Corporate Overview Our Value, Our Science, Our Focus

Transcription

1 Crprate Overview Our Value, Our Science, Our Fcus 2017 Achillin Pharmaceuticals. All rights reserved. NASDAQ:ACHN

2 Frward-Lking Statements This presentatin includes frward-lking statements within the meaning f the Private Securities Litigatin Refrm Act f 1995 that are subject t risks, uncertainties and ther imprtant factrs that culd cause actual results t differ materially frm thse indicated by such frward-lking statements. Achillin may use wrds such as expect, anticipate, prject target, intend, plan, aim, believe, seek, estimate, can, culd, fcus, will, lk frward, cntinue, gal, strategy, may and similar expressins t identify such frward-lking statements. These frward-lking statements are abut Achillin Pharmaceuticals, Inc. and its business and prspects, including, withut limitatin, statements regarding drug discvery, research, clinical develpment, timing f anticipated clinical trials and clinical data fr ur prduct candidates, ur expectatins regarding the ptential safety, efficacy and clinical utility fr ur prduct candidates, regulatry apprval prcesses, market pprtunities, strategic gals, ur cllabratin with Janssen in HCV, intellectual prperty, cmpetitin, and financial results. T the extent that statements cntained in this presentatin are nt descriptins f histrical facts, they are frward-lking statements reflecting management s current beliefs and expectatins. Varius imprtant factrs may cause differences between ur frward-lking statements and actual results, including withut limitatin, unexpected r unfavrable safety r efficacy data, lwer than expected enrllment rates in clinical trials, changes in the cmpetitive landscape fr ur prduct candidates, changes in the regulatry envirnment, changes in market cnditins r future demand fr ur drug candidates, the inability t prtect ur intellectual prperty, ur freedm t perate under third party intellectual prperty, the risk that Janssen may nt advance the HCV prgram in the time frames prjected r at all, ur need fr future capital, the risk f litigatin r ther disputes, and general market and ecnmic cnditins. These and ther risks and uncertainties are described in the reprts filed by Achillin with the U.S. Securities and Exchange Cmmissin ( SEC ), including its annual reprt n Frm 10-K and quarterly reprts n Frm 10-Q, and subsequent filings with the SEC frm time t time. Yu shuld read these reprts, including the Risk Factrs cntained in these reprts with the understanding that ur actual future results may be materially different frm what we expect. All frward-lking statements cntained in this presentatin speak nly as f the date heref, and Achillin undertakes n bligatin t update any f these statements, except as required by law. 2 Crprate Overview

3 Our Value

4 Achillin s Value Prpsitin LEADER IN COMPLEMENT AP INHIBITION First t Clinically Demnstrate AP suppressin with Factr D in Healthy Subjects Lead clinical prgram ACH-4471 advancing thrugh Phase 2 develpment Advancing multiple inhibitrs tward clinical develpment >30 published patent applicatins fr factr D inhibitrs Dysregulatin f the AP is Assciated with Diseases such as C3G, PNH, & GA/dry AMD Advancing Cmplement Bilgy thrugh internal research and external cllabratins Wrldwide HCV Cllabratin with Janssen Once daily regimen achieved 100% cure after six weeks f treatment Glbal Phase 2b OMEGA-1 study cmpleted enrllment with results anticipated 2H17 $386.6 MM in Cash and Equivalents as f March 2017 Strng financial psitin t advance multiple prgrams thrugh key inflectin pints GOAL TO DEVELOP DRUGS TO HELP PATIENTS WITH UNDERSERVED NEEDS 4 Crprate Overview

