DUBLIN, Nov. 14, 2024 /PRNewswire/ — Mallinckrodt plc, a global specialty pharmaceutical company, today announced the winner of the Extracorporeal Immunomodulation Award (EIA). The award recognizes a project aimed at identifying the optimal timing for extracorporeal photopheresis (ECP) initiation and assessing its effectiveness when combined with other graft versus host disease (GvHD) therapies. To recognize the occasion, Mallinckrodt, which provides immunomodulatory therapy via ECP, dedicated the $75,000 grant to this research. This year’s award holds special significance as it marks 30 years since clinicians first used ECP to successfully treat chronic graft versus host disease (cGvHD).1,2

The EIA-winning project was submitted by Dr Andrea Varkonyi, of the South-Pest Central Hospital, National Institute of Hematology and Infectiology’s Department of Hematology and Stem Cell Transplantation, in Budapest, Hungary. Her team will carry out a retrospective and prospective study, comparing ruxolitinib alone to ruxolitinib combined with ECP therapy in the treatment of acute and chronic GvHD. They will also evaluate the impact of ECP on the development of transplant-associated thrombotic microangiopathy (TA-TMA).

“Mallinckrodt is thrilled to recognize Dr. Andrea Varkonyi with this year’s the Extracorporeal Immunomodulation Award and continuing the research in chronic GvHD. As the manufacturer of the THERAKOS CELLEX Photopheresis System we are committed to supporting research that seeks to improve patient outcomes and tackle unmet needs in this important area of medicine.” said Peter Richardson, MRCP (UK), Executive Vice President & Chief Scientific Officer.

Dr. Varkonyi said, “Acute and chronic GvHD, along with TA-TMA, remain unresolved issues following allogeneic bone marrow transplantation. Despite the intent of the procedure, these complications often prevent patients from achieving complete recovery. We are grateful to be receiving this award to advance research in this area. Thank you, Mallinckrodt, for the opportunity to further our research.”

The study’s objective is to identify the optimal timing for introducing ECP and assess its effectiveness when combined with other therapies. It aims to address key areas of interest in allogeneic stem cell transplant-associated fundamental and clinical research.

Entries to the EIA award were invited from clinicians and scientists working on translational or outcomes-based research, as well as collaborative projects, in the field of GvHD-focused ECP. Submissions were assessed on a range of criteria, including scientific merit, originality, and feasibility.

The EIA award recognizes individuals and institutions whose research contributes to the continued advancement of knowledge in this area of medicine and is just one part of our ongoing commitment to the science of immunomodulation through ECP.

In June, the THERAKOS CELLEX System technology secured CE certification under the European Union Medical Device Regulation (EU MDR). It involved a robust quality management system audit, technical and microbiological reviews, and a thorough clinical assessment, demonstrating the organization’s ongoing commitment to ECP evidence generation, post approval.

About THERAKOS CELLEX Photopheresis System

The THERAKOS CELLEX Photopheresis System is the world’s only fully integrated and validated ECP system.3 THERAKOS performs ECP using patented technology that collects, separates and treats a small amount of white blood cells (immune cells) while the patient is connected to the instrument. The treated cells are then returned to the patient where they help to modify the immune response in a process called immunomodulation. It is used to treat a range of immune-mediated diseases. THERAKOS Systems are used by over 300 treatment centres in over 30 countries worldwide.4

About Extracorporeal Photopheresis (ECP)

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has demonstrated efficacy in various T-cell and immune-mediated diseases.³ ECP is recommended by international and national guidelines for a spectrum of diseases, including cutaneous T-cell lymphoma (CTCL), acute and chronic graft-versus-host disease (aGvHD and cGvHD), chronic lung allograft dysfunction-bronchiolitis obliterans syndrome (CLAD-BOS) and after cardiac transplantation. 5,6,7,8,9,10,11,12,13,14,15, 16,17

EU INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR THE THERAKOS PHOTOPHERESIS PROCEDURE

Indications
The THERAKOS CELLEX Photopheresis System is indicated for patients older than 18 years of age for the administration of photopheresis in the following:

• Cutaneous T Cell Lymphoma (CTCL)
• Solid Organ Transplant Rejection (SOT) (heart, lung)

The THERAKOS CELLEX Photopheresis System is indicated in patients older than 3 years of age for the management of:

• Acute and Chronic Graft versus Host Disease (aGvHD, cGvHD)

Contraindications
THERAKOS Photopheresis is contraindicated in:

• Patients possessing a specific history of a light sensitive disease
• Patients who cannot tolerate extracorporeal volume loss or who have white blood cell counts greater than 25,000 / mm3
• Patients who have coagulation disorders or who have previously had a splenectomy

Warnings and Precautions
THERAKOS Photopheresis treatments should always be performed in locations where standard medical emergency equipment is available. Volume replacement fluids and/or volume expanders should be readily available throughout the procedure.

• Do not expose the device to a magnetic resonance (MR) environment. The device may present a risk of projectile injury, and thermal injury and burns may occur. The device may generate artifacts in the MR image, or may not function properly.
• Thromboembolic events, including pulmonary embolism and deep vein thrombosis, have been reported in the treatment of Graft versus Host Disease (GvHD). Special attention to adequate anticoagulation is advised when treating patients with GvHD.
• When prescribing and administering THERAKOS Photopheresis for patients receiving concomitant therapy, exercise caution when changing treatment schedules to avoid increased disease activity that may be caused by abrupt withdrawal of previous therapy.

Adverse Events

• Hypotension may occur during any treatment involving extracorporeal circulation. Closely monitor the patient during the entire treatment for hypotension.
• Transient pyretic reactions, 37.7–38.9°C (100–102°F), have been observed in some patients within six to eight hours of reinfusion of the photoactivated leukocyte-enriched blood. A temporary increase in erythroderma may accompany the pyretic reaction.
• Treatment frequency exceeding labelling recommendations may result in anaemia.
• Venous access carries a small risk of infection and pain.

Please refer to the THERAKOS CELLEX Photopheresis System Operator’s Manual for a complete list of warnings and precautions.

IMPORTANT SAFETY INFORMATION FOR METHOXSALEN USED IN CONJUNCTION WITH THERAKOS PHOTOPHERESIS

Consult the 8-methoxypsoralen (Methoxsalen (20 micrograms / mL)) professional leaflet or the oral 8-methoxypsoralen formulation package insert before prescribing or dispensing any medication.

Warnings and Precautions

• Patients exhibiting multiple basal cell carcinomas or having a history of basal cell carcinoma should be diligently observed and treated.
• Methoxsalen may cause fetal harm when given to a pregnant woman. Women undergoing photopheresis should be advised to avoid becoming pregnant.
• Special care should be exercised in treating patients who are receiving concomitant therapy (either topically or systemically) with known photosensitizing agents.
• Oral administration of methoxsalen followed by cutaneous UVA exposure (PUVA therapy) is carcinogenic.
• Patients should be told emphatically to wear UVA absorbing, wrap-around sunglasses for twenty-four (24) hours after methoxsalen treatment. They should wear these glasses any time they are exposed to direct or indirect sunlight, whether they are outdoors or exposed through a window.

Refer to the package insert for methoxsalen sterile solution (20 micrograms / mL) or the oral 8-methoxypsoralen dosage formulation for a list of all warnings and precautions.

ABOUT MALLINCKRODT
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release contains forward-looking statements, including with regard to Therakos, its potential to improve health and treatment outcomes, and its potential impact on patients. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: the effects of Mallinckrodt’s recent emergence from bankruptcy; satisfaction of, and compliance with, regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues or adverse side effects or adverse reactions associated with THERAKOS; and other risks identified and described in more detail in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of Mallinckrodt’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

Contact

Media Inquiries
Green Room Communications
908-577-4531
mediainquiries@grcomms.com

Investor Relations
Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com

Mallinckrodt, the “M” brand mark, and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners.

^©2024 Mallinckrodt. EU-2400258 10/24

References

1. Owsianowski M, et al. Bone Marrow Transplant. 1994;14(5), 845-848.
2. Solh M, et al. (2023). Bone Marrow Transplant. 2023;58(2), 168-174.
3. Knobler R, et al. J Eur Acad Dermatol Venereol. 2020;34(12):2693-2716.
4. Data on File – Ref-07615. Mallinckrodt Pharmaceuticals.
5. Hart JW, et al. Ther Adv Hematol. 2013;4:320-334.
6. Knobler R, et al. J Eur Acad Dermatol Venereol. 2020;34(12):2693-2716.
7. Trautinger F, et al. Eur J Cancer. 2017;77:57 74.
8. Padmanabhan A, et al. J Clin Apher. 2019;34(3):171-354.
9. Alfred A, et al. Br J Haematol. 2017;177:287-310.
10. Cho A, et al. Front Med (Lausanne). 2018;5:236.
11. Zeiser R. et al. Graft-versus-Host Erkrankung, akut. 2021. Available at: https://www.onkopedia.com/de/onkopedia/guidelines/graft-versus-host-erkrankung-akut/@@view/html/index.html. Accessed August 2024.
12. Bredeson C, et al. Curr Oncol. 2014;21(2):e310-325.
13. Pierelli L, et al. Transfusion. 2013;53(10):2340-2352.
14. Wolff D, et al. Biol Blood Marrow Transplant. 2011;17:1-17.
15. Dignan FL, et al. Br J Haematol. 2012;158(1):30-45; 46-61.
16. Knobler R, et al. J Eur Acad Dermatol Venereol. 2021;25(1):27-49.
17. Costanzo MR, et al. J Heart Lung Transplant. 2010;29(8):914-956.

