Nwq

A atural Choice Expressed in a human cell line.

B-domain deleted.

No chemical modifications.

www.NUWIQUSA.com

Please see accompanying full Prescribing Information.

The Only Recombinant FVIII Produced From a Human Cell Line Without Chemical Modification or Protein Fusion

Powerful Bleeding Control Prophylaxis, On-Demand, and Surgery Prophylaxis in adults and children1*

ZERO Median ABR Spontaneous Bleeds1 IN ADULTS (N=32)

In adults & children

Median ABR for All Bleeds was 0.9

Median ABR for all bleeds was 0.9 in adults and 1.9 in children

50% had zero bleeding episodes 34% had 1 bleeding episode

Dosing Flexibility

Bleeding Control Convenience Safety

IN CHILDREN (N=59)

ZERO

Median ABR for All Bleeds was 1.9 34% had zero bleeding episodes

Median ABR

24% had 1 bleeding episode

1 *Regimen: NUWIQ every other day or 3 times per week for ≥6 months.

2.5 mL diluent volume across ALL vials Potential for 2X weekly infusions with personalized prophylaxis Easy monitoring by chromogenic or one-stage assay

SPONTANEOUS BLEEDS Adults & Children

On-demand treatment in adults (N=986 bleeds)3,4

§ Most bleeds resolved with 1 infusion (90%) or 2 infusions (97%) § Flexibility for patients to redose at 12 to 24 hours Perioperative control and prevention of bleeding (N=33 surgeries)1

§ 100% of minor surgeries, hemostasis rated as “excellent” § 92% of major surgeries, hemostasis rated as “excellent” or “good” Personalized prophylaxis5

Low Inhibitors1,2 ZERO inhibitors in PTPs In PUPs: 16.2% absolute incidence of high-titer inhibitors (17.6% cumulative incidence)

ZERO Median ABR

ALL BLEEDS

3.5

DAYS

Median Dosing Interval

Provides bleeding protection with the potential for 2x weekly dosing

ABR, annualized bleed rate; FVIII, factor VIII; PTP, previously treated patient; PUP, previously untreated patient.

2

Indications and Use NUWIQ® is a recombinant antihemophilic factor [coagulation factor VIII (Factor VIII)] indicated in adults and children with Hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes. NUWIQ is not indicated for the treatment of von Willebrand Disease.

Please see accompanying full Prescribing Information.

Important Safety Information Contraindications NUWIQ is contraindicated in patients who have manifested life-threatening hypersensitivity reactions, including anaphylaxis, to the product or its components.

Please see accompanying full Prescribing Information.

3

Not All Factor VIII Replacements Are the Same

FVIII Sulfation and Natural VWF Binding § Full tyrosine sulfation at Y1680 is essential for the interaction of FVIII with VWF and for full affinity for VWF § Full sulfation increases binding affinity 5-fold naturally

11

11

There are design differences in: 5,6

Human vs Hamster Cell Line

Manufacturing

Purification

NUWIQ is fully sulfated at Tyr1680—similar to plasma-derived FVIII10 NUWIQ

FVIII heavy chain

protein fusion

§ No animal proteins are added during production

VWF binding site (yellow)

Sulfated Y1680

Sulfated Y1680

Intensity (au)

§ Produced in a human cell line, not hamster cell lines § B-domain deleted, no chemical modification or

Human glycan

Intensity (au)

NUWIQ closely resembles natural FVIII 1,3,4,7-10

52

NUWIQ has high binding affinity to endogenous VWF (99% bound)6,7,9,10 cleared from circulation

54

52

Time (min)

FVIII light chain

§ VWF-binding prevents FVIII from being rapidly

Plasma-derived FVIII

54

Time (min)

Other rFVIII concentrates show nonsulfated (minor or absent peak) Y1680-containing peptides10

§ High binding affinity may contribute to

4

Important Safety Information Warnings and Precautions Hypersensitivity reactions, including anaphylaxis, are possible with NUWIQ. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, or pruritus.

Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur. The formation of neutralizing antibodies (inhibitors) to Factor VIII can occur following the administration of NUWIQ. Please see accompanying full Prescribing Information.

