Driven by a novel pharmaceutical platform focused on SELECTIVE IMMUNOMODULATION Exhibit 99.1
Forward Looking Statements This presentation includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among other things, statements, other than historical facts, regarding: the progress, scope, duration or results of clinical trials and preclinical studies of inarigivir soproxil (“inarigivir”), SB 11285 or any of our other product candidates or programs, such as the size, design, population, conduct, cost, objective or endpoints of any clinical trial, or the timing for initiation or completion of or availability of results from any clinical trial (including our Phase 2 clinical trial of inarigivir in patients with chronic Hepatitis B virus); the potential benefits that may be derived from any of our product candidates; our future operations, financial position, revenues, costs, expenses, uses of cash, capital requirements or our need for additional financing; or our strategies, goals, milestones, prospects, beliefs, intentions, plans, expectations, forecasts or objectives. Words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions sometimes identify forward-looking statements. Any forward-looking statement involves known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from those expressed or implied by such forward-looking statement, and, therefore, you are cautioned not to place undue reliance on any forward-looking statement. These factors include, but are not limited to: whether our cash resources will be sufficient to fund our continuing operations for the period anticipated; the components, timing, costs and results of our clinical trials, preclinical studies and other development activities involving our product candidates; whether certain top-line results from our clinical trials materially change as more information becomes available; whether results obtained in preclinical studies and clinical trials will be indicative of results obtained in future clinical trials; whether inarigivir, SB 11285 and any of our other product candidates will advance through the clinical trial process on a timely basis and receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; and whether, if inarigivir, SB 11285 or any of our other product candidates obtain regulatory approval, it will be successfully distributed and marketed. These and other risks and uncertainties that we face are described in our most recent Annual Report on Form 10-K, filed with the Securities and Exchange Commission (SEC) on February 20, 2018, and in other filings that we make with the SEC from time to time. All forward-looking statements speak only as of November 1, 2018 and should not be relied upon as representing our views as of any other date. We specifically disclaim any obligation to update any forward-looking statement, except as required by applicable law. All trademarks, service marks, trade names, logos and brand names identified in this presentation are the properties of their respective owners. This presentation also contains estimates and other statistical data generated by independent parties and by us relating to market size and statistics. These estimates involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. FORWARD LOOKING STATEMENT SPRING BANK PHARMACEUTICALS, INC. © 2018