Logo – https://mma.prnewswire.com/media/2385856/mallinckrodt_standard_color_v3_01_Logo.jpg

DUBLIN, April 14, 2024 /PRNewswire/ — Mallinckrodt plc, a global specialty pharmacy company, today announced that submissions for its 2024 Extracorporeal Immunomodulation Award (EIA) will open on 13 April 2024 during the 50^th Annual Meeting of the European Bone Marrow Transplant Meeting (EBMT), Europe’s largest annual congress in blood and bone marrow transplantation and cellular therapies. In recognition of 30 years since clinicians first used ECP to successfully treat chronic GvHD,¹ Mallinckrodt, provider of immunomodulatory therapy via Extracorporeal Photopheresis (ECP) and manufacturer of the world’s only fully integrated, validated, ECP system, is pleased to mark this important milestone by this year dedicating the award to the study of ECP for cGvHD.

All clinicians and scientists working on translational or outcomes-based research, as well as collaborative projects, in the EMEA region are invited to apply. Submissions will be assessed on a range of criteria, including scientific merit, originality, and feasibility, and the winning project will receive an educational grant of €75,000.

“Mallinckrodt has pioneered ECP immunomodulation through its THERAKOS^TM CELLEX^TM Photopheresis System and is pleased to support continued research that further contributes to this field of medicine,” said Peter Richardson, MRCP (UK), Executive Vice President & Chief Scientific Officer.

Part of Mallinckrodt’s ongoing commitment to the science of immunomodulation through ECP is to recognize individuals and institutions whose research contributes to the advancement of knowledge in this area of medicine.

Previous winners have included a collaboration between The RIGHT institute and University Hospital Besançon, in France. The team, led by Dr Etienne Daguindau, investigated the mechanisms of cell death generated through ECP, and its direct effects on the innate cells involved in the resolution of inflammation. In 2018, the prize went to a team from the Rotherham NHS Foundation Trust’s Department of Haematology. Led by Dr Nick Matthews, the study evaluated the effect of ECP on monocytes in the GvHD setting.

Entries to the 2024 EIA Award will close on 1 September 2024. For full details on how to enter, go to: https://therakos.eu/healthcare-professionals/research-opportunities-educational-grants/

The 2024 EIA is just part of Mallinckrodt’s celebration of 30 years of ECP in GvHD. We are also collaborating with our partners to bring you two symposia at the 2024 EBMT Annual Meeting:

• Symposium: 30 years of ECP in GvHD: Recommendations for the treatment of cGvHD. This event will be presented by the GvHD Hub, and supported through an unrestricted educational grant from Therakos, Mallinckrodt.
  Speakers: Mohamad Mohty, Bipin Savani, Florent Malard, and Zinaida Peric.
  Location: Hall 5
  Date and Time: Sunday, April 14, 4.30 p.m. – 6 p.m. British Summer Time (BST)
• Nurse Symposium: 30 Years of ECP – Patient-centered therapy using Therakos ECP technology, then, now and in the future.
  Speakers: Michelle Kenyon, Francesca Kinsella, Laura Dalling
  Location: Hall 1
  Date and Time: Monday, April 15, 4.30 p.m. – 6 p.m. British Summer Time (BST)

The sessions will be held in person at the meeting’s Glasgow venue. To register, go to the EBMT Annual Meeting website.

ABOUT THERAKOS

Mallinckrodt’s Therakos therapeutic platforms, including the latest generation THERAKOS^TM CELLEX^TM Photopheresis System, are used by academic medical centers, hospitals, and treatment centers in more than 30 countries and have delivered more than 1 million treatments globally.² For more information, please visit www.therakos.eu.

Please see the Indications and Important Safety Information available at therakos.eu.

ABOUT MALLINCKRODT

Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit https://www.mallinckrodt.com.

CONTACT

Investor Relations
Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners.

^©2024 Mallinckrodt. EU-2400078 04/24

References

¹ Owsianowski, M., Gollnick, H., Siegert, W., Schwerdtfeger, R., & Orfanos, C. E. (1994). Successful treatment of chronic graft-versus-host disease with extracorporeal photopheresis. Bone marrow transplantation, 14(5), 845-848. 2 Data on File ref-05174.

THIS INFORMATION IS INTENDED FOR EUROPEAN AUDIENCES ONLY

DUBLIN, Feb. 21, 2024 /PRNewswire/ — Mallinckrodt plc, a global specialty pharmaceutical company, today announced a poster presentation of findings from a systematic literature review and meta-analysis of the safety, efficacy, and real-world outcomes of extracorporeal photopheresis (ECP) treatment for patients with steroid-refractory chronic graft-versus-host disease (SR-cGvHD).¹ An analysis of 47 studies reporting on the THERAKOS CELLEX Photopheresis System showed that treatment of SR-cGvHD with ECP was associated with improvements in patients’ overall survival (OS), failure-free survival (FFS), and overall response rate (ORR).¹ The results will be shared in a poster presentation at the 2024 Tandem Meetings, the combined Transplantation & Cellular Therapy Meetings of the American Society of Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) taking place February 21-24, 2024 in San Antonio, TX.

A systematic review of literature available through October 19, 2022 was first conducted to identify and analyze studies of patients receiving ECP for SR-cGvHD that reported on efficacy, safety, or health-related quality of life (HRQoL) outcomes.¹ The literature review identified 47 studies which uniquely reported on THERAKOS ECP treatment with a sample size ≥ 10 patients, comprising a total of 2,361 patients.¹ Lines of therapy were poorly reported (n=15) and ranged from 0-≥4 lines of previous treatment.¹ Most clinical studies (n=27) used a retrospective case series design.¹

Using the studies identified from the systematic literature review, random effects meta-analyses were then performed for short- and long-term efficacy outcomes including ORR and skin-specific response, and OS and FFS, respectively.¹ A subgroup analysis was also conducted to explore the effect of outcome assessment criteria from the National Institutes of Health (NIH) vs. non-NIH/unknown criteria.¹ Safety and HRQoL outcomes were poorly reported in the existing clinical literature and therefore were not suitable for the meta-analysis.¹

“We are pleased to share this important analysis of real-world data supporting THERAKOS ECP’s efficacy, safety, and associated improvements to short- and long-term outcomes – such as overall survival, failure-free survival, and overall response rate – for patients with steroid-refractory chronic graft-versus-host-disease,¹” said Zachariah DeFilipp, MD, Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, MA. “This analysis not only builds upon the growing body of evidence supporting ECP’s utility in treating patients with this condition, but also reflects the importance of supporting clinicians with treatment options for managing patients who do not respond to other types of therapy, such as steroids.¹”

In assessing the short-term efficacy of THERAKOS ECP, this meta-analysis found¹:

• The ORR (7 studies; 293 patients) at Months 3-4 and at Months 6-8 (13 studies; 540 patients) were 45.34% (95% CI: 26.64 – 65.45) and 58.23% (95% CI: 45.04-70.35), respectively.
• No significant difference in ORR between studies utilizing NIH criteria vs. non-NIH criteria, per the subgroup analysis.
• Skin-specific response at Months 2-3 and at Months 4-6 were 34.86% (95% CI: 13.26-65.21) and 54.22% (95% CI: 35.67-71.67), respectively.

In assessing the long-term efficacy of THERAKOS ECP, this meta-analysis found¹:

• The pooled OS rate (14 studies; 704 patients) at Month 12 was 83.97% (95% CI: 77.33-88.94).
• The OS rate (8 studies; 431 patients) at Month 60 was 57.96% (95% CI: 35.48-77.56).
• The FFS rate (4 studies; 169 patients) at Month 12 was 60.79% (95% CI: 38.94-79.03).

Limitations
Data collected in systematic literature reviews and meta-analyses may have errors or omissions. The studies included in the analysis are heterogeneous and use different patient populations, endpoints, interventions, and dosing.¹ There was considerable heterogeneity across analyses with I² values ranging from 65% to 91%.¹ Most studies included in the meta-analysis were retrospective analyses¹ and these observations may require further investigation in prospective, controlled trials. Statistical evaluations should be interpreted with caution. Outcomes may be influenced by therapies not evaluated in the study and the clinical/health economics outcomes may not be solely attributable to THERAKOS ECP.

This study was sponsored by Mallinckrodt Pharmaceuticals. Presentation details can be found below:

Abstract #340: Systematic Review and Meta-Analysis of Extracorporeal Photopheresis for the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease¹

• Presenter: Zachariah DeFilipp, MD, Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, MA
• Presentation Date: Thursday, February 22, 2024; 6:45 – 7:45 p.m. CST
• Location: Exhibit Hall 4a (Street Level)

IMPORTANT SAFETY INFORMATION FOR THE THERAKOS PHOTOPHERESIS PROCEDURE

Indications
The THERAKOS CELLEX Photopheresis System is indicated for the administration of photopheresis. Please refer to the appropriate product labelling for a complete list of warnings and precautions.

Contraindications
THERAKOS Photopheresis is contraindicated in:

• Patients possessing a specific history of light sensitive disease
• Patients who cannot tolerate extracorporeal volume loss or who have white blood cell counts greater than 25,000 / mm³
• Patients who have coagulation disorders or who have previously had a splenectomy

Warnings and Precautions
THERAKOS Photopheresis treatments should always be performed in locations where standard medical emergency equipment is available. Volume replacement fluids and/or volume expanders should be readily available throughout the procedure. Safety in children has not been established.

• Do not expose the device to a magnetic resonance (MR) environment. The device may present a risk of protective injury, and thermal injury and burns may occur. The device may generate artifacts in the MR image, or may not function properly.
• Thromboembolic events, including pulmonary embolism and deep vein thrombosis, have been reported in the treatment of Graft versus Host Disease (GvHD). Special attention to adequate anticoagulation is advised when treating patients with GvHD.
• When prescribing and administering THERAKOS Photopheresis for patients receiving concomitant therapy, exercise caution when changing treatment schedules to avoid increased disease activity that may be caused by abrupt withdrawal of previous therapy.

