LEO Pharma to Maintain Leadership Role at AAD in 2024 with New Late-Breaking Data Spanning Multiple Therapeutic Areas

NOT FOR UK USE ? NOT INTENDED FOR UK MEDIA

LEO Pharma A/S, a global leader in medical dermatology, will present a breadth of new data on moderate-to-severe chronic hand eczema (CHE), congenital ichthyosis (CI) and atopic dermatitis (AD) at the upcoming 82^nd American Academy of Dermatology (AAD) Annual Meeting. The event is being held from March 8^th to 12^th in San Diego, California.

"Our growing body of clinical evidence reinforces our passion and commitment to advancing the standard of care in medical dermatology," said Kreesten Meldgaard Madsen, LEO Pharma's Chief Development Officer. "We are incredibly excited to have this opportunity at the 2024 AAD Annual Meeting to showcase our efforts to address patient needs across multiple skin conditions, including two late-breaker presentations regarding the potential treatment of CHE and CI, both of which are well known to disrupt the lives of countless people around the world."

With eight abstracts accepted in total for the meeting,^1-8 AAD is the latest major dermatology congress in which LEO Pharma will underscore a commitment to advancing scientific innovation and development in medical dermatology, with the aim of making a fundamental difference for people living with skin conditions.

"The AAD meeting is one of the most important milestones in the medical dermatology calendar in the United States, a country where skin conditions are estimated to affect as many as 1 in 3 people. I am proud that we can follow up on our 2023 AAD program with this level of critical data," said Brian Hilberdink, EVP and President, Region North America, LEO Pharma. "The opportunity to collaborate and deliberate with the research community and healthcare professionals at the scale that this meeting allows is key to bringing about meaningful change and improved outcomes for people living with skin conditions. We are honored to share our latest findings and look forward to engaging with the community while gathering more insights that will help benefit patients."

The first late-breaker presentation on March 9^th will outline the key results of the DELTA-3 trial, which assessed the long-term safety and efficacy of investigational delgocitinib cream in adults with moderate-to-severe CHE. This is the first time the key results have been shared at a medical congress.¹ Additional data for delgocitinib cream will also be presented as e-posters, including pooled analyses of the pivotal phase 3 DELTA-1 and DELTA-2 trials. ^4,5,6

An additional late-breaker presentation on March 10^th will outline the preliminary results from the maximum use arm of the ASCEND trial, which examined the efficacy, safety and pharmacokinetics of investigational TMB-001 in adult and adolescent subjects with moderate-to-severe X-linked and Autosomal Recessive CI.² Additional data, presented as an e-poster, also based on the ASCEND trial, will examine the pharmacokinetics of TMB-001 compared to oral isotretinoin.⁷

Adbry^® (tralokinumab-ldrm) data will be shared during the annual meeting as an e-poster summarizing results from the ECZTEND trial investigating the stability of long-term therapeutic responses to tralokinumab in adults with moderate-to-severe AD.³

Finally, one temtokibart (LEO 138559) e-poster will be delivered and will analyze individual patient responses to IL-22RA1 inhibition in a phase 2a monotherapy trial for moderate-to-severe AD,⁸ following up on the late-breaking presentation of the phase 2a trial that was presented at AAD 2023.

The company's full roster of accepted presentations at the 2024 AAD Congress includes:

Delgocitinib

• Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with Chronic Hand Eczema: results of the Phase 3 open-label extension DELTA-3 trial
  Author: Melinda Gooderham
  Abstract #: 56059
  LB presentation: Saturday March 09 at 11:10 ? 11:20 AM PST
  Location: Room 20BCD
  

• Efficacy and safety of delgocitinib cream in adults with moderate-to-severe chronic hand eczema: pooled results of the Phase 3 DELTA-1 and -2 trials
  Author: Robert Bissonnette
  Abstract #: 52715
  E-poster presentation?
  

