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Investor Day December 18, 2024 Nicklas Westerholm, CEO WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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Tiratricol (Emcitate®) is under development for the treatment of patients with MCT8 deficiency and is not EMA/FDA-approved. Safety and efficacy have not been established.
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3 PRESS © 2024, Egetis Therapeutics. All rights reserved.
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4© 2024, Egetis Therapeutics. All rights reserved. Agenda: Egetis Investor Day, December 18, 2024 Time (CET/ET) Subject Presenter(s) 15:00/9.00am Welcome & corporate update Nicklas Westerholm, CEO 15:10/9.10am MCT8 deficiency: recent advances with tiratricol Prof. Edward Visser, Erasmus Medical Center, NL 15:35/9.35am Q&A Visser & Westerholm 15:45/9.45am Global launch preparations Henrik Krook, Raymond Francot, Henna Oittinen-Corbinelli, Peter Verwaijen 16:20/10.20am Q&A Krook, Francot, Oittinen-Corbinelli, Verwaijen, Westerholm 16:30/10.30am Break 16:50/10.50am US regulatory pathway & ReTRIACt study Westerholm 17:00/11.00am US opportunity for Emcitate Anny Bedard, Ann-Marie Redmond 17:15/11.15am Q&A Bedard, Redmond, Westerholm 17:25/11.25am RTH-beta and the unmet medical need Prof. Aled Rees, Cardiff University, UK 17:50/11.50am Q&A Rees & Westerholm 17:55/11.55am Concluding remarks Mats Blom, Chairman of the Board 18:00/12.00pm Ends
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Several important milestones over the last 6 months 5 Jun 2024 Jul 2024 Sep 2024 © 2024 Egetis Therapeutics. All rights reserved. Aug 2024 Dec 2024 • Survival abstract/data – ETA • Response EMA D120 questions Nov 2024 ETA guidelines diagnosis and management of MCT8 deficiency Sep 2024 Promising Innovative Medicine(PIM) designation in the UK ETA: European Thyroid Association Patent application to the US PTO - “Processes of Preparation” of tiratricol Secured SEK 300m Directed Share Issue Response EMA D180 LoOI EMA approval recommendation for Emcitate® (tiratricol) Jun 2024 Triac Trial II results
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• ETA recommends the use of tiratricol as long-term therapy for all patients with MCT8 deficiency, and for certain patients with RTH-beta. • Inaugural 2024 Guidelines were commissioned by the Executive Committee of the ETA and developed by an independent team of experts. European Thyroid Association (ETA) recommends tiratricol as long-term therapy for all patients with MCT8 deficiency 6 PRESS Jun • Survival abstract/data – ETA • Response EMA D120 questions ETA guidelines diagnosis and management of MCT8 deficiency Promising Innovative Medicine(PIM) designation in the UK Patent application to the US PTO - “Processes of Preparation” of tiratricol Secured SEK 300m Directed Share Issue Response EMA D180 LoOI EMA approval recommendation for Emcitate® (tiratricol) Triac Trial II results Jun Jul Aug Sep Sep Nov Dec © 2024 Egetis Therapeutics. All rights reserved.
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• Abstract published ahead of the ETA Annual Meeting reports that treatment with tiratricol (Emcitate®) in patients with MCT8 deficiency is associated with a 3x lower risk of mortality. • Retrospective real-world cohort study investigated the effects of tiratricol on mortality in 228 patients with MCT8 deficiency. • Tiratricol-treated patients had an approximately three times lower risk of all-cause mortality (Hazard Ratio= 0.28, 95% Confidence Interval= 0.09–0.91, p-value <0.05). Tiratricol (Emcitate®) treatment in patients with MCT8 deficiency is associated with survival benefits 7 PRESS Jun ETA guidelines diagnosis and management of MCT8 deficiency Promising Innovative Medicine(PIM) designation in the UK Patent application to the US PTO - “Processes of Preparation” of tiratricol Secured SEK 300m Directed Share Issue Response EMA D180 LoOI EMA approval recommendation for Emcitate® (tiratricol) Triac Trial II results Jun Jul Aug Sep Sep Nov Dec • Survival abstract/data – ETA • Response EMA D120 questions © 2024 Egetis Therapeutics. All rights reserved.
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Egetis submits patent application to the USPTO 8 • Patent application for “Processes of Preparation” of tiratricol • Processes and compounds described in the patent application • If granted, this would be a significant patent for Egetis • Generally, the exclusivity term of a new patent is 20 years from the date on which the application for the patent was filed in the United States. © 2024, Egetis Therapeutics. All rights reserved. PRESS Jun ETA guidelines diagnosis and management of MCT8 deficiency Promising Innovative Medicine(PIM) designation in the UK Patent application to the US PTO - “Processes of Preparation” of tiratricol Secured SEK 300m Directed Share Issue Response EMA D180 LoOI EMA approval recommendation for Emcitate® (tiratricol) Triac Trial II results Jun Jul Aug Sep Sep Nov Dec • Survival abstract/data – ETA • Response EMA D120 questions
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• Led by Frazier Life Sciences with a USD 10 million investment. • The Directed Issue was oversubscribed and included both existing and new international and Swedish institutional investors. • Subscription price at market price. Egetis carried out directed share issuances amounting to SEK 300 million (approximately USD 30 million) 9 PRESS Jun ETA guidelines diagnosis and management of MCT8 deficiency Promising Innovative Medicine(PIM) designation in the UK Patent application to the US PTO - “Processes of Preparation” of tiratricol Secured SEK 300m Directed Share Issue Response EMA D180 LoOI EMA approval recommendation for Emcitate® (tiratricol) Triac Trial II results Jun Jul Aug Sep Sep Nov Dec • Survival abstract/data – ETA • Response EMA D120 questions © 2024 Egetis Therapeutics. All rights reserved.
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10 “This is the single most important milestone in Egetis’ history and a major step forward in building a sustainable rare disease company” Egetis receives positive CHMP opinion Jun ETA guidelines diagnosis and management of MCT8 deficiency Promising Innovative Medicine(PIM) designation in the UK Patent application to the US PTO - “Processes of Preparation” of tiratricol Secured SEK 300m Directed Share Issue Response EMA D180 LoOI EMA approval recommendation for Emcitate® (tiratricol) Triac Trial II results Jun Jul Aug Sep Sep Nov Dec • Survival abstract/data – ETA • Response EMA D120 questions PRESS © 2024 Egetis Therapeutics. All rights reserved.
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11 To create value for patients, society and shareholders by developing and providing a portfolio of unique products for the treatment of rare diseases with substantial medical need To bring unique therapies to patients with rare diseases that improve and extend life • Successfully develop Emcitate for EU & US approvals in 2025/26 and potentially Aladote post 2026 • Commercialize Emcitate and Aladote through an inhouse organization in Europe/ North America and partnerships in RoW • Realize the full potential of our products via life-cycle management • Ensure fast and broad access to our products for the benefit of patients worldwide • Identify further assets that address the significant unmet medical need for patients with rare diseases • Provide an open culture that encourages Collaboration, Courage & Commitment • Egetis financial objective is to create increased value for shareholders in the long term Building a sustainable orphan drug company WE CARE FOR THE RARE © 2024 Egetis Therapeutics. All rights reserved.
