FALSE000168954800016895482024-11-062024-11-06

 
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 6, 2024

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 2.02. Results of Operations and Financial Condition.
On November 6, 2024, Praxis Precision Medicines, Inc. (the “Company”) announced its financial results for the quarter ended September 30, 2024. A copy of the press release containing these announcements is furnished as Exhibit 99.1 to this Current Report on Form 8-K (the “Current Report”).
Item 7.01. Regulation FD Disclosure.
On November 6, 2024, the Company updated its corporate presentation for use in meetings with investors, analysts and others. The presentation is available in the “Investors + Media” portion of the Company’s website at investors.praxismedicines.com and a copy is furnished as Exhibit 99.2 to this Current Report.
The information in this Current Report under Items 2.02 and 7.01, including Exhibit 99.1 and Exhibit 99.2 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 9.01. Financial Statements and Exhibits.
(d) Exhibits
 
Exhibit
No.
  Description
  
104Cover 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 6, 2024
By: /s/ Marcio Souza
 Marcio Souza
 Chief Executive Officer


image_0a.jpg 
Praxis Precision Medicines Provides Corporate Update and Reports Third Quarter 2024 Financial Results
Interim analysis for Study 1 of Essential3 Phase 3 program for ulixacaltamide in essential tremor (ET) confirmed for Q1 2025; NDA filing anticipated in 2025
Registrational Cohort 2 of EMBOLD study recruiting following unprecedented seizure freedom seen in positive topline EMBOLD results for Cohort 1 in SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs)
Vormatrigine (PRAX-628) on track for topline from POWER1 study in focal epilepsy and RADIANT study in focal and generalized epilepsy in 2025
Maintains runway into 2027
BOSTON, November 6, 2024 — Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today provided a corporate update and reported financial results for the third quarter 2024.
“This quarter we made substantial strides in advancing our pipeline, notably progressing a third molecule with blockbuster potential, relutrigine, into late-stage development, while for ulixacaltamide we have finalized the operational plan to complete the interim analysis for Essential3 Study 1 in mid-Q1 2025. The positive topline results we shared this quarter from EMBOLD cohort 1 underscore relutrigine’s promise as a first- and best-in-class therapy for DEEs, demonstrating unmatched seizure-freedom and reduction in SCN2A and 8A patients, along with disease-modifying effects. As a result, we have rapidly advanced the SCN2A/8A program to registrational stage and are expanding our studies to cover a broader range of DEEs” said Marcio Souza, president and chief executive officer of Praxis.
Mr. Souza continued, “Our ENERGY program for vormatrigine (PRAX-628) is moving forward with strong interest, driven by insights from the ongoing observational EMPOWER study, and we are on track with our RADIANT and POWER1 trials. Additionally, we are actively exploring lifecycle expansion opportunities in Parkinson’s Disease and pain. With strong financial and clinical positioning, we are set to build on this momentum, advancing all four clinical programs towards registrational readiness in 2025.”
Recent Highlights and Anticipated Milestones:
Cerebrum™ Small Molecule Platform
•Ulixacaltamide for Essential Tremor (ET): Results of the planned interim analysis for Essential 3 Study 1 are expected Q1 2025.
oTiming of topline read-out for Study 1 and Study 2 in the Phase 3 Essential3 program will be updated upon review of the interim analysis.
oIn anticipation of positive outcomes with ulixacaltamide in ET, Praxis expects to re-initiate the Parkinson’s disease program in 2025.
oHighlighting the unmet need in ET, Praxis recently shared two surveys at the Movement Disorder Specialist Conference, with neurologist respondents sharing that 85% of their visits with ET patients are about finding treatment, while a survey of 400 ET patients show up to 80% adjust their daily activities due to their disease.
•Vormatrigine (PRAX-628) for Focal Onset Seizures and Generalized Epilepsy: Praxis continues to execute on its broad-ranging ENERGY program in focal onset seizures (FOS) and generalized epilepsy
oThe EMPOWER observational study, in partnership with the Epilepsy Study Consortium, aiming to better characterize seizure burden, started enrolling patients in the third quarter of 2024 and has already enrolled over 1,000 patients. Praxis expects the findings in EMPOWER to positively impact the ability to enroll patients in the ENERGY studies.


