UNITED STATES

SECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): March 2, 2015

AMARANTUS BIOSCIENCE HOLDINGS, INC.

(Exact name of registrant as specified in its charter)

Nevada 333-148922 26-0690857(State or other jurisdiction of

incorporation or organization)(Commission File Number) IRS Employer

Identification No.)

655 Montgomery StreetSuite 900

San Francisco, CA 94111(Address of Principal Executive Offices) (Zip Code)

(408) 737-2734

(Registrant’s telephone number, including area code)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any ofthe following provisions:

¨ Written communications pursuant to Rule 425 under the Securities Act

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 1.01 Entry into a Material Definitive Agreement

On March 2, 2014, Amarantus Bioscience Holdings, Inc. (the “Company”) entered into a securities purchase agreement

pursuant to which the Company agreed to issue 555.55 shares of its Series E Convertible Preferred Stock (”Series E PreferredStock”) for gross proceeds of $500,000 bringing the total amount received by the Company from the sale of its Series E PreferredStock to an aggregate of $7,000,000. The majority of the $500,000 were used to pay the extension payment due to Lonza underthe exclusive option agreement.

On March 3, 2015, the Company filed a Certificate of Amendment to the Certificate of Designation to its Series E

Convertible Preferred Stock to increase the number of Series E Preferred stock to 7,779 shares of Series E Preferred Stock. The sale of the shares of the Series E Preferred Stock were made upon the same terms and conditions of the Series E

Preferred Stock transaction previously disclosed by the Company in its current reports on Form 8-K filed with the Securities andExchange Commission on November 14, 2014, December 24, 2014 and January 14, 2015.

Item 3.02 Unregistered Sales of Equity Securities

The information set forth in Item 1.01 is incorporated by reference herein.

The issuance of the securities described above were completed in accordance with the exemption provided by Section4(a)(2) of the Securities Act of 1933, as amended.

Item 5.03 Amendments to Articles of Incorporation or Bylaws; Change in Fiscal Year

The information set forth in Item 1.01 is incorporated by reference herein. Item 8.01 Other Events

The Company is filing with this 8-K a corporate presentation regarding its Eltoprazine program. The presentation isattached as Exhibit 99.1 to this report on Form 8-K and is incorporated herein by reference

On February 23, 2015, the Company filed an IND with the U.S. Food and Drug Administration for its Phase 2b clinical

trial for Eltoprazine to treat Levodopa-Induced Dyskinesia in patients with Parkinson’s Disease. Item 9.01 Financial Statements and Exhibits

(d) Exhibits ExhibitNo. Description 3.1 Certificate of Amendment to Certificate of Designation of Series E Preferred Stock filed March 3, 2015 99.1 Corporate presentation dated March 2, 2015

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its

behalf by the undersigned thereunto duly authorized.

AMARANTUS BIOSCIENCE HOLDINGS, INC. Date: March 3, 2015 By: /s/ Gerald E. Commissiong Name: Gerald E. Commissiong Title: Chief Executive Officer

Exhibit 3.1

CERTIFICATE OF AMENDMENT OFCERTIFICATE OF DESIGNATION OF

AMARANTUS BIOSCIENCE HOLDINGS, INC.Pursuant to Section 78.1955 of the

Nevada Revised Statutes

SERIES E CONVERTIBLE PREFERRED STOCK

On behalf of Amarantus BioScience Holdings, Inc., a Nevada corporation (the “Corporation”), the undersigned hereby certifies that

the following resolution has been duly adopted by the board of directors of the Corporation (the “Board”): RESOLVED, that, pursuant to the authority granted to and vested in the Board by the provisions of the articles of incorporation of

the Corporation (the “Articles of Incorporation”):

1. The third Whereas clause of the Certificate of Designation of the Corporation for the Series E Convertible Preferred Stock shall be

deleted in its entirety and replaced with the following: WHEREAS, it is the desire of the Board of Directors, pursuant to its authority as aforesaid, to fix the rights, preferences, restrictionsand other matters relating to a series of the preferred stock, which shall consist of, except as otherwise set forth in the PurchaseAgreement, up to 555.55 shares of the preferred stock which the Corporation has the authority to issue, as follows:

2. Section 2 of the Certificate of Designation of the Corporation for the Series E Convertible Preferred Stock shall be deleted in itsentirety and replaced with the following:

Section 2. Designation, Amount and Par Value. The series of preferred stock shall be designated as its Series E 12%Convertible Preferred Stock (the “Preferred Stock”) and the number of shares so designated shall be up to 7,779 (which shall not besubject to increase without the written consent of all of the holders of the Preferred Stock (each, a “Holder” and collectively, the“Holders”)). Each share of Preferred Stock shall have a par value of $0.001 per share and a stated value equal to $1,000, subject toincrease set forth in Section 3 below (the “Stated Value”).