52 54

Time (min)Time (min)

54

XYNTHA®

1.6% 1.6% nonsulfated nonsulfated Y1680 Y1680

52

52 54

54

Time (min)Time (min)

Intensity (au)

Sulfated Sulfated Y1680 Y1680 Intensity (au)

Intensity (au)

8.0% 8.0% nonsulfated nonsulfated Y1680 Y1680

52 au, arbitrary unit; rFVIII, recombinant factor VIII; Tyr, tyrosine; VWF, von Willebrand factor.

Sulfated Sulfated Y1680 Y1680 Intensity (au)

Minimizing unbound FVIII may help reduce the risk of inhibitor development.9

Sulfated Sulfated Y1680 Y1680 Intensity (au)

Advate® Intensity (au)

prolonging FVIII half-life

5.3% 5.3% nonsulfated nonsulfated Y1680 Y1680

52

52 54

54

Time (min)Time (min)

Advate® is a registered trademark of Baxalta Incorporated, a Takeda company. XYNTHA® is a registered trademark of Pfizer Inc.

Important Safety Information Warnings and Precautions (continued) Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests. If the plasma Factor VIII level fails to increase as expected, or if bleeding is not controlled after NUWIQ administration, suspect the presence of an inhibitor (neutralizing antibody).

Please see accompanying full Prescribing Information.

5

Type of FVIII Molecule Can Affect Inhibitor Potential In the NuProtect study, cumulative incidence of high-titer inhibitors for NUWIQ was 17.6%; similar to pdFVIII in the separate SIPPET study1,2

Type of F8 Gene Mutation Can Impact Inhibitor Risk Null F8 mutations are associated with a higher risk of inhibitors vs non-null F8 mutations13 Cumulative Incidence of High-Titer Inhibitors By F8 Mutation in the SIPPET and NuProtect Studies2,12,14-16

Development of High-Titer Inhibitors (% of Patients)

NuProtect | Cumulative Incidence of High-Titer Inhibitors (N=105)1,2* 60

absolute incidence 40

17.6%

(95% CI: 10.0–25.3%)

NUWIQ rFVIII from human cell line 0 10

20

30

40

50

60

70

80

90

100

110

Exposure Days

There were ZERO high-titer inhibitors in PUPs with non-null F8 mutations treated with NUWIQ

* Information from the NuProtect study is presented in

20

0

Null F8 Mutations (N=90)

Data from 105 PUPs treated with NUWIQ were analyzed for inhibitor development, with 95 patients reaching ≥100 EDs or inhibitor development.

16.2%

120

parallel to the SIPPET study for context, but please note that these trials were performed under different conditions and with different populations. The observed incidence of inhibitor formation may be influenced by a number of factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

In the SIPPET study, rFVIII products from hamster cell lines (CHO or BHK) had a higher incidence† of inhibitor development than pdFVIII products12

Development of High-Titer Inhibitors (% of Patients)

SIPPET | Cumulative Incidence of High-Titer Inhibitors (N=251)12 60

High-titer Inhibitors

High-titer Inhibitors

18.9%

ZERO

Null F8 Mutations (N = 197)

Non-null F8 Mutations (N = 38)

pdFVIII/VWF (N=101)

rFVIII hamster cell line (N=96)

pdFVIII/VWF (N=16)

rFVIII hamster cell line (N=22)

22%

30%

ZERO

24%

In PTPs | ZERO Inhibitors With NUWIQ1,14

†Differences in high-titer inhibitor rates between pdFVIII and rFVIII

were not found to be statistically significant. SIPPET authors suggested this may have been due to the small sample size of the study.

28.4%

(95% CI: 19.6–37.2%)

40

20

pdFVIII/VWF

18.6%

(95% CI: 11.2–26.0%)

0 5

10

15

20

25

30

35

40

45

42.9%

The SIPPET Study compared the incidence of inhibitors in PUPs with severe Hemophilia A treated with either pdFVIII or rFVIII derived from hamster cell lines (Chinese hamster ovary [CHO] cells or baby hamster kidney [BHK] cells). Patients were followed for 50 consecutive EDs or 3 years or until inhibitor development was confirmed.

rFVIII from hamster cell lines

0

50

switched from pdFVIII

Important Safety Information Adverse Reactions The most frequently occurring adverse reactions (>5%) in clinical trials were upper respiratory tract infection, headache, fever, cough, lower respiratory tract infection, rhinitis, chills, abdominal pain, arthralgia, anemia, and pharyngitis.

