drna-20200812
FALSE000139952900013995292020-08-122020-08-12

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): August 12, 2020
__________________________________________________
DICERNA PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
__________________________________________________
Delaware001-3628120-5993609
(State or other jurisdiction
of incorporation)
(Commission
File Number)
(IRS Employer
Identification Number)
33 Hayden Avenue
Lexington, Massachusetts
 
 02421
(Address of registrant’s principal executive office)
 (Zip code)
(617) 621-8097
(Registrant’s telephone number, including area code)


(Former name or former address, if changed since last report)
__________________________________________________
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))

Securities registered pursuant to Section 12(b) of the Act:
Title of each classTrading symbol(s)Name of each exchange on which registered
Common Stock, par value $0.0001 per shareDRNAThe Nasdaq Global Select Market
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.
Dicerna Pharmaceuticals, Inc. (the “Company”) from time to time presents and/or distributes to the investment community at various industry and other conferences and/or at other meetings slide presentations to provide updates and summaries of its business. The Company is posting to the “Investors” portion of its website at http://investors.dicerna.com/ a copy of its current corporate slide presentation. These slides are attached to this Current Report on Form 8-K as Exhibit 99.1. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
The information in Item 7.01 of this Form 8-K, including Exhibit 99.1 attached hereto, 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 a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
Exhibit
No.
Description
99.1
104Cover Page Interactive Data File (embedded within the Inline XBRL document).




SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Date: August 12, 2020DICERNA PHARMACEUTICALS, INC.
By:
/s/ Douglas M. Fambrough, III
Douglas M. Fambrough, III, Ph.D.
Chief Executive Officer

drna_20200812xexx991
Exhibit 99.1 Corporate Overview Maximizing the Impact of RNAi on Medicine August 2020


 
Forward-Looking Statements This presentation has been prepared by Dicerna Pharmaceuticals, Inc. (“we,” “us,” “our,” “Dicerna,” or the “Company”) and includes forward-looking statements. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Examples of forward-looking statements include, among others, statements we make regarding: (i) the therapeutic and commercial potential of nedosiran, RG6346 (DCR-HBVS), DCR-A1AT and the GalXC™ platform; (ii) expectations that our cash, cash equivalents and held to maturity investments will fund operations into 2023; (iii) research and development plans and timelines, as well as regulatory pathways and plans, related to nedosiran, RG6346, DCR-A1AT, ALN-AAT02 and GalXC; (iv) the potential of Dicerna’s technology and drug candidates in the Company’s research and development pipeline; (v) the Company’s collaborations with Novo Nordisk A/S; Roche; Eli Lilly and Company; Alexion Pharmaceuticals, Inc., Boehringer Ingelheim International GmbH; and Alnylam Pharmaceuticals, Inc.; and (vi) the Company’s strategy, business plans and focus. The process by which an early-stage investigational therapy such as nedosiran and an early-stage platform such as GalXC could potentially lead to an approved product is long and subject to significant risks. Applicable risks and uncertainties include, but are not limited to, those risks identified under the heading "Risk Factors" included in the Company’s most recent Form 10-K filing and in other subsequent filings with the Securities and Exchange Commission. These risks and uncertainties include, among others, the impact to, and potential for delays in, the current and future conduct of the business of the Company, its clinical programs and operations as a result of the COVID-19 pandemic; the cost, timing and results of preclinical studies and clinical trials and other development activities; the likelihood of Dicerna’s clinical programs being executed within timelines provided and reliance on the Company’s contract research organizations and predictability of timely enrollment of subjects and patients to advance Dicerna’s clinical trials; the potential for future data to alter initial, interim and preliminary results of clinical trials, including the Phase 1 proof of concept data for RG346, an investigational GalXC RNAi treatment candidate for hepatis B virus and the multidose data from PHYOXTM 3 trial of nedosiran; the unpredictability of the duration and results of the regulatory review of Investigational New Drug (IND) applications and Clinical Trial Applications that are necessary to continue to advance and progress the Company’s clinical programs and the regulatory review of submissions relevant to regulatory agencies for marketing approvals, including New Drug Applications (NDAs); market acceptance for approved products and innovative therapeutic treatments; competition; the possible impairment of, inability to obtain and costs of obtaining needed intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated in R&D; that the Company may not realize the intended benefits of its collaborations; general business, financial and accounting risks; and the risks and potential outcomes from litigation. Dicerna is providing this information as of this date and does not undertake any obligation to update or revise it, whether as a result of new information, future events or circumstances or otherwise. Additional information concerning Dicerna and its business may be available in press releases or other public announcements and public filings made after the date of this information. Dicerna™, GalXC™ and PHYOX™ are trademarks of Dicerna Pharmaceuticals, Inc. 2


