Economic Value PropositionUsing and Wound Matrix

Wound Management Devices

MK-XXXX.X | 2018

MK-XXXX.X | 2018

Rx ONLY Refer to IFU supplied with each device for indications, contraindications, and precautions. U.S. Toll-Free: 800-826-2926 | www.acell.com© 2019 ACell, Inc. All Rights Reserved. MK-0553.02 | 2019

1893075-1-EN

Product Item Number Size Quantity

MicroMatrix Micronized Particles MM0020 20 mg 1/box MicroMatrix Micronized Particles MM0030 30 mg 1/box MicroMatrix Micronized Particles MM0060 60 mg 1/box MicroMatrix Micronized Particles MM0100 100 mg 1/box MicroMatrix Micronized Particles, Fine MM0100F 100 mg 1/box MicroMatrix Micronized Particles MM0200 200 mg 1/box MicroMatrix Micronized Particles MM0500 500 mg 1/box MicroMatrix Micronized Particles MM1000 1000 mg 1/box

Cytal Wound Matrix 1-Layer WS0303 3 x 3.5 cm 1/box Cytal Wound Matrix 1-Layer WS0307 3 x 7 cm 1/box Cytal Wound Matrix 1-Layer WS0710 7 x 10 cm 1/box Cytal Wound Matrix 1-Layer WS1015 10 x 15 cm 1/box

Cytal Wound Matrix 2-Layer WSM0505 5 x 5 cm 1/box Cytal Wound Matrix 2-Layer WSM0710 7 x 10 cm 1/box Cytal Wound Matrix 2-Layer WSM1015 10 x 15 cm 1/box

Cytal Wound Matrix 3-Layer WSR0505 5 x 5 cm 1/box Cytal Wound Matrix 3-Layer WSR0710 7 x 10 cm 1/box Cytal Wound Matrix 3-Layer WSR1015 10 x 15 cm 1/box

Cytal Wound Matrix 6-Layer WSX0505 5 x 5 cm 1/box Cytal Wound Matrix 6-Layer WSX0710 7 x 10 cm 1/box Cytal Wound Matrix 6-Layer WSX1015 10 x 15 cm 1/box

ACell, Inc.6640 Eli Whitney Drive Columbia, MD 21046 800-826-2926

www.acell.com

Cost of Wound Care

Whether in an acute or chronic setting, costs of care can be further increased by challenging wound presentations and complications.

A Closer Look – Limb Salvage

$25 BILLION Annual Wound Care Costs to the Nation's Health Care System1

Number of patients is growing annually1

Incidences of difficult to heal cutaneous wounds in the United States2

6.5 MILLION3 MILLION

Major cost savings are associated with salvaging a limb versus amputation.

Cytal Wound Matrix and MicroMatrix are medical devices engineered using ACell’s proprietary MatriStem UBM™

(Urinary Bladder Matrix) technology. The devices maintain an intact epithelial basement membrane and facilitate the body’s ability to remodel site-appropriate tissue. Cytal Wound Matrix devices and MicroMatrix are appropriate for the management of acute and chronic wounds and use in reconstructive procedures.

• Affect approximately 4% - 10% of patients with Diabetes5

• Between 10% - 15% of DFUs do not heal6

• 85% of amputations result from non-healing ulcers7

• Treatment for a single DFU is estimated around $8,000-$17,000; costs can exceed $45,000 if an amputation is required8

Diabetic Foot Ulcers

DFUs

• Affect approximately 1 million adults in the U.S.2

• Around 30% of VLUs do not heal after 24 weeks11

• About 48% of VLUs recur after five years12

• Treatment for a single venous ulcer is estimated around $30,00013

Venous Leg Ulcers

VLUs• Approximately 1 million adults

with stage 3 and 4 PIs in the U.S.2

• 95% of stage 3 and 4 PIs do not heal within 8 weeks9

• Roughly 3.5% - 4.5% of all hospital patients develop hospital-acquired pressure ulcers (HAPUs)10

• Treatment for a single stage 4 PI is estimated to be greater than $120,0009

Pressure Injuries

PIs

Exposed Avascular Structures

Large Excisional Wounds

Increasing Prevalence of Patient Comorbidities

Health Care Costs Associated with Amputation or Reconstruction of a Limb-threatening Injury3

Limb Salvage

$163,282

Amputation

$509,275

• Projected lifetime health care costs for an amputation can be more than 3 times the cost of limb salvage.

