ISTH'26 Takes: A Closer Look At Newly Disclosed Plasmin Inhibitor, HMB-003

Research evidence excerpt

ISTH'26 Takes: A Closer Look At Newly Disclosed Plasmin Inhibitor, HMB-003

ISTH deck, mgmt noted they have

thoroughly characterized the drug's off-tgt profile; 2) engineered peptide+fatty acid conjugate

for chronic SC use does not raise the risk for ADA development; 3) Drug clears by ~day 14;

short duration mitigates risk vs permanent suppression and is not expected to impair plasmin's

physiological function (matrix remodeling, angiogenesis, complement C3 activation, growth factor

activation, and wound healing); plus, ocular/microvascular risks and CNS crossing (seizure risk) are

not expected.

One noteworthy point is that HMB-003 was reported to localize w/ fibrin in a human whole-blood

microfluidic flow model. The implication is that '003 concentrates activity where clot stabilization

is needed. Mgmt downplayed risks of 'over-stabilization' citing extensive clin experience w/ TXA

and high-dose testing w/o emerging signals.

For next steps, '003 ph.I SAD/MAD in healthy volunteers is to start 2H; we expect tPA-ROTEM as

primary PD biomarker, mirroring ALN-6400 ph.I design, and ALNY HV data 2H will be informative.

Interaction b/w HMB-003 and hormonal tx will likely become an important incl/excl criteria. If

TXA already produces ~40–60% menstrual blood-loss reductions, while only partially suppressing Maury Raycroft, Ph.D. * | Equity Analyst

fibrinolysis, how much add'l efficacy is actually available remains an open question, but serves as (212) 323-3990 | mraycroft@jefferies.com

a good ref benchmark. Mgmt noted deeper plasmin inhibition+durability (AUC) of inhibition should Farzin Haque, Ph.D. * | Equity Analyst

translate to better outcomes. Adherence/convenience along w/ performance in TXA failure pts will +1 (212) 778-8349 | fhaque@jefferies.com

also matter.