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): August 13, 2024
(Exact name of registrant as specified in its charter)
(State or other jurisdiction of incorporation) | (Commission File Number) | (I.R.S. Employer Identification No.) | ||||||
Praxis Precision Medicines, Inc.
(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 | ||||||||||||
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 August 13, 2024, Praxis Precision Medicines, Inc. (the “Company”) announced its financial results for the quarter ended June 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 August 13, 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 | |||||||
| 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: August 13, 2024 | By: | /s/ Marcio Souza | |||||||||
| Marcio Souza | |||||||||||
| Chief Executive Officer | |||||||||||
Praxis Precision Medicines Provides Corporate Update and Reports Second Quarter 2024 Financial Results
Up to four programs in registrational phase by 2025
Planned interim analysis for ulixacaltamide Essential3 Study 1 to be conducted in Q4 2024
Topline results for Phase 2 EMBOLD study of relutrigine (PRAX-562) in SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs) expected in Q3 2024
PRAX-628 Phase 2/3 POWER1 study to initiate in Q4 2024
Initiation of additional Phase 2 study (RADIANT) for PRAX-628 in focal and generalized epilepsy in 2H 2024, with topline results expected in 1H 2025
Cash and investments of $434 million as of June 30, 2024 maintains runway into 2027
BOSTON, August 13, 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 second quarter 2024.
“In the second quarter we continued to advance our entire portfolio, and we are poised to soon have up to four programs in registrational stage. The Essential3 program continues to progress well, with a pre-planned interim analysis of Study 1 to be conducted later this year. We remain on track for a successful topline readout enabling an NDA filing in 2025,” said Marcio Souza, president and chief executive officer of Praxis. “We look forward to sharing topline results of the EMBOLD study for relutrigine, formerly known as PRAX-562, in SCN2A and 8A patients later this quarter and believe these indications could be the tip of the iceberg for future application of PRAX-562 in other DEEs.”
Mr. Souza added, “we are also excited to build on the encouraging data generated to date with PRAX-628 by executing on the ENERGY program, a comprehensive set of studies, including a new Phase 2 Study (RADIANT), with topline data expected in the first half of 2025 in focal and generalized epilepsy. Additionally, with elsunersen having initiated the first arm of its global confirmatory study in Brazil, we anticipate the rapid advancement of all four clinical programs in our portfolio towards regulatory registrations. Our strong cash position, which fully funds Praxis through several important readouts into 2027, enables this momentum.”
Recent Highlights and Anticipated Milestones:
Cerebrum™ Small Molecule Platform
•Ulixacaltamide for ET: Topline results of two studies in the Essential3 Phase 3 program for ulixacaltamide are expected in the second half of 2024 to support a planned New Drug Application (NDA) submission in 2025.
oSince beginning recruitment in November 2023, there have been over 75,000 pre-screening forms, of which 11,000 referrals meet pre-qualifying eligibility criteria.
oPraxis to conduct an interim analysis for Study 1 in the Essential3 program in the fourth quarter of 2024. This pre-planned analysis is part of the original Statistical Plan and Protocol for Essential3.
oLong-term safety study enrollment criteria have been expanded to include patients who participated in previous ET studies, including previous suvecaltamide trials.
•PRAX-628 for Epilepsy: Praxis expects to initiate four studies as part of the PRAX-628 ENERGY program, aiming to generate efficacy, safety and pharmacokinetics (PK) data to serve as the basis of regulatory registrations globally.
oEMPOWER is an observational study in partnership with the Epilepsy Consortium expected to start in the third quarter of 2024, aiming to enroll patients with epilepsy to better characterize seizure burden
oRADIANT is a Phase 2 PK, safety and efficacy study in patients with focal onset seizures (FOS) or generalized epilepsy expected to start in the second half of 2024, with topline results 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 is expected to start enrolling patients in the fourth quarter of 2024, with topline results in the second half of 2025. POWER2 is expected to start enrolling patients in the first half of 2025.
•Relutrigine (PRAX-562) for SCN2A and SCN8A DEEs: Praxis expects topline results from the Phase 2 EMBOLD study for the treatment of pediatric patients with DEEs in the third quarter of 2024.
oThe EMBOLD study is a Phase 2 study evaluating the safety, tolerability, efficacy (motor seizure frequency) and PK of relutrigine in pediatric patients aged 2 to 18 years with DEEs, followed by an open-label extension.
oBased on results for the EMBOLD study, Praxis expects to consider a more expansive program of relutrigine in all DEEs with high seizure burden.
