8-K

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): January 31, 2017

Dimension Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

DELAWARE	001-37601	46-3942159
(State or other jurisdiction of incorporation)	(Commission File Number)	(I.R.S. Employer Identification No.)

840 Memorial Drive, 4th Floor Cambridge, MA	02139
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code (617) 401-0011

Not Applicable

(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))

Item 7.01 Regulation FD Disclosure.

On January 31, 2017, Dimension Therapeutics, Inc. (the “Company”) announced clinical trial data in a press release, a copy of which is furnished herewith as Exhibit 99.1.

In addition, on January 31, 2017, the Company posted an updated corporate presentation on its website, www.dimensiontx.com. A copy of this presentation is furnished herewith as Exhibit 99.2.

The information in this Item 7.01 and Exhibits 99.1 and 99.2 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, except as expressly set forth by specific reference in such filing.

Item 8.01 Other Events.

In connection with the announcement of clinical trial data described above, the Company announced preliminary topline safety and early efficacy results of the Company’s multi-center phase 1/2 study of DTX101 for the treatment of adult patients with moderate/severe to severe hemophilia B. DTX101, the Company’s lead AAV candidate, is designed to deliver stable expression of blood clotting Factor IX (FIX) in patients with hemophilia B, a rare genetic bleeding disorder resulting from a deficiency in FIX. The Company is reporting preliminary topline phase 1/2 results from the trial’s first two dose cohorts (Cohort 1: N=3, 1.6 x 10¹² GC/kg; Cohort 2: N=3, 5 x 10¹² GC/kg). Patients in the two cohorts have been in post-treatment follow-up ranging from 6 to 52 weeks.

In the phase 1/2 study, patients received serotype AAVrh10 vector with a codon-optimized FIX gene expressing wild-type FIX protein. Evidence of efficient liver transduction of DTX101 was observed across the two patient cohorts. Patients in the second dose cohort achieved peak FIX expression of 13%, 20%, and 12% at weeks 4, 8, and 8, respectively. FIX activity was 5% and 8% in two patients at 12-weeks follow-up, and 7% for the third patient at 7 weeks. For the low-dose cohort, expression levels achieved 10-11% peak activity, stabilizing between 3-4% at last follow-up (weeks 24, 48, and 52). The findings in the low-dose cohort are comparable to results published by Nathwani et al in the New England Journal of Medicine (2011), where patients have had measurable levels of FIX for 3-5 years or more at last follow-up (Nienhuis et al. 2016). All patients in both cohorts improved from moderate/severe-to-severe to either moderate or mild range in terms of factor levels based on World Federation of Hemophilia (WFH) criteria. In addition, none of the patients in Cohort 2 have required prophylactic or on-demand recombinant FIX transfusion for spontaneous bleeds post-dosing. According to the WFH, people with FIX levels of 5% or more usually bleed only as a result of surgery or major injury, do not bleed often and, in fact, may never have a bleeding problem.^*

Elevations in alanine aminotransferase (ALT) were observed in 5 of 6 patients, with patient 3 in Cohort 2 experiencing a grade 4 adverse event due to an elevated laboratory ALT (defined as >800 IU/L). All elevated liver enzymes were clinically asymptomatic with no elevations of gamma-glutamyl transferase (GGT), alkaline phosphatase or bilirubin, and no patients experienced a drug related serious adverse event (SAE) as of the January 28, 2017 data cutoff. Preliminary Phase 1/2 findings from 2 patients in each of Cohort 1 and 2 prompted administration of a standard tapering course of corticosteroids to treat mild, asymptomatic elevations in ALTs (52-98 IU/L), similar to findings from multiple studies using other AAV serotypes, including AAV8 and AAV9. The third patient in Cohort 2 also received corticosteroids, experiencing a peak ALT of 914 IU/L, and was at 431 IU/L at 6 weeks post-dosing. The Company expects that Cohort 2 will continue to receive a standard tapering course of

corticosteroid therapy and as of the January 28, 2017 data cutoff, 2 of 3 patients’ ALT levels were in the normal range. Cohort 1 patients were all clinically stable and off steroids with ALT levels in the normal range. As required by the trial protocol, the Company reported the ALT levels for patient 3 in Cohort 2 to the Data Safety Monitoring Committee (DSMC), the U.S. Food and Drug Administration (FDA), and the appropriate regulatory authorities and will await their feedback prior to initiating dosing of Cohort 3.

