A Randomized, Double Blind, Placebo-controlled, Dose Response, Phase II, Multicentre Trial to Evaluate the Efficacy and Safety of Oral AP1189 Administered At the Doses of 40, 70, or 100 Mg for 12 Weeks in Combination with Methotrexate, in DMARD-naïve Participants with Early Rheumatoid Arthritis and Active Inflammation.

The study is a randomized, double blind, placebo-controlled, dose response, phase II, multicentre trial to evaluate the efficacy and safety of oral AP1189 administered at the doses of 40, 70, or 100 mg for 12 weeks in combination with methotrexate, in DMARD-naïve participants with early rheumatoid arthritis and active inflammation.

Start Date01 Oct 2024

Sponsor / Collaborator

SynAct Pharma ApS

[+1]

NCT05604885 / RecruitingPhase 2

A Two-part, Randomized, Double-blind, Multi-center, Placebo-controlled Study of the Dose-range, Safety and Efficacy of 4 and 12 Weeks of Treatment With AP1189 in Adult Rheumatoid Arthritis (RA) Patients With an Inadequate Response to Methotrexate (MTX) Alone - (RESOLVE)

The RESOLVE study is a two-part, randomized, double-blind, multi-center, placebo-controlled study of the safety, dose-range finding confirmation, and efficacy of 4 (Part A) and 12 weeks (Part B) of treatment with AP1189 in adult RA patients with an inadequate response to MTX alone.

Start Date30 Nov 2022

Sponsor / Collaborator

SynAct Pharma ApS

[+1]

NCT05516979 / CompletedPhase 2

A Double-blind, Multi-center, Randomized, Placebo-controlled Study of the Safety and Efficacy of 12 Weeks Extended Treatment With AP1189 in Early Rheumatoid Arthritis (RA) Patients naïve to DMARD Treatment

The study is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of 12 weeks daily treatment with 100 mg AP1189 in RA patients who are to start up-titration with methotrexate (MTX).

Start Date26 Sep 2022

Sponsor / Collaborator

SynAct Pharma ApS

[+1]

100 Clinical Results associated with Resomelagon

100 Translational Medicine associated with Resomelagon

100 Patents (Medical) associated with Resomelagon

Literatures (Medical) associated with Resomelagon

01 Apr 2015·Journal of immunology (Baltimore, Md. : 1950)Q2 · MEDICINE

Biased Agonism as a Novel Strategy To Harness the Proresolving Properties of Melanocortin Receptors without Eliciting Melanogenic Effects

Q2 · MEDICINE

Article

Author: Gobbetti, Thomas ; Perretti, Mauro ; Cooray, Sadani N. ; Jonassen, Thomas E. N. ; Montero-Melendez, Trinidad

Abstract:

There is a need for novel approaches to control pathologies with overexuberant inflammatory reactions. Targeting melanocortin (MC) receptors represents a promising therapy for obesity and chronic inflammation, but lack of selectivity and safety concerns limit development. A new way to increase selectivity of biological effects entails the identification of biased agonists. In this study, we characterize the small molecule AP1189 as a biased agonist at receptors MC1 and MC3. Although not provoking canonical cAMP generation, AP1189 addition to MC1 or MC3, but not empty vector, transfected HEK293 cells caused ERK1/2 phosphorylation, a signaling responsible for the proefferocytic effect evoked in mouse primary macrophages. Added to macrophage cultures, AP1189 reduced cytokine release, an effect reliant on both MC1 and MC3 as evident from the use of Mc1r−/− and Mc3r−/− macrophages. No melanogenesis was induced by AP1189 in B16-F10 melanocytes. In vivo, oral AP1189 elicited anti-inflammatory actions in peritonitis and, upon administration at the peak of inflammation, accelerated the resolution phase by ∼3-fold. Finally, given the clinical efficacy of adrenocorticotropin in joint diseases, AP1189 was tested in experimental inflammatory arthritis, where this biased agonist afforded significant reduction of macroscopic and histological parameters of joint disruption. These proof-of-concept analyses with AP1189, an active oral anti-inflammatory and resolution-promoting compound, indicate that biased agonism at MC receptors is an innovative, viable approach to yield novel anti-inflammatory molecules endowed with a more favorable safety profile.

