[Translation] A randomized, open-label, single-dose, four-period, completely repeated crossover, fasting and fed bioequivalence study in healthy subjects

采用单中心、单次给药、随机、开放、四周期、完全重复交叉试验设计，在中国健康成年受试者空腹及餐后状态下的吸收速度和吸收程度，评价受试制剂与参比制剂在空腹及餐后条件下的生物等效性及安全性。

[Translation]

A single-center, single-dose, randomized, open, four-period, completely repeated crossover trial design was used to evaluate the bioequivalence and safety of the test preparation and the reference preparation under fasting and fed conditions by comparing the absorption rate and extent of the test preparation in healthy adult Chinese subjects.

Start Date16 May 2023

Sponsor / Collaborator

SZYY Group Pharmaceutical Ltd.

CTR20231500 / RecruitingPhase 1

雷沙吉兰舌下膜线性动力学研究及与原研Azilect的生物利用度研究

[Translation] Study on the linear kinetics of rasagiline sublingual film and its bioavailability compared with the original Azilect

Ia：雷沙吉兰舌下膜在健康受试者中的线性动力学研究及生物利用度研究主要目的：考察在健康受试者中分别单次给予0.25、0.5、1.0 mg的甲磺酸雷沙吉兰舌下膜和由Teva Neuroscience Inc持证的甲磺酸雷沙吉兰片（Azilect）的线性动力学特征及生物利用度。通过与原研Azilect比较，进行剂量调整优化。次要目的：观察甲磺酸雷沙吉兰舌下膜在健康受试者中单次给药后的安全性。评价舌下膜给药后的动态变化特征及受试者服药感受。 Ib：生物利用度研究主要目的：考察标准餐条件下单次口服由上海上药中西制药有限公司研制的甲磺酸雷沙吉兰舌下膜（受试制剂，规格：根据Ia期试验结果调整）和由Teva Neuroscience Inc持证的甲磺酸雷沙吉兰片（参比制剂，商品名：Azilect ®，规格：1 mg）的药代动力学特征，评价两制剂间生物利用度及其差异。次要目的：观察甲磺酸雷沙吉兰舌下膜在健康受试者中单次给药后的安全性。评价舌下膜给药受试者服药感受。

[Translation]

Ia: Linear kinetics and bioavailability study of rasagiline sublingual film in healthy subjects Main purpose: To investigate the linear kinetics and bioavailability of 0.25, 0.5, and 1.0 mg of rasagiline mesylate sublingual film and rasagiline mesylate tablets (Azilect) certified by Teva Neuroscience Inc. in healthy subjects. Dose adjustment optimization was performed by comparing with the original Azilect. Secondary purpose: To observe the safety of rasagiline mesylate sublingual film after a single administration in healthy subjects. To evaluate the dynamic change characteristics after sublingual film administration and the subjects' medication experience. Ib: Bioavailability study Main purpose: To investigate the pharmacokinetic characteristics of a single oral administration of rasagiline mesylate sublingual film (test preparation, specification: adjusted according to the results of the Phase Ia trial) developed by Shanghai Shangyao Zhongxi Pharmaceutical Co., Ltd. and rasagiline mesylate tablets (reference preparation, trade name: Azilect ®, specification: 1 mg) certified by Teva Neuroscience Inc under standard meal conditions, and to evaluate the bioavailability and differences between the two preparations. Secondary purpose: To observe the safety of rasagiline mesylate sublingual film after a single administration in healthy subjects. To evaluate the medication experience of subjects who received sublingual film administration.

Start Date06 Feb 2023

Sponsor / Collaborator

Shanghai Shangyao Chinese-Western Pharmaceutical Co., Ltd

NCT05611372 / Not yet recruitingPhase 2/3

Efficacy and Safety of Rasagiline in Prodromal Parkinson's Disease

To investigate whether a year of rasagiline may reduce the progression from idiopathic REM sleep behavior disorder (RBD) to Parkinson's disease (PD).

