PRAX-114

Praxis said its internal research efforts give it confidence that small molecules can selectively inhibit the KCNT1 potassium channel. It’s been a tough year of layoffs and pipeline culls for Praxis Precision Medicines, but the biotech is ending 2022 on a positive note courtesy of a collaboration with UCB to develop a potential first-ever treatment for a specific type of epilepsy. The collaboration is based upon Praxis’ PRAX-020 program to discover small-molecule therapeutics as potential treatments of KCNT1-related epilepsies, for which there are currently no approved treatments. As well as an upfront payment from the Belgian biopharma, Praxis will be eligible for development and commercial milestone payments to the tune of up to $100 million, on top of royalties. UCB retains an exclusive option to in-license global development and commercialization rights to any KCNT1 small-molecule candidate that results from the agreement. The money will come as welcome news to Praxis, which laid off staff and halted a clutch of clinical trials after its nervous system drug PRAX-114 failed to deliver in a phase 2 study in June. The company moved to prioritize its programs in movement disorders and epilepsy, a decision that appears to have paid off with the UCB deal. Not that Praxis’ bank account is empty—the Boston-based company had $123.7 million in cash and equivalents as of the end September. It may be a drop of over $150 million on the funds the biotech entered the year with, but Praxis reckoned it was still enough to fund it through the start of 2024, even before any payments from UCB are taken into account. “Our internal research efforts give us confidence that small molecules can selectively inhibit the KCNT1 channel and potentially could be an effective treatment for individuals suffering from KCNT1-related epilepsy,” Praxis CEO Marcio Souza said in a postmarket release Tuesday. “The collaboration with UCB validates this approach and will allow us to accelerate efforts toward a potential treatment for KCNT1 patients.” As well as a number of other potential epilepsy programs in preclinical development, Praxis has one already in phase 2, with others due to enter phase 1 and 2 before the end of the year. One of these, PRA-562, was recently released from an FDA clinical hold.

PRAX-944 Phase 2b Essential1 study topline results for essential tremor expected in 1Q23 PRAX-222 EMBRAVE study forSCN2A-DEE to initiate in 4Q22; topline results for initial dose cohort expected in 2023 PRAX-628 Phase 1 healthy volunteer study to initiate in 4Q22; focal epilepsy study planned for 2023 Cash and investments of $123.7 million as of September 30, 2022 supports runway into 1Q24 BOSTON, Nov. 09, 2022 (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 third quarter of 2022. “With recent progress in the PRAX-944 Essential1 study, we are positioned to deliver topline results next quarter,” said Marcio Souza, president and chief executive officer of Praxis. “On the heels of the positive topline results from our Phase 2a study in essential tremor, we are encouraged by the pro PRAX-944 and look forward to sharing these data in the coming months. With first-in-patient studies for our lead epilepsy programs expected to start shortly, as well as a Phase 1 study for our third clinical-stage epilepsy program, PRAX-628, our pipeline continues to advance, setting us up for an exciting year ahead.” Recent Business Highlights and Upcoming Milestones: Movement Disorders Praxis expects topline results from the ongoing PRAX-944 Essential1 study for the treatment of moderate to severe essential tremor (ET) in the first quarter of 2023. Screening for the Essential1 study will be completed by mid-November 2022. Essential1 is a randomized, double-blind, placebo-controlled, dose-range-finding Phase 2b trial evaluating the efficacy, safety and tolerability of once-daily daytime treatment of 60 mg or 100 mg of PRAX-944 compared to placebo after 56 days. The primary endpoint is change from baseline to day 56 in the modified Activities of Daily Living (mADL1) score, the U.S. Food and Drug Administration’s (FDA) suggested efficacy endpoint for ET. Following topline results, Praxis intends to meet with the FDA for an end-of-Phase 2 meeting in the first half of 2023 and initiate its Phase 3 development program for the treatment of ET in mid-2023. The Company expects to initiate a randomized, double-blind, placebo-controlled Phase 2 trial to evaluate the efficacy, safety and tolerability of once-daily treatment of up to 100 mg of PRAX-944 as a non-dopaminergic treatment for the motor symptoms of Parkinson’s disease in the first quarter of 2023. Topline results are expected in the second half of 2023. Following