Ichthyosis, Lamellar

MADISON, N.J.--( BUSINESS WIRE )-- NOT FOR UK USE – NOT INTENDED FOR UK MEDIA Timber Pharmaceuticals, Inc., a LEO Pharma company, today presents preliminary results from the ASCEND trial in a late-breaking session at the 2024 American Academy of Dermatology (AAD) Annual Meeting. 1 The results offer a first look at the safety, efficacy and pharmacokinetic (PK) data from 17 adult and adolescent participants (aged 12-64 years) enrolled in the open-label maximum use arm of the phase 3 ASCEND trial. 1 These late-breaker results are part of a wide-ranging data program from LEO Pharma at AAD, with eight abstracts accepted in total for the meeting, showcasing an ongoing commitment to advancing the standard of research in medical dermatology. ASCEND is a clinical trial of TMB-001, a polyethylene glycol (iPEG™) based investigational topical isotretinoin being developed for the treatment of moderate-to-severe X-linked and autosomal recessive congenital ichthyosis (CI). 3 CI is a group of rare genetic keratinization disorders that leads to dry, thickened, and scaling skin. 4-7 Currently, no specific treatments are approved by the U.S. Food and Drug Administration (FDA) to treat CI. 2 Patients enrolled in the open-label maximum use arm of the ASCEND trial with 75-90% body surface area involvement and moderate-to-severe disease on the Investigator Global Assessment (IGA) scale (IGA scores ≥3) were included in this analysis. 1 TMB-001 results showed that, from baseline to Week 12, the mean total Investigator Global Assessment (IGA) composite scaling and fissuring score decreased from 3.2 to 1.6 (p=0.0001). In the same timeframe, 59% of patients achieved a ≥2 point decrease in IGA scores from baseline, while 82% demonstrated a clinically significant (≥1 point) improvement in IGA scores from baseline. 1 No serious adverse events (SAEs) were reported. 1 65% of participants experienced at least 1 adverse event (AE), with a total of 35 events. 1 The top three treatment-emergent AEs were erythema (N=7), pruritus (N=4), and stinging/pain (N=2). 1 “ The preliminary findings from the ASCEND trial are encouraging and indicate the potential of TMB-001 to provide hope for those living with X-linked and autosomal recessive CI,” said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. “ We know that the management of this disease can be incredibly challenging and, given the limited treatment options available, we remain focused on pushing the development of TMB-001 forward with the goal of helping to address this considerable unmet need.” The results were taken from participants in the open-label maximal use arm of the ASCEND trial. This arm aimed to analyze the PKs of TMB-001 by determining the level of systemic exposure of isotretinoin and metabolites. 1 To do this, the change from baseline of isotretinoin (ISO), 4-oxo-isotretinoin (4-O-ISO), tretinoin (TR), and 4-oxo-tretinoin (4-O-TR) after 14 days of twice-daily application of TMB-001 was assessed. 1 The data demonstrated low systemic concentrations across all four molecules examined after 14 days of twice-daily application of TMB-001. 1 The steady-state mean peak plasma concentrations (ng/mL) in the 17 participants were 4.5 for ISO, 9.0 for 4-O-ISO, and low to not calculable for TR and 4-O-TR. 1 “ X-linked and autosomal recessive CI can be incredibly challenging to live with, and in my experience patients are often impacted both psychically and psychologically by a host of symptoms,” said Dr. Christopher Bunick, Lead Author and Associate Professor of Dermatology, Yale School of Medicine. “ With no specific treatment currently available, CI patients are currently having to deal with their condition with minimal support. I hope that the data and insights presented today can help provide new knowledge and support for this patient community.” In January 2024, LEO Pharma finalized the acquisition of Timber Pharmaceuticals, a clinical-stage biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases. Upon completion, the Timber Pharmaceuticals lead investigational product candidate, TMB-001, was added to LEO Pharma’s pipeline. TMB-001 is under investigation and has not been evaluated by any health authority. About the ASCEND Trial An ongoing, multicenter phase 3 study to evaluate the efficacy and safety of TMB-001 0.05% topical ointment in the treatment of congenital ichthyosis (CI) in subjects (aged ≥6 years) with either the autosomal recessive congenital ichthyosis (ARCI) or X-linked recessive ichthyosis (XLRI) subtypes. 3 The clinical trial is divided into two parts. The first is a randomized, double-blind, vehicle-controlled phase III study. Its objective is to ascertain the efficacy of TMB-001 0.05% topical ointment as a treatment for CI compared with vehicle during 12 weeks of treatment. 