 
VISION Maximize the impact of RNAi on medicine STRATEGY Develop and commercialize our core high-probability-of-success programs either alone or in collaboration with partners Broadly enable the use of our GalXC technology by collaborating with therapeutic area leaders on non-core opportunities 3


 
The RNAi Modality Has Come of Age Many Thousands of Patients Have Been Treated With RNAi Therapeutics Multiple candidates in Approved registration or Dicerna was founded in Products pivotal 2007 to specialize in RNAi development Multiple committed large pharmas Many of the committed pharmas have chosen to collaborate with Dicerna in Established RNAi safety in large population studies 4


 
Dicerna Pipeline of Core and Collaborative Programs DISCOVERY/ CLINICAL PROOF-OF- REGISTRATION DICERNA’S CANDIDATE TARGET INDICATION PRECLINICAL RESEARCH CONCEPT TRIALS TRIALS PRODUCT RIGHTS Primary Hyperoxaluria Nedosiran 100% Types 1,2,3 Core RG6346 Hepatitis B Virus U.S. opt-in* Programs (DCR-HBVS) DCR-A1AT 100% U.S. A1AT Liver Disease ALN-AAT02 Alnylam ex-U.S. opt-in DCR-proprietary Undisclosed 100% *Under the Dicerna-Roche agreement, Dicerna has the option to co-fund pivotal development, which if exercised, entitles Dicerna to receive enhanced royalties and co-promotion rights in the U.S. NASH Complement-mediated Cardiometabolic HBV infection Liver-related cardiometabolic 1 target 4 targets (CM; liver and non-liver), RG6346 and multiple potential diseases neurodegeneration and pain Discovery/Research Initially two targets; ALXN targets 30+ potential targets Up to 8 CM targets exercised options for two DRNA option to co-fund dev. 2 Novo programs: DRNA opt-in more targets in Dec. 2019 DRNA retains rights to certain and co-promote in U.S. DRNA retains rights to neuro orphan indications • First target selected under 2 new orphan programs • First IND/CTA expected late research and development (Novo retains opt-in rights) 2020 (LY3561774) collaboration • Multiple targets selected • March 2020: LY3819469 (DCR-CM2) advances to LLY preclinical pipeline Currently active discovery or preclinical-stage liver program Currently active discovery or preclinical-stage non-liver program 5


 
We Believe Dicerna Is Creating Best-In-Class Opportunities In Primary Hyperoxaluria Dicerna conducted fundamental disease research to develop the LDHA mechanism to generate the most effective treatment for PH1 and the first treatment for PH2 and PH3 In Hepatitis B Dicerna’s X-sparing approach drives extended duration of effect that may lead to treatments that are both more convenient and more effective than non-X-sparing approaches In A1AT Liver Disease Dicerna and Alnylam have joined forces to potentially develop the best A1AT RNAi therapy for patients with A1AT liver disease In Extending RNAi Throughout the Body Dicerna’s best-in-class platform has powered our collaboration success and enables delivery to other tissues, including CNS, skeletal muscle and adipose, with unparalleled medicinal chemistry flexibility 6


 
Platform Expansion to Achieve Effective Extrahepatic Delivery Including Central and Peripheral Nervous Tissues and Other Extrahepatic Tissues GalNAc sugars to bind hepatocyte ASGPR Liver-targeted GalXC is the basis of our current best-in-class core pipeline programs and most of our collaboration programs New chemistries Enhanced secondary structures and chemistries Our RNAi platform provides remarkable flexibility for medicinal chemistry optimization and expansion • We are modifying the fundamental nucleic acid composition of oligonucleotides to enhance drug-like properties • Optimization of nucleic acid composition alone can drive significant extrahepatic delivery function • We are utilizing a broad range of molecular weights, secondary structures and chemistries 7