the positive topline results of Part B of the Phase 2a study of PRAX-944 for the treatment of ET, the PRAX-944 Parkinson’s disease study design was revised, including changing the primary endpoint to efficacy from safety. Praxis presented the following posters at the 2022 International Congress of Parkinson’s Disease and Movement Disorders (MDS) from September 15 – 18, 2022: The Hidden Disease Burden and Treatment Experience of Patients with Essential Tremor: A Retrospective US Claims Analysis (Abstract Number: 968) A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults with Essential Tremor (Abstract Number: 951) A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of PRAX-944 for the Treatment of Essential Tremor (Abstract Number: 950) In October 2022, Praxis published the findings from an observational study, “The Hidden Burden of Disease and Treatment Experiences of Patients with Essential Tremor: A Retrospective Claims Data Analysis,” in Advances in Therapy2. The large claims-based analysis examines US claims data from 2015 to 2019, including diagnosis rates, comorbidities and treatment patterns in patients diagnosed with ET. Study findings highlight the hidden patient impact as well as the urgent unmet need for more treatment options and complexity of ET diagnosis. Key findings from the study include: Approximately 1 million people were diagnosed and sought treatment for ET from 2015 to 2019 and it is estimated that another 1 million remained untreated Propranolol (24%), primidone (20%) and gabapentin (19%) were the most commonly prescribed therapeutics following diagnosis Two in three patients received pharmacological treatment for ET, with 2-year treatment discontinuation rates of approximately 40% (40% for propranolol, 47% for primidone), or about 200,000 patients annually Nearly all patients (96%) had at least one comorbidity; depression and anxiety rates in ET patients were 2 times greater those in the general population aged 65 years and older Confirmed ET diagnosis was established about 1.5 years after the diagnosis of an initial movement disorder Epilepsy Praxis plans to initiate the first dose cohort of the PRAX-222 EMBRAVE study for the treatment of pediatric patients with early-seizure-onset SCN2A developmental and epileptic encephalopathy (DEE) in the U.S. in the fourth quarter of 2022. Following collection of the safety and efficacy data from the initial cohort of patients in the EMBRAVE study, the data will be evaluated and submitted to the FDA to seek authorization for dose escalation. Topline results from the initial dose cohort are expected in 2023. In October 2022, Praxis received additional detail from the FDA regarding the clinical hold for its Investigational New Drug (IND) application for PRAX-562 for the treatment of pediatric patients with SCN2A and SCN8A DEEs. Based on the feedback from the FDA, the Company expects that no new preclinical or clinical studies will be required to clear the clinical hold. Praxis is currently engaged with the FDA and expects to initiate a Phase 2, placebo-controlled trial in the first quarter of 2023. Praxis expects to initiate a PRAX-628 Phase 1 study in the fourth quarter of 2022 and subsequently initiate a Phase 2 study in focal epilepsy in 2023. Psychiatry Following the completion of the PRAX-114 Phase 2 Acapella Study for the treatment of Major Depressive Disorder in the third quarter of 2022, Praxis does not currently plan to pursue further development of PRAX-114 for psychiatric disorders. The PRAX-114 Phase 2 Acapella study (N=110) was intended to provide additional understanding of the dose range and to evaluate the safety and efficacy of PRAX-114 at doses of 10, 20, 40 and 60 mg. Topline data indicated a linear dose response trend on the primary endpoint of change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D17) total score at Day 15, but were not statistically significant. In multiple secondary endpoints evaluating 40 mg of PRAX-114 relative to placebo, nominal statistical significance was achieved at Day 4, but not maintained at subsequent timepoints. Third Quarter 2022 Financial Results: As of September 30, 2022, Praxis had $123.7 million in cash, cash equivalents and marketable securities, compared to $275.9 million in cash, cash equivalents and marketable securities as of December 31, 2021. This decrease of $152.2 million primarily reflects cash used in operations of $156.2 million during the nine months ended September 30, 2022, partially offset by $4.3 million in net proceeds from at-the-market offerings of shares of the Company's common stock. The Company’s cash, cash equivalents and marketable securities as of September 30, 2022 are expected to fund operations into the first quarter