Positive IdeS phase I data published in scientific journal PLOS ONE

Hansa Medical AB (publ) today announced that the results from the phase I trial
of its candidate drug have been published in PLOS ONE
(http://dx.plos.org/10.1371/journal.pone.0132011).
The trial was a first-in-man, double blind, randomized study with single
-ascending doses of IdeS in twenty-nine healthy male subjects who were given
intravenous doses of placebo or IdeS at 0.01, 0.04, 0.12 and 0.24 mg/kg body
weight. IdeS was considered safe with no serious adverse events. Furthermore,
IdeS converted plasma IgG into single cleaved IgG (scIgG) with impressive
efficacy within minutes after administration.

ScIgG has compromised effector functions with reduced binding to Fcγ receptors
and reduced Fc mediated cytotoxicity (Brezski et al., 2009), i.e. the function
of the antibodies is significantly reduced. Full or close to full effect on IgG,
i.e. conversion into F(ab’)2 and Fc fragments (complete IgG cleavage), was seen
in all subjects dosed with 0.12 and 0.24 mg/kg BW. IgG reached the lowest
concentrations 2-24 hours after dosing and remained low for more than a week,
until newly synthesized IgG appeared in the plasma.

Data demonstrated that the entire extracellular IgG pool and not only the plasma
pool, is cleaved by IdeS. This remarkable efficacy of IdeS outcompetes the
effect of plasma exchange, which typically leaves approximately 35% remaining
IgG. Furthermore, 24 hours after a plasma exchange the IgG levels are restored
to 60% (Ismail et al., 2001).

“A single dose of IdeS rapidly and efficiently inactivates IgG in humans, and
the effect remains for several weeks. IdeS alone or in combination with B-cell
attenuating drugs is a very attractive therapeutic approach for many IgG driven
conditions. The results uncover a new therapeutic concept to eliminate
pathogenic IgG”, commented Hansa Medicals CSO Christian Kjellman.

Since S. pyogenes is a common human pathogen, all subjects had pre-formed anti
-IdeS IgG antibodies and reacted as expected with an IgG response peaking two to
three weeks after the IdeS infusion. Six to twelve months after dosing, all
subjects were back to normal anti-IdeS antibody levels. The half-life of IdeS
was 4.9 (±2.8) hours at 0.24 mg/kg with the main fraction eliminated from plasma
during 24 hours.

The complete, rapid, but temporary removal of IgG provides a new potent
therapeutic opportunity in IgG-mediated pathogenic conditions. IdeS treatment
has the capacity to quickly and effectively remove IgG in HLA sensitized
transplantation patients, thereby allowing transplantation and avoiding acute
antibody-mediated rejection. The safety and efficacy of IdeS in removing anti
-HLA antibodies in sensitized dialysis patients are investigated in ongoing
phase II studies. IdeS is currently also considered for clinical studies within
several acute antibody mediated conditions, e.g. antibody mediated graft
rejection, Guillain-Barré syndrome and Goodpasture’s syndrome.

Brezski RJ, Vafa O, Petrone D, Tam SH, Powers G, Ryan MH, et al. (2009) Tumor
-associated and microbial proteases compromise host IgG effector functions by a
single cleavage proximal to the hinge. Proc Natl Acad Sci U S A 106: 17864
-17869.

Ismail N, Neyra R, Hakim R (2001) Plasmapheresis. In: Daugirdas JT, Blake PG,
Ing TS, editors. Handbook of dialysis, 3rd edn. 3 ed. Philadelphia: Lippincott
Williams Wilkins. pp. 231-262.

The information in this press release is disclosed pursuant to the Securities
Markets Act or the Financial Instruments Trading Act. The information was
released for public disclosure on July 16, 2015, at 08:00 CET.
For further information, please contact:
Hansa Medical AB
Christian Kjellman, Ph.D
Chief Scientific Officer
Mobile: +46 705 717417
E-mail:
christian.kjellman@hansamedical.com

www.hansamedical.com
About IdeS
IdeS, a unique molecule with a novel mechanism, is a bacterial enzyme that
cleaves human IgG antibodies. IdeS aims to degrade immunoglobulin G (IgG) and
has been tested for safety and efficacy in numerous in vitro and in vivo models.
During 2013, a Phase I clinical trial on 29 healthy subjects was conducted,
demonstrating IdeS as efficacious and well tolerated with a favourable safety
profile. During 2014, a Phase II study in 8 sensitized patients awaiting kidney
transplantation was conducted. Preliminary data show that IdeS is effective in
reducing anti-HLA antibody levels in highly sensitized patients on the kidney
transplant waitlist. The study shows that IdeS has the capacity to make
sensitized patients eligible for transplantation by decreasing HLA antibodies to
levels acceptable for transplantation. In addition to transplantation, IdeS has
potential applications in a variety of rare autoimmune diseases. IdeS is
protected by several patents and results of studies with IdeS have been
published in a number of peer reviewed medical and scientific journals.

About Hansa Medical AB
Hansa Medical is a biopharmaceutical company focused on novel immunomodulatory
enzymes. Lead project IdeS is an antibody-degrading enzyme in clinical
development, with potential use in transplantation and rare autoimmune diseases.
Other projects include HBP (a market introduced diagnostic marker for severe
sepsis) and EndoS (an antibody-modulating bacterial enzyme in pre-clinical
development). The company is based in Lund, Sweden. Hansa Medical's share (HMED)
is listed on Nasdaq First North in Stockholm with Remium Nordic AB as Certified
Adviser.