Abivax Sa · EURONEXT:ABVX
Abivax Sa — Investor Presentation (February 2020)
34 slides from Abivax Sa's investor presentation, February 2020
Slide 1: Mobilizing the immune system to fight inflammatory and viral diseases, as well as cancer
Mobilizing the immune system to fight inflammatory and viral diseases, as well as cancer February, 2020 Breaking News 26/02/2020: Abivax includes First Patient in U.S. Phase 1/2 clinical trial of ABX196 to treat hepatocellular carcinoma
Slide 2: Forward looking statements
Forward looking statements This presentation contains information pertaining to Abivax S.A. (“Abivax”). Neither Abivax, nor its management, shareholders, directors, advisors, employees or representatives make any representation or warranty, express or implied, as to the fairness, the accuracy, compl
Slide 3: Key company facts
Key company facts Milestones Shareholder structure1 and market cap2 Focus on inflammatory Founded in 2013 diseases with ABX464 Truffle Capital by Truffle Capital in Sept. 2018 34% Sofinnova € 250m 46% Board & management Abivax went 2% Incubator & founders public in June 2015, 5% Public raising € 57.
Slide 4: Abivax: A strong and diversified pipeline
Abivax: A strong and diversified pipeline Lead generation Research Preclinical Phase 1 Phase 2 Phase 3 ABX464 Phase 2b on going Ulcerative colitis Inflammatory diseases ABX464 Phase 2b - FPI: Q2, 2020 Crohn’s disease ABX464 Phase 2a on going Rheumatoid arthritis HIV ABX464 Phase 2b, subject to third
Slide 5: ABX464: A promising candidate addressing attractive markets
ABX464: A promising candidate addressing attractive markets Coming from the proprietary Abivax library of compounds, Total market size biased to modulate RNA biogenesis (>2200 molecules); in inflammatory Close collaboration with EVOTEC diseases greater than Small molecule (quinoline), administered a
Slide 6: ABX464 showed efficacy in DSS mouse model
ABX464 showed efficacy in DSS mouse model* ABX464 protects mice from death DSS without ABX464 leads ABX464 protects intestinal in the DSS mouse model to intestinal damage structure Relative weight (%) 120 Induction of inflammation by DSS ABX464. 20 days ABX464. 60 days 110 100 90 Days 80 0 5 10 15 2
Slide 7: ABX464-101/102 study design: Phase 2a in ulcerative colitis
ABX464-101/102 study design: Phase 2a in ulcerative colitis • Randomized, double-blind, placebo controlled, multi-national study followed by an open-label maintenance study Induction study (ABX464-101) Open label extension (ABX464-102) 8 weeks of induction treatment (completed) First year completed,
Slide 8: Patient demographics and baseline disease characteristics
Patient demographics and baseline disease characteristics Groups generally well-balanced ABX-464 Placebo Total N = 23 N=9 N = 32 Age (years) Mean (Min-Max) 42.96 (20.0 – 73.0) 44.11 (20.0 – 64.0) 43.28 (20.0 -73.0) Sex Male 12 (52.2%) 8 (88.9%) 20 (62.5%) BMI (kg/m2) at Screening Mean 25.63 (17.6 -
Slide 9: ABX464-101: Statistically significant efficacy achieved for major endpoints (day 56)
ABX464-101: Statistically significant efficacy achieved for major endpoints (day 56) Clinical remission: ABX464 Placebo p Total Mayo Score (TMS) equal or (n=20/23) (n=9/9) value lower than 2 + no sub-score >1 PP/ITT PP/ITT (PP) Clinical remission* 35%/30% 11%/11% 0.16 Endoscopic improvement: Endosco
Slide 10: Mucosal healing in an ABX464 treated patient
Mucosal healing in an ABX464 treated patient Courtesy of Prof. Severine Vermeire Before ABX464 After ABX464 Mobilizing the immune system to fight inflammatory and viral diseases, as well as cancer 10
Slide 11: ABX464-101 Partial Mayo Score Results
ABX464-101 Partial Mayo Score Results Fast onset of action and clear responses in patients previously treated with biologics . Overall Patient Population Patients previously treated with biologics Change from Baseline Partial Mayo Score Change from Baseline Partial Mayo Score D0 D7 D14 D21 D28 D56 D
Slide 12: ABX464-102 Maintenance study: Patient disposition
