Slide 1: Resolving Inflammation Through Melanocortin Biology
SynAct Pharma AB Resolving Inflammation Through Melanocortin Biology ABG 19 May 2022 NON- CONFIDENTIAL
Slide 2: Forward Looking Statements
Forward Looking Statements Certain information set forth in this presentation contains “forward-looking information”, including “future-oriented financial information” and “financial outlook”, under applicable securities laws (collectively referred to herein as forward-looking statements). Except fo
Slide 3: SynAct Pharma – Highlights
SynAct Pharma – Highlights § SynAct Pharma is focused on the development of novel and first-in-class agonists that target the melanocortin system Facts and figures § There is high unmet need in autoimmune and inflammatory diseases for efficacious and safe therapies – current therapies can present si
Slide 4: SynAct Pharma – Pipeline overview
SynAct Pharma – Pipeline overview Next Asset Indication Preclinical Phase I Phase IIa Phase IIb Phase III milestone Filing CTA Q2 Rheumatoid Arthritis 2022 – First line treatment High level data Q3 2023 Pre-IND Rheumatoid Arthritis meeting Q2 2022 – DMARD-IR IND filing AP1189 PH2b H2 2022 Redesigned
Slide 5: Inflammation Resolution can correct dysregulated inflammation without inducing immunosuppression
Inflammation Resolution can correct dysregulated inflammation without inducing immunosuppression The inflammatory response 1 Inflammatory response effectively controlled in extent and time – protects tissues and limits damage 2 Pathways activated to safely terminate the inflammatory response and pro
Slide 6: AP1189: A First-in-Class Selective Melanocortin Receptor 1 and 3 Agonist
AP1189: A First-in-Class Selective Melanocortin Receptor 1 and 3 Agonist MC1R MC2R MC3R MC4R MC5R Steroid dependent effects Targeted by AP1189 § AP1189 was designed to activate melanocortin receptors 1 and 3 § AP1189 exbibits anti-inflammatory activity through stimulation of (MC1R and MC3R), which a
Slide 7: AP1189 is a selective melanocortin agonist with anti-inflammatory and resolution activity
AP1189 is an selective melanocortin agonist having both anti-inflammatory and inflammation resolution activity without immunosuppression § The melanocortin system is an ancient modulatory system comprising a family of 5 widely dispersed melanocortin receptors and a set of naturally occurring melanoc
Slide 8: AP1189 – First-in-class biased MCR agonist – novel mode of action
AP1189 – First-in-class biased MCR agonist – novel mode of action MC1 receptor activation in transfected cells1 AP1189 X § First-in-class biased melanocortin receptor type 1 and 3 agonist- potent inducer of ERG phosphorylation- weak inducer of cAMP stimulation1 § Homology modelling from recently pub
Slide 9: AP1189 – Combined anti-inflammatory and pro-resolving effects in vivo
AP1189 – Combined anti-inflammatory and pro-resolving effects in vivo ? AP1189 Administration at disease induction in peritonitis1 • AP1189 induces anti-inflammation as shown by reduced accumulation of neutrophils and reduced concentration of pro-inflammatory cytokines following systemic administrat
Slide 10: AP1189 – Biased agonism is not associated with melanogenesis
AP1189 – Biased agonism is not associated with melanogenesis X B16-F10 melanoma cells following 24 hours incubation AP1189 § Melanogenesis and thereby skin pigmentation is an unwanted side effect of melanocortin receptor stimulation § Melanogenesis in melanocytes is mediated by cAMP X accumulation f
Slide 11: AP1189 addresses key limitations faced in the development of melanocortin agonists
AP1189 addresses key limitations faced in the development of melanocortin agonists AP1189 – the first oral selective MC agonist • The naturally occurring melanocortin agonists including ACTH PK profile following repeat dosing in man1 (Acthar) and the majority of designed analogs are peptides 1 200 w