Start Date01 Jan 2023

Sponsor / Collaborator

Second Affiliated Hospital Zhejiang University School of Medicine

[+13]

100 Clinical Results associated with Rasagiline mesylate

100 Translational Medicine associated with Rasagiline mesylate

100 Patents (Medical) associated with Rasagiline mesylate

686

Literatures (Medical) associated with Rasagiline mesylate

01 Feb 2024·Behavioural brain research

Safinamide alleviates hyperalgesia via inhibiting hyperexcitability of DRG neurons in a mouse model of Parkinson's disease

Article

Author: Zhang, Li-Ge ; Wang, Fen ; Liu, Chun-Feng ; An, Meng-Qi ; Mao, Cheng-Jie ; Li, Cheng-Jie ; Dong, Li-Guo ; Cheng, Jing ; Wang, Jian-Min

Pain is a widespread non-motor symptom that presents significant treatment challenges in patients with Parkinson's disease (PD). Safinamide, a new drug recently introduced for PD treatment, has demonstrated analgesic effects on pain in PD patients, though the underlying mechanisms remain unclear. To investigate the analgesic and anti-PD effect of safinamide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was used, and rasagiline as positive control on motor symptoms. Notably, only safinamide alleviated hyperalgesia in MPTP mice. Whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons revealed hyperexcitability in MPTP mice, which safinamide counteracted in a concentration-dependent manner. The voltage clamp further demonstrated that sodium current in DRG neurons of MPTP mice was enhanced and safinamide reduced sodium current density. RT-qPCR identified upregulated Nav1.7 and Nav1.8 transcripts (Scn9a and Scn10a) in DRG neurons of MPTP mice. Our results suggest that safinamide could relieve hyperalgesia by inhibiting DRG neuron hyperexcitability in MPTP mice.

01 Feb 2024·Arthritis & rheumatology (Hoboken, N.J.)

Oxidative Stress by the Mitochondrial Monoamine Oxidase B Mediates Calcium Pyrophosphate Crystal–Induced Arthritis

Article

Author: Venegas, Francisca C ; Viola, Antonella ; Angioni, Roberta ; Sánchez-Rodríguez, Ricardo ; Luisetto, Roberto ; Canton, Marcella

Objective:

Calcium pyrophosphate (CPP) crystal deposition in the joints is associated with a heterogeneous set of debilitating syndromes characterized by inflammation and pain, for which no effective therapies are currently available. Because we found that the mitochondrial enzyme monoamine oxidase B (MAO‐B) plays a fundamental role in promoting inflammatory pathways, this study aims at assessing the efficacy of two clinical‐grade inhibitors (iMAO‐Bs) in preclinical models of this disease to pave the way for a novel treatment.

Methods:

We tested our hypothesis in two murine models of CPP‐induced arthritis, by measuring cytokine and chemokine levels, along with immune cell recruitment. iMAO‐Bs (rasagiline and safinamide) were administered either before or after crystal injection. To elucidate the molecular mechanism, we challenged in vitro primed macrophages with CPP crystals and assessed the impact of iMAO‐Bs in dampening proinflammatory cytokines and in preserving mitochondrial function.

Results:

Both in preventive and therapeutic in vivo protocols, iMAO‐Bs blunted the release of proinflammatory cytokines (interleukin [IL]‐6 and IL1‐β) and chemokines (CXCL10, CXCL1, CCL2 and CCL5) (n > 6 mice/group). Importantly, they also significantly reduced ankle swelling (50.3% vs 17.1%; P < 0.001 and 23.1%; P = 0.005 for rasagiline and safinamide, respectively). Mechanistically, iMAO‐Bs dampened the burst of reactive oxygen species and the mitochondrial dysfunction triggered by CPP crystals in isolated macrophages. Moreover, iMAO‐Bs blunted cytokine secretion and NLRP3 inflammasome activation through inhibition of the NF‐κB and STAT3 pathways.