ABX464-102 Maintenance study: Patient disposition ABX464 Evaluable patients at Week 8 Placebo Evaluable patients at Week 8 ABX464 -101 Induction study N = 20 N=9 Full regulatory clearance in 4/6 countries: 22/23 eligible patients enrolled into the maintenance study ABX464 50mg QD N=15 ABX464 50mg QD
Slide 13: Clinical Remission after induction (8 weeks) and Maintenance (52 weeks)
Clinical Remission after induction (8 weeks) and Maintenance (52 weeks) Double Blind ABX464 50mg versus Placebo (centrally randomised) Evaluable Patients /N=19 N=13 N=6 Induction Clinical Remission No Clinical Remission 8 weeks N=5 N=8 52 weeks ABX464 open label oral 50mg qd N=5 N=8 Maintenance CR :
Slide 14: Clinical Remission after induction (8 weeks) and Maintenance (52 weeks)
Clinical Remission after induction (8 weeks) and Maintenance (52 weeks) Double Blind ABX464 50mg versus Placebo ( centrally randomised) Evaluable Patients /N=19 N=13 N=6 Induction Clinical Remission No Clinical Remission 8 weeks N=1 N=5 52 weeks ABX464 open label oral 50mg qd N=1 N=5 Maintenance No
Slide 15: Clinical Remission after induction (8 weeks) and Maintenance (52 weeks)
Clinical Remission after induction (8 weeks) and Maintenance (52 weeks) Double Blind ABX464 50mg versus Placebo ( centrally randomised) Evaluable Patients /N=19 N=13 N=6 Induction Clinical Remission No Clinical Remission Clinical Remission No Clinical Remission 8 weeks N=5 N=8 N=1 N=5 52 weeks ABX46
Slide 16: Changes of Partial Mayo Score and fecal calprotectin during maintenance phase
Changes of Partial Mayo Score and fecal calprotectin during the maintenance phase for all patients and patients previously on biologics Partial Mayo Score – Mean Fecal calprotectin µg/g – median 4,0 350 3,5 300 3,0 250 2,5 200 2,0 150 1,5 100 1,0 0,5 50 0,0 0 Day 0 (OLE) M3 M6 M9 M12 Day 0 (OLE) M3
Slide 17: ABX464-102: Efficacy data at 52 weeks open label extension
ABX464-102: Efficacy data at 52 weeks open label extension ABX464 50 mg, PP ABX464 50 mg, ITT Clinical remission* 75% (N=16) 55% (12/22) Endoscopic improvement* 100% (N=16) 72% (16/22) Total Mayo Score reduction from maintenance baseline - 57% (N=16) - 52% (N=22) Partial Mayo score reduction from ma
Slide 18: ABX464 showed a good safety profile during induction and maintenance
ABX464 showed a good safety profile during induction and 12 months open label maintenance phase Safety profile consistent Overall: No deaths, no malignancies, no severe infections, no significant with previous and ongoing changes in the laboratory parameters including blood cell counts clinical stud
Slide 19: Conclusions
Conclusions Good safety and tolerability of chronic treatment with ABX464 50mg QD in patients with UC ABX464 oral 50mg QD Conclusion is further supported by safety analysis in drug candidate for moderate healthy volunteers and HIV infected patients (no serious adverse reactions, no severe infections
Slide 20: ABX464 ongoing and planned studies
ABX464 ongoing and planned studies Phase 2b in ulcerative colitis: • Conducted with IQVIA as CRO Phase 2b study in 232 patients with moderate to severe • 232 patients, 17 countries, 150+ study sites ulcerative colitis is currently ongoing in Canada and Europe, • 4 study arms (placebo, 25, 50, 100 mg
Slide 21: ABX464 and ABX464-N-Glu: Mechanism of Action
ABX464 and ABX464-N-Glu: Mechanism of Action Mobilizing the immune system to fight inflammatory and viral diseases, as well as cancer 21
Slide 22: miR-124 is a well-known modulator of inflammation
miR-124 is a well-known modulator of inflammation 250 Numbers of articles Between 2005 and 2019, more than 1100 scientific articles 200 150 have been published on miR-124 including 133 papers 100 highlighting the importance of miR-124 in dampening the 50 0 inflammatory process 2005 2007 2009 2011 20
Slide 23: miR-124 is an endogenous microRNA that regulates gene expression
miR-124 is an endogenous microRNA that regulates gene expression by preventing translation of target mRNAs (cyto- and chemokines) miR-124 dampens pro-inflammatory cyto- and chemokine expression miR-124 reduces translation of pro- miR-124 inflammatory cyto- and chemokines Cytokine/chemokine mRNAs DNA
