Ionis Pharmaceuticals, Inc. · NASDAQ:IONS
Ionis Pharmaceuticals — Corporate Update (August 2025)
33 slides from Ionis Pharmaceuticals's corporate update, August 2025
Slide 1: DAWNZERA FDA Approval
T M D AW N Z E R A F D A A P P R O VA L Nasdaq: IONS August 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation includes forward-looking statements regarding the therapeutic and commercial potential of DAWNZERA (donidalorsen), Ionis' technologies, and Ionis’ other products in development. Any statement describing Ionis’ goals, expectations, financial or other proje
Slide 3: On Today's Call
On Today’s Call Brett Monia, Ph.D. Kenneth Newman, M.D. Kyle Jenne Chief Executive Officer Senior Vice President, Executive Vice President, Chief Clinical Development Global Product Strategy Officer 3
Slide 4: Agenda
Agenda Topic Speaker Bringing a Steady Cadence of Transformational Medicines Brett Monia, Ph.D., Chief Executive Officer to People with Serious Diseases DAWNZERATM (donidalorsen): First and Only RNA-Targeted Kenneth Newman, M.D., SVP, Clinical Development Prophylactic Treatment for Hereditary Angioe
Slide 5: Bringing a Steady Cadence of Transformational Medicines to People with Serious Diseases
BRINGING A STEADY CADENCE OF T R A N S F O R M AT I O N A L M E D I C I N E S TO PEOPLE WITH SERIOUS DISEASES Brett Monia, Ph.D. Chief Executive Officer 5
Slide 6: Now Approved
NOW APPROVED To prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older DAWNZERA is approved in the U.S. for hereditary angioedema in adults and pediatric patients 12 years of age and older; see Full Prescribing Information. 6
Slide 7: Delivering a Steady Cadence of Transformational Medicines
Delivering a Steady Cadence of Transformational Medicines Two Additional Planned Independent Launches in 20262 Second Independent Launch Olezarsen First Independent Launch Potential to change the Commercializing treatment paradigm Multiple Medicines BB for people with sHTG through Partners3 First an
Slide 8: DAWNZERA: Transforming the HAE Treatment Paradigm
DAWNZERA: Transforming the HAE Treatment Paradigm Compelling Product Profile6: Efficacy Tolerability Convenience 〉Substantial and 〉Favorable safety and 〉Longest dosing interval sustained HAE attack tolerability option27 rate reduction 〉Low volume autoinjector 〉No loading dose 〉Long-term disease 〉Con
Slide 9: DAWNZERA: First and Only RNA-Targeted Prophylactic Treatment for HAE
D A W N Z E R ATM( d o n i d a l o r s e n ) F I R S T A N D O N LY R N A - TA R G E T E D P R O P H Y L A C T I C T R E AT M E N T F O R H E R E D I TA R Y A N G I O E D E M A Kenneth Newman, M.D. SVP, Clinical Development DAWNZERA is approved in the U.S. for hereditary angioedema in adults and ped
Slide 10: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) 8-11 Swelling of Face/Throat Swelling of A rare, chronic and potentially Stomach/GI Area life-threatening genetic Swelling of condition Genitals Swelling of Hands/Feet Patients experience recurrent attacks of severe swelling in various parts of the body 10
Slide 11: Understanding HAE and Its Impact
Understanding HAE and Its Impact Symptoms of HAE usually appear early in life, most often by puberty, and may increase in severity with age12-17 Diagnosis is typically confirmed through a blood test12-17 ~7,000 On average, it takes five years to diagnosis16 People in Children have a 50% chance of in
Slide 12: DAWNZERA's Novel Target: PKK at the Start of the Kallikrein-Kinin Pathway
DAWNZERA’s Novel Target: PKK at the Start of the Kallikrein-Kinin Pathway Low levels or inadequate C1 esterase inhibitor (C1-INH) activity causes aberrant activation of the kallikrein-kinin pathway18 • Plasma prekallikrein (PKK) is produced in the liver and is the precursor of kallikrein • Uncontrol
Slide 13: DAWNZERA: First and Only RNA-Targeted Medicine for HAE
DAWNZERA: First and Only RNA-Targeted Medicine for HAE 19-21 DAWNZERA is selectively targeted to the liver DAWNZERA binds to prekallikrein (PKK) mRNA to limit plasma protein production at the source — in the liver, where it’s made DAWNZERA binds to PKK mRNA and directs its degradation HAE Attacks DA
Slide 14: Data from DAWNZERA Highlighted in Multiple NEJM Publications
Data from DAWNZERA Highlighted in Multiple NEJM Publications Phase 1 Data Phase 2 Data Phase 3 Data 14
Slide 15: DAWNZERA's Robust Efficacy Profile
DAWNZERA’s Robust Efficacy Profile 22 〉 Met all Q4W primary and secondary endpoints28 94% 〉 81% reduction (p<0.001) in mean HAE attack rate Total Mean compared to placebo, Reduction in HAE increased to an 87% Attack Rates reduction (p<0.001) when across Q4W and measured from the second Q8W over dose
Slide 16: DAWNZERA Substantially Reduced HAE Attack Rates After Switching
DAWNZERA Substantially Reduced HAE Attack Rates After Switching 25 OASIS-Plus Switch Cohort Results 〉 62% overall mean reduction in HAE attack rate from prior prophylactic treatment 〉 93% of patients well-controlled (AECT) 〉 No increase in breakthrough attacks These are not head-to-head data and are
Slide 17: Additional Positive Results from Open-Label Switch Cohort
Additional Positive Results from Open-Label Switch Cohort 25 % Reduction in Mean Monthly HAE Attack Rate After Switching to DAWNZERA 84% of Switch Patients Surveyed Preferred Prior LTP: DAWNZERA n= 31 11 22 Baseline, mean ± SD = 0.69 ± 1.09 1.80 ± 1.92 0.61 ± 0.96 Donidalorsen Q4W, mean ± SD = 0.24