Please see accompanying full Prescribing Information.

48.1% ZERO Inhibitors after switching to

switched from rFVIII

NUWIQ

ED, exposure days; pdFVIII; plasma-derived factor VIII; SIPPET, Survey of Inhibitors in Plasma-Product Exposed Toddlers.

Exposure Days

6

NUWIQ®

human cell line-derived rFVIII

SIPPET In PUPs with non-null F8 mutations treated with pdFVIII, there were ZERO high-titer inhibitors

Non-null F8 Mutations (N=12)

‡

2.2%

6.7%

switched from an unknown FVIII

switched from both rFVIII and pdFVIII

In clinical trials of PTPs (N=135) who switched to NUWIQ, there were ZERO FVIII inhibitors after ≥50 EDs and ≥6 months of treatment1,14‡

In clinical studies (N=135 PTPs), nonneutralizing antibodies without any inhibitor activity were reported in 4 patients.

Please see accompanying full Prescribing Information.

7

Convenient Usage, Comprehensive Support A broad range of dosage strength vials

§ Available in 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 2500 IU, 3000 IU, and 4000 IU vials § Low 2.5 mL diluent volume across the entire range of vial strengths

250 IU

500 IU

1000 IU

1500 IU

2000 IU

2500 IU

3000 IU

4000 IU

A comprehensive, personalized patient support program for people living with bleeding disorders Factor My Way Assistance

Factor My Way Connection

Includes free trial of NUWIQ (up to 6 doses) and co-pay assistance for eligible patients (up to $12,000 per year) on out-of-pocket treatment costs.

Personal support with Patient Experience Managers, educators, and nurses.

Factor My Way Events

Factor My Way Learning

Join scheduled live and on-demand digital information programs and events.

Comprehensive bleeding disorders library (articles, videos, and downloads).

Membership in Factor My Way is complimentary and open to anyone over the age of 18 in the USA.

factormyway.com Octapharma USA, Inc. 117 W. Century Road Paramus, NJ 07652 Tel: 201-604-1130

|

Free Trial, Co-Pay Assistance, and Reimbursement usreimbursement@octapharma.com Tel: 800-554-4440

855-498-4260 Medical Affairs usmedicalaffairs@octapharma.com

For all inquiries relating to drug safety, or to report adverse events, please contact our local Drug Safety Officer: Tel: 201-604-1137 | Cell: 201-772-4546 | Fax: 201-604-1141 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References: 1. NUWIQ full Prescribing Information. Paramus, NJ: Octapharma USA, Inc.; rev 2021. 2. Liesner RJ, et al. Thromb Haemost. 2021;121:1400–1408.

3. Valentino LA, et al. Haemophilia. 2014;20(Suppl. 1):1-9. 4. Kessler C, et al. Haemophilia. 2015;21(Suppl. 1):1-12. 5. Lissitchkov T, et al. Haemophilia.

2017;23:697-704. 6. Cafuir LA, et al. Ther Adv Hematol. 2017;8(10):303-313. 7. Casademunt E, et al. Eur J Haematol. 2012;89:165-176. 8. Winge S, et al.

Protein Expr Purif. 2015;115:165-175. 9. Sandberg H, et al. Thromb Res. 2012;130:808-817. 10. Kannicht C, et al. Thromb Res. 2013;131:78-88. 11. Leyte A. et al. J Biol Chem. 1991;266:740-746. 12. Peyvandi F, et al. N Engl J Med. 2016;374:2054-2064. 13. Oldenburg J, Pavlova A. Haemophilia. 2006;12:15–22.

14. Data on file. Paramus, NJ: Octapharma USA, Inc. 15. Rosendaal F, et al. Blood. 2017;130:1757–1759. 16. Astermark J, et al. Haemophilia. 2010;16:747-766.

©2023. Octapharma USA, Inc. All rights reserved.

Date of preparation: 5/2023. NUW-0713-PSA

www.NUWIQUSA.com