Pipeline
Innovative Clinical Pipeline with Near-Term Catalysts
Xadago® (safinamide) is a New Chemical Entity for the treatment of Parkinson’s Disease with a mode of action characterized by selective MAO-B-inhibition. Results from two double-blind, placebo-controlled, multinational, 6 month studies with over 1,100 patients revealed that safinamide provides statistically significant increases in ON-time without troublesome dyskinesia, as well as a decrease in OFF-time. Safinamide requires a once-daily dose and has no diet restrictions due to its high MAO-B versus MAO-A selectivity.
Xadago®: 1st New Chemical Entity Approved in a Decade for Parkinson's Disease
References:
Mov Disord. 2014 Feb;29(2):229-37.
Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations.
Borgohain R, et al
JAMA Neurol. 2017 Feb 1;74(2):216-224.
Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with parkinson disease and motor fluctuations: a randomized clinical trial.
Schapira AH et al
Significant Commercial Opportunity in Xadago® (Safinamide)
Parkinson’s disease (PD)
Parkinson’s disease (PD) is the second most common chronic progressive neurodegenerative disorder in the elderly after Alzheimer’s disease, affecting 1-2% of individuals aged ≥ 65 years worldwide. It is estimated that more than four million people in the industrialized countries suffer from PD. The prevalence of the PD market is expected to grow in the next years due to the increase in the global population and advancements in healthcare that contribute to an aging population at increased risk for PD. The diagnosis of PD is mainly based on observational criteria of muscular rigidity, resting tremor, or postural instability in combination with bradykinesia. As the disease progresses, symptoms become more severe. L-dopa remains as the most effective treatment for PD, and over 75% of the patients with PD receive L-dopa. However, long-term treatment with L-dopa leads to seriously debilitating motor fluctuations, i.e. phases of normal functioning (ON-time) and decreased functioning (OFF-time). Therefore, as the disease progresses, additional medications are added on to L-dopa to help with management of these motor fluctuations.
References and Useful Links
The Michael J. Fox Foundation
European Parkinson's Disease Association
American Parkinson Disease Association
BMC Oertel. European Handbook of Neurological Management, Vol 1, Chapter 14 & 15, 2011.
Potential to be first add-on therapy for the treatment of patients with positive symptoms of schizophrenia
Evenamide is an orally available New Chemical Entity that specifically targets voltage-gated sodium channels in development as add-on therapy for the treatment of schizophrenia. The compound originates from Newron’s ion channel program and has a unique mechanism of action: glutamate modulation and voltage-gated sodium channel blockade. Evenamide modulates sustained repetitive firing, without inducing impairment of normal neuronal excitability. It normalizes glutamate release induced by aberrant sodium channel activity.
In a Phase IIa clinical study, Newron demonstrated Evenamide’s evidence of efficacy in significantly improving symptoms of psychosis compared with placebo when added to two of the most commonly prescribed atypical antipsychotics in patients with chronic schizophrenia. The study also indicated that Evenamide is devoid of an effect on any of the over 130 neurotransmitters, enzymes, or transporters targeted by most antipsychotics.
Newron and FDA have agreed on the design and conduct of explanatory studies with Evenamide required to address previously announced potential safety issues raised by the FDA, including a four-week explanatory study in patients with schizophrenia. Subject to the successful completion of these additional studies, Newron intends to commence its proposed Phase III clinical trial program with Evenamide comprising of two efficacy studies: one in patients with schizophrenia experiencing worsening of psychosis on atypical antipsychotics and another in treatment-resistant patients not responding to the antipsychotic drug clozapine, an orphan-like indication, which affects 20,000 to 25,000 patients in the U.S.
