VDCCs x SCNA

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, Aug. 13, 2024 (GLOBE NEWSWIRE) -- 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. Since beginning recruitment in November 2023, there have been over 75,000 pre-screening forms, of which 11,000 referrals meet pre-qualifying eligibility criteria.Praxis 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.Long-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. EMPOWER 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 burdenRADIANT 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 2025POWER1 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. The 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.Based 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 First arm of the global confirmatory study initiated in BrazilPivotal 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 UlixacaltamideUlixacaltamide 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-628PRAX-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 PraxisPraxis 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. PRAXIS PRECISION MEDICINES, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(Amounts in thousands)(Unaudited) June 30, 2024 December 31, 2023Assets 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 Ends June 30, Six Months Ended June 30, 2024 2023 2024 2023 Collaboration revenue$357 $781 $788 $1,464 Operating expenses: Research and development 27,260 25,614 54,244 51,118 General and administrative 10,585 10,127 25,918 23,397 Total operating expenses 37,845 35,741 80,162 74,515 Loss from operations (37,488) (34,960) (79,374) (73,051)Other income: Other income, net 4,811 648 7,144 1,284 Total other income 4,811 648 7,144 1,284 Net loss$(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

Plans to initiate two efficacy studies investigating PRAX-628 in focal onset seizures in the second half of 2024 and first half of 2025, respectively Continued strong recruitment for the pivotal Essential3 trials in Essential Tremor (ET), with over 50,000 pre-screening forms and over 7,000 referrals received to date that meet pre-qualifying eligibility criteria; topline results expected in the second half of 2024 Randomization in PRAX-562 Phase 2 EMBOLD study completed in pediatric patients with developmental and epileptic encephalopathies (DEEs), with topline results expected in the third quarter of 2024 Completed two underwritten public offerings in 2024; Cash and investments of $451.2 million as of April 30, 2024 extends runway into 2027 BOSTON, May 13, 2024 (GLOBE NEWSWIRE) -- 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 first quarter 2024. “In the first quarter we made significant progress on all fronts. We strengthened our financial resources and reported positive photo paroxysmal response (PPR) results in PRAX-628, which we believe further de-risks our clinical development program and positions PRAX-628 as the first precision sodium channel modulator for focal onset seizures. The strength and consistency observed across both study arms, combined with a favorable tolerability and safety profile, builds confidence in our planned focal onset seizure studies for PRAX-628, with the first expected to initiate in the second half of 2024,” said Marcio Souza, president and chief executive officer of Praxis. “Looking ahead, we are encouraged by the strong participation we are seeing in our Essential3 Phase 3 studies and remain on track to read out topline results in the second half of this year. These advancements, through patient-guided development strategies, will further position Praxis at the forefront of precision medicine for CNS disorders.” Recent Highlights and Anticipated Milestones: Cerebrum™ Small Molecule Platform Ulixacaltamide for ET: Essential3, the Phase 3 program for ulixacaltamide, continues to progress through patient qualification, enrollment and trial execution, with topline results expected in the second half of 2024 to support a planned New Drug Application (NDA) submission in 2025. Essential3 is comprised of two simultaneous Phase 3 studies including a 12-week, parallel design study and a 12-week randomized withdrawal study for stable responders.Since beginning recruitment in November 2023, there have been over 50,000 pre-screening forms and over 7,000 referrals received to date meeting pre-qualifying eligibility criteria. Randomization pace is now dictated by appropriate patient selection and pre-randomization stability and severity criteria.At the American Academy of Neurology 2024 Annual Meeting, Praxis shared additional posters on the Essential3 study design [link] and the benefits of ulixacaltamide over propranolol as analyzed from the Essential1 