Praxis relutrigine study shows 86% seizure reduction

Available on EDGAR 11/12/2026 - 05:02 PM EST Accepted by SEC EDGAR 11/12/2026 - 05:01 PM EST Learn about SEC filing dates

Rhea-AI Filing Summary

Praxis Precision Medicines, Inc. (PRAX) presented commercial plans and pipeline updates at its November 12, 2026 Investor Day, listing PDUFA dates of December 27, 2026 for relutrigine and January 29, 2027 for ulixacaltamide.

For ulixacaltamide, Praxis said FDA-requested sensitivity analyses of the Essential3 primary endpoint were consistent with the primary result; an early long-term safety study analysis showed durable and improving activities-of-daily-living response after approximately 95 weeks. The company estimated about 9 million people in the U.S. have essential tremor, including about 2 million seeking treatment. Relutrigine open-label extension data in SCN2A/SCN8A developmental and epileptic encephalopathies showed an 86% seizure reduction from baseline at 18 months.

Praxis plans ulixacaltamide studies in Parkinson’s disease, restless legs syndrome and autism spectrum disorder in 2027; two next-generation molecules and a transdermal patch are also planned to enter the clinic in 2027, with patch timing subject to FDA engagement. PRAX-206 is planned for early 2027 clinical entry; PRAX-215’s Phase 1 readout is expected in 2027, while PRAX-110 is expected to enter the clinic in 2028. The company also described six preclinical antisense oligonucleotide programs alongside pivotal-development candidate elsunersen.

Positive

• Minor pointRelutrigine open-label extension showed an 86% seizure reduction from baseline at 18 months.
• Minor pointUlixacaltamide’s long-term study reported ADL response through approximately 95 weeks.

Negative

• None.

Filing Explained

The furnished Investor Day presentation says EMERALD topline results for relutrigine in broad developmental and epileptic encephalopathies are expected in Q4 2026; this is a planned data milestone for a broader population, not a reported outcome.

8-K Event Classification

3 items: 7.01, 8.01, 9.01

3 items

Item 7.01 Regulation FD Disclosure Disclosure

Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.

Item 8.01 Other Events Other

Voluntary disclosure of events the company deems important to shareholders but not covered by other items.

Item 9.01 Financial Statements and Exhibits Exhibits

Financial statements, pro forma financial information, or exhibit attachments filed with this report.

Key Figures

Relutrigine seizure reduction: 86% U.S. essential tremor prevalence: About 9 million people People seeking essential tremor treatment: About 2 million people +5 more

8 metrics

Relutrigine seizure reduction 86% From baseline at 18 months in the open-label extension for SCN2A/SCN8A developmental and epileptic encephalopathies

U.S. essential tremor prevalence About 9 million people Praxis population-based estimate

People seeking essential tremor treatment About 2 million people U.S. population identified as the company’s initial commercial focus

Ulixacaltamide long-term study duration Approximately 95 weeks Average duration in the Essential3 long-term safety study analysis

Relutrigine PDUFA date December 27, 2026 Date listed in the Investor Day presentation

Ulixacaltamide PDUFA date January 29, 2027 Date listed in the Investor Day presentation

PRAX-215 Phase 1 readout Expected in 2027 PRAX-215 is being evaluated in a Phase 1 SAD/MAD study

PRAX-110 clinical entry Expected in 2028 Isoform-biased pain molecule

Key Terms

PDUFA date, open label extension, modified TETRAS-ADL11, first-in-human, +1 more

5 terms

PDUFA date regulatory

"Relutrigine SCN2A & SCN8A DEE — Dec 27, 2026 PDUFA date"

PDUFA date is the deadline the U.S. Food and Drug Administration sets to complete its review of a drug or biologic application and decide whether to approve it. Investors watch it like a court verdict date: the decision can unlock sales and growth if approved or sharply reduce expected value if denied, so markets often move significantly as the date approaches or when the outcome is announced.

open label extension medical

"updated open label extension data from the EMBOLD study"

An open-label extension is a follow-on phase of a clinical trial where participants keep receiving the experimental drug and both doctors and patients know what treatment is being given. It matters to investors because it produces longer-term safety and effectiveness information, helps regulators and companies assess ongoing benefits or risks, and can indicate whether a therapy has staying commercial value — like an extended test drive revealing durability and real-world performance.

modified TETRAS-ADL11 medical

"Change in modified TETRAS-ADL11 from baseline to Day 56"

first-in-human medical

"2 molecules entering first-in-human studies in 1H27"

A first-in-human study is the initial test of a new drug, medical device, or therapy in people to check safety, side effects and appropriate dosing. It matters to investors because it marks a major development milestone: successful early human testing can reduce scientific and regulatory uncertainty, much like moving a prototype from the workshop to a real-world test drive, and often affects a company’s valuation and funding prospects.

antisense oligonucleotide medical

"six preclinical antisense oligonucleotide programs"

An antisense oligonucleotide is a small piece of synthetic genetic material designed to attach to specific molecules in the body’s cells, effectively blocking or modifying how genes are expressed. This technology is important because it can be used to develop targeted treatments for certain diseases, which may influence the value of biotech companies and the broader healthcare sector. Its development reflects advances in personalized medicine and gene-based therapies.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did PRAX report on relutrigine seizure reduction at 18 months?

Praxis reported an 86% reduction in seizures from baseline at 18 months in the EMBOLD open-label extension for SCN2A- and SCN8A-related developmental and epileptic encephalopathies. The presentation described continued seizure reduction through 18 months.

What are the PDUFA dates for PRAX’s ulixacaltamide and relutrigine?

Praxis listed December 27, 2026 for relutrigine and January 29, 2027 for ulixacaltamide. The presentation identified both as PDUFA dates.

Which new indications is PRAX pursuing for ulixacaltamide?

Praxis plans to initiate studies in 2027 for ulixacaltamide in Parkinson’s disease, restless legs syndrome and autism spectrum disorder. The presentation estimated U.S. prevalence at about 1 million, 5 to 8 million and 8 million people, respectively.

AI-generated analysis. How Rhea-AI works. Not financial advice.

Understanding 8-K Material Events →

See more from StockTitan in Google Search and AI answers. Adds StockTitan as a preferred source · opens Google

Add on Google Not now

FALSE000168954800016895482026-11-122026-11-12

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): November 12, 2026

PRAXIS PRECISION MEDICINES, INC.

(Exact name of registrant as specified in its charter)

Delaware			001-39620			47-5195942
(State or other jurisdiction of incorporation)			(Commission File Number)			(I.R.S. Employer Identification No.)

Praxis Precision Medicines, Inc.

99 High Street, 30th Floor

Boston, Massachusetts 02110

(Address of principal executive offices, including zip code)

(617) 300-8460

(Registrant’s telephone number, including area code)

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class

Trade Symbol(s)

Name of each exchange on which registered

Common Stock, $0.0001 par value per share

PRAX

The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company  ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

Item 7.01. Regulation FD Disclosure.

On November 12, 2026, Praxis Precision Medicines, Inc. (the “Company”) hosted an Investor Day event (“Investor Day”). The presentation used at Investor Day is available in the “Investors + Media” portion of the Company’s website at investors.praxismedicines.com and a copy is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

The information in this Current Report on Form 8-K under Item 7.01, including Exhibit 99.1, attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01. Other Events.

On November 12, 2026, at Investor Day, Company management presented on the Company’s commercial strategy and launch plans for relutrigine in SCN2A and SCN8A developmental and epileptic encephalopathies (“DEEs”) and ulixacaltamide in essential tremor (“ET”) and provided an update on its expanded development pipeline. The Company shared the following updates:

Ulixacaltamide

•The Company provided an updated population-based prevalence estimate for ET of about 9 million people in the U.S., including about 2 million who are seeking treatment today and who represent the Company’s initial commercial focus.

•The Company provided sensitivity analyses of the Essential3 primary endpoint, including key sensitivity analyses requested by the U.S. Food and Drug Administration (the “FDA”) during the New Drug Application review, which were consistent with the primary result.

•The Company shared an early analysis of patients in the Essential3 long-term safety study who completed recent efficacy assessments after receiving ulixacaltamide for approximately 95 weeks, which showed durable and improving ADL response over time, further supporting ulixacaltamide’s use as a chronic therapy.

Relutrigine

•The Company shared updated open label extension data from the EMBOLD study in SCN2A- and SCN8A-DEEs, showing continued reduction in seizures through 18 months with 86% reduction in seizures from baseline.

Pipeline Updates

Movement Disorders Expansion

•The Company plans to develop and initiate studies in 2027 with ulixacaltamide in Parkinson’s disease (about 1 million patient prevalence), restless legs syndrome (5 to 8 million patient prevalence) and autism spectrum disorder (8 million patient prevalence).

•The Company will advance two new molecular entities that optimize the t-type calcium channel mechanism of action for the treatment of movement disorders, with expected first in human studies in 2027.

•The Company continues to make progress on its recent collaboration with Remagine Labs to develop an iontophoretic transdermal patch for ulixacaltamide. The patch is designed to improve accessibility for ulixacaltamide and is planned to enter the clinic in 2027.

Pain

•The Company introduced a two-pronged approach utilizing its expertise in sodium channel modulation with a pan-sodium channel strategy and a NaV1.8 isoform biased strategy for developing therapies for chronic and acute pain indications.

•The Company is utilizing its proprietary Praxis Analysis of Concordance (“PAC”) framework in pain to identify an optimized set of pre-clinical models for screening and de-risking development candidates.

•PRAX-215 is a pan-sodium channel molecule currently being evaluated in a Phase 1 SAD/MAD study with a readout expected in 2027 and is being carried forward into chronic and acute pain trials.

•PRAX-110 is an isoform biased molecule and is expected to enter the clinic in 2028.

Other Pipeline Updates

•The Company introduced PRAX-206 in KCNT1 developmental epilepsies, which has shown strong pre-clinical data and is planned to enter the clinic in early 2027.

•The Company shared a portfolio of six preclinical antisense oligonucleotide (“ASO”) programs being advanced within the Solidus™ platform, in addition to elsunersen, which is in pivotal development.

Forward-Looking Statements

This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including, without limitation, statements regarding the Company’s commercial strategy and launch plans, the potential market opportunity for and therapeutic potential of its product candidates, regulatory review and potential approval, and the timing and results of its ongoing and planned clinical and preclinical development. The forward-looking statements included in this Current Report on Form 8-K are subject to a number of risks, including, without limitation: the timing of and the Company’s ability to obtain regulatory approval of its product candidates; the Company’s ability to successfully commercialize its product candidates, if approved; the potential addressable market sizes for its product candidates; uncertainties inherent in clinical trials and pre-clinical development; the expected timing of clinical trials, data readouts and the results thereof; regulatory authorization to conduct trials; and other risks as described in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025 and other filings with the Securities and Exchange Commission. These statements are based only on facts currently known by the Company and speak only as of the date of this Current Report on Form 8-K. As a result, you are cautioned not to rely on these forward-looking statements and the Company undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.						Description
99.1						Praxis Precision Medicines, Inc. 2026 Investor Day Presentation
104						Cover Page Interactive Data File (embedded within the inline XBRL document)

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

			PRAXIS PRECISION MEDICINES, INC.
Date: November 12, 2026			By:						/s/ Marcio Souza
									Marcio Souza
									Chief Executive Officer

Investor Day November 12, 2026 – New York City

2 This presentation may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, relating to our business, operations, and financial conditions, including but not limited to express or implied statements regarding our current beliefs, expectations and assumptions regarding the future of our business and our future plans and strategies, including statements about the estimated market for our product candidates, if approved; regulatory submissions, approvals and timing thereof of any of our product candidates; our commercial launch plans and readiness; our development plans and progress across our pipeline; our clinical and preclinical results; and other future developments, including our cash runway. Any forward-looking statements in this presentation are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including, without limitation, risks relating to: (i) the timing of and our ability to obtain and maintain regulatory approval of any of our product candidates, (ii) our ability to build commercial capabilities and successfully launch and commercialize our product candidates, if approved, (iii) the success and timing of our product development activities, including our ongoing clinical trials and the initiation of new clinical trials, (iv) our plans to advance our pipeline and platforms and to develop additional product candidates, (v) the success and timing of our collaboration partners’ product development activities and our ability to enter into collaborations for the development of new product candidates, (vi) our ability to establish manufacturing capabilities or secure adequate commercial supply, and our reliance on third parties to manufacture, supply and scale production of our product candidates and any approved products, (vii) our ability to obtain, maintain and enforce intellectual property protection, (viii) our estimates of expenses and capital requirements, the sufficiency of our cash runway, and our need for additional financing, (ix) the potential addressable market sizes for product candidates, and (x) our ability to meet any specific milestones set forth herein. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Forward-looking statements speak only as of the date of this presentation. Except as required by applicable law, we undertake no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. For further information regarding the risks, uncertainties and other factors that may cause differences between our expectations and actual results, you should review the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2025 and other filings made with the Securities and Exchange Commission. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. Forward Looking Statements