^*Information sourced from World Federation of Hemophilia

Cautionary Note Regarding Forward-Looking Statements

This Current Report on Form 8-K contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the development, preclinical and clinical results, and the continued progress of the Company’s portfolio and programs, including the initiation, timing, scope, or likelihood of regulatory filings and approvals, and the Company’s ability to develop and advance product candidates into, and successfully complete, clinical studies. All such forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the risks that the Company’s product candidates, including its candidates, DTX101 and DTX301, will not successfully be developed or commercialized in the times indicated or at all; the impact of the observed data in Cohorts 1 and 2, including the adverse event described above and any later safety event on timing, dosing, regulatory action or patient enrollment with respect to DTX101 and DTX301; and the risks described under the caption “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, which is on file with the Securities and Exchange Commission, as well as other risks detailed in the Company’s additional filings with the Securities and Exchange Commission. All information in this Current Report on Form 8-K is as of the date of this Current Report on Form 8-K, and the Company undertakes no duty to update this information unless required by law.

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: January 31, 2017	DIMENSION THERAPEUTICS, INC.
	By:	/s/ Jean Franchi
		Jean Franchi
		Chief Financial Officer

EX-99.1

Exhibit 99.1

Dimension Announces Interim Topline Results from Ongoing Phase 1/2 Clinical Program for DTX101, Dimension’s Lead AAV Product Candidate in Development for Adult Patients with Moderate/Severe to Severe Hemophilia B

Evidence of High-Efficiency Liver Transduction with AAVrh10 Vector

Sub-clinical, Asymptomatic Elevations of ALT Observed in 5 of 6 Patients

CAMBRIDGE, Mass., January 31, 2017 — Dimension Therapeutics, Inc. (NASDAQ:DMTX), a biopharmaceutical company advancing novel, adeno-associated virus (AAV) gene therapies targeting the liver, a key organ for human metabolism, today announced preliminary topline safety and early efficacy results of Dimension’s multi-center phase 1/2 study of DTX101 for the treatment of adult patients with moderate/severe to severe hemophilia B. DTX101, Dimension’s lead AAV candidate, is designed to deliver stable expression of blood clotting Factor IX (FIX) in patients with hemophilia B, a rare genetic bleeding disorder resulting from a deficiency in FIX. Dimension is reporting preliminary topline phase 1/2 results from the trial’s first two dose cohorts (Cohort 1: N=3, 1.6 x 10¹² GC/kg; Cohort 2: N=3, 5 x 10¹² GC/kg). Patients in the two cohorts have been in post-treatment follow-up ranging from 6 to 52 weeks.

In the phase 1/2 study, patients received serotype AAVrh10 vector with a codon-optimized FIX gene expressing wild-type FIX protein. Evidence of efficient liver transduction of DTX101 was observed across the two patient cohorts. Patients in the second dose cohort achieved peak FIX expression of 13%, 20%, and 12% at weeks 4, 8, and 8, respectively. FIX activity was 5% and 8% in two patients at 12-weeks follow-up, and 7% for the third patient at 7 weeks. For the low-dose cohort, expression levels achieved 10-11% peak activity, stabilizing between 3-4% at last follow-up (weeks 24, 48, and 52). The findings in the low-dose cohort are comparable to results published by Nathwani et al in the New England Journal of Medicine (2011), where patients have had measurable levels of FIX for 3-5 years or more at last follow-up (Nienhuis et al. 2016). All patients in both cohorts improved from moderate/severe-to-severe to either moderate or mild range in terms of factor levels based on World Federation of Hemophilia (WFH) criteria. In addition, none of the patients in Cohort 2 have required prophylactic or on-demand recombinant FIX transfusion for spontaneous bleeds post-dosing. According to the WFH, people with FIX levels of 5% or more usually bleed only as a result of surgery or major injury, do not bleed often and, in fact, may never have a bleeding problem.^*

