UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, 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): September 7, 2017
ASSEMBLY BIOSCIENCES, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-35005 | 20-8729264 | ||
|
(State or other jurisdiction of incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification No.) |
|
11711 N. Meridian St., Suite 310 Carmel, Indiana 46032 |
| (Address of principal executive offices, including zip code) |
(317) 210-9311
(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 of the following provisions:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | 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)) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.
Emerging growth company ¨
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
Item 7.01 Regulation FD Disclosure.
Assembly Biosciences, Inc. (the “Company”) is furnishing a corporate presentation, attached as Exhibit 99.1 to this Current Report on Form 8-K, that the Company intends to use from time to time in meetings with investors and others beginning on September 7, 2017. The corporate presentation will also be available on the Company’s website at http://investor.assemblybio.com/events.cfm.
The information in this Item 7.01 and Exhibit 99.1 attached hereto is furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits:
The following exhibit relating to Item 7.01 shall be deemed furnished and not filed.
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Exhibit No. |
Description | |
| 99.1 | Assembly Biosciences, Inc. Corporate Presentation September 2017. |
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 hereunto duly authorized.
| Date: September 7, 2017 | Assembly Biosciences, Inc. | |
| By: | /s/ Derek A. Small | |
| Derek A. Small | ||
| President and Chief Executive Officer | ||
EXHIBIT INDEX
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Exhibit No. |
Description | |
| 99.1 | Assembly Biosciences, Inc. Corporate Presentation September 2017. |
Exhibit 99.1
Assembly Biosciences, Inc. Corporate Presentation September 7, 2017 Nasdaq: ASMB
Cautionary note r egarding forward - looking s tatements The information in this presentation contains estimates and other forward - looking statements regarding future events, including statements about the clinical and therapeutic potential of our HBV - Cure and Microbiome programs, our ability to receive payments from Allergan Pharmaceuticals International Limited (“Allergan”) under the collaboration agreement, timing of the initiation of and availability of data from our ongoing and planned clinical trials in each of these programs, plans, strategies, milestones, a nd intentions related to our programs. Certain forward looking statements may be identified by reference to a future period or periods or b y u se of forward - looking terminology such as “believe”, “planned”, “initiate”, “potential,” “anticipated”, or “expected.” Such forward - looking statements, which we intend to be covered by the safe harbor provisions contained in Section 27A of the Securities Act of 193 3, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, are just predictions and are subject to risks an d uncertainties that could cause the actual events or results to differ materially. These risks and uncertainties include, amon g o thers: the components, timing, cost and results of clinical trials and other development activities involving our product candidates (in clu ding those licensed by Allergan); the unpredictability of the nonclinical and clinical development of our product candidates and of the duration and results of regulatory review of those candidates by the FDA and foreign regulatory authorities; our anticipated cap ital expenditures, our estimates regarding our capital requirements, and our need for future capital; and the possible impairment of, or inability to obtain, intellectual property rights and the costs of obtaining such rights from third parties. These and other pot ential risks and uncertainties that could cause actual results to differ from the results predicted are more fully detailed under the head ing “Risk Factors” in our Annual Report on Form 10 - K for the year ended December 31, 2016 and our Quarterly Report on Form 10 - Q for the quarter ended June 30, 2017 each filed with the Securities and Exchange Commission. It is not possible for Assembly management to predict all risks nor can Assembly assess the impact of all factors on its business or the extent to which any factor, or com bin ation of factors, may cause actual results to differ materially from those contained in any forward - looking statements Assembly may make. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size . These estimates involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In light of these risks, uncertainties and assumptions, the forward - looking events and circumstances discussed in th is presentation may not occur and actual results could differ materially and adversely from those anticipated. Except as require d b y law, we assume no obligation to update publicly any forward - looking statements, whether as a result of new information, future events or otherwise. 2