study [link]. PRAX-628 for Focal Onset Seizures: Praxis reported positive results, with 100% of patients responding in a Phase 2a proof of concept study evaluating PRAX-628 in epilepsy patients with PPR and confirmed plans to initiate two efficacy studies in focal onset seizures. The PPR study had two cohorts, where all patients responded. In the 15 mg cohort (n=5), 80% of patients achieved a complete response and 20% achieved a partial response.In the 45 mg cohort (n=3), 100% of patients achieved a complete response.Safety was consistent with the prior dose escalation study and pharmacokinetic analysis confirmed therapeutic exposures. Praxis plans to initiate two efficacy studies in focal onset seizures. The first study is expected to begin in the second half of 2024, with topline results expected in 2025.The second study is expected to initiate in the first half of 2025, with topline results expected in the first half of 2026. PRAX-562 for SCN2A and SCN8A DEEs: Praxis expects topline results from the PRAX-562 Phase 2 EMBOLD study for the treatment of pediatric patients with DEEs in the third quarter of 2024. The EMBOLD study is a randomized, double-blind, placebo-controlled Phase 2 clinical study to evaluate the safety, tolerability, efficacy (motor seizure frequency) and pharmacokinetics of PRAX-562 in pediatric patients aged 2 to 18 years with DEEs, followed by an open-label extension. Solidus™ Antisense Oligonucleotide (ASO) Platform Elsunersen (PRAX-222) for SCN2A Gain-of-Function (GoF) DEEs: Praxis is completing multiple global regulatory interactions in the first half of 2024 in anticipation of starting the pivotal phase of the program later in 2024. Corporate Update: In January 2024, Praxis completed an underwritten public offering with net proceeds of approximately $161.6 million.In January 2024, Praxis announced a licensing partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide for the treatment of ET in Greater China, including mainland China, Hong Kong, Macau and Taiwan, with total potential consideration of over $275 million.In April 2024, Praxis completed an additional underwritten public offering with net proceeds of approximately $215.8 million.As of April 30, 2024, Praxis had cash, cash equivalents, and marketable securities of $451.2 million. First Quarter 2024 Financial Results: As of March 31, 2024, Praxis had $243.3 million in cash, cash equivalents and marketable securities. Current cash, cash equivalents and marketable securities are expected to fund operations into 2027. Research and development expenses were $27.0 million for the three months ended March 31, 2024, compared to $25.5 million for the three months ended March 31, 2023. The increase in research and development expenses of $1.5 million was primarily attributable to $2.8 million in increased personnel expenses and $1.7 million in increased expenses related to the Company's Cerebrum™ platform, partially offset by $2.4 million in decreased expenses related to the Company’s Solidus™ platform. General and administrative expenses were $15.3 million for the three months ended March 31, 2024, compared to $13.3 million for the three months ended March 31, 2023. The increase in general and administrative expenses of approximately $2.0 million was primarily due to an increase in personnel-related costs, partially offset by a decrease in consulting and professional fees. Praxis reported a net loss of $39.6 million for the three months ended March 31, 2024, including $14.5 million of stock-based compensation expense, compared to $37.5 million for the three months ended March 31, 2023, including $7.6 million of stock-based compensation expense. As of March 31, 2024, Praxis had 13.3 million shares of common stock outstanding. 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 voltage-gated sodium (NaV) channels in the brain that is currently being developed as a once daily, oral treatment for adult focal onset seizures. Preclinical data demonstrates PRAX-628 is differentiated from standard of care, with the potential to be best-in-class for focal onset seizures. 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 onset seizures. 