Stress-induced antinociception (SIA) is due to the activation of several neural pathways and neurotransmitters that often suppress pain perception. Studies have shown that the orexin neuropeptide system is essential in pain modulation. Therefore, this study aimed to investigate the role of orexinergic receptors in the hippocampal CA1 region in modulating SIA response during the formalin test as an animal model of inflammatory pain. The orexin-1 receptor (OX1r) antagonist, SB334867, at 1, 3, 10, and 30 nmol or TCS OX2 29 as an orexin-2 receptor (OX2r) antagonist at the same doses were microinjected into the CA1 region in rats. Five minutes later, rats were exposed to restraint stress (RS) for 3 h, and pain-related behaviors were monitored in 5-min blocks for the 60-min test period in the formalin test. Results showed that applying RS for 3 h reduced pain responses in the early and late phases of the formalin test. The main findings showed that intra-CA1 injection of orexin receptor antagonists reduced the antinociception caused by stress in both phases of the formalin test. In addition, the contribution of OX2r in mediating the antinociceptive effect of stress was more prominent than that of OX1r in the early phase of the formalin test. However, in the late phase, both receptors worked similarly. Accordingly, the orexin system and its two receptors in the CA1 region of the hippocampus regulate SIA response to this animal model of pain in formalin test.

01 Jan 2024·Physiology & behavior

Blockade of the orexin-2 receptors within the ventral tegmental area facilitates the extinction and prevents the reinstatement of methamphetamine-seeking behavior

Article

Author: Haghparast, Abbas ; Zamanirad, Ferdos ; Mousavi, Zahra ; Eskandari, Kiarash

Repeated use of methamphetamine (METH) causes severe effects on the central nervous system, associated with an increased relapse rate. The orexinergic system is highly implicated in the reward circuitry and may be a promising target for treating psychostimulant dependency. The present study aimed to investigate the involvement of the orexin system, mainly the orexin-2 receptors (OX2R) in the ventral tegmental area (VTA) in the extinction and reinstatement of METH-seeking behavior using a conditioned place preference (CPP) paradigm. To this end, animals received METH (1 mg/kg; sc) for a 5-day conditioning period. Then, in the first set of experiments, different groups of rats were given intra-VTA TCS OX2 29 (1, 3, 10, or 30 nmol/0.3 μl DMSO) as an OX2R antagonist over a 10-day extinction period. In another experiment, after the extinction period, a different set of animals received a single dose of TCS OX2 29 (1, 3, 10, or 30 nmol) before the priming dose of METH (0.25 mg/kg; sc) on the reinstatement day. The results revealed that TCS OX2 29 (10 and 30 nmol) remarkably facilitated the extinction of rewarding properties of METH (P < 0.001 for both doses). Furthermore, TCS OX2 29 (3, 10, or 30 nmol) significantly suppressed the METH-induced reinstatement (3 nmol; P < 0.05, 10 nmol; P < 0.01, and 30 nmol; P < 0.001). In conclusion, the current study revealed that the orexinergic system, specifically the VTA OX2R, is involved in METH-seeking behaviors and that manipulation of this system can be considered a potential therapeutics in treating METH dependency.

01 Apr 2023·Neuropeptides

The stress-induced antinociceptive responses to the persistent inflammatory pain involve the orexin receptors in the nucleus accumbens

Article

Author: Haghparast, Abbas ; Nikoohemmat, Mohammad ; Khosrowabadi, Elahe ; Moteshakereh, Seyed Mohammadmisagh ; Salehi, Sakineh ; Farmani, Danial

