Pharma Update

Inavolisib in PI3K-mutant breast cancer H2H trial vs alpelisib initiated; Ph III (INAVO120) results in 1L expected Q4 2023 Potential best-in-class PI3Ka inh Potency/selectivity (inavolisib vs. alpelisib) Potential for differentiated safety, efficacy, and combinability Ph I dose escalation and expansion cohort: Clinical development program 58x Inavolisib + palbociclib + letrozole Pi3Ka potency 6x PI3Ka selectivity vs. ẞ 1 26x PI3Ka selectivity vs. 8 Best % change in SLD -20- -40- -60- 1 -80 32x -100 PI3Ka selectivity vs. V GDC-0077 dose (mg) 996 93 99699699 9939 1 5L 0 10 20 30 40 50 Fold change (inavolisib vs. alpelisib)1 Inavolisib ■Alpelisib 60 70 Time Best response PD PD PD SD SD SD SD SD SD SD PR CPR CPR CPR CPR CPR CPR CPR CPR CPR CPR CPR CPR PR CPR Line of therapy (metastatic) 1L 2L 3L 4L 4L 3L 3L 4L 2L 5L 3L 2L 2L 4L 3L 3L 3L 4L 3L 2L 2L 1L 3L treatment (days) 44 58 55 119 84 196 323 168 278 183 347 677 528 353 586 155 712 359 280 508 436 317 380 351 452 31 20% -30% Indication regimen 1L HR+/HER2-PI3Km mBC inavolisib + palbociclib + fulvestrant Phl Ph II Ph III INAVO120 Post CDK4/6i HR+/HER2-PI3Km MBC inavolisib + fulvestrant INAVO121 1L PI3Km and HER+ mBC inavolisib + Phesgo INAVO122 Roche Differentiated from existing PI3K inhibitors: • More potent and selective for PI3Ka subunit • Better in vivo efficacy • Greater safety margins allow for combination Strong efficacy and favorable safety as single agent or in combination with ET +/- CDK4/6i in patients with PI3K-mutant HR+ breast cancer • Ph III INAVO120 in 1L HR+/PI3Km mBC data expected in Q4 2023 • Ph III INAVO121 post-CDKi (head-to-head vs. alpelisib) achieved FPI in Q2 with ET and palbociclib at standard doses . Ph III INAVO122 in 1L HER2+/PI3Km BC (combination with Phesgo) achieved FPI in Q3 ● 40% of HR+/HER2- patients with PI3K mutations Kalinsky K. et al., AACR 2017; Jhaveri, K., et al, SABCS 2019; H2H-head-to-head; inh-inhibitor; ET-endocrine therapy; HR-hormone receptor; mBC=metastatic breast cancer; FPI-first patient in; PI3K-Phosphoinositide 3- Kinase; ET-Endocrine therapy; HR-Hormone receptor; HER2-Human Epidermal growth factor Receptor 2; CDK4/6i-Cyclin-dependent kinase 4 and 6 inhibitors; BC-Breast cancer 76

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