5 Achillin Develpment Prtfli PROGRAM DELIVERY DISCOVERY : PRECLINICAL CLINICAL Discvery DMPK & Safety Preclinical Phase 1 Phase 2 Phase 3 HEPATITIS C JNJ-4178 (dalasvir+al-335+simeprevir) PNH ACH-4471: Factr D Inhibitr C3G ACH-4471: Factr D Inhibitr Oral 6- and 8-wks treatment duratin Oral Oral AP-mediated diseases Next-Generatin Factr D Inhibitrs Oral GA/dry AMD Factr D inhibitrs Ophthalmic fd: Factr D DMPK: Drug Metablism/Pharmackinetics QD: Once Daily 5 Crprate Overview

6 Our Science

7 Cmplement System The Bdy s Innate Defense Cmplement activatin and regulatin are induced by mre than 30 prteins that are present in plasma (fluid phase) and n cell surfaces (slid phase) The cmplement system is cmpsed f three distinct pathways Classical (CP), Lectin (LP) and Alternative (AP) which lead t a cmmn terminal pathway Activatin f these pathways leads t: Recgnitin and eliminatin f pathgens Recruitment f adaptive immunity Facilitatin f remval f appttic cells Dysregulatin f the cmplement alternative pathway can induce inflammatin and tissue damage and is assciated with a variety f diseases Dysregulatin f the AP is the underlying cause f disease including PNH, C3G and GA/dry AMD 7 Crprate Overview

8 Cmplement System Pathway Activatin Simplified view f the Classical, Lectin and Alternative Pathways Cmplement factr D Surce: Data n file. Achillin Pharmaceuticals, Inc. 8 Crprate Overview

9 Mechanism Matters: Trigger Pint Inhibitin Factr D A critical cntrl pint specifically within the AP Trigger Pint Inhibitr Prevents amplificatin and mdulates dwnstream cmplement cascade Surce: Data n file. Achillin Pharmaceuticals, Inc. 9 Crprate Overview

10 Mechanism Matters: Trigger Pint Inhibitin Factr D A critical cntrl pint specifically within the AP Trigger Pint Inhibitr Prevents amplificatin and mdulates dwnstream cmplement cascade Surce: Data n file. Achillin Pharmaceuticals, Inc Crprate Overview

11 Mechanism Matters: Trigger Pint Inhibitin Factr D A critical cntrl pint specifically within the AP Trigger Pint Inhibitr Prevents amplificatin and mdulates dwnstream cmplement cascade Surce: Data n file. Achillin Pharmaceuticals, Inc Crprate Overview

12 Diseases f The Alternative Pathway Benefits f Factr D Inhibitin MECHANISM MATTERS PNH C3G GA / DRY AMD AP nrmal. RBCs lack CD55 & CD59 making them susceptible t the AP-mediated hemlysis C5-targeted therapies result in subptimal cntrl f hemlysis due t excessive depsitin f C3b n PNH erythrcytes Factr D inhibitrs can reduce C3b prductin and have the ptential t imprve treatment utcmes fr PNH patients AP is ver activated causing pathphysilgy f C3G C3b fragments cntinuusly frmed and depsit in the glmeruli affect kidney functin Factr D inhibitrs can reduce C3b prductin, thus prviding disease mdifying effect fr C3G AP implicated in prgressin: Factr D is a validated target fr GA Physicchemical prperties f ACHN fd inhibitrs cnvey distinct advantages ver bilgics Factr D inhibitrs can ptentially be used with extended delivery technlgy ( 3 mnths) 12 Crprate Overview

13 Achillin Factr D Inhibitrs Advancing Nvel Small Mlecule Cmpunds ~2000 small mlecule factr D inhibitrs Primary pharmaclgy Secndary pharmaclgy ADME/Safety Lead prgrams ACH-4471:Factr D Cmplex 0.8 A X-ray Structure Achillin s cmplement factr D inhibitr platfrm has generated: - ACH-4471: first ptent, specific, ral inhibitr f fd advanced int Phase 2 - Next generatin factr D inhibitrs advancing tward clinical develpment YE17 - Multiple mlecules being prgressed fr extended (3+ mnths) phthalmic delivery Surce: Data n file. Achillin Pharmaceuticals, Inc Crprate Overview