Stress suppresses the sense of pain, a physiological phenomenon known as stress-induced analgesia (SIA). Brain orexin peptides regulate many physiological functions, including wakefulness and nociception. The contribution of the orexinergic system within the nucleus accumbens (NAc) in the modulation of antinociception induced by forced swim stress (FSS) remains unclear. The present study addressed the role of intra-accumbal orexin receptors in the antinociceptive responses induced by FSS during the persistent inflammatory pain model in the rat. Stereotaxic surgery was performed unilaterally on 106 adult male Wistar rats weighing 250-305 g. Different doses (1, 3, 10, and 30 nmol/ 0.5 μl DMSO) of orexin-1 receptor (OX1r) antagonist (SB334867) or OX2 receptor antagonist (TCS OX2 29) were administered into the NAc five minutes before exposure to FSS for a 6-min period. The formalin test was carried out using formalin injection (50 μl; 2.5%) into the rat's hind paw plantar surface, which induces biphasic pain-related responses. The first phase begins immediately after formalin infusion and takes 3-5 min. Subsequently, the late phase begins 15-20 min after formalin injection and takes 20-40 min. The findings demonstrated that intra-accumbal microinjection of SB334867 or TCS OX2 29 attenuated the FSS-induced antinociception in both phases of the formalin test, with the TCS OX2 29 showing higher potency. Moreover, the effect of TCS OX2 29 was more significant during the early phase of the formalin test. The results suggest that OX1 and OX2 receptors in the NAc might modulate the antinociceptive responses induced by the FSS.

News (Medical) associated with ORX-750

26 Sep 2024

·www.globenewswire.com

Centessa Pharmaceuticals Presents Preclinical Data for ORX142, a Novel Orexin Receptor 2 (OX2R) Agonist, at the 27th Congress of the European Sleep Research Society (Sleep Europe 2024)