Solidus™ Antisense Oligonucleotide (ASO) Platform
•Elsunersen (PRAX-222) for early-seizure-onset SCN2A Developmental Epilepsies
oFirst arm of the global confirmatory study initiated in Brazil
oPivotal phase of the program remains on track, and Praxis plans to advance the program within the US and expand to Europe later in 2024.
Second Quarter 2024 Financial Results:
As of June 30, 2024, Praxis had $433.8 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 $352.5 million is primarily due to net proceeds from Praxis’ January 2024 and April 2024 follow-on public offerings plus net proceeds from at-the-market sales of common stock, offset by cash used in operating activities.
Praxis recognized $0.4 million in collaboration revenue during the three months ended June 30, 2024, compared to $0.8 million during the three months ended June 30, 2023. The decrease of $0.4 million is associated with a decrease in revenue recorded under the UCB Collaboration Agreement.
Research and development expenses were $27.3 million for the three months ended June 30, 2024, compared to $25.6 million for the three months ended June 30, 2023. The increase in research and development expenses of $1.6 million was primarily attributable to an increase of $8.1 million in Praxis’ Cerebrum™ platform and a $1.7 million increase in personnel-related costs, primarily offset by a $8.2 million decrease in costs associated with Praxis’ Solidus™ platform. General and administrative expenses were $10.6 million for the three months ended June 30, 2024, compared to $10.1 million for the three months ended June 30, 2023. The increase in general and administrative expenses of approximately $0.5 million was primarily due to increased personnel-related costs.
Praxis reported a net loss of $32.7 million for the three months ended June 30, 2024, including $5.9 million of stock-based compensation expense, compared to $34.3 million for the three months ended June 30, 2023, including $5.8 million of stock-based compensation.
As of June 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 second 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 Investor Relations section of the company’s website at www.praxismedicines.com. 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 PRAX-628
PRAX-628 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 epilepsy. Preclinical data demonstrates PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vitro, PRAX-628 has demonstrated superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of PRAX-628 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 PRAX-628 can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50.
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 Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) from the FDA, and ODD and PRIME designations from the European Medicines Agency (EMA) 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 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.org/.
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, 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)
| June 30, 2024 | December 31, 2023 | ||||||||||
| Assets | |||||||||||
| Cash and cash equivalents | $ | 145,143 | $ | 81,300 | |||||||
| Marketable securities | 288,688 | — | |||||||||
| Prepaid expenses and other current assets | 4,837 | 3,580 | |||||||||
| Property and equipment, net | 369 | 588 | |||||||||
| Operating lease right-of-use assets | 1,610 | 2,064 | |||||||||
| Other non-current assets | 416 | 416 | |||||||||
| Total assets | $ | 441,063 | $ | 87,948 | |||||||
| Liabilities and stockholders’ equity | |||||||||||
| Accounts payable | $ | 8,195 | $ | 5,815 | |||||||
| Accrued expenses | 10,058 | 7,416 | |||||||||
| Operating lease liabilities | 1,946 | 2,495 | |||||||||
| Deferred revenue | 1,764 | 2,553 | |||||||||
| Common stock | 14 | 13 | |||||||||
| Additional paid-in capital | 1,145,308 | 723,577 | |||||||||
| Accumulated other comprehensive loss | (71) | — | |||||||||
| Accumulated deficit | (726,151) | (653,921) | |||||||||
| Total liabilities and stockholders' equity | $ | 441,063 | $ | 87,948 | |||||||
PRAXIS PRECISION MEDICINES, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(Amounts in thousands, except share and per share amounts)
(Unaudited)
Three Months Ended June 30, | Six Months Ended June 30, | ||||||||||||||||||||||
| 2024 | 2023 | 2024 | 2023 | ||||||||||||||||||||
| Collaboration revenue | $ | 357 | $ | 781 | $ | 788 | $ | 1,464 | |||||||||||||||
| Operating expenses: | |||||||||||||||||||||||
| Research and development | 27,260 | 25,614 | 54,244 | 51,118 | |||||||||||||||||||
