Curis’s bump from this year’s EHA meeting was short lived. After being one of the big winners of last month’s abstract drop, the group was down heavily on Friday, with investors apparently spooked by toxicity concerns with its oral Irak-4 inhibitor CA-4948.
As for the winners, these were fewer and further between, but Protagonist Therapeutics led the pack with a 17% share rise on Friday. That company had positive phase 2 data with its lead project rusfertide in polycythemia vera.
PV is a disease of uncontrolled blood cell production that increases the risk of heart disease and stroke. One treatment involves blood draws, with an aim to decrease haematocrit – the proportion of blood that consists of red blood cells – to below 45%.
In Protagonist’s proof-of-concept trial, therapeutic phlebotomies were “essentially eliminated” and the <45% haematocrit target was maintained for the “vast majority” of rusfertide-treated patients. The project is also being studied in hereditary haemochromatosis; Protagonist plans to start a single phase 3 study in early 2022.
|Notable share price moves among companies presenting at EHA 2021|
|Company||Share price change||Note|
|Protagonist Therapeutics||17%||Ph2 data with rusfertide in polycythemia vera|
|Autolus Therapeutics||13%||Ph1 data with obe-cel in indolent B cell lymphomas & adult ALL|
|Crispr Therapeutics||3%||Ph1/2 data with CTX001 in sickle cell & beta-thal|
|Curis||-37%||Ph1/2 data with CA-4948 in AML & MDS|
|Aptose Biosciences||-32%||Ph1 data with luxeptinib in AML & B-cell malignancies|
|Forma Therapeutics||-19%||Ph1 data with etavopivat (FT-4202) in sickle cell|
|Equillium||-12%||Ph1b data with itolizumab in GVHD|
|Vertex Pharmaceuticals||-11%||Ph1/2 data with CTX001 in sickle cell & beta-thal; move down to AATD fail|
|X4 Pharmaceuticals||-7%||Ph1b data with mavorixafor + Imbruvica in Waldenstrom’s macroglobulinemia|
|Agios Pharmaceuticals||-3%||Mitapivat: ph3 data in PKD; ph2 data in beta-thal|
|Imara||-3%||Ph2a data with IMR-687 in sickle cell|
|Note: from market close Thurs June 10 to Friday June 11.|
Things were not so rosy for Curis. The company impressed last month with a 44% overall response rate among nine patients in a phase 1/2 trial of CA-4948 in acute myelogenous leukaemia or myelodysplastic syndrome. Now that response rate has dipped, to five of 17 evaluable patients (29%).
Safety might be causing greater concern, though. The group had already backed away from a 500mg twice-daily dose due to adverse events and on Friday it said that the 400mg dose had been linked with dose-limiting toxicities, namely two cases of grade three rhabdomyolysis. Curis is taking the 300mg twice-daily dose forward, it has now disclosed, and investors will no doubt be keeping a close eye on whether the company has found a therapeutic window.
Higher dose needed?
Meanwhile, Aptose might have the opposite problem: getting the dose of its FLT3/BTK inhibitor luxeptinib high enough. The company reported a complete response with a 450mg twice-daily dose in an acute myeloid leukaemia patient; however, there were no CRs at a 600mg dose and Aptose is pushing on with a 750mg cohort, with plans to dose higher.
Forma, like Curis, suffered on toxicity worries. That company’s etavopivat showed good efficacy in a phase 1 study in sickle cell disease, building on data at last year’s Ash meeting, but two cases of vaso-occlusive crises put a dampener on the announcement.
Both cases were deemed unrelated to the pyruvate kinase R activator, but there had already been concerns about pain crises with etavopivat and a rival project from Agios, mitapivat – the latest update will only add to these (Ash 2020 – Forma gets an early edge over Agios in sickle cell disease, December 7, 2020).
And Equillium was punished after data from the phase 1b Equate study of its anti-CD6 antibody itolizumab in first-line graft-versus-host disease failed to live up to an earlier look. At EHA, the company reported a complete response rate of 55% and an ORR of 70% among 20 patients – down from a 70% complete response rate in 10 patients previously.
As for Vertex, a positive update for its Crispr-partnered gene editing project CTX001 in sickle cell disease and beta thalassaemia was not enough to cancel out the failure of a second alpha-1 antitrypsin deficiency asset, separately announced on Friday.
The road to market for gene editing therapies is uncertain, Leerink analysts noted, and the pressure on Vertex to do a large deal will now surely grow.