Late-breaking poster presentation of non-human primate (NHP) data support ORX142 as novel drug candidate for the treatment of excessive daytime sleepiness (EDS) in select neurological, neurodegenerative, and psychiatric disorders BOSTON and LONDON, Sept. 26, 2024 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients, today shared new preclinical data from non-human primate (NHP) studies of ORX142, an investigational, novel, orexin receptor 2 (OX2R) agonist being advanced for the treatment of excessive daytime sleepiness (EDS) in select neurological, neurodegenerative and psychiatric disorders. ORX142 is the second drug candidate from the Company’s growing pipeline of OX2R agonists and is in IND-enabling studies. The preclinical data were featured today in a late-breaking poster presentation entitled, “ORX142, an Oral, Highly Potent and Selective Orexin Receptor 2 Agonist, Promotes Wakefulness in Non-Human Primates,” by Sarah Wurts Black PhD, Head of Biology for Centessa’s Orexin Agonist Program, at the 27th Congress of the European Sleep Research Society (Sleep Europe 2024) in Seville, Spain. “ORX142 has shown significant activity in promoting wakefulness at very low doses in highly predictive and translational preclinical models,” said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. “More specifically, the preclinical data showed ORX142 achieved significant increases in wake times at 0.03 mg/kg, the lowest oral dose tested in the NHP model. We’re excited to share these data at ESRS highlighting the breadth of ORX142’s potential as a novel treatment for individuals living with EDS in select neurodegenerative, neurological and psychiatric disorders. Based on the totality of data from our OX2R agonist program and the significant potential market opportunity for ORX142, we are focused on rapidly moving ORX142 through IND-enabling studies.” Overview of ORX142 Preclinical Poster Presentation at Sleep Europe 2024: ORX142 is a full OX2R agonist designed by Centessa with the aid of high-resolution crystallography and cryo-EM structural chemistry capabilities.ORX142 potently activated the human OX2R with an EC50 of 0.069 nM and > 13,000-fold selective over the human orexin receptor (hOX1R).1In highly predictive, translational NHP models, oral administration of ORX142 showed significant activity at the lowest dose tested, which was 0.03 mg/kg.ORX142 induced sustained increases in wakefulness that suppressed NREM and REM sleep at the lowest dose tested, 0.03 mg/kg.Wakefulness induced by ORX142 was associated with normal physiological arousal and EEG power spectra signatures of enhanced alertness and attention.No significant pharmacological activity was observed in GPCR selectivity and in vitro safety panels. References: 1. Fluorescent imaging plate reader (FLIPR) assay with Chinese hamster ovary (CHO) cells stably expressing recombinant human OX1R or OX2R; OXA EC50 at hOX2R = 0.035 nM; ORX142 EC50 at hOX1R = 930 nM. Additional meeting information can be found on the Sleep Europe 2024 website at https://esrs.eu/sleep-congress/. The poster will also be available on the Centessa website at https://investors.centessa.com/events-presentations after the conference concludes. About Centessa’s Orexin Agonist ProgramOrexin is a neuropeptide that regulates the sleep-wake cycle, leading to arousal and promoting wakefulness. Low levels of orexin result in excessive daytime sleepiness (EDS) and poor regulation of rapid eye movement (REM) sleep and, in narcolepsy type 1 (NT1), cataplexy and other symptoms. Centessa is developing a pipeline of potential best-in-class orexin receptor 2 (OX2R) agonists, including ORX750 for the treatment of sleep-wake disorders, including NT1, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), and ORX142 for the treatment of EDS in select neurological, neurodegenerative, and psychiatric disorders. ORX750 is in a Phase 1 clinical study. ORX750 and ORX142 have not been approved by the FDA or any other regulatory authority. About Centessa Pharmaceuticals Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients. Our most advanced programs include a hemophilia program, an orexin agonist program for the treatment of narcolepsy and other sleep-wake disorders, and an immuno-oncology program focused on our LockBody® technology platform. We operate with the conviction that each of our programs has the