Paradigm Competition

I wrote a post about a year ago looking at the very real competition that we face and I have rehashed it below for anyone interested. There were two main players and they were Biosplices Lorecivivint and Kolon Life Sciences Gene therapy Invossa.

Im sending Paradigm an email about Biosplices latest phase 3 extension study which appears to potentially have positive results however doesn't look too threatening to us for a few reasons. (will keep you posted)

As for Kolons Invossa gene therapy, I have just come across an article which says that there have been 90 reported tumor-related incidents. Link Below

https://www.koreabiomed.com/news/articleView.html?idxno=22098

Old post below...

Ok so letstake a closer look at and get to know our potential competition. I feel thethree following companies/drugs are in with the best chance of succeeding andall have been mentioned here before on the forums but are often fobbed off as“no chance”. While I personally feel that we are in with the best chance andour evidence to date is exceptional every time, consistent every time and ourMOA is one which takes a “whole disease or multi modal approach” to OA, thefollowing three are also in with a chance as well. They are all targeting OA ofthe knee (with expansion into hip as well) and chasing DMOAD too..

Interestingly,two of these three which are the nearest to completing trials have both beencaught up in controversy and general business/financial issues but have to datesurvived these issues.

KolonsTissue Gene ( Drug TG-C-LD- Invossa)

This is acell and gene therapy.

Singleintra-articular injection. Trials to date have shown that a single intraarticular injection provided meaningful pain and mobility measures for “up to 2years”

Its trialswere initially suspended for a “mislabeling” incident (read possiblyfraudulent) and the company was also de-listed in its home country (Korea)forthe crimes however the FDA has since given it the green light to re-commencetrials which are currently active. Incidentally Kolon has just come to the endof its 1 year grace period to show the Korean exchange how it has improvedprotocols to be considered for relisting so there may be more news on this inthe next month or so.

Invossa iscurrently in two phase 3 trials in the US and the trials are slated forcompletion for the 30^th June 2025.Targeting Kellgren/Lawrencegrade 2/3

https://clinicaltrials.gov/ct2/show/NCT03291470?term=kolon&cond=Osteo+Arthritis+Knee&cntry=US&draw=2&rank=1

https://clinicaltrials.gov/ct2/show/NCT03203330?term=kolon&cond=Osteo+Arthritis+Knee&cntry=US&draw=2&rank=2

Invossa wasrecently licenced to Juniper Biologics for US 600 million for the rights tosell to Asia, Middle East and Africa.

The companybelieves Invossa is DMOAD and the evidence to date according to them shows cartilageregeneration. Ultimately, whether the results are good enough for DMOAD are yetto be seen. Remember even if it shows cartilage regeneration on a consistentscale, it also need to show meaningful pain reductions as well…

Clearlythough, if it has already been able to do a multi regional licencing deal itmeans that Juniper Biologics believes it works and has put its money where itsmouth is…

Lorecivivint– Targeting the Wnt pathway

Lorecivivintis a drug owned by Bio Splice. It is a small molecule drug targeting the Wntpathway.

Bio Splicehas recently come under financial pressure and had to axe one of its other bigprogrammes so a lot rests on the results of lorecivivint for the companiesfuture.

It had twostudies that were axed for “covid reasons” and “business reasons” however theyhave now completed the pivotal phase 3 which finished in Sept 2021 according toclinicaltrials.gov however I cant find results anywhere?

They arecurrently running a phase 3 follow up study with 276 people. This long termextension study is designed to monitor the long term safety and efficacy and isestimated to complete in September 2024.

https://clinicaltrials.gov/ct2/show/NCT03928184?term=lorecivivint&cond=Osteo+Arthritis+Knee&cntry=US&draw=2&rank=4

https://clinicaltrials.gov/ct2/show/NCT04520607?term=lorecivivint&cond=Osteo+Arthritis+Knee&cntry=US&draw=2&rank=5

On anothernote, their phase 2b was a bit of a fail, however after post hoc analysis theybelieve they found a dose and a subset of patient that it was deemed to be safeand efficacious on and then took it to the two phase 3 trials mentioned above.

Bio Splicehas also managed to do some regional deals and has partnered with Haisco whichis a Chinese biotech in a deal worth up to 140 million US. They have alsolicenced out to South Korea to Samil for a deal worth 70 million US

Sichuan Haisco Pharmaceutical has added SM04690(lorecivivint) to its pipeline from a deal worth up to $140 million withBiosplice Therapeutics. Haisco will have the rights to develop andcommercialise the osteoarthritis drug in China by paying $20 million upfront.

Calling China one of the most important pharmaceuticalmarkets, Biosplice's CFO Erich Horsley said the company will work with Haiscoto launch lorecivivint in China in a few years.

Lorecivivint is an investigational CLK/DYRK1A inhibitorthat modulates the Wnt pathway to treat knee osteoarthritis. It is now in phaseIII pivotal trials for treating knee osteoarthritis in the U.S.

Biosplice said in phase II studies, lorecivivintdemonstrated significant and long-term improvements on patient-reportedoutcomes relating to pain and function, as well as medial joint space width asmeasured by x-ray 52 weeks following a single injection in the target knee.

In April 2021, Biosplice also licensed out the SouthKorea rights to develop and exclusively commercialize lorecivivint for kneeosteoarthritis to Samil Pharmaceutical in a $70 million deal.

The final drug which has a good chance of getting to market and being DMOAD is Novartis’ LNA043 in osteoarthritis of the knee which has recently been granted fast track status. They are currently in a phase 2b trial which is slated to end in 2027/8. They are a fair way behind the pack so I wont go into detail on this one however it may become competition further down the line after succeeding phase 2 b trials and then a successful phase 3.

I personally still believe Paradigm has a good shot at beating both of these to market and if our data continues to be as consistent as it has been and if there are no stuff ups by management, with the DMOAD data package that they are compiling at the moment along with their understanding of how the disease works we also have a realistic chance of acceleratedapproval. Even if one of the above drugs beats us and (assuming of course they don’t completely fail – which they may) it is a truly massive market and there would be room for more than one, however I do recognize the first one to get the DMOAD prize will have a first mover advantage and command a higher percentage of the market.