oRADIANT is a Phase 2 pharmacokinetics, safety and efficacy open-label study in patients with FOS or generalized epilepsy; topline results are anticipated in the first half of 2025.
oPOWER1 and POWER2 are 12-week Phase 2/3 studies in patients with FOS aiming to show efficacy of PRAX-628. POWER1 has recently been initiated, with topline results anticipated in the second half of 2025.
oGiven that vormatrigine is a potent Nav 1.7 and 1.8 inhibitor, Praxis is currently evaluating the potential for expansion into pain indications.
•Relutrigine (PRAX-562) for DEEs: In the third quarter, Praxis announced positive topline results for the Phase 2 EMBOLD cohort 1 study (N=15)
oHighlights from the topline results included:
•46% placebo-adjusted reduction in monthly motor seizure from baseline over a 16-week period.
•For patients continuing onto the ongoing open label extension (OLE), n=9, saw a 75% reduction in motor seizures from baseline.
•Over 30% of patients (n=5) achieved seizure freedom status while on relutrigine.
•Meaningful gains observed in alertness, communication and seizure severity suggest relutrigine has a disease modifying effect.
•Relutrigine was generally well-tolerated with no drug-related serious adverse events or dose reductions required.
oBased on the positive results of cohort 1, Praxis initiated a second cohort of the EMBOLD study to be sufficient for registration, aiming to enroll 80 patients, with topline results in the first half of 2026.
oSodium channel blockers are used broadly by DEE patients. Praxis has decided to initiate a registrational study (EMERALD) in all DEEs, which is planned to initiate in the first half of 2025 after alignment with regulators.
oRelutrigine has received Orphan Drug Designation (ODD) and Rare Pediatric Designation (RPD) from the FDA, and ODD from the European Medicines Agency (EMA) for the treatment of SCN2A-DEE and SCN8A-DEE.
Solidus™ Antisense Oligonucleotide (ASO) Platform
•Elsunersen (PRAX-222) for early-seizure-onset SCN2A Developmental Epilepsies: Elsunersen has previously received ODD and RPD from the FDA, and ODD and PRIME designations from the EMA for the treatment of SCN2A-DEE
oIn Q3, Praxis dosed the first patient in Brazil as part of a continuation of Part A of the EMBRAVE study.
oPraxis is continuing to harmonize the registrational study protocol, with plans to expand in the U.S. and Europe.
Third Quarter 2024 Financial Results:
As of September 30, 2024, Praxis had $411.2 million in cash, cash equivalents and marketable securities, compared to $81.3 million in cash and cash equivalents as of December 31, 2023. The increase of $329.9 million is primarily due to net proceeds from Praxis’ January 2024 and April 2024 follow-on public offerings and net proceeds from at-the-market sales of common stock, offset by cash used in operating activities.
Praxis recognized $0.3 million in collaboration revenue during the three months ended September 30, 2024, compared to $0.5 million during the three months ended September 30, 2023. The decrease of $0.2 million is associated with a decrease in the revenue recorded under the UCB Collaboration Agreement due to timing of work performed.
Research and development expenses were $41.9 million for the three months ended September 30, 2024, compared to $17.3 million for the three months ended September 30, 2023. The increase in research and development expenses of $24.6 million was primarily attributable to a $21.6 million increase in expense related to Praxis’ Cerebrum™ platform, a $4.0 million increase in personnel-related costs and a $0.4 million increase in indirect expenses, partially offset by a $1.5 million decrease in expense related to Praxis’ Solidus™ platform. General and administrative expenses were $15.3 million for the three months ended September 30, 2024, compared to $8.7 million for the three months ended September 30, 2023. The increase in general and administrative expenses of approximately $6.6 million was primarily


due to a $4.6 million increase in personnel-related costs, a $1.4 million increase in professional expenses and a $0.5 million increase in other expenses.
Praxis reported a net loss of $51.9 million for the three months ended September 30, 2024, including $12.4 million of stock-based compensation expense, compared to $24.6 million for the three months ended September 30, 2023, including $5.8 million of stock-based compensation.
As of September 30, 2024, Praxis had 17.8 million shares of common stock outstanding.
Conference Call
Praxis Precision Medicines will host a conference call and webcast today at 8:00 a.m. ET to review the third quarter 2024 financial results and recent business highlights. Individuals may register for the conference call by clicking the registration link. Once registered, participants will receive dial-in details and a unique PIN which will allow them to access the call. An audio webcast will be accessible through the Events & Presentation page under the Investor Relations section of the Company’s website. Following the live webcast, an archived replay will also be available.
About Ulixacaltamide 
Ulixacaltamide is a differentiated and highly selective small molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firing in the Cerebello-Thalamo-Cortical (CTC) circuit correlated with tremor activity. Ulixacaltamide, the most advanced program within Praxis’ Cerebrum™ small molecule platform, is currently in late-stage development for the treatment of essential tremor, www.praxisessentialtremor.com.
About Vormatrigine (PRAX-628)
Vormatrigine is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain that is currently being developed as a once daily, oral treatment for adult focal onset seizures and generalized epilepsy. Preclinical data demonstrates vormatrigine is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vitro, vormatrigine has demonstrated superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of vormatrigine have demonstrated unprecedented potency in the maximal electroshock seizure (MES) model, a highly predictive translational model for efficacy in focal epilepsy. Data from the PRAX-628-101 study demonstrated that vormatrigine can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50.
About Relutrigine (PRAX-562)
Relutrigine is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathy (DEE) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in early onset SCN2A-DEE and SCN8A-DEE. Relutrigine’s mechanism of sodium channel blocking is consistent with superior selectivity for disease state sodium channel (NaV) channel hyperexcitability. In vivo studies of relutrigine have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. Relutrigine has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel blocking effects. Relutrigine has received ODD and RPD from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE. To learn more about the EMBOLD study, please visit https://www.emboldstudy.com.
About Elsunersen (PRAX-222)
Elsunersen is an antisense oligonucleotide (ASO) designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early-seizure-onset SCN2A-DEE to treat seizures and other symptoms in patients with gain-of-function SCN2A mutations. In vitro studies of elsunersen have demonstrated reduction in both SCN2A gene expression and protein levels. In vivo, elsunersen has demonstrated significant, dose-dependent reduction in seizures, improvement in behavioral and locomotor activity and increased survival in SCN2A mouse models, with potential to be the first disease-modifying treatment for SCN2A-DEE. Elsunersen has received ODD and RPD from the FDA, and ODD and PRIME designations from the European Medicines Agency for the treatment of SCN2A-DEE. The Elsunersen program is