IN WITNESS WHEREOF, the undersigned have duly signed this Certificate of Amendment to the Certificate of Designation of the

Series E Convertible Preferred Stock as of this 2nd day of March 2015.

Amarantus BioScience Holdings, Inc. /s/ Marc Faerber By: Marc Faerber

Title: Secretary and V.P. Finance

Exhibit 99.1

E L T O P R A Z IN E S elective 5H T 1A /1B receptor partial agonist O T C Q B : A MB S 1

2 T his presentation contains “ forw ard - looking statem ents ” w ithin the m eaning of the “ safe - harbor ” provisions of the P rivate S ecurities L itigation R eform A ct of 1995. S uch statem ents involve know n and unknow n risks, uncertainties and other factors that could cause the actual results of the C om pany to differ m aterially from the results expressed or im plied by such statem ents, including changes from anticipated levels of sales, future international, national or regional econom ic and com petitive conditions, changes in relationships w ith custom ers, access to capital, difficulties in developing and m arketing new products and services, m arketing existing products and services, custom er acceptance of existing and new products and services and other factors. A ccordingly, although the C om pany believes that the expectations reflected in such forw ard - looking statem ents are reasonable, there can be no assurance that such expectations w ill prove to be correct. T he C om pany has no obligation to update the forw ard - looking inform ation contained in this presentation. F orw ard - L ooking S tatem ents

E ltoprazine: V alue P roposition • P ositive P h2a C linical D ata : – L - D opa Induced D yskinesia (L ID ) in P arkinson’s patients: • P ositive clinical data on L ID w ithout affecting L - D opa activity • P re - clinical and clinical data supporting expansion into non - m otor sym ptom s including L - dopa induced psychosis and attention – A D H D : • P ositive data on attention & hyperactivity/im pulsivity in adults • N on - stim ulant, non - scheduled drug w ith advantages over existing m arketed products • E xceptional safety profile: – A dm inistered to 682 hum ans (volunteers and patients) – U p to tw o years dosing studied by S olvay 3

E ltoprazine: H um an D osing S um m ary • T otal num ber of m ale and fem ale hum an subjects (patients & volunteers): N = 682 • H ealthy m ale and fem ale subjects: N = 306 – S A D N = 221 : dose range 0.5 to 30 m g – MA D N = 85 : 5 to 40 m g b.i.d. 5 days, 20 m g b.i.d. 16 days and up to 15 m g b.i.d. 20 days • P atients: N = 376 – A ggression & S chizophrenia: N = 307 patients – A D H D : N = 47 patients – P D - L ID : N = 22 patients • P atient D oses used 2.5 to 60 m g daily (30 m g b.i.d.) • Maxim um duration of patient dosing = 747 days (30 m g b.i.d.) • P atients w ith at least 8 w eeks dosing: N = 262: doses 5 to 30 m g b.i.d • P D L ID patients: N = 22 single doses of 2.5, 5 and 7.5 m g in a crossover design • E xpected future doses in the range 5 to 15 m g daily 4

E ltoprazine: R egulatory H istory • T hree regulatory subm issions already open: • IN D for A D H D w ith U S - F D A • IN D for C IA S w ith U S - F D A • C T A for L ID w ith MP A ( S w eden) • IN D for P D - L ID being subm itted to N eurology D ivision of F D A • C T A for P D - L ID being subm itted to E urope • e - C T D form at being used 5

E ltoprazine - B ackground • S elective 5H T 1A /1B receptor partial agonist • E valuated in several large P hase II studies in m ore than 680 hum ans (volunteers & subjects) for periods up to 1 year at doses as high as 30 m g bid. • G ood S afety P rofile: – R epeat toxicity studies in rat and dog up to six m onths – G enotoxicity , reproductive & developm ental toxicity studies com plete w ith no significant safety pharm acology or tox findings – N o effect on hE R G , Q T or cardiovascular activity – also in hum ans • P harm acokinetics: – P lasm a H alf - life: ~ 8 hrs – G ood oral bioavailability – N o C Y P inhibition & little C Y P m etabolism – L ow binding to plasm a proteins (< 15% ) 6