• Delgocitinib cream reduces itch and pain in adults with moderate-to-severe chronic hand eczema: pooled analyses of the Phase 3 DELTA-1 and -2 trials
  Author: Andrea Bauer
  Abstract #: 53696
  E-poster
  

• Systemic exposure and safety profile of delgocitinib cream in adults with moderate-to-severe chronic hand eczema in the Phase 3 DELTA-2 trial
  Author: Melinda Gooderham
  Abstract #: 53695
  E-poster

Adbry^® (tralokinumab-ldrm)

• Stability of long-term therapeutic responses to tralokinumab in adults with moderate-to-severe atopic dermatitis
  Author: Andrew Blauvelt
  Abstract #: 53133
  E-poster

Temtokibart

• Individual patient responses to IL-22RA1 inhibition in a Phase 2a monotherapy trial for moderate-to-severe atopic dermatitis
  Author: Melinda Gooderham
  Abstract #: 53111
  E-poster

TMB-001

• Efficacy, Safety and Pharmacokinetics of First 17 Adult and Adolescent Subjects in Maximal Use Portion of Vehicle Controlled ASCEND Trial of Polyethylene Glycol (iPEGtm)-Based Topical Isotretinoin 0.05% (TMB-001) for Treatment of Congenital Ichthyosis
  Author: Christopher G. Bunick
  Abstract #: 56255
  LB presentation: Sunday March 10 at 03:00 ? 03:10 PM PDT
  Location: Room 20BCD
  

• The Phase 3 Vehicle-Controlled ASCEND Trial of Polyethylene Glycol (iPEGtm) Based Topical Isotretinoin (TMB-001 0.05% ointment) for Treatment of X-Linked and Autosomal Recessive Congenital Ichthyosis: Analysis of Pharmacokinetic Results Compared with 80 mg Oral Isotretinoin ?
  Author: Christopher G. Bunick
  Abstract #: 51523
  E-poster

About chronic hand eczema

Chronic hand eczema (CHE) is defined as hand eczema (HE) that lasts for more than three months or relapses twice or more within a year.^9,10 HE is the most common skin disorder of the hands¹¹ with a one-year prevalence rate of approximately 9%.¹² In a substantial number of patients, HE can develop into a chronic disease.¹¹ CHE is a fluctuating disorder characterized by itch and pain, and patients may experience signs such as erythema, scaling, lichenification, hyperkeratosis, vesicles, edema, and fissures on hands and wrists.¹³

About atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense itch and eczematous lesions.¹⁴ Atopic dermatitis is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation.¹⁵ Type 2 cytokines, including IL-13, play an important role in the key aspects of atopic dermatitis pathophysiology.^15,16 Excessive IL-22 production is also known to contribute to the pathogenesis of AD.¹⁷

About congenital ichthyosis

Congenital ichthyosis (CI) is a group of rare genetic keratinization disorders that can lead to dry, thickened, and scaling skin.^18-21

Most cases of ichthyosis are inherited, but some types develop in association with genetic syndromes or diseases, such as Hodgkin's Lymphoma.^22,23

People living with CI may have limited range of motion, chronic itching, an inability to sweat normally, high risk of secondary infections, and impaired eyesight or hearing.^18-21

About delgocitinib

Delgocitinib cream is an investigational, potential first-in-class, topical pan-Janus kinase (JAK) inhibitor for CHE. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE.²⁴ Delgocitinib has not been approved by any health authority. The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome.²⁵ LEO Pharma is currently developing delgocitinib in a cream formulation for the treatment of moderate-to-severe chronic hand eczema (CHE) in adults, which is currently not approved by any health authority. In 2014, LEO Pharma A/S and Japan Tobacco Inc. (JT) entered into a license agreement in which LEO Pharma gained exclusive rights to develop and commercialize delgocitinib for topical use in dermatological indications worldwide, excluding Japan, where JT retains rights.

About Adbry^® (tralokinumab-ldrm)

Adbry^® (tralokinumab-ldrm), which is marketed outside of the U.S. under the tradename Adtralza^® (tralokinumab), is a high-affinity fully human monoclonal antibody developed to bind to and inhibit the interleukin (IL)-13 cytokine, which plays a role in the immune and inflammatory processes underlying atopic dermatitis signs and symptoms.^15,16 Adbry^® specifically binds to the IL-13 cytokine, thereby inhibiting interaction with the IL-13 receptor ?1 and ?2 subunits (IL-13R?1 and IL-13R?2).²⁶

Adbry is approved for the treatment of adults and pediatric patients (12 years and above) with moderate-to-severe AD in the U.S., Canada, the European Union, the United Arab Emirates, Great Britain, and South Korea. Adtralza is approved for use in adults with moderate-to-severe AD in Saudi Arabia, Switzerland, and Japan.

U.S. INDICATION AND IMPORTANT SAFETY INFORMATION

What is ADBRY?