Conclusion:

iMAO‐Bs dampen inflammation in murine models of crystal‐induced arthropathy, thereby uncovering MAO‐B as a promising target to treat these diseases. image

01 Feb 2024·Movement disorders : official journal of the Movement Disorder Society

A Randomized Phase 3 Study Comparing P2B001 to its Components (Low‐Dose Extended‐Release Rasagiline and Pramipexole) and to Optimized Doses of Marketed Extended‐Release Pramipexole in Early Parkinson's Disease

Article

Author: Kieburtz, Karl ; Hauser, Robert A ; Kreitzman, David L ; de Marcaida, Joy Antonelle ; Burdick, Daniel J ; McGarry, Andrew ; Gil, Ramon A ; Elmer, Lawrence W ; Olanow, C Warren ; Dhall, Rohit

Abstract:

Background:

There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity.

Objectives:

The objective was to determine if P2B001 (a fixed, low‐dose, extended‐release [ER] combination of pramipexole 0.6 mg and rasagiline 0.75 mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole‐ER.

Methods:

This was a 12‐week, double‐blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole‐ER 0.6 mg or rasagiline‐ER 0.75 mg), or commercial doses of pramipexole‐ER titrated to optimal dose (1.5–4.5 mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole‐ER.

Results:

P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II + III scores were −2.66 (95% CI, −4.33 to −1.00) versus pramipexole‐ER 0.6 mg (P = 0.0018) and − 3.30 (95% CI, −4.96 to −1.63) versus rasagiline‐ER 0.75 mg (P < 0.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole‐ER (mean, 3.2 mg), but significantly less worsening in daytime‐sleepiness (ESS treatment difference: −2.66 [95% CI, −3.50 to −1.81]; P < 0.0001). P2B001 was well‐tolerated with fewer sleep‐related and dopaminergic adverse events than titrated doses of pramipexole‐ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects.

Conclusions:

P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole‐ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once‐daily P2B001 as initial therapy for patients with early PD. © 2023 International Parkinson and Movement Disorder Society.

News (Medical) associated with Rasagiline mesylate

09 Nov 2023

·www.biospace.com

Pharma Two B Announces Publication of Positive Phase 3 Study Results of P2B001, an Investigational Treatment for Early Parkinson’s Disease, in Movement Disorders

