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Basel, Switzerland, January 31, 2023 – Novaremed AG, a privately held clinical-stage biopharmaceutical company focused on innovative non-opioid treatment options for chronic pain management, announces the publication of the pharmacological profile of MP-101, which is in Phase 2 clinical development as a non-opioid treatment for the prevention of chemotherapy-induced peripheral neuropathy (CIPN), including neuropathic pain. “We are delighted with the publication of these data on MP-101,” said Eva Tiecke, PhD, Chief Scientific Officer and Head of R&D of Novaremed. “The study demonstrated that MP-101, a non-racemic enantiomeric mixture containing three parts of R-dimiracetam and one part of S-dimiracetam, is pharmacologically more potent than racemic dimiracetam in several animal models of neuropathic pain, cognition, and depression. The demonstrated efficacy of MP-101 in the oxaliplatin-induced peripheral neuropathic pain model, together with the preclinically and clinically established safety and tolerability profile of racemic dimiracetam, strongly support the development of MP-101 for the prevention of symptoms of peripheral neuropathy, including neuropathic pain induced by chemotherapy, an area with a high unmet medical need.” In this study [1], the effects of dimiracetam, its R- or S-enantiomers, and the R:S 3:1 nonracemic mixture, designated as MP-101, were compared. In vitro, dimiracetam was more potent than its R- or S-enantiomers in reducing the N-methyl-D-aspartate (NMDA)-induced [3H]D-aspartate release in rat spinal cord synaptosomes. Similarly, acute oral administration of dimiracetam was more effective than a single enantiomer in the sodium monoiodoacetate (MIA) paradigm of painful osteoarthritis. Then, the in vitro effects of a broad range of non-racemic enantiomeric mixtures on the NMDA-induced [3H]D-aspartate release were compared. Dimiracetam was a more potent blocker than each isolated enantiomer but the R:S 3:1 non-racemic mixture (MP-101) was even more potent than dimiracetam, with an IC50 in the picomolar range. In the chronic oxaliplatin-induced neuropathic pain model, MP-101 showed a significantly improved anti-neuropathic profile, and its effect continued one week after treatment suspension. MP-101 also performed better than dimiracetam in animal models of cognition and depression. Based on the benign safety and tolerability profile previously observed with racemic dimiracetam, MP-101 appears to be a novel, promising clinical candidate for the prevention and treatment of several neuropathic and neurological disorders. References [1] Bonifacino, T.; Micheli, L.; Torazza, C.; Ghelardini, C.; Farina, C.; Bonanno, G.; Milanese, M.; Di Cesare Mannelli, L.; Scherz, M.W. 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 2022, 11, 4027. (https://doi-org.libproxy1.nus.edu.sg/10.3390/cells11244027) About MP-101 and the prevention of chemotherapy-induced peripheral neuropathy (CINP) The Phase 2 clinical candidate MP-101 is an orally available modulator of glutamate signaling. It works by preventing or reversing the ramped-up signaling that occurs in the spine and brain as a result of damaged peripheral nerves. MP-101 is a patented non-racemic mixture of the dimiracetam enantiomers with patent protection until 2038. In previous Phase 1 and Phase 2 clinical studies, in a total of 176 human subjects, a benign safety and tolerability profile comparable to placebo was noted for dimiracetam, and no signs or symptoms of sedation, dependence or withdrawal symptoms emerged. Based on pre-clinical proof of concept studies and pre-IND discussions with the FDA, MP-101 is being developed for the prevention and treatment of chemotherapy-induced neuropathy and neuropathic pain. About Novaremed Novaremed AG, a privately held clinical-stage biopharmaceutical company, is developing a pipeline of innovative medications for chronic pain management to address the high unmet medical need for better pain relief and as an alternative to opioids. Its lead product is NRD.E1, an orally active non-opioid small molecule with a novel mechanism of action, has FDA Fast Track Designation is being studied in an NIH-sponsored Phase 2b clinical trial for the treatment of painful diabetic peripheral neuropathy (PDPN) as part of the NIH HEAL (Helping to End Addiction Long-termSM) initiative. The earlier stage pipeline includes clinical candidate MP-101 (Phase 2) being developed for the prevention of chemotherapy-induced peripheral neuropathy (CIPN), and MP-103 (preclinical) targeting CIPN and other peripheral neuropathy indications. Novaremed aims to address high unmet patient and societal needs for better relief from pain and peripheral neuropathy associated with diabetes and cancer chemotherapy by providing novel, non-opioid chronic pain therapies and countering overreliance on addictive treatments. For more information: www.novaremed.com. Contact Mark Altmeyer, Executive Member of the Board mark.altmeyer@novaremed.com Download pdf here 2023 01 31_PR_MP-101-publication_final