• ADBRY^® (tralokinumab-ldrm) injection is a prescription medicine used to treat people 12 years of age and older with moderate-to-severe atopic dermatitis (eczema) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. ADBRY can be used with or without topical corticosteroids.
• It is not known if ADBRY is safe and effective in children under 12 years of age.

Do not use ADBRY if you are allergic to tralokinumab or to any of its ingredients.

What should I discuss with my healthcare provider before starting ADBRY?

Tell your healthcare provider about all your medical conditions, including if you:

• have eye problems.
• have a parasitic (helminth) infection.
• are scheduled to receive any vaccinations. You should not receive a "live vaccine" if you are treated with ADBRY.
• are pregnant or plan to become pregnant. It is not known whether ADBRY will harm your unborn baby. There is a pregnancy exposure registry for women who use ADBRY during pregnancy. The purpose of this registry is to collect information about the health of you and your baby You or your healthcare provider can get information and enroll you in this registry by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/adbry-tralokinumab/.
• are breastfeeding or plan to breastfeed. It is not known whether ADBRY passes into your breast milk and if it can harm your baby.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I use ADBRY?

• See the detailed "Instructions for Use" that comes with ADBRY for information on how to prepare and inject ADBRY and how to properly store and throw away (dispose of) used ADBRY prefilled syringes.
• Use ADBRY exactly as prescribed by your healthcare provider.
• Your healthcare provider will tell you how much ADBRY to inject and when to inject it.
• ADBRY comes as a single-dose (150 mg) prefilled syringe with needle guard.
• ADBRY is given as an injection under the skin (subcutaneous injection).
• If your healthcare provider decides that you or a caregiver can give the injection of ADBRY, you or your caregiver should receive training on the right way to prepare and inject ADBRY. Do not try to inject ADBRY until you have been shown the right way by your healthcare provider.
• If you miss a dose, inject the missed dose as soon as possible, then continue with your next dose at your regular scheduled time.
• If you inject -too much ADBRY than prescribed, call your healthcare provider or call Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.
• Your healthcare provider may prescribe other medicines to use with ADBRY. Use the other prescribed medicines exactly as your healthcare provider tells you to.

What are the possible side effects of ADBRY?

ADBRY can cause serious side effects including:

• Allergic reactions (hypersensitivity), including a severe reaction known as anaphylaxis. Stop using ADBRY and tell your healthcare provider or get emergency help right away if you get any of the following symptoms:

• breathing problems
• itching
• skin rash
• swelling of the face, mouth, and tongue
• fainting, dizziness, feeling lightheaded (low blood pressure)
• hives

• Eye problems. Tell your healthcare provider if you have any worsening eye problems, including eye pain or changes in vision.

The most common side effects of ADBRY include:

• Upper respiratory tract infections
• Eye and eyelid inflammation, including redness, swelling, and itching
• Injection site reactions
• High count of a certain white blood cell (eosinophilia)

These are not all the possible side effects of ADBRY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please click here for full U.S. Prescribing Information, including Patient Information and Instructions for Use.

About temtokibart

Temtokibart (LEO 138559) is an investigational monoclonal antibody that targets the IL-22RA1 receptor subunit, currently in Phase 2 development for the potential treatment of moderate-to-severe atopic dermatitis.²⁷ It blocks the IL-22RA1 subunit and thereby inhibits the effects of the IL-22 cytokine, and potentially also to some extent the effects of IL-20 and IL-24.²⁷ Temtokibart does not bind to the IL-22 cytokine itself.²⁷ LEO Pharma has obtained a worldwide exclusive license to develop and commercialize temtokibart from argenx.

About TMB-001

TMB-001, topical isotretinoin in the company's investigational patented polyethylene glycol (IPEGtm) delivery system, is being developed for the treatment of moderate-to-severe subtypes of congenital ichthyosis (CI). During Q4 2021, the positive topline results for its Phase 2b CONTROL Study were announced. In Q1 2022, TMB-001 received both Breakthrough Therapy Designation and Fast Track Status from the U.S. Food and Drug Administration (FDA). The Phase 3 ASCEND clinical trial was initiated in Q2 2022.

About LEO Pharma

LEO Pharma is a global company dedicated to advancing the standard of care for the benefit of people with skin conditions, their families and society. Founded in 1908 and majority owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, and today, the company offers a wide range of therapies for all disease severities. LEO Pharma is headquartered in Denmark with a global team of 4,300 people, serving millions of patients across the world. In 2023, the company generated net sales of DKK 11.4 billion.