of 2024. Research and development expenses were $30.4 million for the three months ended September 30, 2022, compared to $33.1 million for the three months ended September 30, 2021. The decrease in research and development expenses of $2.7 million was primarily attributable to $6.5 million in decreased clinical-related spend for the Company's Psychiatry franchise, partially offset by $5.2 million in increased expenses for the Company's Movement Disorders and Epilepsy franchises. General and administrative expenses were $13.9 million for the three months ended September 30, 2022, compared to $11.6 million for the three months ended September 30, 2021. The increase in general and administrative expenses of approximately $2.3 million was primarily due to increased personnel-related costs due to increased headcount. Praxis reported a net loss of $43.9 million for the three months ended September 30, 2022, including $6.7 million of stock-based compensation expense, compared to $44.7 million for the three months ended September 30, 2021, including $6.5 million of stock-based compensation expense. As of September 30, 2022, Praxis had 46.9 million shares of common stock outstanding. About Praxis Praxis Precision Medicines is a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying insights from genetic epilepsies to both rare and more prevalent neurological disorders, using our understanding of shared biological targets and circuits in the brain. Praxis has established a broad portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit and follow us on LinkedIn and Twitter. 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 expectations, plans and timing for our clinical data, the anticipated timing of our clinical trials and regulatory filings, the development of our product candidates, including the design of our clinical trials and the treatment potential of our product candidates, and the sufficiency of our cash, cash equivalents and marketable securities, and 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 submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; risks, uncertainties and assumptions regarding the impact of the continuing COVID-19 pandemic on Praxis’ business, operations, strategy, goals and anticipated timelines, Praxis’ ongoing and planned preclinical activities, Praxis’ ability to initiate, enroll, conduct or complete ongoing and planned clinical trials and Praxis’ timelines for regulatory submissions; and other risks concerning Praxis’ programs and operations as described in its Quarterly Report on Form 10-Q for the six months ended June 30, 2022 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) September 30, 2022 December 31, 2021 Assets Cash and cash equivalents $ 62,440 $ 138,704 Marketable securities 61,300 137,207 Prepaid expenses and other current assets 8,572 11,498 Property and equipment, net 1,077 1,213 Operating lease right-of-use assets 3,097 3,653 Other non-current assets 416 472 Total assets $ 136,902 $ 292,747 Liabilities and stockholders’ equity Accounts payable $ 10,122 $ 10,780 Accrued expenses 17,884 26,844 Operating lease liabilities 3,733 4,311 Common stock 5 5 Additional paid-in capital 595,165 567,598 Accumulated other comprehensive loss (536 ) (176 ) Accumulated deficit (489,471 ) (316,615 ) Total liabilities and stockholders' equity $ 136,902 $ 292,747 PRAXIS PRECISION MEDICINES, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Amounts in thousands, except share and per share amounts) (Unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 Operating expenses: Research and development $ 30,439 $ 33,139 $ 126,711 $ 76,746 General and administrative 13,851 11,634 46,822 31,929 Total operating expenses 44,290 44,773 173,533 108,675 Loss from operations (44,290 ) (44,773 ) (173,533 ) (108,675 ) Other income: Other income, net 345 73 677 201 Total other income 345 73 677 201 Loss before income taxes $ (43,945 ) $ (44,700 ) $ (172,856 ) $ (108,474 ) Provision for income taxes — (5 ) — (5 ) Net loss $ (43,945 ) $ (44,705 ) $ (172,856 ) $ (108,479 ) Net loss per share attributable to common stockholders, basic and diluted $ (0.96 ) $ (1.00 ) $ (3.79 ) $ (2.61 ) Weighted average common shares outstanding, basic and diluted 45,774,376 44,714,941 45,591,888 41,608,017 1mADL is a composite sum of items 1 to 11 of the TETRAS-ADL subscale and items 6 (bilateral) and 7 of the TETRAS-PS; mADL score is calculated as the sum of all 13 items (item 6 of TETRAS-PS x2) and ranges from 0 to 42 2 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). Investor Contact: Alex Kane Praxis Precision Medicines investors@praxismedicines.com 617-300-8481 Media Contact: Ian Stone Canale Communications Ian.stone@canalecomm.com 619-849-5388