potential to change the current treatment paradigm and establish a new standard of care. For more information, visit www.centessa.com, which does not form part of this release. Forward Looking Statements This press release contains forward-looking statements. These statements may be identified by words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” “aim,” “seek,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements, including statements related to the Company’s ability to discover and develop transformational medicines for patients; its expectations for executing on the Company's pipeline; the timing of commencement of new studies or clinical trials or clinical and preclinical data related to ORX750 and ORX142; its ability to identify, screen, recruit and maintain a sufficient number of or any subjects in its existing and anticipated studies or clinical trials including in respect of ORX750 and ORX142; its expectations on executing its research and clinical development plans and the timing thereof, including its ability to rapidly move ORX142 through IND-enabling studies; its expectations as to the potential results and impact of each of its clinical programs and trials; the Company’s ability to differentiate ORX750 and ORX142 from other treatment options; the development, design and therapeutic potential of ORX750 and ORX142; and regulatory matters, including the timing and likelihood of success of obtaining regulatory clearance, obtaining authorizations to initiate or continue clinical trials. Any forward-looking statements in this press release are based on our current expectations, estimates, assumptions and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to the safety and tolerability profile of our product candidates, including ORX750 and ORX142; whether ORX750 and ORX142 could be shown to be ineffective; our ability to identify, screen and recruit a sufficient number of or any subjects in our existing and anticipated new studies or clinical trials including ORX750 and ORX142 or within anticipated timelines; our expectations relating to the further clinical development of ORX750 and ORX142 including initiation of phase 1 and/or phase 2 studies, including the predicted timing of enrollment, the predicted efficacious doses of ORX750 and ORX142 and our ability to successfully conduct our clinical development of ORX750 and ORX142; whether preclinical and initial clinical results for ORX750 and ORX142 will be predictive of results of further clinical trials; our ability to protect and maintain our intellectual property position; business (including commercial viability), regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company; risks inherent in developing product candidates and technologies; future results from our ongoing and planned clinical trials; our ability to obtain adequate financing, including through our financing facility with Oberland, to fund our planned clinical trials and other expenses; trends in the industry; the legal and regulatory framework for the industry, including the receipt and maintenance of clearances to conduct or continue clinical testing; our operating costs and use of cash, including cash runway, cost of development activities and conducting clinical trials, future expenditures risks; the risk that any one or more of our product candidates will not be successfully developed and/or commercialized; the risk that the historical results of preclinical studies or clinical studies will not be predictive of future results in ongoing or future studies; economic risks to the United States and United Kingdom banking systems; and geo-political risks such as the Russia-Ukraine war or the Middle East conflicts. These and other risks concerning our programs and operations are described in additional detail in our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and our other reports, which are on file with the U.S. Securities and Exchange Commission (SEC). We explicitly disclaim any obligation to update any forward-looking statements except to the extent required by law. Contact: Kristen K. Sheppard, Esq.SVP of Investor Relations investors@centessa.com

Phase 1Clinical Result

12 Sep 2024

·www.globenewswire.com

Centessa Announces Positive Interim Phase 1 Clinical Data with its Novel Orexin Receptor 2 (OX2R) Agonist, ORX750, in Acutely Sleep-Deprived Healthy Volunteers