3 Takeaways For Today 01 Ready to execute commercially at the highest level With • Proven leadership • State-of-the-art infrastructure • Capital to execute at full force 02 Poised to become the preeminent neurology company in the world No other company will match our • Breadth of impact • Depth of pipeline • Scale of revenue potential

4 The needs of patients with CNS disorders are devastatingly urgent. Our mission is to help patients by delivering life-altering treatments faster and more effectively than has ever been done before — and to do it again and again. PRAXIS’ MISSION

5 What It Takes to Do It Again and Again PRAX daily closing share price, $ (split-adjusted) $100 $200 $300 $400 $0 2025 2026 2027 2028 2029 2030 D E F I N I N G T R A I T S T H A T W I L L C A R R Y U S F O R W A R D Focus Resilience Conviction Accountability Again and again. Source: FactSet daily closing prices, January 1, 2025 to November 10, 2026, adjusted for stock splits. BTD: Breakthrough Therapy Designation NDA: new drug application; Ph: Phase

6 Praxis’ Full Pipeline Today DEE: developmental and epileptic encephalopathy; FOS: focal onset seizures; LoF: loss of function; ATM: Ataxia-telangiectasia. MARKETED C E R E B R U M S O L ID U S Essential tremor Ulixacaltamide Parkinson's disease PRAX-051 CaV3.x-selective inhibitor PRAX-050 Pan-CaV3.x inhibitor(s) Restless legs syndrome Autism spectrum disorder Patch delivery SCN2A & SCN8A DEE Relutrigine Broad DEEs Adjunctive FOS Vormatrigine Monotherapy FOS PRAX-215 Pain PRAX-110 Pain PRAX-206 KCNT1 DEE Elsunersen Early-onset SCN2A DEE PRAX-080 PCDH19 PRAX-090 SYNGAP1 PRAX-100 SCN2A LoF autism PRAX-120 ATM PRAX-130 SLC6A1 PRAX-140 KCNQ2

7 2035 Vision: Two Platforms Treating Diseases Across Four Franchises Illustrative scenario. DEE: developmental and epileptic encephalopathy; LoF: loss of function; ATM: Ataxia-telangiectasia. Epilepsy Movement Disorders Neuro- development Pain Relutrigine SCN2A & SCN8A DEE Relutrigine Broad DEEs Vormatrigine Focal onset seizures PRAX-206 KCNT1 DEE Elsunersen Early-onset SCN2A DEE PRAX-080 PCDH19 PRAX-090 SYNGAP1 PRAX-130 SLC6A1 PRAX-140 KCNQ2 Ulixacaltamide Essential tremor Ulixacaltamide Parkinson's disease Ulixacaltamide Restless legs syndrome PRAX-120 Ataxia-telangiectasia Ulixacaltamide Autism spectrum disorder PRAX-100 SCN2A LoF autism PRAX-215 Pain PRAX-110 Pain

8 As Each of Our Late-Stage Assets Is Approved, Consensus Will Push Praxis to the Top Neurology Portfolio Analyst Consensus Sales ($B) $5B $10B $15B 2027E 2028E 2029E 2030E 2031E 2032E 2033E 2034E 2035E $3.7 $3.9 $4.5 $4.4 $5.1 $5.4 $5.6 $10.5 $9.7 $10.6 $13.1 $13.5B 2035E consensus assuming approvals Source: Bloomberg consensus. Products included: AbbVie (Vyalev, Botox, Qulipta, Ubrelvy, Vraylar, Juvmo, Duodopa); Johnson & Johnson (Invega Sustenna, Spravato, Caplyta, Concerta); Roche (Ocrevus, Evrysdi, Fenebrutinib, Enspryng, Madopar, Trontinemab); Novartis (Kesimpta, Zolgensma, Aimovig, Rhapsido, Mayzent, Gilenya); Teva (Austedo, Ajovy, Uzedy, Copaxone, Olanzapine (LAI)); Eli Lilly (Kisunla, Emgality, Remternetug, Prozac); Eisai (Leqembi, Dayvigo, Aricept, Fycompa, Methycobal); Axsome (Auvelity, Sunosi, AXS-12); Biogen (Spinraza, Tysabri, Skyclarys, Vumerity, Zurzuvae, Avonex, Qalsody); Neurocrine (Ingrezza, TAK-653); Takeda (Orzeyful, Vyvanse, Trintellix, Intuniv). Praxis consensus assuming approvals divides each asset's consensus by its consensus probability of success (ulixacaltamide 80%, relutrigine 70%, vormatrigine and elsunersen 60%).

9 Commitment to Commercial Excellence Coupled with a Rapidly Advancing Pipeline $13.1 $10.6 $9.7 $10.5 $5.6 $5.4 $5.1 $4.4$4.5 $3.9 $3.7Ulixacaltamide $10.0 (+$2.3) Relutrigine $5.0 (+$1.7) Vormatrigine $4.0 (+$2.2) Elsunersen $1.0 (+$0.3) $20B+ Praxis peak sales guidance + pipeline Source: Bloomberg consensus. Products included: AbbVie (Vyalev, Botox, Qulipta, Ubrelvy, Vraylar, Juvmo, Duodopa); Johnson & Johnson (Invega Sustenna, Spravato, Caplyta, Concerta); Roche (Ocrevus, Evrysdi, Fenebrutinib, Enspryng, Madopar, Trontinemab); Novartis (Kesimpta, Zolgensma, Aimovig, Rhapsido, Mayzent, Gilenya); Teva (Austedo, Ajovy, Uzedy, Copaxone, Olanzapine (LAI)); Eli Lilly (Kisunla, Emgality, Remternetug, Prozac); Eisai (Leqembi, Dayvigo, Aricept, Fycompa, Methycobal); Axsome (Auvelity, Sunosi, AXS-12); Biogen (Spinraza, Tysabri, Skyclarys, Vumerity, Zurzuvae, Avonex, Qalsody); Neurocrine (Ingrezza, TAK-653); Takeda (Orzeyful, Vyvanse, Trintellix, Intuniv). Praxis consensus assuming approvals divides each asset's consensus by its consensus probability of success (ulixacaltamide 80%, relutrigine 70%, vormatrigine and elsunersen 60%).

10 Agenda Marcio Souza President and CEO Megan Sniecinski Chief Operating Officer Steve Petrou President of R&D Erik Johnson Head of Commercial John Bullock Head of Sales Ulixacaltamide Essential tremor • Unmet need • Clinical data • Commercial strategy • KOL panel Dr. William Ondo Dr. Daniel Kremens Relutrigine SCN2A/8A DEE • Unmet need • Clinical data • KOL panel Dr. Eric Segal Dr. Douglas Smith • Commercial strategy Pipeline Beyond the first two launches • Ulixacaltamide beyond ET • Pain • Epilepsy Break Lunch Reception to follow Q&A

Two First Launches. A Growing Portfolio Ulixacaltamide and Relutrigine Anchor a Commercial Engine Built for Many Ulixacaltamide Relutrigine

12 A First-Principles, Disciplined Approach to Commercialization Built to Repeat Build Exceptional TEAMS Build teams committed to our mindset, operating model and excellence standard Customize the EXPERIENCE Provide solutions so patients and physicians can focus on outcomes. Execute With INSIGHT Combine deep market understanding with real- time data intelligence to monitor and inform execution Invest With CONVICTION Build the capabilities upfront to accelerate patient impact and maximize long-term value

13 Maximizing Long-Term Value by Investing Upfront to Accelerate Patient Impact THE INVESTMENT WHAT IT FUNDS WHY WE DO IT MAXIMIZED FIELD FORCE Full teams in place ahead of launch with full target coverage and dynamic capacity vs. typical incremental build End-to-end oversight of the entire patient and HCP experience vs. disjointed and opaque therapy initiation Accelerated patient impact CUTTING EDGE DATA INFRASTRUCTURE Purpose-built data foundation enabling real-time commercial capabilities vs. retrofitted, time-lagged legacy systems Maximized NPV INVEST WITH CONVICTION INTEGRATED HUB AND CHANNEL NETWORK Setting a new benchmark for launch- year investment BIOTECH’S NOTABLE FIRST LAUNCHES

14 Rigorous and Disciplined Approach to Build and Deploy Dedicated Teams Ahead of Launch HIRING  Sequenced hiring enabled direct leaders to recruit and hire next-level  Track record of exceptional performance TRAINING  Shift from Module-to-Test to an Innovative Learning and Engagement Model 1 AI simulations 2 Teach it back 3 Certified by full simulation BUILD EXCEPTIONAL TEAMS ONBOARDING  High-intensity onboarding  Focus on Mindset Expectations, Operating Model and Market Education OUR VALUES Trust Curiosity Ownership Results Initial screen Manager interview Panel interview Role simulation Culture screen Executive team member interviews every lead candidate

15 Achieving Maximum Value for all Stakeholders is the Core Launch Priority Typical LaunchPrioritize Quantity Prioritize Quality ULIXACALTAMIDE - ET A Strong First Experience RELUTRIGINE - SCN2A/8A DEE Treatment Paradigm Shift Launch progress CUSTOMIZE THE EXPERIENCE

16 State-of-the-Art Infrastructure Integrates Real-Time Data to Monitor Actionable Insights and Launch Execution DATA INPUTS DATA USES Digital Rx Platform Patient Services Field CRM Marketing SP Channel Formulary Claims Medical Information Pharmacovigilance + 20 more platforms PATIENT/PHYSICIAN SUPPORT Access, enrollment, adherence and PA support MARKETING STRATEGY Omnichannel targeting and campaign analytics SALES OPERATIONS Call planning, Next Best Action, Dynamic targeting CHANNEL REPORTING Real-time dispense, inventory and gross-to- net visibility SELF-SERVICE BI Performance monitoring and analysis COMMERCIAL DATA FOUNDATION (CDF) EXECUTE WITH INSIGHT One single, real-time, integrated view of patients, prescribers, payers and channel AI layer runs through CDF to enable process automation, scale and analysis

17 The Hub of the Future Fully Integrates Rx Writing, Patient Services and Specialty Pharmacy, Tailored to Each Market CUSTOMIZE THE EXPERIENCE Digital Prescription Intake Specialty Pharmacy Distribution Office & Patient Support 1 PRESCRIBE Prescribe from the EHR 2 GET ACCESS Coverage answered fast 3 START THERAPY Engaged within minutes 4 STAY ON THERAPY Continued support COMMERCIAL DATA FOUNDATION (CDF) Real-time view of patients, prescribers, payers and channel

18 Two Launches. First of Their Kind. D A R I N G F O R M O R E Dec 27, 2026 Relutrigine SCN2A & SCN8A Developmental and Epileptic Encephalopathy Jan 29, 2027 Ulixacaltamide Essential Tremor

19 E S S E N T I A L T R E M O R Ulixacaltamide The first medicine designed for essential tremor Jan 29, 2027 PDUFA date

20 Essential Tremor Is the Sleeping Giant of Neurology: Common, Disabling and Ready for Change Sources: Louis ED, Ottman R. Tremor Other Hyperkinet Mov (N Y). 2014;4:259; Louis ED, et al. Parkinsonism Relat Disord. 2015;21(7):729-735; Louis ED, et al. Eur J Neurol. 2007;14(10):1138-46; Elble RJ. Curr Neurol Neurosci Rep. 2013;13(6):353; Komodo claims data; Praxis Data on File H I G H D I S E A S E B U R D E N 9 million Americans live with ET, one of the most common movement disorders >85% report functional disability impacting daily activities like writing, eating, drinking and dressing Burden beyond the tremor Embarrassment, depression, anxiety and social isolation L I M I T E D T R E A T M E N T O P T I O N S 1 approved drug with limited effect Propranolol, a decades-old beta-blocker ~50% contraindicated Cardiac disorders, asthma and older age rule out propranolol for half of patients Low retention Patients quickly stop propranolol