L evodopa Induced D yskinesia (L ID ) 7

• A ccording to the P arkinson’s D isease F oundation, at least 1 m illion people in the U S live w ith P arkinson’s D isease; 60,000 A m ericans are diagnosed w ith P arkinson's disease (P D ) each year. • A pproxim ately four m illion people w orldw ide are estim ated to be living w ith P arkinson's disease. • T he com bined direct and indirect cost of P arkinson’s, including treatm ent, social security paym ents and lost incom e from inability to w ork, is estim ated to be nearly $25 billion per year in the U nited S tates alone. P arkinson’s D isease Market 8

L evodopa Induced D yskinesia (L ID ) 9 • L evodopa (L - D opa) is w idely recognized as the m ost effective treatm ent for m otor sym ptom s of P D • L evodopa - induced dyskinesias (uncontrolled m ovem ents) are a disabling unw anted effect of long - term L - D opa treatm ent in P D patients • 60 - 80% of P D patients suffer from this problem during the course of the disease • O nly anti - dyskinetic m edical treatm ent available today is A m antadine - only m oderately effective and has low response rates • Initial dem onstration of eltoprazine (5H T 1A /1B agonist) efficacy show n in rodent and prim ate m odels of L ID and a P hase 2a study in P D - L ID patients

L evodopa Induced D yskinesia (L ID ) 10 • In m oderate to advanced P arkinson’s patients, few dopam ine term inals survive and L - D opa is taken in by the serotonin term inals w here it is converted to dopam ine. • H ow ever, since the serotonin term inals do not have auto - regulatory feedback to control levels of dopam ine, the excessive sw ings in dopam ine levels caused by adm inistration of L - D opa cause dyskinetic m ovem ents. • P harm acological blockade of serotonin neuron activity by 5 - H T 1A /1B agonists m ay provide the basis for effective treatm ent of L - D O P A - induced dyskinesias.

E ltoprazine: L ID R ationale 11 • N orm ally, L - D opa is taken up by dopam ine term inals and converted into dopam ine w hich is released in a controlled m anner • A s P D progresses & dopam ine term inals are lost, L - D opa is taken up by serotonin term inals • L ack of negative feedback on these serotinergic term inals for dopam ine release causes excessive sw ings in dopam ine levels, resulting in L ID C arta et al, B rain, 2007 • A ctivation of pre - synaptic serotonin receptors by 5H T 1A /1B agonists controls dopam ine release, thereby dim inishing L ID E ltoprazine

E ltoprazine L ID T rial D ata R ecently P ublished in journal B R A IN 12

• T reatm ent A rm s: E ach patient underw ent the follow ing treatm ents: – L evodopa challenge dose + placebo (B aseline; T est session 1) – L evodopa challenge dose + 2.5 m g eltoprazine (random ized) – L evodopa challenge dose + 5 m g eltoprazine (random ized) – L evodopa challenge dose + 7.5 m g eltoprazine (random ized) – L evodopa challenge dose + placebo (random ized) • T he tests w ere perform ed at w eekly intervals to allow sufficient w ash - out tim e • V ideo T aping and A ssessm ent: – A t each of the visits, patients w ere asked to perform tasks pertaining to the U P D R S - III and D yskinesia scales prior to m edication and at 30, 60, 90, 120, 150 and 180 m inutes post - treatm ent and w ere video - taped. – E ach video segm ent w as rated by tw o independent raters; the m ean value of the tw o ratings w as used in the analysis. T rial D esign (contd.) 13

T rial P rofile 14

S erum C oncentration of E ltoprazine 15 H ours S e r u m E l t o p r a z i n e ( n g / m l ) 0 1 2 3 4 0 5 10 15 20 25 2.5 m g 5 m g 7.5 m g E ltoprazine concentration in serum w as m easured in 12 patients at 2.5 m g, 5 m g and 7.5 m g. D ata are presented as m ean ± S D .