1 • SPRING BANK PHARMACEUTICALS, INC. © 2018 Novel, proprietary platform of selective small molecule immunomodulators Rapid generation of product candidates, shortening development time Application across multiple therapeutic areas including viral infections, inflammation and oncology Potent antiviral activity against HBV demonstrated with lead program: inarigivir Orally available, liver-selective immunomodulator Potential to become the backbone of curative combination treatments for HBV Favorable safety profile to date with no SAEs observed Second HBV program (SB 9225) progressing towards clinical trials in 2019 Fixed-dose combination opportunities for potential market expansion Gilead clinical collaboration currently in Phase 2 with multiple cohorts Inarigivir part of an HBV development strategy with Gilead Next generation STING agonist program anticipated to enter the clinic in multiple cancers in 2019 Currently funded into mid-2021 with multiple data readouts in the next 12–18 months SPRING BANK (NASDAQ:SBPH) INVESTMENT OPPORTUNITY
2 • SPRING BANK PHARMACEUTICALS, INC. © 2018 DIFFERENTIATED PLATFORM & NEAR TERM CATALYSTS FOR POTENTIAL VALUATION ACCELERATION Small Molecule Nucleotide Hybrid Platform NEAR–TERM DEVELOPMENT CATALYSTS Platform focused on immunomodulatory targets based on endogenous nucleotide ligands Rapid evolution of nucleotide scaffolds into development candidate small molecule nucleotide hybrids Reduces discovery cycle and potentially shortens development time
Inarigivir, selective RIG-I agonist, in Ph II development for HBV with planned initiation of Ph IIb / III in early 2019 Clinical collaboration with Gilead Differentiated, next-generation STING agonist program in Immuno-oncology SB 11285 will potentially be first IV STING agonist to enter the clinic in 2019 3 • SPRING BANK PHARMACEUTICALS, INC. © 2018 DIFFERENTIATED PLATFORM & NEAR TERM CATALYSTS FOR POTENTIAL VALUATION ACCELERATION NEAR–TERM DEVELOPMENT CATALYSTS IN–HOUSE OF SYNTHETIC NUCLEOTIDES NEAR–TERM DEVELOPMENT CATALYSTS
4 • SPRING BANK PHARMACEUTICALS, INC. © 2018 PROGRESSIVE PIPELINE DESIGNED TO MEET SIGNIFICANT UNMET NEEDS Platform Targets RIG-I STING Agonists Compound Inarigivir (oral): Monotherapy Co-Administration with Gilead’s Vemlidy® Co-Administration with NUCs SB 9225 inarigivir + tenofovir disoproxil fumarate (TDF) fixed-dose combination SB 9400 Indication SB 11285 (intravenous, intratumoral) Multiple analogs (nanoparticle, neoadjuvant and ADC development) HBV Other Viral Diseases HBV Immuno-oncology Immuno-oncology Preclinical Phase I HBV HBV Phase II Phase III Funded by Gilead
5 • SPRING BANK PHARMACEUTICALS, INC. © 2018 CHRONIC HBV: A GLOBAL PROBLEM Chronic HBV infection prevalence (approximate) ~257MM GLOBALLY ~17MM US AND EUROPE Estimated Deaths ~900,000 (IN 2017) HBV NUC global therapeutics sales $2.1B (IN 2017) LOW TREATMENT RATES OF CHRONIC HBV PATIENTS Estimated 10-15% in the US and Europe Estimated 1% in the Asia-Pacific region LOW FUNCTIONAL CURE RATES WITH CURRENT STANDARD OF CARE
6 • SPRING BANK PHARMACEUTICALS, INC. © 2018 AN OPPORTUNITY TO CHANGE THE CHRONIC HBV PARADIGM BY ELEVATING THE FUNCTIONAL CURE RATE A meaningful new therapy will need: 3 Achieve finite course of treatment leading to functional cure rates >8-10%* 2 Ease of administration 1 A good safety & tolerability profile HBV is complex and heterogenous Combinatorial approach will be required Immunomodulation will need to be the backbone *Represents the approximate number of patients that achieved HBsAg clearance after 48 weeks of treatment with aIFN + Viread® HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IFN, interferon. “Combination of antiviral and immune modulatory therapies will likely be needed to achieve functional hepatitis B virus cure.” Lok A, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. J Hepatol. 2017;67:847-861.