3 In the second part of the trial, a subset of preselected centers will recruit subjects in parallel with either the ARCI or XLRI subtypes for enrollment into an Optional Maximal Use arm. The primary objective of this part of the trial is to determine systemic exposure of isotretinoin and metabolites after single or multiple applications of TMB-001 0.005% ointment. Its primary endpoint is an assessment of individual concentrations of 4-oxo-isotretinoin (4-O-ISO), tretinoin (TR), 4-oxo-tretinoin (4-O-TR) and change from baseline. 3 About Congenital Ichthyosis Congenital ichthyosis (CI) is a group of rare genetic keratinization disorders that can lead to dry, thickened, and scaling skin. 4-7 Most cases of ichthyosis are inherited, but some types develop in association with genetic syndromes or diseases, such as Hodgkin's Lymphoma. 8,9 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. 4-7 About TMB-001 TMB-001, topical isotretinoin in the company’s investigational patented polyethylene glycol (IPEG™) 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 4,400 people, serving millions of patients across the world. In 2022, the company generated net sales of DKK 10.6 billion. References Bunick CG, 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 (iPEG™)-Based Topical Isotretinoin 0.05% (TMB-001) for Treatment of Congenital Ichthyosis. Presented at American Academy of Dermatology (AAD) 2024 Annual Meeting, San Diego, Ca., March 8-12, 2024. Hernández-Martin A, Aranegui B, Martin-Santiago A, Garcia-Doval I. A systematic review of clinical trials of treatments for the congenital ichthyoses, excluding ichthyosis vulgaris. J Am Acad Dermatol . 2013;69(4):544-549.e8. ClinicalTrials.gov. National Library of Medicine (U.S.). The ASCEND Study: Evaluating TMB-001 in the Treatment of RXLI or ARCI Ichthyosis (ASCEND). Identifier: NCT05295732. https://classic.clinicaltrials.gov/ct2/show/NCT05295732 Oji V, Traupe H. Ichthyosis: clinical manifestations and practical treatment options. Am J Clin Dermatol. 2009;10(6):351-364. Takeichi T, Akiyama M. Inherited ichthyosis: Non-syndromic forms. J Dermatol. 2016;43(3):242-251. Vahlquist A, Gånemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol. 2008;88(1):4-14. Lilly E, Bunick CG. Congenital Ichthyosis: A Practical Clinical Guide on Current Treatments and Future Perspectives. Clin Cosmet Investig Dermatol. 2023;16:2473-2479. Haber R, Feghali J, Nadir U, Yi MD, Cahn BA. Acquired ichthyosis: a clinical review. Arch Dermatol Res. 2023;315(9):2529-2543. Mishra K, Jandial A, Gupta K, Prakash G, Malhotra P. Ichthyosis: A Harbinger of Lymphoma. BMJ Case Rep. 2018;2018:bcr2018224229. MAT-71602 March 2024

MADISON, N.J.--( BUSINESS WIRE )-- 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,” s aid 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 (iPEG™)-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 (iPEG™) 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 hands 11 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 α1 and α2 subunits (IL-13Rα1 and IL-13Rα2). 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 (IPEG™) 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. A bout 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 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. 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 (iPEG™)-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. 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. 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. 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. 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. Bunick G, et al. The Phase 3 Vehicle-Controlled ASCEND Trial of Polyethylene Glycol (iPEG™) 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. 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. Lynde C, Guenther L, Diepgen TL, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg. 2010;14(6):267-284 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. 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. 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. Thyssen JP, Schuttelaar MLA, Alfonso JH, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis. 2022;86(5):357-378. Weidinger S, et al. Atopic dermatitis. Lancet. 2016;387:1109-1122. Boguniewicz M, et al. Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev. 2011;242(1):233-46. Bieber T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis. Allergy. 2020; 75:54-62. Dudakov JA, Hanash AM, van den Brink MR. Interleukin-22: immunobiology and pathology. Annu Rev Immunol. 2015;33:747-785. Oji V, Traupe H. Ichthyosis: clinical manifestations and practical treatment options. Am J Clin Dermatol. 2009;10(6):351-364. Takeichi T, Akiyama M. Inherited ichthyosis: Non-syndromic forms. J Dermatol. 2016;43(3):242-251. Vahlquist A, Gånemo A, Virtanen M. Congenital ichthyosis: an overview of current and emerging therapies. Acta Derm Venereol. 2008;88(1):4-14. Lilly E, Bunick CG. Congenital Ichthyosis: A Practical Clinical Guide on Current Treatments and Future Perspectives. Clin Cosmet Investig Dermatol. 2023;16:2473-2479. Haber R, Feghali J, Nadir U, Yi MD, Cahn BA. Acquired ichthyosis: a clinical review. Arch Dermatol Res. 2023;315(9):2529-2543. Mishra K, Jandial A, Gupta K, Prakash G, Malhotra P. Ichthyosis: A Harbinger of Lymphoma. BMJ Case Rep. 2018;2018:bcr2018224229. 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. Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol Ther. 2019;32(3):e12840. Popovic B, et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017; 429:208-19. 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