Elevations in alanine aminotransferase (ALT) were observed in 5 of 6 patients with patient 3 in Cohort 2 experiencing a grade 4 adverse event due to an elevated laboratory ALT (defined as >800 IU/L). All elevated liver enzymes were clinically asymptomatic with no elevations of gamma-glutamyl transferase (GGT), alkaline phosphatase or bilirubin, and no patients experienced a drug related serious adverse event (SAE) as of the January 28, 2017 data cutoff. Preliminary Phase 1/2 findings from 2 patients in each of Cohort 1 and 2 prompted administration of a standard tapering course of corticosteroids to treat mild, asymptomatic elevations in ALTs (52-98 IU/L), similar to findings from multiple studies using other AAV serotypes, including AAV8 and AAV9. The third patient in Cohort 2 also received corticosteroids, experiencing a peak ALT of 914 IU/L, and was at 431 IU/L at 6 weeks post-dosing. We expect that Cohort 2 will continue to receive a standard tapering course of corticosteroid therapy and as of the January 28, 2017 data cutoff, 2 of 3 patients’ ALT levels were in the normal range. Cohort 1 patients were all clinically stable and off steroids with ALT levels in the normal range. As required by the

trial protocol, we have reported the ALT levels for patient 3 in Cohort 2 to the Data Safety Monitoring Committee (DSMC), the U.S. Food and Drug Administration (FDA), and the appropriate regulatory authorities and will await their feedback prior to initiating dosing of Cohort 3.

“We are encouraged by the apparent efficiency of gene transduction and the early trend we are seeing in sustained FIX activity across both cohorts with our wild-type FIX AAVrh10 vector in patients. We continue to explore the therapeutic window for DTX101 as our data mature and in light of the ALT rises that appear to be associated with a decline in FIX activity,” said Dr. Annalisa Jenkins, MBBS, FRCP, Chief Executive Officer of Dimension.

As the company pipeline and platform progresses, a broad program of translational research, conducted in partnership with the University of Pennsylvania and other academic collaborators, will continue to evaluate the evolving data. These data will add to the scientific understanding of the emerging profile for AAV gene therapy in the clinical setting and will be the subject of future presentations at academic and medical congresses.

DTX101 has received orphan drug designation from U.S. Food and Drug Administration and the European Commission.

^*Information sourced from World Federation of Hemophilia

About Hemophilia B

Hemophilia B is a rare genetic bleeding disorder resulting from a deficiency in FIX. The current standard of care, chronic replacement of FIX protein through routine intravenous infusion, often does not achieve sustained, durable FIX expression, potentially putting patients at risk for spontaneous bleeds and long term joint destruction. In 2013, the World Federation of Hemophilia estimated there were more than 28,000 hemophilia B patients worldwide, including 4,000 patients in the United States.

About the Hemophilia B Phase 1/2 Program

Dimension’s phase 1/2 clinical trial of DTX101 is a single arm, open-label, multi-center study, designed to evaluate the safety, dose, and early efficacy of DTX101 in adult patients with moderate/severe to severe hemophilia B. Patients enrolled in Cohorts 1 and 2 range in age from 28 to 70 years, demonstrating baseline FIX expression of £2% that requires either prophylactic or on demand recombinant FIX transfusion. Dimension is continuing to explore underlying demographics and patient characteristics to optimize dosing of DTX101.

Additional information about Dimension’s Phase 1/2 study of DTX101 may be found at ClinicalTrials.gov, using Identifier NCT: NCT02618915.

About Dimension Therapeutics, Inc.