7 • SPRING BANK PHARMACEUTICALS, INC. © 2018 Potent RIG-I agonist INARIGIVIR: A NOVEL, ORAL, SELECTIVE IMMUNOMODULATOR WITH A DUAL MECHANISM OF ACTION Orally available, liver-selective immunomodulator Demonstrated dose response in HBV DNA and HBV RNA Favorable safety profile to date with no SAEs Deep collaboration with Gilead for co-administration studies with “NUCs” Only oral drug to show significant HBsAg reduction
8 • SPRING BANK PHARMACEUTICALS, INC. © 2018 INARIGIVIR: A NOVEL, ORAL SELECTIVE IMMUNOMODULATOR WITH A DUAL MECHANISM OF ACTION HBV, hepatitis B virus; IFN, interferon; pgRNA, pregenomic RNA; RIG-I, retinoic acid-inducible gene-I. Sato et al. Immunity. 2015;42:123-132. INARIGIVIR is a RIG–I AGONIST which is designed to: Restore hepatic innate and adaptive immune response stimulating the production of type III IFNs Inhibit the HBV replication complex via a direct acting anti-viral effect Result in significant anti-HBV activity with reduction in HBV DNA, HBV RNA, HBsAg and cccDNA RIG-I RIG-I TYPE III IFNs OATP1 DAA EFFECT TARGETING REPLICATION COMPLEX HBV pgRNA 5’ 3’ HBV pgRNA 5’ 3’ Dual antiviral effect against HBV HBV polymerase Reverse transcription Viral replication ε ε INARIGIVIR Hepatocyte RIG-I ACTIVATION AND BINDING TO HBV PGRNA
PRE-CLINICAL DATA Inarigivir binds to CARDs and regulatory domain of RIG-I with activation of IRF-3 and hepato-selective innate immune response Inarigivir up-regulates intra-hepatic RIG-I, activates intra-hepatic ISGs and suppresses HBsAg, HBV DNA, HBV RNA and cccDNA in the woodchuck CLINICAL Inarigivir potent antiviral against HCV with response proportional to ISG activation and IL-28b status Preliminary data shows inarigivir responses in HBV associated with peripheral IP-10 reduction and activation of ISGs in PBMCs Inarigivir activates a B-cell neutralizing HBsAb response in responder patients 9 • SPRING BANK PHARMACEUTICALS, INC. © 2018 INARIGIVIR – MOA STUDIES INDICATE KEY ROLE FOR SELECTIVE HEPATIC IMMUNO-MODULATION
10 • SPRING BANK PHARMACEUTICALS, INC. © 2018 CLINICAL STUDIES OF INARIGIVIR IN HBV DNA, deoxyribonucleic acid; HBeAg, hepatitis B e antigen; RNA, ribonucleic acid; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; QD, once daily. PRIMARY ENDPOINT SECONDARY ENDPOINT Safety and antiviral activity at 12 weeks PK, change in serum HBV DNA, HBsAg, HBV RNA and HBeAg from baseline to weeks 6, 12, 14, 16, and 24 Up to 80 non-cirrhotic HBV subjects, randomized 4:1 between inarigivir and placebo (Adaptive trial design) Inarigivir - 200 mg Placebo Inarigivir - 100 mg Inarigivir - 50 mg Inarigivir - 25 mg Viread® 300 mg All patients switch to Gilead’s Viread® 300 mg monotherapy 12 weeks (inarigivir monotherapy QD) 12 weeks Clinical trial collaboration with Gilead to evaluate inarigivir with nucleotide analog Viread® 300 mg ACHIEVE PHASE II MONOTHERAPY DOSE ESCALATION STUDY