21 ET Severely Limits Patients' Ability to Function Source: Praxis data on file, ET patient survey, Mar/Apr 2026 Speaking 16% Everyday activities affected by ET, % of patients Patients could select multiple activities Writing 86% Eating with a spoon 76% Drinking from a cup 73% Household and hobbies 46% Grooming 37% Using technology 61% Using keys 32% Dressing 22% DAILY FUNCTIONAL IMPACT 1,294 patients surveyed 1 No impact 7 Extreme 5/7 Mean score patients give ET's impact on a typical day

22 An Aging US Demographic Drives ET Growth Faster Than the Overall Population Each dot ≈ 100K people. Sources: 2012: Louis ED, Ottman R. Tremor Other Hyperkinet Mov. 2014;4:259; US Census Bureau intercensal estimates 2010–2020 and 2023 National Population Projections (middle series). 2026 and 2040 hold 2012 age-specific rates fixed. ~7M 2012 ~9M 2026 +0.6M Population growth +1.3M Aging demographic ~11M 2040 +0.4M Population growth +1.6M Aging demographic

23 Today, a Poor Standard of Care Keeps Patients From Seeking Treatment Each dot ≈ 100K patients. Source: Diagnosis rate: Louis and Ottman (2014), Crawford et al. (2020); Treatment rate: Diaz & Louis (2010); Internal claims analysis; Familial History based on Ph2, Ph3, and patient survey data ~9M Living with ET ~2M Actively Managed • Limited treatment options with poor efficacy and tolerability • Often dismissed as “running in the family” (50–70% of cases are familial) • Learned self-coping mechanisms allow patients to manage tremor prior to onset of significant disability: adjusting daily activities, avoiding trigger situations or self-medicating with alcohol

24 Findings From an Observational Study Reinforce That Current ET Care Falls Short ET patients under care confirmed with active claims, linked to MD NPI: Medical Doctor National Provider Identifier Source: Praxis HCP observational quant study, 2026. W H O W A S S T U D I E D >2,300 US physicians >43,000 ET patients under their care 66 Mean ET patients per physician S P E C I A L T Y M I X 44% Neurology 44% PCP 12% Other 37% 57% 66% 66% Contraindications with current therapies Insufficient improvement in daily functioning Efficacy inconsistent across patients Limited treatment options Unmet needs with current ET therapies % of treating physicians citing each (2303)

25 U L I X A C A L T A M I D E ESSENTIAL3: First Positive Phase 3 Program in Essential Tremor Steve Petrou

26 ESSENTIAL3: Innovative Program Designed to Demonstrate Ulixacaltamide Restores and Maintains Patient Function Stable responders defined as those who met the prespecified 3-pt improvement in the mADL11 during the blinded lead-in. STUDY 1 · PLACEBO-CONTROLLED PARALLEL GROUP R 1:1 Ulixacaltamide Placebo PRIMARY ENDPOINT Change in modified TETRAS-ADL11 from baseline to Day 56 STUDY 2 · RANDOMIZED WITHDRAWAL BLINDED LEAD-IN · 8 WKS WITHDRAWAL · 4 WKS Ulixacaltamide Stable responders randomized Placebo Ulixacaltamide PRIMARY ENDPOINT Share of responders who maintain their response after withdrawal TREATMENT · 12 WKS Screening N = 711 Enrolled 2:1 Blinded to Study 1 or 2 N = 473 Randomized N = 238 Randomized

27 ESSENTIAL3 Baseline Demographics Illustrate Functional Disability and Disease Burden Ranked by share scoring 3–4. TETRAS-ADL = Essential Tremor Rating Assessment Scale – Activities of Daily Living. Source: Farmer et al. AAN 2026 Plenary Presentation; Praxis Data on File Baseline TETRAS-ADL score by activity, % of patients (n = 698) 69% 18% 40% 9% 8% 9% 5% 11% 39% 39% 38% 27% 31% 15% 9% 10% 10% 9% 17% 49% 53% 61% 61% 75% 81% 87% 86% 89% 92% 9% 7% Speaking Social impact Dressing Using keys Hygiene Working Writing Drinking Feeding Carrying Pouring Overall disability Score: 0 1 2 3 4 0 = no impact · 4 = unable to perform 31 / 48 mean baseline TETRAS-ADL score 30 years average time living with ET 94% had worsening symptoms in the past 3 years

28 STUDY 2 · RANDOMIZED WITHDRAWAL Clinical Program Solidifies Core Strengths of Ulixacaltamide -4.3 -1.7 p < 0.0001 ULIXACALTAMIDE (n=199) PLACEBO (n=233) 55% 33% p = 0.037 ULIXACALTAMIDE (n=40) PLACEBO (n=40) Primary endpoint met Primary endpoint met mADL11: modified ADL 11-item score, CFB: change from baseline. Shtilbans et al. AAN 2026 Poster Presentation; Farmer et al. AAN 2026 Plenary Presentation STUDY 1 · PARALLEL GROUP Rapid Onset Maintained Effect Deep Response Consistent Robust Effect RESULTS SHOW STRENGTH ACROSS FIVE DIMENSIONS OF EFFICACYmADL11 CFB to Day 56 % Maintain Response

29 Rapid Onset of Effect Experienced by First Assessment (Day 14) Source: Shtilbans et al. AAN 2026 Poster Within 14 days patients saw significant improvement in their disease Rapid Maintained Deep Consistent Robust TETRAS-ADL change from baseline LS mean, points Placebo Study 2 Study 1 -7 -6 -5 -4 -3 -2 -1 0 Baseline Day 14 Day 28 Day 49 Day 56

30 Large Benefit Maintained Across 12 Weeks Across Stringent Response Thresholds MCID = minimum clinically important difference (−1.25 mADL11 points). ROC: receiver operating characteristic. Error bars are 95% CI. Source: Farmer et al. AAN 2026 Plenary Presentation Rapid Maintained Deep Consistent Robust mADL11: Proportion Achieving MCID-Based Improvement Thresholds, Study 1 MCID = −1.25 (ROC Youden J, D56) | ITT Analysis Set 0% 20% 40% 60% 80% Day 56 Day 84 Day 56 Day 84 Day 56 Day 84 Placebo Ulixacaltamide ≥1x MCID ≥2x MCID ≥3x MCID

31 Maintenance of Response and Pharmacological Response is Further Confirmed After Patients Switched to Placebo mADL11: modified 11-item TETRAS-ADL score; CGI-S: Clinical Global Impression of Severity; PGI-S: Patient Global Impression of Severity; PGI-C: Patient Global Impression of Change. Net % change = lead-in % + withdrawal %; negative means improvement retained at Day 84. Error bars are 95% CI. Source: Farmer et al. AAN 2026 Plenary Presentation. Rapid Maintained Deep Consistent Robust Net improvement after withdrawal, Study 2 Net % change at Day 84 -50% -40% -30% -20% -10% 0% 10% mADL11 CGI-S PGI-S PGI-C Stayed on ulixacaltamide Switched to placebo Δ 28% Δ 15% Δ 21% Δ 14%

32 Effect of Ulixacaltamide Treatment is Maintained Over Years, Despite ET’s Progressive Course Essential3 Protocol amended to add TETRAS-ADL Assessment in Study 3 Long Term Safety Study (LTSS); Collection began November 2026 and is ongoing for participants in Study 3 who completed Study 1 or Study 2, n=68 assessed to date with average duration of 95 weeks in study. Rapid Maintained Deep Consistent Robust -7 -6 -5 -4 -3 -2 -1 0 AD L ch an ge fr om b as el in e ADL improvement over time, ESSENTIAL3 LTSS Change from baseline · Observed mean ± SE, n= 68 Baseline Week 12 Week 95 −3.0 −6.0 95 weeks ADL improvement held through nearly 2 years of treatment in the ESSENTIAL3 LTSS

33 Patients Experienced Significant Gains in Daily Functioning Treatment difference p < 0.01 at all responder thresholds (logistic regression). Source: Shtilbans et al. AAN 2026 Poster Patients reaching Responder TETRAS-ADL Thresholds at Day 56 % of ulixacaltamide patients combined Study 1 and Study 2 (N = 474) 19% of ulixacaltamide patients improved by 12 or more TETRAS-ADL points by Day 56. 12 points Equivalent to an improvement across each of the 12 daily activities19% 25% 29% 33% 46% 62% ≥12 points ≥10 points ≥8 points ≥6 points ≥4 points ≥2 points Rapid Maintained Deep Consistent Robust

34 Results Were Consistent Across Multiple Endpoints and Subgroups From Two Independent Studies PGI-C: Patient Global Impression of Change; CGI-S: Clinical Global Impression of Severity. Source: Shtilbans et al. AAN 2026 Poster 0% 20% 40% 60% Placebo Study 1 Study 2 0% 20% 40% 60% Placebo Study 1 Study 2 Global impression responders at Day 56 % of patients PGI-C - Patient-rated CGI-S - Clinician-rated Rapid Maintained Deep Consistent Robust Improvement vs placebo by subgroup LS mean difference vs placebo, TETRAS-ADL points (95% CI) Study 1 Study 2 vs Study 1 placebo Age Sex Other ET meds Propranolol Intention tremor Family history <65 ≥65 Female Male No Yes No Yes No Yes No Yes -2 0 2 4 6 8 -2 0 2 4 6 8 Favors ulixacaltamide

35 Primary Benefit is Robust to Sensitivity Analysis MMRM (MAR) included baseline mADL11, treatment, categorical visit, treatment-by-visit interaction, and randomization strata, with unstructured covariance. MAR MI, copy-reference (CR), and tipping-point analyses each used 100 multiply imputed datasets, generated using MCMC for intermittent missingness followed by monotone regression for trailing missingness. CR used placebo-fitted conditional regression models. Tipping-point analyses added δ points to MAR-imputed values in ulixacaltamide participants missing data. Each completed dataset was analyzed by MMRM, with treatment contrasts combined using Rubin’s rules. BOCF replaced missing scores with baseline values before MMRM analysis. Rapid Maintained Deep Consistent Robust mADL11 treatment difference vs placebo, FDA focused sensitivity analyses LS mean difference vs placebo, points (95% CI); Day 56; Model-based analyses, ITT Analysis Difference (95% CI) Observed-data MMRM (MAR) 2.57 (1.53, 3.62) p < 0.0001 Multiple imputation (MAR) 2.59 (1.59, 3.59) p < 0.0001 Placebo-based imputation (MNAR; CR) 2.12 (1.16, 3.08) p < 0.0001 Baseline observation carried forward (BOCF) 1.41 (0.52, 2.29) p = 0.0019 -1 0 1 2 3 4 Favors ulixacaltamide Delta-shift tipping-point analysis, ITT Shift (δ), points Difference (95% CI) δ = 2.5 1.77 (0.73, 2.80) p = 0.0009 δ = 4.5 1.15 (0.08, 2.21) p = 0.0346 δ = 5.0 0.99 (-0.08, 2.06) p = 0.0696 -1 0 1 2 3 4 Favors ulixacaltamide

36 Ulixacaltamide Delivers Compelling Efficacy Profile Rapid Day 14 ~5 points gained in ADL at the first assessment Maintained 95 weeks benefit held through Day 84 and 95 weeks; lost when switched to placebo Deep ~1 in 5 patients improved 12 or more TETRAS-ADL points Consistent Multiple Endpoints consistent results from two independent studies across multiple endpoints and subgroups Robust 4 of 4 model-based sensitivity analyses stayed significant

37 U L I X A C A L T A M I D E Commercialization Strategy Erik Johnson

38 The Sleeping Giant is Ready to be Awakened with The First Targeted Drug Therapy Abbreviations: DSE, disease state education; DTC, direct-to-consumer; NP/PA, nurse practitioner/physician assistant; PA, prior authorization. M A R K E T D Y N A M I C S Highly prevalent disease Dormant market with little innovation in decades Adult population Broad stakeholder call point: neurologists, movement disorder specialists, neuro-like PCPs, NP/PAs K E Y S T O A S U C C E S S F U L L A U N C H PATH TO PERSISTENCE Titration program sets clear expectations for physicians and patients at initiation, and active support during maintenance, ensuring long-term persistence Quality over quantity: Success depends on a positive first experience for HCPs and patients Payer-aligned specialty pharmacy distribution network 1 2 3 EVERY FIRST EXPERIENCE IS FLAWLESS A large market means high PA volume, so the integrated HUB and SP network must be smooth with minimal burden on physicians DIRECT TO PATIENT ACTIVATION “Essential to Me” DSE campaign and subsequent DTC activate a dormant market and drive treatment discussions