Dimension Therapeutics, Inc. (NASDAQ:DMTX) is the leader in discovering and developing new therapeutic products for people living with devastating rare and metabolic diseases associated with the liver, based on the most advanced, mammalian adeno-associated virus (AAV) gene delivery technology. Dimension is actively progressing its broad pipeline, which features programs addressing unmet needs for patients suffering from inherited metabolic diseases, including OTC deficiency, GSDIa, citrullinemia type 1, PKU, Wilson disease, a collaboration with Bayer in hemophilia A, and a wholly owned clinical

program in hemophilia B. Dimension has two phase 1/2 clinical trials for the treatment of hemophilia B and OTC deficiency. The company targets diseases with readily identifiable patient populations, highly predictive preclinical models, and well-described, and often clinically validated, biomarkers. Founded in 2013, Dimension maintains headquarters in Cambridge, Massachusetts.

For more information, please visit www.dimensiontx.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the development, preclinical and clinical results, and the continued progress of Dimension’s portfolio and programs, including the initiation, timing, scope, or likelihood of regulatory filings and approvals, and our ability to develop and advance product candidates into, and successfully complete, clinical studies. All such forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the risks that Dimension’s product candidates, including its candidates, DTX101 and DTX301, will not successfully be developed or commercialized in the times indicated or at all; the impact of the observed data in Cohorts 1 and 2, including the adverse event described above and any later safety event on timing, dosing, regulatory action or patient enrollment with respect to DTX101 and DTX301; and the risks described under the caption “Risk Factors” in Dimension Therapeutics’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, which is on file with the Securities and Exchange Commission, as well as other risks detailed in Dimension Therapeutics’ additional filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Dimension Therapeutics undertakes no duty to update this information unless required by law.

Contacts:

Jean Franchi

Chief Financial Officer

Dimension Therapeutics

617-714-0709

jean.franchi@dimensiontx.com

Burns McClellan, on behalf of Dimension Therapeutics

Media: Justin Jackson

212-213-0006, ext.327

jjackson@burnsmc.com

EX-99.2

Exhibit 99.2

Dimension Therapeutics

Dimension Therapeutics

1

Forward Looking Statements

These slides and the accompanying oral presentation contain forward-looking statements and information. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward looking statements. For example, all statements we make regarding the initiation, timing, progress and results of our preclinical and clinical studies and our research and development programs, our ability to advance product candidates into, and successfully complete, clinical studies, the timing or likelihood of regulatory filings and approvals, our ability to develop manufacturing processes and engage third parties to manufacture our product candidates for late-stage clinical use or at commercial scale, the success of strategic partnerships, if any, and our expected cash, cash equivalents and marketable securities at year end are forward looking. All forward?looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. These statements are also subject to a number of material risks and uncertainties that are described under the caption

“Risk Factors” in Dimension Therapeutics’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, which is on file with the Securities and Exchange Commission, as well as other risks detailed in Dimension Therapeutics’ additional filings with the Securities and Exchange Commission. Any forward?looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

The information contained in this presentation is not an offer to sell or the solicitation of an offer to buy the Company’s common stock or any other securities of the Company.

© 2017 Dimension Therapeutics 2

2

Dimension Therapeutics

The Leader in Gene Therapy for Rare & Metabolic Diseases

of the Liver

Broad product pipeline addressing rare & metabolic diseases with high unmet need

Leader in

discovering &

developing

new therapeutics

for people living

with devastating

rare diseases

associated with

the liver

Manufactured using mammalian process

Robust scientific AAV gene therapy platform

© 2017 Dimension Therapeutics 3

Clade E AAV-Based Gene Therapy Product Platform

Transgene Cassette Clade E Capsid Vector Peripheral Liver Directed

Enhanced liver targeting Exclusive WW license to RGNX AAV technology*

Durable expression Up to 8 specified disease indications; 1 available**

Well established safety 2013 license & 2015 option/license

25% population NAbs Collaboration with PENN, including related IP

Source: Gao et al. 2004 J Virol; Fagiuoli et al. 2013 J Hepat

*License excludes AAV8 for hemophilia A or B; **Option to license rights to REGENXBIO AAV technology for any 1 additional disease, subject to availability (diseases not licensed in whole or in part to a 3rd party)