n=30 Vemlidy® monotherapy Inarigivir - 50 mg + Vemlidy® Inarigivir - 200 mg + Vemlidy® GLOBAL HBV CLINICAL COLLABORATION WITH GILEAD Inarigivir co-administered with Vemlidy® (tenofovir alafenamide) 25 mg in naïve patients Expanded Gilead Phase 2 HBV Study Vemlidy® 12 weeks 36 weeks Initiated by Gilead in 1H 2018 Executed and funded by Gilead Inarigivir - 100 mg 12 weeks 11 • SPRING BANK PHARMACEUTICALS, INC. © 2018 Inarigivir monotherapy in virally suppressed patients - Patients remain on current oral antiviral n=20 n=10 n=30
Placebo 25 mg HBeAg +ve 25 mg HBeAg -ve 50 mg HBeAg +ve 50 mg HBeAg -ve 100 mg HBeAg +ve 100 mg HBeAg -ve Number 11 9 7 11 5 13 4 Age 40 37 43 36 47 34 46 Gender M:F 7:4 5:5 3:3 9:2 5:0 7:6 3:1 Baseline ALT 69 82 75 75 65 75 90 Baseline HBV DNA log10 6.20 7.86 5.69 7.79 4.55 8.20 5.95 Genotype A 1 1 B 6 4 3 3 3 4 3 C 4 5 1 7 1 8 1 D 2 1 1 In cohort 2 (50 mg), two patients (1 HbeAg +ve and 1 HBeAg –ve) withdrew at day 1 and day 14 from patient choice 12 • SPRING BANK PHARMACEUTICALS, INC. © 2018 ACHIEVE STUDY BASELINE DEMOGRAPHICS COHORTS 1, 2, and 3 Representative demographics of the diverse HBV patient population
13 • SPRING BANK PHARMACEUTICALS, INC. © 2018 HBV DNA 1 0 -1 -2 Placebo 25 mg 50 mg 100 mg Placebo 25 mg 50 mg 100 mg HBV RNA 0.5 0.0 -1.0 -1.5 -0.5 -2.0 Inarigivir 100 mg vs PL *p<0.05 * # Inarigivir vs PL *p<0.03 #p<0.02 Inarigivir Inarigivir Log10 Decline HBV DNA Log10 Decline HBV RNA Inarigivir Dose Inarigivir Dose INARIGIVIR DEMONSTRATES A CONTINUING POSITIVE DOSE RESPONSE IN HBeAg +VE PATIENTS AT WEEK 12
14 • SPRING BANK PHARMACEUTICALS, INC. © 2018 INARIGIVIR DEMONSTRATES A CONTINUING POSITIVE DOSE RESPONSE IN HBeAg -VE PATIENTS AT WEEK 12 HBV DNA HBV RNA Placebo 25 mg 50 mg and 100 mg 4 2 -2 -4 0 -6 2 1 -1 -2 0 -3 Placebo 25 mg 50 mg 100 mg All groups p<0.01 All groups p<0.01 5 patients undetectable HBV RNA at baseline Inarigivir Dose Inarigivir Dose Log10 Decline HBV DNA Log10 Decline HBV RNA
Patients: HBsAg <4 log: 16 HBeAg –ve, 10 HBeAg +ve 15 • SPRING BANK PHARMACEUTICALS, INC. © 2018 IN ALL COHORTS: BASELINE HBsAg PREDICTOR OF RESPONSE OF BOTH DNA AND RNA TO INARIGIVIR 1 -1 -2 0 -3 Subjects with Baseline HBsAg >4 log Subjects with Baseline HBsAg <4 log HBV DNA p<0.001 Subjects with Baseline HBsAg >4 log Subjects with Baseline HBsAg <4 log 2 -2 -4 0 -6 HBV RNA p<0.007 HBsAg >4 log: 1 HBeAg –ve, 19 HBeAg +ve Log10 Decline HBV DNA Log10 Decline HBV RNA
16 • SPRING BANK PHARMACEUTICALS, INC. © 2018 EFFECT OF ORAL INARIGIVIR (25, 50, AND 100 MG) ON HBsAg Only oral drug candidate to show meaningful effect on HBsAg in clinical studies Effect on HBsAg seen at all doses in both monotherapy and after TDF switch Overall, 13 of 47 (28%) patients experienced a 0.5 log10 reduction on inarigivir alone or at 24 weeks after TDF switch HBsAg response seen in 6 HBeAg -ve and 7 HBeAg +ve patients across all genotypes Mean HBsAg reduction 0.8 log10 (range 0.5 – 1.4 log10) in 13 responder patients
17 • SPRING BANK PHARMACEUTICALS, INC. © 2018 EFFECT OF ORAL APPROVED OR INVESTIGATIONAL HBV DRUGS ON HBsAg* TLR-7 (Vesatolimod 4 mg) Week 12 mean reduction: 0.05 log10 No patient >0.5 log10 reduction No effect reported on HBsAg at week 4 TDF / TAF Week 48 mean reduction: HBeAg +ve 0.3 log10 HBeAg –ve 0.017 log10 <1% HBsAg loss cPAM/CAPSID Inarigivir Week 12 or 24 mean reduction: 0.8 log10 in responder population No other oral drug has shown this level of decline 13 of 47 (28%) patients achieved at least a 0.5 log10 reduction, superior to any other oral HBV drug in development * Comparisons are not based on head-to-head studies and therefore conclusions should not be drawn about comparative effect.
