Control With Confidence The only antivenom derived from native US pit vipers to treat envenomations from all species of North American pit vipers1

CroFab is the only antivenom   Derived from geographically and clinically relevant US snakes for comprehensive coverage of all North American pit viper envenomations1   Designed with small, venom-specific protein (Fab) fragments for rapid neutralization of venom toxins throughout affected tissue1,2   With Level 1 evidence in the treatment of copperhead envenomation3   Manufactured to yield the highest level of quality, purity, and safety1   With a proven efficacy and safety profile, backed by >20 years of clinical experience1   Reliably supplied throughout the United States4

CroFab meets World Health Organization (WHO) guidelines for effective antivenom, utilizing venom from 4 clinically relevant pit viper species native to the United States.1,5

Indication CroFab® Crotalidae Polyvalent Immune Fab (Ovine) is a sheep-derived antivenin indicated for the management of adult and pediatric patients with North American crotalid envenomation. The term crotalid is used to describe the Crotalinae subfamily (formerly known as Crotalidae) of venomous snakes which includes rattlesnakes, copperheads and cottonmouths/water moccasins. Important Safety Information Contraindications Do not administer CroFab® to patients with a known history of hypersensitivity to any of its components, or to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available. Warnings and Precautions Coagulopathy: In clinical trials, recurrent coagulopathy (the return of a coagulation abnormality after it has been successfully treated with antivenin), characterized by decreased fibrinogen, decreased platelets, and elevated prothrombin time, occurred in approximately half of the patients studied; one patient required re-hospitalization and additional antivenin administration. Recurrent coagulopathy may persist for 1 to 2 weeks or more. Patients who experience coagulopathy due to snakebite should be monitored for recurrent coagulopathy for up to 1 week or longer. During this period, the physician should carefully assess the need for re-treatment with CroFab® and use of any type of anticoagulant or anti-platelet drug. Hypersensitivity Reactions: Severe hypersensitivity reactions may occur with CroFab®. In case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment. Patients allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may also have an allergic reaction to CroFab®. Follow-up all patients for signs and symptoms of delayed allergic reactions or serum sickness (e.g., rash, fever, myalgia, arthralgia).

Please see additional Important Safety Information on reverse and enclosed full Prescribing Information. Strength and Speed When You Need It Most

CroFab is clinically proven to arrest local injury, resolve systemic effects, and reduce hematologic effects of envenomation1

• 98% of patients treated with CroFab 100

achieved initial control 90 • Local signs of 98% Based on Investigator envenomation were 95% n=41/42 Clinical Assessment (ICA), • 95% of patients treated with CroFab 80 arrested (leading n=40/42 edge of local injury in which the investigator were judged by the investigator to 70 not progressing) assessed whether initial have clinically relevant control of control was clinically 60 • Systemic symptoms relevant (pretreatment envenomation as assessed 1 hr were resolved signs and symptoms of 50 after initial control1,6 • Coagulation parameters envenomation were arrested had normalized or were or improved) as assessed

Patients (%) Patients 40 trending toward normal 1 hr after initial control1,6 30 Based on 2 open-label trials with 42 patients with mild or moderate envenomation. Exclusion criteria for both trials included envenomation 20 by copperhead snakes. In study 1, patients were given up to 2 doses 10 of 4 vials each to gain initial control. In study 2, patients were given up to 2 doses of 6 vials each to gain initial control. 0 Initial Control Clinical Response

Appropriate dosing of CroFab achieves initial and sustained control of envenomation1

• CroFab should be administered as soon as possible in INITIAL DOSE* MAINTENANCE DOSE† patients with any sign of envenomation (eg, local, systemic, or hematologic effects) to prevent clinical deterioration INITIAL • Administer an initial dose of 4-6 vials and monitor 4-6 2 CONTROL for signs of progression* VIALS VIALS – Administer an additional 4-6 vials if initial control q6h x 3 is not achieved ~1 hr after initial dose

• Once initial control is achieved, administer an additional NO 2 vials every 6 hr for up to 18 hr (total of 3 doses)† Scheduled maintenance dosing In 67%pre- ofand patients postmarketing achieved studies, 67-88% of patients reduced the incidence of coagulation – Scheduled maintenance dosing reduced the incidence achievedintial control initial with control 4-6 vials* with an initial dose of 4-6 vials of coagulation abnormalities due to residual venom when given according to recommendedabnormalities dosing.7,8 due to residual venom

*Initial dose may vary from 4-12 vials based on clinical judgment and severity of envenomation.1 † 9 Maintenance dosing may not be indicated in certain situations (eg, minor envenomations). CroFab has an established safety and efficacy profile1,3

• Postmarketing data from 2 studies showed low rates of hypersensitivity reactions 10,11 OVER (1.4%; N=1340 and 2.7%; N=373) in patients treated with CroFab OVER • A systematic review of published postmarketing cohort studies (including retrospective 50K YRS and prospective observational studies and clinical trials) showed low rates of reported PATIENTS 20 TREATED CLINICAL late bleeding (0.9%; N=1017) and medically significant late bleeding (0.5%; N=1017) EXPERIENCE following administration of CroFab12

Important Safety Information (continued) Adverse Reactions The most common adverse reactions (incidence ≥5% of subjects) reported in the clinical studies were urticaria, rash, nausea, pruritus and back pain. Adverse reactions involving the skin and appendages (primarily rash, urticaria, and pruritus) were reported in 12 of the 42 patients. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment and one patient discontinued CroFab® due to an allergic reaction. Recurrent coagulopathy due to envenomation and requiring additional treatment may occur.

References: 1. CroFab® [prescribing information]. BTG International Inc.; August 2018. 2. Laustsen AH et al. Toxicon. 2018;146:151-175. 3. Gerardo CJ et al. Ann Emerg Med. 2017;70(2):233-244.e3. 4. Data on file. Conshohocken, PA; BTG International Inc. 5. World Health Organization. WHO guidelines for the production, control and regulation of snake antivenom immunoglobulins. https://www.who.int/bloodproducts/AntivenomGLrevWHO_TRS_1004_web_Annex_5.pdf. Accessed April 9, 2020. 6. Dart RC et al. Ann Intern Med. 1997;30(1):33-39. 7. Dart RC et al. Arch Intern Med. 2001;161(16):2030-2036. 8. Lavonas EJ et al. Ann Emerg Med. 2004;43(2):200-206. 9. Lavonas EJ et al. BMC Emerg Med. 2011;11:2. 10. Khobrani M et al. Clin Toxicol (Phila). 2019;57(3):164-167. 11. Kleinschmidt K et al. [Published correction appears in Clin Toxicol (Phila). 2018 Aug;56(8):802]. Clin Toxicol (Phila). 2018;56(11):1115-1120. 12. Lavonas EJ et al. Ann Emerg Med. 2014;63(1):71-78.e1. Follow CroFab:

© 2021 BTG International Inc. All rights reserved. US-CRF-2100066 May 2021 BTG and the BTG roundel logo are registered trademarks of BTG International Ltd. CroFab® is a registered trademark of BTG International Inc.

Please see additional Important Safety Information on reverse and enclosed full Prescribing Information.