Slide 1: SynAct Pharma AB: Resolving Inflammation Through Melanocortin Biology
SynAct Pharma AB Resolving Inflammation Through Melanocortin Biology August 2022
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 Share Summary There is high unmet need in autoimmune and inflammatory diseases for efficacious and safe therapies – current therapies can • Founded in
Slide 4: SynAct Pharma – Pipeline overview
SynAct Pharma – Pipeline overview Asset Indication Preclinical Phase I Phase IIa Phase IIb Phase III Milestones 1st-line in CTA Filed 2Q22 combination Topline data Rheumatoid with MTX available 2H23 Arthritis Initiation 2H22 DMARD-IR Dose-range data available 2H23 AP1189 Restart amended Nephrotic sy
Slide 5: Targeted melanocortin agonism can provide both anti-inflammatory and pro-inflammation resolution activity
Targeted melanocortin agonism can provide both anti-inflammatory and pro-inflammation resolution activity 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 respons
Slide 6: AP1189 is an oral selective melanocortin agonist
AP1189 is an oral selective melanocortin agonist with both anti-inflammatory and pro-inflammation resolution activity MC1R MC2R MC3R MC4R MC5R Steroid dependent effects Targeted by AP1189 AP1189 selectively targets melanocortin receptors 1 and 3 (MC1R AP1189 exbibits anti-inflammatory activity v
Slide 7: SynAct Pharma: 2021 Accomplishments and 2022 Milestones
SynAct Pharma: 2021 Accomplishments and 2022 Milestones • 2021 was a productive year for SynAct: ⁃ Successfully completed two Phase 2a studies in early severe RA and COVID-19 respiratory insufficiency ⁃ Filled additional compositional patents that will extend IP protection past 2040 ⁃ Successfully t
Slide 8: AP1189 - Rheumatoid Arthritis
AP1189 - Rheumatoid Arthritis
Slide 9: RA affects about 1% of the global population
RA affects about 1% of the global population, and while there are several classes of approved therapies remission can remain elusive DMARD patients do not 1% Global population affected 70% achieve remission and require therapy escalation Biologics patients do not achieve $30b Expected global market
Slide 10: Preclinical models for RA demonstrate AP1189’s promising activity
Preclinical models for RA demonstrate AP1189’s promising activity Collagen-induced arthritis K/BxN-induced arthritis Combination treatment with (30 mg/kg, p.o.) (25/50 mg/kg, i.p.) methotrexate Cumulated disease disease score score Veh Veh 100 100% 25 mg/kg Clinical score (0–12) Proportion with seve
Slide 11: BEGIN: 4-week P2a trial of AP1189 + MTX in severely active early RA
BEGIN: 4-week P2a trial 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) severely active RA defined as CDAI >22, who • % of pati
Slide 12: Significant improvements seen in CDAI change and ACR20 with 100mg AP1189
Significant improvements seen in CDAI change and ACR20 with 100mg AP1189 Mean change in CDAI from baseline ACR 20/50/70 Response Rates 0 70 * 60,6 60 Change in CDAI score -5 50 Percentage (%) 40 37,9 33,3 -10 -9,3 30 24,2 -12 20 13,3 12,1 -15 6,9 10 -15,5 3,3 0 * 0 -20 Placebo (n=30) AP1189 50 mg (n
Slide 13: Improvements in DAS28 (CRP) and FACIT-Fatigue Scores
Improvements in DAS28 (CRP) and FACIT-Fatigue Scores 80 Responders going from severe to at 10 Mean change in FACIT-Fatigue score least moderate (>5.1 to <5.1 at 1-mo) 70 9 68 8 60 8 61,1 Mean Change in Score 50 7 Percentage (%) 40 5,9 6 36,8 4,8 30 5 20 4 10 3 0 2 Placebo (n=19) AP1189 50 mg (n=18)
Slide 14: AP1189 was safe and well tolerated in this 4-week study
AP1189 was safe and well tolerated in this 4-week study 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
Slide 15: 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 16: 100mg AP1189 ACR20 scores are in the range of the JAK inhibitors
100mg AP1189 ACR20 scores are in the range of the JAK inhibitors in P3 MTX-Naïve trials - Response rates should increase over time with 3-mo dosing as seen with JAKs and biologics 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-
Slide 17: The emerging AP1189 clinical profile supports RA development in multiple treatment positions
The emerging AP1189 clinical profiles supports RA development in multiple treatment positions Multiple RA Positioning Opportunities Emerging AP1189 Clinical profile • DMARD-IR - Patients who have had an • Once-Daily Oral Dosing – new oral solid incomplete response, lost response or are formulation r
Slide 18: High volume US rheumatologists expressed a high degree of interest in AP1189 for DMARD-IR patients
High volume US rheumatologists expressed a high degree of interest in AP1189 for DMARD-IR patients US Rheum Interest in AP1189 in DMARD-IR The combination of efficacy, safety, 10 tolerability and oral convenience positions 8 AP1189 well for DMARD-IR 6 4 8,9 9 Recent FDA labelling actions with RA JAK