© 2017 Dimension Therapeutics 4

Leveraging Mammalian Biology

Three platforms for production

HEK293 Adherent

Well-described

Regulator experience

Transient triple transfection

Serum-containing production

Limited scalability

HEK293 Suspension

Well-known

Emerging platform

Transient triple transfection

Serum-free production

Bioreactors

Scalable up to 200-500L

HeLa Producer Cell

Well-known

Clonal, high productivity

Similar to CHO platform

Serum-free production

Large scale bioreactors

Scalable up to 2000L

Sources: Martin J et al. 2013 Hum Gene Ther Meth; Grieger and Samulski 2012 Meth Enzymology; Zhang H et al. 2009 Hum Gene Ther

© 2017 Dimension Therapeutics

5

Investing in Capabilities Today for Production Access Tomorrow

CMO

GMP

Cambridge

PD Engineering

Woburn

Advanced PD/ Tech Transfer

CMO: contract manufacturing organization; GMP: good manufacturing practice; PD: process development

© 2017 Dimension Therapeutics

6

The Potential of AAV and Metabolic Disease

>400 Described Rare & Metabolic Diseases Associated with the Liver

Believe a Subset Well-Suited to Gene Therapy

Hem B

Proof of science

Replicate existing data

Activity supports IMD TPPs*

Learnings applied pipeline

IMDs

Known disease biology

Restore 5-10% of activity

Biomarkers, animal models

Orphan drug designation

Expansion

Leverage learning of IMDs

Harness liver biology

Bring new tools to bear

Target larger diseases

* TPP: Target Product Profile

© 2017 Dimension Therapeutics

Hem B

IMDs

Other Metabolic

7

Broad Clinical

Pipeline

CANDIDATE SELECTION IND-ENABLING PHASE 1/2 PHASE 3 PARTNERS

Inherited Metabolic Disease (IMD) Portfolio

OTC Deficiency

GSDIa

PKU

Wilson Disease

Citrullinemia*

Hemophilia B

Hemophilia A

DTX301 AAV8 OTC

DTX401 AAV8 G6Pase

DTX501 AAV PAH

DTX701 AAV ATP7B

DTX601 AAV ASS1

Hemophilia Programs

DTX101 AAVrh10 FIX

DTX201 AAV FVIII

*Citrullinemia type 1

© 2017 Dimension Therapeutics

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Executing Key Milestones

ADVANCING 7 PROGRAM PORTFOLIO

Initiate OTC phase 1/2 trial

GSDIa US orphan designation

GSDIa EU orphan designation

OTC EU orphan designation

Expanded IMD portfolio

2016

Hem B available data

OTC initial data

Hem B additional data

File GSDIa and Hem A IND

PKU and Wilson Disease development candidates

2017+

© 2017 Dimension Therapeutics

9

Inherited Metabolic Disease Programs

© 2016 Dimension Therapeutics

Ornithine Transcarbamylase (OTC) Deficiency

Disease

X-linked, urea cycle disorder (UCD)

Genetic defect in ammonia detoxification

Adverse cognitive & neurological effects, coma, death

Treatments limited, non-curative

Patient Population

~10,000 patients WW ~80% late onset

Most common UCD, ~55%

Severe, early onset in males

Late onset in males & females

Sources: National Urea Cycles Disorder Foundation; NORD; Batshaw et al. Mol Gen Metab 2014; Tuchman et al 2008; Enns N Engl J Med 2007; Foschi et al. World J Gastro ESPS Manuscript no: 13209; carolguze.com/text/442-11-clinical_genetics.shtml

© 2017 Dimension Therapeutics

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DTX301: Reestablishing Ureagenesis