Evenamide Novel MoA: Synergistic with Marketed Antipsychotics
Evenamide’s Unique MOA Demonstrated
Evenamide: PoC in Patients with Schizophrenia Demonstrated
References
Interim Results from the First International Randomized Trial of an NCE as an Add-on in Patients with Treatment-Resistant Schizophrenia (TRS): Benefits of Glutamate Modulation with Evenamide
Ravi Anand, Richard Hartman, Valentina Lucini, Alessio Turolla and Rodolfo Giuliani
33rd CINP Hybrid World Congress of Neuropsychopharmacology, 9-12 June 2022, Taipei, Taiwan
Design for an International Potentially Pivotal Clinical Trial for Evenamide as Add-on Treatment for Patients with Treatment-Resistant Schizophrenia not Benefiting from Atypical Antipsychotics
Ravi Anand, Richard Hartman, Alessio Turolla and Stephen Graham
33rd CINP Hybrid World Congress of Neuropsychopharmacology, 9-12 June 2022, Taipei, Taiwan
Safety Profile of Evenamide, a Novel Add-on Treatment for Patients with Schizophrenia Showing Inadequate Response to Antipsychotics
Ravi Anand, Richard Hartman, Alessio Turolla and Rodolfo Giuliani
33rd CINP Hybrid World Congress of Neuropsychopharmacology, 9-12 June 2022, Taipei, Taiwan
New strategies in the development of treatment for “poor responding” patients with schizophrenia
Ravi Anand, Richard Hartman, Rodolfo Giuliani, Valentina Lucini, Laura Faravelli
32nd ECNP Congress 6-10 September 2019, Copenhagen, Denmark
Glutamate modulation by Evenamide, a Na+ channel blocker, may benefit treatment resistant schizophrenic (TRS) patients not responding to clozapine
R. Anand, M. Bortolato, L. Faravelli
31th ECNP Congress, 6-9 October 2018, Barcelona, Spain
Preclinical and Clinical Findings suggest that Evenamide Improves Symptoms in Patients with Schizophrenia through Glutamatergic Modulation
R. Anand
31th ECNP Congress, 6-9 October 2018, Barcelona, Spain (Abstract and oral presentation)
Addition of Evenamide, a Selective Voltage Gated Sodium Channel (VGSC) Antagonist, to Atypical Antipsychotics is Efficacious in Patients Worsening on their Current Medication
R. Anand, R. Hartman, E. Forrest, and S. M Graham
CINP 16-19th June 2018, Vienna, Austria
Antipsychotic Efficacy of Evenamide (NW3509) is Due to Modulation of Glutamatergic Dysregulation
R. Anand, E. Forrest, R. Hartman, S. M. Graham, L. Faravelli
SIRS 2018, 4-8 April 2018, Florence, Italy
The Antipsychotic-like Properties of Evenamide (NW-3509) Reflect the Modulation of Glutamatergic Dysregulation
M. Bortolato L. Faravelli, R. Anand
SIRS 2018, 4-8 April 2018, Florence, Italy
Evenamide, a voltage-gated sodium channel blocker in the treatment schizophrenia: results from a placebo-controlled study
R. Anand, E. Forrest, R. Hartman, S. M. Graham, L. Faravelli
30th ECNP Congress, 2-5 September 2017, Paris, France
Evenamide, a Putative Antipsychotic, Targets Abnormal Electrical Activity and Glutamatergic Abnormalities to Improve Psychotic Symptoms in Patients with Schizophrenia: Results from a Phase II, Placebo-Controlled Trial
R. Anand, R. Hartman, S. M. Graham, E. Forrest, L. Faravelli
ICOSR 25-28 March 2017, San Diego, US
Evenamide (formerly NW-3509) targets new mechanisms, and represents a new approach to the management of untreated symptoms in schizophrenia
L. Faravelli, R. Anand, E. Forrest
29th ECNP Congress, 17-20 September 2016, Vienna, Austria
Evenamide (NW-3509), a Putative Antipsychotic, Targets Abnormal Electrical Activity and Glutamatergic Abnormalities in Improving Psychotic Symptoms in Patients with Schizophrenia in a Phase II, Placebo-Controlled Trial
R. Anand, R. Hartman, L. Faravelli, E. Forrest
SIRS 2016, 2-6 April 2016, Florence, Italy (Abstract and oral presentation)
NW-3509A Targets new Mechanism, and represents a new Approach to the Treatment of Schizophrenia
L. Faravelli, M. Bortolato, E. Forrest, M.T. Leibowitz, R. Anand
SIRS 2014, 4-9 April 2014, Florence Italy (Poster)
Adjuvant activity of the novel sodium channel blockerNW-3509 in combination therapy with antipsychotics.
E. Izzo, A. Ieraci, S. Meli, M. Bortolato, R. Frau, V. Bini, P. Salvati, R. Anand.
SFN 13-17 Novembre 2010, San Diego CA (Poster)
Adjuvant activity of the novel sodium channel blocker NW-3509 in combination therapy with antipsychotics
E. Izzo, A. Ieraci, S. Meli, M. Bortolato, R. Frau, V. Bini, P. Salvati, R. Anand
CINP 6-10 June 2010, Hong Kong
NW-3509: A novel potent sodium channel blocker with antipsychotic potential
E. Izzo, L. Faravelli, E. Colombo, A. Ieraci, M. Calabresi, S. Meli, S. Parini, C. Sabido-David, C. Caccia, P. Melloni, K. Wedzony, M. Bortolato, R. Frau, V. Bini, P. Salvati