References

1. Gooderham M, et al. Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with Chronic Hand Eczema: results of the Phase 3 open-label extension DELTA-3 trial. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
2. Bunick G , et al. Efficacy, Safety and Pharmacokinetics of First 17 Adult and Adolescent Subjects in Maximal Use Portion of Vehicle Controlled ASCEND Trial of Polyethylene Glycol (iPEGtm)-Based Topical Isotretinoin 0.05% (TMB-001) for Treatment of Congenital Ichthyosis. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
3. Blauvelt A, et al. Stability of long-term therapeutic responses to tralokinumab in adults with moderate-to-severe atopic dermatitis. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
4. Bissonnette R, et al. Efficacy and safety of delgocitinib cream in adults with moderate-to-severe chronic hand eczema: pooled results of the Phase 3 DELTA-1 and -2 trials. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
5. Bauer A, et al. Delgocitinib cream reduces itch and pain in adults with moderate-to-severe chronic hand eczema: pooled analyses of the Phase 3 DELTA-1 and -2 trials. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
6. Gooderham M, et al. Systemic exposure and safety profile of delgocitinib cream in adults with moderate-to-severe chronic hand eczema in the Phase 3 DELTA-2 trial. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
7. Bunick G, et al. The Phase 3 Vehicle-Controlled ASCEND Trial of Polyethylene Glycol (iPEGtm) Based Topical Isotretinoin (TMB-001 0.05% ointment) for Treatment of X-Linked and Autosomal Recessive Congenital Ichthyosis: Analysis of Pharmacokinetic Results Compared with 80 mg Oral Isotretinoin. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
8. Gooderham M, et al. Individual patient responses to IL-22RA1 inhibition in a Phase 2a monotherapy trial for moderate-to-severe atopic dermatitis. Presented at the 2024 American Academy of Dermatology Annual Meeting; March 8-12 2024; San Diego, CA.
9. Lynde C, Guenther L, Diepgen TL, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg. 2010;14(6):267-284
10. Diepgen TL, Andersen KE, Chosidow O, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015;13(1):e1-e22.
11. Bissonnette R, Diepgen TL, Elsner P, et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol. 2010;24 Suppl 3:1-20.
12. Thyssen JP, Johansen JD, Linneberg A, Menné T. The epidemiology of hand eczema in the general population?prevalence and main findings. Contact Dermatitis. 2010;62(2):75-87.
13. Thyssen JP, Schuttelaar MLA, Alfonso JH, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis. 2022;86(5):357-378.
14. Weidinger S, et al. Atopic dermatitis. Lancet. 2016;387:1109-1122.
15. Boguniewicz M, et al. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-46.
16. Bieber T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020; 75:54-62.
17. Dudakov JA, Hanash AM, van den Brink MR. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. 2015;33:747-785.
18. Oji V, Traupe H. Ichthyosis: clinical manifestations and practical treatment options. Am J Clin Dermatol. 2009;10(6):351-364.
19. Takeichi T, Akiyama M. Inherited ichthyosis: Non-syndromic forms. J Dermatol. 2016;43(3):242-251.
20. Vahlquist A, Gånemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol. 2008;88(1):4-14.
21. Lilly E, Bunick CG. Congenital Ichthyosis: A Practical Clinical Guide on Current Treatments and Future Perspectives. Clin Cosmet Investig Dermatol. 2023;16:2473-2479.
22. Haber R, Feghali J, Nadir U, Yi MD, Cahn BA. Acquired ichthyosis: a clinical review. Arch Dermatol Res. 2023;315(9):2529-2543.
23. Mishra K, Jandial A, Gupta K, Prakash G, Malhotra P. Ichthyosis: A Harbinger of Lymphoma. BMJ Case Rep. 2018;2018:bcr2018224229.
24. Dubin C, Del Duca E, Guttman-Yassky E. Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges. Ther Clin Risk Manag. 2020;16:1319-1332.
25. Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol Ther. 2019;32(3):e12840.
26. Popovic B, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13R?1 and IL-13R?2. J Mol Biol. 2017; 429:208-19.
27. Thaçi D, et al. Efficacy and safety of IL-22R inhibition in patients with moderate-to-severe atopic dermatitis: results from a phase 2a monotherapy trial. Presented at the 2023 American Academy of Dermatology Annual Meeting; March 17?21 2023; New Orleans, LA.

MAT-71520 March 2024