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 ElsunersenElsunersen is an ASO designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early onset SCN2A-DEE to treat seizures and other symptoms in patients with GoF 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.org/. About PRAX-562 PRAX-562 is a first-in-class small molecule in development for the treatment of DEEs 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. PRAX-562’s mechanism of NaV channel modulation is consistent with superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of PRAX-562 have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. PRAX-562 has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV modulation. PRAX-562 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 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; 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. PRAXIS PRECISION MEDICINES, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(Amounts in thousands)(Unaudited) March 31, 2024 December 31, 2023Assets Cash and cash equivalents$151,980 $81,300 Marketable securities 91,309 — Prepaid expenses and other current assets 4,388 3,580 Property and equipment, net 476 588 Operating lease right-of-use assets 1,840 2,064 Other non-current assets 416 416 Total assets$250,409 $87,948 Liabilities and stockholders’ equity Accounts payable$9,404 $5,815 Accrued expenses 6,976 7,416 Operating lease liabilities 2,224 2,495 Deferred revenue 2,122 2,553 Common stock 13 13 Additional paid-in capital 923,141 723,577 Accumulated other comprehensive loss 3 — Accumulated deficit (693,474) (653,921)Total liabilities and stockholders' equity$250,409 $87,948 PRAXIS PRECISION MEDICINES, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Amounts in thousands, except share and per share amounts)(Unaudited) Three Months EndedMarch 31, 2024 2023 Collaboration revenue$431 $683 Operating expenses: Research and development 26,984 25,504 General and administrative 15,333 13,270 Total operating expenses 42,317 38,774 Loss from operations (41,886) (38,091)Other income: Other income, net 2,333 636 Total other income 2,333 636 Net loss$(39,553) $(37,455)Net loss per share attributable to common stockholders, basic and diluted$(2.84) $(10.58)Weighted average common shares outstanding, basic and diluted 13,904,374 3,540,185

Over 3,000 referrals received to date meet pre-qualifying eligibility criteria for ulixacaltamide Phase 3 studies in the Essential3 program for essential tremor (ET); enrollment on track to be completed in 1H 2024 with topline results in 2H 2024 Topline results from the PRAX-628 study in epilepsy patients with photo-paroxysmal response (PPR) expected in 1Q 2024; preliminary analysis of 15 mg cohort exceeded expectations Tolerability and efficacy results from Part 1 of the EMBRAVE study of elsunersen were presented at the American Epilepsy Society 2023 Annual Meeting, showing 43% median reduction in seizures; received PRIME designation from the European Medicines Agency for the treatment of SCN2A gain-of-function developmental and epileptic encephalopathy (DEE) Announced licensing partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide for ET in Greater China with total potential consideration of over $275 million Completed underwritten public offering with over $160 million in net proceeds to extend cash runway into 2026 BOSTON, March 05, 2024 (GLOBE NEWSWIRE) -- 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 fourth quarter and full-year 2023. “2023 was a transformational year for Praxis. Living by our Dare for More™ motto, we made significant advancements across our portfolio of precision therapies for CNS disorders, established strategic collaborations and strengthened our financial position, which we believe will carry us beyond our upcoming milestones in the year ahead,” said Marcio Souza, president and chief executive officer of Praxis. “Notably, the strong participation we are seeing in our Essential3 Phase 3 studies in ulixacaltamide for essential tremor continues to highlight the significant unmet need for new therapies in essential tremor. We are also encouraged by the latest data supporting our highly differentiated epilepsy portfolio, including elsunersen and PRAX-628.” Mr. Souza continued, “Looking ahead, we plan to report topline results from the PRAX-628 study in the first quarter, complete enrollment in Essential3 in the first half of this year and expect topline results from the Phase 2 EMBOLD study of PRAX-562 for the treatment of pediatric patients with DEEs mid-year. Together, these advancements, through patient-guided development strategies, will further position Praxis at the forefront of precision medicine for CNS disorders.” Recent Highlights and Anticipated Milestones: Cerebrum™ Small Molecule Platform Ulixacaltamide for ET: In November 2023, Praxis initiated Essential3, the Phase 3 program for ulixacaltamide. Enrollment in Essential3 is expected to complete in the first half of 2024, with topline results expected in the second half of 2024 to support a planned New Drug Application (NDA) submission in 2025. Essential3 is comprised of two simultaneous Phase 3 studies including a 12-week, parallel design study and a 12-week randomized withdrawal