Overview and Mechanism of Action
CM24 is a first-in-class clinical stage mAb targeting CEACAM1, a novel immune checkpoint inhibitor with significant potential to treat multiple cancers. CEACAM1 is associated with angiogenesis, and is an inter-cellular adhesion regulator of Fas-mediated apoptosis via interaction with β-catenin that enhances natural killer cell cytotoxicity against tumor cells. High CEACAM1 expression is known to be associated with poor disease prognosis in a number of tumor types. CEACAM1- CEACAM1 and CEACAM1-CEACAM5 immune checkpoint pathways prevent the death of tumor cells through the inhibition of the immune activity of TILs, lowering phosphorylation of immuno-receptors, and reducing SHP1/2 phosphorylation level in T and NK cells. CM24 (Humanized IgG4 mAb) binds specifically to the extracellular domain of CEACAM1 with nano-molar affinity. Blocking CEACAM1- CEACAM1 and CEACAM1-CEACAM5 interactions with CM24 is associated with anti-angiogenic, immune access, and checkpoint release mechanisms and enables cytotoxic activity of lymphocytes and the killing of tumor cells by T and NK cells.
Clinical Studies
In a Phase 1 dose-escalation study, CM24 demonstrated a good safety profile and promising efficacy signals. We are developing CM24 in collaboration with Bristol Myers-Squibb via a Phase 1/2 trial combining CM24 with nivolumab in NSCLC and pancreatic cancer patients expressing high CEACAM1 levels.
Overview and Mechanism of Action
NT219 is a first-in-class, novel small molecule targeting both IRS1/2 and STAT3, important oncogenic drivers and major drug resistance pathways in many hard-to-treat cancers. In preclinical studies, NT219 demonstrated strong efficacy in preventing acquired resistance and reversing tumor resistance when administered as a monotherapy and in combination with various existing oncology therapies.
Clinical Study
A Phase 1/2 first-in-human clinical trial in the U.S. is ongoing, in which NT219 is used both as a monotherapy and in combination with cetuximab (Erbitux™), with plans to expand the combination study to include patients with recurrent or metastatic SCCHN cancer in 2021.
About CONSENSI®
Consensi®️ is a fixed-dose combination of celecoxib, a non-steroidal anti-inflammatory drug (NSAID) for the treatment of pain caused by osteoarthritis, and amlodipine besylate, a drug designed to treat hypertension. The FDA approved Consensi®️ oral tablets for marketing in May 2018 and the drug is partnered for commercialization in the U.S., China and South Korea. Consensi®️ is under patent protection in the U.S. until 2030 and is the only NSAID with labeling that indicates a reduction of blood pressure and consequent risk reduction of heart attack, stroke and death.
Full U.S. Prescribing Information, including BOXED WARNING and Medication Guide is available at: www.consensi.com
Indications and Usage:
Consensi®️ is a combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate. Lowering blood pressure reduces the risk of fatal and nonfatal CV events, primarily strokes and myocardial infarctions.
Limitations of Use:
Consensi®️ is only available in a celecoxib strength of 200 mg and is only to be taken once daily.
Important Safety Information (ISI) for Consensi®️
The following ISI is based on the Highlights section of the U.S. Prescribing Information for Consensi®️. Please consult the full Prescribing Information for all of the labeled safety information for Consensi®️.
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use.
Consensi®️ is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events, including bleeding, ulceration and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.
Consensi®️ is contraindicated in patients with a known hypersensitivity to amlodipine, celecoxib or any of its inactive ingredients.
Consensi®️ is contraindicated in patients with a known history of asthma, urticaria or other allergic-type reactions after taking aspirin or other NSAIDs and in the setting of CABG surgery.
Consensi®️ is contraindicated in patients with known demonstrated allergic-type reactions to sulfonamides.
Significant warnings and precautions related to Consensi®️ include the following:
Patients should be warned about the potential signs and symptoms of hepatotoxicity and hepatic failure. Physicians should discontinue Consensi®️ if abnormal liver tests persist or worsen, or if clinical signs and symptoms of liver disease develop.
Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Physicians should carefully monitor blood pressure.
Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis.
Worsening angina and acute myocardial infarction, particularly in patients with severe obstructive coronary artery disease, is possible.
Physicians should avoid use of Consensi®️ in patients with severe heart failure.
Physicians should monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia, and avoid the use of Consensi®️ in patients with advanced renal disease.
Patients should seek emergency help if an anaphylactic reaction occurs.
Consensi®️ is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity).
Physicians should discontinue Consensi®️ at the first appearance of skin rash or other signs of hypersensitivity.
NSAIDs such as Consensi®️ can cause premature Closure of Fetal Ductus Arteriosus.
Avoid use in pregnant women starting at 30 weeks of gestation.
Physicians should monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia.
Consensi®️ is not recommended in patients with moderate or severe hepatic impairment or severe renal insufficiency.
Consensi®️ is not recommended in Poor Metabolizers of CYP2C9 Substrates.
To report SUSPECTED ADVERSE REACTIONS, contact Coeptis Pharmaceuticals at 1-888-275-1264 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
June 2021,APhase 1 2 Study with Open Label, Dose Escalation Phase Followed bySingle Arm Expansion at the Maximum Tolerated Dose to Assess theSafety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy ofNT 219 Injection Alone and in Combination with Cetuximab in Adults withAdvanced Solid Tumors and Head and Neck Cancer.Presented at the annual ASCO meeting 2021
February 2020,A phase I/II, Open-label, Dose Escalation Followed by Single-arm. Expansion to Assess the Safety and Efficacy of NT219 in Combination with Cetuximab in Patients with R/M HNSCCPresented at the Multidisciplinary Head and Neck Cancers Symposium 2020