Slide 24: miR-124 can modulate multiple pathways involved in inflammation
miR-124 can modulate multiple pathways involved in inflammation STAT3 (A key regulator of JAK signaling, decreases miR-124 can reduce the IL6 and TNFa) translation of targets’ mRNAs IL6R (reducing IL6 action) and thereby protein expression: MCP1 (Macrophage chemoattractant protein 1) PTBP1 (a splici
Slide 25: ABX464 is the only small molecule that can specifically induce miR-124 expression
ABX464 is the only small molecule in clinical development that can specifically induce miR-124 expression ABX464 main metabolite, ABX464-N-Glu also induces miR-124 expression Out of 1105 microRNAs, miR-124 was the only microRNA upregulated Mobilizing the immune system to fight inflammatory and viral
Slide 26: ABX464 and ABX464 N-Glu induce upregulation of miR-124 in human macrophages
Both ABX464 and ABX464 N-Glu induce upregulation of miR-124 in purified human monocyte-derived macrophages and decrease MCP1/CCL2 expression miR-1246 controls Induction Fold Induction 4 ABX 3,36 2,96 3 2 1,00 1 0 DMSO ABX GLUC Gluc Mobilizing the immune system to fight inflammatory and viral disease
Slide 27: ABX464 reduces pro-inflammatory cytokines and chemokines in the colon of DSS mice
In ABX464 treated DSS mice, ABX464 reduces pro-inflammatory cytokines and chemokines in the colon ABX464 induces miR-124 and reduces pro-inflammatory cytokines in PBMC and in colon tissue ABX464 treated DSS mice Chebli & al. Scientific Reports 2017 Jul 7;7(1) Mobilizing the immune system to fight in
Slide 28: ABX464 induces miR-124 expression by inducing splicing of a single lncRNA
ABX464 induces miR-124 expression by specifically inducing the splicing of a single Long-Non-Coding RNA (lncRNA00599-205) miR-124 is transcribed from 3 genomic loci, but ABX464 induces miR-124 expression only from Locus 1 Locus miR-124-1 contains the Long Non-Coding RNA, lncRNA00599-205, whose splic
Slide 29: ABX464 and ABX464-N-Glu bind to the Cap Binding Complex
ABX464 and ABX464-N-Glu bind to the Cap Binding Complex (CBC), which is key factor for RNA processing CBC binds to the 5’ end of all RNAs generated in the nucleus and ensures their processing Binding of ABX464 and ABX464 N-Glu to CBC was demonstrated by: ➢ UV crosslinking with chemically modified AB
Slide 30: ABX464 and ABX464-N-Glu bind to the same site on CBC
ABX464 and ABX464-N-Glu bind to the same site on CBC CBC 20 ABX 464 ABX 464-NGlu CBC 80 ABX464-CBC at 5.8A resolution ABX464 N-Glu-CBC at 4.6A resolution Mobilizing the immune system to fight inflammatory and viral diseases, as well as cancer 30
Slide 31: Inducing specifically the biogenesis of miR-124 opens a novel way to treat inflammatory diseases
Inducing specifically the biogenesis of miR-124 by the drug candidate ABX464 in immune cells opens a novel way to treat Inflammatory Diseases LINC00599 464 Spliced Lnc Changes in Therapeutic effects in miR-124 secretion of inflammatory diseases cyto- and chemokines by immune cells miR-124 Reduction
Slide 32: Summary ABX464 mechanism of action
Summary ABX464 mechanism of miR-124 anti-inflammatory properties have been extensively described in the literature action Abivax’s oral drug candidate ABX464 is the only small molecule in clinical development that specifically induces the overexpression of a miR-124 miR-124 expression by ABX464 is t
Slide 33: Interview of Prof. Sandborn – UEG Week 2019
Interview of Prof. Sandborn – UEG Week 2019 https://youtu.be/VB4fo0xkycY Mobilizing the immune system to fight inflammatory and viral diseases, as well as cancer 33
Slide 34: Highly experienced Executive Committee
Highly experienced Executive Committee • Prof. Hartmut Ehrlich, M.D. • Chief Executive Officer Former Head of Global R&D, Baxter BioScience • Didier Blondel • Pierre Courteille • Jérôme Denis • Alexandra Pearce • Chief Financial Officer & Pharmacist, MBA Ph.D. Ph.D. Board Secretary • Chief Commercia