Demonstrated that P2B001 provides benefits comparable with commercially used doses of marketed pramipexole-ER (PramiER) while minimizing associated daytime sleep–related and dopaminergic side effects associated P2B001 provided superior efficacy on motor symptoms and activities of daily living, compared to each of its individual components The convenient dosing of P2B001, as a no-titration, once-daily single pill, may be a valuable option for patients, neurologists, and particularly non-specialists who are often the only physicians treating PD patients REHOVOT, Israel, Nov. 09, 2023 (GLOBE NEWSWIRE) -- Pharma Two B Ltd., a private, late-stage pharmaceutical company, today announced that data from a Phase 3 study evaluating P2B001, a fixed, low-dose extended-release (ER) combination of pramipexole 0.6 mg and rasagiline 0.75 mg, were published in Movement Disorders. Results from the international, multicenter, randomized, double-blind parallel-group study evaluated the safety and efficacy of P2B001 in patients with early Parkinson’s disease compared to its components and to commercial doses of the dopamine agonist pramipexole (mean 3.2 mg per day). The study included 544 untreated patients with Parkinson’s disease who were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or marketed PramiER individually titrated to optimal dose (1.5-4.5 mg). “The present study demonstrates that each component contributes to the benefits of P2B001, and that it provides benefits comparable to commercially used doses of Pramipexole ER but with a reduced frequency of sleep-related and dopaminergic adverse events," said C. Warren Olanow, M.D., FRCPC, Chairman Emeritus of the Department of Neurology and Professor Emeritus in the Department of Neuroscience at the Mount Sinai School of Medicine in New York City. Further, he stated that “P2B001 is a once-a-day treatment that requires no titration. As such, if approved, P2B001 represents an important consideration for initiating treatment in patients with early PD.” “P2B001 represents a novel and easy-to-use therapeutic approach, as there has been a clear unmet need for a once-daily treatment that has demonstrable efficacy and safety, requires no titration and has a lower incidence of excessive daytime sleepiness, a commonly reported side effect among people with PD, often caused by dopamine agonist treatment,1-3” said Robert Hauser, M.D., M.B.A., Director, Parkinson’s Disease & Movement Disorders Center, University of South Florida. The primary endpoint was change from baseline to week 12 in Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III comparing P2B001 to its individual components. The key secondary endpoint was the change from baseline to week 12 in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of commercially available PramiER. The change from baseline in total UPDRS (primary endpoint) showed that P2B001 was significantly superior to each of its individual components demonstrating that each contributed to the P2B001 benefit. Least squares mean (LSM) (standard error) treatment difference between P2B001 and pramipexole ER (PPX-ER 0.6 mg) was –2.66 ± 0.85 points (p = 0.0018), and between P2B001 and rasagiline ER (RAS-ER 0.75 mg) was –3.30 + 0.85 points (p = 0.0001). The change from baseline to week 12 in total UPDRS score between P2B001 and PramiER (individually titrated to optimal dose; mean, 3.2 mg/day) was not significantly different (–8.35 ± 0.86 vs. 7.98 ± 0.60; p = 0.7197). Analysis of the key secondary endpoint (change from baseline to week 12 in the ESS score) demonstrated no worsening in the sleepiness scale with P2B001 treatment, whereas optimized doses of PramiER (mean dose, 3.2 mg) caused significant worsening in ESS. LSM difference between groups was –2.66 ± 0.43 (p < 0.0001). P2B001 was generally well tolerated and showed fewer sleep-related and dopaminergic adverse events in comparison to commercially used doses of pramipexole ER. "We are grateful to the patients, families and clinicians who have contributed to this study as we look to deliver a new, convenient treatment option for patients with early Parkinson’s disease,” said Dan Teleman, CEO of Pharma Two B. “We look forward to moving P2B001 forward towards an NDA submission to make this potential treatment option available to patients.” About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of Parkinson’s disease (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people with Parkinson’s disease. Extended release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. Pharma Two B owns worldwide-granted patents for both pharmaceutical composition and method of treatment with P2B001, which are expected to remain in effect until January 2033. About Pharma Two B Pharma Two B is a private, late-stage pharmaceutical company established in 2008 in Rehovot, Israel. Our mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders, with a clear unmet need, that are based on previously approved oral drugs and that may offer meaningful clinical benefits, as well as improved safety and enhanced convenience through easier administration. Our company is led by a highly experienced team in Parkinson’s disease, supported by top-tier scientific and clinical key opinion leaders and backed by a dedicated group of investors. For more information, please visit: . Forward-Looking Statements Some of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as “will,” “expect,” “could,” “if,” “expected,”” “anticipate,”” look forward,” “believe,” “potential,” “propose” and “continue” or negative variants of such terms. These and similar forward-looking statements discuss the company’s future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially. Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results. Amara AW, Chahine LM, Caspell-Garcia C, et al. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease. JNeurol Neurosurg Psychiatry. 2017;88(8):653-662. doi:10.1136/jnnp-2016-31502 Suzuki K. Current update on clinically relevant sleep issues in Parkinson’s disease: a narrative review. J Parkinsons Dis. 2021;11(3):971-992. doi: 10.3233/JPD-202425 Avorn J, Schneeweiss S, Sudarsky LR, et al. Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol. 2005;62(8):1242-1248. doi: 10.1001/archneur.62.8.1242 CONTACT INFORMATION Dan Teleman CEO Pharma Two B Ltd. Cell + 972-54-550-0804 Email: dan@pharma2b.com U.S. media contact: Cali Mangel Director Cell: 215-694-1577 Email: Cali.Mangel@calciumco.com

Clinical ResultPhase 3

28 Aug 2023

·www.globenewswire.com

Pharma Two B to Present Additional Phase 3 Positive Results of P2B001, a once-daily, fixed-dose combination of low-dose pramipexole and low-dose rasagiline, at 2023 International Congress of Parkinson’s Disease and Movement Disorders®

