PRAX-562

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

Pictured: a physician looks at a brain scan on a computer screen/iStock, gorodenkoff With a plethora of promising candidates moving through clinical trials, there are several upcoming data readouts of interest in both the neurodegenerative and neuropsychiatric spaces. Targeting amyotrophic lateral sclerosis (ALS), major depressive disorder, Huntington’s disease and many other worthy indications, here are six mid- to late-stage data readouts for candidates you’ll want to have on your radar. 1. Sanofi and Denali’s SAR443820/DNL788 Amyotrophic lateral sclerosis In the ALS space, Sanofi is expected to announce topline results from the Phase II HIMALAYA trial of SAR443820/DNL788, which it is developing with partner Denali Therapeutics, according to a Denali press release. SAR443820/DNL788 is a small molecule inhibitor of RIPK1, a critical signaling protein in a canonical inflammatory and cell death pathway, according to Denali. Increased RIPK1 activity in the central nervous system is thought to drive neuroinflammation and cell death, contributing to neurodegeneration. Part A of the double-blinded, randomized, placebo-controlled HIMALAYA trial, which has completed enrolling all 305 participants, involves evaluating patients’ change from baseline on the ALS Functional Rating Scale-Revised (ALSFRS-R), a tool used to determine disease progression. The primary outcome for Part B of the HIMALAYA program, the open-label extension, is the combined assessment of the function and survival (CAFS) score. SAR443820/DNL788 holds the FDA’s Fast Track designation for the treatment of ALS. Sanofi and Denali are also developing SAR443820/DNL788 for multiple sclerosis, for which it is being tested in the Phase II K2 study. 2. Intra-Cellular Therapies’ Lumateperone Major depressive disorder According to Graig Suvannavejh, senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas, major depressive disorder (MDD) is an area to watch this year. “There are several readouts in major depressive disorder,” he told BioSpace. Among those, he highlighted anticipated Phase III datasets for Intra-Cellular Therapies’ Caplyta (lumateperone). Intra-Cellular’s lead asset, lumateperone won approval in 2019 for schizophrenia and received a label expansion in December 2021 for depressive episodes associated with bipolar disorder. Now the company is seeking a third indication, MDD, and expects data from two Phase III studies during the first half of 2024. Lumateperone, an oral antipsychotic medication, is currently being assessed in a three-part Phase III program for MDD. Studies 501, 502 and 505 are testing the drug in adult patients who are having inadequate response to an approved antidepressant. The primary endpoint for these studies is change in Montgomery Asberg Depression Rating Scale (MADRS) total score after six weeks, while a key secondary endpoint is change in CGI-S score over the same period of time. The company anticipates topline data from Study 501 in the first quarter of 2024 and for Study 502 in Q2, according to a January corporate presentation. In another Phase III trial, reported in March 2023, lumateperone eased the burden of depressive episodes in patients with MDD or bipolar depression with mixed features. Suvannavejh said these data, along with lumateperone’s approval for depressive episodes associated with bipolar disorder, “gives us a level of confidence” in the drug. 3. Annexon Biosciences’ ANX005 Guillain-Barré syndrome Brisbane, Calif.–based Annexon Biosciences is expecting pivotal data from a Phase III trial of its lead candidate ANX005, being developed for Guillain-Barré syndrome (GBS), during the first six months of 2024. There are no FDA-approved treatments for GBS, a potentially fatal, serious autoimmune condition of the nervous system that can cause paralysis, neurodegeneration and cognitive impairment, according to an Annexon press release outlining expected 2024 milestones. GBS is caused by an autoantibody attack on the peripheral nerves, triggering the complement cascade (C1q). ANX005 is designed to inhibit C1s along with the entire complement pathway. It has received both Fast Track and Orphan Drug designations from the FDA in this indication. A Phase III study testing the efficacy, safety, pharmacokinetics and pharmacodynamics of ANX005, an investigational monoclonal antibody, completed enrollment in 2023 and is on track to read out data before July, Annexon noted in the press release. In a Phase Ib trial, ANX005 “showed rapid and consistent improvement in muscle strength” and “improvement in neuronal damage and clinical function in patients with GBS,” according to Annexon. 4. Wave Life Sciences’ WVE-003 Huntington’s disease One of the most intractable neurodegenerative illnesses, Huntington’s disease continues to stump biopharma, but companies aren’t giving up. One of these is Cambridge, Mass.–based Wave Life Sciences, which is testing an antisense therapy, WVE-003, in the Phase Ib/IIa SELECT-HD trial. Wave anticipates sharing data from the 30 mg multi-dose cohort of this study with extended follow-up, along with all single-dose data, in the second quarter of 2024, according to a company press release outlining 2024 milestones. Huntington’s disease is caused by a CAG repeat in the first exon of the huntingtin (HTT) gene. This mutation causes brain cells to die, leading to a host of progressive cognitive, psychiatric and movement symptoms, including an involuntary jerking or writhing movement, also known as chorea. WVE-003 is designed to preferentially lower mutant HTT (mHTT) protein levels by targeting a single nucleotide polymorphism called SNP3 that appears on the mHTT transcript, Wave CEO Paul Bolno told BioSpace in a previous interview. An estimated 40% of adults with Huntington’s carry SNP3 in association with the Huntington’s mutation, Bolno said. Wave presented data in September 2022 from SELECT-HD showing early indications of decreases in mHTT in the cerebrospinal fluid. Wildtype HTT [wtHTT]—the good type of huntingtin protein—was preserved at both doses, the company reported. A recently posted preclinical study reinforced the importance of wtHTT-sparing biology and that the protein’s preservation is also “important in delaying the progression of the disease,” Bolno told BioSpace last week. “These data will be the first repeat-dose assessment of wildtype [huntingtin] preservation with mutant huntingtin knockdown.” For Wave, the anticipated results also have implications for an existing collaboration agreement with Takeda, which has the option to co-develop and co-commercialize WVE-003. Per the press release, these data are expected to inform Takeda’s decision on whether or not to opt in. However, under the terms of the agreement, Wave retains control of development and regulatory approval in either case, Bolno noted. So the company is more focused on whether the program “goes the distance in terms of delivering a medicine to patients,” he said. 5 and 6. Praxis Precision Medicines’ PRAX-562 and PRAX-628 Epilepsy Two key anticipated data readouts in the epilepsy space come from Praxis Precision Medicines. First, topline results from the Phase IIa PPR study of PRAX-628 in patients with photo-paroxysmal response (PPR) epilepsy are expected in the first quarter of this year. Positive preliminary analysis of the study’s 15-mg cohort “exceeds expectations” in terms of drug activity, according to a Praxis clinical portfolio update. The new data are expected to be released following completion of the 45-mg cohort. PRAX-628, which targets focal epilepsy, is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain. Initial data show the candidate “has a good tolerability profile, a potentially wide therapeutic index” and the ability to reach efficacious concentrations within 24 hours, according to Praxis. Also expected during the first half of 2024 are results from the Phase II EMBOLD study testing PRAX-562, a unique sodium channel modulator, in pediatric patients with SCN2A and SCN8A developmental epilepsies. PRAX-628 and PRAX-562 are both based on Praxis’ Cerebrum small molecule platform, which leverages a “deep understanding of neuronal excitability and neuronal networks,” according to Praxis’ website. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.