Adverse Events

• Hypotension may occur during any treatment involving extracorporeal circulation. Closely monitor the patient during the entire treatment for hypotension.
• Transient pyretic reactions, 37.7–38.9 ᵒC (100–102 ᵒF), have been observed in some patients within six to eight hours of reinfusion of the photoactivated leukocyte-enriched blood. A temporary increase in erythroderma may accompany the pyretic reaction.
• Treatment frequency exceeding labelling recommendations may result in anaemia.
• Venous access carries a small risk of infection and pain.

Please refer to the THERAKOS CELLEX Photopheresis System Operator Manual for a complete list of warnings and precautions.

IMPORTANT SAFETY INFORMATION FOR METHOXSALEN USED IN CONJUNCTION WITH THERAKOS PHOTOPHERESIS

Contraindications
Methoxsalen is contraindicated in:

• Patients exhibiting idiosyncratic or hypersensitivity reactions to methoxsalen, psoralen compounds, or any of the excipients
• Patients with co-existing melanoma, basal cell or squamous cell skin carcinoma
• Patients who are pregnant, and sexually active men and women of childbearing potential unless adequate contraception is used during treatment
• Patients with aphakia because of the significantly increased risk of retinal damage to the absence of a lens

Warnings and Precautions

• Special care should be exercised in treating patients who are receiving concomitant therapy (either topically or systemically) with known photosynthesizing agents.
• Oral administration of methoxsalen followed by cutaneous UVA exposure (PUVA therapy) is carcinogenic.
• Patients should be told emphatically to wear UVA absorbing, wrap-around sunglasses for twenty-four (24) hours after methoxsalen treatment. They should wear these glasses anytime they are exposed to direct or indirect sunlight, whether they are outdoors or exposed through a window.
• Safety in children has not been established.

Refer to the package insert for methoxsalen sterile solution (20 micrograms / mL) or the oral 8-methoxpsoralen dosage formulation for a list of all warnings and precautions.

Please refer to the THERAKOS CELLEX Photopheresis System Operator Manual for a complete list of warnings and precautions and adverse events.

About Extracorporeal Photopheresis (ECP)
ECP, a blood based immunomodulatory therapy developed more than 30 years ago, is recommended by the International Society for Heart and Lung Transplantation (ISHLT)² and other clinical societies^3,4,5 as an adjunctive therapy for the prevention and treatment of ACR after heart transplantation. Additionally, ECP may be considered to treat AMR with or without donor specific antibodies.^6,7 In countries where it is approved, ECP is used to treat a range of immune-mediated diseases, including skin manifestations of cutaneous T-cell lymphoma (CTCL), graft-versus-host disease (GvHD), solid organ transplant rejection and other autoimmune diseases. During ECP treatment, a small amount of white blood cells is collected and treated with a drug that is activated by ultraviolet light.

ABOUT MALLINCKRODT
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release contains forward-looking statements, including with regard to THERAKOS ECP, its potential to improve health and treatment outcomes, its potential impact on patients, and the planned presentation regarding the THERAKOS ECP study results. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: the effects of Mallinckrodt’s recent emergence from bankruptcy; satisfaction of, and compliance with, regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues or adverse side effects or adverse reactions associated with THERAKOS ECP; and other risks identified and described in more detail in the “Risk Factors” section of Mallinckrodt’s most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

CONTACT

Media Inquiries
Green Room Communications
908-577-4531
mediainquiries@grcomms.com

Investor Relations
Daniel J. Speciale
Senior Vice President, Finance and Chief Financial Officer, Specialty Generics
314-654-3638
daniel.speciale@mnk.com

Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners.

^©2024 Mallinckrodt. EU-2400019 02/24

References

¹ Data on File – Ref-07190. Mallinckrodt Pharmaceuticals.
² Costanzo MR, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Trans. 2010:29(8);914–956.
³ Alfred et al. The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society. Br J Haematol. 2017;177(2):287-310.
⁴ Padmanabhan et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019;34:171–354.
⁵ Knobler et al. European dermatology forum – updated guidelines on the use of extracorporeal photopheresis 2020 – part 2. Eur Acad Dermatol Venereol. 2021;35(1):27-49.
⁶ Colvin et al. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2015;131(18):1608-1639.
⁷ Barten et al. The clinical impact of donor-specific antibodies in heart transplantation. Transplant Rev (Orlando). 2018;32(4):207-217.

DUBLIN, June 13, 2023 /PRNewswire/ — Mallinckrodt plc (NYSE American: MNK), a global specialty pharmaceutical company, today announced the publication of findings from a retrospective, observational, single arm, European chart review study assessing the real-world use of extracorporeal photopheresis (ECP) and its impact on clinical outcomes in the modern era of heart transplantation.¹ An online version of the data manuscript – the largest-known study of ECP in heart transplant patients – is currently published on the Journal of Heart and Lung Transplantation website in advance of print publication in the second half of 2023.

Interim results of this study were presented in a late-breaking session at the 20^th Congress of the European Society for Organ Transplantation (ESOT) in 2021 in Milan, Italy.²

The study, titled “European Multicenter Study on The Real-World Use and Clinical Impact of Extracorporeal Photopheresis After Heart Transplantation,” examined data from the medical charts of 105 patients who received ECP following heart transplantation at seven medical centers in Austria, Germany, France, Hungary, and Italy between 2015 – 2021. At time of data extraction, 58 patients (55.2%) had completed their ECP treatment and 47 patients’ (44.8%) ECP treatment was ongoing.¹

“These findings from the largest European and first multicenter study investigating the real-world use of ECP in heart transplant patients support ECP as a treatment for various types of graft rejection and in prevention of graft rejection with varied treatment schedules,¹” said Markus Barten, M.D., Surgical Director of Heart Failure Clinic, University Heart and Vascular Center Hamburg. “This data not only builds upon the growing body of real-world evidence supporting the use of ECP in heart transplant patients, but also reflects the importance of supporting clinicians with treatment modalities for transplant rejection and stabilization.¹”

About the Study¹

Mean age of patients at start of ECP was 47.7 (SD 14.4) years (min. 16 years to max. 74 years), and most patients (70.5%) were male. They were followed for a mean time of 25.1 (SD 16.8) months from ECP treatment initiation to last visit at the transplant center (follow-up time for outcome overall survival). Mean time from ECP treatment initiation to last visit right censored at 2 years after the end of ECP treatment was 22.5 (SD 13.7) months (follow-up time for outcomes graft function, response, and complications).

Cardiomyopathy was the primary reason for heart transplantation (n=81 patients; 77.1%), followed by coronary heart disease (n=11 patients; 10.5%), heart valve disease (n=5 patients; 4.8%), and myocarditis (n=5 patients; 4.8%). The main reason to start ECP treatment was acute cellular rejection (ACR; n=37 patients; 35.2%), followed by prevention of rejection (n=34 patients; 32.4%), mixed rejection (n=19 patients; 18.1%), and antibody-mediated rejection (AMR; n=15 patients; 14.3%).

The prevention of rejection subgroup included patients who started ECP treatment without biopsy-proven rejection and with standard or reduced immunosuppressive therapy.

Key Findings¹

• Graft function was stable for almost all patients throughout the study who completed ECP and had graft function change assessed (97.2%; n=35/36).
• In patients who started ECP to treat ACR, AMR or mixed rejection (n=26), completed ECP treatment and had a biopsy at the start and end of treatment, 92.3% (n=24) were classified as responders, having demonstrated an improvement of ACR and/or AMR International Society for Heart and Lung Transplantation (ISHLT) grading after a mean ECP treatment duration of 5.4 months. The remaining patients had stable grades.
• In patients who started ECP to prevent rejection (n=34), 88.2% (n=30) remained free from any rejection over a mean follow-up of 26 months despite being considered at high risk for rejection and reduced immunosuppressive therapy.
• All patients started ECP treatment while on immunosuppressive therapy, and almost all remained on immunosuppressants until last reported visit prior to data extraction. Tacrolimus and mycophenolate derivatives were the most frequently used immunosuppressants. The number of patients on steroid therapy decreased slightly over time.
• Among patients with ongoing ECP treatment who remained on steroid therapy (n=34), steroid dose was reduced on average by 63.0% from start of ECP to last reported visit for 41.2% (n=14) of patients. Steroid dose increased for 5.9% (n=2) of patients and was stable in 52.9% (n=18) of patients.
• Among patients who completed ECP treatment and remained on steroid therapy (n=42), steroid dose was reduced on average by 67.0% from start of ECP to last reported visit for 52.4% (n=22) of patients. Steroid dose increased for 4.8% (n=2) of patients and was stable in 42.9% (n=18) of patients.
• Amongst the 19 patients in the prevention group, 16 (84.2%) received tacrolimus at the start of ECP and last reported visit. In 11/16 patients, tacrolimus trough levels were available of which 7 (63.6%) patients experienced an average trough level decrease of 34.0%.
• Amongst the 19 patients in the prevention group, 14 (70.4%) received mycophenolate derivatives at the start of ECP and last reported visit. In 4/14 patients, mycophenolate doses were available of which 100% of patients remained on stable mycophenolate derivate dose.
• Seventeen of 105 included patients (16.2%) experienced a complication after ECP treatment initiation, the most common of which was infections (n=13, 12.4%). Four of 105 patients (3.8%) experienced an endocrine/respiratory/blood/cardiac disorder, 2 patients (1.9%) an intolerance of high-dose immunosuppressive therapy, and 1 patient (1.0%) an acute kidney injury.
• Overall survival was 95.2% (n=100) over a mean follow-up of 25.1 (SD 16.8) months. Of the 5 deceased patients, 3 (60.0%) died with a functioning graft and 4 (80.0%) died after end of ECP treatment. No deaths were related to ECP.
• No major safety events occurred. Eighteen of 105 included patients (17.1%) had at least one ECP-related safety event, the most common of which was complications with venous access (n=13; 12.4%). Two (15.4%, n=2/13) patients stopped their ECP treatment as a result. Furthermore, 6/105 patients (5.7%) had ECP-related anemia, 3 patients (2.9%) ECP-related hypotension, 1 patient (1.0%) ECP-related fever, and 2 patients (1.9%) had an unspecified ECP-related safety event, but none of them discontinued their ECP treatment as a result.