14 Alternative Pathway Achillin s Cmplement Factr D Inhibitr Platfrm Achillin has generated a platfrm f ptent and specific inhibitrs f the alternative pathway (AP) These mlecules: Reversibly bind t factr D with highaffinity Inhibit the AP by preventing the interactin between factr D and factr B Can be ptimized fr ral systemic r phthalmic administratin X Factr D ACH-4471 inhibiting cleavage f factr B by factr D Factr B C3B A disruptive apprach t ptentially treat cmplement AP-mediated diseases such as C3G, PNH, and dry AMD 14 Crprate Overview

15 Our Areas f Fcus

16 Parxysmal Ncturnal Hemglbinuria (PNH) Unmet Patient Needs Smatic mutatin results in red bld cells (RBCs) deficient in CD55 and CD59 Prevalence f apprximately 4,000 U.S and 4,000 EU patients with an incidence f 3-10 cases/millin/year 1 Current treatment is effective but a significant prtin f PNH patients achieve subptimal respnse 2,3,4 Even n currently available treatment, PNH patients cntinue t have unmet needs: Up t a third f patients have less than nrmal hemglbin levels Nearly 1 in 6 patients remain dependent n bld transfusins Up t 20% f patients require increased dses f mab C5 inhibitr All patients require frequent treatment administratin by intravenus infusin Surce: 1. Sliris Package Insert, Schubert et al. Triumph, 2008, Br J Hemta. 3. Hiillmen et al, Lng term fllw-up, 2013, Br J Hema. 4. Brdsky et al, Shepard, 2008, Bld. Data n file. Achillin Pharmaceuticals, Inc Crprate Overview

17 Parxysmal Ncturnal Hemglbinuria (PNH) Factr D and Prtectin frm Intra- / Extra-vascular Hemlysis Type III PNH erythrcytes N treatment Intravascular hemlysis Anti-C5 therapy C3 fragment depsitin Breakthrugh and Extravascular hemlysis C3 fragment psnizatin via RES macrphages (liver, spleen) Factr D inhibitr Prtected PNH erythrcytes PNH treated with a fd inhibitr may be prtected frm bth Intra- and Extravascular hemlysis Adapted frm Luzzatt L, Risitan AM, Ntar R. Haematlgica 2010;95(4): Harder M., et al. Bld. 2017; 129(8) Crprate Overview

18 C3 Glmerulpathy (C3G) A Rare Disease with N Available Treatment C3G includes bth Dense Depsit Disease (DDD) and C3 glmerulnephritis (C3GN) Estimated prevalence f 8-12 peple affected per millin in majr markets Incidence rate f 1-2 per millin patients diagnsed with C3G n an annual basis There are n apprved treatments fr patients with C3G Nn-specific treatment appraches include bld pressure cntrl and brad immunsuppressin Renal Survival (%) DDD AND C3GN IMPACT ON RENAL SURVIVAL Significant unmet medical need as nearly half f C3G patients prgress t endstage renal disease 30-50% prgress t ESRD within 10 years ~70% f patients experience disease recurrence pst renal transplant, with a 50% chance f graft lss Years frm Diagnsis C3GN (n=49) DDD (n=26) Barbur et al. (2015); NICE C3G Evidence Summary (2015); Surces: Servais et al (2013); Medjeral-Thmas et al (2014); Data n File. Achillin Pharmaceuticals Crprate Overview

19 Gegraphic Atrphy (GA) and Dry AMD Factr D Inhibitrs in Ophthalmlgical Disease Gegraphic Atrphy (GA), advanced frm f Age-related Macular Degeneratin (dry AMD) Genetic plymrphisms in multiple alternative cmplement pathway lci are assciated with GA and the risk f dry AMD Factr D is a validated target Phase 2 results with lampalizumab reprted 44% reductin rate in gegraphic atrphy at 18 mnths in patients with factr I plymrphs Phase 3 trial with lampalizumab underway evaluating intravitreal injectins every 4 r 6 weeks Achillin s small mlecule factr D inhibitrs leverage the same mechanism as lampalizumab, but have the ptential t be delivered t the eye with a frequency f 3 mnths Surce: 19 Crprate Overview