70-80% of chronic HBV patients Dominant population in US & EU Older age group Lower viral burden SB 9225 + different MOA Inarigivir + existing oral anti-viral “Suppress & Shock” Inarigivir monotherapy “Stop & Shock” INARIGIVIR DEVELOPMENT PLAN ACCOUNTS FOR HBV HETEROGENEITY Naïve or new to treatment NUC-Suppressed ~12-15% ~10-12% 20-30% of chronic HBV patients Younger population High viral burden 18 • SPRING BANK PHARMACEUTICALS, INC. © 2018 POTENTIAL MARKET ENTRY POTENTIAL EXPANSION OPPORTUNITY HBeAg - ve HBeAg + ve Opportunity to increase treatment rates with improved functional cure Treatment rates SB 9225 (inarigivir + TDF) ~17 Million infected with HBV in US and EU OR Further expand HBV population eligible for functional cure Potentially reduce treatment duration for other HBV MOAs
19 • SPRING BANK PHARMACEUTICALS, INC. © 2018 “SHOCK” inarigivir once daily for 12-24 weeks Durable HBsAg loss “SUPPRESS & SHOCK” ADDING INARIGIVIR IN VIRALLY SUPPRESSED PATIENTS Host immune system activated with the goal of clearing the virus Inarigivir immunomodulation anticipated to be studied in a Phase 2b/3 trial for its ability to promote HBsAg loss in NUC-suppressed patients “SUPPRESS” Patients on NUC treatment experience viral suppression Virally suppressed patients continue on NUC treatment
S 20 • SPRING BANK PHARMACEUTICALS, INC. © 2018 “SHOCK” inarigivir once daily for 12-24 weeks Virally suppressed patients stop NUC treatment 10-20% OF PATIENTS Host immune system detects and clears virus Experienced durable HBsAg loss up to 2 years after stopping treatment Inarigivir monotherapy anticipated to be studied in a Phase 2b/3 trial for its potential to improve current functional cure rate (10-20%) and reduce relapse rates following cessation of SOC therapies Virus begins to emerge in body “STOP & SHOCK” – INARIGIVIR MONOTHERAPY Clinical or virologic relapse Host immune system “shocked” by inarigivir with the goal of increasing viral clearance 80-90% OF PATIENTS NUC treatment re-established Potential to accelerate time to cure and increase response rate
“STOP & SHOCK” – INARIGIVIR MONOTHERAPY 21 • SPRING BANK PHARMACEUTICALS, INC. © 2018 “STOP & SHOCK” – INARIGIVIR MONOTHERAPY “Stop” approach is at the forefront of current innovative clinical HBV treatment + Adding inarigivir (“Shock”) to the “Stop” regimen, i.e., “Stop and Shock,” could enhance the clinical trend of ending “NUC” treatment and allowing the host immune system to clear remaining infection in treatment-suppressed patients Objective is to enhance the reactivation of the immune system Exploit the unique immunomodulatory MOA of inarigivir Phase IIb / III program planned to initiate in EU and Asia in early 2019
SB 9225 (inarigivir + TDF) Ph IIb / III program in US, EU and ASIA (anticipated Q3 2019) Newly diagnosed chronic HBV patients SB 9225 once-daily vs. TDF alone 24 week duration of treatment Primary endpoints: HBV DNA & durable HBsAg loss SB 9225 + other MOA (i.e., siRNA, capsid) – addressing HBsAg high viral burden population Ph II program (anticipated mid 2019) 22 • SPRING BANK PHARMACEUTICALS, INC. © 2018 SB 9225 – FIXED-DOSE COMBINATION FOR NAÏVE HBV
INARIGIVIR and SB 9225 LEADING THE WAY AS BACKBONE FOR HBV DEVELOPMENT – PLANNED CLINICAL STUDIES 23 • SPRING BANK PHARMACEUTICALS, INC. © 2018 Q1 Q2 Q3 Q1 Q2 Q3 Q4 2018 Q4 2019 Ph 2 ACHIEVE 200 mg monotherapy arm “Stop & Shock” inarigivir monotherapy Ph 2b/3 in low viral burden patients “Suppress & Shock” inarigivir monotherapy Ph 2b/3 in virally suppressed patients Ph 2 Gilead study: 50 mg inarigivir + Vemlidy® in naïve patients Ph 2 Gilead study: 200 mg inarigivir + Vemlidy® in naïve patients Ph 2 Gilead study: 100 mg inarigivir in virally suppressed patients Triple combo with SB 9225 and complimentary MOA SB 9225 Ph 2b/3 24 week study in treatment naïve, low viral burden patients