KNOWN DISEASE BIOLOGY; PRECLINICAL MODELS

BIOMARKERS

Serum ammonia; neurotoxic

13C-acetate; ureagenesis

carbamoyl phosphate converted to orotic acid; urinary orotic acid

PATH TO HPOC DEFINED

US/EU orphan drug designation hPOC serum ammonia

Adult males and at-risk females

Sources: DMTX-PENN data (ASGCT 2015, ECRD 2016)

© 2017 Dimension Therapeutics

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DTX301: Phase 1/2 Clinical Trial Design

DTX101

Vector capsid Clade E AAV8

Gene cassette OTC

Liver specific enhancer-promoter

HEK293 process for hPOC

TPP* targeting re-establishment of ureagenesis

Phase 1/2 Study Ongoing

Open-label, safety, dose finding study

Bayesian adaptive design

Primary endpoints safety & ureagenesis

(13C-acetate test)

Up to 9 adult males and females with late onset OTC deficiency

Dosing: 2e12-1e13 GC/kg, single peripheral venous infusion

* TPP: Target Product Profile

© 2017 Dimension Therapeutics

13

Glycogen Storage Disease Type Ia (GSDIa)

Disease

Autosomal recessive, inborn error of glucose metabolism

Deficient glucose-6-phosphatase (G6Pase)

Reduced QOL, long term risks

Strict diet and frequent feedings of uncooked starch or Glycosade®

Patient Population

~6,000 patients WW Dx at birth

Most common GSD, ~25%

No approved drug therapies

Sources: Weinstein et al. Hum Gen Ther 2010; Lee et al. Hepatology 2012; Chou et al Nat Rev Endo 2010; Boers et al. Orphanet Journal of Rare Diseases 2014; www.curegsd.org; The

Children’s Fund for GSD Research

© 2017 Dimension Therapeutics

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DTX401: Reestablishing Glucose Metabolism

KNOWN DISEASE BIOLOGY; PRECLINICAL MODELS

Improved G6Pase Activity in Canines

Single dose AAV8 gene therapy increases G6Pase

Corresponding reduction in hepatic glycogen

BIOMARKERS

Fasting blood glucose

Glycogen stores; build up in liver

Inability to release glucose, raise risk for hypoglycemia

PATH TO HPOC DEFINED

Time to hypoglycemia

Adult males and females

Sources: Weinstein et al. Hum Gen Ther 2010; Lee et al. Hepatology 2012; Chou et al Nat Rev Endo 2010; Boers et al. Orphanet Journal of Rare Diseases 2014; www.curegsd.org; The Children’s Fund for GSD Research

© 2017 Dimension Therapeutics

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Broad Inherited Metabolic Disease Portfolio

Wilson Disease

PKU

Citrullinemia Type 1

DISEASE BIOLOGY; PRECLINICAL MODELS

Autosomal recessive copper disorder

Deficiency in copper transporter P-type ATPase

Autosomal recessive disorder

Deficiency in phenylalanine hydrolase

Autosomal recessive UCD

Deficiency in argininosuccinate synthetase

BIOMARKERS

Copper

Phenylalanine

Ammonia

OPPORTUNITY

WW prevalence >50K patients

~50K prevalent patients developed world

14% of all UCDs

WW prevalence ~2K

Sources: Barends MGM 2014; Batshaw MGM 2014; Citrullinemia Type I NCBI Bookshelf; Engel et al Hum Mut 2009; Foschi World J Gastro 2015; Marti?n-Herna?ndez Orph J Rare Dis 2014; NORD; Ruder Ped Neuro 2014; Ruegger J Inherit Metab Dis 2014; Summar Acta Paediatr. 2008; Summar Crit Care Clin 2005; Tuchman et al Mol Genet Metab 2008; Berry Genet Med 2013; Hanley J Genet Disor Genet Rep 2013; Vockley Gen Med 2014; Zerjav Orph J Rare Dis 2015; Beinhardt Clin Gast Hepat 2014; Bull Nat Gen 1993; EASL Prac Guide; Gomes Ann Hum Bio 2015; Kaler Nat Rev Neurol 2011; Roberts & Schilsky Hepat 2008; Schilsky Biochimie 2009; WD Pathogenesis Semin Liver Dis 2000