Slide 12: Ready for development with once daily dosing with tablets
Ready for 12 weeks development with once daily dosing with tablets Toxicology: AP1189-CS004 STUDY – ORAL • Three Months Tox studies with recovery groups DOSING WITH 100 MG successfully been completed Suspension (n=12) Tablet Acetate (n=12) 350 • NOAEL rat: 100 mg/kg 300 • NOAEL pig: 50 mg/kg AP1189
Slide 13: AP1189 in COVID-19 patients with respiratory insufficiency
AP1189: Once daily dosing to COVID-19 pts with respiratory insufficiency: patients achieved recovery (no need for supplementary oxygen) 4 days and hospital discharge 3.5 days earlier than placebo-treated patients Average respiratory recovery time* Average hospital discharge time 12 12 P=0.04 11,2 10
Slide 14: AP1189 PoC as first line treatment in combination with MTX
AP1189- PoC as first line treatment in combination with MTX- -4 wks once daily oral dosing Statistically significant reduction in disease activity Statistically significant higher ACR20 response rate (primary study readout) (secondary study readout) 0 70 * 60,6 60 Change in CDAI score -5 50 Percenta
Slide 15: AP1189 is well protected with composition running through 2042
AP1189 is well protected with composition running through 2042 with additional layers of protection Portfolio Coverage Composition of Matter Granted: Genus of AP1189 Pending: Polymorphs; Salts* IP Strategy Formulation Pending: Oral administration/tablets* Method of Use Granted (EP): Arthritis/AP1189
Slide 16: The BEGIN study
The BEGIN study A double-blind, multi-centre, two-part, randomized, placebo-controlled study of the safety, tolerability, and efficacy of 4 weeks of treatment with AP1189 in early rheumatoid arthritis patients with active joint disease Completed Q4 2021
Slide 17: BEGIN: P2a POC 4-week study of AP1189 + MTX in severely active early RA
BEGIN: P2a POC 4-week study of AP1189 + MTX in severely active early RA Study Population Primary safety endpoint Primary efficacy endpoint Adult patients (aged 18 to 85 years) with • Mean change in CDAI or Safety of AP1189 vs placebo (AEs and SAEs) severe RA defined as CDAI >22, who are • % of patie
Slide 18: Baseline characteristics of randomized population
Baseline characteristics of randomized population Placebo (n=34) AP1189 50 mg (n=35) AP1189 100 mg (n=36) Female, % 79.4 77.1 77.8 Age (years) Mean±SD 56.4±13.1 56.4±13.1 55.3±13.9 Median (range) 61 (26–78) 57 (28–79) 56.5 (27–77) 18–64 years/65–84 years (%) 73.5/26.5 71.4/28.5 72.2/27.8 Race, White
Slide 19: Baseline disease activity in efficacy assessment population
Baseline disease activity in efficacy assessment population Placebo (n=30)* AP1189 50 mg (n=29)* AP1189 100 mg (n=33)* CDAI 36.7±8.7 36.1±9.7 39.5±9.1 SJC 10.4±3.7 10.2±3.9 12.1±4.9 TJC 13.7±6.1 13.6±6.0 15.2±6.0 DAS-28 5.5±1.0 5.4±0.8 5.7±0.9 Patient Global Assessment (VAS) 6.5±1.8 6.1±2.1 5.8±2.2
Slide 20: BEGIN P2a POC RA study topline results
BEGIN P2a POC RA study topline results: AP1189 100mg once-daily oral dose group was efficacious and safe • After 1-mo of treatment, the 100mg once-daily oral AP1189 group had: o Significantly better CDAI improvement Vs placebo and that was above the established minimally important clinical differenc
Slide 21: Change in CDAI score
AP1189 100mg group had a mean improvement in CDAI above the established minimally important clinical difference (MCID)+ score and was significant Vs placebo CDAI at Baseline and End of Treatment Mean change in CDAI from baseline to Week 4 40 39,5 0 35 36,7 36,1 Change in CDAI score 30 -5 25 27,4 24,
Slide 22: Proportion of patients achieving ACR20/50/70 response at 1-mo
Proportion of patients achieving ACR20/50/70 response at 1-mo 70 ACR 20/50/70 Response Rates * 60,6 60 50 Percentage (%) 40 37,9 33,3 30 24,2 20 13,3 12,1 10 6,9 3,3 0 0 Placebo (n=30) AP1189 50 mg (n=29) AP1189 100 mg (n=33) ACR20 ACR50 ACR70 Robust 1-Mo ACR20/50/70 response rates for 100mg AP1189