Limitations¹

The effectiveness of ECP in comparison with other treatment options was not assessed due to the descriptive, single-arm design of this study. Study limitations include that data generation for this observational study was not standardized. Patient examination schedules varied and not all data were available at all centers. No source data verification was performed and therefore, transmission errors cannot be excluded. Not all demonstrated benefits may be solely attributable to ECP treatment, as transplanted patients may have received multiple therapies at time of ECP treatment. In patients with AMR or mixed rejection, ECP is commonly used in combination with other treatments.

This study was funded by Mallinckrodt.

IMPORTANT SAFETY INFORMATION FOR THE THERAKOS PHOTOPHERESIS PROCEDURE

Indications
The THERAKOS CELLEX Photopheresis System is indicated for the administration of photopheresis. Please refer to the appropriate product labelling for a complete list of warnings and precautions.

Contraindications
THERAKOS Photopheresis is contraindicated in:

• Patients possessing a specific history of light sensitive disease
• Patients who cannot tolerate extracorporeal volume loss or who have white blood cell counts greater than 25,000 / mm³
• Patients who have coagulation disorders or who have previously had a splenectomy

Warnings and Precautions
THERAKOS Photopheresis treatments should always be performed in locations where standard medical emergency equipment is available. Volume replacement fluids and/or volume expanders should be readily available throughout the procedure. Safety in children has not been established.

• Do not expose the device to a magnetic resonance (MR) environment. The device may present a risk of protective injury, and thermal injury and burns may occur. The device may generate artifacts in the MR image, or may not function properly.
• Thromboembolic events, including pulmonary embolism and deep vein thrombosis, have been reported in the treatment of Graft versus Host Disease (GvHD). Special attention to adequate anticoagulation is advised when treating patients with GvHD.
• When prescribing and administering THERAKOS Photopheresis for patients receiving concomitant therapy, exercise caution when changing treatment schedules to avoid increased disease activity that may be caused by abrupt withdrawal of previous therapy.

Adverse Events

• Hypotension may occur during any treatment involving extracorporeal circulation. Closely monitor the patient during the entire treatment for hypotension.
• Transient pyretic reactions, 37.7–38.9 ᵒC (100–102 ᵒF), have been observed in some patients within six to eight hours of reinfusion of the photoactivated leukocyte-enriched blood. A temporary increase in erythroderma may accompany the pyretic reaction.
• Treatment frequency exceeding labelling recommendations may result in anaemia.
• Venous access carries a small risk of infection and pain.

Please refer to the THERAKOS CELLEX Photopheresis System Operator Manual for a complete list of warnings and precautions.

IMPORTANT SAFETY INFORMATION FOR METHOXSALEN USED IN CONJUNCTION WITH THERAKOS PHOTOPHERESIS

Contraindications
Methoxsalen is contraindicated in:

• Patients exhibiting idiosyncratic or hypersensitivity reactions to methoxsalen, psoralen compounds, or any of the excipients
• Patients with co-existing melanoma, basal cell or squamous cell skin carcinoma
• Patients who are pregnant, and sexually active men and women of childbearing potential unless adequate contraception is used during treatment
• Patients with aphakia because of the significantly increased risk of retinal damage to the absence of a lens

Warnings and Precautions

• Special care should be exercised in treating patients who are receiving concomitant therapy (either topically or systemically) with known photosynthesizing agents.
• Oral administration of methoxsalen followed by cutaneous UVA exposure (PUVA therapy) is carcinogenic.
• Patients should be told emphatically to wear UVA absorbing, wrap-around sunglasses for twenty-four (24) hours after methoxsalen treatment. They should wear these glasses anytime they are exposed to direct or indirect sunlight, whether they are outdoors or exposed through a window.
• Safety in children has not been established.

Refer to the package insert for methoxsalen sterile solution (20 micrograms / mL) or the oral 8-methoxpsoralen dosage formulation for a list of all warnings and precautions.

Please refer to the THERAKOS CELLEX Photopheresis System Operator Manual for a complete list of warnings and precautions and adverse events.

About Extracorporeal Photopheresis (ECP)
ECP, a blood based immunomodulatory therapy developed more than 30 years ago, is recommended by the International Society for Heart and Lung Transplantation (ISHLT)³ and other clinical societies^4,5,6 as an adjunctive therapy for the prevention and treatment of ACR after heart transplantation. Additionally, ECP may be considered to treat AMR with or without donor specific antibodies.^7,8 In countries where it is approved, ECP is used to treat a range of immune-mediated diseases, including skin manifestations of cutaneous T-cell lymphoma (CTCL), graft-versus-host disease (GvHD), solid organ transplant rejection and other autoimmune diseases. During ECP treatment, a small amount of white blood cells is collected and treated with a drug that is activated by ultraviolet light.

ABOUT MALLINCKRODT 
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release contains forward-looking statements, including with regard to ECP and its potential impact on patients. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; and other risks identified and described in more detail in the “Risk Factors” section of Mallinckrodt’s most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

Contact

Media Inquiries
Heather Guzzi
Senior Vice President, Green Room Communications
973-524-4112
hguzzi@grcomms.com

Investor Relations
Daniel J. Speciale
Global Corporate Controller & Chief Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com

Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners.

^©2023 Mallinckrodt. EU-2300168 06/23

References

1 Barten, MJ et al. European multi-center study on the real-world use and clinical impact of extracorporeal photopheresis after heart transplantation. J Heart Lung Transplant. 2023. https://doi.org/10.1016/j.healun.2023.03.005.
2 Barten, MJ. et al. Real World Use and Clinical Impact of Extracorporeal Photopheresis in Heart Transplant Patients – Results From a European Multi-Centre Study. Abstract presented at: European Society for Organ Transplantation (ESOT) Congress 2021. August/September 2021.
3 Costanzo MR, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Trans. 2010:29(8);914–956.
4 Alfred et al. The role of extracorporeal photopheresis in the management of cutaneous T-cell lymphoma, graft-versus-host disease and organ transplant rejection: a consensus statement update from the UK Photopheresis Society. Br J Haematol. 2017;177(2):287-310.
5 Padmanabhan et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019;34:171–354.
6 Knobler et al. European dermatology forum – updated guidelines on the use of extracorporeal photopheresis 2020 – part 2. Eur Acad Dermatol Venereol. 2021;35(1):27-49.
7 Colvin et al. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2015;131(18):1608-1639.
8 Barten et al. Transplant Rev (Orlando). The clinical impact of donor-specific antibodies in heart transplantation. 2018;32(4):207-217.

DUBLIN – March 9, 2023 – Mallinckrodt plc, (NYSE American: MNK)(“Mallinckrodt” or the “Company”), a global specialty pharmaceutical company, today announced that Japan’s National Health Insurance (NHI) system has approved reimbursement for the CELLEX^® extracorporeal photopheresis (ECP) system for the treatment of steroid-resistant or -intolerant chronic graft versus host disease (cGvHD).

“We are very pleased that we have received approval for reimbursement in Japan for the CELLEX ECP System. As a pharmaceutical company focused on improving outcomes for under-served patients with severe and critical conditions, we strive to develop treatment options that address unmet medical needs,” said Masatoyo Gunji, Mallinckrodt General Manager of Japan.

Following the approval of the CELLEX ECP System in Japan in late 2020, with the reimbursement approval, healthcare providers in Japan can now begin to prescribe the CELLEX ECP System and treat patients suffering from cGvHD who are steroid-resistant or -intolerant.

The approved uses for the CELLEX ECP System differ depending upon the country. Please refer to each country’s Operator’s Manuals and labeling for approved uses.

“Chronic graft versus host disease is a highly debilitating disease with a significant impact to the health of these patients with limited treatment options in Japan. The reimbursement approval and subsequent launch of the CELLEX ECP System in Japan represents a crucial milestone that will provide these patients, and their care providers, access to an important therapeutic option where there has been a high unmet medical need,” said Lisa French, Executive Vice President and Chief Commercial Officer of Mallinckrodt Pharmaceuticals.

About Chronic Graft Versus Host Disease (cGvHD)
Graft versus host-disease is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT) resulting in significant morbidity and mortality. It can be classified as acute or chronic based on the clinical presentation and the time of occurrence after the transplantation. Signs and symptoms of cGvHD nearly always occur within the first year post transplantation but can occasionally happen several years later. In cGvHD, the skin is the most frequently affected organ with manifestations of itchy rash, hyper or hypopigmentation and changes in texture2 . However, the disease can affect multiple sites, which may have a major impact upon a patient’s quality of life.2,  Chronic GvHD can lead to debilitating consequences, such as joint contractures, loss of sight, end-stage lung disease, or mortality resulting from profound chronic immune suppression leading to recurrent or life-threatening infections.¹

IMPORTANT SAFETY INFORMATION FOR JAPAN

Intended Use or Efficacy
This system is used as extracorporeal photopheresis therapy in steroid-resistant or -intolerant, chronic graft versus host disease.