BRITISH JOURNAL OF PHARMACOLOGY

Effects of a pro‐resolving drug in COVID‐19: preclinical studies to a randomized, placebo‐controlled, phase Ib/IIa trial in hospitalized patients

Article

Author: Silva, Barbara L. V. ; Costa, Vivian V. ; Almeida, Pedro R. J. ; Milhorato, Larissa B. ; Queiroz‐Junior, Celso M. ; Jonassen, Thomas E. N. ; Teixeira, Danielle C. ; Teixeira, Mauro M. ; Periard, Alexandre M. ; Fonseca, Talita C. M. ; Tana, Fernanda L. ; Avila, Renata E. ; Perretti, Mauro ; Serufo, Angela V. ; Alcantara, Katlen M. M. ; Resende, Carolina B. ; Santos, Felipe R. ; Souza, Renan P.

Introduction:

Pro‐resolving molecules may curb disease caused by viruses without altering the capacity of the host to deal with infection. AP1189 is a melanocortin receptor‐biased agonist endowed with pro‐resolving and anti‐inflammatory activity. We evaluated the preclinical and early clinical effects of treatment with AP1189 in the context of COVID‐19.

Methods:

C57BL/6j mice were infected intranasally with MHV‐A59 or hK18‐ACE2 mice with SARS‐CoV‐2. AP1189 (10 mg·kg−1, BID, s.c.) was given to the animals from day 2 and parameters evaluated at day 5. Human PBMCs from health donors were infected with SARS‐CoV‐2 in presence or absence of AP1189 and production of cytokines quantified. In the clinical study, 6 patients were initially given AP1189 (100 mg daily for 14 days) and this was followed by a randomized (2:1), placebo‐controlled, double‐blind trial that enrolled 54 hospitalized COVID‐19 patients needing oxygen support. The primary outcome was the time in days until respiratory recovery, defined as a SpO2 ≥ 93% in ambient air.

Results:

Treatment with AP1189 attenuated pulmonary inflammation in mice infected with MHV‐A59 or SARS‐CoV‐2 and decreased the release of CXCL10, TNF‐α and IL‐1β by human PBMCs. Hospitalized COVID‐19 patients already taking glucocorticoids took a median time of 6 days until respiratory recovery when given placebo versus 4 days when taking AP1189 (P = 0.017).

Conclusion:

Treatment with AP1189 was associated with less disease caused by beta‐coronavirus infection both in mice and in humans. This is the first demonstration of the effects of a pro‐resolving molecule in the context of severe infection in humans.

News (Medical) associated with Resomelagon

23 Sep 2024

·synactpharma.com

SynAct initiates the Phase 2b ADVANCE study with resomelagon (AP1189) in the US

SynAct Pharma AB (“SynAct”) (Nasdaq Stockholm: SYNACT), a clinical-stage biotechnology company focused on resolving inflammation through selective activation of the melanocortin system, today announces that the ADVANCE study, a Phase 2b randomized, double-blind placebo controlled clinical multi-center study in patients with newly diagnosed severe rheumatoid arthritis (RA) with the company's lead compound resomelagon (AP1189) actively recruits patients following initiation of sites in the USA. “We are very excited about the perspective of having the ADVANCE study up running in the US. Pending approval in Europe we plan to have active recruitment at more than 20 sites in a total of 7 countries in Q4 2024,” said Thomas Jonassen, CSO at SynAct Pharma. Resomelagon (AP1189) is a biased melanocortin receptor type 1 and 3 agonist that in Phase 2 clinical trials in newly diagnosed RA patients with high disease activity and signs of systemic inflammation showed significant treatment effect compared to placebo treatment with a good safety profile supporting first line treatment with the compound in combination with methotrexate (MTX). The primary aim of the ADVANCE study is to confirm the treatment potential of the compound and to identify optimal doses for Phase 3 development in patients with newly diagnosed RA. “The initiation of the ADVANCE is a cornerstone in the strategy put forward in the spring and we are pleased that the team in in collaboration with our CRO and advisors has been able to execute on the ambitious schedule that was laid out for updating the IND in the US, filing trial applications in Europe as well as managing the complex operations related to initiation of a clinical trial,” said Jeppe Øvlesen, CEO at SynAct Pharma. “We have focused resomelagon as a new innovative oral treatment option in early RA with high disease activity where there is a need for new safe medicines. We strongly believe in resomelagon as a treatment option for these patients as well as for several groups of patients suffering from autoimmune and/or inflammatory disease. Our strategy balances the risks and the opportunities to create most value for the patients, our investors and for our potential partners.” In the ADVANCE study four cohorts of RA patients, diagnosed within 6 months and showing signs of severe RA (DAS28-CRP >5.1; CDAI >22) including signs of systemic inflammation, defined as hsCRP to be above normal range (>3 mg/L) are given either placebo or one of three doses of resomelagon (40, 70, 100 mg) once daily for 12 weeks in combination with MTX treatment. The study is designed to randomize 240 patients using treatment induced reduction in DAS28-CRP as the primary efficacy readout in line with the current guidelines from FDA and EMA. The study will be conducted at clinical sites in the US and in Europe with enrolment of all patients planned to be completed in Q4 2025. Capital Markets Day SynAct Pharma will hold a Capital Markets Day on Monday, September 23, 10:00-13:00 CEST at GT30, Grev Turegatan 30 in Stockholm. The presentations will give an update on SynAct Pharma’s strategy and offer an opportunity for participants to learn more about resomelagon’s role in resolving inflammation through selective activation of the melanocortin system and the company’s next clinical development of resomelagon with the Phase IIb clinical study ADVANCE in the US and Europe. Location: Grev Turegatan 30, 114 38 Stockholm Date: Monday, September 23, 2024 Time: 10:00-13:00. The venue opens at 09:30. The Capital Markets Day will be held in English. Presentation material will be available on SynAct’s website afterwards. Registration for the Capital Markets Day is made by emailing: investor.relations@synactpharma.com For further information, please contact: Jeppe Øvlesen CEO, SynAct Pharma AB Phone: + 45 2844 7567 E-mail: investor.relations@synactpharma.com About SynAct Pharma AB SynAct Pharma AB (Nasdaq Stockholm: SYNACT) is a clinical stage biotechnology company focused on the resolution of inflammation through the selective activation of the melanocortin system. The company has a broad portfolio of oral and injectable selective melanocortin agonists aimed at inducing anti-inflammatory and inflammation resolution activity to help patients achieve immune balance and overcome their inflammation. For more information: www.synactpharma.com. Attachments SynAct initiates the Phase 2b ADVANCE study with resomelagon (AP1189) in the US

