Post on 25-Jun-2020
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