2.5 mg dose restored normative wakefulness with mean sleep latency of 32 minutes as measured by the Maintenance of Wakefulness Test (MWT) Favorable safety and tolerability profile with no observations of frequently reported on-target adverse events (AEs) associated with other OX2R agonists, visual disturbances or hepatotoxicity as of the data cutoff date 1 PK profile supports once-daily dosing Company plans to rapidly initiate Phase 2 studies of ORX750 in patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) Sept. 10, 2024 -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients, today announced positive interim data from an ongoing Phase 1 trial of its highly potent and selective orexin receptor 2 (OX2R) agonist, ORX750, in acutely sleep-deprived healthy volunteers. ORX750 showed clinically meaningful and statistically significant improvements in mean sleep latency at the first two doses evaluated (1.0 mg and 2.5 mg) in the Maintenance of Wakefulness Test (MWT) compared to placebo. More specifically, the 2.5 mg dose was shown to restore normative wakefulness2 with a mean sleep latency of 32 minutes as measured by the MWT. ORX750 was also shown to have a favorable safety and tolerability profile with no observations of frequently reported on-target adverse events (AEs) associated with other OX2R agonists, and no cases of hepatotoxicity or visual disturbances across all three dose levels tested (1.0 mg, 2.0 mg, and 2.5 mg), as of the data cutoff date.1 Based on the interim data, the Company plans to rapidly advance ORX750 into Phase 2 studies in patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) beginning in the fourth quarter of 2024. “The Phase 1 acutely sleep-deprived healthy volunteer sleep study set a high bar for ORX750, and the early data generated has exceeded our expectations, giving us the confidence to accelerate the program into the next stage of clinical development earlier than anticipated,” said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. “We are very pleased that the data support the potential for ORX750 to restore normative wakefulness in patients with NT1, NT2, and IH at very low, once-daily oral doses. Underpinning these data is a favorable initial safety and tolerability profile for ORX750, which provides us with the flexibility to explore the therapeutic potential of OX2R agonists. Given the strength of the data generated to date and the exciting potential opportunities we see with ORX750, we are aggressively pursuing our clinical development plans and expect to initiate Phase 2 studies of ORX750 in patients with NT1, NT2 and IH beginning in the fourth quarter of 2024.” The Phase 1 clinical study is an ongoing first-in-human, randomized, placebo-controlled study designed to evaluate the safety, tolerability and pharmacokinetics (PK) of single-ascending doses (SAD) and multiple-ascending doses (MAD) of ORX750 in healthy adult subjects. In parallel to the SAD, a placebo-controlled cross-over pharmacodynamic (PD) assessment is being performed utilizing the MWT and Karolinska Sleepiness Scale (KSS) in acutely sleep-deprived healthy adult subjects with the goal of rapidly generating early efficacy data to inform dosing for planned studies in patients. As of September 10, 2024, the study has completed three SAD cohorts of healthy volunteers (27 active, 9 placebo) with doses of 1.0 mg, 2.0 mg, and 2.5 mg, and has advanced through two cohorts within the cross-over assessment of acutely sleep-deprived healthy volunteers with doses of 1.0 mg (n=8) and 2.5 mg (n=8), administered as a single oral dose. Dosing in the MAD portion of the study is also ongoing. The interim Phase 1 clinical data for ORX750 demonstrated: Significantly increased wakefulness in acutely sleep-deprived healthy volunteers compared to placebo at both doses tested. Treatment with ORX750 resulted in statistically significant (p<0.05) and clinically meaningful increased sleep latency on the MWT (time to sleep onset over the four sessions performed at ~2, 4, 6, and 8 hours after dosing at 11 p.m., maximum 40 minutes per session) compared to placebo across all doses. Mean sleep latencies, as measured by the MWT, for 1.0 mg dose of ORX750 and placebo were 18 minutes and 10 minutes, respectively (p-value = 0.04) (least squares mean). Mean sleep latencies, as measured by the MWT, for 2.5 mg dose of ORX750 and placebo were 32 minutes and 17 minutes, respectively (p-value = 0.01) (least squares mean). The 2.5 mg dose was shown to restore normative wakefulness with a mean sleep latency of 32 minutes as measured by the MWT. Favorable safety and tolerability observed as of the data cutoff date.1All observed treatment related AEs were mild and transient with none leading to treatment discontinuation. No observations of frequently reported on-target AEs associated with other OX2R agonists, including urinary frequency, urinary urgency, insomnia, blood pressure increases, and salivary hypersecretion. No cases of hepatotoxicity, visual disturbances or hallucinations were observed. Additionally, there were no clinically meaningful treatment-emergent changes in hepatic and renal parameters, vital signs, or electrocardiogram (ECG) parameters. Acutely sleep-deprived healthy volunteers who received a 2.5 mg dose of ORX750 showed a significant 1.6 point improvement versus placebo in mean KSS score compared to baseline (p-value = 0.03). Encouraging linear PK profile supports the use of ORX750 as a once-daily oral dosing regimen with rapid absorption (plasma concentrations of ORX750 peaked at 2h after the first dose). The systemic exposure of ORX750 increased in an approximately dose-proportional manner. “With these interim data, we believe we have successfully demonstrated a potential best-in-class profile for ORX750 having achieved normative wakefulness at once-daily low doses in subjects with normal orexin tone, coupled with a favorable safety and tolerability profile,” said Mario Alberto-Accardi PhD, President, Centessa Orexin Program. “Consistent with what we’ve seen preclinically, we believe these data validate our unique structural biology driven orexin research platform and accelerate translation of our growing pipeline of orexin agonists, including the future development of ORX142, our second orexin agonist development candidate. We are excited to leverage these data to expedite the progression of our multi-asset orexin franchise to potentially treat sleep-wake disorders and excessive daytime sleepiness (EDS) across multiple conditions.” Data cutoff date of August 26, 2024. Doghramji K, et al., A normative study of the maintenance of wakefulness test (MWT). Electroencephalogr Clin Neurophysiol 1997; 103:554-62. Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients. Our most advanced programs include a hemophilia program, an orexin agonist program for the treatment of narcolepsy and other sleep-wake disorders, and an immuno-oncology program focused on our LockBody® technology platform. We operate with the conviction that each of our programs has the potential to change the current treatment paradigm and establish a new standard of care. For more information, visit www.centessa.com, which does not form part of this release. Orexin is a neuropeptide that regulates the sleep-wake cycle, leading to arousal and promoting wakefulness. Low levels of orexin result in excessive daytime sleepiness (EDS) and poor regulation of rapid eye movement (REM) sleep and, in narcolepsy type 1 (NT1), cataplexy and other symptoms. Centessa is developing a pipeline of potential best-in-class orexin receptor 2 (OX2R) agonists, including ORX750 for the treatment of sleep-wake disorders, including NT1, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), and ORX142 for the treatment of EDS in select neurological, neurodegenerative, and psychiatric disorders. The Company’s lead asset, ORX750, is in a Phase 1 clinical study. ORX750 and ORX142 have not been approved by the FDA or any other regulatory authority. The content above comes from the network. if any infringement, please contact us to modify.

