New MF drugs in development by Incye

[CanadaG]

Hi All, just as a quick update, Incyte has started the phase 1 trial for the CALR anyibody and they also disclosed a new potential treatment for the JAK mutation which may enter clinicial trials in the coming months which they say could also be disease modifying. See some quotes from their 3Q 2023 earnings call transcript below. It's early days in terms of evaluating these treatments but it is promising and exciting. Incyte developed Rux.

"We also dosed the first patient for the Phase I study of our novel anti-mutant CALR targeted monoclonal antibody with the potential to eradicate the malignant clone in certain patients with myeloproliferative neoplasms and significantly modified disease outcomes. CALR mutations are responsible for disease development in approximately 25% to 35% of patients with MF and ET."

We are disclosing today for the first time, a program targeting the JAK2V617F mutation, the most common somatic mutation in myeloproliferative neoplasms. The JAK2V617F mutation is located in the JH2 domain of the JAK2 receptor and is present in 55%, 60% and 95% of patients with MF, ET and PV, respectively."

"Okay. Great. Thank you. So as Pablo said in his remarks, a remarkable effort from our research group to come up with compounds that now target new areas of biology. So in terms of mutant CALR it's about 25% to 30% of myelofibrosis and ET. It's a neoantigen that's expressed and the antibody targets that and could eradicate the clone. So you could be talking about a very new treatment paradigm that's disease-modifying or potentially in “curable” if you eliminate the clone in those settings. Obviously, we're early in the clinic. We need to prove it safe and get there. But there's a lot of excitement and obviously, you've got a plenary at ASH last year because of that with the mutant CALR antibody.

In terms of where it fits in, it won't be an agent that's in the way we think about spleen volume reduction and symptom improvement, it could be, as I said, to be a little bit repetitive, eliminate the clone and sort of get rid of the disease, if you will. The same with V617F, a target that many have pursued for a long time. And again, credit to our research group for coming up with, as Pablo pointed out, a very novel way of targeting the mutation in the JH2 domain.

And then again, the idea would be to eliminate the clone and disease modified, and this is a bigger population. It's about 50% of MF, 60% of ET and 95% plus of polycythemia vera. So for the first time now, we've been able to show you that I mean we've come up with a target in PV where it's an area where we haven't been able yet to give you anything new beyond Rux. So we're very excited about that. Again, it's early. We have to get the IND across the finish line and get into the clinic, but it's a superb science and would be a very different way of thinking about those entities. So thanks for the question."

[hunter5582]

Thanks for posting this update. It is very hopeful to see the science moving forward in this way. Perhaps we will hear more in the near future.

[CanadaG in reply to hunter5582]

You're welcome. These could be major breakthroughs to treat MPNs

[Green1988]

Thanks for this update. I pray to god it works 🙏🏾

[KLCTJC]

Thank you for posting this! Gives all hope for the future. I have seen so many medicines become so specific targeting one thing. I have faith since they know the cause they would find a way to block it or turn off that mutation. Good to see them working towards it.

[Spanelmad]

Just what I needed to hear today, let's hope it works.

[Pv2003]

Any articles on mouse studies or preclinical research on the jak2 drug? I have not seen or heard of anything directly targeting the jak2 mutation.

[CanadaG in reply to Pv2003]

Not that I'm aware if. This is the first time they disclosed it. I believe they are presenting the discovery at ASH in December

[Pv2003]

the abstract just came out and will be discussed at ASH! This could be the drug of the future for jak2 positive mpns. No mention of trials yet that I saw in the abstract, but if you said it was mentioned to be next year, then this is very promising. Hopefully few to zero side effects.

[ETinNYC]

How exciting! Now hopefully someone out there is also looking at a similar solution for those of us with mutated MPL.

As someone with a rare mutation (MPL) for a rare disease (ET), I hope we aren't forgotten as incredible advances are made in his field of MPNs!

[CanadaG]

hi. I don't know but would expect they are looking at options for MPL too. They would likely have a good understanding of the MPL mutation having developed and produced Rux all these years