Potential to more than double the addressable patient population living with hypoglycemia resulting from insulin receptor over-activation (tumor hyperinsulinism)REDWOOD CITY, Calif., March 06, 2024 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (“Rezolute” or the “Company”), a clinical-stage biopharmaceutical company committed to developing novel, transformative therapies for serious metabolic and rare diseases, today announced results from a preclinical pharmacology study that validate the potential for its lead clinical compound, RZ358, to treat individuals with non-islet cell tumors (NICTs) that have uncontrolled hypoglycemia. Tumor hyperinsulinism (HI) may be caused by a variety of different tumor types, resulting in islet cell tumor hypoglycemia (ICTH) and NICTH. The Company previously reported on the successful use of RZ358 under its Expanded Access Program (EAP) to treat patients with insulin-producing pancreatic islet cell tumors (ICTs), or insulinomas, causing severe and uncontrolled hypoglycemia. The therapeutic potential of RZ358 in this setting was anticipated given that ICTH is mediated by insulin and that RZ358 is known to work at the insulin receptor to decrease excess insulin binding and activity. However, it was unknown if RZ358 would have utility in NICTH where hyperinsulinism is mediated by hormones such as insulin-like growth factor-2 (IGF-2) or its variants, which likewise cause hypoglycemia by binding to and activating the insulin receptor. To test this, the Company recently completed in vitro pharmacology studies to evaluate the impact of clinically relevant concentrations of RZ358 on insulin receptor activation by IGF-2, compared to insulin. This was tested at the relative concentrations of each ligand that activate the insulin receptor and are physiologically relevant in tumor HI caused by ICTH and NICTH, respectively. These experiments successfully demonstrated the ability of RZ358 to similarly blunt both IGF-2 and insulin-mediated insulin-receptor signaling, at levels of these ligands that are disease-relevant in humans. “These data demonstrate proof of the ligand-agnostic mechanism of action of RZ358 and therefore validate its broad utility in treating hypoglycemia resulting from any form of hyperinsulinism, including expanded tumor indications,” said Dr. Brian Roberts, Chief Medical Officer of Rezolute. “Coupled with known outcomes from our clinical trials in congenital HI and the positive outcomes seen with ICTH in our expanded access program, we are excited by the potential for RZ358 to provide dramatic therapeutic benefit to cancer patients who often have limited treatment options for managing serious and uncontrolled hypoglycemia, which can accompany their cancer and disrupt treatment plans.” The Company recently reported on its successful interaction with the U.S. Food and Drug Administration (FDA) in January 2024 regarding the potential to initiate a single registrational study in patients with hypoglycemia due to tumor HI. The Company will continue to evaluate the feasibility of a development program in this indication, with the possibility of including both ICTH and NICTH patients. The inclusion of NICTH patients in a potential addressable market for RZ358 in tumor HI would more than double the population. The Company is also currently evaluating RZ358 in a Phase 3 clinical trial in congenital HI, which is a rare pediatric condition where, similar to ICTH, children overproduce insulin creating a dangerous hypoglycemic state. About Tumor Hyperinsulinism (HI)Tumor HI may be the result of two distinct types of tumors: islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which lead to hypoglycemia due to excessive activation of the insulin receptor. Insulinomas are the most common type of functional ICT and cause hypoglycemia because of over production of insulin. NICTs can cause hypoglycemia by producing and secreting insulin-like paraneoplastic substances such as IGF-2 or related variants that bind to and activate the insulin receptor. This form of hypoglycemia can occur in more than 15 different tumor types, 60 percent of which are malignant, including hepatocellular carcinoma. The total addressable market for the combined indications causing tumor HI is estimated to be approximately 4,500 patients in the U.S. alone, including approximately 1,500 with ICTH and 3,000 with NICTH. The unique mechanism of action of RZ358 to attenuate excess insulin receptor activation