D em ographics of study participants 16 V ariable IT T population (n= 22 ) A ge (years) 66 . 6 ( 8 . 8 ) Male/F em ale 16 ( 72 . 7 % )/ 6 ( 27 . 3 % ) H eight (cm ) 172 . 6 ( 10 . 1 ) Weight (kg) 69 . 9 ( 12 . 0 ) C aucasian 22 ( 100 % ) D isease duration (years) 11 . 6 ( 3 . 1 ) H oehn & Y ahr stage 2 . 86 ( 0 . 44 ) Y ears of L ID s 3 . 41 ( 1 . 40 ) U P D R S IV - 32 1 . 86 ( 0 . 83 ) U P D R S IV - 33 1 . 68 ( 0 . 95 ) U P D R S IV - 34 0 . 91 ( 1 . 11 ) D ystonia 7 ( 31 . 8 % ) P eak - dose dyskinesias 22 ( 100 % ) L - dopa 22 ( 100 % ) D A agonist 17 ( 77 % ) MA O B - I 9 ( 41 % ) C O MT - I 15 ( 68 % ) L E D (m g) 1191 ( 495 ) Intention T o T reat (IT T ) study population. T he m easures are taken from the day of screening. F or categorical variables; n (% ) is presented. F or continuous variables; m ean (S D ). L ID severity is indicated by results from questions 32 - 34 of U P D R S pats IV , indicating duration, disability and painfulness of L ID s. L - dopa equivalent (L E D ) w as calculated according to T om linson and co - w orkers (2010).

E ffects of E ltoprazine on prim ary outcom es; C D R S A U C 0 - 3 and U P D R S - III 17 D yskinesias assessed as m ean C D R S A U C 0 - 3 . and C hange w ithin test session of U P D R S - III. A t each visit, the change in U P D R S - III w as determ ined as the difference betw een the U P D R S - III score prior to any study m edication and the highest U P D R S - III score post dosing for 3 hours. D ifferences in random ized placebo response to the test session placebo 1 and the dosages of eltoprazine w hen com pared to random ized placebo are also presented. A ll data are from the IT T population (n= 22). D ata are presented as m ean ± S D . ** p< 0.01 using paired Wi1coxon S igned R ank T est.

18 E ffects of E ltoprazine on S econdary O utcom e m easures V ariable T est S ession 1 P lacebo R andom ized P lacebo E ltoprazine 2.5 m g E ltoprazine 5 m g E ltoprazine 7.5 m g D ifference R andom ized P lacebo – T est S ession 1 P lacebo D ifference E ltoprazine 2.5 m g – R andom ized P lacebo D ifference E ltoprazine 5 m g – R andom ized P lacebo D ifference E ltoprazine 7.5 m g – R andom ized P lacebo Maxim um C D R S after study m edication 9.02 (3.37) 9.73 (3.87) 8.91 (3.55) 8.59 (3.36) 9.11 (3.70) 0.71 (2.06) p= 0.145 - 0.82 (1.89) p= 0.069 - 1.14 (1.59) p= 0.005** - 0.61 (1.53) p= 0.077 R D R S A U C 0 - 3 1.73 (0.51) 1.67 (0.52) 1.65 (0.54) 1.53 (0.50) 1.65 (0.53) - 0.05 (0.29) p= 0.521 - 0.02 (0.19) p= 0.615 - 0.15 (0.23) p= 0.003** - 0.03 (0.21) p= 0.555 U P D R S - III A U C 0 - 3 22.7 (6.3) 22.2 (6.2) 22.7 (6.2) 22.5 (6.8) 22.6 (6.4) - 0.57 (3.41) p= 0.826 0.49 (2.84) p= 0.814 0.35 (3.14) p= 0.988 0.45 (1.97) p= 0.766 H ighest U P D R S after study m edication 26.5 (6.9) 25.0 (7.2) 26.3 (8.8) 27.8 (10.5) 26.4 (8.1) - 1.50 (5.34) p= 0.342 1.30 (6.40) p= 0.639 2.80 (8.51) p= 0.388 1.35 (4.92) p= 0.150 D ifference in H A D S - A prior and 3 hrs after study m edication - 0.86 (0.94) - 0.50 (1.14) - 0.27 (1.39) 0.18 (1.30) - 0.14 (0.77) 0.36 (1.43) p= 0.283 - 0.14 (0.77) p= 0.303 0.58 (1.91) p= 0.044 * 0.36 (1.36) p= 0.282 D ifference in H A D S - D prior and 3 hrs after study m edication - 0.18 (1.10) - 0.05 (0.58) - 0.27 (0.99) - 0.18 (0.96) 0.09 (0.87) 0.14 (1.17) p= 0.716 - 0.23 (1.34) p= 0.672 - 0.14 (0.99) p= 0.617 0.14 (1.17) p= 0.716 D yskinesia m easures on m axim um observed C D R S postdosing for 3 hours and m ean R D R S A U C 0 - 3 . P arkinsonian m otor scores on U P D R S - III A U C 0 - 3 as w ell as highest U P D R S part III postdosing for 3 hours. T he difference in m ood scores of H A D S anxiety (H A D S - A ) and depression (H A D S - D ) prior to and postdosing for 3 hours. D ifferences in random ized placebo response to the test session placebo 1 and the dosages of eltoprazine w hen com pared to random ized placebo are also presented. A ll m easures are from the IT T population (n= 22). D ata are presented as m ean ± S D . ** p< 0.01; * p< 0.05 using paired Wi1coxon S igned R ank T est.