Warnings
Directions for Use:

• When conducting extracorporeal photopheresis therapy for patients receiving other therapy, exercise caution when changing treatment schedules to avoid increased disease activity that may be caused by abrupt withdrawal of previous therapy.
• Taking into account the condition of the patient, administer an appropriate amount of anticoagulant through the CELLEX device, as thromboembolic events may occur.

Contraindications / Prohibitions
Directions for Use:

• Do not re-use (Procedural Kit and Methoxsalen Solution).
• Do not operate the instrument in the presence of flammable anesthetic gases, external radio or electromagnetic disturbances that may interfere with proper performance of the device. There is the risk of ignition and malfunction.

Applicable subject (patient)
Do not use for the following population.

• Patients who cannot tolerate extracorporeal volume loss as the patient has possibility of hypotension and shock disease.
• Patients exhibiting idiosyncratic reactions to psoralen compounds including methoxsalen, or possessing a specific history of a light-sensitive disease state.
• Patients with aphakia because of the significantly increased risk of retinal damage due to the absence of a lens.
• Patients possessing a specific history of a disordered coagulation or patients who have had previous splenectomy as anticoagulants is used during therapy.
• Patients during pregnancy and lactation as it is likely to cause harm to the unborn child or suckling infant.
• Patients who have white blood cell counts greater than 25,000/mm3.

ABOUT THE THERAKOS CELLEX ECP SYSTEM FOR JAPAN
The CELLEX System delivers extracorporeal photopheresis (ECP), and consists of an instrument, procedural kit, methoxsalen solution and a UVA lamp. ECP was initially developed as a therapy for patients with skin symptoms of Cutaneous T-Cell Lymphoma (CTCL).

The CELLEX System was designated as a medical device to be introduced early in Japan by the 15th Study Panel on Early Introduction of Highly Needed Medical Devices. This meeting was organized by the MHLW and held on February 17, 2011.

CELLEX was also designated as an orphan medical device by the MHLW on January 18, 2017.

APPROVED USES FOR THE THERAKOS CELLEX ECP SYSTEM
The approved uses for CELLEX ECP differ depending upon the country. Please refer to each country’s Operator’s manuals and labeling for approved uses.

ABOUT MALLINCKRODT 
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release contains forward-looking statements, including concerning the use of the CELLEX System including potential benefits associated with its use. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; and other risks identified and described in more detail in the “Risk Factors” section of Mallinckrodt’s most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

Contact

Media Inquiries
Heather Guzzi
Green Room Communications
+1 973-524-4112
hguzzi@greenroompr.com

Investor Relations        
Daniel Speciale
Global Corporate Controller and Chief Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com

Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com

Mallinckrodt Pharma K.K.
Junichi Yoshimura
Sales & Marketing, Product Manager
+81 3 6441 3604
junichi.yoshimura@mnk.com

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners.

^© 2023 Mallinckrodt. JP-2300001 3/23

DUBLIN, Nov.16, 2022 — Mallinckrodt plc (NYSE American: MNK), a global specialty pharmaceutical company, today announced the recipient of 2022’s Advancing Extracorporeal Photopheresis (ECP) Immunomodulation Investigator Award. Andrew Fisher, the project’s principal investigator won this year’s award for a project to help address significa­­nt unmet medical need by evaluating responses to extracorporeal photopheresis therapy (ECP) in chronic lung allograft dysfunction (CLAD).

The study hopes to identify potential novel biomarkers that could guide a precision-medicine approach to ECP treatment, and help people avoid the disability and mortality associated with CLAD – a devastating complication that affects more than half of lung transplant recipients within five years.

Lung transplantation is the only treatment offering a meaningful improvement in survival and quality of life to selected patients with life-threatening chronic lung disease. However, long-term survival is significantly poorer than that in other organ transplants, mainly due to the development of progressive immune mediated damage to the lung allograft.

More than 50%¹ of lung transplant recipients will develop CLAD within five years. This can progress rapidly, leading to lung function decline, respiratory failure, and death. As such, there is an urgent need to identify new treatments that can arrest the alloimmune mechanisms that drive CLAD as early as possible, preserving longevity and quality of life while also reducing the risk of repeat lung transplantation.

“There is an urgent need for treatments to stop CLAD early to protect lung function, help preserve quality of life, and hopefully prolong survival in lung transplant patients,” said the award-winning project’s principal investigator, Andrew Fisher, Professor of Respiratory Transplant Medicine at Newcastle University, and Honorary Consultant Respiratory and Transplant Physician at The Newcastle upon Tyne Hospitals NHS Foundation Trust’s Institute of Transplantation.

The E-CLAD UK study is a clinical trial funded by the National Institute for Health and Social Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) program. It is aimed at assessing if the addition of ECP to current treatment is more effective at stabilizing the function of transplanted lungs compared to standard treatments for CLAD.

The Mallinckrodt 2022 Investigator Award winning project, ‘Predicting Response to ECP in the Treatment of CLAD after Lung Transplantation’, is an in-depth mechanistic evaluation of participants’ immune responses. It is hoped it will address a currently unmet clinical need and provide powerful insights into how ECP treatment is working at immunological level.

Professor Fisher was presented with the €50,000 prize at a Therakos Institute-supported Workshop on Solid Organ Transplantation and Extracorporeal Photopheresis in Monte Carlo, in September.

The award, now in its fifth year, is part of Mallinckrodt’s ongoing commitment to the science of immunomodulation through ECP across therapeutic applications. It was designed to recognize individuals and institutions whose innovative research contributes to the advancement of knowledge in this broad area of medicine.

Entries were invited from clinicians and scientists working on translational or outcomes-based research, as well as collaborative projects. Submissions were assessed on a range of criteria, including scientific merit, originality, and feasibility.

“Every year, the investigator award showcases the huge array of cutting-edge, innovative, and ambitious research being conducted in the use of ECP across a broad spectrum of disease settings – and 2022 was no exception,” said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer of Mallinckrodt. “As a pioneer in ECP immunomodulation, Mallinckrodt is proud to support those who continue to investigate this exciting field of medicine. Congratulations to Professor Fisher and his team on winning this extremely competitive award. We’re looking forward to seeing the results in the fullness of time.”

The 2023 Advancing ECP Immunomodulation Investigator Award will be open for entries during the first quarter of 2023

ABOUT THERAKOS

Mallinckrodt’s Therakos therapeutic platforms, including the latest generation THERAKOSTM CELLEXTMPhotopheresis System, are used by academic medical centres, hospitals, and treatment centres in more than 30 countries and have delivered more than 1 million treatments globally. For more information, please visit www.therakos.eu.

ABOUT MALLINCKRODT

Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The Company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the Company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

Contact

Investor Relations

Daniel Speciale
Global Corporate Controller and Chief Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com

Derek Belz
Vice President, Investor Relations
314-654-3950
derek.belz@mnk.com

Media

Michael Freitag / Aaron Palash / Aura Reinhard
Joele Frank, Wilkinson Brimmer Katcher
+1 212-355-4449

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ^© 2022 Mallinckrodt Item code: EU-2200265
Date of preparation: Nov 2022.

DUBLIN, Dec. 13, 2021 /PRNewswire/ — Mallinckrodt plc, (OTCMKTS: MNKKQ) a global biopharmaceutical company, today announced results of a retrospective, observational medical chart review study assessing real world treatment outcomes among cutaneous T-cell lymphoma (CTCL) patients who initiated therapy with extracorporeal photopheresis (ECP). Investigators presented the findings during a poster presentation at the annual meeting of the American Society for Hematology, taking place virtually and live in Atlanta, Ga. from December 11-14. The poster is available here on the company’s website.

In the United States, ECP is FDA-approved for the palliative treatment of the skin manifestations of CTCL that is unresponsive to other forms of treatment. UVADEX^® (methoxsalen) Sterile Solution is used in combination with the THERAKOS^® CELLEX^® Photopheresis System and approved for use as a monotherapy. Safety and efficacy beyond six months have not been evaluated by the FDA.

The retrospective medical chart review study assessed the results of ECP in CTCL-diagnosed patients who initiated ECP treatment between January 1, 2017 and February 28, 2019. ECP was assessed as both a monotherapy and as a concomitant therapy. Physicians selected patients who were 18 years of age or older when they initiated ECP treatment, received at least three months of ECP treatment and had response data charted and available. Five U.S. clinical sites participated in the study and enrolled a total of 52 patients with a median age at ECP initiation of 69 years. Twenty-six patients (50 percent) were diagnosed with Sézary syndrome and 19 (36.5 percent) were diagnosed with mycosis fungoides. The median body surface area (BSA) involvement with plaques/patches was 77.5 percent at diagnosis.¹

The study examined patient data from CTCL diagnosis to 18 months post-initiation of ECP. Clinical outcomes collected every three months during treatment for up to 18 months included the BSA affected, appearance of new skin lesions and the physician-rated Clinical Global Impression-Improvement (CGI-I) scores. Patients may have been on concomitant therapies at the time of ECP treatment.

“It is important to continually evaluate real world patterns and outcomes of ECP treatment for CTCL to better understand patients’ response to ECP,” said Michael Girardi, M.D., FAAD, lead investigator and Director of the Photopheresis and Phototherapy Unit at the Yale Comprehensive Cancer Center and Yale-New Haven Hospital.