mediated by insulin and related substances makes the therapy a potential universal treatment for hypoglycemia resulting from any form of hyperinsulinism. About RZ358RZ358 is a fully human monoclonal antibody that works downstream from the pancreas and other sources of insulin or related paraneoplastic substances, and instead binds to a unique allosteric site on insulin receptors in the liver, fat, and muscle. The antibody counteracts excess insulin receptor activation by insulin and other effector substances (such as IGF-2), thereby improving hypoglycemia. Because RZ358 acts downstream from the pancreas at the insulin receptor, it has the potential to be universally effective at treating hypoglycemia due to congenital HI, regardless of the causative genetic defect, as well as acquired forms of HI such as those mediated by insulinomas (ICTs) and other tumor types (NICTs). RZ358 received Orphan Drug Designation in the United States and European Union for the treatment of congenital HI, as well as Orphan Drug Designation and Pediatric Rare Disease Designation in the U.S. In the Phase 2 RIZE study, participants with congenital HI ages two and older nearly universally achieved significant improvements in hypoglycemia across multiple endpoints, including the primary and key secondary endpoints planned for the sunRIZE study. At doses and exposures that are planned for the Phase 3 study, RZ358 was generally safe and well-tolerated, and resulted in median improvements in hypoglycemia exceeding 80%. Based on the RIZE clinical trial outcomes and the evidence of benefit in this serious condition with substantial unmet medical need, RZ358 was subsequently granted a priority medicines (PRIME) designation by the European Medicines Agency (EMA) and an Innovation Passport designation by the U.K. Innovative Licensing and Access Pathway (ILAP) Steering Group for the treatment of congenital HI. RZ358 also received Orphan Drug Designation status in the European Union for the treatment of Insulinoma, the primary cause of ICTH. About Rezolute, Inc. Rezolute strives to disrupt current treatment paradigms by developing transformative therapies for devastating rare and chronic metabolic diseases. Its novel therapies hold the potential to both significantly improve outcomes and reduce the treatment burden for patients, treating physicians, and the healthcare system. Rezolute is steadfast in its mission to create profound, positive, and lasting impacts on patients’ lives. Patient, clinician, and advocate voices are integrated in the Company’s drug development process. Rezolute places an emphasis on understanding the patient’s lived experiences, enabling the Company to boldly address a range of severe conditions. For more information, visit www.rezolutebio.com. Forward-Looking Statements This release, like many written and oral communications presented by Rezolute and our authorized officers, may contain certain forward-looking statements regarding our prospective performance and strategies within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and are including this statement for purposes of said safe harbor provisions. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, and expectations of Rezolute, are generally identified by use of words such as "anticipate," "believe," "estimate," "expect," "intend," "plan," "project," "seek," "strive," "try," or future or conditional verbs such as "could," "may," "should," "will," "would," or similar expressions. These forward-looking statements include, but are not limited to statements regarding the Innovation Passport designation, the RZ358 Expanded Access Program, the ability of RZ358 to become an effective treatment for congenital hyperinsulinism, the effectiveness or future effectiveness of RZ358 for the treatment of congenital hyperinsulinism, and statements regarding clinical trial timelines for RZ358. Our ability to predict results or the actual effects of our plans or strategies is inherently uncertain. Accordingly, actual results may differ materially from anticipated results. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Except as required by applicable law or regulation, Rezolute undertakes no obligation to update these forward-looking statements to reflect events or circumstances that occur after the date on which such statements were made. Important factors that may cause such a difference include any other factors discussed in our filings with the SEC, including the Risk Factors contained in the Rezolute’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, which are available at the SEC’s website at www.sec.gov. You are urged to consider these factors carefully in evaluating the forward-looking statements in this release and are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement. Investors & Media:Christen BaglaneasRezolute, Inc.cbaglaneas@rezolutebio.com (508)272-6717 A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/165f8dbc-1fce-47b8-ac3f-0cf6fb4170cb