 
Key Achievements and Multiple Upcoming Milestone Targets ✓ Nedosiran: Positive first multidose results from PHYOX3 open-label clinical trial – Q1 2020 ✓ RG6346: Positive Phase 1 proof-of-concept data from all existing cohorts – Q3 2020 ✓ GalXC: Positive data presented for extending GalXC technology to additional tissues – Q3 2020 ✓ Nedosiran: Positive updated multidose data from PHYOX3 open-label clinical trial – Q3 2020 ❑ Nedosiran: PHYOX2 pivotal clinical trial enrollment completion – Q4 2020 ❑ Collaborative Program: IND or CTA filing for LY3561774 – late 2020 ❑ DCR-A1AT/ALN-AAT02: Program selection & potential initiation of patient dosing – Q1 2021 ❑ Nedosiran: PHYOX2 last patient out 1H 2021 ❑ DCR-proprietary: IND or CTA filing – mid-2021 ❑ Nedosiran: NDA submission – Q3 2021 8


 
Nedosiran for the Treatment of Primary Hyperoxaluria


 
Primary Hyperoxaluria A Family of Ultra-Rare, Life-Threatening Genetic Disorders Resulting in Renal Complications Known Types of Primary Hyperoxaluria The three known types of PH all PH1 PH2 PH3 result in overproduction of oxalate, Genetic mutation Genetic mutation Genetic mutation AGXT GRHPR HOGA1 which can lead to: Targeting GO blocks GO • Recurrent kidney stones glyoxylate in PH1 only (lumasiran) • Nephrocalcinosis (deposition of Glyoxylate Glyoxylate Glyoxylate calcium in the kidney) • Chronic kidney disease that may progress to end-stage renal disease, NedosiranNedosiran blocksblocks final final common common pathway pathway of oxalate of oxalate productionproduction by silencingby silencing LDHA LDHA • Systemic oxalosis, which also impacts the heart, skin, eyes, bones Oxalate Oxalate Oxalate Kidney • Patients may require chronic dialysis function preservation and a joint liver-kidney transplant Calcium oxalate crystallization Impacted Kidney GO = glycolate oxidase by ESRD & stones LDHA = lactate dehydrogenase A systemic oxalosis 10


 
Positive Interim Results: Nedosiran PHYOX3 Multidose Open-Label Trial Mean Value for All Participants (n=11) in Near-Normal Range Starting Day 60 • PHYOX3 ongoing, three-year, multidose, Mean 24-Hour Urinary Oxalate Values open-label extension study (n=11, minimum 5 doses) ‒ Participants are Phase 1 trial patients 2.5 who have rolled over into PHYOX3 ‒ Interim results* for the 11 of 16 2.0 SEM participants who have received at least ± five monthly subcutaneous doses of 1.5 nedosiran (Days 1, 30, 60, 90 and 120) Mean ‒ Values standardized for body surface /24hr) /24hr) area 2 1.0 ≥0.460 and <0.600 Near normal • Mean Uox value reaches near-normal Oxalate Urinary hr 24 0.5 <0.460 Normal range by Day 60 and is maintained (mmol/1.73m • Includes PH1 and PH2 participants 0.0 BL (101) BL (301) 30 60 90 120 Days • Mean reduction is 54.3% = 170 mg subcutaneous injection 11 Uox = urinary oxalate *Results shown reflect data from interim analysis on July 10, 2020


 
PHYOX3 Interim Analysis: Normalization or Near-Normalization of Uox Levels in 100% of PH1 Patients at One or More Timepoints • 4 of the 11 participants have reached normal Uox concentrations at 3 consecutive visits and are eligible for weaning off disease management, including hyperhydration – 1 additional patient who has not yet reached Day 120 also achieved normal Uox at 3 consecutive visits • For PH1 participants, the average Uox level achieved is in the normal range (mean Uox= 0.404 mmol/1.73m2/24 hr, 66% reduction) at Day 120 • For PH2 participants, 2 of 3 patients achieved normalization at one or more timepoints through Day 120 Patients Reaching Normalization or Patients Reaching Normalization PH Type Near-Normalization at One or More at One or More Timepoints Timepoints PH1 (n=8) 6 (75%) 8 (100%) PH2 (n=3) 2 (66%) 2 (66%) PH1+PH2 (n=11) 8 (73%) 10 (91%) Normalization: Uox at or below 0.460 mmol/1.73m2/24hr Near-Normalization: Uox between 0.460 and 0.600 mmol/1.73m2/24hr (~130% of normal) 12