3 Delivering oral, synthetic live biotherapeutics to targeted location Allergan partnership for GI assets, rest of pipeline wholly owned HBV Deep pipeline of CpAMs with potential to achieve CURE Large market opportunity with high unmet need Microbiome Team Industry leaders w/ expertise in drug discovery drug development Strong balance sheet with cash through anticipated inflection points Assembly Biosciences: Overview Clinical stage company focused on two key INNOVATIVE areas of drug development
Program Drug Candidate (Mech. / Indication) Discovery Lead Op / Selection IND Enabling Phase 1 Rights Hepatitis B ABI - H0731 ( CpAM ) CpAM 2 nd Generation CpAM 3 rd Generation Novel Target Microbiome ABI - M201 (Ulcerative Colitis ) ABI - M301 (Crohn’s Disease) IBS compounds NASH, I/O & Other Clostridium difficile ( C.diff ) Gemicel ® (targeted oral delivery system) Leveraging our Microbiome Platform to Expand to Other High - rationale Indications Gastrointestinal Oncology • Immuno - oncology • Colorectal cancer Metabolic Disease • Obesity • Type 2 Diabetes CNS • Neurodegenerative • Psychiatric 4 Liver • NASH • PSC Development Pipeline Clinical POC achieved
Our Timeline Highlights Significant Progress to Date 5 x $2.8B Microbiome collaboration in GI with Allergan x ABI - H0731 Phase 1 a completed x Initiated ABI - H0731 Ph 1b o Advance 2 nd gen HBV compounds o Potential ABI - H0731 Ph 1b interim data x Expanded senior leadership team x Ph 1a/1b HBV trial initiated x Clinical microbiome candidate selected for c.diff o Initial POC HBV clinical data expected o Initiate trials with next generation HBV compounds o Expansion of microbiome indications o Advancements with collaboration partners x Raised $ 100M x Gemicel ® POC achieved x 1 st clinical candidate selected for HBV x HBV Program Launched ( Assembly ) x MB Program Launched ( Ventrus ) x Merger formed ASMB
Hepatitis B – Cure Program
Significant need for curative HBV therapies Market Opportunity ~ 240 million patients worldwide, ~90 million in China, ~2 million in US and >600,000 deaths/year globally CURE Eliminate (or Silence) Existing cccDNA Inhibit cccDNA Formation Prevent Virus Replication Limited to nucleos (t)ide analogs ( Nucs ) [ entecavir , tenofovir ] or pegylated - interferon - alpha ( PegIFN - α) Nucs suppress and maintain viral load at undetectable levels for years, BUT: – Less than 10% of patients achieve a sustained response off therapy 1 – NOT curative because they have limited effect on cccDNA • IFN’s are poorly tolerated, compliance is challenging, and cure rates are low Current therapies are inadequate ASMB believes a cure is possible • Decreasing/silencing cccDNA levels likely required to increase cure rates • Some patients have been cured • Woodchuck model shows cure correlated with elimination of detectable cccDNA 2 7 1 Marcellin, P . et al. (2016). Combination of Tenofovir Disoproxil Fumarate and Peginterferon - 2a Increases Loss of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B. Gastroenterology, 150(1), 134 – 144.e10. https:// doi.org/10.1053/j.gastro.2015.09.043 2 R . Colonno, et al. JID 2001;184:1236 - 45
HBV Life Cycle: Complicated with Limited Targets cccDNA Maintenance 8 • HBV genome only encodes FOUR known genes: Core, X, Polymerase and S ( HBsAG )
cccDNA Maintenance HBV Life Cycle: Failure of Nucs to Inhibit cccDNA ? CpAMs CpAMs CpAMs CpAMs 9 cccDNA Maintenance Nucleos (t)ides
HBV Life Cycle: New Antiviral Targets Being Pursued cccDNA Maintenance Nucs & Non - Nucleoside Entry Inhibitor RNA Interference 10
cccDNA Maintenance HBV Core Protein Is Required Throughout Lifecycle CpAMs ( C ore P rotein A llosteric M odulators) target Core protein and functions related to cccDNA generation ? CpAMs CpAMs CpAMs CpAMs 11
CpAMs and ETV inhibit HBV Replication by Distinct Mechanisms 12 cccDNA CpAM AAA... AAA... AAA... ETV pgRNA 0 20 40 60 80 100 DMSO 100 nM ETV 1 uM ABI-H0731 1 uM GLS4 Percent of DMSO Control Total Intracellular Extracellular Encapsidated HBV pgRNA Levels 0 50 100 150 200 DMSO 100 nM ETV 1 uM ABI-H0731 1 uM GLS4 Percent of DMSO Control Total Intracellular Extracellular Encapsidated HBV DNA Levels • CpAMs ABI - H0731 & GLS4 inhibit encapsidation of both viral DNA and pgRNA • ETV inhibited HBV DNA synthesis, but increased levels of pgRNA in intracellular capsids by failing to create the RNA:DNA duplex digested by RNaseH
CpAMs inhibit cccDNA generation in primary human hepatocytes Viral DNA, pgRNA, HBeAg and HBsAg in Primary Human Hepatocytes EC 50 ( nM ) Compound Viral DNA HBeAg HBsAg pgRNA ABI - H0731 154 2,210 3,000 1,840 Prototype ABI - H0808 80 196 310 305 ETV <0.1 Incomplete Incomplete Incomplete Viral DNA HBeAg HBsAg pgRNA CpAM - ABI - H0731 0.01 0.1 1 10 0 20 40 60 80 100 120 Concentration (mM) % o f C o n t r o l Prototype CpAM - ABI - H0808 0.01 0.1 1 10 0 20 40 60 80 100 120 Concentration (mM) % o f C o n t r o l Nuc - Entecavir 0.0001 0.001 0.01 0.1 0 20 40 60 80 100 120 Concentration (mM) % o f C o n t r o l • CpAMs reduced viral HBV DNA levels and known surrogate markers for cccDNA ( HBeAg , HBsAg and pgRNA ) • ETV was highly effective at inhibiting HBV DNA levels, but exhibited limited effect on cccDNA surrogates 13 • Presented at AASLD 2016
