Developing a clinically important class of glycan-targeted biologics with unprecedented tumor specificity

Funding First Human Data

May 2018

Executive Summary

Siamab platform unlocks exciting but historically challenging target space– Glycans: cancer specific & immunosuppressive/chemoresistant– Initiated discovery collaboration w/ Boehringer Ingelheim using Siamab’s platform in 2017

Lead ST1-ADC program moving rapidly to clinical trials in ovarian cancer– Compelling efficacy in multiple xenograft & PDX models– Favorable safety profile in pilot cyno tox study

Raising $15-20m B-round to fund through clinical proof of concept– Raised $14m A round from Novartis, Momenta, family offices to date– $3m+ in grants won to date

Seeking lead institutional investor– Alternative funding history – highly capital efficient but challenging to transition

2

Cancers Consistently Alter GlycosylationMultiple TACA Targets: Tumor Associated Carbohydrate Antigens

3

Mutated DNA alters proteins

Similarly, glycans are mutated on proteins

TACAs Promote an Aggressive, Immunosuppressive PhenotypeAttractive but Challenging Targets

Suppress innate immunity (MDSCs and NK cells) Confer chemoresistance and a cancer stem-cell phenotype Enable tissue invasion & metastases

4

Siamab’s Platform Unlocks TACA TargetingEnables Unprecedented Specificity

Target is the glycan itself – not the glycoprotein– Binds multiple glycoproteins

Glycan-binding mAbs – rare to find with high affinity and specificity– Multiple format potential – ADC, TCR/bispecific, CAR-T

Siamab’s platform solves this problem– Validated with lead program and Boehringer Ingelheim collaboration

Pharma needs new targets!

Siamab’s glycan microarray confirms anti-glycan binding specificity

5

STn(Neu5Ac/Neu5Gc)

9-O Acetylated STn (Neu5Ac/Neu5Gc)

Siamab Pipeline

6

Discovery Pre-Clinical Phase I Phase II Status

Glycan Target: STnOvarian & Other Solid

Tumors

Cell Line Development Initiated; IND: 2019

(Unpartnered)

Glycan Target: N/DSolid Tumors

Partnered with Boehringer Ingelheim

Glycan Target: N/DBreast, Colon & Other

Solid Tumors

Discovery InitiatedQ4 2017

(Unpartnered)

ST1-ADC

ST2

ST3

Siamab’s Leadership Team

Jeff Behrens, MBA, MS, President & CEO– Biogen Idec Incubator: co-founder, led 3 deals – Alnylam, led alliance with Takeda pharmaceuticals– Edimer, Third Rock Ventures Dan Dransfield, PhD, SVP R&D

– Dyax, ArQule, Tokai– Tufts, Yale, Medical College of Georgia Gregg Beloff, JD, MBA, CFO

– Cerulean Pharma, Immunogen, Archemix Rebecca Dabora, PhD, Consulting Head of CMC

– Biogen, Altus, Merck William Slichenmyer, MD, Consulting CMO

– Pfizer, Merrimack, Aveo

7

Siamab Board & Key Advisors

8

Glycobiology Advisors Ajit Varki, MD, PhD (Founder) – UCSD Joy Burchell, PhD – Kings College London Zach Shriver, PhD – VP Research, Visterra

Oncology Advisors Ron Drapkin, MD, PhD – UPenn Bo Rueda, PhD – Mass General Hospital

Lead Program Development & Company Building Morris Rosenburg, PhD – former EVP, Seattle Genetics Peter Kiener, PhD – CSO, Sucampo Pharmaceuticals Haifeng Bao, PhD – Preclinical Consultant, former

MedImmune

John Edwards – Genzyme, Genetics Institute, TKT, Adnexus, F-Star

Board of Directors Jeff Behrens - President & CEO Brad Curley - Boston Harbor Angels (Chair) Adam Feire - Novartis Ganesh Kaundinya - Momenta Pharma Peter Kroon - Exan Capital Gary Pforzheimer - PG Calc Todd Zion - SmartCells

Link to Leadership Team

Siamab’s Lead ST1 Program (SIA01-ADC)IND-ready for FIM in 2019; Initiated Backup TCE Program

Platform discovered multiple mAbs against top priority target: STn MGH collaboration ongoing chemoresistant/CSC phenotype Humanized leads conjugated to vc-MMAE ADC format

– Excellent therapeutic window for ADC approach Compelling xenograft & PDX efficacy data IHC and tissue cross reactivity (TCR) studies completed Pilot cyno tox study excellent safety profile