SB 11285 A NOVEL SYNTHETIC STING AGONIST LEAD COMPOUND A NOVEL SYNTHETIC
ATP cGAS 5’ 2’ 3’ 6’ GTP STING AGONIST – POTENT ACTIVATOR OF INNATE IMMUNE RESPONSE Potential component of I/O strategies to turn cold tumors “hot” IV administration could be next frontier of STING agonist development Activation of Type I IFN could enhance efficacy in combination with checkpoint inhibitors or other I/O MOAs GTP ATP cGAS GTP ATP 2’3’-cGAMP ATP GTP cGAS DNA STING STING STING STING 25 • SPRING BANK PHARMACEUTICALS, INC. © 2018 STING STING TBK1 IRF3 IKK 1xBg NFxB ER IRF3 IRF3 P P IRF3 IRF3 P P NFxB Type I Interferons Nucleus P P Degradation
26 • SPRING BANK PHARMACEUTICALS, INC. © 2018 SB 11285 – Lead next generation STING agonist Shown to be highly potent & efficacious across multiple preclinical cancer models with associated abscopal and tumor memory responses Potentially first IV STING agonist to enter clinic Differentiated cyclic dinucleotide Distinctive chemistry allows for potential nanoparticle formulation and conjugation with ADCs for targeted delivery Observed to turn “cold” tumors “hot” in preclinical studies ADC, antibody-drug conjugates; IV, intravenous; ; IT, intratumoral; STING, STimulator of INterferon Genes. Unique chemistry allows for “self assembly” could enhance immune cell recruitment via IV administration
27 • SPRING BANK PHARMACEUTICALS, INC. © 2018 SB 11285 SIGNIFICANTLY INHIBITED TUMOR GROWTH IN RELEVANT ONCOLOGY MODELS Efficacy in relevant oncology animal models observed with intravenous (IV), intraperitoneal (IP) and intratumoral (IT) delivery 1600 1400 1200 1000 800 600 400 200 0 1 5 9 12 Days Post Initiation of Treatment Tumor volume (mm3) CT26 Colon Cancer (IV) B16 Melanoma (IV) Day 33 Day 25 Day 40 SB 11285 Vehicle 4T1 Metastatic Breast Cancer (IP)
28 • SPRING BANK PHARMACEUTICALS, INC. © 2018 2018 2019 THE PATH FORWARD FOR SPRING BANK POTENTIAL FOR MULTIPLE CATALYSTS 1. As of September 30, 2018. CMC, chemistry, manufacturing and controls; IND, Investigational new drug. 2H 2018 Complete monotherapy dosing in the 200 mg cohort of the ACHIEVE Phase II study Gilead initiates additional cohorts in Phase II of inarigivir + NUC combo dosing SB 9225 (inarigivir + tenofovir disoproxil fumarate) fixed-dosed combination ready for clinical trials Gilead completes first cohort of combination trial: inarigivir 50mg + Vemlidy NASDAQ SBPH Market Cap ~$200MM1 Available Funding $71MM1 Into mid-2021 Shares Outstanding ~16.4MM1 1H 2019 2H 2019 Complete 24 week dosing in the 200 mg cohort of the ACHIEVE Phase II study Initial data from inarigivir + NUC combo dosing Initiate global Phase IIb / III “Suppress & Shock” trial Submit IND for SB 11285 Initiate global Phase IIb / III SB 9225 24 week trial Initiate global Phase IIb / III “Stop & Shock” trial Targeted Milestones
29 • SPRING BANK PHARMACEUTICALS, INC. © 2018 SPRING BANK PHARMACEUTICALS, INC. A FOCUS ON SIMPLICITY, SAFETY, AND SELECTIVITY SB 9225 (inarigivir + TDF) Simplifies combination therapy Next-generation STING agonist program: Lead SB 11285 anticipated to enter clinic in multiple cancers in 2019 Anticipate multiple data points for potential valuation enhancements in the next 12–18 months World class expertise in HBV Deep clinical collaboration in HBV with Gilead Unique in-house platform Focused on small molecule nucleotide hybrid immunomodulatory molecules Orally administered inarigivir has clinically shown potent antiviral activity in HBV Favorable safety profile to date with no SAEs observed