 
PHYOX3 Interim Safety Data 301 Study • Favorable risk/benefit profile in this Category n (%) study Total TEAEs 16 (94.1) TEAEs occurring in >=10% of participants in group (n, %) Injection site discomfort 6 (35.3) • AEs mostly related to SC injection Injection site pain 6 (35.3) Injection site erythema 4 (23.5) • Flank pain 3 (17.6) Drug-related ISRs in 3/16 participants Injection site discoloration 3 (17.6) Aspartate aminotransferase increased 2 (11.8) • ALT elevations <2.5 ULN; both Headache 2 (11.8) participants started study with Injection site atrophy 2 (11.8) Injection site hematoma 2 (11.8) elevated ALT Pyrexia 2 (11.8) ISRs (n, %) 3 (17.6) • One SAE of nephrolithiasis TEAEs leading to discontinuation of study treatment (n, %) 0 TEAEs leading to study withdrawal (n, %) 0 Death (n, %) 0 • No other clinically significant Serious TEAEs (n, %) 1 (5.9) laboratory abnormalities, ECG findings Severity of TEAEs (n, %) [1] Mild 12 (70.6) and vital signs Moderate 3 (17.6) Severe 1 (5.9) Treatment-emergent adverse event (TEAE) is defined as any adverse event that begins on or after the first dose of study intervention. Safety population n= 16; [1] The severity shown is the greatest severity reported for a particular subject (Severe > Moderate > Mild) Abbreviations: SC, subcutaneous; BL, baseline, ALT, alanine transaminase; ULN, upper level of normal, ECG, electrocardiograph 13 Based on availability of data as of July 10, 2020


 
Nedosiran Target Profile: The Only RNAi Drug Candidate in Development for All PH Types High Unmet Medical Need Across All PH Types Can Be Addressed Expected US Prevalence* Education Patient & Diagnostic Caregiver Testing Support Nedosiran Availability Similar numbers for major EU markets Estimated PH Diagnosis Rates PH1 PH2 PH3 Nedosiran’s target profile provides a comprehensive treatment option for all PH patients with convenient once Current Diagnosis monthly dosing, including self administration ^ ~40% – 50% ~10% ~7% Projections Dicerna estimates nedosiran *Prevalence based on PH mutant alleles found in the National Heart, Lung, and Blood Institute Exome Sequencing Project global sales >$500M (NHLBI ESP) and calculated according to Hardy-Weinberg equilibrium for each PH type using the sum of all alternate PH1, PH2 or PH3 alleles (known, or known and scored as pathogenic) and all wild type alleles. 1. Hopp K, et al. J Am Soc Nephrol. 2015;26(10):2559-2570. 2. U.S. Census Bureau population on a date: February 20, 2020. United States Census Bureau website, 2020. 14 ^ Sources: Dicerna internal estimates PH claims/registry analysis and scientific advisors. Analysts projections


 
RG6346 for the Treatment of Hepatitis B Virus (HBV) Infection


 
Hepatitis B: A Severe, Global Unmet Medical Need • Significant worldwide prevalence: ~292 million infected • Causes more than 887,000 deaths per year • Current treatments are rarely effective in achieving functional cures • Dicerna is collaborating with Roche to develop RG6346 and potentially other agents for the treatment of HBV Electron micrograph of HBV showing infectious viral particles (~42 nm) and non-infectious aviral “decoy” particles (~22 nm) and filaments Sources: Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. The Lancet Gastroenterology and Hepatology. Volume 3, Issue 6, June 2018, Pages 383-403. World Health Organization. Finding a cure for hepatitis B: are we close? https://www.who.int/hepatitis/news-events/hbv-cure-overview/en/. Accessed Aug. 4, 2020. 16


 
The Promise of RNAi for the Treatment of Chronic HBV Organization of the HBV Genome Enables Effective RNAi Targeting of Multiple Viral Functions Overlapping mRNAs enable targeting multiple HBV genes with RNAi Dicerna’s RG6346 molecule targets the Conserved S Region Preclinical analysis shows this is the S gene (HBsAg) ideal target region, yielding extended Surface protein. Involved in viral coat and immune duration viral silencing and covering tolerizing agent nearly all viral genotypes P gene Polymerase. Involved in Conserved S Region viral genome production C gene Silences S, P and C encoding mRNAs RG6346 targets this region Core protein. Involved in capsid assembly and viral gene regulation Conserved X Region X gene Silences S, P, C and X encoding mRNAs Involved in maintenance of cccDNA and viral gene regulation 17