9

STn Target OpportunitySerum STn+ Associated with Poor Prognosis

Kobayashi et al. 1992

10

STn- (Serum)

STn+ (Serum)

Months on Study

Perc

ent S

urvi

val

Overall Survival (n=89)

Myleoid-Derived Suppressor Cells (MDSCs) are STn+ and Offer Immune Reengagement Potential

Quantified STn expression on primary patient tumor samples and MDSCs– Fresh samples analyzed by flow cytometry– Both tumor cells and tumor infiltrating MDSCs express STn in patient samples

STn+ MDSCs linked to STn+ tumors in MDA-MB-231 STn+/- model

ST1 ADC depletes STn+ MDSCs in OVCAR3 mouse xenografts

11

ST1-ADC Lead Program ResultsDramatic PDX Efficacy in Ovarian Cancer PDX Models

12

Cisplatin 3mg/kg, q7dx3SIA01/ST1 5mg/kg (IV), QW (arrow indicates when treatment ended)# of animals/group = 3-5

75% of animals in ST1 group are completely tumor free

Tumors regressed by >50% in 75% of the animals in the ST1 group

Chart2

ST206A Ovarian PDX Model (Chemoresistant)

Vehicle Control12.24420581336318415.31079932596591126.23017315993196253.63254892320529278.63517645430712883.8183869088399488.105618072856302123.5607538986391310371014172124283135384246505356596366707377221.41600000000003344.65600000000006487.96799999999996588.84799999999996725.50400000000002833.35200000000009963.45599999999991081.808Cisplatin20.79999999999987326.52000000000013114.03999999999977732.93333333333314517.33333333333314717.33333333333314720.97333333333363572.799999999999514100.459789191718610371014172124283135384246505356596366707377224.64000000000001326.04000000000002407.16454.13333333333338554.66666666666663554.66666666666663734.06666666666672827.840000000000151034.1066666666666SIA0122.30589383996974135.12599037749678424.699999999999928032.760000000000794021.61599407846180757.11602927375141510371014172124283135384246505356596366707377228.67000000000002360.36445.90000000000003572722.28755.040000000000081010.87999999999991158.04ST1123.92000000000004130.29223167744505637.5577777120353668.30350601055042168.30350601055042168.30350601055042168.30350601055042155.77833271082955981.32141661333750470.19807404765454455.26060290417879638.47999999999999746.37016964960702151.72774980607604156.09712143535828956.09712143535828961.72778196781952480.65879307304318580.65879307304318591.166989639891042128.81812760632721138.70051670175326150.614505166888450371014172124283135384246505356596366707377227.76349.83483.6580.06000000000006580.06000000000006580.06000000000006580.06000000000006428.48335.4314.08000000000004216.71150.80000000000001130.38999999999999112.7100000000000199.4599.45115.69999999999999137.67000000000002137.67000000000002148.19999999999999185.9208224.25

Days

Tumor Volume (mm3)

Sheet1

ST206ATumor VolumeSEM

DaysVehicle ControlCisplatinSIA01ST1Isotype-ADCDaysVehicle ControlCisplatinSIA01ST1Isotype-ADC

022122522922822801221222424

334532636035033631527353053

748840744648440472614253847

1058945457258049210543306880

14726555722580571147917336895

1783355575558058217841706890

219637341011580582218821226890

24108282811584285822412473575690

2810343354662810081103

313144663170103

35217364355578

38151316383873

Last Day of Dosing42130295424699

461132654652113

50992545056119

53992505356121

561162545662119

591382825981119

631382936381122

661483356691137

7018633870129135

7320844173139165

7722448977151155

ST2569Tumor VolumeSEM

DaysVehicle ControlCisplatinSia01ST1Isotype-ADCDaysVehicle ControlCisplatinST1ST1-ADCIsotype-ADC

021220721021321302334365353

328225025326027832965417478

7465358365267367753823596106

106062624842074201081421296122

14765895716942414127224331154

1888249678243861810788910123

22119617754134412219810694156

25989784892551015166

Last Day of Dosing28111110136032861568211

311621645311015220

3517874635108268

381188863868311

4211810304268384

451184568

49984958

52945254

561185668

ST206A Ovarian PDX Model (Chemoresistant)