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Key upcoming milestones 2025-2026 12 Emcitate® • EU approval and launch • Topline results ReTRIACt for US NDA • Filing US NDA – priority review • Middle East & North Africa partnership/s © 2024 Egetis Therapeutics. All rights reserved. MCT8 deficiency RTH-beta • Potential initiation of Investigator Initiated Study - Egetis Industry collaborator • Japan – Development plan agreed with PMDA • US Patent granted - Processes and compounds • US approval and launch • US Rare Pediatric Disease Priority Review Voucher 2025-2026
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Time (CET/ET) Subject Presenter(s) 15:00/9.00am Welcome & corporate update Nicklas Westerholm, CEO 15:10/9.10am MCT8 deficiency: recent advances with tiratricol Prof. Edward Visser, Erasmus Medical Center, NL 15:35/9.35am Q&A Visser & Westerholm 15:45/9.45am Global launch preparations Henrik Krook, Raymond Francot, Henna Oittinen-Corbinelli, Peter Verwaijen 16:20/10.20am Q&A Krook, Francot, Oittinen-Corbinelli, Verwaijen, Westerholm 16:30/10.30am Break 16:50/10.50am US regulatory pathway & ReTRIACt study Westerholm 17:00/11.00am US opportunity for Emcitate Anny Bedard, Ann-Marie Redmond 17:15/11.15am Q&A Bedard, Redmond, Westerholm 17:25/11.25am RTH-beta and the unmet medical need Prof. Aled Rees, Cardiff University, UK 17:50/11.50am Q&A Rees & Westerholm 17:55/11.55am Concluding remarks Mats Blom, Chairman of the Board 18:00/12.00pm Ends 13© 2024, Egetis Therapeutics. All rights reserved. Agenda: Egetis Investor Day, December 18, 2024
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MCT8 deficiency: recent advances with tiratricol (Triac) Edward Visser Erasmus MC, Rotterdam, The Netherlands
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Erasmus MC receives royalties and service fees from Egetis Therapeutics (no personal benefits) Disclosure
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Brief context of thyroid hormone signaling MCT8 deficiency: key features & mechanisms of disease Triac Trial I Real world data QoL, survival data & Triac Trial II Outline
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Brief context of thyroid hormone signaling MCT8 deficiency: key features & mechanisms of disease Triac Trial I Real world data QoL, survival data & Triac Trial II Outline
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Thyroid gland produces thyroid hormones
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Thyroid gland produces thyroid hormones
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Thyroid gland produces thyroid hormones
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Thyroid gland produces thyroid hormones
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T3 target cell
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T3 target cell: hormones enter
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T3 target cell: hormones enter by transporter proteins
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T3 regulates developmental and metabolic process via its receptor
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MCT8 is a key transporter
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Thyroid hormone signaling disorders
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Brief context of thyroid hormone signaling MCT8 deficiency: key features & mechanisms of disease Triac Trial I Real world data QoL, survival data & Triac Trial II Outline
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MCT8 deficiency: developmental & metabolic disorder
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No head control Hypotonia Dystonia Wheel chair bound Low body weight & feeding problems Sleep disturbance Epilepsy Tachycardia Frequent infections Low muscle mass Hypokinesia MCT8 deficiency: developmental & metabolic disorder Friesema, Lancet 2004; Dumitrescu, AJHG 2004; Groeneweg, Lancet D&E 2020 Scoliosis
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MCT8 deficiency: mechanisms of disease
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MCT8 deficiency: mechanisms of disease
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Groeneweg, Lancet Diab Endocrinol 2020 0 20 40 60 80 0 50 100 145 68 23 8 4 Individuals at risk Total patients events 145 32 Age at last follow-up (in years) Overall survival (%) High mortality rate
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Therapy: dual action Increase thyroid hormone action Reduce thyroid hormone action
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T3 analog tiratricol (Triac) – principle in MCT8 defective cells T3 Triac (TA3)
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Metabolic phenotype Triac Trial I Neurological phenotype Triac Trial II Is Triac effective in patients with MCT8 deficiency? Triac
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Brief context of thyroid hormone signaling MCT8 deficiency: key features & mechanisms of disease Triac Trial I Real world data QoL, survival data & Triac Trial II Outline
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Baseline (T0) Dose-finding Stable dose End-study (T12) Long-term treatment extension period 1 yr 3 yr Triac Trial I: international phase 2 trial N=46 Median age 7.1 yrs (range 0.8 – 66.8)
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Primary outcome: T3 concentrations normalize Reference interval Groeneweg, Lancet Diab Endocrinol 2019 0 2 4 6 8 10 Patients T3 (nmol/l)
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A Change in body weight to age z score at month 12 Secondary outcomes: body weight improves Groeneweg, Lancet Diab Endocrinol 2019 -10 -8 -6 -4 -2 0 2 Patients Body weight (z score) Reference in healthy children
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A Change in body weight to age z score at month 12 Secondary outcomes: heart rate improve & PACs subside 60 80 100 120 140 160 Patients Heart rate (bpm) T0 T12 0.1 1 10 100 1000 10000 0 PAC (per 24h) Groeneweg, Lancet Diab Endocrinol 2019
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Secondary outcomes: biochemical markers improve 0 100 200 300 400 T0 T12 Patients SHBG (nmol/L) Groeneweg, Lancet Diab Endocrinol 2019
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Brief context of thyroid hormone signaling MCT8 deficiency: key features & mechanisms of disease Triac Trial I Real world data QoL, survival data & Triac Trial II Outline
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Triac: real world data
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A Change in body weight to age z score at month 12 Real world data: long-term reduction T3 Van Geest, JCEM 2022 0 2 4 6 8 10 Baseline Last visit Patients T3 (nmol/L)
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A Change in body weight to age z score at month 12 Real world data: sustained improvement of body weight Van Geest, JCEM 2022 0 5 10 15 20 -10 -8 -6 -4 -2 0 2 Age (years) Body weight-for-age (Z score) Reference in healthy children Natural history in untreated MCT8 deficiency
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Brief context of thyroid hormone signaling MCT8 deficiency: key features & mechanisms of disease Triac Trial I Real world data QoL, survival data & Triac Trial II (boring slides) Outline
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Post-hoc analyses on caregiver-reported patient-centered outcome measures from TT1 Semi-structured interviews (baseline, F-U visits, EoS visit in n=40) on complex needs and daily care challenges Most prominent changes Positive: improved interaction (22/39), improved alertness (19/39), improved motor skills (12/39), improved sleep (8/39) Negative: Increased constipation, increased unsettledness (1/39) Less perspiration (8,1% vs 48,6, EoS vs baseline) 40/40 preferred to continue Triac treatment Triac: effects on QoL