ongoing under a collaboration with Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), and RogCon, Inc. To learn more about the EMBRAVE study, please visit https://www.embravestudy.com/.
About Praxis 
Praxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, LinkedIn and Twitter/X.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Praxis’ future expectations, plans and prospects, including, without limitation, statements regarding the anticipated timing of our clinical trials, the development of our product candidates and plans to initiate new clinical programs, the anticipated timing of regulatory submissions and interactions and our projected cash runway, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “endeavor,” “estimate,” “expect,” “anticipate,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995.
The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical trials; preliminary analyses from ongoing studies differing materially from final data from preclinical studies and completed clinical trials; the expected timing of clinical trials, data readouts and the results thereof, and submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; and other risks concerning Praxis’ programs and operations as described in its Annual Report on Form 10-K for the year ended December 31, 2023 and other filings made with the Securities and Exchange Commission. Although Praxis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on information and factors currently known by Praxis. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Praxis undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.
Investor Contact: 
Praxis Precision Medicines  
investors@praxismedicines.com  
857-702-9452 
Media Contact:
Dan Ferry
Life Science Advisors
Daniel@lifesciadvisors.com
617-430-7576






PRAXIS PRECISION MEDICINES, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(Amounts in thousands)
(Unaudited)
September 30, 2024December 31, 2023
Assets
Cash and cash equivalents$168,645 $81,300 
Marketable securities242,528 — 
Prepaid expenses and other current assets3,016 3,580 
Property and equipment, net277 588 
Operating lease right-of-use assets1,374 2,064 
Other non-current assets416 416 
Total assets$416,256 $87,948 
Liabilities and stockholders’ equity
Accounts payable$15,010 $5,815 
Accrued expenses15,457 7,416 
Operating lease liabilities1,660 2,495 
Deferred revenue1,463 2,553 
Common stock14 13 
Additional paid-in capital1,159,382 723,577 
Accumulated other comprehensive gain1,331 — 
Accumulated deficit(778,061)(653,921)
Total liabilities and stockholders' equity$416,256 $87,948 



PRAXIS PRECISION MEDICINES, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS 
(Amounts in thousands, except share and per share amounts)
(Unaudited)
Three Months Ended
September 30,
Nine Months Ended
September 30,
2024202320242023
Collaboration revenue$302 $468 $1,090 $1,932 
Operating expenses:
Research and development41,881 17,260 96,125 68,378 
General and administrative15,256 8,724 41,174 32,121 
Total operating expenses57,137 25,984 137,299 100,499 
Loss from operations(56,835)(25,516)(136,209)(98,567)
Other income:
Other income, net4,925 884 12,069 2,168 
Total other income4,925 884 12,069 2,168 
Net loss$(51,910)$(24,632)$(124,140)$(96,399)
Net loss per share attributable to common stockholders, basic and diluted$(2.75)$(2.72)$(7.21)$(16.73)
Weighted average common shares outstanding, basic and diluted18,884,5629,039,42717,210,6045,763,121



CORPORATE OVERVIEW November 2024 ®

 
2 Forward-looking statements This presentation may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial conditions, including but not limited to express or implied statements regarding the current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, , including statements regarding the estimated market for our product candidates, if approved, our development plans, our preclinical and clinical results and other future conditions, including our cash runway, and the safety, efficacy, and regulatory and clinical design or progress, potential regulatory submissions, approvals and timing thereof of any of our product candidates. 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 success and timing of our ongoing clinical trials, (ii) the success and timing of our product development activities and initiating clinical trials, (iii) the success and timing of our collaboration partners’ product development activities, (iv) the timing of and our ability to obtain and maintain regulatory approval of any of our product candidates, (v) our plans to research, discover and develop additional product candidates, (vi) our ability to enter into collaborations for the development of new product candidates, (vii) our ability to establish manufacturing capabilities, and our collaboration partners’ abilities to manufacture our product candidates and scale production, (viii) our ability to meet any specific milestones set forth herein, and (ix) the potential addressable market sizes for product candidates. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly 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, 2023 filed with the Securities and Exchange Commission (“SEC”) and our other filings with the SEC. 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.