20 ACH-4471 Phase 1 SAD Healthy Vlunteer Study Safety, pharmackinetic and pharmacdynamic trial (6 active subjects per grup) Grups 1-3: Single dse f 200-, 600-, r 1200 mg Grup 4: Tw dses f 1200 mg given Q12H Assessments Inhibitin f serum AP activity in ex viv assays Safety fr AEs/SAEs thrugh the last scheduled visit at Day 28 PK / PD assessed frm Day 1 t Day 7 Demgraphics 36 subjects dsed and evaluated (35 males + 1 female) Results Well-tlerated at all evaluated dse levels First demnstratin f up t 100% AP cmplement inhibitin after ral dsing Ptential fr in viv bimarker Bb and Ba levels (cleavage prducts f factr B) are ptentially useful as in viv bimarkers f fd inhibitin Prfile supprts nging develpment prgram ANZCTR: Achillin data f file. 20 Crprate Overview

21 ACH-4471 Bb levels: In viv Bimarker fr AP Activity Bb cmplement prtein is generated thrugh the interactin f factr D with factr B and C3 Cmplement prtein levels have been well characterized in humans Individuals and healthy vlunteers have median Bb levels ~0.85 mg/l C3G patients have 30% higher levels f Bb indicating ver-activatin f the AP Fllwing a single dse f ACH-4471 (200mg) administered t healthy subjects, up t 41% reductin in Bb levels bserved ver dsing perid 50% 40% Cnditin Nrmal subjects Bb level (mg/l) 0.85 C3GN 1.33 DDD % 20% 10% 0% -10% -20% -30% Nrmal (0.85mg/l) C3GN (1.33 mg/l) DDD (1.28 mg/l) Relative Change in Bb level Max Δ pst ACH-4471 in healthy subjects -40% -50% Surces: Zhang Y., et al. Clin J Am Sc Nephrl 9: , Achillin data f file. 21 Crprate Overview

22 ACH-4471 Phase 1 MAD Healthy Vlunteer Study Multiple-ascending dse (MAD) healthy vlunteer study Safety, tlerability and PK/PD; dsing up t 14 days Expsure ptimizatin t supprt Phase 2 prgram fr PNH and C3G Pharmackinetics/Pharmacdynamics 200, 500, 800 mg BID and 75mg TID (8 active + 2 placeb subjects per chrt) Activity/Bimarkers Safety Rapid reductin in cmplement prtein Bb, demnstrating that ral administratin f ACH-4471 results in inhibitin f factr D Rapid and cmplete suppressin f AP hemlytic activity Generally well tlerated acrss all dse grups Tw cases f pst-treatment, transient and self-limited elevatins in ALT was bserved in ne subject each in 500mg (grade 3 ALT elevatin) & 800 mg (grade 4 ALT elevatin) dse grups Thrugh safety, PK/PD evaluatin, and eculizumab benchmarking cmpleted and is supprtive f Phase 2 clinical develpment ANZCTR: Achillin data f file. 22 Crprate Overview

23 ACH-4471 Benchmarking t Eculizumab in PNH Hemlysis Assay Enhance the understanding f PK/PD relatinships in PNH Prjectins fr efficacius dsing are based n: Benchmarking f ACH-4471 with eculizumab fr lysis f PNH red bld cells PK/PD prfile f ACH-4471 frm the Phase I prgram Ability t maintain expsures abve necessary trugh cncentratins ACH-4471 well absrbed thrughut GI tract Extended release frmulatin in develpment ACH-4471 was benchmarked using eculizumab fr inhibitin f hemlysis using PNH red bld cells Surce: Data n file. Achillin Pharmaceuticals, Inc Crprate Overview

