Novaremed’s pipeline to address peripheral neuropathy and neuropathic pain focuses on three non-opioid development projects with entirely different modes of action:

Novaremed’s lead product NRD.E1 (or NRD135S.E1) is a new chemical entity, that is orally available and being developed to replace opioids for the treatment of painful diabetic peripheral neuropathy (PDPN).

The mechanism of action of NRD.E1 is different to that of approved pain therapies as the investigational drug does not bind to or interact with receptors for opioids, serotonin, GABA, NMDA, cannabinoid; it does also not interact with sodium or calcium channels or kinases and a large number of additional pain-related targets. NRD.E1 decreases phosphorylation of Y-507 of Lyn kinase, which has been shown to be involved in upregulation of P2X4, the purinergic receptor, critical for pain processing in the central nervous system.

NRD.E1 has shown efficacy in multiple preclinical models for neuropathic pain (Chung and Streptozotocine). In addition, NRD.E1 has demonstrated a very good tolerability profile in the 13-week toxicology studies both in rats and dogs.

Completed clinical studies with NRD.E1 include four Phase 1 studies (single ascending dose, multiple dose, food-effect and mass balance study). Results of the first three studies are published here [1]. The Phase 2a Proof of Concept study (ClinicalTrials.gov Identifier: NCT02345291) was a 3-week, dose finding, placebo-controlled, randomized, multi-center study. The study was conducted in 88 patients with moderate to severe PDPN and compared three doses (10 mg, 40 mg and 150 mg/day) of NRD.E1 to placebo. Results showed a clinically relevant, dose-related pain reduction; NRD.E1 was well tolerated at all tested doses. Results of this trial are published here [2].

NRD.E1 is currently tested in the NIH-supported Phase 2b trial EN21-01 (ClinicalTrials.gov Identifier: NCT05480228). This is a 12-week, multicenter, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of NRD.E1 versus placebo in adult and elderly patients with PDPN. The primary efficacy endpoint aims to demonstrate superiority of NRD.E1 compared to placebo in relieving PDPN. The secondary objectives of the study are to evaluate the pharmacokinetics, safety and tolerability of NRD.E1, and assess several additional endpoints, including the effect of NRD.E1 on sleep and quality of life indicators.

In December 2020, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to NRD.E1 for the treatment of PDPN.

Besides evaluation of NRD.E1 in PDNP, further indications will be explored as part of a comprehensive life-cycle management. Preliminary efficacy has been demonstrated in multiple preclinical models of pain, such as inflammation, and other indications. Information on Expanded Access can be found here.

The Phase 2 clinical candidate MP-101 is an orally active combination product containing racemic dimiracetam and its R-enantiomer as active ingredients. These drug substances are glutamate signaling modulators, a novel mechanism of action that promises to innovate therapy of CIPN which is an area with currently no approved treatment. CIPN is a disease of the peripheral nervous system characterized by pain and sensory abnormalities, which is caused by antineoplastic agents such as paclitaxel, vincristine and oxaliplatin. The use of MP-101 as preventive therapy of CIPN is based on the results of numerous preclinical studies published here [3]. The development of MP-101 is further supported and facilitated by the preclinical and clinical data reported for racemic dimiracetam which, for example given at doses up to 1600 mg twice daily, was well tolerated in the completed clinical pharmacology studies including 113 healthy subjects and in the Phase 2 study including 116 patients with HIV and painful distal neuropathy. Long intellectual property protections of MP-101 include worldwide granted patents with protection until 2038 (plus patent extensions). The development pathway of MP-101 is straight forward and considers global regulations to ensure registration and commercialization in all major regions.

MP-103, is an orally active combination product containing the glutamate signaling modulators NT-24336 (R-enantiomer) and its S-enantiomer (NT-24781). MP-103 has demonstrated higher effectiveness in comparison to NT-24336 alone in in vivo model of CIPN. The development of MP-103 as therapy of other forms of peripheral neuropathy is further supported by the preclinical data reported for NT-24336 showing beneficial effects in a wide array of rodent models. MP-103 will address a substantial unmet medical need, and with its mechanism of action and potency offers a potentially better treatment option compared to the currently used pain therapies.

[1] Tiecke E, Rainisio M, Guentert T, Müller S, Hochman L, Kaplan E, Mangialaio S (2022). First-in-Human Single-Ascending-Dose, Multiple-Dose, and Food Interaction Studies of NRD.E1, an Innovative Nonopioid Therapy for Painful Diabetic Peripheral Neuropathy. Clinical Pharmacology in Drug Development;11(9), 1012-1027
[2] Tiecke E, Rainisio M, Eisenberg Elon, Wainstein J, Kaplan E, Silverberg M, Hochman L, Mangialaio S (2022). NRD.E1, an innovative non-opioid therapy for painful diabetic peripheral neuropathy—A randomized proof of concept study. European Journal of Pain;26:1665-1678
[3] Bonifacio T, Micheli L, Torazza C, Ghelardini C, Farina C, Bonanno G, Milanese M, Di Cesare Mannelli L, Scherz MW (2022), Pharmacological Profile of MP-101, a Novel Non-racemic Mixture of R- and S-dimiracetam with Increased Potency in Rat Models of Cognition, Depression and Neuropathic Pain. Cells;11(24),4027

Disease Areas

Peripheral neuropathy, caused by nerve injury from various origin, may result in chronic and severe intractable pain: neuropathic pain (NP). Despite its varied etiologies, NP conditions share certain clinical characteristics: spontaneous, continuous pain, usually of a burning character; hyperalgesia to noxious stimulation or allodynic hypersensitivity to innocuous stimulation (e.g., light touch and cold).