 
RG6346’s X-Sparing Approach Demonstrates Superior HBsAg Reduction When Targeting Only the Conserved S Region HBsAg Levels in HBV Core Protein HDI-HBV Plasmid Mouse Model Vehicle • With no treatment, Core (cccDNA-dependent) protein is in nucleus and 100 cytoplasm of liver cells Vehicle control 10 S and X Conserved SEM - Regions targeted 1 X and S Regions Targeted • Silencing of X gene leads to 0.1 Only Conserved S nuclear Core protein likely %HBsAg +/ %HBsAg Region targeted (Normalized to d0) to (Normalized driving HBsAg rebound 0.01 (RG6346 strategy) 2/3 BLOQ 3/3 BLOQ 0.001 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 3mg/kg qWx3 Time (weeks) Only S Region Targeted (RG6346) • Sparing the X gene leads to cytoplasmic Core protein, likely maintaining HBsAg • Conserved S Region only: ≥3.9 log reduction, long duration of activity silencing and driving • Conserved S & X Regions: 3.0 log reduction, shorter duration of activity extended duration 18


 
RG6346 Phase 1: Three-Part Safety, Tolerability, PK/PD Study in Healthy Volunteers and Participants With Chronic Hepatitis B Randomized 2:1 active vs placebo, single-ascending- Completed RG6346 dose cohorts: Group A dose study in adult healthy volunteers n=30 0.1, 1.5, 3.0, 6.0, 12.0 mg/kg Randomized 5:3 active vs placebo, single-dose study Ongoing RG6346 dose cohort: Group B in NUC-naïve participants with chronic HBV infection n=9* 3.0 mg/kg Ongoing Randomized 2:1 active vs placebo, multiple- RG6346 dose cohorts: n=18 Group C ascending-dose study in participants with chronic 1.5, 3.0, 6.0 mg/kg; Currently dosing 6.0 HBV infection on stable NUC therapy 4 monthly doses mg/kg cohort • Key inclusion/exclusion criteria: ‒ HBeAg positive with HBsAg >1000 IU/mL or HBeAg negative with HBsAg >500 IU/mL; NUC naïve with screening serum HBV DNA >2000 IU/mL and ALT ≥35 U/L (males) or ≥30 U/L (females) ‒ Clinical history compatible with compensated liver disease, with no evidence of cirrhosis ‒ Group B participants have no current or prior use of nucleoside or nucleotide analogue (NUC) therapy • After completion of the treatment period, study participants with ≥1 log HBsAg reduction are followed in a conditional follow-up *One additional subject was enrolled in Group B (total N=9) to replace a subject determined to be ineligible after the study dose had been administered. 19


 
RG6346 Showed Strong, Durable Reduction in HBsAg Levels at All Doses Validates Predicted Long Duration of Effect Group C Dosing Cohorts Conditional Follow-Up • Mean maximal HBsAg reduction was 1.88 ⱡ log10 IU/mL (3 mg/kg cohort) ‒ 6 mg/kg cohort ongoing (only 2 of 4 ⱡ participants had reached Day 112) ⱡ • HBsAg reductions maintained through * n=2 (1.5 mg/kg) Day 336. Rebound not yet observed. * n=2 (6 mg/kg) • Longest-treated participant has 2.21 ⱡ n=3 (1.5 mg/kg) log10 IU/mL reduction at Day 392 n=3 (3 mg/kg) * ⱡ ⱡ n=3 (6 mg/kg) • 6 of 10 Group C participants who * completed Day 112 had HBsAg <100 ⱡ ⱡ IU/mL at last reported visit. ⱡ ⱡ ⱡ * ⱡ * * Results shown as of June 25, 2020 data cutoff; 4 participants dosed with RG6346 Days in each dosing cohort at each time point unless otherwise noted 20


 
NUC-Naïve Patient With Beneficial Flare As Defined in Clinical Trial Protocol, Suggesting Enhanced Patient Immune Response Two Additional Group B NUC-Naïve Patients Had Similar Beneficial Responses Reductions in All Viral Markers Synthetic and Excretory Liver Function Preserved Coincides with Beneficial ALT Flare During Beneficial ALT Flare Days Days • Transient ALT flares with viral marker reductions represent activation of patient immune response to the virus • This response meets the “beneficial ALT flare” definition in our FDA agreed upon clinical trial protocol1 Patient from Group B, 3 mg/kg cohort 1. Fontana RJ et al. (2020) J Viral Hepat (2) 96-109 21


