“Jefferies: SGMO providing reasons for pts+docs to hesitate to use Valrox.
New ISTH HemeA Data Stand Out W/ Consistent
Efficacy, Durability, and Safety
July 7, 2019
Key Takeaway
SGMO reported new '525 hemeA data at ISTH that were in-line w/ our expectations here
-- data showed durable F8 in follow-up for two high-dose (3E13) pts and consistent F8
efficacy in two new 3E13 pts w/ favorable safety. Data add more support to case for
'525 being differentiated -- tracking superior to Valrox and SPK-8011; more data at ASH.
SGMO noted in their PR they are working w/ PFE to move '525 into a registrational trial. RMAT
announced too.
Recall, normal F8 levels were achieved rapidly for the two initial pts dosed at 3E13 (last
cut reported on 4/2); the ISTH cut shows that F8 levels were maintained in the longerterm
follow up. For these two pts both reached a normal F8 range (50-170%) w/in 6 wks
w/ F8 levels tracking better than both BMRN's Valrox and Roche/ONCE's SPK-8011 w/
in this timeframe; longer-term data showed normal F8 was maintained out to 24 and 19
wks for the two pts (#7 and #8, respectively). Notably, the follow-up data also showed at
the 1E13 dose pt #6 had F8 durable to wk 52 and #5 some durability to wk 32.
First look at two new expansion pts who received high-dose 3E13 (pts #9 and 10) showed
consistent F8 kinetics w/ two initial 3E13 pts. W/ new pts #9 and 10 we saw F8 ramp
up rapidly post tx; notably, pt #9 had the lowest baseline F8 (of the 4 high-dose pts), and
showed rapid F8 increase after wk 1, which continued to ramp up at wks 2-5. The slide
deck noted after the ISTH cut pt #9 reached normal F8 at wk 7. Pt #10 has only been on tx
for 3 wks, and this pt is showing a similar trajectory. Together, the data from the two new
pts support consistency, and total follow-up support durability, giving us greater confidence.
Also, the total '525 safety profile so far looks good, even w/ no prophylactic steroid used.
No new notable safety events were observed; in the two new pts (according to the PR)
there was one add'l transient Gr1 ALT (both ALTs managed w/ oral tapering) and a new
Gr2 pyrexia. We view the overall safety profile so far as a favorable.
What is SGMO doing differently to stack up better vs the rest? Safety and efficacy may
go hand-in-hand -- better SGMO profile could be driven in part by the low total viral load
used (vs Valrox), a benefit that resonates w/ experts... and has manufacturing advantages
too, which may reflect a better transgene/expression system w/ '525 that enables '525
to come out on top of SPK-8011. SGMO has highlighted their modified F8 transgene
including optimized liver-specific promoter and cassette, which led to better preclin NHP
data vs BMRN and ONCE -- seems to be panning out in the clinic. Could also be related
to the different AAV serotypes used, which may improve '525 tropism/transduction.
SGMO's high-dose data are early and small #s, but looking relatively good so far. BMRN
ahead, but SGMO providing reasons for pts+docs to hesitate to use Valrox.
RMAT, add'l data at ASH, and talk about a registrational path. SGMO is expected to
present add'l data (follow-up+new pts) at ASH -- PR notes pt 11 is expected to be treated
soon (may treat two more at 3E13 for 7 total). The PR also announced RMAT, which we
view as an important positive that should help w/ advancement to a registrational.”
AI