Sub-group analyses of patients with early Parkinson's disease (PD) at different age groups or baseline disease severities who were treated with P2B001 showed consistently greater symptomatic control versus its components (pramipexole 0.6 mg and rasagiline 0.75 mg) and comparable efficacy to currently marketed, optimally titrated, extended-release pramipexoleData analysis also showed P2B001 to be consistently superior to currently marketed, optimally titrated, extended-release pramipexole on the Epworth Sleepiness Scale (ESS) score, which is especially important for younger people with PD leading active lives and for older people who typically cannot tolerate dopamine agonist side effects such as excessive daytime sleepiness (EDS) REHOVOT, Israel, Aug. 28, 2023 (GLOBE NEWSWIRE) -- Pharma Two B, a private, late-stage pharmaceutical company, today announced that sub-group analysis results from the Phase 3 pivotal clinical trial evaluating P2B001 are being presented at the 2023 The International Parkinson and Movement Disorder Society® annual meeting, August 27-31, in Copenhagen, Denmark. The data are being presented as a poster presentation on Monday, August 28. In all subgroups, the results demonstrate greater symptomatic benefit of P2B001 versus its components, and comparable efficacy with currently marketed, optimally titrated, extended-release pramipexole, yet with reduced EDS. EDS is a commonly reported side effect among people with PD, which often worsens with dopamine agonist therapy1: The efficacy and safety profile of P2B001 was not significantly different in younger versus older patients (<66 vs >66 years), nor when patients were analyzed by baseline severity (≤29 vs >29 Total-Unified Parkinson’s Disease Rating Scale (UPDRS) score).Across all subgroups, P2B001 provided numerically greater symptomatic benefit versus its components, as assessed by Total-UPDRS, and statistically significant greater benefit in Activities of Daily Living (UPDRS Part II) versus components.Across all subgroups, P2B001 provided comparable symptomatic efficacy versus currently marketed, optimally titrated, extended-release pramipexole.P2B001 was consistently superior to extended-release pramipexole across all subgroups on ESS scores. In the full study cohort, there was significantly less daytime sleepiness compared to extended-release pramipexole at 12 weeks (-2.66 points; p≤0.001). “This study's findings, demonstrating greater symptomatic benefits of P2B001 as compared to its individual components in patients of all ages and disease severities, support the potential usage of P2B001 in patients with early PD. Moreover, the data showed comparable efficacy to the established extended release pramipexole regimen titrated to optimal dosage, exemplifying a potential approach to optimizing patient care, while challenging traditional paradigms,” says Drew Falconer, M.D., of the Inova Parkinson’s and Movement Disorders Center, and a trial investigator. Dan Teleman, CEO of Pharma Two B, adds, “We are encouraged by the consistency of the Phase 3 trial's sub-group analyses. They reinforce our commitment to advancing P2B001 and improving the lives of people with Parkinson's disease.” About the Study The international, multicenter, randomized, double-blind, parallel-group study in adult patients (35-80 years old) with early, untreated PD (<3 years from diagnosis) compared once-daily P2B001 with its individual components, as well as to optimally titrated, extended-release pramipexole (mean dose of 3.2 mg). A total of 544 participants were enrolled and randomized into the study. The primary endpoint was change from baseline to Week 12 in Total-UPDRS score (sum of Parts II and III) comparing P2B001 to its individual components. The key (first) secondary endpoint was the change from baseline to Week 12 in the ESS score comparing P2B001 to the optimized dosage of extended-release pramipexole. For the current analyses, subgroups were categorized by age (< median of 66 years vs > median of 66 years) and baseline severity ( median of 29 of Total-UPDRS (Part II+III scores)). The data are consistent with the positive Phase 3 topline efficacy and safety results presented previously, reemphasizing the potential of P2B001, if approved, to offer a new treatment approach for people with early PD, despite their age. About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of Parkinson’s disease (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people of all ages with PD. Extended-release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. Pharma Two B owns worldwide-granted patents for P2B001 for both pharmaceutical composition and method of treatment, which are expected to remain in force until January 2033. About Pharma Two BPharma Two B is a private, venture-backed, late-stage pharmaceutical company established in 2008 in Rehovot, Israel. Our mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders with a clear unmet need, that are based on previously approved oral drugs and that offer meaningful clinical benefits, as well as improved safety and enhanced convenience through easier administration. The company is led by a team highly experienced in PD, supported by top-tier scientific and clinical key opinion leaders, and backed by a dedicated group of investors. For more information, please visit: www.pharma2b.com. Forward Looking StatementsSome of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as “will,” “expect,” “could,” “if,” “expected,” “anticipate,” ”look forward,” “believe,” “potential,” “propose,” and “continue,” or negative variants of such terms. These and similar forward-looking statements discuss the company’s future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially. Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance, or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results. 1 Amara et al, J Neurol Neurosurg Psychiatry, 2017; Suzuki, J Park Dis, 2021; Avorn et al, Arch Neurol, 2005. Contact:Dan TelemanCEOPharma Two B Ltd.Cell. + 972-54-550-0804email: dan@pharma2b.com www.pharma2b.com U.S. media contact:Cali MangelAssociate DirectorCali.Mangel@calciumusa.com 215-694-1577

