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Bioverativ's Investigational BIVV009 Demonstrates Safety, Tolerability and Efficacy in Phase 1b Clinical Trial in Cold Agglutinin Disease (CAgD) Patients


- Phase 1b results achieve primary and secondary endpoints in CAgD

- Six of six primary CAgD patients had an increase in hemoglobin of 4
g/dl or more, and remained
transfusion-free during treatment

- Largest CAgD natural history study to date quantifies increased
risk of thromboembolic events

(NASDAQ:BIVV), a global biopharmaceutical company
dedicated to transforming the lives of people with rare blood disorders,
today presented data demonstrating that BIVV009, its first-in-class
monoclonal antibody currently in Phase 3 clinical development for the
treatment of cold agglutinin disease (CAgD), was generally well
tolerated, rapidly halted hemolysis, and improved anemia in six of six
severely anemic primary CAgD patients in a Phase 1b clinical trial. The
data were shared in an oral presentation at the 59th Annual
Meeting of the American Hematology Society.

CAgD is a rare blood disease that results in the premature destruction
of red blood cells (hemolytic anemia) by the body's immune system. There
are currently no approved treatments for the disease. BIVV009 has been
designed to block the classical complement pathway – a key pathway that
triggers the immune system to remove damaged cells. It is believed that
this approach may limit the immune system from mistakenly removing red
blood cells and potentially interrupt the CAgD disease process. BIVV009
was awarded Breakthrough Therapy Designation by the U.S. Food and Drug
Administration based on earlier data from the Phase 1b study.

Primary and secondary outcome measures were achieved in the six patients
with primary CAgD in the study. Hemoglobin levels increased in all six
patients (median >4g/dl), eliminating the need for transfusions while on
treatment. Endpoints included tolerability, pharmacokinetic profile
supporting biweekly dosing, classical complement pathway inhibition as
evidenced by decreased total complement activity, and improved
biomarkers associated with rapid hemolysis resolution and corresponding
improvement in hemoglobin levels.

Hemolysis and anemia recurred upon clearance of BIVV009 from circulation
(3-4 weeks following the final dose), and efficacy was restored in all
patients upon re-exposure to BIVV009 during a subsequent Named Patient
Program. Maintenance therapy has demonstrated a sustained response for
more than 18 months, including control of hemolysis. Safety data through
December 21, 2016 demonstrated that BIVV009 was generally well
tolerated. Five of 6 patients (83.3%) in the primary CAgD group
experienced at least one adverse event (AE); no AE was reported by more
than one patient. One unrelated, serious AE occurred in a patient with
CAgD who was hospitalized for a pre-existing condition. There were no
serious AEs assessed as related to BIVV009 by the investigator.

"These Phase 1 results reinforce our confidence in the potential for
BIVV009 to make a real difference in the lives of CAgD patients, who
today have no approved treatments to manage their disease," said Joachim
Fruebis, Senior Vice President of Development, Bioverativ. "These data
show that BIVV009 has the potential to address patients' anemia as well
as the underlying hemolysis, which, based on early data may contribute
to the increased thromboembolic risk observed in CAgD patients."

Natural History Study Reveals Increased Thromboembolic Event Risk
separate poster presentation provided the results of the largest
retrospective study of CAgD natural history to date, evaluating clinical
characteristics and the occurrence rate of thromboembolic (TE) events,
such as stroke. A review of de-identified patient information related to
claims, medications, laboratory results, procedures and clinical results
over a 10-year period in the United States identified 814 CAgD patients,
which were compared with a 7,960-member cohort matched for age, gender,
race, region and other measures.

The analysis found a statistically significant 55% overall increased
rate of thromboembolic events in CAgD patients vs. matched controls (31%
vs. 20%), as well as a statistically significant higher frequency of
multiple thromboembolic events. The risk of thromboembolic events
correlated with biomarkers of hemolysis, bilirubin and lactate
dehydrogenase (
LDH) levels, but not with anemia severity.

The review also showed that hemolysis was not resolved in 90% of
patients receiving treatment with rituximab, as demonstrated by
persistently elevated levels of bilirubin and LDH within 12 months of
the last dose. Rituximab is an unapproved but commonly used treatment
option for CAgD, and the only therapy included in the analysis.

