Why Cynata's GvHD Treatment Might Not Need a Phase Two Trial for FDA Approval

It has been a busy week for Cynata, with the Diabetic Foot Ulcer trial delivering good results overall, with particularly strong results for patients with large, non-healing wounds. Then, a surprise capital raise was conducted, giving the company funding through to mid-2026.

Lost in all of this is the progress of the original treatment that Cynata decided to put into the clinic, CYP-001 for Graft vs Host Disease (GvHD). This intravenous therapy was initially designed to treat Steroid-Resistant (SR) GvHD. However, after excellent results from the Phase 1 trial, and perhaps because of the 2019 approval of Incyte's Jakafi (Ruxolitnib) in SR-GvHD, the company decided to pivot to High-Risk (HR) GvHD. This means that patients would be treated as soon as they were identified as having GvHD, rather than when they become classified as 'Steroid Resistant,' which occurs 72 hours after demonstrating no response to steroid treatment.

This is a massive advantage for patients, as GvHD is an incredibly debilitating and painful condition to suffer. It is also a massive advantage for Cynata. CYP-001 had no negative safety events from the initial Phase 1 trial. Should that continue, and it be approved one day, in theory basically any patient that begun showing GvHD symptoms could receive CYP-001, doubling the TAM compared to SR-GvHD.

Now, to the headline. Remember Ruxolitnib? It was approved by the FDA for treatment of patients over 12 on the back of a 49 person, single arm Phase 2 trial in SR-aGvHD: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ruxolitinib-acute-graft-versus-host-disease

Cynata, on the other hand, are conducting a randomised, controlled 60 person Phase 2 trial in HR-GvHD. So you get more patients in a more robust framework.

Cynata have published their own information comparing CYP-001 with Ruxolitnib based on efficacy and the implied benefits of CYP-001. However, what is more interesting is that Ruxolitnib is also quite a toxic when used in real life: https://www.astctjournal.org/article/S2666-6367(21)01330-0/fulltext

“The most frequent side effects included cytopenias and these cases improved after a ruxolitinib dose reduction and/or addition of an erythropoietin-stimulating agent (ESA) for anemia.”<<[ This drug is really bad for your blood and your kidneys. You can reduce the dose and it may make that symptom better. However then you are still battling the extremely deadly GvHD. Great success.]

With all that in mind, Incyte received initial results from their Phase 2 trial on June 21, 2018. They were then granted Priority Review by the FDA on October 25, 2018. Finally, FDA approval was received on May 24, 2019. Putting that all together:

IF Cynata can recruit all the patients by 31 December 2025, then they could receive FDA approval before the end of 2026.