New Type 2 Jak inhibitor just started trial for MF

[EPguy]

Quick message: There are now 2 exciting new pills in early trials for Jak2 disease.

--

Rux is a type1 Jak-i. It targets the "active configuration" of Jak2. But Jak2 is more vulnerable when it's sleeping in the inactive config. Type 2 Jak-i's target this inactive config. But the two early ones were duds, NVP-BBT594 and NVP-CHZ868. They were not viable drug candidates, not sure why.

I've been looking for a not-dud, and one just entered phase 1 trial last month.

clinicaltrials.gov/study/NC...

According to the company's press release:

"...AJ1-11095 has been shown in preclinical studies to reverse marrow fibrosis, reduce mutant allele burden and maintain efficacy against MPN cells that become resistant to chronic Type I JAK2 inhibition."

If this holds thru trials it is a truly magic pill.

This joins INCB160058 as a new generation of Jak-i's in trials. Best I can tell INCB160058 does not require a particular active/not active state of Jak2, as it is a new class of drug.

INCB160058 trial:

clinicaltrials.gov/study/NC...

For members with Rux resistant/intolerant MF, these trials are worth a look. Both are US only for this small phase 1.

[Loubprv Volunteer]

morning. Not sure where you’re getting your info from but patients here have been taking Ruxolitinib for some time. Louise

[EPguy in reply to Loubprv]

Correct, Rux was approved for MF in 2011 and PV in 2014. And long term data is increasingly bring reported. This post discusses progress on what comes after Rux. These new agents use modern design with hope to improve upon Rux.

[Luthorville]

This is obviously great news. Stage 1 is very early but need to start somewhere. Remarkable that it has the ability to reverse progression. Has it been fast tracked? I wasn’t expecting this, Fingers crossed.

[EPguy in reply to Luthorville]

No fast track I'm aware of. I think that requires crazy good case studies. I think these had no human pts prior to the ph 1. I relate to fast tracking, an autoimmune that I don't have has a potentially curative Tx in ph 1 fast track based on some case studies. (anyone with Lupus may inquire)

One catch with these new agents is they are very Jak2 specific, whether or how they address other driver and non-drivers is TBD. Rux also targets Jak1, which may explain some of its good and bad effects.

[Bainbridge]

thanks for sharing this information. unfortunately some of these trials require the patient to stop RUX which is not recommended for my husband from his MPN doctor. He has MF and his Dr is always looking for clinical trials for him and I am as well since we are based in the USA. I hope they can find something that combines Rux with another drug that will slow down the progression

[EPguy in reply to Bainbridge]

These trials require failure on Rux "Previously treated with at least 1 JAK inhibitor for ≥ 12 weeks and resistant, refractory, intolerant to, or have lost response to JAK inhibitor treatment" So if he is doing ok on Rux he would not qualify. But if not ok he should qualify. All the trial pts will be transitioning from Rux in some manner, so they should have a protocol for this (but again only if Rux is not working out)

[MPort]

Thanks for doing the research and posting. One of your future posts will have the vital information. Looking forward to it.

[Pv2003]

INCB160058. Anyone on this site on this drug!

If so how are they responding?