Paradoxically, these hypersensitivities can occur in areas in which the patient also complains of and demonstrates a loss of sensation.

The most common forms of neuropathic pain are painful diabetic peripheral neuropathy (PDPN) and chemotherapy-induced peripheral neuropathy (CIPN), frequent complications of diabetes and of cancer treatment, respectively. The increasing prevalence of diabetes and cancer as well as the limitations of the currently available therapies make the prevention and treatment of chronic neuropathy and neuropathic pain a condition of high unmet medical need.

Painful diabetic peripheral neuropathy
Diabetic polyneuropathy is one of the most frequent complications of diabetes and develops in about 50% of diabetic patients. Up to 25% of patients with diabetic polyneuropathy develop PDPN [1]. Of these PDPN patients, about 2/3 (or more than 15 million patients) experience chronic debilitating pain that interferes with day-to-day functioning and sleep, causes anxiety and weakening, and substantially impairs quality of life.

The clinical management of patients with PDPN remains a major challenge since most available drugs fail to achieve a relevant pain reduction or are often poorly tolerated [2]. It is estimated, that 2/3 patient with PDPN requiring treatment do not obtain substantial pain relief with current treatments. In addition, many of the currently available drugs are often not well tolerated by the patients, due to their central nervous system or gastrointestinal side effects. Furthermore, many therapies for patients with PDPN, such as treatment with tricyclic antidepressants or classical opioids, are prescribed off-label and can be associated with risk of abuse, physical dependence, and withdrawal symptoms upon discontinuation. The rapidly increasing prevalence of diabetes, as well as the limitations of the available therapies, makes the treatment of neuropathic pain one of the strongest unmet medical needs of the upcoming years.

Chemotherapy-induced peripheral neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN) is a disease of the peripheral nervous system characterized by pain and sensory abnormalities, which is caused by antineoplastic agents such as paclitaxel, vincristine and oxaliplatin. The symptoms of chemotherapy induced peripheral neuropathy depend on the type of chemotherapy and which nerve fibers are affected and include e.g. numbness, tingling, weakness and pain in the hands and feet that produces deficits in balance, gait and fine motor function. Early and late CIPN symptoms are the main cause of dose modification and premature discontinuation in patients receiving chemotherapy. In addition, CIPN can persist post-chemotherapy, and significantly impact the health and quality of life of cancer survivors.

The highest prevalence rates of CINP are reported for widely used platinum-based drugs like oxaliplatin (i.e., 70-100%) [3]. Prevention would be therefore the best therapy for these patients [4]. However, there are currently no approved or effective agents for CIPN prevention. Duloxetine is the only medication recommended for the treatment of CIPN. It is anticipated that between 2018 and 2040, the number of patients requiring first-course chemotherapy annually will increase from 9.8 million to 15.0 million, a relative increase of 53% [5]. In view of this sharp increase in demand of chemotherapy in the next years and the high prevalence of CIPN, there is a high unmet medical and social need for effective preventive therapy of CIPN.

[1] Ziegler D, Fonseca V (2015). From guideline to patient: a review of recent recommendations for pharmacotherapy of painful diabetic neuropathy. J Diabetes Complications;29(1):146-156.
[2] Tiecke E, Rainisio M, Guentert T, Müller S, Hochman L, Kaplan E, Mangialaio S (2022). First-in-Human Single-Ascending-Dose, Multiple-Dose, and Food Interaction Studies of NRD.E1, an Innovative Nonopioid Therapy for Painful Diabetic Peripheral Neuropathy. Clinical Pharmacology in Drug Development;11(9), 1012-1027
[3] Jordan B (2022), Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO–EONS–EANO Clinical Practice Guidelines for diagnosis, prevention, treatment and follow-up. Annals of Oncology;31(10):13061.
[4] Ibrahim EY, Ehrlich BE (2020). Prevention of chemotherapy-induced peripheral neuropathy: A review of recent findings. Critical Reviews in Oncology/Hematology; 145:102831.
[5] Wilson BE, Jacob S, Yap ML, Ferlay J, Bray F, Barton MB (2019). Estimates of global chemotherapy demands and corresponding physician workforce requirements for 2018 and 2040: a population-based study. Lancet Oncology;20(6):769-780.


January 31,2023

Novaremed announces publication of pharmacological profile of MP-101, a clinical development candidate for the prevention of chemotherapy-induced peripheral neuropathy


July 21, 2022

Novaremed enters into an exclusive option and license agreement with NeuroFront for the non-opioid neuropathic pain treatment, NRD.E1, for Greater China and Singapore


June 23, 2022

Novaremed announces publication of Phase 1 and Phase 2a study data with NRD.E1 demonstrating the potential of this investigational non-opioid pain treatment


December 21, 2021

Novaremed’s Non-opioid Lead Compound, NRD.E1, to be Tested in NIH HEAL Initiative Phase 2 Trial for the Treatment of Chronic Pain

See all news


For ​more information contact: