Pipeline

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

NRD.E1
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.

MP-101
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
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