 
In Phase 1 Patients, RG6346 Appeared To Be Safe and Generally Well Tolerated as of the Interim Analysis No Dose Effect on Liver Function Tests Observed in Healthy Volunteers at Dosages ≤12 mg/kg • No serious adverse events (SAEs) associated with RG6346 observed as of June 25, 2020 in Groups B or C ‒ One participant in Group A (healthy volunteer on placebo) experienced one SAE not related to study drug • No dose-limiting toxicities • No safety-related discontinuations • No dose/exposure dependent increase in frequency or severity of safety parameters: AEs, safety labs, ECG or vital signs ‒ In all participants with flares, or flare-like ALT/AST elevations, overall liver synthetic and excretory functions were preserved ‒ No cases of simultaneous elevations of ALT >3x ULN and total bilirubin >2x ULN • The most commonly reported AEs were related to the injection site ‒ All injection site reactions (ISRs) were mild with exception of a single patient who had two moderate ISRs 22


 
RG6346 Phase 1: Encouraging HBsAg Reduction and Duration of Response • Phase 1 proof-of-concept study confirms X-sparing hypothesis and potential for best-in-class activity • Extended duration of effect: 1.5 mg/kg cohort with no reduction in silencing at Day 336 • Beneficial ALT flares consistent with enhanced patient immune responses observed in 50% of RG6346 treated Group B patients with indications of similar activity in Group C • Trial ongoing; additional participants in Group C expected to complete treatment period in September 2020 ‒ May see additional dose response from two ongoing participants in 6.0 mg/kg dosing cohort • Plan to present Phase 1 data at future scientific conference • Roche is responsible for post-Phase 1 development of RG6346 23


 
DCR-A1AT and ALN-AAT02 for the Treatment of Alpha-1 Antitrypsin Deficiency-Associated Liver Disease


 
Alpha-1 Antitrypsin Deficiency-Associated Liver Disease Most Disease Is Caused by a Single Missense Allele That Forms Aggregates in Hepatocytes • Alpha-1 antitrypsin (A1AT): predominantly 1-Antitrypsin Deficiency produced in liver and secreted into blood Z mutation Glu342→Lys342 • Pi*ZZ genotype of the SERPINA1 gene affects 95% Polymerization of 1-antitrypsin of patients with A1AT deficiency • The Z-allele of the SERPINA1 gene produces an abnormal form of A1AT protein that aggregates and then can accumulate in the liver and lead to liver disease Intracellular accumulation Plasma deficiency neonatal hepatitis, liver cirrhosis early-onset emphysema ‒ Aggregation of A1AT in the liver results in low levels of A1AT throughout the body, which can lead to lung disease, especially in smokers • DCR-A1AT and ALN-AAT02 designed specifically to target A1AT deficiency-associated liver disease Toxic gain of function Loss of function deficiency Janciauskiene et al. 2013: Acute Phase Proteins 25


 
Sustained Duration of Activity Seen in Mice and Non-Human Primates Dosed With DCR-A1AT Sustained, Dose-Dependent Knockdown of A1AT Protein in Both Mice and Monkeys Z-AAT Protein Knockdown in PiZ Mice A1AT Protein Knockdown in Monkeys BS 3.0 mg/ g 1 5 3.0 mg/ g 1 5 10.0 mg/ g 10.0 mg/ g 100 100 SEM SEM 5 5   50 50 Mean Mean AAT Protein Concentration Protein AAT - 5 5 0 Relative A1AT Protein Concentration Protein A1AT Relative 0 Relative Z Relative 0 1 3 4 5 6 9 0 4 6 10 1 14 16 1 0 4 Single Weeks Post-Dose Single Weeks Post-Dose Subcutaneous Dose Subcutaneous Dose • DCR-A1AT is currently in a Phase 1 proof-of-concept study in healthy volunteers 26


 
A1AT Clinical Development Program Seeking a Rapid Path to Approval With the Strongest Candidate • Dicerna and Alnylam are collaborating on their DCR-A1AT and ALN-AAT02 programs • Dicerna is responsible for clinical development through approval, and Alnylam has rights to ex-U.S. commercialization of the approved product • We expect to advance only one of the two programs to approval • After completion of Phase 1 studies for both programs, a single program will be advanced to a multidose Phase 2 study in patients • We believe the planned development program can enable a pivotal trial without additional studies 27