 
3 4 >$9B 5 2 2027 Praxis is positioned to bring more innovation to patients Assets in late stage Commercial opportunity across the portfolio High value clinical readouts within the next eighteen months Discovery platforms to optimize drug development Cash runway into

 
4 GENETICS Focus on therapeutic targets identified through human genetics TRANSLATIONAL TOOLS Translational tools validate potential of target and product candidate and can provide early proof of biology EFFICIENT & RIGOROUS Efficient, rigorous clinical development paths to proof- of-concept in humans applying an agile way of working PATIENT-GUIDED Patient-guided development strategies to deliver on what patients actually need Four pillars guide how we develop medicines

 
5 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 SOLIDUS ANTISENSE OLIGONUCLEOTIDE (ASO) PLATFORM Solidus is an efficient, targeted precision medicine discovery and development engine for ASOs anchored on proprietary, computational methodology Two platforms to generate optimized therapies for defined patient populations Molecule Indication Mechanism ulixacaltamide Essential Tremor T-type calcium channel modulator vormatrigine Focal Onset Seizures & Generalized Epilepsy Sodium channel functional state modulator for broad use relutrigine* DEE Epilepsies Sodium channel functional state modulator for pediatric use PRAX-020^ KCNT1 Epilepsy KCNT1 specific inhibitor PRAX-050 Not disclosed Not disclosed Molecule Indication Mechanism elsunersen** SCN2A GoF Gapmer ASO PRAX-080+ PCDH19 Mosaic expression Gapmer ASO PRAX-090+ SYNGAP1 LoF Splice switching ASO PRAX-100+ SCN2A LoF Splice switching ASO ^PRAX-020 (KCNT1) is a research collaboration with UCB +PRAX-080 (PCDH19 ), PRAX-090 (SYNGAP1) & PRAX-100 (SCN2A-LoF) ASOs are a collaboration with The Florey Institute of Neuroscience and Mental Health * Relutrigine has received ODD and RPD from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE ** Elsunersen has received ODD and RPD from the FDA, and ODD and PRIME designations from the European Medicines Agency (EMA) for the treatment of SCN2A-DEE

 
6 Program Pre clin Ph 1 Ph 2 Ph 3 Upcoming Catalyst Ulixacaltamide Essential Tremor ESSENTIAL3 Study1 placebo controlled Q1 2025 interim for Study 1 ESSENTIAL3 Study 2 randomized withdrawal Vormatrigine Focal Onset Seizures & Generalized Epilepsy EMPOWER observational study Enrolling RADIANT open label 1H 2025 topline results POWER1 Phase 2/3 2H 2025 topline results POWER2 Phase 2/3 1H 2025 begin enrollment Relutrigine DEEs EMBOLD Cohort 2 SCN2A and SCN8A DEEs 1H 2026 topline results EMERALD Other DEEs 1H 2025 begin enrollment PRAX-020 KCNT1 Elsunersen SCN2A GoF DEE Phase 1/2 Enrolling Registrational Harmonize global protocol PRAX-080 PCDH19 PRAX-090 SYNGAP1 PRAX-100 SCN2A LoF Four clinical stage assets and multitude of early-stage programs *PRAX-020 (KCNT1) is a research collaboration with UCB +PRAX-080 (PCDH19 ), PRAX-090 (SYNGAP1) & PRAX-100 (SCN2A-LoF) ASOs are a collaboration with The Florey Institute of Neuroscience and Mental Health CEREBRUM SMALL MOLECULE PLATFORM SOLIDUS ASO PLATFORM

 
7 CEREBRUM SMALL MOLECULE PLATFORM

 
8 Ulixacaltamide Milestones Q1 2025: Study 1 interim analysis 2025: NDA filling

 
9 Essential tremor market is significantly underserved and ready for disruption $4bn+ US ET Market 1. Louis ED, Ottman R. Tremor Other Hyperkinet Mov (N Y). 2014;4:259. 2. Elble RJ. Curr Neurol Neurosci Rep. 2013 Jun;13(6):353. 3. Putzke JD, et al. J Neurol Neurosurg Psychiatry. 2006 Nov;77(11):1235-7. 4. Vetterick, C., Lyons, K.E., Matthews, L.G. et al. The Hidden Burden of Disease and Treatment Experiences of Patients with Essential Tremor: A Retrospective Claims Data Analysis. Adv Ther (2022). https://doi.org/10.1007/s12325-022- 02318-8 • Essential Tremor (ET) is the most prevalent movement disorder • People with ET experience significant disturbance of their daily activities • Hallmark feature of ET is action tremor that primarily affects the hands2,3 • Almost all ET patients suffer from at least one comorbid condition (e.g., depression, anxiety, sleep disorders, cognitive dysfunction)4 Vast majority of patients are left without any treatment option • <30% of patients are eligible to receive propranolol due to other medications/health conditions • Of those who start propranolol >50% discontinue after only 1 month • Of those who start propranolol <20% still receive propranolol after 2 years ~2M ET patients seeking treatment 7M US Prevalence1

 
10 Speaking Dressing Using Keys Hygiene Pouring Working Writing Drinking from a glass Feeding with a spoon Carrying food trays, plates or similar items Overall disability with most affected task Each point reduction provides benefit to a patient’s ability to perform regular activities • Improvement based on regaining function • ADL assessment performed by a physician • Aligned with FDA as primary endpoint for Essential3 studies Modified Activities of Daily Living 11 (mADL11) as Primary Endpoint TETRAS = TRG Essential Tremor Rating Assessment Scale; ADL = Activities of Daily Living Each item is individually scored, up to a total of 33 0 = Slightly abnormal. Tremor is present but does not interfere with __. 1 = Mildly abnormal. Spills a little. 2 = Moderately abnormal. Spills a lot or changes strategy to complete task. 3 = Severely abnormal. Cannot drink from a glass or uses straw or sippy cup. 11 items from the well-established TETRAS ADL scale