39 HCPs are Naturally Aligned With the Profile of Ulixacaltamide Source: HCP observational quant study, March 2026 (N = 2,303 US physicians treating ET). 0% 0% 1% 8% 21% 33% 36% 1 2 3 4 5 6 7 0% 1% 3% 11% 25% 35% 25% 1 2 3 4 5 6 7 90% Regaining one function is meaningful (e.g. brushing teeth, pouring coffee) 1 = unfavorable · 7 = favorable 85% comfortable counseling on titration and tolerability 1 = disagree · 7 = agree 0% 0% 1% 6% 20% 36% 36% 1 2 3 4 5 6 7 92% Maintaining function over time is clinically meaningful 1 = disagree · 7 = agree

40 HCPs View Ulixacaltamide Favorably and are Motivated to Prescribe to their ET Patients Source: HCP observational quant study, March 2026 (N = 2,303 US physicians treating ET). 0% 1% 2% 9% 35% 42% 12% 1 2 3 4 5 6 7 88% rate ulixacaltamide’s overall profile as favorable 1 = unfavorable · 7 = favorable I N I T I A L A D O P T I ON I N T E N T 36% Mean % of each physician’s ET patients Today’s typical treatment approach for patients when symptoms… 18% I aim to treat as early as possible 41% Begin to interfere with 1 routine daily activity 31% Interfere with multiple daily activities/work tasks 10% Are highly disruptive, substantial disability 90% treat before symptoms become highly disruptive

41 The ESSENTIAL TO METM DSE Campaign has been Successful in Driving Confidence to Treat and Empowering Patients to Seek Care HCPs will recognize:  ET as a serious disease warranting active treatment  The importance of ADL-based functional improvement  The importance of proper use of ICD-10 G25.0 diagnosis code at the point of care Patients will see:  An opportunity for better management and the confidence to re-engage with their HCPs  Their lived experience with ET as reason enough to seek care

42 DTC Will Further Mobilize the Market at Launch FOR INITIAL LAUNCH FOR LONG-TERM Drives Awareness • Empowers patients to raise ET with their HCP now Engages Undertreated & Discontinued Patients • Reframes ET as actionable and treatable Addresses ET Underdiagnosis • A new treatment drives reason for diagnostic coding • Patients often dismiss tremor as normal aging rather than a treatable condition • Drive patient self-recognition and prompt a diagnostic conversation Direct-to-patient recruitment established the capability to deploy for commercialization DSE campaign performing better than ESSENTIAL3 metrics

43 With Neurologists Ready to Treat, Praxis Adds Support From the First Prescription Through Maintenance THE NEUROLOGIST PERSPECTIVE Strong enthusiasm for the profile Rapid onset Once-daily dosing Adjunctive to current ET meds CONVERSATION BEFORE THE FIRST PATIENT A Praxis conversation with each physician before their first patient starts therapy Neurologists routinely manage tolerability with titrated CNS drugs Not viewed as a barrier to prescribing HCP COUNSELS PATIENT Discuss expectations for treatment and titration phase COMPREHENSIVE SUPPORT FOR INITIATION AND PERSISTENCE Tailored services to support titration experience and retention PRAXIS SUPPORT

44 The Hub of the Future Fully Integrates the Rx Writing, Patient Services and Specialty Pharmacy Abbreviations: EHR, electronic health record. BI/BV benefits investigation/benefits verification 1 PRESCRIBE Prescribe from the EHR The prescription goes straight from the EHR with required info 2 GET ACCESS Coverage answered fast Benefits verified the same day; Hub routes eRx to correct in-network SP post- BI/BV 3 START THERAPY Engaged within minutes Outreach begins within minutes of the eRx; Real- time status for Patients and Offices 4 STAY ON THERAPY Continued support Enhanced services tailored to support titration and adherence Digital Prescription Intake Specialty Pharmacy Distribution Office & Patient Support COMMERCIAL DATA FOUNDATION (CDF) Real-time view of patients, prescribers, payers and channel

45 Praxis Has Built Supply and Distribution Ahead of Approval so Patients Get Ulixacaltamide From Day One Specialty Pharmacy Network Product Supply CDMO Network 3PL Patient S U P P L Y I N V E S T M E N T A N D P R E P A R E D N E S S A L I G N T O P A Y E R - O W N E D P H A R M A C I E S Proactively invested to ensure we are well- positioned to meet anticipated demand and distribution needs Account for the majority of covered lives across Medicare Part D

46 Price Corridor Captures Value While Maintaining Access Gross annual price for selected analogs; not to scale. Austedo: WAC $5,278.17/60 × 6 mg tablets, $5,937.96/60 × 9 mg tablets and $7,917.14/60 × 12 mg tablets. Ingrezza: WAC $9,072/30 × 80 mg capsules. Nuplazid: WAC $5,120/30 × 34 mg capsules. Juvmo: WAC $4,900/30 tablets at each maintenance strength (5, 10 and 15 mg). Rezdiffra: WAC $4,239.38/30 tablets at each strength (60, 80 and 100 mg). Abbreviations: HD, Huntington’s disease; MASH, metabolic dysfunction-associated steatohepatitis; PD, Parkinson’s disease; TD, tardive dyskinesia; WAC, wholesale acquisition cost P R I C I N G P R I N C I P L E S • Responsible launch pricing to maximize drug value without restricting access • Launch price benchmarked to in-market analogs • Reflect first-in-class value and demonstrated clinical benefitU L I X A C A L T A M I D E P R I C I N G C O R R I D O R $50K–$100K WAC per year PRICE DISEASE U.S. PREV. ~$110K TD + HD chorea ~1.5M ~$110K TD + HD chorea ~1.5M ~$62K PD psychosis ~1M ~$52K F2–F3 MASH ~7–9M ~$60K PD ~1M

47 The Scale of Unmet Need in ET Means Every Point of Penetration Generates Blockbuster Sales ILLUSTRATIVE SALES MATH 2M ET patients seeking treatment today × 1% penetration × $50K annual net price = $1B annual revenue Source: Internal claims analysis

48 The Opportunity is Vast, and Our Launch is Built to Match It Illustrative. Peak sales = 2M ET patients seeking treatment × penetration × $50K annual net price. Avg. analyst model: mean peak patients on drug across sell-side models ÷ 2M. HCP study: mean % of ET patients physicians would prescribe to (March 2026, N = 2,303). Penetration Drivers First ET-specific therapy Standard of care is ineffective and poorly tolerated DTC empowers patients to start the conversation with their physicians Field team at scale deployed from day 1 ANNUAL PEAK SALES By penetration of 2M ET patients seeking treatment 1% 10% Avg. analyst model 36% HCP study $1B $10B $36B No near-term competition in clinical development

49 U L I X A C A L T A M I D E Activating Demand and Pull Through John Bullock

50 Precision Targeting Puts Our Field Team in Front of the Physicians Who Matter Most – Driving Impact S T E P 1 Identify diagnosed ET patients Through diagnosis and Rx claims S T E P 2 Map to their physicians All specialties identified for each patient S T E P 3 Rank on ET impact Based on factors such as treatment initiations, diagnosis, etc. T R E A T I N G P H Y S I C I A N S I D E N T I F I E D B Y S P E C I A L T Y Academic neurologist Community neurologist NP/PA in neurology Geriatric medicine Primary care Other

51 Every Key ET Prescriber Is Covered by a ~300 Field Team with Capacity for Dynamic Targeting ~19K WHO WE CALL ON target HCPs, where ET patient volume and influence are concentrated = 13 - 15K Neurologists Top-tier neurologists, including movement disorder specialists 4.5 - 5.5K PCPs High-volume, high-influence primary care physicians +

52 Offices Are Ready Before the First Patient Asks: Educated, Prepared and Connected PRE-APPROVAL DISEASE EDUCATION OFFICE OPERATIONS HCP EDUCATION First new ET therapy in decades; data consistent with label READINESS FOR PATIENT DIALOGUE Set expectations for rapid onset and possible common side effects AWARENESS OF THE PRAXIS HORIZONS HUB An integrated digital pathway supports smooth patient access while keeping burden off physicians and offices AT LAUNCH STANDARD Rx WORKFLOW FDA APPROVAL

53 A High-Touch Experience Supports Initiation, Maintenance and Adherence 1 WELCOME Set expectations Pharmacist call covers the disease, product and side effects to expect 2 EARLY TITRATION Manage tolerability Nurse or pharmacist check-ins 3 DOSE PROGRESSION Confirm readiness Confirm the patient is ready to advance; escalate to the prescriber if tolerability concerns 4 MAINTENANCE Prevent gaps Coordinate the maintenance refill so therapy continues without interruption 5 PERSISTENCE Protect therapy Refill outreach, adherence monitoring

54 Broad Ulixacaltamide Coverage Expected with a Predictable Path to Treatment OUR ACCESS OBJECTIVE Broad coverage aligned with the anticipated label Launch 3-6 months Ongoing Launch and early access As payer policies develop ~65% Medicare Part D Formulary exception requests available at launch; approvals depend on clinical justification EXP ECTED REQUIREMENTS Prior authorization: diagnosis confirmation and specialist consultation Step therapy: Propranolol first step may be required~30% Commercial Some plans apply new-to-market exclusions until P&T review; exception availability varies

55 01 A large and growing market 02 A therapy patients need and physicians want 03 The people, systems and strategy to deliver A Large Market, the Right Drug and a Launch Built to Win

56 D E V E L O P M E N T A L & E P I L E P T I C E N C E P H A L O P A T H I E S Relutrigine First medicine designed for SCN2A and SCN8A DEEs Dec 27, 2026 PDUFA date

57 Sodium Channels are Key in Seizure Activity in DEEs Illustrative. Scheffer et al. Nat Rev Dis Primers. 2024; Wengert et al. J Neurosci. 2021; Guerrini et al. Physiol Rev. 2023; Berecki et al. PNAS. 2018. Abbreviations: AP, action potential; DEE, developmental and epileptic encephalopathy; NaV, voltage-gated sodium channel NaV channels are either the primary genetic cause of hyperexcitability or the point where diverse upstream causes converge Healthy neuron AP output SCN2A / SCN8A DEE Direct mutation of NaV1.2 and NaV1.6 channels AP output Broad DEEs AP output Normal NaV Channels Hyperexcited NaV Channels Hyperexcited NaV Channels Upstream dysfunction (e.g., genetic, acquired, idiopathic) mV 30 0 –70 0 100 200 300 mV 30 0 –70 0 100 200 300 mV 30 0 –70 0 100 200 300

58 Children and Families Face Severe Disease Burden Living with SCN2A and SCN8A DEEs Photos shared at Praxis 2024 DEEP Dive Day. Sources: Zuberi SM, et al. Epilepsia. 2022; Gallop K, et al. Epilepsy Behav. 2021; Thurman DJ, et al. Epilepsia. 2014; CHOP SCN2A-related disorders. No medicine has ever been specifically designed for children with SCN2A or SCN8A DEEs W H A T T H E C H I L D F A C E S W H A T T H E F A M I L Y S H O U L DER S Profound developmental delay Lifelong supportive care High seizure rate from birth Management of multiple medications with burdensome administration A shortened life The risk of early loss

59 R E L U T R I G I N E EMBOLD: First Study Ever Done For SCN2A and SCN8A DEE Patients Steve Petrou

60 EMBOLD Enrolled a Severe Population of SCN2A/8A Patients ASM=antiseizure medication; OLE=open-label extension. Source: Kamireddy et al. AES 2025; Frizzo et al. IEC 2025; NCT05818553 PATIENT PROFILE Heavily pre-treated pediatric SCN2A/SCN8A population ASMs at baseline: ~1/3 1–2 ASMs ~2/3 3–6 ASMs ~55 Median motor seizures per month at baseline; highly skewed, with many patients >100 DOUBLE-BLIND TREATMENT · 16 WKS (4 × 4-WK PERIODS) WKS 1–4 WKS 5–8 WKS 9–12 WKS 13–16 OLE COHORT 1 · 0.5 MG/KG/DAY R 1:1 Relutrigine n=8 Placebo arm n=8 COHORT 2 · 1 MG/KG/DAY R 1:1 Relutrigine n=28 Placebo arm n=25 Relutrigine Placebo PRIMARY ENDPOINT Change from baseline in monthly motor seizure frequency calculated as the period on relutrigine versus period on placebo

61 Significant Seizure Reduction in the EMBOLD Study Primary endpoint: placebo-adjusted change in monthly (28-day) motor seizure frequency, Cohort 2. Primary analysis used NB1 regression, adjusted for baseline motor-seizure rate and treatment-evaluable days. Relutrigine periods from both randomized arms were compared with Arm B’s placebo period: 53 participants contributed 51 relutrigine and 25 placebo treatment-period records. The two-sided interim significance boundary was 0.04. Source: Kamireddy et al. AES 2025; Bialer et al. Epilepsia 2026 53% PRIMARY ENDPOINT placebo-adjusted reduction in motor seizures p < 0.0002 66% KEY SECONDARY ENDPOINT increase in motor seizure-free days vs. placebo p = 0.0340 Best-in-Disease Efficacy Seizure Freedom Functional Gains Well-Tolerated Patient Centric BENEFITS ACROSS MULTIPLE DIMENSIONS

62 Unprecedented Seizure Reduction Deepening Over Time Months with at least 10 contributing participants are shown. Data cutoff 14 August 2026. Month 5 (start of open-label period), n=67; Month 6, n=67; Month 7, n=66; Month 8, n=65; Month 9, n=61; Month 10, n=57; Month 11, n=54; Month 12, n=49; Month 13, n=39; Month 14, n=31; Month 15, n=25; Month 16, n=21; Month 17, n=14; Month 18, n=10. OLE=open-label extension. Deepening Response Seizure Freedom Functional Gains Well-Tolerated Patient Centric Reduction in motor seizures by months of exposure % change from baseline in monthly motor seizures 86% seizure reduction at 18 months 98% of eligible patients continued into the OLE-90% -80% -70% -60% -50% -40% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

63 Patients Experienced Significant Increase in Seizure-Free Days Source: Kamireddy et al. AES 2025; Bialer et al. Epilepsia 2026 Best-in-Disease Efficacy Seizure Freedom Functional Gains Well-Tolerated Patient Centric Days without a motor seizure Mean days per 28 days, 16-week double-blind period +66% more motor seizure-free days on relutrigine than on placebo (p=0.034) 10.4 days 17.3 days Placebo Relutrigine ~7 additional seizure-free days per month

64 Gains Observed Across Multiple Areas Beyond Seizures Source: Kamireddy et al. AES 2025; Bialer et al. Epilepsia 2026 Best-in-Disease Efficacy Seizure Freedom Functional Gains Well-Tolerated Patient Centric Participants improving by domain, last visit on relutrigine % of Cohort 2 participants, clinician- vs caregiver-rated Clinician Caregiver 35% 67% 78% 78% 27% 53% 78% 78% Disruptive behavior Communication Alertness Seizure severity & intensity Global impression of improvement vs placebo Adjusted difference at last visit (95% CI) Clinicians and caregivers both saw statistically significant functional improvement over placebo -2.62 -3.70 -7 -6 -5 -4 -3 -2 -1 0 CGI-I CgGI-I p<0.0001 p=0.002

65 Relutrigine Was Well Tolerated, With No Drug-Related SAEs No clinically significant findings in vital signs, laboratory results, physical exams or ECGs. AE=adverse event; ASM=antiseizure medication; ECG=electrocardiogram; SCB=sodium channel blocker; SAE=serious adverse event; TEAE=treatment-emergent adverse event. Source: Kamireddy et al. AES 2025; Bialer et al. Epilepsia 2026 Best-in-Disease Efficacy Seizure Freedom Functional Gains Well-Tolerated Patient Centric No drug-related SAEs; all SAEs consistent with disease background Mostly mild-to-moderate AEs; no dose reductions were required Tolerated with complex regimens: 3–4 concurrent ASMs, 79% on SCBs Minimal drug-drug interactions, given relutrigine's selectivity Adverse event Relutrigine Placebo Pyrexia 11.7 13.4 Upper respiratory infection 9.8 4.5 Somnolence 9.1 13.4 Irritability 5.2 4.5 Diarrhea 4.6 8.9 Constipation 3.9 8.9 Cough 3.9 0.0 Vomiting 3.9 8.9 Most common TEAEs, rate per 100 patient-months of exposure, Cohort 2

66 Relutrigine Offers a Patient-Friendly Dosing and Administration Paradigm G/J tube=gastrostomy/gastrojejunostomy/jejunostomy tube. Best-in-Disease Efficacy Seizure Freedom Functional Gains Well-Tolerated Patient Centric Once Daily • One dose a day for patients and caregivers No Titration • No dose titration or tapering required • Seizure reduction seen from Month 1 Flexible Administration • Liquid formulation suitable for oral or G/J tube delivery • Compatible with ketogenic diet • May be taken with or without food

67 Relutrigine Sets a New Bar in SCN2A/8A DEE Across Every Dimension SAE=serious adverse event. Source: Kamireddy et al. AES 2025; Bialer et al. Epilepsia 2026 Best-in-Disease Efficacy -86% mean reduction at 18 months in the OLE Seizure Freedom 7 more motor seizure-free days than placebo in Cohort 2 Functional Gains 78% improved in alertness, as rated by clinicians and caregivers Well-Tolerated 0 drug-related SAEs and no dose reductions required Patient Centric 1× daily dose with no titration, keto- friendly and given orally or by G/J tube

68 What Positions Relutrigine for Efficacy in EMERALD? EMBOLD COMPLETED · POSITIVE P O P U L A T I O N SCN2A, SCN8A DEEs N a V C H A N N E L S Mutated EMERALD TOPLINE 4Q26 P O P U L A T I O N Broad DEEs >50 etiologies N a V C H A N N E L S Mostly normal The unique biophysical actions of relutrigine demonstrate why it is uniquely positioned for efficacy in broad DEEs with non-NaV etiologies

69 Diverse DEE Genes Converge on the Common Output Stage AIS, axon initial segment; DAPC, dynamic action-potential clamp; DEE, developmental and epileptic encephalopathy. Data: Berecki (Florey Institute) DAPC; AIS physiology: . RELUTRIGINE REDUCES NEURONAL FIRING IN WT NAV CHANNELS DAPC Firing evoked by 12 pA and 6 pA current injection Yes, and diverse DEE genes converge on NaV- dependent spike generation at the axon initial segment B A S E C A S E — E F F I C A C Y E S T A B L I S H E D SCN2A, SCN8A Changes in the spike generator itself H A R D E S T C A S E - S H A R P E S T D I F F E R E N T I A T I O N SCN1A loss of function in Dravet Disinhibited networks burst through wild-type Naᵥ KCNQ2, KCNQ3 M-current brake shares the AIS compartment KCNA1, KCNA2 Low-threshold K⁺ current raises spike threshold KCNT1, KCNH1 More K⁺ current reducing interneuron output HCN1 Iₕ cation leak raises intrinsic excitability STXBP1, SLC6A1, CDKL5 Synaptic and network drive onto wild-type Naᵥ Phenotype-selected patients Selected on firing phenotype, not gene name A XO N I N IT IA L SE GM EN T IS THE TARGET PRESENT WHEN THE NAV CHANNELS ARE NORMAL? DEE MUTATIONS CAN DIRECTLY OR INDIRECTLY INVOLVE THE AIS

70 Targeting Activity-Dependent Current – Recovery from Fast Inactivation Praxis data on file. Berecki (Florey Institute) Yes, NaV availability falls ~25% at burst rates, but only ~3% at sparse 1–2 Hz firing RECOVERY FROM FAST INACTIVATION (WT NAV1.2) WHAT THAT MEANS FOR A FIRING NEURON CAN THE DRUG TELL PATHOLOGICAL FIRING FROM NORMAL FIRING?

71 Persistent Current Sustains Pathological Firing Whether or Not the Channel Is Mutated Praxis data on file. Berecki (Florey Institute) Abbreviations: INaP, persistent sodium current. No, a lower baseline current reaches the critical level with a smaller reduction V424L · INaP unaltered 89% AUC inhibition F1651C · INaP increased 60% AUC inhibition FIRING INHIBITION VS. PERSISTENT CURRENT PHENOTYPE INHIBITION NOT DEPENDENT ON INaP BASE LEVEL IS NORMAL INaP A HARDER TARGET THAN ELEVATED INaP?

72 A Severe, Diverse Population Means EMERALD Results Will Apply Across the Entire DEE Spectrum ASM, antiseizure medication Baseline characteristics · median age 13 years HIGH, EARLY-ONSET SEIZURE BURDEN BROAD, REPRESENTATIVE ETIOLOGIES SIGNIFICANT FUNCTIONAL IMPAIRMENT 58 median motor seizures per 28 days at baseline 3 median ASMs before dosing 56% seizure onset before age 1 >50 distinct genetically defined pathological etiologies 51% unable to walk independently 31% unable to sit independently 21% tube used for food and/or medications 58% 36% 6% Genetic Other/Unknown Structural

73 R E L U T R I G I N E Commercialization Strategy Erik Johnson

74 SCN2A and SCN8A Market Opportunity Demands a High-Touch, Specialized Execution Model M A R K E T D Y N A M I C S Ultra-rare disease Activated and engaged market among those diagnosed Caregivers and children Centers of excellence and specialized pediatric neurologists Single-specialty pharmacy distribution W H A T I T M E A N S F O R L A U N C H High-touch & specialized • Every family engaged one-to-one • Field teams built around centers of excellence • Support from first script through refills

75 For SCN2A and SCN8A Families, a Long and Complicated Journey Begins at Birth Data source: Internal claims data. Abbreviations: ASM, anti-seizure medication; DEE, developmental and epileptic encephalopathy; ER, emergency room INITIAL MANIFESTATION Early onset, rapid progression and developmental delays TREATMENT Formal diagnosis usually within the first 18 months DIAGNOSIS Seizure severity prompts treatment before diagnosis MANAGEMENT Families struggle to find a regimen that works Symptom onset present with seizures ER or primary care Seizure urgency speeds entry into care Neurologist ~50% seen within 2 months Genetic diagnosis ~45% diagnosed within 6 months Early treatment ASMs before diagnosis Treatment cycling Continuous ASM Adjustment Active management 60–70% managed at academic centers Compared to the broader DEE population, SCN2A/SCN8A patients follow a more acute, seizure-driven entry into care

76 With No Guidelines or Targeted Options, DEE Seizures Persist Despite Aggressive Off-Label Polytherapy Quotes and ASM figures from HCP market research. Abbreviations: ASM, anti-seizure medication; CDKL5, CDKL5 deficiency disorder; LGS, Lennox-Gastaut syndrome; TSC, tuberous sclerosis complex T H E C U R R E N T S T A N D A R D O F C A R E F O R D E E s No guidelines or established treatment algorithm Treatment reacts to seizure presentation; no defined order exists for SCN2A/SCN8A or broader DEEs A fragmented landscape Generic ASMs used in combination; the few branded options are used on label for Dravet, LGS, TSC and CDKL5 Seizures persist despite aggressive polytherapy HCPs struggle to achieve monotherapy, escalating doses and adding ASMs; patients average 2.6 ASMs and 78% are not seizure-free

77 HCPs Value Relutrigine Profile of Improved Efficacy and Quality of Life and Intend to Broadly Use it Data on File; Analysis is based on DEE Treaters from Quantitative Research conducted (N=128); Abbreviations: ASM: Anti-Seizure Medication; DEEs: Developmental and Epileptic Encephalopathies; HCP: Healthcare Provider P E R C E I V E D V A L U E Attributes HCPs rate significantly better than current therapies: E X P E C T E D U S E 98% of HCPs shown the blinded relutrigine profile expect to use it HOW THEY EXPECT TO USE IT 10% 41% 47% As monotherapy only Both monotherapy and in combination In combination with other ASMs Efficacy Quality of life Tolerability

78 The Hub of the Future Accelerates Relutrigine Access and Delivers White-Glove Support for Every Family Abbreviations:; EHR, electronic health record. P R E S C R I P T I O N I N T A K E Praxis Horizons Digital Pharmacy • Receives e-Rx via EHR • Immediate text to patient/caregiver • Starts BI, PA and access support the same day C O O R D I N AT I O N Praxis In-House Care Coordinator • Case oversight • Logistics for Patient Services Programs • Personalized ongoing support to offices and families E D U C A T I O N Praxis In-House Patient Education Liaison • Disease and treatment education • Dosing support • Setting expectations • Resource navigation F U L F I L L M E N T Single Specialty Pharmacy • PA managed by dedicated access specialists • Dispenses and delivers medication COMMERCIAL DATA FOUNDATION (CDF) Real-time view of patients, prescribers, payers and channel

