otenaproxesul (ATB-346) / Antibe, Nuance Biotech - LARVOL DELTA

SENP3 Drives Abdominal Aortic Aneurysm Development by Regulating Ferroptosis via De-SUMOylation of CTH. (PubMed, Adv Sci (Weinh)) - "Additionally, supplementation with ATB346, a novel H2S-donating naproxen derivative, prevented AAA development in mice. These studies suggest that SENP3-mediated CTH deSUMOylation regulates macrophage ferroptosis and AAA development. The SENP3/CTH axis is therefore an important therapeutic target for aortic aneurysmal diseases."

Journal • Cardiovascular • Oncology • Targeted Protein Degradation • SENP3 • SUMO3

A hydrogen sulphide-releasing non-steroidal anti-inflammatory, ATB-346, significantly attenuates human myometrial contractions. (PubMed, Pharmacol Rep) - "ATB-346 exhibits potent tocolytic properties in human myometrium. These exciting results call for further exploration of ATB-346, with a view to repurposing this or similar drugs as novel therapies for delaying preterm labour."

Journal • Immunology • Inflammation • Pain • Rheumatology

A Phase 1b Study to Assess Pharmacokinetics and Safety of Otenaproxesul , a non-abusable, novel anti (IASP 2024) - "Otenaproxesul was shown to be safe and well tolerated across all treatment regimens. The well-behaved and predictable PK characteristics afford flexibility for the design of safe, acute pain treatment regimens. Investigation of the otenaproxesul's efficacy in patients undergoing abdominoplasty or bunionectomy is warranted."

Clinical • P1 data • PK/PD data • Aesthetic Medicine • Gastrointestinal Disorder • Pain

Antibe Completes First Clinical Study of Otenaproxesul’s New Formulation (Businesswire) - P1 | N=84 | NCT03220633 | Sponsor: Antibe Therapeutics Inc. | "Antibe Therapeutics Inc...is pleased to announce the completion of the pharmacokinetic/pharmacodynamic ('PK/PD') study of otenaproxesul’s faster-absorbing formulation for acute pain. The study was designed to confirm the drug’s safety and inform treatment regimens for the upcoming Phase II trial, on track to launch in calendar Q1 2024....All subjects completed the study with no clinically significant, drug-related adverse events and no elevation in liver enzymes during treatment or in post-treatment follow up."

New P2 trial • P1 data • Pain

MITOCHONDRIA-TARGETED DELIVERY OF HYDROGEN SULFIDE (H2S)-PRODRUG COUNTERACTS GASTROTOXICITY OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS. INVOLVEMENT OF HEME OXYGENASE PATHWAY (UEGW 2023) - "Importantly, new derivatives of NSAIDs, such as H2S-naproxen (ATB-346, Antibe Therapeutics Inc., Canada) or H2S-ketoprofen (ATB-352) exerted GI safety compared to mother compounds in preclinical or clinical studies. We showed that mitochondria-targeted H2S, released from very low i.g. doses of AP-39 improved gastric mucosal capacity to cope with NSAIDs-induced mitochondrial dysfunction and redox imbalance, mechanistically requiring the activity of anti-oxidative HMOX-1 and mitochondrial SOD-2. We assume that mitochondria-targeted H2S moieties could significantly increase the GI-safety of NSAIDs-pharmacology."

Gastrointestinal Disorder • Hematological Disorders • Inflammation • Metabolic Disorders • Mucositis • HMOX1 • IL10 • IL1B • SOD2 • STAT3 • TGFB1 • TNFA

Antibe Reports Q3 2023 Interim Financial and Operating Results - “Progress for otenaproxesul on formulation and IP: Transitioned to faster-dissolving formulation that accelerates onset of action; also enables treatment regimens with lower drug doses, providing additional safety buffer and a potential pathway to address chronic pain indications. Filed patent application for new formulation, strengthening IP protection to 2043....Upcoming Milestones: The following summarizes the Company’s estimated timeline for its key upcoming milestones: Ready tablets of otenaproxesul's new formulation – calendar Q2 2023; Initiate clinical PK/PD study for otenaproxesul – calendar Q3 2023; Initiate Phase II bunionectomy trial of otenaproxesul – calendar Q4 2023; Deliver Phase II bunionectomy top-line data of otenaproxesul – calendar Q1 2024.”