© 2017 Dimension Therapeutics 16

16

Hemophilia Programs

© 2016 Dimension Therapeutics

17

~$6.2B WW Market for Hemophilia B and A Products

Disease

Deficiency of blood coagulation factor IX (FIX) or factor VIII (FVIII)

Joint hemorrhages, potential for severe disabilities; brain micro-bleeds

Frequent, invasive, non-curative infusions of factor replacement

Patient Population

~28,000 Hem B patients WW ~140,000 Hem A patients WW

~68% Hem B, 78% Hem A moderate/severe to severe disease

$100,000-$300,000+ annual costs per patient

Sources: Riley et al. Haemophilia 2011; National Hemophilia Foundation; World Federation of Hemophilia; www.fiercepharmamarketing.com/story/biogens-alprolix-nod-just-first-tremor-hemophilia-market-shake/2014-04-02; Stonebraker et al. Haemophilia (2011), 1–4; Baker et al. Haemophilia (2012); Stonebraker et al. Haemophilia (2010), 16, 20–32; National Hemophilia Foundation; www.ptcommunity.com/news/2014-12-29-000000/hemophilia-market-likely-undergo-major-changes; Johnson and Zhou. ASH Annual Meeting Educational Program. 2011; Ponder. Haemophilia 2008; Manco-Johnson et al. NEJM 2007

© 2017 Dimension Therapeutics

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Goal of Hemophilia Gene Therapy

Reduce frequency of bleeds

Extend time between rFIX

Durable benefit from one infusion

Improve health outcomes and quality of life

Sources: den Uijl et al Haemophilia 2011

© 2017 Dimension Therapeutics

Consistent FIX activity confers

favorable effects on likelihood of

future bleeds, joint destruction and

need for rFIX replacement

19

DTX101: Phase 1/2 Clinical Trial Design

Vector capsid Clade E AAVrh10

Gene cassette wild type factor IX

Liver specific enhancer-promoter

HEK293 process for hPOC

TPP* targeting stable FIX activity >10

Reduce dependency for on demand prophylactic rFIX therapies

DTX101

Phase 1/2 Study Ongoing

Open-label, safety, dose finding stu

Bayesian adaptive design, 3 dose c

Primary endpoints safety & FIX ac

Up to 12 males with moderate/sev severe Hem B (£2% FIX levels)

Dosing: 1.6e12-1e13 GC/kg, single peripheral venous infusion

Cohorts 1 & 2 dosing complete

* TPP: Target Product Profile

© 2017 Dimension Therapeutics

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Participant Demographics

Patient Dose Age FIX Activity

1 Low 70 <1.0%

2 Low 55 2.0%

3 Low 53 2.0%

4 Second 28 1.5%

5 Second 48 <1.0%

6 Second 48 <1.0%

All patients moderate/severe-to-severe

FIX Level Severity Description

50-150% Normal

Bleed only as a result of surgery or major injury

5-40% Mild

Do not bleed often and, in fact, may never have a bleeding problem

Less frequent bleeds, about once a month 1-5% Moderate Bleed for a long time after surgery, injury, or dental work

Rare spontaneous bleeding

Frequent bleeds into muscles/joints

May bleed 1-2 times per week

<1% Severe

Bleeding often spontaneous, and happens for no obvious reason

Sources: Information sourced from World Federation of Hemophilia, https://www.wfh.org/en/page.aspx?pid=643 (link current as of January 27, 2017)

© 2017 Dimension Therapeutics

21

All Patients Improved from Moderate/Severe-to-Severe to Moderate or Mild

Patient Dose Peak FIX FIX* Severity

1 Low 11% 3% Moderate

2 Low 10% 3% Moderate

3 Low 5% 4% Moderate

4 Second 12% 5% Mild

5 Second 20% 8% Mild

6 Second 13% 7% Mild

*Data cutoff January 28, 2017; follow-up: low dose (1.6e12 GC/kg) 24-52 weeks; second dose (5e12 GC/kg) 7-12 weeks