• Studies have shown jeopardized flaps and skin grafts can increase wound management costs up to 58%4.

Projected Lifetime Medical Costs*

Common Challenges in Wound Care

Facilitates remodeling of site-appropriate tissue14

Provides an alternative option in the reconstructive ladder15

Successfully used in limb salvage procedures15, 17

A Closer Look – Chronic Wounds

MatriStem UBM Devices Can Provide a Cost-Effective Alternative for the Management of Complex Wounds

* Costs include: initial hospitalization, rehospitalizations related to limb injury, inpatient rehabilitization, outpatient doctor visits, outpatient PT/OT, and prosthetic devices/services. No drug costs included.

Evaluation of Tissue Engineering Products for the Management of Neuropathic Diabetic Foot Ulcers: An Interim Analysis*

STUDY DESIGN

OUTCOME MEASURES

Average Diabetic Foot Ulcer Scale Scores (DFS)**

Adverse Events

Prospective, multicenter, randomized study to evaluate the combination of MicroMatrix and Cytal Wound Matrix products compared to Dermagraft® (Organogenesis Inc., Canton, MA) for the management of non-healing Diabetic Foot Ulcers (DFUs). Subjects whose DFUs decreased in size by ≤30% or increased by ≤50% during the four-week standard of care (SOC) run-in phase were randomized into the treatment phase of the study. A total of 56 subjects, MicroMatrix/Cytal (n=27) and Dermagraft (n=29), were randomized into the treatment phase. A two-week post-treatment SOC phase followed the treatment phase for any wounds that did not heal by the end of eight weeks.

The study evaluated the incidence of ulcer closure, rate of ulcer healing, wound characteristics, patient quality of life, cost-effectiveness, and recurrence.

⚫ Comparable healing rates, with no significant difference between treatment groups.

⚫ Patients treated with MicroMatrix and Cytal had a significant improvement in quality of life scores (QOL) and significantly lower treatment costs.

Frykberg RG, Cazzell SM, Arroyo-Rivera J, Tallis A, Reyzelman AM, Saba F, Warren L, Stouch BC, Gilbert TW§. Journal of Wound Care. 2016 July; 25 Suppl 7:S18-25.

Cytal/MicroMatrix Dermagraft P-Value

Time of Consent 181.56 (±53.04) 184.46 (±61.03) 0.851

Randomization 196.22 (±64.91) 193.897 (±64.85) 0.894

End of Treatment (8 weeks) 151.11 (±72.86) 195.73 (±81.59) 0.074

End of post-treatment SOC (10 weeks) 134.15 (±74.35) 201.13 (±72.13) 0.023

0

2000

4000

6000

8000

10000

12000

MicroMatrix/Cytal Dermagraft

Average Treatment Costs

Wound Closure Rates at 90 Days

MicroMatrix/Cytal Apligraf Dermagraft OASIS

62% 58% 58% 63%

A Comparative Analysis of Skin Substitutes Used in the Management of Diabetic Foot Ulcers

STUDY DESIGN

OUTCOME MEASURES

Retrospective review of Medicare claims data from 2011 to 2014 with the aim to compare relative product costs and clinical outcomes of skin substitutes used as adjunctive treatment for DFUs. The review included beneficiaries who had inpatient or outpatient visits with foot ulcers as the primary diagnosis and a diagnosis of diabetes, treated with either Apligraf®, Dermagraft®, OASIS®, or MicroMatrix and Cytal Wound Matrix.