The data analysis found that 19 patients (36.5 percent) had at least a 50 percent reduction in affected BSA with a median time to response of 6.5 months. New skin lesions appeared in 13 patients (25 percent) within a median time of 5.9 months from the initiation of ECP. Among those patients with available data, 27 out of 51 patients (52.9 percent) at three months and 16 out of 20 patients (80 percent) at 18 months, reported as improved (minimally, much or very much) in CGI-I severity scores.¹ If exact timepoint was unavailable, physicians were advised to enter the date from closest visit (± four weeks). Per the Prescribing Information, there is no clinical evidence to show that treatment with UVADEX beyond six months provides additional benefit.

The limitations of this retrospective chart review include that the study relied on real world medical charts which could be missing data or may have used site-specific measurement schedules and procedures. Due to the retrospective nature of this analysis, it is hypothesis-generating; no formal conclusions should be drawn. Not all benefit from the analysis may be solely attributable to ECP treatment as patients may have been on multiple therapies at the time of ECP treatment. The study was granted a waiver for ethics review by the WCG [IRB], and when required, by the local IRB at each site.

“As a pioneer in immunomodulation therapy, Mallinckrodt is committed to furthering knowledge and data on the treatment outcomes for CTCL,” said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. “The results of this retrospective medical chart review analysis support the importance of continued collection of real-world data to help inform patients’ treatment options.”

The study was funded by Mallinckrodt.

About Cutaneous T-Cell Lymphoma (CTCL)
Cutaneous T-cell lymphoma (CTCL) is an umbrella term for a group of non-Hodgkin lymphomas involving T lymphocytes that localize in the skin. It is a relatively rare cancer that mostly impacts men between the ages of 40 and 60 and there are about 2,500 to 3,000 new cases of CTCL in the U.S. each year.² The age of onset is typically greater than 50 years, with the incidence rising significantly in the later decades of life.³ CTCL causes visible skin symptoms ranging from a small rash to extensive redness, peeling, burning, soreness, and itchiness all over the body, CTCL falls into different categories based on the severity of the disease and symptoms.⁴ 

About Therakos Immunotherapy
Therakos immunotherapy is delivered through CELLEX systems to harness the power of the patient’s immune system to treat the skin manifestations of CTCL, and is used by academic medical centers, hospitals, and treatment centers in more than 25 countries. Therakos photopheresis systems are fully integrated closed systems and U.S. Food and Drug Administration (FDA)-approved for the palliative treatment of the skin manifestations of CTCL in persons who have not been responsive to other forms of treatment.

IMPORTANT SAFETY INFORMATION

CAUTION: READ THE THERAKOS CELLEX PHOTOPHERESIS SYSTEM’S OPERATOR’S MANUAL PRIOR TO PRESCRIBING OR DISPENSING THIS MEDICATION.

CONTRAINDICATIONS
UVADEX is contraindicated in:

• Patients exhibiting idiosyncratic or hypersensitivity reactions to methoxsalen, other psoralen compounds, or any of the excipients
• Patients possessing a specific history of a light-sensitive disease state, including lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, and albinism
• Patients with aphakia because of significantly increased risk of retinal damage
• Patients that have contraindications to the photopheresis procedure

WARNINGS AND PRECAUTIONS

• Patients who are receiving concomitant therapy (either topically or systemically) with known photosensitizing agents such as anthralin, coal tar or coal tar derivatives, griseofulvin, phenothiazines, nalidixic acid, halogenated salicylanilides (bacteriostatic soaps), sulfonamides, tetracyclines, thiazides, and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal, and methyl orange may be at greater risk for photosensitivity reactions with UVADEX
• Oral administration of methoxsalen followed by cutaneous UVA exposure (PUVA therapy) is carcinogenic. Methoxsalen also causes DNA damage, interstrand cross-links and errors in DNA repair
• Methoxsalen may cause fetal harm when given to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant. If UVADEX is used during pregnancy, or if the patient becomes pregnant while receiving UVADEX, the patient should be apprised of the potential hazard to the fetus
• Severe photosensitivity can occur in patients treated with UVADEX. Advise patients to wear UVA absorbing, wrap-around sunglasses and cover exposed skin or use a sunblock (SPF 15 or higher), and avoid all exposure to sunlight for twenty-four (24) hours following photopheresis treatment
• After methoxsalen administration, exposure to sunlight and/or ultraviolet radiation may result in “premature aging” of the skin
• Since oral psoralens may increase the risk of skin cancers, monitor closely those patients who exhibit multiple basal cell carcinomas or who have a history of basal cell carcinomas
• Serious burns from either UVA or sunlight (even through window glass) can result if the recommended dosage of methoxsalen is exceeded or precautions are not followed
• Exposure to large doses of UVA light causes cataracts in animals. Oral methoxsalen exacerbates this toxicity
• Safety in children has not been established
• Thromboembolic events, such as pulmonary embolism and deep vein thrombosis, have been reported with UVADEX administration through photopheresis systems for treatment of patients with graft-versus-host disease, a disease for which UVADEX is not approved

ADVERSE REACTIONS

• Side effects of photopheresis (UVADEX used with THERAKOS Photopheresis Systems) were primarily related to hypotension secondary to changes in extracorporeal volume (>1%)

ABOUT MALLINCKRODT
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; analgesics and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release includes forward-looking statements related to an ongoing, retrospective study in ECP. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: final results of the underlying study; satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; and other risks identified and described in more detail in the “Risk Factors” section of Mallinckrodt’s most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

Contact

Media Inquiries
Lisa Wolfe
Green Room Communications
914-588-4733
lwolfe@greenroompr.com

Investor Relations
Daniel J. Speciale
Vice President, Finance and Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com

Government Affairs
Derek Naten
Vice President, Government Affairs & Patient Advocacy
derek.naten@mnk.com

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ^©2021 Mallinckrodt. US-2100806 12/21

DUBLIN, Ireland and LAKEWOOD, Colo. USA – October 28, 2021 – Mallinckrodt plc (OTCMKTS: MNKKQ), a global biopharmaceutical company, and Terumo Blood and Cell Technologies, a global leader in blood component, therapeutic apheresis and cellular technologies, and the exclusive distributor of the Therakos extracorporeal photopheresis (ECP) platform in Australia, announced today that both the Medical Services Advisory Committee (MSAC) and the Pharmaceutical Benefits Advisory Committee (PBAC) recently recommended that UVADEX^® (methoxsalen) for extracorporeal administration with the THERAKOS^® CELLEX^® Photopheresis System be listed on the Pharmaceutical Benefits Scheme (PBS) in Australia for the treatment of steroid dependent, intolerant or resistant chronic graft versus host disease (cGvHD) in adults.

In this two-part evaluation, the PBAC supported the cost-effectiveness of UVADEX, the pharmaceutical component of the treatment system; and the MSAC accepted the claim of superiority for safety and non-inferiority for efficacy between ECP with UVADEX and comparators. The role of both committees is to advise the Australian Minister for Health to help inform Australian Government decisions about public funding. The full assessment report related to the MSAC recommendation can be found in the published public summary document. The PBAC recommendation, found here, states:

The PBAC recommended the Section 100 (Highly Specialised Drugs Program – Public and Private Hospital) Authority Required (STREAMLINED) listing for methoxsalen, delivered as part of an integrated, closed system ECP service for the treatment of patients with steroid dependent, steroid intolerant or steroid refractory cGVHD. The PBAC was satisfied that ECP involving methoxsalen provides, for some patients, a significant improvement in efficacy over current standard of care. The PBAC noted that MSAC accepted that ECP had likely superior
clinical effectiveness and non-inferior safety compared with current standard of care. Further, the PBAC noted that MSAC advised that ECP plus methoxsalen has acceptable cost-effectiveness in the treatment of cGVHD compared with current standard of care for the proposed patient population.

UVADEX is indicated for extracorporeal administration with the THERAKOS CELLEX Photopheresis System for the treatment of steroid‑refractory and steroid‑intolerant cGVHD in adults following allogeneic hematopoietic stem cell transplantation; and for palliative treatment of the skin manifestations of cutaneous T-cell lymphoma that is unresponsive to other forms of treatment.

“Treatment for patients with cGvHD who do not respond to steroids has long been a challenge, and as a pharmaceutical company focused on improving outcomes for underserved patients with severe and critical conditions, we strive to provide treatment options that address unmet medical needs,” said Maro Williams, Ph.D., Country Medical Director, International Medical Affairs at Mallinckrodt. “The positive reimbursement recommendation is an important step to help ensure that UVADEX with the THERAKOS ECP system is broadly available to patients who may benefit from this treatment.”

In July 2020, UVADEX also received recommendations from both the MSAC and the PBAC to be listed on the PBS in Australia for the treatment of cutaneous T-cell lymphoma in adults.

“The PBAC assessment supports THERAKOS ECP with UVADEX as a cost-effective option for the treatment of patients with cGvHD in Australia, compared to other standard-of-care therapies,” said Xavier Dubois, General Manager Australia and New Zealand, Terumo Blood and Cell Technologies. “This important milestone underscores the value of this treatment option for patients who are unresponsive to other forms of treatment.”

About Chronic Graft Versus Host Disease (cGvHD)
Graft versus host-disease is a common complication of hematopoietic stem cell transplantation resulting in significant morbidity and mortality. It can be classified as acute or chronic based on the clinical presentation and the time of occurrence after the transplantation. Signs and symptoms of cGvHD nearly always occur within the first year post transplantation, but can occasionally happen several years later. In cGvHD, the skin is the most frequently affected organ with manifestations of itchy rash, hyper or hypopigmentation and changes in texture. However, the disease can affect multiple sites, which may have a major impact upon a patient’s quality of life.3 , Chronic GvHD can lead to debilitating consequences, such as joint contractures, loss of sight, end-stage lung disease, or mortality resulting from profound chronic immune suppression leading to recurrent or life-threatening infections.2

Minimum Product Information: UVADEX^® (methoxsalen) Concentrated Injection for extracorporeal circulation via photopheresis (ECP)

▼ This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events at www.tga.gov.au/reporting-problems.