Vehicle Control12.24420581336318415.31079932596591126.23017315993196253.63254892320529278.63517645430712883.8183869088399488.105618072856302123.5607538986391310371014172124283135384246505356596366707377221.41600000000003344.65600000000006487.96799999999996588.84799999999996725.50400000000002833.35200000000009963.45599999999991081.808Cisplatin20.79999999999987326.52000000000013114.03999999999977732.93333333333314517.33333333333314717.33333333333314720.97333333333363572.799999999999514100.459789191718610371014172124283135384246505356596366707377224.64000000000001326.04000000000002407.16454.13333333333338554.66666666666663554.66666666666663734.06666666666672827.840000000000151034.1066666666666SIA0122.30589383996974135.12599037749678424.699999999999928032.760000000000794021.61599407846180757.11602927375141510371014172124283135384246505356596366707377228.67000000000002360.36445.90000000000003572722.28755.040000000000081010.87999999999991158.04ST1123.92000000000004130.29223167744505637.5577777120353668.30350601055042168.30350601055042168.30350601055042168.30350601055042155.77833271082955981.32141661333750470.19807404765454455.26060290417879638.47999999999999746.37016964960702151.72774980607604156.09712143535828956.09712143535828961.72778196781952480.65879307304318580.65879307304318591.166989639891042128.81812760632721138.70051670175326150.614505166888450371014172124283135384246505356596366707377227.76349.83483.6580.06000000000006580.06000000000006580.06000000000006580.06000000000006428.48335.4314.08000000000004216.71150.80000000000001130.38999999999999112.7100000000000199.4599.45115.69999999999999137.67000000000002137.67000000000002148.19999999999999185.9208224.25Isotype-ADC23.91999999999988852.68962706263923946.82454911688952880.05678234853053395.16577168289016790.08427831758444990.08427831758444990.084278317584449103.06237334740547103.0623733474054778.15566411549021172.63402210167544198.842041493823203113.18125816582888118.986176648102120.61842479488779118.986176648102118.81525884049292122.10137686911372137.48869080764428135.38345886161034164.8124359183291154.8314553528018710371014172124283135384246505356596366707377227.76000000000002336.44403.52492.18571.09581.62581.62581.62465.92465.92363.61316.02999999999997295.23265.45999999999998253.63250.38253.63282.10000000000002292.63335.01338.26440.83000000000004488.67000000000007

Days

Tumor Volume (mm3)

ST2569 Ovarian PDX Model (Chemo-naive)

Vehicle Control22.54222491237280928.68609586541887152.73374327695687981.140264135631199127.02777296323826106.89528079386857198.1295808707018910371014182225283135384245495256211.952281.94400000000002465.4606.11199999999997765.12799999999993882.336000000000011195.5840000000001Cisplatin33.65346011597885965.11176169564997581.96962472634476242.08253477790213321.7351982839919177.80000000000001949.63209449935186514.68000000000000065.62465998972382329.64612069406372729.63209449935186515.62465998972382325.6246599897238232655610371014182225283135384245495256206.61333333333334250.4666666666667358.10666666666663262.0889.0933333333333249.417.3333333333333329.360000000000001210.9215.77333333333333317.33333333333333210.9210.92119911Sia0136.08103102739718140.57020704901560735.34557916722631212.1589966691335243.41837821322558789.46024722374359368.771351593523448101.36410475771663155.9637402304352310371014182225283135384245495256209.56252.85000000000002365.43484.38570.82999999999993677.95753.74897.261110.2ST1153.41170408565275173.84194539690837296.02451561971037195.58253867731282630.65161822808055110.385635913767314.42954850972421444.82403358197266218.072570842055213815.3383473686052648.328.328.3288480371014182225283135384245495256212.68259.87266.5207.0900000000000369.0324.31000000000000212.878.191320.938.328.328.328848Isotype-ADC53.41170408565275177.949283511780891105.89386447445068122.24284178088577153.72727658638422122.69502570737461155.92624367522833165.98734771060123211.35137567567432220.35153391796476267.53721005995914310.82402824320599384.0270412353796110371014182225283135384245495256212.68278.46000000000004366.86420.29424.45385.84000000000003440.69999999999993489.05999999999995603.19999999999993645.19000000000005745.55886.081030.3800000000001

Days

Tumor Volume (mm3)

Chart1

ST2569 Ovarian PDX Model (Chemo-naive)