Commercial • New P2 trial • New trial • P2 data • Patent • CNS Disorders • Pain

"Antibe Provides Development Update for Otenaproxesul https://t.co/j9TcoLQnkN" (@NewsFromBW)

Potent anti-inflammatory effects of an H2S-releasing naproxen (ATB-346) in a human model of inflammation (PAINWeek 2022) - "We have shown that ATB-346, is potently anti-inflammatory, as evidenced by a significant reduction in neutrophil numbers at 4h compared to untreated controls. We observed a significant reduction in the expression of CD14 on CM and IM in both drug treatment groups compared to untreated controls at 48h, which could represent a switch to a more anti-inflammatory phenotype given its role in LPS-induced monocyte activation and role in fighting infection. Both ATB-346 and naproxen significantly reduced pain and tenderness at 4h compared to untreated, the time-point of maximal neutrophil infiltration, suggesting a reduction in numbers of inflammatory cells mediators may contribute to the analgesic effect of both drugs."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • CD14 • CD19 • CD20 • CRP • IL10 • NCAM1 • TNFA

Efficacy and Safety of ATB-346 Versus Placebo in Osteoarthritis Patients (clinicaltrials.gov) - P2b | N=381 | Completed | Sponsor: Antibe Therapeutics Inc. | Unknown status ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology • CYP2C9

"Antibe Therapeutics Outlines Plan for Otenaproxesul's Acute Pain Program https://t.co/Cd14jkjmD0" (@NewsFromBW)

Pain

Potent anti-inflammatory effects of an H S-releasing naproxen (ATB-346) in a human model of inflammation. (PubMed, FASEB J) - "Furthermore, both classical and intermediate monocyte subsets infiltrating the site of inflammation at 48 h expressed significantly lower levels of CD14 compared to untreated controls, demonstrating a shift toward an anti-inflammatory phenotype. Collectively, we have shown for the first time in humans that ATB-346 is potently anti-inflammatory and propose that ATB-346 represents the next generation of H S-NSAIDs, as a viable alternative to conventional NSAIDs, with reduced adverse effects profile."

Journal • Gastrointestinal Disorder • Immunology • Inflammation • Pain • CD14

"#AntibeTherapeutics #Antibe #Otenaproxesul $ATE $ATE.TO $ATBPF $TSX #Investors #Billionaire @CanaccorGenuity @BayerPharma" (@MoCooray)

MTUS1

Antibe Therapeutics Reports 2021 Year-End Financial Results and Business Highlights (Businesswire) - "Phase III-enabling activities for otenaproxesul proceeding well; AME study begins next week. Ended year with a strong $72 million cash position, providing over two years of runway and fully funding Phase III adaptive trial....Fully funded for over two years with 100% ownership of underlying intellectual property: Successfully raised $40 million in a bought deal public offering, providing over two years of cash runway and fully funding otenaproxesul’s Phase III adaptive efficacy trial....Upcoming Milestones: Completion of single-dose IND-opening study – Q3 2021. Completion of AME study – Q4 2021. Request FDA meeting prior to start of Phase III program – Q4 2021. Initiation of Phase III adaptive trial – Q1 2022."

FDA event • Financing • IND • New P3 trial • New trial • Trial completion date • CNS Disorders • Osteoarthritis • Pain

A Proof-of-Concept, Phase 2 Clinical Trial of the Gastrointestinal Safety of a Hydrogen Sulfide-Releasing Anti-Inflammatory Drug. (PubMed, Br J Pharmacol) - "This phase 2B study provides unequivocal evidence for a marked reduction of GI toxicity of the H S-releasing analgesic/anti-inflammatory drug, ATB-346, as compared to the conventional dose of naproxen which produced equivalent suppression of cyclooxygenase."

Clinical • Journal • P2 data • Dyspepsia • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Pain

[VIRTUAL] IMPACT OF NOVEL HYDROGEN SULFIDE-RELEASING KETOPROFEN (ATB-352) ON MOLECULAR PATHWAYS AND MICROBIOME PROFILE IN GASTROINTESTINAL (GI) TRACT WITH POSSIBLE DEVELOPMENT OF GI-SAFE POLYPHARMACY WITH OTHER NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) (DDW 2021) - "H2S-releasing NSAIDs derivatives seem to be promising safer and more effective alternatives; H2S-naproxen (ATB-346) successfully finished phase II clinical trial...Omeprazole decreased ketoprofen-induced injury score to the level of ATB-352 applied alone... ATB-352 applied alone or in polypharmacy with aspirin effectively inhibits COX activity, is GI-safe due to its H2S-releasing ability and has lower impact on molecular oxidative- or inflammatory-response pathways and intestinal microbiome composition as compared with its parent drug. We conclude that GI-safety of H2S-releasing ketoprofen does not require polypharmacy with PPIs and involves maintenance of intestinal microbiota profile and HMOX-1, CREB and SOCS3 pathways activation. ["

Gastrointestinal Disorder • Inflammation • HMOX1

"$ATBPF Antibe Therapeutics Receives FDA Clearance of IND Application for Otenaproxesul for Osteoarthritis Pain https://t.co/366UN6fsdm" (@stock_titan)

IND • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Antibe Therapeutics Receives FDA Clearance of IND Application for Otenaproxesul for Osteoarthritis Pain (Businesswire) - "Antibe Therapeutics...today announced that the U.S. Food and Drug Administration ('FDA') has cleared the Company’s Investigational New Drug ('IND') application for otenaproxesul, in development for the treatment of osteoarthritis pain...Antibe anticipates initiating its Phase III program later this year."

