NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

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NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by MPN-MATE Admin »

Evening all... :-)

Below is a most exciting Update from Prof. Daniel Thomas concerning the imminent CALR "Monoclonal" antibodies, and he also goes on to mention further interesting events concerning JAK2 & CMML. Anyways, all very welcome and potentially "ground-breaking news"

Thank you Prof. Thomas...

Steven


Dr Thomas writes "We are indebted to MPNmate for supporting MPN patients and building strong bridges with genuine researchers. This is an exciting time for MPN treatments. Firstly, the Incyte anti-mutant CALR antibody developed by an American company is now open for clinical trial in Melbourne and Adelaide for patients with CALR mutations. For patients with advanced disease not responding to hydroxyurea or ruxolitinib I would recommend at least inquiring whether you can fit entry criteria. The pre-clinical data presented in December at the American Society of Haematology meeting was compelling.

Secondly, our own antibody therapy for CALR patients has been successfully humanized and we are ramping up production for a phase I/II trial starting after June this year in at least 4 centres in Australia. We have found at least two different binding sites enabling us to make multiple antibodies with therapeutic activity. The best antibody is currently being converted into a CAR T cell which could be useful for patients with residual disease that want to completely eradicate the CALR mutant cells if they respond well to anti-CALR antibodies. This work will be published soon including a crystal structure of the mutant CALR protein. This data will be extremely useful for improving therapies going forward.

Thirdly good news for JAK2 patients: we have generated the first simulated molecular structures of mutant JAK2 compared to normal JAK2 and found new pockets for precision drug binding. This means, in theory, we can inhibit the mutant JAK2 without targeting normal cells. Some of this will be released in an upcoming publication in Blood Cancer Discovery which will be very useful for other researchers as well. We are currently testing our new JAK2 inhibitors in models of JAK2 polycythaemia and myelofibrosis.

Fourthly, we are seeing encouraging responses in our national clinical trial for CMML, chronic myelomonocytic leukaemia, a poorly studied disease that overlaps with MPN and myelodysplasia using a new antibody therapy we have repurposed for leukaemia. The trial (PREACH-M) is being run in Brisbane, Melbourne, Adelaide, Perth and Sydney is opening a site at Royal North Shore very soon. Encourage participation if you have CMML that is high risk. Data will be released at the American Society of Hematology meeting in December this year and in the American Association for Cancer Research annual meeting in April."


Personally, I am really excited about being able to read through all of these exciting new Papers, (as soon as possible), and that these trials are actually happening right here in Australia... 8-)

Thank you Prof. Thomas, and we are certainly looking forward to learning more about all of your excellent news...

Steven
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by Alkemist »

Thanks for posting this Steve. Exciting developments!!
Allan
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

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Evening Allan ... 8-)

Yes, all very welcome news...
Hopefully we will all learn more as the CALR June Trails eventually commence here, (as Prof. Thomas), mentions above...

Wouldn't it be something if our "Mutant Drivers" could be completely eradicated, w/out the need for a Stem Cell Transplant?

Extremely heartening news indeed Allan... and such a pleasure & privilege to be able to bring it here to MATES.

Watch this space I guess... :-)

Kind regards

Steve
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by paul et »

Hi David, is there already a publication on the mutated JAK2 without targeting normal cells (upcoming publication in Blood Cancer Discovery) ?
I can't find it yet... Greetings Paul
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by MPN-MATE Admin »

Evening again Paul,

All such very promising news, is it not?

This is Steve answering your Post, as best I can etc...

I am yet to see the article thus far. However, as soon as I do I shall Post more about this again...

Hope you are doing well Paul...

Best wishes

Steve
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by paul et »

Thanks Steve … of course😅😅 thanks!! hopefully everything is fine there.. Maybe after 40 years we'll finally get rid of current horse tools.... Greetings Paul
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by paul et »

Hello fellow warriors...I am wondering if any MPNérs have experience using Isoquercitrin ? This is a powerful natural LSD1 inhibitor from Quercetin. Of has been several research done with LSD1 inhibitors and MPN, one example is Bomedemstat. Greetings Paul Netherlands
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by MPN-MATE Admin »

Greetings Paul... :-)

Great to be hearing from you again, & hoping all's well in your world too... as it is in my own... 8-)

I am afraid I've not heard of "Isoquercitrin" at this stage... Not sure I like it though as it's acronym is "LSD" (?) Is that just a coincidence Paul?

Anyways, happy to read any articles you may have on the subject...

Best wishes buddy, stay happy, safe & well my friend...

Steve
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by paul et »

MPN-MATE Admin wrote: Sun Mar 05, 2023 12:27 am Evening all... :-)

Below is a most exciting Update from Prof. Daniel Thomas concerning the imminent CALR "Monoclonal" antibodies, and he also goes on to mention further interesting events concerning JAK2 & CMML. Anyways, all very welcome and potentially "ground-breaking news"
----------------
Thirdly good news for JAK2 patients: we have generated the first simulated molecular structures of mutant JAK2 compared to normal JAK2 and found new pockets for precision drug binding. This means, in theory, we can inhibit the mutant JAK2 without targeting normal cells. Some of this will be released in an upcoming publication in Blood Cancer Discovery which will be very useful for other researchers as well. We are currently testing our new JAK2 inhibitors in models of JAK2 polycythaemia and myelofibrosis.
----------------

Thank you Prof. Thomas, and we are certainly looking forward to learning more about all of your excellent news...

Steven
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Why not testing for JAK2+ Essential Thrombocytose?
Regards Paul
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Re: NEW UPDATES ON CALR & JAK2 CLINICAL TRIALS

Post by MPN-MATE Admin »

You must've missed something there Paul... :-)

This is specifically a CALR monoclonal antibody, because of the special properties of that particular type of "Driver" MPN mutation.

However, Dr Thomas does mention other research into JAK2+ as well, whether that is ET or one of the other MPNs...

Best wishes

Steve
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