Clinical ResultPhase 3

25 Apr 2023

·www.biospace.com

Pharma Two B to Present Additional Positive Results from P2B001 Phase 3 Trial at 2023 American Academy of Neurology Annual Meeting

Results showed P2B001, a once-daily fixed-dose combination of low dose pramipexole and low dose rasagiline, showed comparable efficacy to marketed optimally titrated pramipexole, with significantly reduced sleep-related and dopaminergic side effects Data analysis also confirmed patients treated with P2B001 developed significantly less new-onset excessive daytime sleepiness when compared to marketed pramipexole REHOVOT, Israel, April 23, 2023 (GLOBE NEWSWIRE) -- Pharma Two B, a private, venture-backed, late-stage pharmaceutical company, today announced that additional results from the Phase 3 pivotal clinical trial evaluating P2B001, will be presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27 in Boston, MA. The data are being presented as an oral (Abstract 3733) and poster (Abstract 2396) presentation. The data in both presentations are consistent with the positive Phase 3 topline efficacy and safety results presented previously, reemphasizing the potential of P2B001, if approved, to offer a new treatment approach for people with early Parkinson’s disease (PD). Pharma Two B plans to submit a New Drug Application (NDA) for P2B001 to the U.S. Food and Drug Administration (FDA) in 2023. The Phase 3 trial was a global, multi-center, double-blind, parallel group design that enrolled 544 treatment naïve patients with PD (Hoehn-Yahr <3). The primary endpoint was the change from baseline to week 12 in total Unified Parkinson’s Disease Rating Scale (UPDRS) for P2B001 versus its individual components. The key secondary endpoint compared the change from baseline in Epworth Sleepiness Scale (ESS) for P2B001 versus commercial pramipexole-ER (Prami-ER). Excessive daytime sleepiness (EDS) is a commonly reported side effect among people with PD, which often worsens with dopamine agonist (DA) treatmenti. “The results of this Phase 3 trial represent positive news for newly diagnosed PD patients, as there has been a clear unmet need for an initial, once-daily treatment that has demonstrable efficacy and safety, requires no titration and has a lower incidence of excessive daytime sedation compared to pramipexole monotherapy,” says Lawrence W. Elmer, M.D. Ph.D., Department of Neurology, University of Toledo College of Medicine and Life Sciences, and trial investigator. “As a clinician caring for PD patients, I know the side effects from dopamine agonists (DAs) as monotherapy for early PD may be challenging and often limit treatment options, especially for younger people who may be required to drive for their employment and also for older people who often cannot tolerate DA side effects, including excessive daytime somnolence.” The results presented in abstract 3733 demonstrate comparable changes from baseline to week 12 with P2B001 and commercial Prami-ER in total UPDRS scores (-7.98 ±0.6 vs -8.35 ±0.86, p=0.7197) and non-inferiority (post-hoc) of P2B001 was confirmed (margin of 3 points, p=0.0052). Similarly, no significant differences between P2B001 and Prami-ER were seen in total UPDRS responders (≥4-point improvement), UPDRS Part II (activities of daily living/ADL) and UPDRS Part III (motor) scores. Importantly, patients receiving P2B001 versus Prami-ER reported less dopaminergic-related side effects (44.7% vs. 66.2%) and specifically less somnolence (14.7% vs. 31.1%,) and orthostatic hypotension (2.7% vs. 12.2%,) side effects. Trial participants treated with P2B001 had better outcomes in daytime sleepiness, with significantly less worsening (shown by a lower ESS change from baseline) than that with Prami-ER (key secondary endpoint; p < 0.0001). Results highlighted in abstract 2396 show that patients treated with P2B001 developed significantly less new-onset EDS, often a limiting factor for traditional dosing of DAs. Data