Natera, Inc. · NASDAQ:NTRA
Natera — Investor Presentation (October 2025)
18 slides from Natera's investor presentation, Oct 23, 2025
Slide 1: Natera, Inc. Post-ESMO Investor Call
Natera, Inc. Post-ESMO Investor Call October 23, 2025
Slide 2: Safe harbor statement
Safe harbor statement This presentation contains forward-looking statements under the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation, including statements regarding our market opportunity, our a
Slide 3: Today’s speakers
Today’s speakers Professor Thomas Powles, Lead Principal Investigator of IMvigor011 Professor of Genitourinary Oncology Chair of Barts Cancer Centre at St. Bartholomew’s Hospital Steve Chapman, Chief Executive Officer, Natera Mike Brophy, Chief Financial Officer, Natera Solomon Moshkevich, President
Slide 4: IMvigor011 study design
IMvigor011 study design Screening D> * MIBC within 6-24 weeks of radical cystectomy * Histologically confirmed (y)pT2-T4aNOMO or (y)pTO-T4aN+M0 urothelial cancer + No evidence of radiographic disease + Prior neoadjuvant chemotherapy permitted + ECOG PS 0-2 Ne Surveillance ctDNA monitoring until 1 y
Slide 5: DFS and OS in subgroups based on timing of ctDNA+ test
DFS and OS in subgroups based on timing of ctDNA+ test INV-assessed DFS os Atezolizumab Placebo ‘Atezolizumab Placebo (n=99) (n=49) (n=99) (n=49) 100 DFS, median (95% Cl), mo 8.3(6.2,12.6) 4.2 (2.4, 7.7) 100 5 OS, median (95% Cl), mo 27.7 (22.0, 35.9) 18.2 (10.9, NE) 0 Unstratified HR (95% Cl) 0.62
Slide 6: DFS and OS in patients who persistently tested ctDNA-
DFS and OS in patients who persistently tested ctDNA- INV-assessed DFS os No treatment . No treatment (n=357) Median follow-up: (n=357) Events, n (%) 39 (10.9) 21.8 mo from cystectomy Events, n(%) 14 (3.9) DES, median (95% Cl), mo NE (NE) OS, median (95% Cl), mo NE (NE) 1004 100 9 90 4 90 4 804 80 7
Slide 7: Published in The New England Journal of Medicine
Published in The New England Journal of Medicine 7 Not for reproduction or further distribution.
Slide 8: Adjuvant nivolumab vs placebo for high-risk muscle-invasive urothelial carcinoma: CheckMate 274
Single timepoint ctDNA analysis, no serial testing Adjuvant nivolumab vs placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274 Matthew D. Galsky,1 Jürgen E. Gschwend,2 Matthew I. Milowsky,3 Michael Schenker,4 Begoña P. Valderrama,5 Yoshihiko
Slide 9: ctDNA detectable status relationship with DFS and OS
ctDNA detectable status relationship with DFS and OS CheckMate 274 in each treatment arm 100 DFS NIVO: detectable 100 OS NIVO: detectable PBO: detectable PBO: detectable Disease-free survival probability (%) NIVO: undetectable NIVO: undetectable Overall survival probability (%) PBO: undetectable PBO
Slide 10: Conclusions
Conclusions1,2 • Adjuvant immunotherapy improved DFS and OS by 1.5-2x in the SignateraTM ctDNA-positive groups o Similar treatment efficacy was observed in patients who tested positive in first test vs. subsequent tests, and those with and without neoadjuvant therapy • Signatera ctDNA-negative patie
Slide 11: ctDNA in MIBC patients who received perioperative durvalumab in NIAGARA
2025 ASCO ANNUAL MEETING Circulating tumor DNA (ctDNA) in patients with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA Thomas Powles,' Michiel S. van der Heijden,? Ying Wang,° James W. F. Catto,* Joshua J. Meeks,° Hikmat Al-Ahmadie,® Hiroyuki Nishiyama,” A
Slide 12: Niagara visual, pie charts or outcomes clearance
Niagara visual, 9 pie charts (blue/green) or outcomes clearance 12
Slide 13: New standard of care emerging
New standard of care emerging • Adjuvant treatment decision can benefit from ctDNA guidance, regardless of neoadjuvant regimen • The duration of ADC therapy could be tailored by ctDNA analysis in the perioperative setting • Frequent ctDNA assessment (q6w in y1) is needed to catch MRD before visible
Slide 14: MIBC indication overview
MIBC indication overview • ~30k new MIBC patients per year in the U.S.1,2,3, ~150k worldwide4,5 • Envision 10-14 tests per MIBC patient over 5-year journey, <10% penetration • Majority of our MIBC patients have Medicare6, opportunity to expand coverage with commercial payers • In the US, bladder can
Slide 15: Significant ongoing investments and clinical pipeline in MIBC
Significant ongoing investments and clinical pipeline in MIBC Phase 2/3 MODERN trial (Alliance A032103) • Targeting enrollment of >3k patients from >300 clinical sites across North America • Randomized: escalation for Signatera-positives, observation for Signatera-negatives Phase 3 ARCHER trial (NRG
Slide 16: Implications for future trial designs
Implications for future trial designs MRD-enriched • Randomize Signatera-positive; observe Signatera-negative with prespecified randomized trials TOMR / conversion triggers • Incorporate Signatera kinetics/clearance as an early indicator reasonably Surrogate endpoints likely to predict clinical bene
Slide 17: Summary
Summary IMvigor011 establishes new SOC for post-surgical Signatera-guided IO treatment Not all MRD assays are the same, need prospective validation Additional studies planned in MIBC with Signatera across entire care continuum TOMR concept derisked and likely applicable in other histologies Not for
Slide 18: ©2025 Natera, Inc. All Rights Reserved.
® ©2025 Natera, Inc. All Rights Reserved. Not for reproduction or further distribution.