study for stable responders.Essential3 incorporates learnings from the Phase 2 Essential1 study including the use of a single 60 mg dose, using a modified Activities of Daily Living scale (mADL11) as the primary endpoint based on feedback from the U.S. Food and Drug Administration (FDA), and conducting the study in a decentralized manner. In the Phase 2 Essential1 study, mADL11 produced a statistically significant and clinically meaningful response in ulixacaltamide when compared to placebo after 8 weeks of treatment (p=0.042, nominal).Essential3 has over 3,000 referrals who have met the pre-qualifying eligibility criteria from the ongoing recruitment campaign started in November 2023. PRAX-628 for Focal Epilepsy: The Phase 2a PPR study to evaluate the efficacy and safety of PRAX-628 across two cohorts, dosed at 15 mg and 45 mg, continues to advance, with plans to report topline results in the first quarter of 2024. PPR studies measure electroencephalogram (EEG) signatures after intermittent photic stimulation and are widely used as a marker of anti-seizure efficacy and to aid in dose determination.Preliminary analysis of the 15 mg cohort exceeded Praxis’ drug activity expectations and confirmed its decision to initiate a Phase 2b study of PRAX-628 in focal epilepsy in the second half of 2024.The Phase 2a study builds on positive results from the Phase 1 dose escalation study in healthy volunteers. PRAX-628 was generally well-tolerated at all tested doses. Pharmacokinetic data demonstrated dose-dependent exposure supporting once-daily dosing without titration to achieve potentially therapeutically effective drug concentration levels.Further analysis of patients in the Phase 1 study using qEEG data showed a pharmacodynamic effect at all dose levels and was significantly different from placebo. PRAX-562 for SCN2A and SCN8A DEEs: Praxis expects topline results from the PRAX-562 Phase 2 EMBOLD study for the treatment of pediatric patients with DEEs in mid-2024. The EMBOLD study is a randomized, double-blind, placebo-controlled Phase 2 clinical study to evaluate the safety, tolerability, efficacy (motor seizure frequency) and pharmacokinetics of PRAX-562 in pediatric patients aged 2 to 18 years with DEEs, followed by an open-label extension. Up to 20 participants with SCN2A-DEE or SCN8A-DEE are expected to be enrolled. Solidus™ Antisense Oligonucleotide (ASO) Platform Elsunersen (PRAX-222) for SCN2A Gain-of-Function (GoF) Developmental Epilepsies: At the American Epilepsy Society 2023 Annual Meeting, Praxis shared data from Part 1 of the EMBRAVE study, where four patients were dosed once a month for a four-month period. Results showed a 43% median reduction in seizures from baseline, a 48% increase in seizure-free days from baseline and no drug-related treatment-emergent adverse events or serious adverse events. Elsunersen received PRIME designation from the European Medical Agency (EMA) for the treatment of SCN2A GoF DEEs. The EMA’s PRIME designation provides enhanced development support for priority medicines that target an unmet need and was granted based on the Part 1 data from the EMBRAVE study that showed a reduction in seizures and improvement in seizure free days, as well as preclinical data.Praxis is completing multiple global regulatory interactions in the first quarter of 2024 in anticipation of starting the pivotal phase of the program later this year. Corporate Update: In January 2024, Praxis completed an underwritten public offering. The net proceeds from the offering were approximately $161.7 million. As of February 29, 2024, Praxis had cash and cash equivalents of $247.6 million, which is anticipated to fund operations into 2026.In January 2024, Praxis announced a licensing partnership with Tenacia Biotechnology to develop and commercialize ulixacaltamide for the treatment of ET in Greater China, including mainland China, Hong Kong, Macau and Taiwan, with total potential consideration of over $275 million. Fourth Quarter and Full Year 2023 Financial Results: As of December 31, 2023, Praxis had $81.3 million in cash and cash equivalents, compared to $100.5 million in cash, cash equivalents and marketable securities as of December 31, 2022. This decrease of $19.2 million primarily reflects cash used in operations of $111.1 million during the year ended December 31, 2023, partially offset by $63.4 million in net proceeds from the June 2023 follow-on public offering and $28.2 million in net proceeds from at-the-market offerings. The Company’s cash and cash equivalents as of December 31, 2023, combined with $161.7 million net proceeds from the January 2024 follow-on offering and $5.3 million from January 2024 at-the-market offerings, are