 
11 Surveys of >400 ET patients across the US highlight ongoing hidden burden of ET and associated challenges in managing everyday life Praxis data on file. The Essential Tremor Patient Research was conducted by Fuel Insights (www.fuelinsights.com) from June-July 2024. Two separate surveys were completed online and included 150 US adults living with ET and a further 261 US adults living with ET who were pre-screened, but did not qualify, for the Essential3 study (https://essential3study.com/) ET burden has a profound impact on daily activities Patients with ET experience high psychosocial burden Nearly all patients with ET experience a level of psychosocial burden, with many reporting feeling: ET is inadequately managed and undertreated Up to 80% working / attending social events writing drinking from a glass frustratedworried Up to 77% Up to 50% of patients do not feel their ET symptoms are manageable with current treatments of patients are not receiving treatment for their ET of patients with ET reported needing to adjust how they complete daily tasks due to their symptoms Top Challenges: ashamed sad hopeless

 
12 US neurologists emphasize the need for more effective treatments and the importance of patient-physician dialogue in ET Praxis data on file. The Essential Tremor HCP Research was conducted by Fuel Insights (www.fuelinsights.com) in April 2024. The survey was fielded at the American Academy of Neurology meeting and included 152 neurologists who treat ET in the US, and who were primarily affiliated with academic centers. ET burden has a profound impact on daily activities Patients with ET experience high psychosocial burden ET is inadequately managed and undertreated 60% of neurologists reported mental and emotional challenges among the top three challenges for their ET patients 40% >90% of patients seen by neurologists are not receiving treatment of neurologists stated their patients’ descriptions of their ET symptoms and impact on daily activities influence treatment decisions 85% of neurologist visits are for patients seeking ET treatment Nearly 1/2 of neurologists rarely refer ET patients for specialist management

 
13 • Alignment with FDA on dose and primary endpoint • Phase 3 program design structured around patient needs • Robust recruitment strategy Essential1 Phase 2b study set foundation for the Essential3 Phase 3 program Sets up a clear path to registration • Strong efficacy signal with robust endpoint (mADL11) • Early clinical benefit in 8-Week Study • Long-term, durable benefit • Well-tolerated with a differentiated safety profile • Tested Phase 3 design concepts Validated the clinical hypothesis p = 0.042 ULIXACALTAMIDE (n=78) PLACEBO (n=38) Improvement in mADL11 in 8 weeks -2.69 -0.88 Im pr ov em en t Results from Essential1 study, p value is nominal

 
14 Using Essential1 to define clinical meaningfulness in essential tremor MSD=Meaningful Score Difference, PGI-C = Patient Global Impression of Change 8 6 4 2 0 -2 -4 -6 -8 -10 -12 -14 -16 -18 -20 • Patient response on mADL11 endpoint was well-correlated to PGI-C response • Aligned with recently issued guidance from Clinical Outcomes Assessment for novel endpoints ESSENTIAL1 ANCHOR-BASED ASSESSMENT PGI-C:mADL11

 
15 31% 55% 64% 0% 10% 20% 30% 40% 50% 60% 70% PLACEBO ULIXACALTAMIDE ULIXACALTAMIDE MAINTAINED Majority of patients achieved at least a 3-point change in mADL11 at 8 weeks Durable response in extension study patients who continued through 14 weeks Results from Essential1 study measuring participants achieving meaningful change at 8 and 14 weeks based on ≥3-point improvement from baseline https://praxismedicines.com/wp-content/uploads/2023/09/Giroux_MDS2023_E1_MSD_SUBMIT.pdf Essential1 Study – 8 weeks Essential1: % participants achieving > 3-point improvement in mADL11 Essential1 Extension–14 weeks p = 0.023

 
16 25% 48% 0% 10% 20% 30% 40% 50% Week 8 PROPRANOLOL + PLACEBO PROPRANOLOL + ULIXACALTAMIDE Adding ulixacaltamide benefitted more patients on propranolol Results from Essential1 study showing % of participants on stable propranolol dose achieving meaningful change at 8 weeks based on a meaningful score difference of ≥3 points Essential1: % of patients achieving a >3-point improvement in mADL11 Among patients who could tolerate propranolol, adding ulixacaltamide led to ~2-fold increase in the proportion achieving at least a 3-point improvement in mADL11

 
17 Essential3: An innovative Phase 3 program that optimizes all aspects of study conduct Single Recruiting Expert Review for Eligibility Screening Blinded Study Randomization Study 1: Placebo-controlled Parallel Group Study Ulixacaltamide, 60 mg Placebo Study 2: Randomized Withdrawal Study Ulixacaltamide, 60 mg Randomization 60 mg Placebo Long-term Safety Study Ulixacaltamide CT.gov NCT06087276 8 weeks 4 weeks 12 weeks

 
18 Essential3 Program is well powered Study Study 1 – Parallel Design Study 2 – Randomized Withdrawal Participants 400 200 Primary endpoint and power mADL11 Change from Baseline to Week 12 between ulixacaltamide and placebo 90% power to detect difference Difference in maintenance of response rate during the 4- week RW period between ulixacaltamide and placebo 90% power to detect difference Stratification Intention tremor status, family history, and propranolol use Main Secondary endpoints o TETRAS-ADL o CGI o PGI CGI = Clinical Global Impression (Severity); PGI = Patient Global Impression (Severity and Change)