Indications in Australia: UVADEX (methoxsalen) is indicated for extracorporeal administration with the THERAKOS CELLEX Photopheresis System for the:

• treatment of steroid‑refractory and steroid‑intolerant chronic graft versus host disease (cGVHD) in adults following allogeneic HSC transplantation.
• palliative treatment of the skin manifestations of cutaneous T-cell lymphoma (CTCL) that is unresponsive to other forms of treatment.

Contraindications: History of idiosyncratic or hypersensitivity reaction to methoxsalen, psoralen compounds or any excipients of UVADEX; co‑existing melanoma, basal cell or squamous cell skin carcinoma; lactation; aphakia. ECP procedure contra-indications: Photosensitive disease; inability to tolerate extracorporeal volume loss; WBC count > 25,000 mm3; previous splenectomy; coagulation disorders. Special warnings and precautions: Only physicians who have special competence in the diagnosis and treatment of cGVHD and CTCL who have special training and experience with the THERAKOS CELLEX Photopheresis System should use UVADEX. Psoralen and ultraviolet radiation therapy should be under constant supervision of such a physician. Because of the possibilities of ocular damage, the patient should be fully informed by the physician of the risks inherent in this therapy. UVADEX should only be used ex vivo and administered directly into the photoactivation bag. Visually inspect for haemolysis. In the event of unscheduled damage to the blood during the photopheresis procedure (e.g. >43ºC alarm sounding), the fractionated blood should only be reinfused into the patient if haemolysis has not occurred. Both Men and women being treated with UVADEX should take adequate contraceptive precautions both during and after completion of photopheresis treatment. Exposure to large doses of UVA causes cataracts in animals, an effect enhanced by the administration of oral methoxsalen. As the concentration of methoxsalen in the human lens is proportional to the serum level, the concentration will be substantially lower
following ex vivo methoxsalen treatment (with UVADEX) compared to that seen following oral administration. Nonetheless, if the lens is exposed to UVA during the time methoxsalen is present in the lens, photochemical action may lead to an irreversible binding of methoxsalen to protein and DNA components of the lens. For this reason the patient’s eyes should be protected from UVA light by wearing wrap-around, UVA-opaque sunglasses during the treatment cycle and during the following 24 hours. Following oral administration of psoralen, where serum concentrations may exceed 200 ng/mL, exposure to sunlight or ultraviolet radiation (even through window glass) may result in serious burns and, in the long‑term, “premature aging” of the skin. Oral psoralens may increase the risk of skin cancer. Extracorporeal use of UVADEX is associated with much lower systemic exposure than from oral methoxsalen. The phototoxicity of UVADEX has not been characterised; as a precaution, patients should avoid exposure to sunlight during the 24 hours following photopheresis treatment. Thromboembolic events, such as pulmonary embolism and deep vein thrombosis, have been reported with UVADEX administration through photopheresis systems for treatment of patients with graft versus host disease. This product contains 4.1% w/v ethanol and each 1 mL of UVADEX contains 40.55 mg of ethanol. Caution is advised in patients with liver disease, alcoholism, epilepsy, brain injury or disease. No specific information is available for use in renal or hepatic impairment and there is no evidence for dose adjustment in the elderly. Since hepatic biotransformation is necessary for urinary excretion, this may lead to prolonged photosensitivity requiring continued precautions against exposure to sunlight beyond 24 hours following photopheresis treatment. The potential benefits of photopheresis treatment should be weighed against any possible risk before embarking on the procedure. The safety and efficacy of UVADEX have not been established in children. Use in pregnancy: Category D. Use in Lactation: UVADEX is contra-indicated. Interactions with other medicines: Effects on P450 system metabolism may affect clearance / activation of other drugs (caffeine, paracetamol) or may extend the methoxsalen half-life leading to prolonged photosensitivity in patients. Methoxsalen binding to albumin may be displaced by dicoumarol, warfarin, promethazine and tolbutamide with potential for enhanced photosensitivity. Caution when treating with concomitant photosensitising agents. Adverse effects: In the clinical trials, published information and postmarketing surveillance of UVADEX/ECP, adverse events were usually mild and transient and in most cases, related to the underlying pathology. Very common: diarrhoea, anaemia, nausea, headache, hypertension, sinusitis, upper respiratory tract infection, fatigue, pain in extremity, pyrexia, cough, dyspnoea, cushingoid, dry eye, photophobia, toothache, anorexia. Common: depression, lacrimation increased, abdominal pain, hypokalaemia, paraesthesia oral, pharyngolaryngeal pain, tachycardia, conjunctivitis, eye pain, visual acuity reduced, dysphagia, chills, mucosal inflammation, nasopharyngitis, contusion, blood pressure diastolic decreased, haemoglobin decreased, hyperglycaemia, hypocalcaemia, neuropathy peripheral, tremor, rash, hypotension. Additional adverse effects seen in clinical trials include vomiting, infections. Adverse events related to the ECP/CELLEX procedure – thromboembolism and severe allergic reactions, vascular access complication, vasovagal spasm, hickman catheter infection/thrombosis, headache, hypercoagulability, haemolysis. Additional adverse events identified post-marketing: anaphylactic reaction, allergic reaction, dysgeusia, exacerbation of congestive heart failure, sepsis, endocarditis, vomiting and photosensitivity reactions. Dosage and Administration: Chronic Graft versus Host Disease: Three ECP treatments in the first week then two ECP treatments per week for at least 12 weeks, or as clinically indicated. Cutaneous T-cell Lymphoma: ECP treatment on two successive days each month for six months. Patients who show an increase in skin scores after eight treatment sessions may have their treatment schedule increased to two successive days every two weeks for the next three months. Refer to full Product Information and THERAKOS CELLEX Operator’s Manual for information regarding administration.

Store below 25°C. Date of first approval: 16 September 2019. Date of revision: 19 November 2020.

Indications and Prescribing Information for UVADEX vary globally. Please refer to the individual country product label for complete information.

Before prescribing UVADEX, please refer to the full Product Information also available by calling +61 2 9429 3606.

ABOUT THERAKOS
Mallinckrodt is the world’s only provider of approved, fully integrated systems for administering immunomodulatory therapy through ECP. Its Therakos ECP platforms, including the latest generation THERAKOS^® CELLEX^® Photopheresis System, are used by academic medical centres, hospitals, and treatment centres in nearly 40 countries and have delivered more than 1 million treatments globally. For more information, please visit  www.therakos.eu.

Terumo Blood and Cell Technologies is the exclusive distributor of the Therakos ECP platform in Australia, as well as Latin America and select countries in Europe. To learn more about Terumo Blood and Cell Technologies, visit www.terumobct.com.

UVADEX (methoxsalen) and THERAKOS CELLEX Photopheresis Systems are separately approved in a number of global markets. Please refer to your local approved labelling for UVADEX and the Operator’s Manual for CELLEX for more information on approved uses for specific indications.

Before administering therapy using the THERAKOS CELLEX Photopheresis System, please refer to the Operator’s Manual available at +61 2 9429 3606.   

ABOUT MALLINCKRODT 
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; analgesics and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

About Terumo Blood and Cell Technologies
Terumo Blood and Cell Technologies is a medical technology company. Our products, software and services enable customers to collect and prepare blood and cells to help treat challenging diseases and conditions. Our employees around the world believe in the potential of blood and cells to do even more for patients than they do today.

Terumo Blood and Cell Technologies’ customers include blood centers, hospitals, therapeutic apheresis clinics, cell collection and processing organizations, researchers and private medical practices. Our customers are based in over 130 countries across the globe. We have 750+ granted patents, with an additional 150 pending.

We have global headquarters in Lakewood, Colo., U.S.A., along with five regional headquarters, six manufacturing sites and six innovation and development centers across the globe. Terumo Blood and Cell Technologies is a subsidiary of Terumo Corporation (TSE: 4543), a global leader in medical technology. TERUMOBCT.COM

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release includes forward-looking statements concerning the use of UVADEX with the THERAKOS CELLEX Photopheresis System including potential benefits associated with its use. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues; and other risks identified and described in more detail in the “Risk Factors” section of Mallinckrodt’s most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

Contact

Mallinckrodt Media Inquiries
Tara DiFlumeri
Senior Vice President, Green Room Communications
908-577-4531
tara@greenroompr.com

Terumo Media Inquiries
Christine Romero
Terumo Blood and Cell Technologies
press@terumobct.com

Investor Relations
Daniel J. Speciale
Vice President, Finance and Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com

Government Affairs
Derek Naten
Vice President, Government Affairs & Patient Advocacy
derek.naten@mnk.com

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ^© 2021 Mallinckrodt. AU-2100055 10/21

DUBLIN – September 2, 2021 – Mallinckrodt plc (OTCMKTS: MNKKQ), a global biopharmaceutical company, announced today interim results^[i] from a retrospective, explorative, single-arm, pan-European multicenter study to evaluate the real world use of extracorporeal photopheresis (ECP) and therapy-related outcomes in heart transplant patients. The first results from the largest known study of ECP in heart transplantation patients were reported during a late-breaking oral presentation at the 20^th Congress of the European Society for Organ Transplantation (ESOT) in Milan, Italy.