24 ACH-4471 Phase 2 Prgram fr PNH Phase 2 trial fr untreated PNH patients Status: Enrllment f patients nging. - Endpints: Reductin in lactate dehydrgenase (LDH), imprvements in Hgb, and patient reprted assessments (FACIT) - Assessments: safety, tlerability, and PK/PD - Starting dse: 100 mg TID with ptential fr intra-patient escalatin - Key Inclusin Criteria: Currently untreated PNH patients PNH Type III erythrcyte and/r granulcyte clne size 10% and anemia (Hgb < 12g/dL) with adequate reticulcytsis Lactate dehydrgenase (LDH) 1.5X the upper limit f nrmal (ULN) Vaccinatin fr N. meningitidis, H. influenza, and S. pneumniae Anticipate reprting interim results during 2Q17 ClinicalTrials.gv Identifier: NCT Crprate Overview

25 ACH-4471 Phase 2 Prgram fr C3G Phase 2 clinical trial fr C3G Aim t demnstrate trigger pint inhibitin and reductin in AP activity Gal: Changes in C3 and Bb levels relative t baseline Assessments: safety, tlerability, and PK/PD Initiatin: estimated fr 2H 2017 Natural Histry Study f C3G Imperial Cllege f Lndn Gal: Lngitudinal study t track curse f the disease ver time Enrllment: Three year study estimated t track apprximately 400 participants 25 Crprate Overview

26 ICW 2016 Cngress ACH-4471: Effect n Bactericidal Activity Bactericidal Activity f Human Serum Remains Unchanged in Presence f ACH-4471 Inhibitin f Factr D (alternative pathway) with ACH-4471 des nt affect bactericidal activity against E.Cli Bactericidal activity is preserved in presence f at least ne (alternative, classical r lectin) pathway Bactericidal activity is ablished if the terminal pathway (C5 inhibitin) is blcked Surce: Zha et al. Internatinal Cmplement Wrkshp, Japan. Abstract 62, Crprate Overview

27 ICW 2016 Cngress ACH-4471: Effect n Opsnphagcytsis Opsnphagcytsis is nt impaired by ACH-4471 Opsnphagcytic activity f mncytes and granulcytes is nt impaired by ACH-4471 (inhibitin f alternative pathway) Opsnphagcytsis is impaired significantly in absence f classical+alternative pathway Absence f terminal pathway (C5 depletin) has mderate effect n psnphagcytsis Surce: Zha et al. Internatinal Cmplement Wrkshp, Japan. Abstract 62, Crprate Overview

28 ASH 2016 Annual Meeting Vaccinatins and Effects f C5 and Factr D Inhibitin Data suggest that vaccinatin shall be mre effective in decreasing the risk f meningcccal disease in the presence f an AP inhibitr as cmpared t a C5 inhibitr. Surces: Granff, et al, Effect f cmplement inhibitin by anti-c5 (eculizumab) r a small mlecule inhibitr f Factr D (ACH-4471) n survival f meningccci in bld frm vaccinated adults Presented at: American Sciety f Hematlgy; Decmeber 3-6, 2016.; San Dieg; Data n file. Achillin Pharmaceuticals, Inc Cnfidential