 
19 Path to success De-risked Trial design based on key learnings from Essential1 Regulatory alignment based on successful End-of-Phase 2 meeting High Quality and Efficient Focused execution Single protocol: Optimized screening, enrollment, analysis Decentralized study to expand reach and reduce study burden to participants Patient-driven Approach mADL11 as a clinically meaningful primary endpoint NDA Readiness Clear path to filing in 2025 Interim Analysis Increases optionality, including potential for sample size re-estimation

 
20 Vormatrigine (PRAX-628) Milestones 1H 2025: Topline results for RADIANT 1H 2025: Begin enrolling POWER2 2H 2025: Topline results for POWER1

 
21 The Praxis epilepsy portfolio targets significant unmet need in both the common and rare epilepsy markets >$2.5B+ US Common Epilepsy Market Opportunity 3.5M US Prevalence for Common Epilepsy Praxis Epilepsy Portfolio Vormatrigine

 
22 Differentiated Profile Goal: Preferential action against neuronal hyperexcitability Vormatrigine: Precision medicine therapeutic for focal onset seizures and generalized epilepsy Next generation, functionally selective small molecule targeting the hyperexcitable states of sodium channels in the brain, with the potential to address limitations of current treatments  Ideal safety/tolerability profile  Achieves brain penetration  Rapidly achieves therapeutic concentrations without titration  Favorable half-life and PK profile  Optimized efficacy STIMULATION LEVEL epileptic range IDEAL DRUG healthy neuron non preferring drug NE UR AL A CT IV IT Y Untreated neuron

 
23 0.1 1 10 100 0 25 50 75 100 Dose (mg/kg) Pe rc en t p ro te ct ed PRAX-628 Cenobamate Lamotrigine XEN1101 Carbamazepine NBI-921352 Vormatrigine shows a differentiated pre-clinical profile Protective index (PI) measured as tolerability / efficacy (TD50 / ED50); MES = maximal electroshock seizure Praxis data on file; Bialer et al 2024 Epilepsia Vormatrigine has differentiated potency in the MES model Preclinical decision tree optimized for focal seizure drug discovery Progress Development Abandon Progress DevelopmentAbandon PI >2 PI >2 PI >2 PI < 2 PI < 2 PI < 2 Audiogenic MES (mouse) 6-Hz, 32mA (mouse) Vormatrigine Results

 
24 Source: Praxis data on file (Ph1 study), Cenobamate Cmax: >46,100 ng/mL, 400 mg Cmax (Vernillet et al 2020), XEN1101 Cmax: >107 ng/mL (Phase 1 data) x MES EC50 = multiple of predicted human EC50 based on the rodent MES model; IEC2023_628-SAD-MAD 4.8 2.5 5.0 15.0 CENOBAMATE 400mg XEN1101 25mg vormatrigine 20mg vormatrigine 30mg Mean Fold of MES EC50 achieved at Steady State Expected efficacy Additional tolerated margin for vormatrigine toxicity and tolerability levels No tolerability concerns Ability to significantly exceed therapeutic concentrations while well tolerated Vormatrigine has unprecedented margins over best-in-class ASMs based on MES efficacy and clinical tolerability in humans

 
25 - 5 10 15 20 25 0 1 2 3 4 5 6 7 8 QE EG C OM PO SI TI VE C HA NG E HOURS POST DOSE 0 5 23 0 4 8 12 16 20 24 Cenobamate XEN1101 vormatrigine • Composite endpoint from qEEG showed separation of drug versus placebo in the SAD and MAD cohorts • Difference between vormatrigine and placebo significant for all doses at first point measured • Effect consistent with known PK profile • Vormatrigine achieves nearly complete coverage on Day 1 400 mg 25 mg 30 mg Vormatrigine composite qEEG change Hours of day 1 drug coverage Phase 1 study demonstrated brain activity and rapid achievement of therapeutic concentrations SAD = single ascending dose; MAD = multiple ascending dose Garimella et al AES 2023; Praxis data on file

 
26 • Patients must demonstrate PPR response during screening and baseline to be evaluable • Response Assessment • Partial: Reduction, other than to zero, in the number of generalized PPR events at any assessment period vs baseline • Complete: Reduction to zero in the number of generalized PPR events at any assessment period vs baseline • Safety monitored and PK samples collected during observation period The Phase 2 vormatrigine Photo Paroxysmal Response (PPR) study demonstrated proof of concept; de-risks advancing to studies in focal and generalized epilepsy https://investors.praxismedicines.com/static-files/edc15000-7fcb-4d6d-b1de-1819898214a8 15 mg 45 mg Part A Part B Assessment Screening Baseline 24h Dose Categorical Response Response Rate 15 mg None 0% (0/5) Partial 20% (1/5) Complete 80% (4/5) 45 mg None 0% (0/3) Complete 100% (3/3) Evaluable Response 100% (8/8) Study Results • 100% response in treated patients • Vormatrigine achieved between 3-13x multiples of MES EC50 exposure • Safety was consistent with prior dose escalation study and AEs were mild