P ost H oc A nalyses of C D R S A U C 0 - 3 and P eak D ose D yskinesia S cores 19 (A ) R atio of L east S quares G eom etric Means (E ltoprazine/R andom ized P lacebo) in C D R S A U C 0 - 3 . (B ). D ifferences of L east S quares Means in peak dose C D R S (90 m inutes post L - dopa) from R andom ized P lacebo. A ll m easures are from the IT T population (n= 22). * p< 0.05. A . D ose of E ltoprazine R atio of L east S quares G eom etric Means C D R S A U C 0 - 3 (E ltoprazine/R andom ized P lacebo) E stim ate L ow er 95% C I U pper 95% C I p - value 2.5 m g 0.94 0.84 1.05 0.2709 5 m g 0.85 0.77 0.94 0.0027 * 7.5 m g 0.91 0.81 1.01 0.0827 B . D ose of E ltoprazine D ifference in L east S quares Means P eak dose C D R S (E ltoprazine - R andom ized P lacebo) E stim ate L ow er 95% C I U pper 95% C I p - value 2.5 m g - 0.8178 - 1.8872 0.2517 0.1314 5 m g - 1.0186 - 1.9601 - 0.07702 0.0345 * 7.5 m g - 1.0533 - 2.0707 - 0.03580 0.0427 *

H A D S – A nxiety & D epression S cores D ifference from P lacebo Mean ( S D ) 2.5 m g - T est session 1 P lacebo 5 m g - T est session 1 P lacebo 7.5 m g - T est session 1 P lacebo -0.056 (1.984) -0.778 (1.629) -0.056 (1.392) p= 0.6960 p= 0.0576 p= 0.9146 0.500 (1.339) 0.444 (1.294) 0.667 (1.680) p= 0.1489 p= 0.2183 p= 0.1406 0.556 (1.423) 1.22 (1.40) 0.722 (1.227) p= 0.1112 p= 0.0037 p= 0.0283 V ariable D ifference from placebo (n= 18) H A D S T otal score A nxiety pre-dose H A D S T otal score A nxiety 3h post-treatm ent D ifference in H A D S T otal score A nxiety pre-dose to 3h post-treatm ent 20

A nalysis of anxiety score • C linical observations and double - blind studies (Z uardi, 5 - H T related drugs and H um an E xperim ental A nxiety, N euroscience and B ehavioral R eview s, V ol. 14, pp: 507 - 510) dem onstrate that there is a latency of several w eeks for the anxiolytic effect of serotonin drugs to take place. • T here is actually a bi - phasic effect – an acute anxiogenic effect, follew ed by an anxiolytic effect after chronic use. • T his is further corroborated by data from our A D H D clinical trial; the P rofile of Moods S cale (P O MS ) show ed a significant anxiolytic effect at the sam e dose ranges as the L ID study after 14 days of dosing. 5m g bid 10m g bid O verall P O MS S core 0.006 0.972 T ension/A nxiety S core 0.046 0.972 A nger/H ostility S core < 0.001 0.036 D ifference from placebo (p-values) 21

F orthcom ing E ltoprazine P hase 2 study 22 • D ouble - blind placebo - controlled, dose range finding study • E xpert P D centers in U S and E U • T rial initiation planned for Q 1 2015, F irst P atient in early Q 2 2015 • E valuation of dose response effect of chronic dosing on safety, tolerability and dyskinesia severity using state - of - the - art rating scales, diaries and m otion sensors • P K and P D relationship w ill be evaluated to guide late stage developm ent in this indication, including optim isation of the form ulation