Skin substitutes were compared on episode length, amputation rate, skin substitute utilization, and skin substitute costs.

Martinson M, Martinson N. Journal of Wound Care. 2016 Oct; 25(Sup 10)S8-S17.

⚫ Apligraf and Dermagraft had significantly longer episode lengths compared to MicroMatrix/Cytal and OASIS.

⚫ The MicroMatrix/Cytal treatment group had a significantly lower cost per DFU episode compared to Apligraf and Dermagraft.

Data from the interim analysis showed that MicroMatrix and Cytal Wound Matrix provide results for healing DFUs that are similar to the results obtained for Dermagraft at a significant quality of life and economic advantage.

The comparative analysis provided evidence that MicroMatrix and Cytal Wound Matrix can successfully be used for the management of DFUs and, in this analysis, at a lower cost compared to the studied skin substitutes.

$0

$3,000

$6,000

$9,000

$12,000

$15,000

Average Cost of Materials

MicroMatrix/Cytaln=279

Apligrafn=4926

Dermagraftn=5530

OASISn=2458

Cytal/MicroMatrix (n=27) Dermagraft (n=29) P-Value

Number of subjects with at least one adverse event

8 (29.6%) 10 (34.5%)

0.6974Mild 2 5

Moderate 4 4

Severe 2 1

Adverse events with the highest frequency of occurrence

N/ACellulitis 3 (11.1%) 1 (3.4%)

Osteomyelitis 1 (3.7%) 1 (3.4%)

Wound infection 1 (3.7%) 2 (6.9%)

❊ indicates p<0.05 compared to MicroMatrix/Cytal

❖ indicates p<0.05 compared to OASIS

❊ ❖

❊ ❖

** The DFS is a validated QOL instrument that consists of 58 items grouped into eleven lifestyle domains. The scoring algorithm provides a health-related QOL response score, where a lower score correlates with a more positive subject assessment. DFS scores fall on a range of 58-290.16

*ACell, Inc. financially supported this study

STUDY DESIGN

OUTCOME MEASURES

Retrospective case review to assess the healing progression and costs associated with the treatment for patients with chronic complex wounds. A total of ten complex wound cases were examined, including a stage IV sacral pressure ulcer, a pilonidal wound, an open abdominal wound, a radiation wound, a wound related to hidradenitis suppurativa, an ostomy wound, and various surgical wounds.

An analysis of the cost of care was provided and compared with documented weekly cost of care in the same institution when conventional methods such as Negative Pressure Wound Therapy (NPWT) are utilized.

Complex Wounds Treated with MatriStem Xenograft Material: Case Series and Cost AnalysisSasse KC‡, Ackerman EM, Brandt JR. OA Surgery. 2013 Dec 01; 1(1):3.

This case series demonstrates there may be a cost savings in using MicroMatrix/Cytal instead of NPWT.

⚫ All wounds treated with MicroMatrix and Cytal healed without complication or infection with a median treatment time of eleven weeks.

⚫ Using MicroMatrix and Cytal resulted in a lower burden of office visits and less dressing changes compared to the historical use of NPWT.

Up to 70% less compared to NPWT

Estimated Weekly Treatment CostsNPWT vs. UBM Devices

Negative Pressure Wound Therapy

Cytal/MicroMatrix

References

1. Brem H, Stojadinovic O, Diegelmann R, Entero H, Lee B, Pastar I, Golinko M, Rosenberg H, Tomic-Canic M. Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement. Molecular Medicine. 2007 Jan-Feb; 13(1-2): 30-39.

2. SmartTRAK. (2019). US Hard-to-Heal Wound Volume Projections. [online] https://app.smarttrak.com/markets/qs/2f491c456352f41ac0a80237b1942c19 [Accessed 10 Oct. 2019].