The natural history study also showed:

  • Nearly 10% of all CAgD patients had venous TE events vs. 3% of matched
  • 25% of all CAgD patients had cerebral TE events vs. 16% of matched
  • 8% of CAgD patients had arterial TE events vs. 5% of matched
  • All TE event measurements were statistically significant when compared
    to matched comparisons

"For the first time, we have been able to quantify the true frequency of
thromboembolic events for CAgD patients, a complication that, until now,
has been underappreciated due to the rarity of the disease," said
Catherine Broome, M.D., Associate Professor, Georgetown University. "The
data in this study also provide much needed clarity that markers of
hemolysis, and not severity of anemia, predict an increased risk of
these life-threatening events. This can help us better manage patients
and highlights the need for new treatments that can rapidly control
hemolysis in CAgD patients."

About BIVV009
BIVV009 is a first-in-class, humanized,
monoclonal antibody that is designed to target C1s, a serine protease
within the C1-complex in the complement pathway of the immune system,
and directly impact the central mechanism of CAgD. With a unique
mechanism of action and high target specificity, BIVV009 is designed to
selectively inhibit disease processes in the classical complement
pathway while maintaining activity of the alternative and lectin
complement pathways, which are important for immune surveillance and
other functions.

About Cold Agglutinin Disease (CAgD)
CAgD is a debilitating
autoimmune hemolytic anemia in which autoantibodies target red blood
cells, leading to red blood cell destruction via complement activation
initiated by the C1 complex, causing chronic anemia, severe fatigue, and
potentially fatal thrombotic events. There are no approved therapies for
CAgD, which occurs in approximately 16 people per million, affecting an
estimated 10,000 people in the United States and Europe. Symptom onset
typically begins around age 60, and treatment is aimed at normalizing
hemoglobin levels through blood transfusions, steroids, or off-label
immunotoxic therapy. However, current treatment options are often
intensive, incomplete, or nondurable, leaving patients dependent upon
frequent transfusions, which can lead to chronic iron overload.

About Bioverativ
Bioverativ (NASDAQ:BIVV) is a global
biotechnology company dedicated to transforming the lives of people with
hemophilia and other rare blood disorders through world-class research,
development and commercialization of innovative therapies. Launched in
2017 following separation from Biogen Inc., Bioverativ builds upon a
strong heritage of scientific innovation and is committed to actively
working with the blood disorders community. The company's mission is to
create progress for patients where they need it most and its hemophilia
therapies when launched represented the first major advancements in
hemophilia treatment in more than two decades. For more information,
or follow @bioverativ
on Twitter.

Bioverativ Safe Harbor
This press release contains
forward-looking statements, including statements about the potential
benefits, safety and clinical effects of BIVV009. These forward-looking
statements may be accompanied by such words as "anticipate," "believe,"
"could," "estimate," "expect," "forecast," "intend," "may," "plan,"
"potential," "project," "target," "will" and other words and terms of
similar meaning. You should not place undue reliance on these
statements. Drug development and commercialization involve a high degree
of risk, and only a small number of research and development programs
result in commercialization of a product. Results in early stage
clinical trials may not be indicative of full results or results from
later stage or larger scale clinical trials and do not ensure regulatory
approval. Factors which could cause actual results to differ materially
from Bioverativ's current expectations include: uncertainties relating
to the initiation, enrollment and completion of stages of clinical
trials; reliance on third parties for aspects of clinical trials;
unexpected concerns may arise from data, analysis or results obtained
during clinical trials or post hoc analysis of studies; regulatory
authorities may require additional information or further studies, or
may fail or refuse to approve or may delay approval of product
candidates; or Bioverativ may encounter other unexpected hurdles; and
other risks and uncertainties associated with Bioverativ's drug
development and commercialization activities described in the Risk
Factors section of Bioverativ's filings with the Securities and Exchange
Commission. These statements are based on Bioverativ's current beliefs
and expectations and speak only as of the date of this press release.
Bioverativ does not undertake any obligation to publicly update any
forward-looking statements.

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