Phase 2Clinical Result

13 Sep 2024

·synactpharma.com

SynAct Pharma to present clinical data on resomelagon (AP1189) at ACR Convergence

SynAct Pharma AB (“SynAct”), a clinical-stage biotechnology company focused on resolving inflammation through selective activation of the melanocortin system, today announced that an abstract for resomelagon (AP1189) has been selected for presentation at the American College of Rheumatology (ACR) Convergence 2024 conference, being held in Washington DC, USA, from November 14 to 19. At the conference SynAct Pharma will present clinical data from the Phase 2b EXPAND study with focus on the treatment potential of resomelagon (AP1189) in newly diagnosed rheumatoid arthritis patients with high disease activity and signs of active inflammation. “We look very much forward to presenting the EXPAND-study clinical data at the ACR Convergence 2024, the world's premier rheumatology event,” said SynAct’s CSO Thomas Jonassen. “The development of resomelagon (AP1189) in the patient population is continued in the Phase 2b ADVANCE study.” Resomelagon is a novel, once-daily tablet with anti-inflammatory and pro-resolving effects with the potential to treat active rheumatoid arthritis. Further information related to the accepted abstract will, due to embargo policies, be shared at a later timepoint when the abstract is published in a special online supplement of the scientific journal Arthritis & Rheumatology. For further information, please contact:Jeppe ØvlesenCEO, SynAct Pharma ABPhone: + 45 2844 7567E-mail: investor.relations@synactpharma.com About SynAct Pharma ABSynAct Pharma AB (Nasdaq Stockholm: SYNACT) is a clinical stage biotechnology company focused on the resolution of inflammation through the selective activation of the melanocortin system. The company has a broad portfolio of oral and injectable selective melanocortin agonists aimed at inducing anti-inflammatory and inflammation resolution activity to help patients achieve immune balance and overcome their inflammation. For more information: www.synactpharma.com. AttachmentsSynAct Pharma to present clinical data on resomelagon (AP1189) at ACR Convergence

Phase 2

30 Aug 2024

·synactpharma.com

First scientific publication showing treatment potential of a pro-resolving compound in human virus infection