79 • Launch pricing to maximize drug value without restricting access • Benchmarked to rare-disease analogs, led by SEPHIENCE as the latest launch • Other branded DEE drugs are widely recognized as significantly underpriced, making them not the most relevant comparators P R I C I N G P R I N C I P L E S ~5KFA~$415K ~10KSMA~$430K ~12KPKU~$622K ~1–1.5KHPP~$1,800K U.S. PREV.DISEASEPRICE R E L U T R I G I N E P R I C I N G C O R R I D O R $400K–$600K WAC per year Relutrigine Pricing Strategy Balances Value With Access Strensiq: WAC $68,983.20/12 × 80 mg vials. Weight reference: Seefried et al. Bone. 2023; (doi:10.1016/j.bone.2023.116856). Sephience: WAC $15,735/30 × 1,000 mg packets and $3,933.75/30 × 250 mg packets. Weight reference: AMPLIPHY trial, Metabolism. 2026. Evrysdi: WAC $35,335.70/30 × 5 mg tablets. Skyclarys: WAC $34,019.51/90 × 50 mg capsules. Abbreviations: FA, Friedreich ataxia; HPP, hypophosphatasia; PKU, phenylketonuria; SMA, spinal muscular atrophy; WAC, wholesale acquisition cost

80 Precedents Show List Prices Held Steady Even as Labels Expanded to Populations up to 20x Larger than Launch Index = WAC (list price before rebates and discounts) per unit on the day before expansion approval = 100. Kalydeco → Trikafta indexed on cost per day of therapy at labeled adult dose, switching products at Trikafta approval (10/21/2019). Brukinsa’s annual increase took effect 1/12/2023, one week before CLL approval. Populations approximate. Sources: Bloomberg (WAC, as of 10/21/2026); Alnylam, Alexion and Vertex estimates; published PNH and gMG prevalence; American Cancer Society. DRUG INITIAL LABEL EXPANDED LABEL US PATIENTS Amvuttra vutrisiran · Alnylam Hereditary ATTR polyneuropathy (2022) ATTR cardiomyopathy, incl. wild-type (Mar 2025) ~10K → ~200K prevalence Soliris eculizumab · Alexion PNH (2007) AChR+ generalized myasthenia gravis (Oct 2017) 5-8K → ~50K+ label-eligible prevalence Brukinsa zanubrutinib · BeOne Relapsed/refractory mantle cell lymphoma (2019) CLL/SLL, including first line (Jan 2023) ~25K → ~240K new US cases/yr Kalydeco → Trikafta Vertex Kalydeco: CF gating and residual-function mutations (2012–17) Trikafta: ≥1 F508del allele, age 12+ (Oct 2019) ~3K → ~18K eligible at launch Expansion -36 -24 -12 0 12 24 36 Months from expansion approval $406K $477K $549K $432K $509K $585K $150K $176K $203K $265K $312K $358K ANNUALIZED LIST PRICE PER PATIENT ($K)

81 Most SCN2A/8A Patients Are Invisible in Data, Not to Our Field Team Each dot ≈ 100 patients. 1. GeneDx and Invitae genetic testing data tokenized to Komodo claims plus 2025 GeneDx results. 2. Sederman R, et al. AES 2022 Poster 1.409: 3. Diagnosis rate from Musante L, et al. Genes 2022. ~1.9K Visible in Genetic and Claims Data1 ~5K Diagnosed2 10K+ Prevalent3 Field team profiling has already identified more patients than in the genetic and claims data

82 Beyond SCN2A/8A, more Than 300K DEE Patients Still Lack Effective Treatment Each dot ≈ 100 patients, drawn to scale; SCN2A/8A ~10K (Musante L, et al. Genes 2022). Poke G, et al. Neurology 2023;100:e1363–e1375, Sederman R, et al. AES 2022 poster 1.409. DEE, developmental and epileptic encephalopathy. ~10K SCN2A/8A>300K broad DEE 30× High Unmet Need Remains Majority of DEE patients lack treatment options that are: Effective Durable Targeted B R O A D D E E P O P U L A T I O N

83 SCN2A/SCN8A Alone Supports a $1B Peak, While Minimal Penetration into the Broad DEE Market Could Add Multi-Blockbuster Potential Each dot ≈ 100 patients. Illustrative; assumes $400K net annual price. I L L U S T R A T I V E P E A K S A L E S : 2,500 SCN2A/8A patients $1B 25% penetration of ~10K prevalent patients 10,000 broad DEE patients $4B 3.3% penetration of >300K broad DEE $5B combined peak revenue 12.5K patients, ~4% of >300K

84 R E L U T R I G I N E Field Readiness for First SCN2A & SCN8A Targeted Therapy John Bullock

85 Deep Where Patients Concentrate, Broad Enough to Reach Everyone 100% Coverage From Day 1 Abbreviations: HCO, healthcare organization; HCP, healthcare provider, Data based on Claims Data HCOs treating known & diagnosed SCN2A/8A patients Dots = HCOs with treating HCPs; shading = known patients by state HCO Known SCN2A/8A patients: low high Top 200 Accounts ~65% of known & diagnosed patients

86 Prescribing Patterns Allow Us to Extend the Reach to HCPs Who Will Help Us Find Patients Source: Internal Claims Data. 52% of first ASM prescriptions come from pediatric neurologists ~75% of claims for branded ASMs are from pediatric neurologists 0% 2% 4% 8% 14% 19% 52% Genetics PCP Neurology Neuro NP/PA Other Pediatrics Pediatric neurology 74% 76% 75% 74% 14% 12% 16%Ztalmy (N=160) Fintepla (N=2.2K) Epidiolex (N=15.3K) Diacomit (N=516) Pediatric neurology Neuro NP/PA Neurology Pediatrics Other

87 Dedicated Field Team in Place Ready to Activate and Engage Critical Stakeholders Sales Medical Affairs Patient Services Sizing Enables Full Coverage at Launch Enables the team to shift coverage as more patients are identified, without disruptive changes after launch Foundation ready to expand for broader DEE Supporting Caregivers and Patient Access Experienced team to work with families and caregivers transitioning onto relutrigine KOL & Scientific Exchange Profile of relutrigine as a precision sodium channel modulator, clinical results and safety profile

88 Field Team Has Reached Every Priority Account Ahead of PDUFA 100% of top 10 accounts per territory 100% of Tier 1 and Tier 2 target HCPs As of today, the rare epilepsy field team has profiled: KEY INSIGHTS FROM ACCOUNT PROFILING SCN2A/8A and overall DEE patients under care confirmed EMR and prescription ordering dynamics Genetic testing workflow Office visit scheduling and key staff

89 Clear Unmet Need and Pre-Qualified Patients Point to Favorable Access for Relutrigine A C C E S S L A N D S C A P E P A Y E R M I X ~45% Medicaid ~50% Commercial Prescribed by a specialist Trial of prior ASMs Diagnosis confirmation Reauthorization criteria P A Y E R A C C E S S S T R A T E GY High unmet need Positions relutrigine as the only targeted therapy against the limited efficacy of current ASMs, supporting favorable placement Patients arrive pre-qualified for PA Early onset of disease leads to diagnosis; specialist confirmation and a prior ASM trial will usually be satisfied by the time a prescription is written Analogs support access Recent ultra rare pediatric analogs suggest reimbursement with manageable PA criteria E X P E C T E D P A C R I T E R I A

90 CEREBRUM SMALL MOLECULE PLATFORM Cerebrum utilizes deep understanding of neuronal excitability and neuronal networks and applies a series of computational and experimental tools to develop orally available precision therapies

91 Praxis Is Building on the T-Type Calcium Channel MOA on 3 Fronts Abbreviations: ASD, autism spectrum disorder; ET, essential tremor; PD, Parkinson’s disease; RLS, restless legs syndrome. T-TYPE CALCIUM CHANNEL 1 · NEW INDICATIONS Ulixacaltamide beyond ET Trials starting in PD, RLS and ASD 2 · NEXT-GEN MOLECULES Innovation in T-type Ca Inhibitors Pan-Cav3.x and isoform-selective molecules 3 · BETTER DELIVERY Once-weekly patch with Remagine Labs Easier to take, customizable dosing, better adherence

92 Praxis Is Building on the T-Type Calcium Channel MoA on 3 Fronts Abbreviations: ASD, autism spectrum disorder; ET, essential tremor; PD, Parkinson’s disease; RLS, restless legs syndrome. T-TYPE CALCIUM CHANNEL 1 · NEW INDICATIONS Ulixacaltamide beyond ET Trials starting in PD, RLS and ASD 2 · NEXT-GEN MOLECULES Innovation in T-type Ca Inhibitors Pan-Cav3.x and isoform-selective molecules 3 · BETTER DELIVERY Once-weekly patch with Remagine Labs Easier to take, customizable dosing, better adherence

93 Ulixacaltamide Line Extensions: One Target, Four Large Populations With Significant Unmet Needs 1. Louis ED, Ottman R. How many people in the USA have essential tremor? Tremor Other Hyperkinet Mov (N Y). 2014;4:259. 2. Allen RP, Walters AS, Montplaisir J, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med. 2005;165(11):1286-1292. 3. Marras C, Beck JC, Bower JH, et al. Prevalence of Parkinson’s disease across North America. NPJ Parkinsons Dis. 2018;4:21. 4. Zablotsky B, et al. Pediatrics. 2026. 5. Dietz PM, Rose CE, McArthur D, Maenner M. National and state estimates of adults with autism spectrum disorder. J Autism Dev Disord. 2020;50(12):4258-4266. 6. US Census Bureau. National population estimates by age, Vintage 2025. ET adjusted for population growth and age mix.¹ RLS reflects the moderate-to-severe population (2–3% of US adults).² ASD combines pediatric⁴ and adult⁵ prevalence applied to US Census Bureau Vintage 2025 population counts.⁶ Essential Tremor 1 ~9M Restless Legs Syndrome 2 ~5–8M Parkinson’s Disease 3 ~1M Autism Spectrum Disorder 4-6 ~8M US prevalence, millions of people …AND BEYOND

94 Ulixacaltamide’s Potential to Fill Treatment Gaps in PD, RLS and ASD Source: Pasquini et al, 2023; Silber et al, 2026; Praxis data on file INDICATION CURRENT TREATMENT UNMET NEED ULIXACALTAMIDE COULD OFFER PD Parkinson's disease Levodopa and other dopaminergic drugs • Tremor often resists dopaminergic therapy (≥38% with action tremor) • Rising doses drive motor fluctuations and dyskinesia Non-dopaminergic, tremor- specific option that could lower dopaminergic burden RLS Restless legs syndrome Gabapentinoids first line; dopamine agonists; opioids for refractory cases • Dopamine agonists cause augmentation in up to 70% of patients • Gabapentinoids and opioids bring sedation, fall and misuse risk Non-dopaminergic option with no mechanism for augmentation ASD Autism spectrum disorder Risperidone and aripiprazole, approved for irritability only • Antipsychotics cause weight gain and movement side effects • No approved treatment for core symptoms or other phenotypes Treatment aimed at core symptoms, beyond irritability

95 T-Type Channels Set the Thalamus's Firing Mode; When Gating Fails, Abnormal Bursts Reach the Cortex TTCC, T-type calcium channel. Spike trains are schematic, not recorded data. Matthews et al, 2023 THALAMUS Relays converging inputs to the cortex RELAY MODE Steady, faithful spikes BURST MODE Clustered bursts T-type channels set which mode the thalamus is in WHEN INHIBITORY GATING FAILS The thalamus loses control of the gain, timing and synchrony of signals sent to the cortex Hyperexcitability Neurons fire too easily Aberrant bursting Bursts fire when they should not Hyperconnectivity Circuits over-synchronize

96 Ulixacaltamide Blocks T-Type Channels at the Thalamus and at Each of Its Inputs Cav3, T-type calcium channel family; TRN, thalamic reticular nucleus. Spike trains are schematic, not recorded data. Cortex Thalamus Sensorimotor gating Thalamic reticular nucleus Cerebellum Movement timing Basal ganglia Movement planning and initiation Spinal cord Sensory input T-type sites ulixacaltamide blocks WHAT ULIXACALTAMIDE DOES 1 Blocks T-type channels All three subtypes (Cav3.1, 3.2, 3.3), dense in the thalamus, its TRN, the cerebellum and basal ganglia 2 Dampens excess bursting Resolves the abnormal rhythm 3 Leaves relay firing intact Normal signals still get through WITHOUT TREATMENT WITH ULIXACALTAMIDE Aberrant bursts Steady relay firing