 
27 Vormatragine presents an ideal precision ASM profile https://praxismedicines.com/wp-content/uploads/2023/12/Kahlig_AES2023_628-In-Vivo_Poster_Final.pdf https://praxismedicines.com/wp-content/uploads/2023/09/IEC2023_628-SAD-MAD.pdf Ability to significantly exceed therapeutic concentrations while well tolerated Rapidly achieves therapeutic concentrations after once-daily dose Significantly more potent than competitive molecules in highly translatable pre-clinical models Ideal Treatment Proof of concept achieved in epilepsy patients Three efficacy trials in the ENERGY program

 
28 Vormatrigine ENERGY program to demonstrate efficacy and bring an improved therapy to focal and generalized epilepsy patients • Registry to help epilepsy patients track their seizures • In partnership with The Epilepsy Study Consortium POWER1 designed to maximize opportunity to demonstrate efficacy POWER2 additionally designed to evaluate broader dosing Evaluate efficacy, safety and extensive PK in broader epilepsy patients EMPOWER POWER1 POWER2 RADIANT 2H 2024 1H 20261H 2025 2H 2025Objective

 
29 EMPOWER Observational Study to better understand patient journey In partnership with The Epilepsy Study Consortium (TESC) PA TI EN T PA TH W AY Multi-channel engagement of epilepsy patients to EMPOWER Patient consented and provides core medical data Patient is given a seizure diary/epilepsy tracker, trained using TESC guided materials Subset of patients contacted directly by a nurse navigator to help define their epilepsy/seizures Patients who may be eligible will receive direct follow up and/or be directed into the POWER trials

 
30 • Measuring seizure frequency, seizure freedom, safety and pharmacokinetics • Will allow the evaluation of vormatrigine in a broader population, including generalized epilepsy • Topline results in 1H 2025 RADIANT Phase 2 open label study to evaluate safety and efficacy in focal onset or generalized epileptic seizures QD = Once daily Screening / Observation 4 weeks 30 mg vormatrigine QD 8 weeks n ~ 50 Safety Follow-up 2 weeks post dose

 
31 Proposed study designs for POWER1 and POWER2 6 weeks, 30mg 12 weeks placebo • Screening • Observation • Randomization POWER1, n= 200 Safety follow-up • POWER1 initiated in Q4 2024 with topline readout 2H 2025 • POWER2 to initiate in 1H 2025 6 weeks, 20 mg POWER2, n= 300 • Screening • Observation • Randomization 6 weeks, 30 mg 12 weeks 10 mg 6 weeks, 20 mg 12 weeks placebo 6 s, 30 g Safety follow-up Open Label Extension or Open Label Extension or

 
32 Relutrigine (PRAX-562) Milestones 2H 2024: EMBOLD Cohort 2 enrolling 1H 2025: Initiate EMERALD study

 
33 >$500M US Market Opportunity * Poke G, Stanley J, Scheffer IE, Sadleir LG. Epidemiology of Developmental and Epileptic Encephalopathy and of Intellectual Disability and Epilepsy in Children >100k Developmental Epilepsies with high seizure burden using sodium channel blockers* >$2B+ Opportunity for DEEs ~5K SCN2/8A US patients Relutrigine Addressable Patients Peak Revenue Potential Relutrigine is poised to disrupt the DEE market

 
34 Superior selectivity for disease-state NaV channel hyperexcitability Unprecedented therapeutic window with potential for superior safety and efficacy Generally well-tolerated with mostly mild to moderate AEs, no drug-related SAEs and no relutrigine dose reduction required Demonstrated robust seizure reduction and unprecedented seizure-free status per 28-day period Preclinical and emerging clinical data demonstrate relutrigine has the potential to be a first- and best-in-class small molecule for DEEs RELUTRIGINE SCN2A, SCN8A FORMULATED FOR PEDIATRIC USE SMALL MOLECULE FUNCTIONAL STATE MODULATOR

 
35 Relutrigine Phase 1 summary Source: Praxis data on file; https://investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-provides-corporate-update-and-5 * Co-administration of supra-therapeutic doses of relutrigine and oxcarbazepine led to additive sodium blocking effects, including resulting in SAEs All TEAEs mild to moderate as stand-alone therapy*, with headache & dizziness most common TEAEs Significant changes observed between placebo and relutrigine on qEEG biomarkers Relutrigine has been generally well tolerated in over 130 healthy volunteers No MTD at exposures multiple fold above therapeutic range indicates potential for superior therapeutic index

 
36 KEY ENDPOINTS: • Incidence and severity of treatment-emergent adverse events (TEAEs) • Change from baseline in monthly (28-day) motor seizure frequency • Seizure freedom achieved for a 4-week period • Clinical and Caregiver Global Impression of Improvement and Severity Relutrigine Phase 2 EMBOLD study design and endpoints * Participants receive either 0.5 mg/kg/day relutrigine QD for 16 weeks or 0.5 mg/kg/day relutrigine QD for 12 weeks & matching placebo QD for 4 weeks. Participants in the relutrigine/placebo arm will receive placebo for 4 consecutive weeks during the 16-week treatment period, with timing of placebo administration blinded for both participants and investigator. Dose adjustment permitted to a max of 1.0 mg/kg/day and a min of 0.25 mg/kg/day. DOUBLE-BLIND TREATMENT PERIOD (4 x 4-week periods => 16 WEEKS) Relutrigine 1:1 Randomization and Baseline N=16 (SCN2A/SCN8A) OLE TREATMENT PERIOD (48 WEEKS) Relutrigine for 4 x 4 weeks 0.5 mg/kg/day Placebo for 1 x 4 weeks Relutrigine for 3 x 4 weeks* 0.5 mg/kg/day