SynAct Pharma AB (“SynAct”) (Nasdaq Stockholm: SYNACT), a clinical-stage biotechnology company focused on resolving inflammation through selective activation of the melanocortin system, today announced the publication of clinical and preclinical data in a scientific journal supporting the potential of the company’s lead compound resomelagon (AP1189) as a novel innovative treatment option to control virus-induced hyper-inflammation, including COVID-19 infection. The peer-reviewed article, published in British Journal of Pharmacology, states it is the first scientific publication in literature showing treatment effects of a pro-resolving molecule in human infection. The major findings in the article are: Resomelagon significantly reduced disease activity in an animal model of betacoronavirus (MHV-A59 virus) induced pulmonary infection and in an animal model of SARS-CoV-2 virus induced pulmonary infection. Resomelagon significantly reduced the pro-inflammatory activity of human peripheral blood mononuclear cells (monocytes and lymphocytes) challenged with SARS-CoV-2 virus. In a randomized clinical trial (the RESOVIR-1 study) in COVID-19 patients, resomelagon significantly reduced time to recovery of respiratory insufficiency (measured on time to normalization of oxygen saturation on ambient respiration) and significantly reduced time to discharge of hospitalization when compared placebo treatment in patients that despite standard treatment, including low dose glucocorticoid treatment, developed severe respiratory insufficiency. “As highlighted in the article, this is the first peer-reviewed scientific report demonstrating the effects of a pro-resolving compound in the context of severe infection in humans,” said Thomas Jonassen, CSO at SynAct Pharma and co-author of the article. “The encouraging results show the potential of resomelagon to re-balance the inflammatory response in severe viral infection, not only seen in COVID-19 infected patients, but in a number of viral infections including severe influenza and dengue fever among others. We will therefore, in parallel with the continued development of the compound in the Phase 2b ADVANCE study in rheumatoid arthritis, continue to investigate the potential of the compound within viral infections in the RESOVIR collaboration.” “I am very happy to see these results. Although our priority is to continue development of resomelagon in RA, these very interesting data create opportunities in other indications with severe virus infections. This further strengthen our possibilities in finding partnerships with Big Pharma, or receiving soft money, to pursue these activities,” said Jeppe Øvlesen, CEO of SynAct Pharma. The publication is based on data generated as part of the RESOVIR collaboration, a scientific and clinical development collaboration between the University of Minas Gerais, Belo Horizonte, Brazil, William Harvey Research Institute, London, UK and SynAct Pharma. Link to the research article in the British Journal of Pharmacology:https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.17322 or through Pub Med:https://pubmed.ncbi.nlm.nih.gov/39159951/ For further information, please contact:Jeppe ØvlesenCEO, SynAct Pharma ABPhone: + 45 2844 7567E-mail: investor.relations@synactpharma.com About SynAct Pharma ABSynAct Pharma AB (Nasdaq Stockholm: SYNACT) is a clinical stage biotechnology company focused on the resolution of inflammation through the selective activation of the melanocortin system. The company has a broad portfolio of oral and injectable selective melanocortin agonists aimed at inducing anti-inflammatory and inflammation resolution activity to help patients achieve immune balance and overcome their inflammation. For more information: www.synactpharma.com. AttachmentsFirst scientific publication showing treatment potential of a pro-resolving compound in human virus infection

Phase 2Clinical Result

100 Deals associated with Resomelagon

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Phase 2	US	SynAct Pharma ApS	01 Oct 2024
Nephrotic Syndrome	Phase 2	SE	SynAct Pharma ApS	30 Jan 2022
Respiratory Distress Syndrome, Adult	Phase 2	SE	SynAct Pharma ApS	30 Jan 2022
Idiopathic Membranous Glomerulonephritis	Phase 2	DK	SynAct Pharma ApS	31 Aug 2020
Infantile multisystem neurologic-endocrine-pancreatic disease	Phase 2	DK	SynAct Pharma ApS	31 Aug 2020
Proteinuria	Phase 2	DK	SynAct Pharma ApS	31 Aug 2020
Rheumatoid Arthritis	Phase 2	DK	SynAct Pharma ApS	26 Aug 2019
Rheumatoid Arthritis	Phase 2	NO	SynAct Pharma ApS	26 Aug 2019

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04004429 (BEGIN, CTgov)	Phase 2	Rheumatoid Arthritis	105	50 mg AP1189 (50 mg AP1189)	rrwuizrbem(wsnroxifyu) = nzdkubcvip tldgfkncwh (kmkxcsjxqd, wvsvhiviks - qedbhocsnr) View more	-	10 Jul 2024
				AP1189 (100 mg AP1189)	rrwuizrbem(wsnroxifyu) = dxcbldritl tldgfkncwh (kmkxcsjxqd, egtwtmmqdp - yycwvmfmjy) View more

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