Slide 18: Favorable Long-Term Safety and Tolerability
Favorable Long-Term Safety and Tolerability 1 The safety of DAWNZERA reflects an average Adverse Reactions (≥ 5% with DAWNZERA and more common than placebo) in OASIS-HAE at Week 24 exposure duration of 14 months in 171 patients aged ≥12 y/o across 3 clinical trials Adverse DAWNZERA DAWNZERA Placebo
Slide 19: Setting a New Bar for Prophylactic HAE Treatment
Setting a New Bar for Prophylactic HAE Treatment 6,27 DAWNZERA: First and Only RNA-Targeted Medicine for HAE Efficacy Tolerability Convenience Longest dosing interval Substantial and sustained Favorable safety and HAE attack rate reduction tolerability No loading dose Long-term disease control Low v
Slide 20: DAWNZERA: Transforming the HAE Treatment Paradigm
D A W N Z E R ATM ( D O N I D A L O R S E N ) T R A N S F O R M I N G T H E H A E T R E AT M E N T PA R A D I G M Kyle Jenne Chief Global Product Strategy Officer DAWNZERA is approved in the U.S. for hereditary angioedema in adults and pediatric patients 12 years of age and older; see Full Prescribi
Slide 21: DAWNZERA: Transforming the HAE Treatment Paradigm
DAWNZERA: Transforming the HAE Treatment Paradigm 6,27 Compelling Product Profile 〉 Substantial durable efficacy, with favorable safety and tolerability 〉 Self-administration with an autoinjector 〉 Longest dosing option: every four- or eight-weeks 〉 Impressive switch data, including strong patient p
Slide 22: U.S. HAE Market Dynamics Underscore DAWNZERA's Potential
U.S. HAE Market Dynamics Underscore DAWNZERA’s Potential 27 ~75% ~1,000 >90% ~7,000 of people ~20% people with allergists/ of people are interested with HAE in the immunologists HAE have switched in trying a new U.S. are on treat in the U.S.15 treatments prophylactic Prophylactic 90% annually therap
Slide 23: Remaining Unmet Need: Efficacy, Tolerability, Convenience
Remaining Unmet Need: Efficacy, Tolerability, Convenience 27 People with Continued need Frequent dosing HAE still for a increases experience prophylactic treatment breakthrough treatment burden attacks offering Nearly all prophylactic with current improved treatments require daily, medications toler
Slide 24: DAWNZERA's Compelling and Comprehensive Profile
DAWNZERA’s Compelling and Comprehensive Profile 6,27 Efficacy: ✓ Substantial and sustained attack rate reduction with long-term durability ✓ Strong disease control Tolerability: ✓ Patient-friendly self-administered autoinjector ✓ Low 0.8mL volume ✓ Contains no citric acid, which is associated with i
Slide 25: Switch Data Confirm DAWNZERA's Compelling Profile Resonated with Study Participants
Switch Data Confirm DAWNZERA’s Compelling Profile Resonated with Study Participants 25 Reasons participants chose for preferring DAWNZERA of switch patients Efficacy Tolerability Convenience 84% surveyed 63% 50% 65% preferred DAWNZERA chose chose chose “it works better “less injection- “less time to
Slide 26: DAWNZERA Launch Strategy Designed for Success
DAWNZERA Launch Strategy Designed for Success Patient & HCP Commercial Comprehensive Coverage & Omnichannel Focus Execution Support Program Reimbursement Engagement Unmet need Experienced U.S. Patients and HCP services Market access team Targeted HCP and education commercial team to enable seamless
Slide 27: Ionis Every Step: Innovating to Meet the Needs of the HAE Community
Ionis Every Step Innovating to Meet the Needs of the HAE Community Dedicated personal support from Patient Education Managers Disease education, injection training and connection to additional resources TM DAWNZERA Direct digital companion Free trial program Financial support programs30 DAWNZERA is
Slide 28: Now Approved
NOW APPROVED To prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older DAWNZERA is approved in the U.S. for hereditary angioedema in adults and pediatric patients 12 years of age and older; see Full Prescribing Information. 28
Slide 29: Accelerating Value Through Excellence in Commercial Execution
A C C E L E R AT I N G VA L U E T HROUGH EXCEL L ENCE IN COMMERCIAL EXECUTION Brett Monia, Ph.D. Chief Executive Officer 29
Slide 30: Multi-Billion Dollar Opportunity from these 4 Launches
Delivering a Steady Cadence of Transformational Medicines 2 2 Independent Launches in 2 Planned Independent <1 year1,4 Launches Next Year2 Olezarsen (sHTG) | Zilganersen (AxD)31 Multi-Billion Dollar Opportunity from these 4 Launches5 Advancing Additional Potentially Transformational Wholly Owned Med
Slide 31: Q&A
Q&A Brett Monia, Ph.D. Kenneth Newman, M.D. Kyle Jenne Chief Executive Officer Senior Vice President, Executive Vice President, Chief Clinical Development Global Product Strategy Officer 31
Slide 32: Thank You
THANK YOU ZO . IONIS DAWNZERA)
Slide 33: References
References 1. DAWNZERA is approved in the U.S. for hereditary angioedema in adults and pediatric patients 12 years of age and older; see Full Prescribing Information. 2. Timing and expectations based on current assumptions and subject to change. 3. Co-developing and commercializing WAINUA for ATTRv-
Ionis Pharmaceuticals — Corporate Update (August 2025) on 6ix