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Triac: effects on mortality International multi-center cohort study (n=173 sites; n=48 countries; n=484 screened patients) Excluded patients (DOB < 2004, n=152; limited data, n=66; unknown LoF, n=36) Baseline characteristics with (n=111) or without (n=117) Triac similar (except untreated patients less in Western countries) Median F-U: 4.8 yrs (IQR=2.7-8.4); 5 deaths in treated, 27 in untreated group Triac treated patients had ~ 3-times lower risk of all-cause mortality (HR=0.28, 95%CI=0.09-0.91, p<0.05) Ongoing analyses: confirm robustness; increase number of patients
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Metabolic phenotype Triac Trial I Real world data Neurological phenotype Triac Trial II Is Triac effective in patients with MCT8 deficiency? Triac Yes
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Triac Trial II - background
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WT Mct8/Oatp1c1 DKO + Triac- Triac Triac normalizes brain development in mouse model Mct8/Oatp1c1 DKO Kersseboom, Mol Endo 2014
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Triac Trial I – GMFM (exploratory analysis) 0 10 20 30 40 T0 T12 Patients GMFM score (%) Groeneweg, Lancet Diab Endocrinol 2019
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Triac Trial II – in/exclusion criteria International multi-center open label trial Inclusion criteria Male patient with MCT8 deficiency Aged ≤ 30 months at baseline Exclusion criteria Previous Triac treatment Previous L-T4 and/or PTU treatment for > 3 months
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Triac Trial II – outcomes Primary outcomes GMFM-88 total score BSID-III Gross Motor Domain Secondary outcomes Item 10 (head control) and 24 (sitting) of GMFM-88 Complete BSID-III Motor milestone responder analysis of standardized neurological examination (HINE) Parameters of thyrotoxicosis Triac dosing up to 200 ug/kg/day Comparison with historical controls
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Triac Trial II – cohort Screened (n=23) Enrolled (n=22) Finalized 96w (n=21)
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Triac Trial II – primary outcomes No statistical (and clinical) relevant change in GMFM or BSID
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Triac Trial II – secondary outcomes Strong reduction in T3 concentrations Triac well tolerated
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Triac Trial II – conclusions No effect on brain development with Triac in early life Confirmation of reduction in T3 concentrations Ongoing analyses (subgroups)
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Metabolic phenotype Triac Trial I Real world data Neurological phenotype Triac Trial II Is Triac effective in patients with MCT8 deficiency? Triac Yes No (analysis in progress)
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Take home message MCT8 deficiency: hypothyroid & thyreotoxic features Triac alleviates metabolic/thyreotoxic phenotype does not improve neurodevelopment in patients < 30 months (full analysis in progress) Persani, ETJ 2024
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Thyroid group Robin Peeters Marcel Meima Nilhan Gunhanlar Christiaan Stavast Zhongli Chen Wenjun Liao Anna Lopez Lizette Blankers Merel Stegenga Leonoor Schonebaum Tim Korevaar Leonie Waringa Joris Osinga Arash Derakhshan Layal Chaker Yanning Xu Erasmus MC (NL) René de Coo Marie-Claire de Wit Yolanda de Rijke Corstiaan den Uil Ingrid van Beynum Petra de Haan Carola Zillikens Sandra Smits Femke Aarsen Marieke van der Knoop Hans van Toor Ronald van der Wal Monique de Waart Sjoerd van den Berg Erica van den Akker Daniëlle van der Kaay Australia Patricia Crock Joel Vanderniet Jan Fairchild Peter Simm Tony Huynh Belgium Linda De Meirleir † Silvia Depoorter Brasil Felipe Monti Lora Canada Jill Hamilton Alexander Chesover Nina Lenherr Jacqueline Curtis Czech Republic Jan Lebl Klara Rozenkova Jana Malikova France Michel Polak Athanasia Stoupa Isabelle Oliver Regís Coutant Germany Heiko Krude Michaela Linder-Lucht Christina Reinhauer Hungary Katalin Müller Dóra Ferenzci Lilla Szeifert Italy Marco Cappa Enrico Bertini Anna Dolcetta- Capuzzo Laura Paone Davide Tonduti Federica Zibordi Francesco Porta Gerarda Cappuccio India Anna Simon Praveen Paul Rachana Dubey Belinda George Abhishek Kulkarni Israel Amnon Zung Poland Jolante Wierzba Anna Kłosowska Romania Dana Craiu Diana Barca Alice Dica Iuliu Bacos Spain Alberto Alcantud The Netherlands Martien Manshande † Paul Vrijmoeth Ineke Lunsing Jurgen Jansen Nicole Wolf Frank Visser Stan Nowak Angelique Zandstra Nitash Zwaveling Anne-Marie van Wermeskerken Jet van der Spek David Koolen South Africa Adri van der Walt Turkey Serap Turan United Kingdom Krishna Chatterjee Carla Moran Greta Lyons Anne McGowan Yogen Singh Paul Dimitri Jonathan Gallichan USA Amy Lawson Yuen Cheyenne Dewey Andy Bauer Stephen LaFranchi Bedankt Funding Sherman foundation Animal studies Essen, Germany: Heike Heuer Acknowledgements Matthijs Freund Ferdy van Geest Stefan Groeneweg Floor van der Most
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Investor Day December 18, 2024 Q&A WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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Global Launch Preparations December 18, 2024 Henrik Krook VP Commercial Operations ©2024 Egetis Therapeutics. All rights reserved.
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Focused on Broad Patient Access and Value Creation Everyone who can benefit from treatment, gets access to reimbursed Emcitate asap after regulatory approval Fast and accurate diagnosis of affected patients Reimbursement & physicians prescribing Disease awareness including educational initiatives Deliver solid value proposition to key stakeholders LAUNCH VISION CRITICAL SUCCESS FACTORS EXAMPLES OF KEY ENABLERS ©2024 Egetis Therapeutics. All rights reserved.
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Preparing for Emcitate launch by Egetis and partners 67 Executing the US & European market preparations and launches through the Egetis team Optimizing additional countries through partners To optimize the launch, we will focus our own resources on US and Europe (> 70% of sales for most ultra-orphans) Japan license deal with Fujimoto MENAT partnering dialogues ©2024 Egetis Therapeutics. All rights reserved.
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Launch possible with lean & agile team 68 Addressing unmet medical need Treatment guidelines Unique setting for Emcitate in MCT8 deficiency KOL support No competition Global community Country External Key Stakeholders: • Caregivers connected through international & national advocacy groups • International KOLs & physicians at selected specialist centers • Global strategy and local interactions with payers Global/ HQ Egetis: Seizing opportunity for cost-effective value creation • Targeted stakeholder interactions • Efficiency gains through global-country team coordination ©2024 Egetis Therapeutics. All rights reserved.
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• ETA recommends the use of tiratricol as long-term therapy for all patients with MCT8 deficiency, and for certain patients with RTH-beta. • Inaugural 2024 Guidelines were commissioned by the Executive Committee of the ETA and developed by an independent team of experts. European Thyroid Association (ETA) recommends tiratricol as long-term therapy for all patients with MCT8 deficiency 69 PRESS ©2024 Egetis Therapeutics. All rights reserved.