| General and administrative | 10,585 | 10,127 | 25,918 | 23,397 | |||||||||||||||||||
| Total operating expenses | 37,845 | 35,741 | 80,162 | 74,515 | |||||||||||||||||||
| Loss from operations | (37,488) | (34,960) | (79,374) | (73,051) | |||||||||||||||||||
| Other income: | |||||||||||||||||||||||
| Other income, net | 4,811 | 648 | 7,144 | 1,284 | |||||||||||||||||||
| Total other income | 4,811 | 648 | 648 | 7,144 | 1,284 | ||||||||||||||||||
| Net loss | $ | (32,677) | $ | (34,312) | $ | (72,230) | $ | (71,767) | |||||||||||||||
| Net loss per share attributable to common stockholders, basic and diluted | $ | (1.74) | $ | (7.38) | $ | (4.41) | $ | (17.51) | |||||||||||||||
| Weighted average common shares outstanding, basic and diluted | 18,824,479 | 4,649,371 | 16,364,421 | 4,097,833 | |||||||||||||||||||
CORPORATE OVERVIEW August 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 >$7B 5 2 2027 Praxis is positioned to bring more innovation to patients Assets in late stage in 2024 Commercial opportunity across the portfolio 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 PRAX-628 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
6 Program Pre clin Ph 1 Ph 2 Ph 3 Upcoming Catalyst Ulixacaltamide Essential Tremor ESSENTIAL3 Study1 placebo controlled Q4 2024 interim, 2H 2024 topline results ESSENTIAL3 Study 2 randomized withdrawal PRAX-628 Focal Onset Seizures & Generalized Epilepsy EMPOWER observational study Q3 2024 begin enrollment RADIANT open label 2H 2024 begin enrollment, 1H 2025 topline results POWER1 Phase 2/3 Q4 2024 begin enrollment, 2H 2025 topline results POWER2 Phase 2/3 1H 2025 begin enrollment Relutrigine DEEs EMBOLD SCN2A and SCN8A DEEs Q3 2024 topline results PRAX-020 KCNT1 Elsunersen SCN2A GoF DEE Phase 1/2 Enrolling Registrational Harmonize global protocol, 2H 2024 initiate 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 Q4 2024: Interim analysis of Essential3 Study 1 2H 2024: Topline results for Essential 3 2025: NDA filling
9 Essential tremor market is significantly underserved and ready for disruption $4bn+ US ET Market 1. GHOSH (2016) (P.231, C.1, PH.1, L.1-2), 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 • 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 • 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
12 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
13 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 change in mADL11 Essential1 Extension–14 weeks p = 0.023
14 25% 48% 0% 10% 20% 30% 40% 50% Week 8 PROPRANOLOL + PLACEBO PROPRANOLOL + ULIXACALTAMIDE Adding ulixacaltamide benefited more patients on propranolol with > 3-point improvement 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 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
15 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 Placebo Study 2: Randomized Withdrawal Study Ulixacaltamide Randomization 60 mg Placebo Long-term Safety Study Ulixacaltamide CT.gov NCT06087276 8 weeks 4 weeks 12 weeks
16 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)
17 Path to success De-risked Trial design based on key learnings from Essential1 Regulatory alignment based on successful End-of-Phase 2 meeting Efficient Focused execution Single protocol: Optimized screening, enrollment, analysis Streamlined Design 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
18 PRAX-628 Milestones Q3 2024: Begin enrolling EMPOWER observational study 2H 2024: Begin enrolling RADIANT open label study Q4 2024: Begin enrolling POWER1 registrational study 1H 2025: Begin enrolling POWER2 registrational study 1H 2025: Topline results for RADIANT 2H 2025: Topline results for POWER1
19 The Praxis epilepsy portfolio targets significant unmet need in both the common and rare epilepsy markets >$3B+ US Common and Developmental Epilepsy Market Opportunity 3.5M US Prevalence for Common Epilepsy 14K+ US Prevalence for Rare Epilepsies covered by Praxis’ Portfolio1 1 SCN2A Gof, SCN2A LoF, SYNGAP1, PCDH19, SCN8A, KCNT1 2 PRAX-020 (KCNT1) is a research collaboration with UCB 3 PRAX-080 (PCDH19 ), PRAX-090 (SYNGAP1) & PRAX-100 (SCN2A-LoF) ASOs are a collaboration with The Florey Institute of Neuroscience and Mental Health 4 Poke G, Stanley J, Scheffer IE, Sadleir LG. Epidemiology of Developmental and Epileptic Encephalopathy and of Intellectual Disability and Epilepsy in Children Praxis Epilepsy Portfolio PRAX-628 PRAX-0202 PRAX-0803 PRAX-0903 PRAX-1003 elsunersen relutrigine >100k Developmental Epilepsies with high seizure burden using sodium channel blockers4
20 Differentiated Profile Goal: Preferential action against neuronal hyperexcitability PRAX-628: 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