June 23, 2022 13:01 UTC Three Phase 1 studies displayed favorable pharmacokinetics and good tolerability of NRD.E1 after oral administration The Phase 2a, proof of concept study demonstrated clinically meaningful reductions in pain across primary and secondary endpoints and a benign side effect pro > In summary, data from these 4 studies now published demonstrate the potential of NRD.E1 as an innovative non-opioid treatment option for patients with painful diabetic peripheral neuropathy (PDPN) Based on available data, the National Institutes of Health (NIH) in the US has selected and included NRD.E1 to the NIH-HEAL Initiative® under which the NIH sponsors and executes a Phase 2b trial with study recruitment starting in 3Q 2022 BASEL, Switzerland--(BUSINESS WIRE)-- Novaremed AG, a privately held clinical-stage biopharmaceutical company focused on innovative non-opioid treatment options for chronic pain management announces the simultaneous publication of data from three Phase 1 studies in Clinical Pharmacology in Drug Development and one Phase 2a, placebo-controlled, dose-finding, proof of concept study in European Journal of Pain with the Company’s lead investigational drug candidate NRD.E1, an innovative non-opioid therapy for painful diabetic peripheral neuropathy. “We are delighted with the publication of our Phase 1 and Phase 2a studies which collectively demonstrate the drug candidate’s potential as an innovative non-opioid treatment option for patients with chronic pain,” said Eva Tiecke, PhD, Chief Scientific Officer and Head of R&D of Novaremed and lead author of both publications. “In the Phase 2a proof of concept study, the primary endpoint showed a clinically relevant placebo-corrected treatment effect in pain reductions at 40 and 150 mg/day of 0.82 Numerical Rating Scale points, p = 0.034 and 0.66, p= 0.061, respectively, though it narrowly missed the pre-specified value of p = 0.016 due to multiplicity. Overall, the study showed robust results given the consistent performance across multiple endpoints. Based on the data now published in peer-reviewed journals, we are encouraged about the potential of NRD.E1 to address the high unmet medical need for a non-opioid agent to treat chronic pain.” In three Phase 1 studies NRD.E1 was well tolerated as single dose up to 1200 mg and repeated doses of 300 mg/day for five consecutive days. The studies revealed dose-dependent absorption, small increased exposure to NRD.E1 at peak when administered with food and no relevant accumulation after oral administration. The Phase 2a study was a randomized, double-blind, placebo-controlled, dose-finding, proof-of-concept study in 88 patients with PDPN. The study investigated NRD.E1 at 10, 40, or 150 mg/day or placebo over a 3-week treatment period. Primary, pre-specified secondary and post-hoc secondary endpoints analyses consistently demonstrate a clinically meaningful reduction in pain. NRD.E1 was safe and well tolerated. References: [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 non-opioid therapy for painful diabetic peripheral neuropathy. Clinical Pharmacology in Drug Development (CPDD) ( ). [2] Tiecke E., Rainisio M., Eisenberg E., 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 ( ). About NRD.E1 and the treatment of chronic pain NRD.E1, an orally active small molecule with a novel mechanism of action and patent protection until 2040, is Novaremed's lead compound currently being developed to treat PDPN. On the basis of the results now published, NRD.E1 was selected by the NIH as the only oral agent to be included in the NIH-HEAL (Help End Long-term Addiction) program. The NIH will sponsor and execute by the and conducted by EPPIC-Net (Early Phase Pain Investigation Clinical Network) a 12-week, double-blind, placebo-controlled Phase 2b study in patients with moderate to severe PDPN in the US. Novaremed has an open IND and received Fast Track Designation from the FDA for NRD.E1. About Novaremed Novaremed AG, a privately held clinical-stage biopharmaceutical company, is developing a pipeline of innovative medications for chronic pain management to address the high unmet medical need for better pain relief and as an alternative to opioids. Its lead product is NRD.E1, an orally active non-opioid small molecule with a novel mechanism of action, has FDA Fast Track Designation and IND-approval to proceed with a Phase 2b clinical trial for the treatment of painful diabetic peripheral neuropathy (PDPN). The earlier stage pipeline addressing chronic pain includes the development candidates MP-101 (early clinical development stage), and MP-103 (preclinical stage), targeting the unmet medical need of prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN). For more information: . Read the full press release at or click here.