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Emcitate supplied globally in managed access programs 70 Managed access programs confirm the significant unmet medical need in MCT8 deficiency and the view on how Emcitate addresses it Patient Prescriber National Approval MEDICINES AGENCY• Managed access programs ‒ mechanisms to allow early access to a medicine prior to regulatory marketing approval ‒ granted to pharmaceuticals under development for situations with high unmet medical needs and where no available treatment alternatives exist or are suitable • FDA approved Expanded Access Program - Simplifies Process for Accessing Emcitate • Emcitate is being supplied in managed access programs, following individual approval from the national medicines agencies, to ‒ Around 230 patients ‒ Over 25 countries Patients Receiving Emcitate in Managed Access Programs ©2024 Egetis Therapeutics. All rights reserved. 80 100 120 140 160 180 200 220 240 Q1 21 Q2 21 Q3 21 Q4 21 Q1 22 Q2 22 Q3 22 Q4 22 Q1 23 Q2 23 Q3 23 Q4 23 Q1 24 Q2 24 Q3 24 Q4 24 Number of patients Date
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Step-wise building team to execute on key activities at the right time for launch success Key projects driven by recognized industry talents recruited to the Egetis Commercial & Medical Affairs Team – Core team brings launch skills and best practices from in total 150+ years at international companies Henrik Krook, SE VP , Commercial Operations Henna Oittinen Corbinelli, CH Medical Director Europe & International Nadia Georges, CH Global Head, Market Access & Pricing Peter Verwaijen, NL Global Head Brand Strategy & Commercial Business Expansion, GM Benelux Anny Bedard, US President Egetis North America Nigel Nicholls, UK Global Patient Advocacy Director & GM UK, Northern Europe & Iberia Raymond Francot, NL GM for DACH, IT, Central & Eastern Europe Azza Trad, FR GM France Susana Roche, FR Associate Director Global Medical Affairs Operations Ann-Marie Redmond, US Head of Market Access & Pricing, North America ©2024 Egetis Therapeutics. All rights reserved.
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72 Driving disease awareness, including educational initiatives, to support diagnosis of affected patients Meetings with MCT8 community • Advisory boards • Caregivers • Medical Experts • Congresses • Regular meetings with physicians Digital channels for broader reach • Website • Social media • Email campaigns • Electronic Continuous Medical Education ©2024 Egetis Therapeutics. All rights reserved.
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Key assets hosted on the platform: HCP/Patient/Caregiver videos Mode of disease video Resource centre including: MoD animation HCP/Patient & Caregiver videos ‘Get involved’ with ongoing studies HCP section: About MCT8 Deficiency Diagnosing MCT8 Deficiency Research & resources Contact mct8deficiency.com is our central disease awareness hub Raise awareness around importance of fast and accurate diagnosis of MCT8 deficiency to ensure optimal care and management ©2024 Egetis Therapeutics. All rights reserved.
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Expanding disease awareness momentum 74 Amplified by External Efforts Scientific community generating more data Constructive dialogues at scientific congresses Great work ongoing by several patient advocacy groups Example from Annual Meeting of the European Thyroid Association Van der Most, F. et al. T3 analogue Triiodothyroacetic acid (Triac) treatment and survival in MCT8 deficiency: an international real-world cohort study Freund, M. et al. Effect of the T3 analogue Triac on patient-centered outcome measures in patients with MCT8 deficiency: post-hoc analysis of the international Triac Trial I 5 additional abstracts related to MCT8 deficiency ©2024 Egetis Therapeutics. All rights reserved.
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Recently further supported by Egetis sponsored Caregiver study* Deliver solid Emcitate clinical and economic value proposition to enable reimbursement & broad access 75 Key for payer assessments to describe burden of disease, unmet need & benefit of treatment Significant unmet medical need High burden of MCT8 deficiency Emcitate benefit validated by physicians and regulators Currently no drug developed and regulatory approved for MCT8 deficiency The existing clinical experience and data contributed to: • European Thyroid Association (ETA) recommending Emcitate as long-term therapy for all patients with MCT8 deficiency • Positive CHMP opinion * Posters presented at congresses 2024, at ESPE (European Society of Pediatric Endocrinology) and ISPOR (International Society for Pharmacoeconomics and Outcomes Research). ©2024 Egetis Therapeutics. All rights reserved.
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Wave 1 Initiated right after pending EC decision Germany, France, Spain & Italy Phased EU launch: Germany first Germany: 1 year, but immediate funded access in parallel France, Spain, Italy & rest of EU: 1-2 years Wave 2 Additional countries EC Decision Timelines P&R process for similar ultra-orphans Pricing & Reimbursement (P&R) strategy execution in 2 waves, starting with EU4 Timing P&R processes ©2024 Egetis Therapeutics. All rights reserved.
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Summary • Preparing for launch in Europe and US by lean and agile Egetis team, other regions through partners • Disease awareness initiatives to support diagnosis of affected patients • Deliver solid value proposition to secure reimbursement & broad access 77 Broad patient access and value creation – building sustainable rare disease company ©2024 Egetis Therapeutics. All rights reserved.
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Launch Readiness Germany Dr. med. Henna Oittinen Corbinelli, Medical Director Europe & International Raymond Francot, General Manager for DACH, Italy and Central & Eastern Europe ©2024 Egetis Therapeutics. All rights reserved.
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Pricing & Reimbursement • Dossier Development • Benefit Assessment • Price Negotiations Find Patients • Disease Awareness • Diagnosis • Target Customer Interaction Stakeholder Engagement • Key Opinion Leaders & HCPs • Payers/Health Insurers • Patient Advocates 79 Ensure Access to Emcitate for all Eligible Patients upon obtaining European Marketing Authorization Critical Elements of a successful Emcitate Launch Ensure market price which reflects value and ensures broad access Support HCPs to identify eligible Emcitate patients Leverage strongest stakeholder support ©2024 Egetis Therapeutics. All rights reserved.
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Pricing & Reimbursement • Dossier Development • Benefit Assessment • Price Negotiations Find Patients • Disease Awareness • Diagnosis • Target Customer Interaction Stakeholder Engagement • Key Opinion Leaders and HCPs • Payers/Health Insurers • Patient Advocates 80 Ensure Access to Emcitate for all Eligible Patients upon obtaining European Marketing Authorization Critical Elements of a successful Emcitate Launch ©2024 Egetis Therapeutics. All rights reserved.
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Benefit assessment and price negotiations for new drugs follow a strict and transparent process 81 AMNOG Process is well-defined and led by G-BA for benefit assessment and by GKV for price negotiations Submission G-BA initial benefit assessment Final G-BA resolution Price negotiations GKV- SV Agreement No Agreement GKV-SV arbitration G-BA: Gemeinsamer Bundesausschuß - Federal Joint Commission GKV-SV: Gesetzliche Krankenversicherung Spitzenverband - Statutory Health Insurance IQWiG: Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen – Institute for quality and Efficiency in Health Care KOLs: Key Opinion Leaders Written statement and oral hearing (company/KOLs) prior to final resolution IQWIG initial benefit assessment For orphan drugs: population size and annual therapy costs For orphan drugs: added benefit granted by law Rebate Pre-Approval Managed (Early) Access Development of Benefit Dossier 4 parties involved in AMNOG process: ©2024 Egetis Therapeutics. All rights reserved.
