I had a flip though...I will add this to the list of things to...

I had a flip though...I will add this to the list of things to do (that list is not getting smaller) but the very high level summary, nothing on that lists worries me at this juncture, we have covered a few of these in the past for sure.......nice to see us there too though!

Drug	Mechanism of Action	Status	Investigator(s)
TPX-100[5] (Matrix Extracellular Phosphoglycoprotein)	23-amino acid peptide that induces articular cartilage formation[6]reduces pathological shape change of joint bones.[7]	A one-year study of 93 patients revealed that TPX-100 treatment was associated with significant and sustained improvements in critical knee functions, preservation of knee cartilage thickness, reduced pathologic changes in underlying bone, and a >60% decrease in use of pain medications.[6]	Orthotrophix
AKL4 / APPA[8]	Oral NFkB and Nrf2 modulator	National Institute for Health Research(NIHR)-approved Phase I study successfully completed 1Q 2020. Phase 2 150-patient started 4Q 2020 with NBCD (Nordic Bioscience) and due to complete 3Q 2021.[9]	AKL Research & Development[10]
SM04690 / Lorecivivint[11]	Wnt pathwayinhibitor	Phase 2 study completed, showing improvement in pain, function and joint space width.[12] Phase 3 study started in May 2019.[13] In May 2020, it was reported that phase 2a trial failed to meet primary endpoint.[14][15]But a phase 2b trial in early 2021 met primary endpoint.[16] BioSplice(ex-Samumed) expects to release phase3 results in late 2021.[17]	Biosplice Therapeutics
KA34 / Kartogenin	Induces MSCs to differentiate into chondrocytes[18]via its lytic product4-aminobiphenyl(known as acarcinogen)[19]	Phase 1 study started in May 2018 to evaluate safety of kartogenin in humans.[20]	Calibr[21]
UBX0101 (Senolytic agents)	p53/MDM2 inhibitor, inducesapoptosisofsenescentcells to create a favourable healing environment[22]	Phase 1 study complete in June 2019,[23]results were encouraging leading to plans for a phase 2 study. Phase 2 study results did not show any improvements and led to drug being discontinued from investigation.[24]	Unity Biotechnology
BMP7(Bone Morphogenetic Protein 7)	Supports transcription of osteogenic genes[25]	Phase 1 study completed in 2010.[26] Phase 2 study completed in 2015,[27]suggesting the ability to prevent cartilage loss.	Ember Therapeutics[28]
FGF-18/ Sprifermin	Promote chondrogenesis through fibroblast growth factor receptor FGFR3[29]	Phase 2 study completed in 2017, with results failing to show improvement in pain or function. It did however show prevention of cartilage loss meaning it may be able to be used as a prevention.	Merck Nordic Bioscience
LNA043	Chondrogenesisenhancer[30]	Phase 1 study started in 2015.[31]	Novartis
GLPG1972 (Proteinases Inhibitors)	ADAMTS-5inhibitor	Phase 1 study completed in 2019. Phase 2 study started in 2019.[32] In October 2020, Servier reported phase 2 trial failed.[33]	Galapagos
M6495	ADAMTS-5inhibitor	Phase 1 safety study completed.[34]	Novartis[35]
MIV-711 (Cathepsin K inhibitors)	Cathepsin Kinhibitor[36]	Phase 2 study completed in 2019, showing prevention of cartilage damage but did not show reduction in patient pain.[37]	Medivir
Invossa-K (Transforming Growth Factor- β)	Cell/Gene therapy	Human studies halted byFDAfor false ingredient claim.[38][39]There are claimsFDAallowed for phase 3 trials to resume in the US.[40]As of January 2022, phase 3 clinical trial has resumed in the US.[41]	Kolon Life Science
Amniotic fluidallograft (ReNU, Palingen InovoFlo, AmnioFix, Clarix Flo)	Note: Amniotic fluid is not a single drug and instead contains around 226 growth factors,[42]includingBMP7. Inflammation reducer[43]and cartilage growth enhancer.[44]	Initial 6 patient study in 2015 showed improvement in pain and function.[45]Arandomised controlled trialof 200 patients completed in 2019,[46]also showing improved pain and function. A 2019 non-randomised study in 20 patients showed improvement in joint tissue health.[47]	Organogenesis Amnio Technology MiMedx Amniox Medical, Inc.
Polysulfate Sodium (PPS)	Pentosan Polysulfate Sodium(PPS) is a semi-synthetic drug manufactured from European beech xylans that are sulfated to produce a negatively charged product that mimics glycosaminoglycans (GAGs).	Paradigm's IND application to commence its phase 3 pivotal clinical trial investigating Pentosan Polysulphate Sodium (PPS) for the treatment of pain associated with knee osteoarthritis has been cleared by the US FDA. Approximately 65 sites have been identified throughout the US and Australia. Contracting with many of those sites has been completed. The first 4 sites in Australia have initiated screening participants. Screening at the US sites is expected to begin prior to the end of CY2021. The Company is now in a position to accelerate recruitment by adding approximately 10 sites in the United Kingdom (UK) and Europe, with site initiation and subject screening expected to commence in 1H CY 2022.[48][49][50]	Paradigm Biopharmaceuticals (ASXAR)