IND • New P3 trial • Osteoarthritis • Pain

Antibe Therapeutics Reports Q3 2021 Interim Financial and Operating Results (Businesswire) - "Otenaproxesul, lead product candidate entering Phase III trials for osteoarthritis pain...Completed a strategic licensing deal with Nuance Pharma for the commercialization of otenaproxesul in the Greater China region, with milestone payments totaling US$100 million and a double-digit royality...Research and development expenses, net of research tax credits, amounted to $3.4 million for the quarter ended December 31, 2020, compared to $1.6 million for the same period in fiscal 2020."

Commercial • Licensing / partnership • New P3 trial • CNS Disorders • Osteoarthritis • Pain

Antibe’s breakthrough osteoarthritis pain relief drug in the spotlight on World Arthritis Day (Proactiveinvestors) - "...Antibe Therapeutics Inc....is developing a NSAID alternative that could be a home run....The American Council on Science and Health (ACSH) has said Antibe’s lead drug otenaproxesul...could be a potentially 'much safer and possibly more effective option' for the treatment of chronic pain and inflammation than anything currently on the market....If the drug is approved, it could achieve peak sales of US$3.9 billion in the major markets, according to third-party commercial projections."

Review • Sales projection • CNS Disorders • Osteoarthritis • Pain

Nonsteroidal Anti-Inflammatory Drugs and Their Neuroprotective Role After an Acute Spinal Cord Injury: A Systematic Review of Animal Models. (PubMed, Global Spine J) - "PubMed/MEDLINE, CINAHL, PsycINFO, Embase, and Scopus were reviewed linking the keywords of "ibuprofen," "meloxicam," "naproxen," "ketorolac," "indomethacin," "celecoxib," "ATB-346," "NSAID," and "nonsteroidal anti-inflammatory drug" with "spinal." Results were reviewed for relevance and included if they met inclusion criteria. There are no published human studies evaluating the safety and efficacy of these drugs after a traumatic cord injury. There is a need for well-designed prospective studies evaluating ibuprofen or indomethacin after adult spinal cord injuries."

Journal • Review • CNS Disorders • Complement-mediated Rare Disorders • Immunology • Musculoskeletal Diseases • Orthopedics

Antibe Therapeutics plans to file IND with regulator for lead drug otenaproxesul (Proactiveinvestors) - "Antibe Therapeutics Inc...has revealed that it plans to file an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) for its lead drug otenaproxesul, formerly known as ATB-346, within the next six months, to allow for Phase 3 clinical trials in the US....'The company anticipates that the Phase 3 program for otenaproxesul will commence in late calendar Q1 or early calendar Q2 2021 and will take approximately 2 years to complete...'"

IND • New P3 trial • Osteoarthritis • Pain

Antibe Therapeutics engages Stern IR to expand its investor relations program and broaden visibility within US capital markets (Proactiveinvestors) - "Antibe Therapeutics Inc....said it has engaged Stern Investor Relations, Inc. to expand the company’s investor relations program and support efforts to broaden visibility within the US capital markets."

Licensing / partnership • Osteoarthritis • Pain

Antibe Therapeutics Provides Corporate Update (Businesswire) - "Having completed the analysis of primary and secondary data from ATB-346’s recent placebo-controlled efficacy trial, we can confidently report strong results across all key measures....With the successful conclusion of ATB-346’s Phase II studies and acceleration of partnering activities, preparation for Phase III trials is well underway....As part of Phase III preparation, we completed our Pre-IND ('Investigational New Drug') meeting for ATB-346...We are moving expeditiously to complete and submit an IND application to the FDA for ATB-346. Prior to the start of the first Phase III trial, we anticipate an End-of-Phase II Meeting with the FDA and the equivalent meeting with the EMA, which will strengthen Antibe’s position with potential large market partners."

FDA event • New P3 trial • Osteoarthritis • Pain

Antibe Therapeutics Provides Corporate Update (Businesswire) - "Third Party Commercial Studies Validate Blockbuster Potential of ATB-346: For the OA market alone, Antibe’s initial focus, peak annual sales of $5.3 billion are projected for ATB-346 in these seven countries, and cumulative revenues in excess of $28 billion by the early 2030s. These projections conservatively assume peak adoption of 21% and only represent 65% of the global market....The forecasts assumed a price of US$6 per day in the US, in line with today’s branded prescription NSAIDs, with corresponding pricing in the other markets....We are pleased to have recently received approval for ATB-346’s International Nonproprietary Name: otenaproxesul."

Clinical • Pricing • Sales projection • Osteoarthritis • Pain

Antibe Therapeutics Announces Closing of $28.75 Million Bought Deal Offering (Yahoo Finance) - "Antibe Therapeutics Inc....announced that it closed its previously announced bought deal public offering of 62,500,000 units of the Company (the 'Units') at a price of $0.40 per Unit (the 'Offering Price') plus the exercise in full of the Underwriters' over-allotment option of 9,375,000 units for aggregate gross proceeds of $28,750,000 (the 'Offering')...The Company intends to use the net proceeds of the Offering to fund certain activities required to support large market partnering and begin the Phase 3 program for ATB-346, for business development activities, and for advancing the other drugs in the Company's pipeline including ATB-352."

Financing • CNS Disorders • Osteoarthritis • Pain