expected to fund operations into 2026. Praxis recognized $0.5 million and $2.4 million in collaboration revenue during the three months and year ended December 31, 2023, respectively, related to its Option and License Agreement with UCB which was entered into in December 2022. Research and development expenses were $18.4 million for the fourth quarter of 2023, compared to $28.3 million for the fourth quarter of 2022. Research and development expenses were $86.8 million for the year ended December 31, 2023, compared to $155.0 million for the year ended December 31, 2022. The decrease in research and development expenses for full year 2023 of $68.2 million was primarily attributable to $61.4 million in decreased expenses related to the Company’s Cerebrum™ platform. General and administrative expenses were $9.9 million for the fourth quarter of 2023, compared to $13.1 million for the fourth quarter of 2022. General and administrative expenses were $42.1 million for the year ended December 31, 2023, compared to $59.9 million for the year ended December 31, 2022. The decrease in general and administrative expenses for full year 2023 of $17.8 million was primarily attributable to a decrease of $7.6 million in professional fees and consulting expenses, $7.4 million in personnel-related expenses due to a decrease in headcount, and $2.9 million in other general and administrative expenses. Praxis incurred a net loss of $26.9 million for the fourth quarter of 2023, including $5.7 million of stock-based compensation expense, compared to $41.2 million for the fourth quarter of 2022, including $6.4 million of stock-based compensation expense. Praxis reported a net loss of $123.3 million for the year ended December 31, 2023, including $24.9 million of stock-based compensation expense, compared to a net loss of $214.0 million for the year ended December 31, 2022, including $28.6 million of stock-based compensation expense. As of December 31, 2023, Praxis had 8.8 million shares of common stock outstanding. 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 (PRAX-222) 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 PRAX-222 have demonstrated reduction in both SCN2A gene expression and protein levels. In vivo, PRAX-222 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. PRAX-222 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 PRAX-222 program is ongoing under a collaboration with Ionis Pharmaceuticals, Inc. and RogCon, Inc. To learn more about the EMBRAVE study, please visit https://www.embravestudy.com/. About PRAX-562 PRAX-562 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. PRAX-562’s mechanism of sodium channel block is consistent with superior selectivity for disease state sodium channel (NaV) channel hyperexcitability. In vivo studies of PRAX-562 have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. PRAX-562 has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel blocking effects. PRAX-562 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 to be filed 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. PRAXIS PRECISION MEDICINES, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(Amounts in thousands) (Unaudited) December 31, 2023 December 31, 2022Assets Cash and cash equivalents$81,300 $61,615 Marketable securities — 38,874 Prepaid expenses and other current assets 3,580 10,351 Property and equipment, net 588 971 Operating lease right-of-use assets 2,064 2,901 Other non-current assets 416 416 Total assets$87,948 $115,128 Liabilities and stockholders’ equity Accounts payable$5,815 $14,672 Accrued expenses 7,416 15,850 Operating lease liabilities 2,495 3,500 Deferred revenue 2,553 5,000 Common stock 13 5 Additional paid-in capital 723,577 606,918 Accumulated other comprehensive loss — (173)Accumulated deficit (653,921) (530,644)Total liabilities and stockholders' equity$87,948 $115,128 PRAXIS PRECISION MEDICINES, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Amounts in thousands, except share and per share amounts) (Unaudited) Three Months EndedDecember 31, Year Ended December 31, 2023 2022 2023 2022 Collaboration revenue$515 $— $2,447 $— Operating expenses: Research and development 18,388 28,329 86,766 155,040 General and administrative 9,933 13,124 42,054 59,946 Total operating expenses 28,321 41,453 128,820 214,986 Loss from operations (27,806) (41,453) (126,373) (214,986)Other income: Other income, net 928 280 3,096 957 Total other income 928 280 3,096 957 Net loss$(26,878) $(41,173) $(123,277) $(214,029)Net loss per share attributable to common stockholders, basic and diluted$(2.97) $(12.98) $(18.69) $(69.65)Weighted average common shares outstanding, basic and diluted 9,060,813 3,172,981 6,594,316 3,073,100