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Opportunities for a successful AMNOG Process are identified 82 • Orphan disease status offers respective argumentations • High unmet medical need for treating at all ages • Emcitate is already prescribed through managed access program by renowned hospitals and KOLs have positive experience treating patients with Emcitate • Strong stakeholder support is emerging (KOL, PAG) • No available treatment to treat thyrotoxicosis in MCT8 deficiency • ETA Guidelines support Emcitate treatment Opportunities • Implement comprehensive and sound dossier strategy supported by and aligned with EPAR/SmPC • Focus on 1st treatment for ultra-rare MCT8 deficiency, addressing a high unmet medical need • Strong value story around the meaning/burden of thyrotoxicosis in short- and long-term aspect • Stakeholder support is crucial to outline necessity, unmet need and relevance of Emcitate • Prepare and execute negotiation strategy to agree on price that reflects value and ensure access for eligible patients Implications KOLs: Key Opinion Leaders PAG: Patient Advocacy Group EPAR: European Public Assessment Report SmPC: Summary of Product Characteristics ©2024 Egetis Therapeutics. All rights reserved.
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Pricing & Reimbursement • Dossier Development • Benefit Assessment • Price Negotiations Find Patients • Disease Awareness • Diagnosis • Target Customer Interaction Stakeholder Engagement • Key Opinion Leaders & HCPs • Payers/Health Insurers • Patient Advocates 83 Ensure Access to Emcitate for all Eligible Patients upon obtaining European Marketing Authorization Critical Elements of a successful Emcitate Launch ©2024 Egetis Therapeutics. All rights reserved.
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• Importance of strengthening awareness about MCT8 deficiency as a debilitating disease with distinct concomitant clinical presentations and the importance of its early treatment • Through disease awareness initiatives and conversations at congresses and at other occasions, we are aware of that more and more patients are diagnosed • Through the Emcitate Managed Access Program, HCPs are able to gain first-hand experience 84 Increasing Disease Awareness during pre-launch phase is an important success factor for successful launch of Ultra-Orphan drugs ©2024 Egetis Therapeutics. All rights reserved.
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Pricing & Reimbursement • Dossier Development • Benefit Assessment • Price Negotiations Find Patients • Disease Awareness • Diagnosis • Target Customer Interaction Stakeholder Engagement • Key Opinion Leaders & HCPs • Payers/Health Insurers • Patient Advocates 85 Ensure Access to Emcitate for all Eligible Patients upon obtaining European Marketing Authorization Critical Elements of a successful Emcitate Launch ©2024 Egetis Therapeutics. All rights reserved.
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HCP Engagement Strategy Building strong Expert base to advance management of MCT8 deficiency MCT8 deficiency Experts • Engage experts in increasing disease awareness in Germany • Advance collaborative efforts on monitoring and treatment guidance of MCT8 deficiency • Support clinical studies and basic research • Advocate for importance of local publications & clinical training in managing MCT8 deficiency HCPs involved in patient journey • Collaborate with all SPZs and ZSEs involved in MCT8 deficiency patient journey and subsequent disease management • Increase disease awareness and encourage discussions in local educational training sessions in multidisciplinary HCP teams • Develop customized awareness campaign to HCPs as well as patient support materials in collaboration with disease advocates 36 Centers for Rare Diseases (ZSE) 39 associated Social Pediatric centers (SPZ) IIS: Investigator Initiated Studies SPZs: Sozialpädiatrische Zentren – Social Pediatric Centers ZSEs: Zentren für Seltene Erkrankungen – Centers for Rare Diseases ©2024 Egetis Therapeutics. All rights reserved.
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Strong German Expert support for increasing disease awareness Cross-functional core Expert group • Endocrinology/Pediatric Endocrinology • Pediatric Neurology • Thyroid hormone research & clinical studies • Clinical chemistry/laboratory specialists Main Topics 2023-2024 • Improvement of Diagnostic pathways • Laboratory monitoring and newborn screening • Thyrotoxicosis in MCT8 deficiency • Cross-functional guidance on clinical monitoring Improving patient care in MCT8 deficiency Experts agree that interdisciplinary clinical monitoring is needed to improve standard of care in MCT8 deficiency The shared objective is to increase expertise in MCT8 deficiency by interdisciplinary exchange and collaboration of main specialities managing the patients Awareness & collaboration is key for adequate diagnosis and treatment ENDOCRINOLOGIC EXPERTISE NEUROLOGIC EXPERTISE ©2024 Egetis Therapeutics. All rights reserved.
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Providing Access in MENAT Peter Verwaijen Global Head of Brand Strategy & Commercial Business Expansion General Manager Benelux
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The MENAT-region 89 Opportunity for patient access based on EMA approval in the Middle-East, North-Africa and Turkey • MENAT-region has a large population with well established healthcare systems • EMA approval allows for access in some of the countries without the need for national regulatory submissions • Different healthcare systems require local knowledge and expertise ©2024 Egetis Therapeutics. All rights reserved.
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Egetis’ approach to the MENAT-region 90 Serving patients in the MENAT-region by working together with local partners • Given that Europe and the US are the priorities for Egetis together with the need for local resources in the MENAT-region, Egetis is currently identifying strategic partners for collaboration and access • Important criteria for the selection are: ‒ Proven track record and reputation ‒ Experienced in providing access for rare diseases ‒ Full set of functions (Regulatory, Market Access, Medical Affairs, Commercial, Supply Chain and Pharmacovigilance) with local representatives ‒ Committed to deliver the value of Emcitate® to patients in the region • Egetis’ ambition is to sign the first partnership agreement for MENAT in 2025 ©2024 Egetis Therapeutics. All rights reserved.