21 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 PRAX-628 shows a differentiated pre-clinical profile Protective index (PI) measured as tolerability / efficacy (TD50 / ED50); MES = maximal electroshock seizure 1. https://praxismedicines.com/wp-content/uploads/2023/12/Anderson_AES2023_Predictive-Validity_Poster_Final.pdf; 2. Praxis data on file 3. https://praxismedicines.com/wp-content/uploads/2023/12/Kahlig_AES2023_628-In-Vivo_Poster_Final.pdf PRAX-628 has differentiated potency in the MES model3 Preclinical decision tree optimized for focal seizure drug discovery1 Progress Development Abandon Progress DevelopmentAbandon PI >2 PI >2 PI >2 PI < 2 PI < 2 PI < 2 Audiogenic MES (mouse) 6-Hz, 32mA (mouse) PRAX-628 Results2
22 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 PRAX-628 20mg PRAX-628 30mg Mean Fold of MES EC50 achieved at Steady State Expected efficacy Additional tolerated margin for PRAX-628 toxicity and tolerability levels No tolerability concerns Ability to significantly exceed therapeutic concentrations while well tolerated PRAX-628 has unprecedented margins over best-in-class ASMs based on MES efficacy and clinical tolerability in humans
23 - 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 PRAX-628 • Composite endpoint from qEEG showed separation of drug versus placebo in the SAD and MAD cohorts • Difference between PRAX-628 and placebo significant for all doses at first point measured • Effect consistent with known PK profile • PRAX-628 achieves nearly complete coverage on Day 1 400 mg 25 mg 30 mg PRAX-628 composite qEEG change Hours of day 1 drug coverage Phase 1 study demonstrated brain activity and rapid achievement of therapeutic concentrations
24 • 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 PRAX-628 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 • PRAX-628 achieved between 3-13x multiples of MES EC50 exposure • Safety was consistent with prior dose escalation study and AEs were mild
25 PRAX-628 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 Initiate three efficacy trials in the ENERGY program
26 PRAX-628 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
27 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 for the interventional part of the POWER program will receive direct follow up and/or be directed into the POWER trials
28 • Measuring seizure frequency, seizure freedom, safety and pharmacokinetics • Will allow the evaluation of PRAX-628 in a broader population, including generalized epilepsy • Initiate in 2H 2024 with 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 PRAX-628 QD 8 weeks n ~ 50 Safety Follow-up 2 weeks post dose
29 Proposed study designs for POWER1 and POWER2 6 weeks, 30mg 12 weeks placebo • Screening • Observation • Randomization POWER1, n= 200 Safety follow-up • POWER1 to initiate 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
30 Relutrigine (PRAX-562) Milestones Q3 2024: Topline results in Phase 2 EMBOLD Study
31 Preclinical and emerging clinical data demonstrate relutrigine has the potential to be a first- and best-in-class small molecule for DEEs Superior selectivity for disease-state NaV channel hyperexcitability Convenient auto-titration regimen with stable PK Unprecedented therapeutic window with potential for superior safety and efficacy RELUTRIGINE SCN2A, SCN8A FORMULATED FOR PEDIATRIC USE SMALL MOLECULE FUNCTIONAL STATE MODULATOR
32 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
33 Relutrigine Phase 2 EMBOLD study topline data expected in Q3 2024 + 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 is permitted to a max of 1.0 mg/kg/day and a min of 0.25 mg/kg/day. Safety Follow- Up SAFETY FOLLOW- UP PERIOD (4 WEEKS) DOUBLE-BLIND TREATMENT PERIOD (16 WEEKS) Relutrigine 1:1 Randomization N=~20 (SCN2A/SCN8A) OLE TREATMENT PERIOD (48 WEEKS) Relutrigine 0.5 mg/kg/day Placebo for 4 weeks/relutrigine for 12 weeks+ 0.5 mg/kg/day PRIMARY ENDPOINT: Incidence and severity of treatment-emergent adverse events (TEAEs) KEY SECONDARY: Change from baseline in monthly (28 day) motor seizure frequency
34 EMBOLD is the tip of the iceberg for the potential of relutrigine in broader DEE population SCN2A, SCN8A EMBOLD study Potential future development Many DEEs already use sodium channel blockers Broad applicability for relutrigine in genetic driver with high seizure burden >100k patients High Seizure Burden Genetic epilepsies
35 Elsunersen (PRAX-222) SOLIDUS ASO PLATFORM
36 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
37 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)
®