Vehicle Control22.54222491237280928.68609586541887152.73374327695687981.140264135631199127.02777296323826106.89528079386857198.1295808707018910371014182225283135384245495256211.952281.94400000000002465.4606.11199999999997765.12799999999993882.336000000000011195.5840000000001Cisplatin33.65346011597885965.11176169564997581.96962472634476242.08253477790213321.7351982839919177.80000000000001949.63209449935186514.68000000000000065.62465998972382329.64612069406372729.63209449935186515.62465998972382325.6246599897238232655610371014182225283135384245495256206.61333333333334250.4666666666667358.10666666666663262.0889.0933333333333249.417.3333333333333329.360000000000001210.9215.77333333333333317.33333333333333210.9210.92119911SIA0136.08103102739718140.57020704901560735.34557916722631212.1589966691335243.41837821322558789.46024722374359368.771351593523448101.36410475771663155.9637402304352310371014182225283135384245495256209.56252.85000000000002365.43484.38570.82999999999993677.95753.74897.261110.2ST1153.41170408565275173.84194539690837296.02451561971037195.58253867731282630.65161822808055110.385635913767314.42954850972421444.82403358197266218.072570842055213815.3383473686052648.328.328.3288480371014182225283135384245495256212.68259.87266.5207.0900000000000369.0324.31000000000000212.878.191320.938.328.328.328848

Days

Tumor Volume (mm3)

Sheet1

ST206ATumor VolumeSEM

DaysVehicle ControlCisplatinSIA01ST1Isotype-ADCDaysVehicle ControlCisplatinSIA01ST1Isotype-ADC

022122522922822801221222424

334532636035033631527353053

748840744648440472614253847

1058945457258049210543306880

14726555722580571147917336895

1783355575558058217841706890

219637341011580582218821226890

24108282811584285822412473575690

2810343354662810081103

313144663170103

35217364355578

38151316383873

Last Day of Dosing42130295424699

461132654652113

50992545056119

53992505356121

561162545662119

591382825981119

631382936381122

661483356691137

7018633870129135

7320844173139165

7722448977151155

ST2569Tumor VolumeSEM

DaysVehicle ControlCisplatinSIA01ST1Isotype-ADCDaysVehicle ControlCisplatinSIA01ST1-ADCIsotype-ADC

021220721021321302334365353

328225025326027832965417478

7465358365267367753823596106

106062624842074201081421296122

14765895716942414127224331154

1888249678243861810788910123

22119617754134412219810694156

25989784892551015166

Last Day of Dosing28111110136032861568211

311621645311015220

3517874635108268

381188863868311

4211810304268384

451184568

49984958

52945254

561185668

ST206A Ovarian PDX Model (Chemoresistant)

Vehicle Control12.24420581336318415.31079932596591126.23017315993196253.63254892320529278.63517645430712883.8183869088399488.105618072856302123.5607538986391310371014172124283135384246505356596366707377221.41600000000003344.65600000000006487.96799999999996588.84799999999996725.50400000000002833.35200000000009963.45599999999991081.808Cisplatin20.79999999999987326.52000000000013114.03999999999977732.93333333333314517.33333333333314717.33333333333314720.97333333333363572.799999999999514100.459789191718610371014172124283135384246505356596366707377224.64000000000001326.04000000000002407.16454.13333333333338554.66666666666663554.66666666666663734.06666666666672827.840000000000151034.1066666666666SIA0122.30589383996974135.12599037749678424.699999999999928032.760000000000794021.61599407846180757.11602927375141510371014172124283135384246505356596366707377228.67000000000002360.36445.90000000000003572722.28755.040000000000081010.87999999999991158.04ST1123.92000000000004130.29223167744505637.5577777120353668.30350601055042168.30350601055042168.30350601055042168.30350601055042155.77833271082955981.32141661333750470.19807404765454455.26060290417879638.47999999999999746.37016964960702151.72774980607604156.09712143535828956.09712143535828961.72778196781952480.65879307304318580.65879307304318591.166989639891042128.81812760632721138.70051670175326150.614505166888450371014172124283135384246505356596366707377227.76349.83483.6580.06000000000006580.06000000000006580.06000000000006580.06000000000006428.48335.4314.08000000000004216.71150.80000000000001130.38999999999999112.7100000000000199.4599.45115.69999999999999137.67000000000002137.67000000000002148.19999999999999185.9208224.25

Days

Tumor Volume (mm3)

ST2569 Ovarian PDX Model (Chemo-naive)