97 Four Diseases, Four Circuits, One Common Target BGTC, basal ganglia–thalamocortical; CTC, cerebello-thalamo-cortical; DBS, deep brain stimulation; PLMS, periodic limb movements in sleep; STN, subthalamic nucleus; TRN, thalamic reticular nucleus; TTCC, T-type calcium channel; Vim, ventral intermediate nucleus. Source: Matthews et al, 2023; Helmich, 2018; Ferré et al, 2019; Tai, 2022; Murata et al, 2007; Jang, Takahashi & Huguenard, Sci Adv 2025 Cortex Thalamus Sensorimotor gating Thalamic reticular nucleus Cerebellum Movement timing Basal ganglia Movement planning and initiation Spinal cord Sensory input T-type sites ulixacaltamide blocks DISEASE DRIVER IMPLICATED CIRCUIT DISEASE PRESENTATION ET Rhythmic cerebellar bursts CTC Tremor oscillations in the thalamic Vim and cortical projections Tremor PD Dopaminergic denervation CTC + BGTC Vim tremor oscillations Tremor BGTC STN bursting Bradykinesia and rigidity RLS Iron deficiency; dopaminergic dysregulation Spinal cord, BGTC Hyperactive sensory cortical activity Sensory symptoms, urge to move, PLMS ASD TTCC gene variants TRN, sensory cortex TRN hyperactivity; hyperactive sensory cortex Sensory over- responsiveness; restricted, repetitive behaviors

98 Four Diseases, Four Circuits, One Common Target BGTC, basal ganglia–thalamocortical; CTC, cerebello-thalamo-cortical; DBS, deep brain stimulation; PLMS, periodic limb movements in sleep; STN, subthalamic nucleus; TRN, thalamic reticular nucleus; TTCC, T-type calcium channel; Vim, ventral intermediate nucleus. Source: Matthews et al, 2023; Helmich, 2018; Ferré et al, 2019; Tai, 2022; Murata et al, 2007; Jang, Takahashi & Huguenard, Sci Adv 2025 Cortex Thalamus Sensorimotor gating Cerebellum Movement timing T-type sites ulixacaltamide blocks DISEASE DRIVER IMPLICATED CIRCUIT DISEASE PRESENTATION ET Rhythmic cerebellar bursts CTC Tremor oscillations in the thalamic Vim and cortical projections Tremor

99 Both PD Motor Circuits Pass Through Ulixacaltamide Targets BGTC, basal ganglia–thalamocortical; CTC, cerebello-thalamo-cortical; DBS, deep brain stimulation; ET, essential tremor; GPi, globus pallidus internus; STN, subthalamic nucleus; Vim, ventral intermediate nucleus of the thalamus. Source: Helmich, 2018; Du et al, 2018; Miwa et al, 2011; Beurrier et al, 1999; Tai, 2022; Yang et al, 2014; Murata et al, 2007 Cortex Thalamus Sensorimotor gating Cerebellum Movement timing Basal ganglia Movement planning and initiation T-type sites ulixacaltamide blocks Parkinson's disease Tremor Vim thalamus • Dopamine loss in the BGTC drives tremor; the CTC sets its severity • PD tremor shares ET's Vim DBS response; • Ulixacaltamide is effective in a rat tacrine- induced tremor model Bradykinesia and rigidity STN and GPi bursting • STN bursting tracks bradykinesia and rigidity and is driven by T-type channels • Zonisamide, a partial T-type blocker, suppressed STN bursting in animals and improved PD motor symptoms in placebo-controlled trials Potential non-surgical, non-dopaminergic treatment for PD tremor and other motor symptoms

100 RLS Stems From Thalamic and Spinal Overexcitation DBS, deep brain stimulation; ET, essential tremor; GPi, globus pallidus internus; PLMS, periodic limb movements in sleep; STN, subthalamic nucleus; Vim, ventral intermediate nucleus. Source: Ferré et al, 2019; Clemens et al, 2006; Gorges et al, 2016; Winkelman & Wipper, 2026; Klepitskaya, 2018; Dulski, 2022; Kedia, 2004; Evidente, 2022; Casoni, 2020 Cortex Thalamus Sensorimotor gating Spinal cord Sensory input T-type sites ulixacaltamide blocks Restless legs syndrome WHERE THE OVEREXCITATION SITS Thalamocortical Worse in the evening and at rest • Low iron weakens adenosine control, so glutamate signaling rises • fMRI: sensory thalamic connectivity rises with severity Spinal sensorimotor Weaker descending (A11) dopamine control 80–90% of patients also have PLMS DBS CLUES: STIMULATION THAT CALMS THESE CIRCUITS EASES RLS STN PD + RLS Mixed, mostly favorable; new-onset RLS reported Cohorts Vim ET + RLS Lower RLS severity with stimulation on Study GPi Refractory RLS Sustained relief Case report Hypothesis: like DBS, T-type blockade with ulixacaltamide could dampen thalamocortical hyperexcitability and RLS severity

101 Ulixacaltamide Reversed ASD-Like Behaviors in Three Mouse Models BTBR, inbred mouse strain with ASD-like behaviors; Cntnap2, contactin-associated protein-like 2 knockout; Scn2a, sodium channel gene variant model; TRN, thalamic reticular nucleus. Grooming: 10–12 mice per group; open-arm time (elevated plus maze): 12 per group; asterisks mark significance vs vehicle, one-way ANOVA. BTBR positive control: baclofen 3 mg/kg i.p. Source: Praxis data on file Cortex Thalamus Sensorimotor gating Thalamic reticular nucleus T-type sites ulixacaltamide blocks Autism spectrum disorder WHY T-TYPE CHANNELS Genetics CACNA1G/H/I variants (Cav3.1–3.3) linked to ASD risk Cntnap2 mice Higher T-type currents; ulixacaltamide calmed the overactive TRN ULIXACALTAMIDE IN ASD MOUSE MODELS Repetitive grooming Cntnap2−/− · 30 mg/kg p.o. Grooming fell to wildtype level Repetitive grooming BTBR · 10 mg/kg p.o. As effective as baclofen Risk-taking Scn2aRX/+ · 30 mg/kg p.o. Back to wildtype level

102 PD Is the Lowest-Risk Line Extension; RLS and ASD Offer Larger Markets at Higher Risk Positioning is qualitative, based on internal assessment. Bubble area proportional to estimated US prevalence (RLS: moderate-to-severe).. Sources: Marras et al, 2018; Allen et al, 2005; Dietz et al, 2020; Pasquini et al, 2023; Silber et al, 2026; Praxis data on file Clinical risk vs. reward, ulixacaltamide line extensions Lower HigherCLINICAL RISK RE W A RD ( UN M ET N EE D × US P A TI EN TS ) PD ~1M ASD ~8M RLS ~5–8M PD · LOWER CLINICAL RISK Biology Tremor circuits shared with ET Execution ET tremor endpoints de-risk execution ASD · MEDIUM CLINICAL RISK Biology Thalamic link; 3 positive animal models Execution Untested endpoints, longer clinical program RLS · HIGHER CLINICAL RISK Biology Sensory driven; no reliable preclinical model Execution High placebo response typical of RLS trials

103 Praxis Is Building on the T-Type Calcium Channel MOA on 3 Fronts Abbreviations: ASD, autism spectrum disorder; ET, essential tremor; PD, Parkinson’s disease; RLS, restless legs syndrome. T-TYPE CALCIUM CHANNEL 1 · NEW INDICATIONS Ulixacaltamide beyond ET Trials starting in PD, RLS and ASD 2 · NEXT-GEN MOLECULES Innovation in T-type Ca Inhibitors Pan-Cav3.x and isoform-selective molecules 3 · BETTER DELIVERY Once-weekly patch with Remagine Labs Easier to take, customizable dosing, better adherence

104 Next-Gen T-Type Calcium Channel Inhibitors Cav3.x, T-type voltage-gated calcium channel isoforms (Cav3.1, Cav3.2, Cav3.3) 1 · D I S C O V E R 2 · D E S I G N Pan-Cav3.x Block all three T-type isoforms Isoform-selective Target Cav3 isoforms 3 · D I F F E R E N T IA TE 2 molecules entering first-in-human studies in 1H27 Target Engagement with Novel Molecule High-throughput screens for novel leads CaV3.x PROFILE TOLERABILITY TITRATION

105 Next-Gen Molecules Show a Distinct CaV3.x Profile From Ulixacaltamide 10 100 1,000 ULIXACALTAMIDE PRAX-050 IC50, nM, log scale (lower = more potent) CaV3.1 CaV3.2 CaV3.3 Tonic block (TB) Voltage dependent block (VDB) ULIXACALTAMIDE Most potent at CaV3.1, with a wide gap between tonic and voltage-dependent block PRAX-050 Flatter across CaV3.1–3.3, with a narrower gap between tonic and voltage-dependent block A distinct CaV3.x profile could produce a differentiated clinical profile

106 Praxis Is Building on the T-Type Calcium Channel MOA on 3 Fronts Abbreviations: ASD, autism spectrum disorder; ET, essential tremor; PD, Parkinson’s disease; RLS, restless legs syndrome. T-TYPE CALCIUM CHANNEL 1 · NEW INDICATIONS Ulixacaltamide beyond ET Trials starting in PD, RLS and ASD 2 · NEXT-GEN MOLECULES Innovation in T-type Ca Inhibitors Pan-Cav3.x and isoform-selective molecules 3 · BETTER DELIVERY Once-weekly patch with Remagine Labs Easier to take, customizable dosing, better adherence

107 Novel Delivery Technology Could Improve Patient Access, Dosing and Adherence: Active, Transdermal Patch Collaboration with Remagine Labs. Regulatory path and timing subject to FDA engagement. Abbreviations: ET, essential tremor; PK, pharmacokinetic. Electronic Transdermal Drug Delivery System (eTDDS). A low current controls drug delivery into the bloodstream with one patch holding about a week of drug. Drug delivery can be controlled through wireless interface. ACCESSIBILITY No pill bottles to open; built for a segment of the population TITRATION Fully customizable dosing, adjustable remotely from the physician’s office ADHERENCE Consistent exposure with nothing to remember each day Entering the clinic in 2027

108 Ulixa eTDDS Flux Data Support Therapeutic Ulixacaltamide Exposure CUMULATIVE DRUG PERMEATION Ulixacaltamide (µg/cm²) 0 4 8 12 16 20 24 Time (h) Current: mean, n=3, measured 0 to 6 h; dashed line projects to 24 h at the measured flux. V2 dotted line spans the 3 to 19 h sampling gap. ELECTRODE GENERATION PERFORMANCE Drug flux µg/cm²/h Transport factor % of current carried by drug V1 passive V1 V2 V3 V1 V2 V3 V2 electrode V3 electrode Technology progression

109 Simulated Patch Exposure Sits Within Oral Dosing Concentration Model: oral PK parameters; patch input from in vitro porcine flux 0 1 2 3 4 5 6 7 Pl as m a co nc en tr at io n Time (days) Ulixa eTDDS Ulixa oral PEAK-TO-TROUGH RATIO 2.4× 1.0× Oral once daily Ulixa eTDDS patch

110 Building the Leading T-Type Ca Channel Franchise: Timeline to Next Key Clinical Milestones 2027 2028 2029 2030 1 · LINE EXTENSIONS PD Trial Readout RLS Trial Readout ASD Trial Readout 2 · NEXT-GEN MOLECULES PRAX-050 (Pan CaV3.x) FIH Data PRAX-051 (CaV3.x selective) FIH Data 3 · BETTER DELIVERY Transdermal Patch Bioequiv Data Timelines estimated based on historical studies in the respective indications

111 CEREBRUM Epilepsy Pipeline

112 KCNT1 Epilepsy Is Severe and Has No Approved Therapy EIMFS: epilepsy of infancy with migrating focal seizures; SHE: sleep-related hypermotor epilepsy (formerly ADNFLE). Source: Gras et al., Brain Commun 2026; Bonardi et al., Brain 2021; Mathieu Kuchenbuch et al. Brain 2019. INFANT ONSET KCNT1-DEE EIMFS, EOEE, West Syndrome 1.4 mo mean age at seizure onset 96% have daily seizures at onset 47% mortality median 3 years (1.5-15.4) CHILDHOOD ONSET SHE Sleep-related hypermotor epilepsy 6 yrs mean age at seizure onset 2 in 3 are drug-resistant 65% inherit the variant from a parent CAUSE KCNT1 gain-of-function, autosomal dominant. TREATMENT No FDA-approved therapy; standard antiseizure drugs rarely help