Slide 19: Further Clinical Development in RA
Further Clinical Development in RA
Slide 20: EXPAND STUDY P2b study in previous treatment naïve RA patients
EXPAND STUDY P2b study in previous treatment naïve 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 posi
Slide 21: 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 22: AP1189 — Nephrology Program
SYNACT [J PHARMA AP1189 — Nephrology Program
Slide 23: MCRs are widely distributed in the kidney
MCRs are widely distributed in the kidney and provide both direct protective actions as well as provide immunomodulation and anti-inflammatory benefits Melanocortins can both directly protect MCRs are widely expressed in renal parenchymal cells1 Glomerular cells and provide immunomodulation 2 1. Cha
Slide 24: MC therapy is effective in reducing proteinuria and inducing remission
MC therapy is effective in reducing proteinuria and inducing remission in patients with nephrotic syndrome or diabetic nephropathy Select published studies with Acthar Gel in nephrology (Acthar is an ACTH preparation, ACTH is a melanocortin agonist) Study Patients Outcomes 44 patients with nephrotic
Slide 25: AP1189 is effective in pre-clinical nephritis models
AP1189 is effective in pre-clinical nephritis models 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 † 6 000 umol/24 hrs umol/24 hrs 3 000 umol/24 hrs
Slide 26: SynAct is in process of amending the ongoing P2a trial in iMN
SynAct is in process of amending the ongoing P2a trial idiopathic membranous nephropathy (iMN) ACE – inhibitor treatment 2:1 randomization Final analysis AP1189 100mg Follow up Placebo Follow up 3 Months 1 Month 24 hour urine 24 hour urine 24 hour urine collection collection collection • The P2a stu
Slide 27: AP1189 - Respiratory Insufficiency Program
AP1189 - Respiratory Insufficiency Program
Slide 28: RESOVIR-1: AP1189 versus placebo in hospitalized COVID-19 patients
RESOVIR-1: AP1189 versus placebo in hospitalized patients with COVID-19 with respiratory insufficiency 2:1 randomisation Interim analysis Final analysis Open label AP1189 100 mg QD (n=54) (n=6) AP1189 100 mg QD Placebo Up to 2 weeks Up to 2 weeks Key inclusion criteria Key secondary endpoints Posi
Slide 29: RESOVIR-1: Greater proportion of patients achieving respiratory recovery quicker than placebo
RESOVIR-1: Treatment with AP1189 resulted in a greater proportion of patients achieving respiratory recovery quicker than placebo Average respiratory recovery time* Cumulative respiratory recovery by Day 4* 12 60 10 50 9,9 50% Proportion of patients (%) 8 40 Days (n) 34% 6 30 5,9 4 20 2 10 0 0 AP118
Slide 30: RESOVIR-1: Patients treated with AP1189 were discharged faster
RESOVIR-1: Patients treated with AP1189 were discharged from hospital faster than those receiving placebo Average hospital discharge time Hospital discharge by Day 4 14 50 45 12 40 11,2 41% 10 Proportion of patients (%) 35 30 8 Days (n) 7,9 25 6 20 4 15 10 2 5 0% 0 0 AP1189 all (n=42) Placebo (n=18)
Slide 31: AP1189 can target viral-induced respiratory insufficiency in and beyond COVID-19
AP1189’s broad anti-inflammatory and pro-resolution mechanism can target viral-Induced respiratory insufficiency in and beyond COVID-19 21 US COVID-19 cases per 100,000 population COVID-19 require hospitalization1 Up to $54,000 hospital costs and almost $200,000 hospital charges per hospitalized pat
Slide 32: SynAct Pharma: 2021 Accomplishments and 2022 Milestones
SynAct Pharma: 2021 Accomplishments and 2022 Milestones • 2021 was a productive year for SynAct: ⁃ Successfully completed two Phase 2a studies in early severe RA and COVID-19 respiratory insufficiency ⁃ Filled additional compositional patents that will extend IP protection past 2040 ⁃ Successfully t
Slide 33: Thank You
SYNACT [J PHARMA Thank You
Slide 34: Leadership
SYNACT [J PHARMA Leadership
Slide 35: 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 36: SynAct Pharma – Board of Directors
SynAct Pharma – Board of Directors Torbjørn Bjerke, MD – Chairman Marina Bozilenko, BA, MA – Independent Board Member >25 years track record from pharma 30 years of investment banking and other healthcare industry as Head, R&D and CEO industry expertise, including raising >$30b in capital and (p
Slide 37: SynAct Pharma – Senior Advisors
SynAct Pharma – Senior Advisors Scientific Advisory Board Thierry Duvachelle, MD – Early Clinical Development Advisor Mauro Perretti, Professor MD, Independent consultant with Professor of immunopharmacology and dean of science (Dean More than 30 years experience with of Research) at Barts and L