29 JNJ-4178 Highlighted by J&J Reprduced with permissin f Jhnsn & Jhnsn 29 Crprate Overview

30 JNJ-4178 Highlighted as Tp Ten Develpment Candidate Reprduced with permissin f Jhnsn & Jhnsn 30 Crprate Overview

31 Janssen s HCV Develpment Prgram Glbal develpment f JNJ-4178 (dalasvir, AL-335, simeprevir) nging Prgram cnsists f multiple therapeutic and NDA supprting studies: OMEGA-1: Phase 2b Efficacy, Safety and PK Trial Trial fully enrlled as f April 2017 (n=365) 2-arm trial evaluating triplet regimen fr 6 and 8 weeks - ODV (25 mg QD); AL-335 (800 mg QD); SMV (75 mg QD) - Patient ppulatin: GT 1,2,4,5,6; nn-cirrhtics Milestnes and Ryalties under the Cllabratin Milestnes - $115 millin clinical-based $15 millin earned fllwing start f Phase 2b enrllment - $290 millin regulatry-based - $500 millin sales-based Ryalties - Mid-teens t lw-twenties percent - Ryalties n full net sales nt pr-rated Surce: Clinicaltrials.gv: as f 3/6/17 31 Crprate Overview

32 Achillin Financial Summary Capitalizatin and Ownership Balance Sheet Metrics As f 3/31/2017 Cash, cash equivalents, marketable securities and interest receivable Debt bligatins $386.6 millin $0.6 millin Shares utstanding Tp Sharehlders millin Psitin Jhnsn & Jhnsn Develpment Crp millin (13%) RA Capital 13.6 millin (10%) Orbimed Advisrs 13.1 millin (9.6%) Blackrck Institutinal 9.3 millin (7%) Vanguard Grup 8.9 millin (7%) State Street Glbal Advisrs 5.1 millin (4%) Janus Capital Management 4.7 millin (3%) Gldman Sachs & C. 3.7 millin (3%) T. Rwe Price 3.0 millin (2%) Numeric Investrs 2.6 millin (2%) BVF Partners 2.4 millin (2%) Based upn mst recent SEC filings as f 2/15/ Crprate Overview

33 Our Prgress & Milestnes COMPLEMENT FACTOR D INHIBITOR PLATFORM Small mlecule, ral factr D inhibitrs fr rare disease ACH-4471 First ral fd inhibitr t demnstrate inhibitin f the AP after ral dsing Phase 2 trial fr untreated PNH nging Next-generatin cmpunds being advanced thrugh IND-enabling studies Advancing internal factr D candidates fr phthalmlgy Preclinical cmpunds being advanced fr the treatment f dry AMD Targeting 3 mnth delivery apprach HCV Cllabratin with J&J: JNJ-4178 Triple cmbinatin includes Achillin discvered and develped NS5A inhibitr, dalasvir Glbal Phase 2b OMEGA-1 clinical trial fully enrlled (n=365). Results anticipated during 2H17 COMPLEMENT RESEARCH Presentatins at ASH 2016 address issues assciated with cmplement inhibitin N bystander effect with bacteria Dr. Rbert Brdsky, Jhns Hpkins Bactericidal and psnphagcytic killing maintained in presence f a fd inhibitr, but nt a C5 inhibitr Dr. Dan Granff, UCSF Beniff 33 Crprate Overview

34 Achillin s Value Prpsitin LEADER IN COMPLEMENT AP INHIBITION First t Clinically Demnstrate AP suppressin with Factr D in Healthy Subjects Lead clinical prgram ACH-4471 advancing thrugh Phase 2 develpment Advancing multiple inhibitrs tward clinical develpment >30 published patent applicatins fr factr D inhibitrs Dysregulatin f the AP is Assciated with Diseases such as C3G, PNH, & GA/dry AMD Advancing Cmplement Bilgy thrugh internal research and external cllabratins Wrldwide HCV Cllabratin with Janssen Once daily regimen achieved 100% cure after six weeks f treatment Glbal Phase 2b OMEGA-1 study cmpleted enrllment with results anticipated 2H17 $386.6 MM in Cash and Equivalents as f March 2017 Strng financial psitin t advance multiple prgrams thrugh key inflectin pints GOAL TO DEVELOP DRUGS TO HELP PATIENTS WITH UNDERSERVED NEEDS 34 Crprate Overview

35 Crprate Overview Our Value, Our Science, Our Fcus 2017 Achillin Pharmaceuticals. All rights reserved. NASDAQ:ACHN