Total Number of Bleeds

Number of Bleeds*

33

30

73%

20

15

9

10 100%

4**

0

0

Cohort 1 Cohort 2

12 Mo Prior Post-Dose All Post-Dose Spontaneous

*Data cutoff January 28, 2017; **Cohort 1 spontaneous bleeds: right shoulder, eye/conjunctivitis, right ankle (2)

© 2017 Dimension Therapeutics

Clinically Asymptomatic Elevations in Liver Enzymes

5 of 6 patients in the normal range

Elevations in laboratory ALT* observed in 5 of 6 patients; 4 in normal range

o Patient 3 in Cohort 2 experienced a grade 4 adverse event due to an elevated laboratory ALT o Cohort 1 clinically stable, off steroids*

All elevated liver enzymes were clinically asymptomatic

o No elevations of GGT*, alkaline phosphatase or bilirubin o No patients have experienced a drug related serious adverse event (SAE) as of the January 28, 2017 cutoff date

*ALT: alanine aminotransferase; cohort 2 continues to receive a standard tapering course of corticosteroid therapy; GGT: gamma-glutamyl transferase

Patient Dose Peak ALT ALT*

1 Low 98 22

2 Low 40 21

3 Low 60 39

4 Second 52 19

5 Second 62 39

6 Second 914 431

*Data cutoff January 28, 2017; follow-up: low dose (1.6e12 GC/kg) 24-52 weeks; second dose

(5e12 GC/kg) 6-12 weeks; ALT measured in international units per liter (IU/L); normal ALT ?40

IU/L

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Summary of Interim Findings and Next Steps

Evidence of high-efficiency liver transduction with AAVrh10 vector

All patients in both cohorts improved from moderate/severe-to-severe to either moderate or mild

Notable reduction in spontaneous bleeds

Stable and durable elevations in FIX activity up to 52 weeks (range 6-52)

Sub-clinical, asymptomatic elevations of ALT observed in 5 of 6 patients; 4 currently in normal range

Explore therapeutic window in light of ALT rises & FIX decline

Broad program of translational research ongoing

Multiple hypotheses under consideration

T cell activation, general immune responses, cellular responses

Future presentations at academic and medical congresses

Await feedback from regulatory bodies prior to initiating cohort 3

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DTX201: Global Collaboration with Bayer

A LEADING GENE THERAPY COMPANY

GLOBAL LEADER IN HEMOPHILIA DRUG

DEVELOPMENT & COMMERCIALIZATION

$20M upfront, up to $232M in milestones

High single-digit to low double-digit royalties not exceeding the mid-teens

R&D expense reimbursement

DMTX responsible for preclinical activities and Phase I/II clinical trial, funded by Bayer

Bayer to fund subsequent trials and commercial activities at clinical POC

Partnered since June 2014

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DTX201: Durable FVIII Expression in NHPs

DTX201 for Hem A

hFVIII Expression in Non Human Primates

Seven male cynomolgus macaques administered IV with 1.2e13 GC/kg

Sustained FVIII expression in NHPs beyond 60 weeks

3 of 7 animals retain expression greater than 16 weeks; 2 of 7 beyond 34 weeks

Sustained RNA expression

Reduced incidence of anti-FVIII inhibitors

Sources: DMTX-PENN data (ASGCT 2016, EHA 2016)

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Dimension

A Leader in

Liver Directed

Gene Therapy

Advancing Product Portfolio Focus on Inherited Metabolic Diseases Building Gene Therapy Product Platform Highly Experienced Team Well-Capitalized

Broad 7 program pipeline; multiple near-term milestones

Addressing severe, debilitating unmet medical need

Investing in scalable, quality HeLa manufacturing

Strong R&D and manufacturing capabilities

Expected cash runway through 1Q 2018

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Thank you

January 2017

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