3. Chung KC, Saddawi-Konefka D, Haase SC, Kaul G. A cost-utility analysis of amputation versus salvage for Gustilo type IIIB and IIIC open tibial fractures. Plastic and Reconstructive Surgery. 2009 Dec; 124(6):1965-73. doi: 10.1097/PRS.0b013e3181bcf156.

4. Fife CE, Carter MJ, Walker D, Thomson B. Wound Care Outcomes and Associated Cost Among Patients Treated in US Outpatient Wound Centers: Data From the US Wound Registry. Wounds. 2012 Jan; 24(1): 10-17.

5. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005 Jan 12; 293(2):217-28.

6. Pemayun TG, Naibaho RM, Novitasari D, Amin N, Minuljo TT. Risk factors for lower extremity amputation in patients with diabetic foot ulcers: a hospital-based case-control study. Diabetic Foot & Ankle. 2015 Dec 7; 6:29629. doi: 10.3402/dfa.v6.29629. eCollection 2015.

7. Frykberg RG, Zgonis T, Armstrong DG, Driver VR, Giurini JM, Kravitz SR, Landsman AS, Lavery LA, Moore JC, Schuberth JM, Wukich DK, Andersen C, Vanore JV; American College of Foot and Ankle Surgeons. Diabetic foot disorders. A clinical practice guideline (2006 revision). The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons. 2006 Sep Oct; 45(5 Suppl):S1-66.

8. Blackman E, Moore C, Hyatt J, Railton R, Frye C. Topical wound oxygen therapy in the treatment of severe diabetic foot ulcers: a prospective controlled study. Ostomy/Wound Management. 2010 Jun; 56(6):24-31.

9. Brem H, Maggi J, Nierman D, Rolnitzky L, Bell D, Rennert R, Golinko M, Yan A, Lyder C, Vladeck B. High cost of stage IV pressure ulcers. American Journal of Surgery. 2010 Oct; 200(4):473-7. doi: 10.1016/j amjsurg.2009.12.021.

10. Lyder CH, Wang Y, Metersky M, Curry M, Kliman R, Verzier NR, Hunt DR. Hospital-acquired pressure ulcers: results from the national Medicare Patient Safety Monitoring System study. Journal of American Geriatrics Society. 2012 Sep; 60(9):1603-8. doi: 10.1111/j.1532-5415.2012.04106.x.

11. Parker CN, Finlayson KJ, Edwards HE. Predicting the Likelihood of Delayed Venous Leg Ulcer Healing and Recurrence: Development and Reliability Testing of Risk Assessment Tools. Ostomy/Wound Management. 2017 Oct; 63(10):16-33.

12. Hussain SM. A comparison of the efficacy and cost of different venous leg ulcer dressings: a retrospective cohort study. International Journal of Vascular Medicine. 2015; 2015:187531. doi: 10.1155/2015/187531. Epub 2015 Apr 14.

13. O’Donnell TF Jr, Lau J. A systematic review of randomized controlled trials of wound dressings for chronic venous ulcer. Journal of Vascular Surgery. 2006 Nov; 44(5):1118-25.

14. Brown BN, Londono R, Tottey S, Zhang L, Kukla KA, Wolf MT, Daly KA, Reing JE, Badylak SF¶. Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomaterialia. 2012; 8:978-987.

15. Lanier ST, Ruter DI, Valerio IL. Regenerative medicine for soft tissue coverage of the hand and upper extremity. Current Orthopaedic Practice. 2017; 29(2): 120-126.

16. Abetz L, Sutton M, Brady L, McNulty P, Gagnon DD. The Diabetic Foot Ulcer Scale (DFS): a quality of life instrument for use in clinical trials. Practical Diabetes Int. 2002; 19(6); 167-175.

17. Micallef CJ, et al. A value analysis of microsurgical lower extremity reconstruction vs. acellular UBM for radiation wounds of the lower extremity. Journal of Surgical Case Reports. 2019; 3,1-3

¶ Consultant