 
Extrahepatic Platform


 
Expanding RNAi Delivery to Other Tissues Expect Future Pipeline and Collaborations to Include Delivery Beyond Liver Non -Human Primate Gene Silencing Four Weeks After a Single RNAi Dose 1 SEM 5 ± 0 1 2 5 a C S 1 F Central Nervous System 0 0 (i .c .m 7 . Single 45 mg i.c.m. Dose 5 ) 5 % Target mRNA0 Remaining R Target mRNA/(GAPDH/RPL23)2 N 5 A i (i .c . 0 m .) Prefrontal Cortex 29 Frontal Cortex (grey matter) Frontal Cortex (white matter) i.c.m. = intracisterna magna Parietal Cortex (grey matter) Parietal Cortex (white matter) Temporal Cortex (grey matter) Temporal Cortex (white matter) Midbrain SingleSkeletal Subcutaneous Muscle Dose 1 4 Occipital Cortex (grey matter) 0 1 2 SEM) 0 Occipital Cortex (white matter) ± 1 0 0 Cerebellum 8 0 Brainstem 6 0 (rel to 4PBS, Mean % Target mRNA0 Remaining 2 0 0 Single AdiposeSubcutaneous Tissue Dose 1 PBS 4 0 1 2 0 10 mg/kg SEM)1 ± 0 0 8 30 mg/kg 0 6 0 (rel to4 PBS, Mean % Target mRNA0 Remaining 2 0 0 PBS 10 mg/kg 30 mg/kg


 
Corporate Collaborations


 
Successfully Executing on High-Value Collaboration Strategy Collaborations Have Delivered >$500M in Upfront Payments $175M upfront $75M total annuals $200M upfront $50M equity • 30+ potential $100M upfront • RG6346 and targets for liver- $100M equity multiple potential related CM diseases HBV-related • Up to 8 targets • 2 Novo programs: DRNA opt-in cardiometabolic • DRNA option to co- targets, liver and fund development • DRNA retains rights non-liver and co-promote in to 2 new orphan programs (Novo $22M upfront • Neurodegeneration U.S. retains opt-in rights) $15M equity & pain targets • DRNA retains rights • 4 complement- $10M upfront to certain neuro mediated targets orphan indications Dicerna retains opt-in rights • 1 NASH Target • $20M option • $5M option exercised exercised signed Nov. 2017 Oct. 2018 Oct. 2018 Oct. 2019 Nov. 2019 31


 
Summary


 
Key Achievements and Multiple Upcoming Milestone Targets ✓ Nedosiran: Positive first multidose results from PHYOX3 open-label clinical trial – Q1 2020 ✓ RG6346: Positive Phase 1 proof-of-concept data from all existing cohorts – Q3 2020 ✓ GalXC: Positive data presented for extending GalXC technology to additional tissues – Q3 2020 ✓ Nedosiran: Positive updated multidose data from PHYOX3 open-label clinical trial – Q3 2020 ❑ Nedosiran: PHYOX2 pivotal clinical trial enrollment completion – Q4 2020 ❑ Collaborative Program: IND or CTA filing for LY3561774 – late 2020 ❑ DCR-A1AT/ALN-AAT02: Program selection & potential initiation of patient dosing – Q1 2021 ❑ Nedosiran: PHYOX2 last patient out 1H 2021 ❑ DCR-proprietary: IND or CTA filing – mid-2021 ❑ Nedosiran: NDA submission – Q3 2021 33


 
Well Positioned for Near- and Long-Term Success Driving Growth with Diversified Pipelines and Expanding Technology Platforms • Core Pipeline: Current pipeline yields multiple major milestones over next year+ ‒ Nedosiran: A differentiated therapy for all PH types (PH1, PH2 and PH3) ‒ RG6346: Potential best-in-class therapeutic with strong and durable HBsAg reduction for treatment of chronic HBV ‒ DCR-A1AT/ALN-AAT02: Two options enable opportunity to choose best candidate for A1AT liver disease • Partner of Choice: Collaborative pipeline with leading global biopharmas expected to yield multiple clinical programs for years to come • Going Beyond GalXC: Unparalleled medicinal chemistry flexibility enables expansion beyond foundational GalXC liver delivery to additional tissues and indications • Strong Balance Sheet: Cash into 2023 provides runway through projected nedosiran commercialization ‒ $669.2 million in cash, cash equivalents and marketable securities as of June 30, 2020 34