 
37 Relutrigine demonstrated robust reduction in motor seizures and unprecedented seizure-free status per 28-day period *Percent reduction derived from log-transformed placebo-adjusted relutrigine effect **Assessment of motor seizures over the controlled plus open-label periods through August 21, 2024 • 33% of patients seizure- free after initiating on relutrigine** • Longest follow-up >200 days seizure-free 5 patients 1,778 Motor Seizures at Baseline (n=15) 46% placebo-adjusted reduction in motor seizures over double-blind period* Seizure Freedom Periods Never Seen Before in this Population

 
38 -90% -80% -70% -60% -50% -40% -30% -20% -10% 0% Relutrigine patients demonstrated significant improvement over the short and long-term in motor seizures Long-term extension data for 8 patients with data available for at least one 28-day period as of August 21, 2024 Placebo (n=7) -1.6% Relutrigine (n=8) -27% Relutrigine (n=8) -75% 7 patients increased the dose of relutrigine to 1 mg/kg during the double- blind period, 2 additional patients during the long-term extension Seizure freedom associated with exposures achievable by 1 mg/kg Long-term extensionSingle 28-day period M ed ia n Im pr ov em en t

 
39 Meaningful and consistent impact in days without motor seizures for relutrigine treated patients * Inclusive of OLE period 3 3 20 46 0 5 10 15 20 25 30 35 40 45 50 Baseline all Placebo Relutrigine Relutrigine Double-Blind Treatment Period All drug periods* Mean of longest period without seizures Se iz ur e Fr ee D ay s

 
40Clinical Global Impression of Improvement and Caregiver Global Impression of Improvement assessed at Week-16 visit 57% 71% 43% 29% 69% 62% 31% 23% 0% 10% 20% 30% 40% 50% 60% 70% 80% Alertness Seizure Severity and Intensity Communication Disruptive Behavior Clinician Caregiver Relutrigine treatment led to disease modifying impact Meaningful gains in overall well-being of patients, despite severity and historical lack of improvement with available treatments % of patients showing improvement in the CGI-I and CgGI-I domains

 
41 SCN2A and SCN8A are the tip of the iceberg in addressing the significant unmet needs across the spectrum of other DEEs *Based on PubMed Search of DEEs that could use SCBs to treat focal seizures when they presented. >$500m peak revenue Low tolerability and inadequate response >70% DEE patients treated with sodium channel blockers* SCN2A, SCN8A Other DEEs High Seizure Burden + Genetic Epilepsies >$2bn peak revenue market opportunity >100,000 patients ~5,000 patients

 
42 Regulatory agency input • EMBOLD registrational Cohort 2 initiated • Leveraging EMBOLD successful study design Next steps Initiated EMBOLD cohort 2 registrational trial for SCN2A and 8A, begin enrollment for EMERALD trial in 1H 2025 2H 2024 1H 2025 Initiate EMERALD Trial 1:1 Randomization N=80 (SCN2A/SCN8A) Relutrigine for 4 x 4 weeks 1 mg/kg/day Placebo for 1 x 4 weeks Relutrigine for 3 x 4 weeks 1 mg/kg/day SCN2A /8A DEES DEEs Relutrigine Placebo Ongoing Study Preliminary Design

 
43 Elsunersen (PRAX-222) SOLIDUS ASO PLATFORM

 
44 Elsunersen specifically designed for SCN2A GoF patients DISEASE OVERVIEW • Epilepsy and developmental impairment before the age of 16 years occurs in 1 in 340 children • The majority of these cases result from sporadic de novo genetic variation • In both de novo and familial forms of epilepsy some 900 genes have been identified • Many of these genes also represent opportunities for intervention in other neurological disorders • Patients with SCN2A-DEE have a debilitating and ultimately fatal trajectory • Affects approximately 1,500 patients in the US RESEARCH APPROACH Modifying gene expression to address both gain and loss of function disorders is achieved through various ASO modalities to either silence harmful genes or enhance expression of reduced function or missing genes

 
45 Significant reduction in seizures observed for SCN2A patients Data from Part 1 of EMBRAVE Study, https://praxismedicines.com/wp-content/uploads/2023/12/Frizzo_AES2023_EMBRAVE_Poster_Final.pdf -39% -43% Im pr ov em en t Mean Median 52% 48% Mean Median Im pr ov em en t • No TEAEs or SAEs considered related to study drug • All TEAEs recovered/resolved Overall % reduction in seizures from 28-day baseline (n=4) Overall relative % increase in seizure-free days from 28-day baseline (n=4)

 
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v3.24.3
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Nov. 06, 2024
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