P D - L ID S tudy: E ltodys 09 23 S ingle dose placebo - controlled 4 - w ay crossover study of acute treatm ent of L ID follow ing levodopa challenge in 22 patients w ith P D L ID . D oses used 2.5, 5 and 7.5 m g. 0 5 10 15 20 25 30 0 2 4 6 8 E ltoprazine C onc. (ng/m L ) T im e (hrs) 2.5 m g (H ealthy) 5 m g (H ealthy) 10 m g (H ealthy) 2.5 m g (P D ) 5 m g (P D ) 7.5 m g (P D ) 0 200 400 600 800 1000 1200 0 1 2 3 4 5 6 S inem et (100/25m g) concentration (ng/m L ) T im e (hr) ▪ E ltoprazine has linear P K w ith C m ax at approxim ately, 2.3 hours and a t ½ of around 7 hours ▪ Inter - individual variability is low ▪ P K in P D patients w as sim ilar to that seen in healthy subjects

Morning loading dose follow ed by m idday top up – total daily dose of 10 or 15 m g 24 L oading dose follow ed by sm aller top up dose(s) can optim ise daytim e exposure w hile m inim ising dose. C onsider bi - or tri - layer tablet

E ltoprazine C onclusions 25 x P re - clinical data identified hum an equivalent effective daily doses of betw een 3 and 30 m g and plasm a concentrations of 9 to 17 ng/m l x C onsistent w ith the anim al data, clinical data suggest effective daily doses of 5 to 10 m g w ith a desired daytim e plasm a concentration in the range of 10 to 30 ng/m l x P K m odeling dem onstrates a variety of dosing com binations w hich could achieve the target daytim e plasm a concentration range x O rally - adm inistered eltoprazine has favorable P K and galenic characteristics that lend them selves to creating an oral form ulation, that could optim ize the daily exposure profile w ith a single daily dose of eltoprazine x T he results of the P hase 2 P D - L ID trial in 2015 w ill enhance the understanding of the efficacy of eltoprazine and enable further developm ent of the optim al form ulation for the treatm ent of P D - L ID and A D H D for use in pivotal efficacy studies

A D H D 26

C om petitive A dvantage of E ltoprazine D rug C lass P otential L iabilities S ource E ltoprazine P sycho-stim ulants (am phetam ines & m ethylphenidates) A buse L iability N ID A T estim ony, July 26, 2006N ot expected S tunted grow th in children Journal of A m erican A cadem y of C hild & A dolescent P sychiatry, A ugust 2007 N ot expected B lack box w arning for adverse cardiovascular events F D A P ress R elease dated F eb 21, 2007 (A ppendix I) N o clinically m eaningful changes in Q T c in hum ans to date S trattera (A tom oxetine) B lack box w arning for adverse cardiovascular and psychiatric events (suicidal ideation) F D A P ress R elease dated F eb 21, 2007 (A ppendix I) N o indication of cardiovascular events ot suicidal ideation to date P oor m etabolizers (P Ms) of C Y P 2D 6 have a 10-fold higher A U C and a 5-fold higher peak concentration to a given dose of atom oxetine as com pared w ith extensive m etabolizers (E Ms). T he higher blood levels in P Ms leads to a higher rate of som e adverse effects of the drug. S traterra P ackage Insert N o C Y P Inhibition or m etabolism by C Y P 2D 6 and other cytochrom e P 450 isoform s Intuniv (G uanfacine) R esearch has show n that the potent 5H T 2B agonism could potentially lead to cardiac valvulopathy H uang,X -P , et al., Molecular P harm acology F ast F orw ard, July 1, 2009 A ntagonist at the 5H T 2B receptor P otent alpha2A adrenergic agonist- could potentially cause low blood pressure/reduced heart rate Intuniv P ackage Insert N o binding to alpha2A receptor 27

E ltoprazine R esem bles A D H D T reatm ents 28 A lexandrov et al: E ur Journal P harm acology 750, 82 - 89 (Jan 2015)