CpAMs block cccDNA formation in HBV infected cells Primary Human Hepatocytes (PHH) U p to ~ 125x EC 50 Entecavir DMSO 20 nM 100 nM DMSO 3.3 µM 10 µM ABI - H0731 >1,000x EC 50 Entecavir DMSO 100 nM ABI - H0731 DMSO 1.25 µM 2.5 µM 5.0 µM 10.0 µM cccDNA • Only CpAMs reduced cccDNA formation in HepG2 - NTCP and PHH • ETV (125 - 1000x EC 50 ) had minimal effect on cccDNA levels! Prototype ABI - H0808 Prototype ABI - H0808 DMSO 0.19 µM 0.56 µM 1.67 µM 5 .0 µM cccDNA DMSO 0.6 µM 3.0 µM To directly show inhibition of cccDNA levels Infection of HepG2 - NTCP and PHH Extraction of extrachromosomal DNA Sequential digestion with T5 exonuclease and EcoRI endonuclease Southern Blot Monitoring of HBV cccDNA Levels • Presented at AASLD 2016
ABI - H0731: Candidate Summary • Differentiated mechanism(s) that target core protein and impact cccDNA – Exhibits activity not seen with current SOC therapies • Proprietary chemistry designed for optimal treatment regimen – Highly potent and selective – Good bioavailability and metabolically stable in liver hepatocytes – Oral, once daily profile • Phase 1a Complete: Dose ranging well tolerated in all cohorts ‒ Single doses 100 - 1,000 mg, multiple doses 800 mg QD and 800 mg BID x 7 days ‒ Favorable PK profile with a half - life consistent with potential for QD dosing ‒ Well absorbed and associated with plasma concentrations that we believe will be sufficient to suppress viral replication and cccDNA generation ‒ No SAEs, no clinically significant AEs and no withdrawals due to AEs ‒ Treatment emergent AEs deemed “possibly related,” such as headache and rash, were mild and transient and only observed at the highest doses ‒ No clinically significant: treatment emergent laboratory abnormalities, vital sign changes or ECG findings ‒ Data to presented at AASLD, October 2017 in Washington, DC 15
HBV Program: ABI - H0731 Anticipated Updates and Milestones 16 H 2 2017 o Interim Phase 1b data o Select and advance 2 nd generation CpAM H2 2018 o Phase 2a initial POC data H1 2018 o Phase 2a initiation x ABI - H0731 was safe and well tolerated in Phase 1a study x Phase 1b initiated (preliminary antiviral efficacy w/ monotherapy over 28 days)
Robust HBV Pipeline F ocused on Targeting cccDNA 17 Program Drug Candidate Discovery Lead Op / Selection IND Enabling Phase 1 Phase 2 ABI - H0731 ( CpAM ) CpAM 2 nd Generation CpAM 3 rd Generation Novel Target Hepatitis B • Lead product ABI - H0731 completed Phase 1a earlier this year, and initiated Phase 1b in HBV patients • We have a pipeline of next generation molecules in research stages nearing candidate selection • All of our molecules in discovery and development focus on inhibition of cccDNA formation
Microbiome Program
The Microbiome : Realizing the Promise Modulating the gut microbiome has the potential to revolutionize the management of a broad range of therapy areas Infectious diseases GI disorders Oncology Metabolic diseases Neurosciences/CNS PoC data has demonstrated that fecal microbiota transplants (FMT) can restore dysbiotic microbiome to health But, FMT is inadequate as a therapy: lack of consistency, not scalable, not controlled, unreliable, poor route of administration safety risk 19
The Microbiome : Challenges 20 Mechanisms of disease pathology must be considered in context with environment, genome and microbiota Lack of consistency, not scalable, not controlled, unreliable, poor route of administration Diversity is needed for optimal microbiotic therapeutics Unique microhabitats require targeted delivery • pH • Oxygen • Antimicrobials • Nutrients Strain selection Manufacturing Targeted delivery
ASMB Solution: Proprietary Microbiome P latform Proprietary & scientifically rigorous, rational strain selection methodologies, including: • Human FMT studies • Sequencing and analysis protocols • Pathology - driven mechanisms • In vitro and in vivo models Differentiated Manufacturing Approach • Isolation • Development of appropriate culture media & cultivation conditions • Scale up • GMP cell banking of pure strains and bulk drug substance Gemicel ® delivery technology • Enables targeted delivery to specific regions of the colon • Delivers select strains of vegetative bacteria - Spores - Non - spores Commensal organisms viewed as safe • Potentially shortens time to clinical trials • Robust CMC data Rapid Clinical Development Targeted Drug Delivery cGMP Manufacturing Strain Selection Our differentiated and fully - integrated platform to deliver synthetic live biotherapeutics (LBT) 21
First/outer capsule: for bolus release of API in ileum Second/inner capsule: for bolus release of API in right colon GEMICEL®: ASMB’s proprietary targeted delivery technology 22 • GRAS ingredients • Manufacturing amenable to biologic products GEMICEL® Capsule The colon is an attractive site for drug delivery, particularly for microbiotic therapies if they can be delivered reliably.