Phase 1Clinical Result

11 Sep 2024

·www.globenewswire.com

Nxera Pharma’s Partner Centessa Announces Positive Interim Phase 1 Clinical Data with its Novel Orexin Receptor 2 (OX2R) Agonist, ORX750, in Acutely Sleep-Deprived Healthy Volunteers

ORX750 showed clinically meaningful and statistically significant improvements in mean sleep latency and had a favorable safety and tolerability profile with no observations of frequently reported adverse eventsCentessa plans to rapidly advance ORX750 into Phase 2 studies beginning in the fourth quarter of 2024 Tokyo, Japan and Cambridge, UK, 11 September 2024 – Nxera Pharma Co., Ltd. (“Nxera” or “the Company”; TSE 4565) – formerly known as Sosei Group or Sosei Heptares – notes the announcement by Centessa Pharmaceuticals on 10 September 2024 reporting positive interim clinical data from its Phase 1 clinical trial with ORX750 in acutely sleep-deprived healthy volunteers. The full announcement from Centessa can be found by clicking here. ORX750 is an investigational, orally administered, highly potent and selective orexin receptor 2 (OX2R) agonist designed using Nxera technology to directly target the underlying pathophysiology of orexin neuron loss in narcolepsy type 1 (NT1), with potential applicability to narcolepsy type 2 (NT2), idiopathic hypersomnia, and other sleep-wake disorders with normal orexin levels. Centessa reported that ORX750 showed clinically meaningful and statistically significant improvements in mean sleep latency at the first two doses evaluated (1.0 mg and 2.5 mg) in the Maintenance of Wakefulness Test (MWT) compared to placebo. More specifically, the 2.5 mg dose was shown to restore normative wakefulness with a mean sleep latency of 32 minutes as measured by the MWT. ORX750 was also shown to have a favorable safety and tolerability profile with no observations of frequently reported on-target adverse events (AEs) associated with other OX2R agonists, and no cases of hepatotoxicity or visual disturbances across all three dose levels tested (1.0 mg, 2.0 mg, and 2.5 mg), as of the data cutoff date. Based on the interim data, Centessa plans to rapidly advance ORX750 into Phase 2 studies in patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) beginning in the fourth quarter of 2024. Nxera will disclose if a milestone event is reached that results in a material payment from Centessa to Nxera. -END- About Nxera PharmaNxera Pharma (formerly Sosei Heptares) is a technology powered biopharma company, in pursuit of new specialty medicines to improve the lives of patients with unmet needs in Japan and globally. In addition to several products being commercialized in Japan, we are advancing an extensive pipeline of over 30 active programs from discovery through to late clinical stage internally and in partnership with leading pharma and biotech companies. This pipeline is focused on addressing major unmet needs in some of the fastest-growing areas of medicine across neurology, GI and immunology, metabolic disorders and rare diseases, and leverages the power of our unique and industry leading GPCR-targeted structure-based drug discovery NxWaveTM platform to provide a sustainable source of best- or first-in-class candidates. Nxera employs over 350 talented people at key locations in Tokyo and Osaka (Japan), London and Cambridge (UK), Basel (Switzerland) and Seoul (South Korea) and is listed on the Tokyo Stock Exchange (ticker: 4565). For more information, please visit www.nxera.lifeLinkedIn: @NxeraPharma | X: @NxeraPharma | YouTube: @NxeraPharma Enquiries: Nxera – Media and Investor RelationsKentaro Tahara, VP Investor Relations and Corporate StrategyShinichiro Nishishita, VP Investor Relations, Head of Regulatory DisclosuresMaya Bennison, Communications Manager+81 (0)3 5210 3399 | +44 (0)1223 949390 |IR@Nxera.life MEDiSTRAVA (for International Media)Mark Swallow, Frazer Hall, Erica Hollingsworth+44 (0)203 928 6900 | Nxera@medistrava.com Forward-looking statementsThis press release contains forward-looking statements, including statements about the discovery, development, and commercialization of products. Various risks may cause Nxera Pharma Group’s actual results to differ materially from those expressed or implied by the forward looking statements, including: adverse results in clinical development programs; failure to obtain patent protection for inventions; commercial limitations imposed by patents owned or controlled by third parties; dependence upon strategic alliance partners to develop and commercialize products and services; difficulties or delays in obtaining regulatory approvals to market products and services resulting from development efforts; the requirement for substantial funding to conduct research and development and to expand commercialization activities; and product initiatives by competitors. As a result of these factors, prospective investors are cautioned not to rely on any forward-looking statements. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Phase 1Clinical Result

100 Deals associated with ORX-750

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Indication	Highest Phase	Country/Location	Organization	Date
Narcolepsy 1	Phase 1	-	Orexia TherapeuticsStartup	-
Narcolepsy	Preclinical	GB	Nxera Pharma Co., Ltd.	12 Oct 2022
Narcolepsy	Preclinical	GB	Orexia TherapeuticsStartup	12 Oct 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


GlobeNewswire Manual	Phase 1	-	36	ORX750	zukykrijxo(aqshghvmyp) = sqsbdylzhk qzjhenrasm (liimcfecqy )	Positive	10 Sep 2024
				Placebo	zukykrijxo(aqshghvmyp) = kheqetutsw qzjhenrasm (liimcfecqy )

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