C linical D ata – A dults A D H D 29

P hase - II A D H D T rial: S tudy O verview S tudy D esign D ouble-blind, placebo-controlled, m ultiple-dose, cross-over P rim ary O bjective C om pare the doses of tw o doses of eltoprazine on sym ptom s of A D H D in adults. P rim ary efficacy param eter is the A ttention D eficit/H yperactivity R ating S cale (A D H D -R S -IV ) S econdary O bjective • C om pare the effects of eltoprazine versus placebo on the C onnors C ontinuous P erform ance T est (C P T ) and C linical G lobal Im provem ent S cale (C G I-I) • T o assess the safety and tolerability of m ultiple doses of eltoprazine S ubjects 47 subjects random ized, 36 com pleted K ey Inclusion C riteria • A D H D -R S -IV score of at least 35 at baseline and screening • C G I score of 4 or greater at baseline and screening K ey E xclusion C riteria • A ny other psychiatric disorder including depression, bipolar disorder and schizophrenia • T aking any psychotropic m edication on a regular basis, other than non-5H T 1A anxiolytics 30

O riginal S tudy D esign patients tested using A D H D R ating S cale V ersion IV (A D H D - R S - IV ) at these points Week: 0 1 2 3 4 5 6 S equence 1 Washout 5 m g 5 m g placebo placebo 10 m g 10 m g S equence 2 Washout 10 m g 10 m g placebo placebo 5 m g 5 m g T he original protocol random ized patients into either the 5 m g bid or 10 m g bid for a period of tw o w eeks 31

O riginal S tudy D esign D iscontinuations due to A E s * S ubject N o. D ose (m g/day) D ays on D rug A dverse E vent (MedD R A T erm s) 01-05 5 7 F atigue F atigue D izziness N ausea D izziness A sthenia D izziness N ausea A bdom inal pain upper F atigue N ightm are03-09 10 4 03-01 10 8 03-07 10 7 03-03 10 5 O riginal P rotocol * F ive subjects dropped out; 4/5 of the drop - outs w ere in the high dose (10m g) group 32

A m ended S tudy D esign Week 0 1 2 3 4 5 6 G roup 1 Washout 5 m g 5 m g P lacebo P lacebo 5 m g 10 m g G roup 2 Washout 5 m g 10 m g P lacebo P lacebo 5 m g 5 m g patients tested using A D H D R ating S cale V ersion IV (A D H D - R S - IV ) at these points T he protocol w as am ended such that patients random ized to the high dose group w ere dose titrated to receive 5 m g bid during the first w eek of the tw o w eek treatm ent period and 10 m g bid during the second w eek . T his reduced drop - outs due to A E ’s significantly (as show n on the next slide) 33

A m ended S tudy D esign D iscontinuations due to A E s S ubject N o. D ose (m g/day) D ays on D rug A dverse E vent (MedD R A T erm s) 03-17 5 9 H eart rate increased 01-12 10 8 H ypoaesthesia 02-02 5 7 S inus bradycardia w ith com peting junctional rhythm N ausea A bdom inal pain upper C onstipation A m ended P rotocol 04-11 5 6 * * * - R elationship to drug treatm ent unlikely 34

A D H D - R S - IV T otal S core C hange from baseline in total A D H D score com pared to placebo (p - values) • Magnitude of drug effect com parable to stim ulants • Magnitude of placebo effect higher in this trial than in other A D H D trials • R esponse rates in this trial com parable to those in other studies in both the A D H D - R S - IV and the C G I - I scores 5m g bid 10m g bid P lacebo N = 38 N = 37 N = 38 B aseline S core 42.4 42.7 42.4 P ost T reatm ent S core 24.5 25.3 28.8 C hange from B aseline -17.9 (42% ) -17.4 (41% ) -13.6 (32% ) E ltoprazine vs. P lacebo p< 0.003 p< 0.037 % R esponders ( ≥ 30% change) 61% 68% 55% 35

A D H D - R S - IV S ub - S cores C hange from baseline in A D H D sub - scores com pared to placebo (p - values) Inattention 5m g bid 10m g bid P lacebo N = 38 N = 37 N = 38 B aseline S core 23.8 23.8 23.8 P ost T reatm ent S core 14.5 14.8 17 C hange from B aseline -9.4 (39% ) -9.0 (38% ) -6.8 (29% ) E ltoprazine vs. P lacebo p< 0.003 p< 0.039 H yperactivity/ 5m g bid 10m g bid P lacebo Im pulsivity N = 38 N = 37 N = 38 B aseline S core 12.5 12.8 12.5 P ost T reatm ent S core 6.6 7.2 8.1 C hange from B aseline -5.9 (47% ) -5.5 (43% ) -4.4 (35% ) E ltoprazine vs. P lacebo p< 0.014 p< 0.084 36

