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

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Tara DiFlumeri

Senior Vice President, Green Room Communications

908-577-4531

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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.

Contact

Media Inquiries
Caren Begun
Green Room Communications
+1 201-396-8551
caren@greenroompr.com

Investor Relations
Daniel J. Speciale, CPA
Vice President, Finance and Investor Relations Officer
+1 314-654-3638
daniel.speciale@mnk.com

Mallinckrodt Pharma K.K.
Kazuo Nishiyama
Sales & Marketing, Product Manager
+81 3 6234 1650
kazuo.nishiyama@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. 1/21