Slide 23: Change in DAS28 (CRP) in very active subset
Change in DAS28 (CRP) - subset of ‘very active’ with >5.1 score at baseline Patients going from ‘very active’ (>5.1) to Mean Change in DAS28 from Baseline to Week 4 80 ‘active’ (5.1-3.2) 0 70 68 Change in DAS28 60 61,1 Percentage (%) 50 40 -1 -0,9 -0,9 30 36,8 -1,3 20 10 0 -2 Placebo (n=19) AP1189 5
Slide 24: Mean change in FACIT-Fatigue score at 1-mo
Mean change in FACIT-Fatigue score at 1-mo 10 Mean change in FACIT-Fatigue score from baseline 9 8 8 Mean Change in Score 7 5,9 6 5 4,8 4 3 2 Placebo (n=30) AP1189 50 mg (n=29) AP1189 100 mg (n=33) Mean change in 100mg group is 2x the established minimally important clinical difference (MCID)+ (+) C
Slide 25: Primary safety endpoint: AEs
Primary safety endpoint: AEs Placebo (n=32) AP1189 50 mg (n=31) AP1189 100 mg (n=35) Total (n=98) SAEs, n (%) 0 0 0 0 AEs, n reported from baseline and on 21 38 27 86 AE severity (mild/moderate/severe) 18/2/1 26/12/0 22/5/0 66/19/1 Discontinuation due to IMP related AEs, n (%) 0 0 0 0 Discontinuatio
Slide 26: AP1189 1-mo ACR20 scores comparable to JAKs
AP1189 100mg 1-mo ACR20 scores are comparable to JAKs ACR20 in MTX-Naïve P3 trials - Response rates should increase over time with 3-mo dosing as with JAKs 90 1-mo actual and 3-mo proj. ACR20 Rates Range of 80 3-mo JAK data (75-80%) 70 Range of 60 1-mo JAK data ACR20 (%) (58-65%) 50 Projected 61%* A
Slide 27: BEGIN study summary
BEGIN study summary • In this 4-week study, patients treated once-daily with 100 mg AP1189 achieved a significantly greater reduction in mean Clinical Disease Activity Score (CDAI) as compared to placebo • Change in disease activity from severe to moderate was numerically higher in groups treated wi
Slide 28: AP1189 - Rheumatoid Arthritis: Positioning and next development steps
AP1189 -Rheumatoid Arthritis Positioning and next development steps
Slide 29: The current treatment paradigm for RA leaves significant potential for new therapies
The current treatment paradigm for RA leaves significant potential for new meaningful therapies RA diagnosis Unmet need in the RA treatment paradigm DMARD monotherapy (typically methotrexate) § Rheumatologists tend to treat aggressively with the variety of treatment options available, but RA treatme
Slide 30: AP1189 has the potential to be positioned for several potential uses in RA
AP1189 has the potential to be positioned for several potential uses in RA Multiple RA Positioning Opportunities Emerging AP1189 Clinical profile § The emerging AP1189 clinical profile supports RA development at several treatment inflection points: • Once-Daily Oral Dosing – new oral solid formulati
Slide 31: Rheumatologists expressed high degree of interest in AP1189 in DMARD-IR
Rheumatologists expressed high degree of interest in AP1189 in DMARD-IR Rheum Interest in AP1189 in DMARD-IR 10 The combination of efficacy, safety, tolerability and 8 oral convenience positions AP1189 well for 6 4 8,9 9 DMARD-IR Recent FDA labelling actions with JAKs in RA reduces direct competitio
Slide 32: High Volume US Rheumatologists Reacted Very Favorably to the AP1189 Profile
High Volume US Rheumatologists Reacted Very Favorably to the AP1189 Profile Respondents were all pleased that so many of their unmet needs were addressed with the AP1189 Profile: Novel MOA Oral ROA Clean Safety Profile Potential to be combined with other advanced therapies A We know from oncology…th
Slide 33: Further Clinical Development in RA
Further Clinical Development in RA
Slide 34: EXPAND STUDY P2 study in previous treatment naive RA patients
EXPAND STUDY P2 study in previous treatment naive RA patients Patient Population: § Previous treatment naïve, eligible Final analysis AP1189 100* mg, cont. MTX for initiation of DMARD treatment (MTX) § CDAI >22 at baseline – min of 6 Placebo, cont. MTX swollen and tender joints § Rheuma factor posit