S econdary and S afety S cales • S econdary S cales: – B oth the 5m g bid dose (p < 0.023) and 10m g bid dose (p < 0.004) show ed statistical significance in the C linical G lobal Im provem ent S core (C G I - I) – P rofile of Moods S cale (P O MS ) also show ed im provem ent • S afety S cales: – N o treatm ent related effects w ere seen in: • A bnorm al Involuntary Movem ent S cale (A IMS ) • S im pson A ngus S cale (S A S ) 5m g bid 10m g bid O verall P O MS S core 0.006 0.972 T ension/A nxiety S core 0.046 0.972 A nger/H ostility S core < 0.001 0.036 D ifference from placebo (p-values) 37

C om parison to O ther A D H D T rials T he w eighted average % change from baseline for placebo in the trials listed above is approxim ately 22 % as com pared to the higher placebo response of 32 % in the P sychoG enics trial . H ow ever, the change from baseline for E ltoprazine is com parable to that of the other drugs . P lacebo D rug (% decrease from baseline) (% decrease from baseline) Methylphenidate 1.1m g/kg/day A dults P arallel, 6 w k, placebo 146 15% (2 w k) 15% (6 w k) 34% (2 w k) 58% (6 w k) O R O S - MP H (m ax. 1.3 m g/kg/day) A dults P arallel, 6 w k, placebo 141 40% (2 w k) 40% (6 w k) 45% (2 w k) 57% (6 w k) B uproprion X L A dults P arallel, 8 w k, placebo 162 19% (8 w k) 35% (8 w k) B uproprion S R 362 m g/day A dults P arallel, 6 w k, placebo 40 24% (6 w k) 42% (6 w k) A dderall X R (10-40 m g/kg/day) A dolescent P arallel, 4 w k, placebo 258 28% (8 w k) 41-60% (4 w k) Modafinil 170-425 m g/kg/day C hildren & A dolescents P arallel, 9 w k, placebo 198 26% (2 w k) 34% (2 w k) 31% (9 w k) ns 52% (9 w k) Modafinil 300 m g/day C hildren P arallel, 4 w k, placebo 223 7% (4 w k) 33% (4 w k) A tom oxetine (1.2 m g/kg/day) & A tom oxetine (1.8 m g/kg/day) C hildren & A dolescents P arallel, 8 w k, placebo 44/84 44/85 16% (8 w k) 16% (8 w k) 36% (8 w k) 36% (8 w k) E ltoprazine (5 m g/day) & E ltoprazine (10 m g/day) A dults C ross-over, placebo 38 37 32% 32% 42% 41% T reatm ent S ubjects D esign N 38

R esponse R ates - C om parison to other trials R esponse R ates – A D H D - R S - IV R esponse R ates – C G I - I S tudy N um ber of patients/ D uration and D esign of S tudy D rug/D ose Im provem ent C ut-off R esponse R ates S pencer et al, 2002 147 / 12 w eeks, parallel design A tom oxetine < 2 m g/kg A D H D -R S -IV ≥ 25% 64.0% S pencer et al, 2001 27 / 7w eeks, cross-over design Mixed am phetam ine salts, 54 m g A D H D -R S -IV ≥ 30% 70.0% Michelson et al, 2002171 / 6 w eeks, parallel design A tom oxetine 1-1.5 m g/kg A D H D -R S -IV ≥ 25% 59.5% K elsey et al, 2004 197 / 8 w eeks, parallel design A tom oxetine 1-1.5 m g/kg A D H D -R S (P ) ≥ 25% 62.7% P sychoG enics 36 / 2 w eeks, cross-over design 5 m g/day A D H D -R S -IV ≥ 30% 61.0% 10 m g/day 68.0% S tudy N um ber of patients/ D uration and D esign of S tudy D rug/D ose Im provem ent C ut-off R esponse R ates K em ner et al, 2005651 / 3 w eeks, open-label O R O S MP H , 37.8 m g C G I-I ≤ 2 68.6% A tom oxetine 1.08 m g/kg 52.8% S pencer et al, 200127 / 7 w eeks, cross-over Mixed A m phetam ine salts 54 m gC G I-I ≤ 2 66.7% P sychoG enics 36/ 2 w eeks, cross-over 5 m g/day C G I-I ≤ 2 (very m uch im proved) 39.5% 10 m g/day 40.5% P sychoG enics 36/ 2 w eeks, cross-over 5 m g/day C G I-I ≤ 3 (som e im provem ent) 68.4% 10 m g/day 81.1% 39