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Investor Day December 18, 2024 Q&A WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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Investor Day December 18, 2024 Break WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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US regulatory pathway and the ReTRIACt study December 18, 2024 Nicklas Westerholm, CEO WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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Time (CET/ET) Subject Presenter(s) 15:00/9.00am Welcome, CHMP opinion & corporate update Nicklas Westerholm, CEO 15:10/9.10am MCT8 deficiency: recent advances with tiratricol Prof. Edward Visser, Erasmus Medical Center, NL 15:35/9.35am Q&A Visser & Westerholm 15:45/9.45am Global launch preparations Henrik Krook, Raymond Francot, Henna Oittinen-Corbinelli, Peter Verwaijen 16:20/10.20am Q&A Krook, Francot, Oittinen-Corbinelli, Verwaijen, Westerholm 16:30/10.30am Break 16:50/10.50am US regulatory pathway & ReTRIACt study Westerholm 17:00/11.00am US opportunity for Emcitate Anny Bedard, Ann-Marie Redmond 17:15/11.15am Q&A Bedard, Redmond, Westerholm 17:25/11.25am RTH-beta and the unmet medical need Prof. Aled Rees, Cardiff University, UK 17:50/11.50am Q&A Rees & Westerholm 17:55/11.55am Concluding remarks Mats Blom, Chairman of the Board 18:00/12.00pm Ends 94© 2024, Egetis Therapeutics. All rights reserved. Agenda: Egetis Investor Day, December 18, 2024
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Emcitate regulatory pathway in US 95 • Completed 2018 (Groeneweg, 2019) • Open-label, international, multi-centre study • Completed 2021 (van Geest, 2022) • N= 27 from Triac Trial I & N= 40 new pts from managed access program • Open-label, international, multi- centre study • Focus on neurocognition, but did not meet its primary endpoints • 96 weeks safety data in young patients • Retrospective data, 2003 to 2019 (Groeneweg, 2020) • N= 16 • Placebo controlled • Ongoing Robust data set in an ultra rare genetic disease Data included in MAA © 2024 Egetis Therapeutics. All rights reserved. ReTRIACt Trial N=16 Triac Trial I N=46 EMC cohort study N=67 Triac Trial II N=22 Natural history N=151 Survival study N~228 • Retrospective cohort data • Comparing treated vs untreated patients on survival • Abstract at ETA by EMC Included in D120 response
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• A 30-day, randomized placebo-controlled withdrawal study in 16 patients • Design agreed with FDA • The study allows for inclusion of patients that are already on therapy and patients that are treatment naïve • Treatment naïve patients require a longer run-in period to stabilize T3 levels around normal range before randomization • A higher proportion of treatment naïve patients will lead to an extended study duration * ULN: Upper Limit of Normal ** Randomized treatment period ends after 30 days or when rescue criterion (T3 >ULN) is met, whichever comes first tiratricol placebo R tiratricol tiratricol Day 0 Baseline Day 30** Randomized treatment period Follow-up period (6 weeks) n=8 n=8 Run-in period Primary endpoint Primary endpoint: Proportion of participants who meet the rescue criterion (T3>ULN*) during the 30-day double-blind randomized treatment period 96 tiratricol tiratricol Patients already on therapy Treatment naïve patients Requested by the FDA 96 Design of the ReTRIACt clinical trial © 2024 Egetis Therapeutics. All rights reserved.
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Current status of ReTRIACt trial (as of Dec. 18, 2024) Egetis Therapeutics | June 2023 97 Addenbrooke’s Hospital Cambridge, UK Erasmus Medical Center Rotterdam, NL CHOP Philadelphia Map not to scale New sites opened • 18 patients have been included so far, of which 8 patients have completed the randomized phase, 1 patient in the randomized phase and 4 patients are in the run-in period. • 4 patients planned for screening in January and another 6-8 patients under evaluation for study inclusion • 6 sites currently open, including new sites from mid 2024 in Georgia, North Carolina, Texas. • Recruitment will continue until at least 16 patients have completed the randomized phase. Egetis will update the market as soon as recruitment has been completed, and subsequently when top-line results and NDA filing can be expected. © 2024 Egetis Therapeutics. All rights reserved. New sites opened
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Time (CET/ET) Subject Presenter(s) 15:00/9.00am Welcome, CHMP opinion & corporate update Nicklas Westerholm, CEO 15:10/9.10am MCT8 deficiency: recent advances with tiratricol Prof. Edward Visser, Erasmus Medical Center, NL 15:35/9.35am Q&A Visser & Westerholm 15:45/9.45am Global launch preparations Henrik Krook, Raymond Francot, Henna Oittinen-Corbinelli, Peter Verwaijen 16:20/10.20am Q&A Krook, Francot, Oittinen-Corbinelli, Verwaijen, Westerholm 16:30/10.30am Break 16:50/10.50am US regulatory pathway & ReTRIACt study Westerholm 17:00/11.00am US opportunity for Emcitate Anny Bedard, Ann-Marie Redmond 17:15/11.15am Q&A Bedard, Redmond, Westerholm 17:25/11.25am RTH-beta and the unmet medical need Prof. Aled Rees, Cardiff University, UK 17:50/11.50am Q&A Rees & Westerholm 17:55/11.55am Concluding remarks Mats Blom, Chairman of the Board 18:00/12.00pm Ends 98© 2024, Egetis Therapeutics. All rights reserved. Agenda: Egetis Investor Day, December 18, 2024
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99 US Launch Opportunity for Emcitate December 18, 2024 Anny Bedard, President North America Ann-Marie Redmond, Head Market Access & Pricing ©2024 Egetis Therapeutics. All rights reserved.
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Progressing Strategic Priorities to Drive Launch Success Build a high- performing & fit for purpose organization Optimize pricing & access at launch Identify treatment centers & build referral networks Accelerate patient identification and diagnosis Key Drivers Shaping Egetis US Commercial Success • Refined our understanding of MCT8 deficiency patient journey and profile for maximizing patient finding • Solidify our access strategy to achieve right balance between treatment cost and coverage criteria Key Progress Areas Driving Impactful steps towards a successful launch ©2024 Egetis Therapeutics. All rights reserved.
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Empowering Patient Finding Through Collaboration, Education and Innovation 101 Collaborations & Partnerships • Partnering with Advocacy Groups to maximize impact through aligned strengths • Engaging social media-savvy advocates to amplify patient outreach • Partnering with high-impact media channels to expand disease awareness • Collaborating with genetic diagnostic labs to increase disease identification Education & Awareness • Clinical trial recruitment • Expanded Access Program • Targeted conferences • Continued Medical Education (CME) program • Digital campaigns Innovative Data-Driven Approach • Leverage advanced analytics of Real- World Data and genetic test results to develop a “blueprint” of MCT8 deficiency • Develop tools to enable identification of patients who might otherwise be missed • Support physicians and patient Advocacy Groups to recognize MCT8 deficiency earlier ©2024 Egetis Therapeutics. All rights reserved.
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Building Momentum to Scale Patient Finding Efforts Accelerate patient finding efforts by integrating advanced data-driven insights into our existing initiatives Known confirmed diagnosed MCT8 deficiency patients 2022 2023 2024 102 >100 Hospitals with known MCT8 deficiency patients Naive or treated under early access Tiratricol Expanded Access Program sites ©2024 Egetis Therapeutics. All rights reserved.
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103 Establishing Strong Payer Relationships to Support Broad Access Across Priority Segments Medicaid ~83% Commercial ~9% Tricare ~2% Medicare ~6% Medicaid and Commercial Early engagement to raise awareness and education of MCT8 deficiency to support speed to coverage and reimbursement upon approval Source: Real world data analysis 2024/Accenture Anticipated Payer Mix ©2024 Egetis Therapeutics. All rights reserved.
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Balancing Annual Treatment Costs and Broad Access Skyclarys® Small molecule Procysbi® Small molecule Ravicti® Small molecule Exondys® Antisense oligonucleotide Friedreich ataxia Nephropathic cystinosis Urea cycle disorder Duchenne Muscular Dystrophy Product Disease Estimated annual treatment cost (WAC) ~$400K ~$550K ~$750K ~$750K Analogues Access Less restrictive • Prior Authorization to label • Genetic Test Attestation/documentation • Specialist prescribing More restrictive • Prior Authorization beyond label • Attestation of clinical benefit • Medical exception with appeal ©2024 Egetis Therapeutics. All rights reserved.
