean OS Hazard ra%o 0.9 (months) (95% CI) Log-rank p-value Nera%nib + Capecitabine 24.0 0.8 0.88 (0.72–1.07) 0.2086 Lapa%nib + Capecitabine 22.2 0.7 OS probability 0.6 0.5 Restric%on: 48 months 0.4 0.3 0.2 1.7 months 0.1 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45

  12. Slide 12: OS: Forest plot

    NALA OS: Forest plot Hazard ra%o Events Hazard ra%o Interac%on test Subgroup N (95% CI) N+C vs L+C (95% CI) p-value Overall 621 192 vs 218 0.88 (0.72–1.07) Age group <65 years 492 149 vs 171 0.86 (0.69–1.08) 0.941 ≥65 years 129 43 vs 47 0.86 (0.57–1.30) Race White 355 113 vs 122 0.88 (0.68–1.13) 0.9

  13. Slide 13: Time to intervention for CNS metastases

    NALA Time to interven%on for CNS metastases 100 Nera%nib + Capecitabine Lapa%nib + Capecitabine Interven%on (n=55/307) (n=75/314) 90 Radia%on therapy 11% 15% 80 Surgery/procedure 2% 3% Cumula%ve incidence (%) 70 An%cancer medica%on 1% 1% 60 50 Nera%nib + Capecitabine Overall cumula%ve incidence (Gra

  14. Slide 14: Response rate and duration of response

    NALA Response rate and dura%on of response 1.0 Nera%nib + Capecitabine Lapa%nib + Capecitabine (n=256) (n=270) p-value 0.9 Objec%ve response rate 33% 27% 0.1201 Probability of con%nuing response 0.8 Clinical benefit rate 45% 36% 0.0328 0.7 Median dura%on of response 8.5 months 5.6 months 0.6 Hazard r

  15. Slide 15: Treatment exposure

    NALA Treatment exposure Nera%nib + Capecitabine Lapa%nib + Capecitabine (n=303) (n=311) Lapa%nib/Nera%nib Median dura%on of treatment, months 5.7 4.4 Dose reduc%on, n (%) 73 (24) 61 (20) Dose hold, n (%) 145 (48) 134 (43) Capecitabine Median dura%on of treatment, months 5.5 4.8 Dose reduc%on, n (%)

  16. Slide 16: Most frequent grade 3/4 adverse events

    NALA Most frequent grade 3/4 adverse events Nera%nib + Capecitabine (n=303) Lapa%nib + Capecitabine (n=311) All grade Grade 3/4 All grade Grade 3/4 Treatment-emergent AE, % 100 61 99 60 Diarrhea 83 24* 66 13* Hand-foot syndrome 46 10 56 11 Hypokalemia 12 5 14 6 Nausea 53 4 42 3 Vomi%ng 46 4 31 2 Fa%

  17. Slide 17: Incidence and duration of diarrhea

    NALA Incidence and dura%on of diarrhea Nera%nib + Capecitabine Lapa%nib + Capecitabine (n=303) (n=311) Maximum toxicity, n (%) Grade 1 91 (30) 111 (36) Grade 2 87 (29) 56 (18) Grade 3 74 (24) 39 (13) Time to first onset of diarrhea, days Grade 2 or 3 9 18 Grade 3 11 38 Median cumula%ve dura%on per pa

  18. Slide 18: Patient reported outcomes

    NALA Pa%ent reported outcomes EORTC QLQ-C30 summary score EORTC QLQ-C30 Global health status Mean score over %me Mean score over %me 100 100 90 90 80 80 70 70 Mean score ± SE Mean score ± SE 60 60 50 50 40 40 Nera%nib + Capecitabine Nera%nib + Capecitabine 30 30 20 Lapa%nib + Capecitabine 20 Lapa%ni

  19. Slide 19: Conclusions

    NALA Conclusions • NALA met its primary objec%ve: N+C superior to L+C in ≥3L HER2+ MBC – Significant PFS benefit favoring N+C: HR=0.76; p=0.0059 – Numerical improvement in OS favoring N+C: HR=0.88; p=0.2086 • Fewer pa%ents required interven%on for symptoma%c CNS metastases with N+C (p=0.043), sugges%v

  20. Slide 20: Thank you

    Thank you The authors would like to thank pa%ents and their families, and the inves%gators and site staff for par%cipa%ng in this trial We also thank the Independent Data Monitoring CommiBee and the Steering CommiBee 20 Adam Brufsky

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