113 PRAX-206 Is Potent, Selective and Well Tolerated in Preclinical Models, With First-in-Human Planned for 2027 Number of spontaneous seizures across 9 days (quantified 12 h post-dose each day) and nesting score on Day 9; 300 mg/kg PRAX-206. Acute panel: single dose. *p<0.05, **p<0.01, ****p<0.0001; Kruskal-Wallis followed by Dunn's. WT, wild type; Kcnt1PL/PL, Kcnt1 P905L mice. Spontaneous seizures Subchronic treatment Nesting behavior Subchronic treatment Spontaneous seizures Acute treatment PRAX-206 Oral, selective KCNT1 inhibitor targeting the cause of disease in KCNT1-DEE and SHE FIRST IN HUMAN 2027

114 CEREBRUM Pain Pipeline

115 Why Pain: >150M US Patients With a Significant Unmet Need Source: Baskozos et al (2023), BioSpace (2024), CDC, Cunningham et al (1984), Dalke Meucci et al (2015), DelveInsight (2024), DiBonaventura et al (2017), EvaluatePharma (2024), Freburger et al (2009), George et al (2024), Lopez et al (2023), National Fibromyalgia Association, Osteoarthritis Action Alliance, OARSI, Shmagel et al (2017), Stefano et al (2020), US Pain Foundation (2024), Walitt et al (2015), Yawn et al (2009); BioPharma Dive, “Cancer patients are living longer than ever. Pain drugmakers haven’t kept up.” Insufficient response to current options • ~50–80% of chronic pain patients are refractory to first- and second-line treatments (e.g., NSAIDs, acetaminophen, anti-seizure meds) • ~40–60% refractory to opioids • ~30–70% of acute pain patients do not achieve a favorable response Safety, tolerability and abuse potential • Current options, particularly opioids, cause vomiting, constipation, drowsiness, dizziness and impaired cognition • Opioids are highly addictive with potential for abuse Few novel mechanisms • Largely genericized market, with very few novel MOAs approved for pain in the past 20 years ~80M Acute pain ~10M Neuro- pathic ~30M Lower back ~10M Osteo- arthritis Broader pain >150M est. US patients across pain indications

116 Transmission of Pain Involves Multiple NaV Isoforms in Different Compartments PERIPHERAL NERVOUS SYSTEM Nerves in the skin, muscles and organs detect injury and fire the pain signal NaV1.7 NaV1.8 CENTRAL NERVOUS SYSTEM The brain and spinal cord relay the signal and process it into the perception of pain NaV1.2 NaV1.6 NaV1.6

117 Designing a Wide Range of Molecules and Using a Differentiated Preclinical Development Framework to Pick the Best Candidates PAC-PAIN, Praxis Analysis of Concordance for Pain. PERIPHERAL NERVOUS SYSTEM CENTRAL NERVOUS SYSTEM NaV1.2 NaV1.6 NaV1.7 NaV1.8 DATA-LED DECISION-MAKING 1 Pursue multiple approaches Advance several chemical series in parallel rather than betting on one 2 Fine-tune the isoform profile Dial each molecule toward the NaV isoforms we want to hit for a given pain type 3 Test in PAC-PAIN Framework Move forward only candidates that work in the preclinical models most predictive of clinical results TUNABLE SODIUM CHANNEL CHEMISTRY

118 PAC-PAIN Develops Pain Model Cascades for Each Indication to Reduce Translational Risk Acute Pain Neuropathic Pain Chronic Pain Inflammatory Pain M1 M2 M3 M4 M5 M6 M7 M8 M9 Acute Pain M1 M2 M3 M4 Neuropathic Pain M1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M11 M12 M13 Post-op M1 Visceral M1 Osteoarthritis M1 M2 M3 PAC-PAIN, Praxis Analysis of Concordance for Pain. Darker cells = higher concordance; models scored –1 to +1 vs. clinical outcomes. PI, protective index. Source: Anderson, et al. 2026 AAN; Praxis analysis. P R EC LI N IC A L M O D EL S CL IN ICAL RESULTS PAC-PAIN first scores how well each preclinical pain model concorded with the clinical results of 58 FDA-approved pain drugs Some of the most-used models are among the least predictive WHY IT GIVES US AN EDGE • Indication-specific cascades: each pain indication can be best predicted by a cascade of pain models • Tolerability gated early: compounds advance only with PI above 2 • Proven platform: the same framework behind our epilepsy programs

119 Suzetrigine's Approval Clinically Validates Sodium Channel Targeting in Pain Illustrative. Suzetrigine (Journavx, Vertex), NaV, voltage-gated sodium channel. PERIPHERAL NERVOUS SYSTEM CENTRAL NERVOUS SYSTEM NaV1.2 NaV1.6 NaV1.7 NaV1.8 SUZETRIGINE'S PROFILE CLINICALLY PROVEN Suzetrigine (Journavx), FDA-approved January 2025 • NaV1.8 selective inhibitor • For moderate-to-severe acute pain • The first new acute pain drug class in over 20 years

120 PRAX-215 Pairs Balanced Pan-NaV Potency With Praxis Functional State Selectivity Illustrative slider positions based on PRAX-215 IC50s. Model X, Y, Z: preclinical pain models. PERIPHERAL NERVOUS SYSTEM CENTRAL NERVOUS SYSTEM NaV1.2 NaV1.6 NaV1.7 NaV1.8 PRAX-215 PROFILE PHASE 1 ONGOING PRAX-215 • Balanced potency at NaV1.2, 1.6, 1.7 and 1.8, covering both PNS and CNS pain signals • Functional state selectivity acts on hyperactive neurons while sparing normal activity Model X Model Y Model Z PRAX-215 dose (mg/kg) % re ve rs al In Vivo Pain Model

121 PRAX-110 Is Biased Toward NaV1.8 While Keeping Activity Across Other Pain Isoforms Illustrative slider positions. Praxis data on file. PERIPHERAL NERVOUS SYSTEM CENTRAL NERVOUS SYSTEM NaV1.2 NaV1.6 NaV1.7 NaV1.8 PRAX-110 PROFILE IND SUBMISSION IN 2027 PRAX-110 Profile • Biased potency at NaV1.8, while maintaining functional state selectivity at other isoforms across the PNS and CNS • Functional state selectivity acts on hyperactive neurons while sparing normal activity 0 5 10 15 Protective Index – Pain Model X PRAX-215 3.7x PRAX-110 Profile 15x

122 NaV1.x Pain Franchise Development Milestones 2027 2028 2029 2030 215 · PAN-NaV Acute pain Chronic pain SAD / MAD Trial Readout Trial Readout 110 · NaV1.8-BIASED Acute pain Chronic pain IND SAD / MAD Trial Readout Trial Readout PAC-PAIN guides indication selection and preclinical model prioritization for acute and chronic pain across both programs.

123 SOLIDUS ASO PLATFORM Solidus is an efficient, targeted precision medicine discovery and development engine for ASOs anchored on a proprietary, computational methodology

124 1 PIVOTAL-STAGE ANCHOR Elsunersen (PRAX-222) in the EMBRAVE3 registrational study N MULTIPLE RNA CONTROL MECHANISMS Silencing, splice switching, NAS suppression and other expression upregulation approaches 6 EARLY-STAGE TARGETS Focused programs across genetically defined CNS disorders REPEATABLE DISCOVERY LOGIC Genetic cause → Mechanism selection → Optimized ASO → Translational readout → Clinical evidence Multiple Routes to Address Genetically Defined Disease

125 Elsunersen (PRAX-222) Targets the Source of SCN2A Gain-of- Function Disease DISEASE BIOLOGY WITH ELSUNERSEN SCN2A GAIN-OF-FUNCTION Hyperactive NaV1.2 channels contribute to neuronal hyperexcitability and severe early-onset seizures. RNA-LEVEL INTERVENTION An RNase H1-active ASO reduces SCN2A mRNA, designed to decrease pathogenic NaV1.2 current. Intrathecal Every 4 weeks FDA Breakthrough Therapy Designation (June 2026)

126 EMBRAVE Part A Showed Marked Seizure Reduction and Disease- Modifying Benefits, Earning it Breakthrough Therapy Designation Q4W: every 4 weeks; GOF: gain of function; DEE: developmental and epileptic encephalopathy; SAE: serious adverse event Source: ClinicalTrials.gov NCT05737784; Praxis data on file STUDY DESIGN KEY RESULTS AT 24 WEEKS Ages 2–18 early-onset SCN2A GOF DEE 3:1 Elsunersen 1 mg Q4W (n=7) Sham procedure Q4W (n=2) Open-label extension Optional escalation up to 8 mg 77% placebo-adjusted seizure reduction (p=0.015) 71% of patients with >50% seizure reduction 57% of patients with ≥28-day seizure freedom 100% with gains in sleep, motor function, tone or attention Well tolerated: No drug-related SAEs • No discontinuations • No neuroinflammation signals up to 8 mg PRIMARY

127 EMBRAVE3: Pivotal Single-arm Registrational Study with Expected 2027 Topline and NDA Filing Primary endpoint: % change in monthly motor seizure frequency from baseline. Q4W: every 4 weeks; DEE: developmental and epileptic encephalopathy; NDA: new drug application Source: ClinicalTrials.gov NCT07019922 STUDY DESIGN OBSERVATION Baseline seizure frequency ELSUNERSEN 1 mg intrathecal Q4W · 24 weeks EXTENSION Continued open-label treatment PATIENT COHORTS Ages 2–18: ~30 | Ages 1–2: ~5 | Under age 1: ~5 PRIMARY ENDPOINT Median % change in monthly motor seizure frequency from baseline FDA-aligned single-arm design, following removal of sham control.

128 Six Genetically Defined Targets Extend Solidus Beyond Elsunersen PRAX-080 PCDH19 Mosaic expression disorder MODALITY Gapmer / RNA silencing PRAX-090 SYNGAP1 Haploinsufficiency DEE MODALITY SYNGAP1 upregulation PRAX-100 SCN2A Loss-of-function neurodevelopmental disorder MODALITY SCN2A upregulation PRAX-120 ATM Ataxia-telangiectasia MODALITY ATM upregulation PRAX-130 SLC6A1 SLC6A1-related DEE MODALITY GAT-1 upregulation PRAX-140 KCNQ2 Dominant-negative DEE MODALITY Allele-selective gapmer IND Enabling Tox IND Enabling Tox IND Enabling Tox IND Enabling Tox Lead Optimization Lead Optimization

129 AI-guided ASO Discovery: From Screening Data to Predictive Design 01 DESIGN Generate ASO candidates Use 5′UTR sequence and specificity filters to shortlist designs. 131 candidate 20-mers 22 filtered 02 MEASURE + LEARN Train predictive models Relate sequence features to measured gene upregulation. Sequence features Measured activity LR model 03 PREDICT + VALIDATE Prioritize new designs Use model scores to rank untested ASOs for future wet-lab studies. PILOT 5′UTR MODEL PERFORMANCE 0.80 ROC AUC NEXT: TEST GENERALIZABILITY Validate on independent data and across new target sequences. Source: Praxis pilot ASO upregulation model-development data; Pilot ROC AUCs describe model discrimination.

130 The Platform Opportunity Is Disciplined, Repeatable Advancement of RNA Programs 1 GENETIC INSIGHT Causal variant and direction of dysfunction 2 MECHANISM MATCH Silence, splice or increase expression 3 ASO DESIGN Sequence and chemistry optimization 4 TRANSLATIONAL PROOF RNA/protein, functional readouts, exposure 5 CLINICAL PROGRAM Patient selection and measurable outcomes

131 Praxis’ Full Pipeline Today DEE: developmental and epileptic encephalopathy; FOS: focal onset seizures; LoF: loss of function; ATM: Ataxia-telangiectasia. MARKETED C E R E B R U M S O L ID U S Essential tremor Ulixacaltamide Parkinson's disease PRAX-051 CaV3.x-selective inhibitor PRAX-050 Pan-CaV3.x inhibitor(s) Restless legs syndrome Autism spectrum disorder Patch delivery SCN2A & SCN8A DEE Relutrigine Broad DEEs Adjunctive FOS Vormatrigine Monotherapy FOS PRAX-215 Pain PRAX-110 Pain PRAX-206 KCNT1 DEE Elsunersen Early-onset SCN2A DEE PRAX-080 PCDH19 PRAX-090 SYNGAP1 PRAX-100 SCN2A LoF autism PRAX-120 ATM PRAX-130 SLC6A1 PRAX-140 KCNQ2

Filing Exhibits & Attachments

4 documents

Press Releases

• EX-99.1 EX-99.1 121.9 KB

Other Documents

• EX-101 XBRL TAXONOMY EXTENSION SCHEMA DOCUMENT 1.8 KB
• EX-101 XBRL TAXONOMY EXTENSION LABEL LINKBASE DOCUMENT 22.0 KB
• EX-101 XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE DOCUMENT 12.7 KB