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Early Engagement • Foster Key Opinion Leader (KOL) champions with strong understanding of MCT8 deficiency • Payer education on MCT8 deficiency • Engagement strategy (i.e., who, what messaging, when) Seamless Patient Provider Experience • Operationalize fit for purpose provider patient experience model • Design of support services to navigate Prior Authorization for providers and patients • Patient assistance programs for out- of-pocket cost concerns Importance of Normalizing T3 • Payer value proposition and objection handler • Real world evidence to support documentation of benefit outside of clinical trial setting Prioritizing Impactful Activities to Optimize Access EMCITATE® (TIRATRICOL) AND MCT8 DEFICIENCY CORE DECK @2024, Egetis Therapeutics. All Rights Reserved. CONFIDENTIAL - FOR INTERNAL USE ONLY.©2024 Egetis Therapeutics. All rights reserved.
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Building Our Team, Capabilities and Infrastructure in Stepwise Approach for a Successful US Launch 106 Supply Chain • 3PL • Specialty Pharmacy Market Access • Patient Services • Payer Engagement Medical Affairs • Medical Scientific Liaisons • Medical Info Marketing • Brand Manager Commercial Operations • Business Insights & Analytics • CRM ©2024 Egetis Therapeutics. All rights reserved. 3PL: Third party logistics
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Delivering Impact at Launch • ReTRIACt results and NDA submission • Patient readiness for treatment at launch • Strong HCP commitment • Committed and active patient advocacy community • Maximized access • Purposed built organization 107 Critical Priorities 2025 ©2024 Egetis Therapeutics. All rights reserved.
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Investor Day December 18, 2024 Q&A WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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Resistance to Thyroid Hormone β and the Unmet Medical need Professor Aled Rees Consultant Endocrinologist Cardiff University United Kingdom 18th December 2024
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Resistance to Thyroid Hormone BETA = RTHβ
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Understand how hormones work – in health and disease Endocrinology
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Overview 1. Overview of Thyroid Hormone 2. What is Resistance to Thyroid Hormone β? 3. Diagnosis of Resistance to Thyroid Hormone β 4. Effects of Resistance to Thyroid Hormone β 5. Treatment options, unmet needs 6. Future research priorities
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Overview 1.Overview of Thyroid Hormone
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Thyroid Hormone productionThyroid Hormone Production Thyroid Stimulating Hormone (TSH) Thyroid Hormones T4 and T3 +
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Thyroid Hormone productionThyroid Hormone Production: “The Feedback Loop” Thyroid Stimulating Hormone (TSH) Thyroid Hormones T4 and T3 +-
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Thyroid Hormone productionThyroid Hormone Production: “The Feedback Loop” Example Thyroid Stimulating Hormone (TSH) Thyroid Hormones T4 and T3 +- Overactive Thyroid Gland Example levels Normal Levels TSH LOW <0.03 0.27-4.2 T4 HIGH 45 12-22 T3 HIGH 22 3.1-6.8
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Normal Thyroid Hormone action Muscle Bone CNS T4T3 TRH TSH Liver Metabolic Rate Bone maturation Bone turnover Growth Brain development Myelination Inotropic effects Chronotropic effects SHBG production Cholesterol metabolism Heart Adapted from Moran C. Best Pract Res Clin Endocrinol Metab. 2015. PMID 26303090
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Thyroid Hormone Action IIBut how do Thyroid Hormones actually work? To answer this we need to go inside the cell Nucleus
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Thyroid Hormone Action IIBut how do Thyroid Hormones actually work? Any cell Genes switched OFF DNA (genes) Cell Nucleus Thyroid Hormone Receptor
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Thyroid Hormone Action IIBut how do Thyroid Hormones actually work? Any cell Genes switched ON DNA (genes) Cell Nucleus Thyroid Hormone Receptor T3 T4 Thyroid Hormone Present T3
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Thyroid Hormone Receptors – TWO FORMS Muscle Bone CNS T4T3 TRH TSH Liver Metabolic Rate Bone maturation Bone turnover Growth Brain development Myelination Inotropic effects Chronotropic effects SHBG production Cholesterol metabolism Heart 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽𝛽𝛽 >𝛼𝛼 𝛽𝛽 >𝛼𝛼 Adapted from Moran C. Best Pract Res Clin Endocrinol Metab. 2015. PMID 26303090
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Overview 1. What is Thyroid Hormone, and what does it do? 2.What is Resistance to Thyroid Hormone β? 3. How might Resistance to Thyroid Hormone affect me?
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RTH𝛽𝛽: Thyroid Receptor β is Resistant to Thyroid Hormone Muscle Bone CNS T4T3 Hypothalamus Pituitary thyrotrophs Thyroid gland TRH TSH Liver Heart 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽𝛽𝛽 >𝛼𝛼 𝛽𝛽 >𝛼𝛼 Adapted from Moran C. Best Pract Res Clin Endocrinol Metab. 2015. PMID 26303090 Sensitive pathway Resistant pathway
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Overview 1. What is Thyroid Hormone, and what does it do? 2. What is Resistance to Thyroid Hormone? 3.How is Resistance to Thyroid Hormone 𝛽𝛽 diagnosed? 4. How might Resistance to Thyroid Hormone affect me? 5. Research
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“The Feedback Loop” in RTHβ Thyroid Stimulating Hormone (TSH) Thyroid Hormones T4 and T3 +- Example levels Normal Levels TSH NORMAL RANGE 4.0 0.27-4.2 T4 HIGH 45 12-22 T3 HIGH 22 3.1-6.8
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RTH𝛽𝛽: Abnormal Thyroid blood tests Muscle Bone CNS T4T3 Hypothalamus Pituitary thyrotrophs Thyroid gland TRH TSH Liver Heart 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽𝛽𝛽 >𝛼𝛼 𝛽𝛽 >𝛼𝛼 High FT4 High FT3 Normal range TSH Goitre 70% Adapted from Moran C. Best Pract Res Clin Endocrinol Metab. 2015. PMID 26303090 Sensitive pathway Resistant pathway
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DNA testing for RTHβ Cell DNA GeneBlood test “THRB”
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Inheritance of RTHβ Unusually inherited in an autosomal dominant pattern So for a father/mother with RTHβ, each of their children has a 1 in 2 chance of having the condition 1 in 20,000 to 40,000 Males = Females Can be diagnosed at any age Can cause many symptoms Some people have no symptoms Symptoms can vary over time
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Overview 1. What is Thyroid Hormone, and what does it do? 2. What is Resistance to Thyroid Hormone? 3.How is Resistance to Thyroid Hormone diagnosed? 4. Effects of Resistance to Thyroid Hormone 𝛽𝛽 5. Research