23 Expertise in microbiome therapeutics, fully - integrated platform Expertise in gastrointestinal drug development and commercialization Collaboration Highlights: • Rights for GI development programs: ‒ ABI - M201 for Ulcerative Colitis (UC) ‒ ABI - M301 for Crohn’s Disease (CD) ‒ 2 compounds targeting Irritable Bowel Syndrome (IBS) ‒ ASMB has limited option to co - promote in US and China Financial Highlights • $50M upfront payment • Milestones & Royalties ‒ Up to ~$630M in development milestones ‒ Up to ~$2.15B in commercial milestones ‒ Tiered royalties up to mid - teens on net sales • Development Funding ‒ $75M R&D funding through POC (shared 2/3 by AGN, 1/3 by ASMB) ‒ AGN assumes all post - POC development costs Significant microbiome platform collaboration with focus on GI disorders Assembly and Allergan Enter Microbiome Collaboration
Summary: AGN/ASMB Microbiome Collaboration 1. Expedites our efforts into multiple GI indications 2. Leverages our end - to - end microbiome technology platform 3. Advances our ability to move microbiome candidates rapidly into clinical development with strategic partners 4. Aligns with our strategic goals for the company » Leverages both our Microbiome and HBV programs long term financially, commercially, and globally We intend to continue identifying appropriate development and commercial partners to rapidly advance our Microbiome program into other indications » Such as Liver disease/NASH, Immuno - oncology, Metabolic diseases, C .diff , CNS, etc. 24
Microbiome Program Discovery Lead Selection IND Enabling Phase 1b ABI - M201 (Ulcerative Colitis ) ABI - M301 (Crohn’s Disease) IBS Compounds NASH, I/O & Other Clostridium difficile ( C.diff ) Gemicel ® (targeted oral delivery system) Other Indications for Our Microbiome Platform Gastrointestinal Oncology • Immuno - oncology • Colorectal cancer Metabolic Disease • Obesity • Type 2 Diabetes CNS • Neurodegenerative • Psychiatric 25 Liver • NASH • PSC Microbiome Platform Clinical POC achieved Capturing the potential of the human microbiome for development of novel therapeutics
Financial Summary 26 Nasdaq ASMB Cash, cash equivalents & marketable securities ~$78.6M as of June 30, 2017 Shares outstanding ~ 17.3M Fully diluted ~ 22M
2017 ASMB Anticipated Milestones 27 x Microbiome collaboration for GI indications x ABI - H0731 dose ranging Ph 1a portion complete x Initiate ABI - H0731 Ph 1b trial x AASLD: 3 abstracts accepted □ H2 : ABI - H0731 Ph 1a safety and PK profile □ H2: ABI - H0731 Phase 1b (interim) results □ H2: 2nd Gen CpAM HBV selection 2018 □ Initiate Phase 2 trial of ABI - H0731 □ Select next indications for microbiome □ POC HBV clinical data expected □ Initiate trials with next gen HBV □ Advancements with collaboration partners
28 Delivering oral, synthetic live biotherapeutics to targeted location Allergan partnership for GI assets, rest of pipeline wholly owned HBV Deep pipeline of CpAMs with potential to achieve CURE Large market opportunity with high unmet need Microbiome Team Industry leaders w/ expertise in drug discovery drug development Strong balance sheet with cash through anticipated inflection points Assembly Biosciences: Overview Clinical stage company focused on two key INNOVATIVE areas of drug development
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