analysis showed the rate of new-onset EDS was significantly lower in patients treated with P2B001 (8.5%) as compared to commercial Prami-ER (35.7%; adjusted odds ratio 0.17 (95% CI: 0.08-0.36; P<0.0001). “We believe the data presented at AAN this year continue to support the development of P2B001 as a potential first-line therapy for people with PD,” says Dan Teleman, President, Pharma Two B. “Our unique and proprietary formulation shown through our dose selection, extended-release formulation, and no need for titration supports our plan to submit a New Drug Application to the U.S. Food and Drug Administration.” P2B001 Clinical Data Presentations Abstract Title Abstract # Presentation Lead Author P2B001 significantly reduced risk of daytime sleepiness: results from a randomized controlled phase 3 trial with active pramipexole arm in early Parkinson’s disease (PD) 2396 POSTER 001 Neighborhood 11 Sunday, April 23 11:45am—12:45pm P2: Movement Disorders: Clinical Trials in Parkinson’s Disease 2 Kreitzman, D., et. al. P2B001 (low dose combination of extended-release pramipexole and rasagiline) versus titrated extended-release pramipexole in the management of early Parkinson’s disease: Exploratory findings from a randomized, controlled trial. 3733 ORAL 010 Tuesday, April 25 5:18pm S32: Movement Disorders: Trials Elmer, L., et. al. About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of Parkinson’s disease (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people with Parkinson’s disease of all ages. Extended-release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. Pharma Two B owns worldwide granted patents for both pharmaceutical composition and method of treatment with P2B001, which are expected to remain in force until January 2033. About Pharma Two B Pharma Two B is a private, venture-backed, late-stage pharmaceutical company established in 2008 in Rehovot, Israel. Our mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders, with a clear unmet need, that are based on previously approved oral drugs and that offer meaningful clinical benefits, as well as improved safety and enhanced convenience through easier administration. The company is led by a highly experienced team in Parkinson Disease, supported by top tier scientific and clinical key opinion leaders, and backed by a dedicated group of investors. For more information, please visit: . Forward Looking Statements Some of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as” “will,” “expect,” “could,” “if,” “expected”,” “anticipate”,” look forward”, “believe” “potential,” “propose” and “continue” or negative variants of such terms. These and similar forward-looking statements discuss the company’s future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially. Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance, or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results. _____________________________ i Amara et al, J Neurol Neurosurg Psychiatry, 2017; Suzuki J Park Dis, 2021; Avorn et al, Arch Neurol, 2005 Contact: Dan Teleman President Pharma Two B Ltd. Cell. + 972-54-550-0804 email: dan@pharma2b.com U.S. media contact: Cali Mangel Associate Director Cali.Mangel@calciumusa.com 215-694-1577

Clinical ResultPhase 3

100 Deals associated with Rasagiline mesylate

External Link

KEGG	Wiki	ATC	Drug Bank
D02562	Rasagiline mesylate	N04BD02	DB01367

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Parkinson Disease	EU	Teva Pharmaceuticals Europe BV	21 Feb 2005
Parkinson Disease	IS	Teva Pharmaceuticals Europe BV	21 Feb 2005
Parkinson Disease	LI	Teva Pharmaceuticals Europe BV	21 Feb 2005
Parkinson Disease	NO	Teva Pharmaceuticals Europe BV	21 Feb 2005

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Restless Legs Syndrome	Phase 3	US	Teva Neuroscience, Inc.	01 Sep 2010
Young onset Parkinson disease	Phase 3	-	Teva Neuroscience, Inc.	01 Jul 1997
Primary Parkinson's disease	Phase 1	CN	Univision Pharmaceutical Co., Ltd.	19 Aug 2015