The interim analysis examined data from medical charts of 71 patients who received ECP treatment following heart transplantation at four medical centers in Germany, France and Hungary between 2015 and 2021. Of the 71 patient charts examined, 51 patients (72 percent) were no longer receiving ECP treatment and treatment was ongoing for 20 patients (28 percent). Mean follow up time was two years from the start of ECP treatment to last visit. Median time from heart transplant to start of ECP was eight months, and on average, 26 individual ECP treatments were performed over a mean duration of nine months. The three main reasons to start ECP treatment were: acute cellular rejection (ACR) in 31 patients (44 percent), antibody mediated rejection (AMR) in 15 patients (21 percent) and prevention of rejection (PR) in 16 patients (23 percent).

Forty-eight of the 51 patients had graft function measurements at the start and end of ECP treatment and of these, 29 patients (60 percent) showed improved graft function at the end of ECP treatment. Improvement in graft function was defined as at least 15 percent-point increase in ejection fraction and/or improvement in at least one grade of ACR, AMR, Chronic Allograft Vasculopathy (CAV), or stable CAV, or at least one New York Heart Association (NYHA) class lower, without any worsening in any of the other parameters. The remaining 19 patients (40 percent) showed stable graft function at the end of ECP treatment.

Study limitations include that, as an explorative single-arm study, comparative effectiveness cannot be assessed. The study relied on real world medical charts which could be missing data or may have used site-specific measurement schedules and procedures. There was no source data verification and low patient numbers limited analysis by reason to start ECP treatment. Due to the retrospective nature of this analysis, it is hypothesis-generating; no formal conclusions should be drawn. In addition, the assessments of ECP treatment were completed at different time points. The ECP treatment platform varied based on the treatment center. Dosing and frequency of treatment varied, with no minimum amount of treatment required. Not all benefits from this analysis may be solely attributable to ECP treatment as patients may have been on multiple therapies at the time of ECP treatment.

In a sub-analysis of patients grouped by the three main reasons to start ECP treatment, rejection improvement from the start to end of ECP treatment was demonstrated in 17 of 21 ACR patients (81 percent) and five of seven AMR patients (71 percent). In the PR group, 12 patients (75 percent) remained free from any biopsy-proven rejection after starting ECP over a mean follow-up of 2.8 years. Four patients (25 percent) developed ACR.

Among the 71 patients reviewed, eight (11 percent) had at least one ECP-related safety event. In total, six patients (8 percent) had complications with venous access, two (3 percent) had hypotension events and two (3 percent) had unspecified events. The interim analysis showed overall survival was 93 percent among all 71 patients. Five patients died, three with a functioning graft. No deaths were deemed related to ECP treatment.

The findings from the interim analysis are limited to trends relative to the study’s endpoints of efficacy and are not necessarily indicative of the final results to be announced from the completed analysis.

The study was funded by Mallinckrodt.

“These results suggest that ECP has the potential to be an effective treatment for acute cellular rejection, as well as an option for antibody mediated rejection with and without donor specific antibodies, and in rejection prevention in heart transplantation,” said presenting author, Markus Barten, M.D., Surgical Director of Heart Failure Clinic, University Heart Center Hamburg. “We are encouraged by the results of this multicenter study and believe that additional data around the efficacy and safety of ECP as a potential treatment option may be warranted to help advance the scientific understanding of ECP in heart transplant patients.”

Mallinckrodt also awarded a €50,000 educational grant to ESOT supporting its commitment to advancing education and research in transplantation. The 2021 winner, determined by an ESOT jury, was awarded during the Science Slam Symposium at the ESOT Congress 2021 on Tuesday, August 31st. The educational grant award was established to recognize and support researchers who are working to advance the knowledge of ECP immunomodulation in solid organ transplantation within the Europe, Middle East and Africa region.

“As a pioneer in ECP immunomodulation, Mallinckrodt is committed to furthering understanding of the use of ECP in heart transplant patients and its potential to improve clinical outcomes in this patient population,” said Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt. “Organ rejection after heart transplantation due to ACR or AMR is a therapeutic challenge for clinicians and patients, and modalities that can improve graft function and prevent rejection are greatly needed.”

About Extracorporeal Photopheresis (ECP)        

ECP, a blood based immunomodulatory therapy developed more than 30 years ago, is recommended by the International Society for Heart and Lung Transplantation (ISHLT)^[ii] and other clinical societies^{[iii],[iv],[v]} as an adjunctive therapy for the prevention and treatment of ACR after heart transplantation. Additionally, ECP may be considered to treat AMR with or without donor specific antibodies.^[vi],[vii] In countries where it is approved, ECP is used to treat a range of immune-mediated diseases, including skin manifestations of cutaneous T-cell lymphoma (CTCL), graft-versus-host disease (GvHD), organ transplant rejection and other autoimmune diseases. During ECP treatment, a small amount of white blood cells is collected and treated with a drug that is activated by ultraviolet light.

 ABOUT MALLINCKRODT 
Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company’s Specialty Brands reportable segment’s areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; analgesics and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS
This release includes forward-looking statements related to an ongoing, retrospective study in ECP. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: final results of the underlying study; satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; and other risks identified and described in more detail in the “Risk Factors” section of Mallinckrodt’s most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law.

Contact

Media Inquiries
Tara DiFlumeri

Senior Vice President, Green Room Communications

908-577-4531

tara@greenroompr.com

Investor Relations
Daniel J. Speciale
Vice President, Finance and Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com

Government Affairs
Derek Naten

Vice President, Government Affairs & Patient Advocacy

derek.naten@mnk.com

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ^©2021 Mallinckrodt. EU-2100165 09/21

Dublin, Ireland, March 19, 2021 – A project that will analyze the immunomodulatory effects of extracorporeal photopheresis therapy (ECP) through innate cells has won Mallinckrodt plc’s 2021 Advances in Immunomodulatory ECP research award.

This is the fourth year that Mallinckrodt, provider of approved, fully integrated systems for the administration of immunomodulatory therapy via ECP, will present the €50,000 prize during the annual meeting of the European Group for Blood and Marrow Transplant (EBMT).

The winning project, submitted by the RIGHT institute (UMR1098) in collaboration with the University Hospital Besançon, France, seeks to investigate mechanisms of cell death generated through ECP and the direct effects on the innate cells involved in the resolution of inflammation. The team is led by Dr. Etienne Daguindau.

Research funded from the inaugural investigator award, which was founded in 2018 to mark the 30th anniversary of Mallinckrodt’s pioneering THERAKOS ECP ImmunomodulationTM, was also presented at this year’s EBMT.

Part of the Company’s ongoing commitment to the science of immunomodulation through ECP across therapeutic applications, the initiative was designed to recognize individuals and institutions whose research contributes to the advancement of knowledge in this broad area of medicine.

Steven Romano, M.D., Executive Vice President and Chief Scientific Officer of Mallinckrodt, said: “Entries to this year’s investigator award, as ever, covered a broad spectrum of disease settings demonstrating the vast ambition and vision of our research community and the potential, wide-ranging applications of ECP.”

Entries were invited from clinicians and scientists working on translational or outcomes-based research, as well as collaborative projects. Submissions were assessed on a range of criteria, including scientific merit, originality, and feasibility.

Congratulating the winning team, Romano added: “As a pioneer in ECP immunomodulation, Mallinckrodt is proud to support the work of those who continue to investigate this exciting field of medicine. I congratulate Dr. Daguindau and his team and look forward to seeing their results.”

In 2018, the prize went to a team from the Rotherham NHS Foundation Trust Department of Haematology. Led by Dr. Nick Matthews, the study evaluated the effect of ECP on monocytes in the setting of graft versus host disease (GvHD).

Dr. Matthews said: “It meant a lot to the team to be selected for the research award. We were very honored, very surprised, and very relieved because we needed the funding to continue our work.

“It is such a wide research field, with lots of competition and many pressing research questions, but this award is purely for ECP immunomodulation research, which makes it very special.”

The 2022 Advancing ECP Immunomodulation Investigator Award will be open for entries in September. For full details on how to enter, go to https://www.therakos.eu/healthcare-professionals/research-opportunities-educational-grants/educational grants

ABOUT THERAKOS

Mallinckrodt’s therapeutic platforms, including the latest generation THERAKOSTM CELLEXTM Photopheresis System, are used by academic medical centres, hospitals, and treatment centres in more than 30 countries and have delivered more than 1 million treatments globally. For more information, please visit www.therakos.eu

ABOUT MALLINCKRODT

Mallinckrodt is a global business that develops, manufactures, markets and distributes specialty pharmaceutical products and therapies. Areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, nephrology, pulmonology and ophthalmology; immunotherapy and neonatal respiratory critical care therapies; analgesics and gastrointestinal products. The company’s core strengths include the acquisition and management of highly regulated raw materials and specialized chemistry, formulation and manufacturing capabilities. The company’s Specialty Brands segment includes branded medicines and its Specialty Generics segment includes specialty generic drugs, active pharmaceutical ingredients and external manufacturing. To learn more about Mallinckrodt, visit www.mallinckrodt.com.

Mallinckrodt uses its website as a channel of distribution of important company information, such as press releases, investor presentations and other financial information. It also uses its website to expedite public access to time-critical information regarding the company in advance of or in lieu of distributing a press release or a filing with the U.S. Securities and Exchange Commission (SEC) disclosing the same information. Therefore, investors should look to the Investor Relations page of the website for important and time-critical information. Visitors to the website can also register to receive automatic e-mail and other notifications alerting them when new information is made available on the Investor Relations page of the website.

Contact

Investor Relations
Daniel J. Speciale
Vice President, Finance and Investor Relations Officer
314-654-3638
daniel.speciale@mnk.com

Trade Media Inquiries
James Tate
Managing Director
The Henley Group
M: +44 7976 794 398
james@henley.co.uk

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ^© 2021 Mallinckrodt.  Item code: EU-2100042. Date of preparation: March 2021.