SFN 17-21 October 2009, Chicago IL
NW-3509: a novel potent sodium channel blocker with antipsychotic potential
E. Izzo, L. Faravelli, A. Ieraci, C. Sabido-David, C. Caccia, P. Melloni, K. Wedzony, M. Bortolato, R. Frau, P. Salvati.
22nd ECNP Congress 12-16
Schizophrenia
Schizophrenia is a long-term mental health condition that causes a range of different psychological symptoms. It is one of the most common serious mental health conditions. About 1 in 100 people will experience schizophrenia in their lifetime, with many continuing to lead normal lives. Schizophrenia is most often diagnosed between the ages of 15 and 35. Men and women are affected equally. There is no single test for schizophrenia. It is most often diagnosed after an assessment by a mental health care professional, such as a psychiatrist. It is important to diagnose schizophrenia as early as possible, as the chances of recovery improve the earlier it is treated. Schizophrenia is often described in terms of positive and negative (or deficit) symptoms. Positive symptoms are those that most individuals do not normally experience but are present in people with schizophrenia. They can include delusions, disordered thoughts and speech, and tactile, auditory, visual, olfactory and gustatory hallucinations, typically regarded as manifestations of psychosis. Hallucinations are also typically related to the content of the delusional theme. Positive symptoms generally respond well to medication. Negative symptoms are deficits of normal emotional responses or of other thought processes and are less responsive to medication.
Schizophrenia: No Effective Treatment that Reduces Burden of Disease in Last 20 Years
Useful Links
Schizophrenia International Research Society (SIRS)
The Johns Hopkins Schizophrenia Center
The European Psychiatric Association
Ralfinamide is a unique, well-tolerated New Chemical Entity that specifically targets voltage-gated sodium channels originating from Newron’s ion channel program and is developed for a rare neuropathic pain indication. It is believed to mediate its potent analgesic effect through the inhibition of sodium channels, including Nav 1.7, N-type Calcium channels and NMDA receptor. Newron is looking for partners to advance the program into potentially pivotal studies in orphan indications in neuropathic pain.
Ralfinamide-oral New Chemical Entity targeting orphan neuropathic pain
Neuropathic Pain (NP)
Neuropathic pain is a type of chronic pain initiated or caused by a primary lesion of nervous system. While epidemiological studies indicate the incidence of neuropathic pain is 1%, most experts conclude this figure is most certainly an underestimate. Conditions associated with a high incidence of neuropathic pain include diabetes (10%), post-herpetic neuralgia (25%) and others. Neuropathic pain does not respond well to conventional pain therapy and may worsen over time. Pain is felt when special nerve terminals called nociceptors are stimulated. Following peripheral nerve injury, changes occur in the nervous fibers transmitting non-nociceptive stimuli, leading to neuropathic pain. Among these changes is an irregular membrane excitability, substained by profound alteration in the pattern of the sodium channel expression, including up-regulation of certain channels not normally observed in nociceptors, and down-regulation of others, thereby causing the brain to recognize pain from sources not normally painful. Up to 7% to 8% of the population is affected, and in 5% of individuals it may be severe.
Useful links
The European Pain Federation
Pain Alliance Europe
International Association for the Study of Pain (IASP)
Partnering
To progress the development and maximise the potential value of its novel CNS compounds, Newron has entered into a number of strategic relationships with established pharmaceutical companies.
In May 2012, Newron entered a strategic collaboration and licence agreement with Italian chemical and pharmaceutical company, Zambon, for Newron’s lead compound safinamide in all territories of the world with the exclusion of Japan and certain Asian territories. Since then, Newron has received significant success based regulatory milestone payments as well as customary royalty payments on future sales of safinamide in the licensed territories. Zambon has granted the commercialization rights to Supernus for the U.S., to Valeo Pharma for Canada, to Seqirus for Australia and New Zealand and to Medison for Israel.
Meiji Seika Pharma Co., Ltd.
In February 2012 Newron signed a license agreement with Meiji Seika Pharma Co., Ltd., covering the research, development, manufacturing, and marketing of safinamide in Japan and key Asian territories. In April 2017, Meiji Seika and Eisai entered into a collaboration for the development and commercialization of safinamide in Parkinson’s disease for Japan and Asia.
Newron is committed to developing novel therapies for patients with diseases of the central and peripheral nervous system. We are looking to build our portfolio of products through in-house efforts as well as licensing and acquiring novel CNS compounds at various stages of development.
Newron has proven expertise in developing novel CNS and orphan products having taken a number of programs through pre-clinical, clinical phases and to market.
We are seeking partners who can complement our in-house CNS development capabilities and who share our ambition to deliver effective treatments to patients living with debilitating neurodegenerative and or rare diseases. We have a promising pipeline of novel therapies and are looking to enter licensing or co-development agreements that will enable us to realize their full potential.
To further explore collaboration opportunities with Newron please contact us at [email protected].