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RTH𝛽𝛽: Summary of Features Muscle Bone CNS T4T3 Hypothalamus Pituitary thyrotrophs Thyroid gland TRH TSH Liver Raised Metabolic Rate Failure to Thrive in Childhood Low BMD Delayed bone age 29-47% Short stature 18-25% ADHD 40-60% Poor attention, concentration Reduced IQ 30% Anxiety Hyperkinetic behaviour 33-68% Palpitations 33-75%Non raised SHBG High Cholesterol Insulin Resistance Heart 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽𝛽𝛽 >𝛼𝛼 𝛽𝛽 >𝛼𝛼 High FT4 High FT3 Normal range TSH Goitre 70% Also: ENT infections 55% Hearing impairment 10-22% Adapted from Moran C. Best Pract Res Clin Endocrinol Metab. 2015. PMID 26303090 Sensitive pathway Resistant pathway
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Increased Mortality RTH𝛽𝛽 Okosieme, Lancet Diabetes Endocrinology 2023. PMID 37475119 Welsh cohort 55 patients RTH Beta 2750 Age and sex matched controls Median age 1 st event 56 vs 67 2.84 3.49 6.35
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Features of RTHβ: focus on heart Atrial Fibrillation (Risk is increased)
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Features of RTHβ: focus on heart Heart Failure (Risk is increased)
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Monitoring of RTHβ How? How often? Clinical Clinical assessment; symptoms Examination (weight, Blood Pressure, goitre, heart exam) Growth, school performance, hearing, behaviour Annual Blood tests Fasting bloods for Cholesterol and Diabetes tests TSH, FT4, FT3 Annual Scans DXA scan for bone health Bone age Xray (to assess bone maturation) Ultrasound thyroid scan (sometimes) Every 2-5 years Every 1-3 years As indicated Heart Health ECG (Sticker Test on chest, takes a few minutes) Holter (24 hr monitoring of heart rate) Echocardiogram (ultrasound test of heart) Annual Every 1-2 years Every 2-3 years Others Hearing Test ADHD testing Cardiology consultation request Offer first degree relative screening If indicated If indicated If indicated If desired Both Children and adults Children only Adults only
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Overview 1. What is Thyroid Hormone, and what does it do? 2. What is Resistance to Thyroid Hormone? 3.How is Resistance to Thyroid Hormone diagnosed? 4. Treatment options, Unmet Needs 5. Research
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RTH𝛽𝛽: Treatment T4T3 Hypothalamus Pituitary thyrotrophs Thyroid gland TRH TSH𝛽𝛽 >𝛼𝛼 High FT4 High FT3 Normal range TSH Goitre 70% Adapted from Moran C. Best Pract Res Clin Endocrinol Metab. 2015. PMID 26303090 Current treatment options are not optimal Conventional Treatments for an Overactive Thyroid Gland not recommended - Anti-thyroid drugs - Surgery to remove Thyroid gland - Radioiodine treatment These do not address the imbalance in Thyroid Hormone exposure in all tissues
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RTH𝛽𝛽: Treatments Muscle Bone CNS T4T3 Hypothalamus Pituitary thyrotrophs Thyroid gland TRH TSH Liver Raised Metabolic Rate Failure to Thrive in Childhood Low BMD Delayed bone age 29-47% Short stature 18-25% ADHD 40-60% Poor attention, concentration Reduced IQ 30% Anxiety Hyperkinetic behaviour 33-68% Palpitations 33-75%Non raised SHBG High Cholesterol Insulin Resistance Heart 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽 𝛼𝛼>𝛽𝛽𝛽𝛽 >𝛼𝛼 𝛽𝛽 >𝛼𝛼 High FT4 High FT3 Normal range TSH Goitre 70% Also: ENT infections 55% Hearing impairment 10-22% Adapted from Moran C. Best Pract Res Clin Endocrinol Metab. 2015. PMID 26303090 Sensitive pathway Resistant pathway
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Tiratricol Thyroid Stimulating Hormone (TSH) Thyroid Hormones T4 and T3 Tiratricol Tiratricol = Tri-iodothyroacetic Acid = TRIAC = “Emcitate”
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Tiratricol • Managed access programme at Cambridge • 8 adults with RTH𝛽𝛽 treated with Tiratricol monotherapy • Mean age 36 years • Duration of treatment 13-143 months (mean 40 months)
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Thyroid Hormone Concentration on Triac Treatment 1 2 0 10 20 30 40 50 60 fT4 Baseline to Nadir fT4 (pmol/L) A1 A2 A3 A4 A5 A6 A7 A8 Baseline Nadir 1 2 0 1 2 3 TT3 Baseline to Nadir fT4 TT3 (nmol/L) A1 A2 A3 A4 A5 A6 A7 A8 Baseline Nadir Free T4 Concentration Total T3 Concentration (LCMS)
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Symptoms on Tiratricol Treatment Baseline Nadir fT4 0 5 10 15 20 25 Hyperthyroid Symptom Score Timepoint HSS SCORE A1 A2 A3 A4 A5 A6 A7 A8 Mean HSS Score ↓ 8 Points
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Resting Energy Expenditure -1,5 -1 -0,5 0 0,5 1 1,5 2 2,5 3 3,5 A7 A1 A4 A8 A2 A3 A6 A5 Resting Energy Expenditure (Z score) Baseline Nadir
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Overview 1. What is Thyroid Hormone, and what does it do? 2. What is Resistance to Thyroid Hormone? 3. Ho 4. w might Resistance to Thyroid Hormone affect me? 6. Future Research Priorities
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Patient Webinar Feedback Treatments Understanding Heart Health Health Registry
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Tack Thank you Diolch
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Investor Day December 18, 2024 Q&A WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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Concluding remarks December 18, 2024 Mats Blom, Chairman of the Board WE CARE FOR THE RARE ©2024 Egetis Therapeutics. All rights reserved.
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Time (CET/ET) Subject Presenter(s) 15:00/9.00am Welcome, CHMP opinion & corporate update Nicklas Westerholm, CEO 15:10/9.10am MCT8 deficiency: recent advances with tiratricol Prof. Edward Visser, Erasmus Medical Center, NL 15:35/9.35am Q&A Visser & Westerholm 15:45/9.45am Global launch preparations Henrik Krook, Raymond Francot, Henna Oittinen-Corbinelli, Peter Verwaijen 16:20/10.20am Q&A Krook, Francot, Oittinen-Corbinelli, Verwaijen, Westerholm 16:30/10.30am Break 16:50/10.50am US regulatory pathway & ReTRIACt study Westerholm 17:00/11.00am US opportunity for Emcitate Anny Bedard, Ann-Marie Redmond 17:15/11.15am Q&A Bedard, Redmond, Westerholm 17:25/11.25am RTH-beta and the unmet medical need Prof. Aled Rees, Cardiff University, UK 17:50/11.50am Q&A Rees & Westerholm 17:55/11.55am Concluding remarks Mats Blom, Chairman of the Board 18:00/12.00pm Ends 148© 2024, Egetis Therapeutics. All rights reserved. Agenda: Egetis Investor Day, December 18, 2024
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Concluding remarks • Egetis – a de-risked biotech with substantial unlocked potential ‒ Strong data in clinical trials, demonstrating significant effects on key clinical outcomes ‒ Already passed most of typical drug development risks ‒ Significant market opportunity • CHMP opinion for Emcitate® (tiratricol) for the treatment of MCT8 deficiency ‒ Major step forward in building a sustainable rare disease company • Maturing into commercial stage ‒ EU launch ‒ NDA submission • Opportunity for indication expansion into RTH-beta 149 © 2024, Egetis Therapeutics. All rights reserved.