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Biospace Manual	Phase 3	Parkinson Disease First line	544	P2B001	npkywjjuaz(twqryxunaf) = zgbxdofqig bgyaourrpg (ucbgwppqfy, 0.86)	Positive	09 Nov 2023
				pramipexole	-
NCT02789020 (CTgov)	Phase 2	Parkinson Disease	96	functional Magnetic Resonance Imaging+Rasagiline (Rasagiline)	ewpmejarbw(gausyuepcr) = btsfvlreye jezrphzdjh (olxwcrrusv, bynunhjwkw - njiloqmtnl) View more	-	06 Sep 2023
				functional Magnetic Resonance Imaging (Placebo)	ewpmejarbw(gausyuepcr) = aqnocwzbrf jezrphzdjh (olxwcrrusv, fgjjurorih - ffujcxbrym) View more
NCT02359552 (CTgov)	Phase 2	Alzheimer Disease	50	Placebo (Placebo)	xwmokvsegm(cfowisdreu) = bumzwflzpr yiedoqjiog (wpbwhbyjzp, rolldqfaqe - krprvefyag) View more	-	20 Oct 2020
				Rasagiline (Rasagiline)	xwmokvsegm(cfowisdreu) = dxrvkonref yiedoqjiog (wpbwhbyjzp, lmbljkyped - fpcrblfrxm) View more
NCT01786603 (CTgov)	Phase 2	Amyotrophic Lateral Sclerosis	80	Rasagiline (Rasagiline)	rdhyxfjooc(omhlgzxaqr) = evemjwqfgs wwmdehclrw (frfpdsuzem, ctshrbpsfj - ewoycuocif) View more	-	27 Jan 2020
				Placebo (Placebo)	rdhyxfjooc(omhlgzxaqr) = xltjpgkcjr wwmdehclrw (frfpdsuzem, igyfyelpel - mbaygqnwsf) View more
BIPARK-I and II (MDS2019)	Not Applicable	Parkinson Disease	-	Opicapone 50mg	hwiwxlkixi(fhfawcadff) = rdgqzlxyoe pnodcgwoxg (evylxfxfnf ) View more	-	22 Sep 2019
NCT02337764 (CTgov)	Phase 3	Parkinson Disease	222	TVP-1012	yhtygvqhsi(grzjejdcgr) = fpwdvuozch dhofecqyjq (enemvtflga, cdzibwrelb - jawcvuwpiu) View more	-	19 Apr 2019
NCT02337725 (Pubmed) Manual	Phase 3	Parkinson Disease	244	Rasagiline	wuovqiqbde(vekenmhoyy): difference = -6.39 (95% CI, -8.530 to -4.250), P-Value = <0.0001 View more	Positive	01 Mar 2019
				Placebo
NCT02337751 (Pubmed \| J Neural Transm (Vienna))	Phase 3	Young onset Parkinson disease	210	Placebo	xrbmjxfsav(xohivoufpp) = zxfsgcvzum blidracgsn (zfkfjnaihs ) View more	-	01 Mar 2019
				Rasagiline 1 mg/day	xrbmjxfsav(xohivoufpp) = gtjdszvyfi blidracgsn (zfkfjnaihs ) View more
NCT02337751 (CTgov)	Phase 3	Young onset Parkinson disease	198	Placebo+TVP-1012 (Placebo + TVP-1012 Group)	tofpxytfxe(hwxewlzohv) = wdylcbmhsz firkzzmuyi (vquldbdfvz, rhensvjrcq - slkpdlyyaw) View more	-	28 Feb 2019
				TVP-1012 (TVP-1012 + TVP-1012 Group)	tofpxytfxe(hwxewlzohv) = vtnilihuiy firkzzmuyi (vquldbdfvz, xpcnsiiwak - uxfzysetaw) View more
NCT02337738 (CTgov)	Phase 2/3	Parkinson Disease	404	Placebo	sxywuzqblg(cyyzqolvuf) = dpzfbcawcq zwupdjvktt (xnrekvytwz, wlavsqfmwp - cneqbjrgtm) View more	-	28 Feb 2019

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