Slide 35: AP1189 - Proposed adaptive P2 trial design in DMARD-IR patients
AP1189- Proposed adaptive P2 trial design in DMARD-IR patients Part A – 4 weeks dosing Part B – 12 weeks dosing AP1189 60* mg, cont. MTX AP1189 Dose 1; cont. MTX Interim analyses Final analysis AP1189 80* mg, cont. MTX AP1189 Dose 2, cont. MTX (optional) AP1189 100* mg, cont. MTX Placebo, cont. MTX
Slide 36: High level milestones for 2022 in Rheumatoid Arthritis
AP1189 as novel compound treatment of Rheumatoid Arthritis- High level milestones for 2022 Q2 2022 § Conduct FDA meting § File CTA for EXPAND study – 12 weeks efficacy study in treatment naïve pts (100 mg vs placebo) Q4 2021 H2 2022 § Report BE data on new tablet § Open IND followed by formulation-
Slide 37: Important milestones 2022 and 2023
Important milestones 2022 and 2023 Kvartal 4 2023 q Data on NS Kvartal 3 2023 q Topline results EXPAND q Interimdata DMARD-IR Kvartal 4 2022 part I q Initiate DMARD-IR Kvartal 3 2022 q IND q Initiate EXPAND Kvartal 2 2022 study q Rights issue q Pre-IND q Re-design NS q Nasdaq uplift 37
Slide 38: AP1189 – Phase II Development in Nephrotic Syndrome
AP1189 – Phase II Development in Nephrotic Syndrome Positioning as alternative to immuno-suppressive Therapy
Slide 39: Nephrotic Syndrome
Nephrotic Syndrome Unmet Need c.150k Prevalence across US and EU § Limited clinical guidelines exist for the proper management of Nephrotic Syndrome § Management consists of therapeutic treatment with diuretics, ACE inhibitors, anti-infectives, lipid-lowering agents, and immunosuppressants Limited T
Slide 40: MC1R-mediated pathways activated in Nephrotic Syndrome
MC1R-mediated pathways activated in Nephrotic Syndrome MC1R & Nephrotic Syndrome § MC1R expression is increased in nephrotic syndrome, both in rat models and in humans § MC1R agonism induced protection of podocytes from stress fiber loss § Actin stabilization through the MC1R consisted of ERK1/2 dep
Slide 41: AP1189 Shows Benefits in Models of Nephritis
AP1189 Shows Benefits in Models of Nephritis Vehicle (n=12) Membranous nephropathy rat model (passive Heymann Nephritis) AP1189 (n=12) Creatinine Clearance (ml/min/g KW) Albumin excretion rate Reduction in AER (day 14-42) 1,0 8 000 4 000 0,8 † umol/24 hrs umol/24 hrs 6 000 umol/24 hrs 3 000 0,6 * 0,
Slide 42: AP1189 – Phase IIa Trial in Nephrotic Syndrome
AP1189 – Phase IIa Trial in Nephrotic Syndrome- - Revision aim to apply 12 weeks dosing with tablets is pending ACE – inhibitor treatment 2:1 randomization Final analysis AP1189 100mg Follow up Placebo Follow up 4 weeks 4 weeks 24 hour urine 24 hour urine 24 hour urine collection collection collecti
Slide 43: Leadership
SYNACT JJ PHARMA Leadership
Slide 44: SynAct Pharma – Experienced Management
SynAct Pharma – Experienced Management Jeppe Øvli Øvlesen, MBA – CEO Patrik Renblad, MSc – CFO § >20 years of CEO experience § >20 years’ experience from finance § Founding Board Member of more than roles in pharma 10 biotech/medtech companies § Former head of R&D Finance at LEO § Co-founder of TXP
Slide 45: SynAct Pharma – Board of Directors
SynAct Pharma – Board of Directors Torbjørn Bjerke, MD – Chairman Thomas Jonassen, MD – Board Member, Founder § >25 years track record from pharma § Associate Professor, KU in Denmark industry as Head, R&D and CEO § Visiting Professor, WHRI, UK (private and public), BD § Co-founder of TXP Pharma and
Slide 46: SynAct Pharma – Board of directors
SynAct Pharma – Board of directors Kerstin Hasselgren, MSc – Board Member § CFO Xspray Pharma, NASDAQ Stockholm § Former VP Corporate Business Control SSAB, CFO Alstom Transport Nordic, VP Finance Global Operations AstraZeneca and VP Finance Global FoU AstraZeneca. § Board member since 2022 46