Vehicle Control22.54222491237280928.68609586541887152.73374327695687981.140264135631199127.02777296323826106.89528079386857198.1295808707018910371014182225283135384245495256211.952281.94400000000002465.4606.11199999999997765.12799999999993882.336000000000011195.5840000000001Cisplatin33.65346011597885965.11176169564997581.96962472634476242.08253477790213321.7351982839919177.80000000000001949.63209449935186514.68000000000000065.62465998972382329.64612069406372729.63209449935186515.62465998972382325.6246599897238232655610371014182225283135384245495256206.61333333333334250.4666666666667358.10666666666663262.0889.0933333333333249.417.3333333333333329.360000000000001210.9215.77333333333333317.33333333333333210.9210.92119911SIA0136.08103102739718140.57020704901560735.34557916722631212.1589966691335243.41837821322558789.46024722374359368.771351593523448101.36410475771663155.9637402304352310371014182225283135384245495256209.56252.85000000000002365.43484.38570.82999999999993677.95753.74897.261110.2ST1153.41170408565275173.84194539690837296.02451561971037195.58253867731282630.65161822808055110.385635913767314.42954850972421444.82403358197266218.072570842055213815.3383473686052648.328.328.3288480371014182225283135384245495256212.68259.87266.5207.0900000000000369.0324.31000000000000212.878.191320.938.328.328.328848

Days

Tumor Volume (mm3)

ST1 Lead Program ResultsPilot Cyno PK/Tox Study Demonstrates Safety & Therapeutic Window

2 doses ST1-ADC administered: Days 1, 22 @ 1, 3, 6mg/kg– Designed based on MMAE history/Adcetris® preclinical package

Results demonstrate excellent safety profile of ST1– No deaths, no body weight loss (animals maintained weights between 2.20-2.47 kgs)– No gross pathologic changes across all organs assessed– Histopathologic changes limited to the bone marrow (MMAE class effect)– All clinical chemistry results (e.g., LFT’s (ALT/AST/ALP), kidney function (CREAT)) normal

throughout study

Half-life ~4 days; exposure data in-line with published findings for other MMAE ADCs

Derisked IND-enabling GLP tox solid therapeutic window

13 CONFIDENTIAL

ST1-ADC – Ready to Enter the Clinic

Cell line development complete in early Q2 2018 Next steps

– Select CMO and initiate GMP scaleup– IND-enabling GLP tox studies designed– Pre-IND meeting w/FDA in Q3 2018

Phase I/Ib studies design in place– Standard 3x3 study with single patient cohorts at lowest doses– Expansion cohorts for phase Ib

• Ovarian• Confirmed STn+ tumors• Possible 3rd cohort: pancreatic or gastric

– STn expression to be assessed in serum and by IHC when samples available

14

Lead ST1-ADC Program: Large Commercial PotentialSTn Glycan Present in Many Carcinomas (and Rare In Normal Tissue)

Ovarian cancer – Potential first indication– High unmet medical need– Chemoresistant recurrence common– 5 year survival rate: 30%– US incidence: 22,500 cases diagnosed/yr– Peak sales potential approaches $1b/yr

Other key indications– Pancreatic– Gastric (diffuse subtype)– Prostate (>80% expression)

15

STn Cancer Tissue Expression

Individual studyMean

% p

ositi

ve ca

ses

Julien et al, Biomolecules 2012

Siamab Series B Investment Summary

Advance lead program to clinical proof-of-concept (phase Ib)– 3 years– $17M program-specific costs: CMC, GLP tox, PhI/Ib studies

• Australia strategy could reduce this by ~$5m (tax rebate)– G&A $3M

Advance pipeline– 1-2 lead candidate programs $5M pipeline costs

Complete second pharma deal– >$10M free cash flow (2018-2020)– Incremental to raise and budget

16

Lead ST1 ProgramDevelopment Timeline

17

Developing a clinically important class of glycan-targeted biologics with unprecedented tumor specificity��Funding First Human Data �Executive SummaryCancers Consistently Alter Glycosylation�Multiple TACA Targets: Tumor Associated Carbohydrate AntigensTACAs Promote an Aggressive, Immunosuppressive Phenotype�Attractive but Challenging TargetsSiamab’s Platform Unlocks TACA Targeting�Enables Unprecedented SpecificitySiamab PipelineSiamab’s Leadership TeamSiamab Board & Key AdvisorsSiamab’s Lead ST1 Program (SIA01-ADC)�IND-ready for FIM in 2019; Initiated Backup TCE ProgramSTn Target Opportunity�Serum STn+ Associated with Poor Prognosis Myleoid-Derived Suppressor Cells (MDSCs) are STn+ and �Offer Immune Reengagement PotentialST1-ADC Lead Program Results�Dramatic PDX Efficacy in Ovarian Cancer PDX ModelsST1 Lead Program Results�Pilot Cyno PK/Tox Study Demonstrates Safety & Therapeutic WindowST1-ADC – Ready to Enter the ClinicLead ST1-ADC Program: Large Commercial Potential�STn Glycan Present in Many Carcinomas (and Rare In Normal Tissue)Siamab Series B Investment SummaryLead ST1 Program�Development Timeline