Viral News in Gene Therapy: NVS and KITE are racing CAR-T to the finish line

Highlights of the week (26 March-1 April): 1) Novartis AG (Buy) announced the FDA accepted the BLA filing andgranted Priority Review for chimeric antigen receptor (CAR)-T therapy, CTL019, for pediatric and young adult patientswith B-cell acute lymphoblastic leukemia (ALL). 2) Kite Pharma (unrated) announced completion of the rolling BLAsubmission for CAR-T therapy, axicabtagene ciloleucel, for the treatment of patients with relapsed or refractory (r/r)aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant (ASCT). 3) OlivierDanos, PhD, who has been instrumental in some of the most important partnerships in the gene therapy (GT) space,joined REGENXBIO (Buy) (which has >20 partnered products) as Chief Scientific Officer, from Biogen (unrated),where he was Senior Vice President, Cell and Gene Therapy.

Looking forward (2-8 April) (Figure 1): Kite Pharma will present four oral presentations and one poster from theZUMA-1 trial of CAR-T therapy, axicabtagene ciloleucel, on 2-4 April at the American Association of Cancer Research(AACR) Annual Meeting in Washington, D.C.. On 4 April, GenSight Biologics will present one oral presentation andtwo posters for AAV-based GT, GS010, for the treatment of Leber's hereditary optic neuropathy (LHON) at the 2017North American Neuro-Ophthalmology Society (NANOS) 43rd Annual Meeting in Washington, D.C. RXiPharmaceuticals (unrated) will present one poster on CAR-T activity via PD-1 knockdown by self-delivering RNAi atAACR on 5 April. Spark Therapeutics (Neutral) will present updated data for AAV-based GT, SPK-9001, forhemophilia B at the 2017 Scientific Symposium of the Hemostasis and Thrombosis Research Society (HTRS), takingplace on 6-8 April 2017 in Scottsdale, AZ.

Weekly price moves (Figure 2): In vivo gene therapy +4.2% (AAV +1.4%, sRNA -1.3%, in vivo gene editing +18.9%).Notable performers: ToolGen (Buy) +31.5%, DRNA (Neutral) +29.3%, ALNY (Buy) -2.3%, RGNX (Buy) -4.2%.

Gene expressions

During the week, Chardan initiated on five gene therapy (GT) companies: all four public CRISPR companies, includingToolGen (Buy), Editas Medicine (Buy), CRISPR Therapeutics (Buy), Intellia Therapeutics (Buy); and AAV-basedGT company, GenSight Biologics (Buy). Please refer to the discussion of the initiations below.

Chardan gene therapy research reports

CRSP (Buy): Initiate Buy (PT $23.50): Risk-reward on CRISPR clinical lead offsets IP risks (27 March)

• We initiated coverage on CRISPR Therapeutics with a Buy rating and a $23.50 PT, on our view of possible upsidefor CRSP on clinical leadership in CRISPR therapy in the year ahead overriding the risk of possible downside fromthe company's IP exposure on longer horizons.

• We believe that CRISPR Therapeutics' foundational IP from the UC is less robust than IP from the Broad/EditasMedicine and from ToolGen .

• This IP risk is more than overridden by the company's potential entry into the clinic with its lead asset for thetreatment of beta-thalassemia. IND/CTA filings expected by late 2017.

EDIT (Buy): Initiate Buy (PT $65): Broad IP provides broad gene editing optionality (27 March)

• We initiated coverage on Editas Medicine with a Buy rating and a $65 PT, on our view of the company's IP breadthand strength providing significant upside potential for shares, via both internal and partnered program opportunities.

• We believe that Editas' foundational IP from the Broad Institute is more robust than that of the UC and the UC'slicensees, such as CRISPR Therapeutics and Intellia.

• Partnerships with Adverum Biotechnologies (Neutral), Allergan (unrated), and Juno Therapeutics (unrated)suggest optionality value for Editas' IP, as Editas' exclusive license to the Broad IP could generate additionalrevenue through sub-licensing.

Industry UpdateApril 2, 2017

Biotechnology & Pharmaceuticals

INDUSTRY NOTEGbola Amusa, MD, CFA , Head of HC Research, +1-646-465-9024

gamusa@chardan.com

Madhu Kumar, PhD , Senior Research Analyst, +1-646-465-9071mkumar@chardan.com

Sales and trading 7 a.m. to 7 p.m. ET, (646) 465-9090

Please refer to important disclosure information and Regulation Analyst Certification found on pages 9 - 16 of this report.

• Beyond partnerships, further upside could be achieved through clinical entry of the company's lead asset for thetreatment of Leber's congenital amaurosis type 10, with IND filing expected by late 2017.

NTLA (Buy): Initiate Buy (PT $19): Leverage to sector valuation overrides IP risk (27 March)

• We initiated coverage on Intellia Therapeutics with a Buy rating and a $19 PT, on our view of possible downsidedriven by the company's IP weakness overridden by relative under-valuation of the CRISPR sector.

• We believe that Intellia's foundational IP from the University of California (UC) is less robust than IP from the BroadInstitute (Broad)/Editas Medicine and ToolGen .

• These IP challenges are more than offset by our broader bullishness on the CRISPR sector, for which even modestexposure for Intellia should provide significant upside.

199800.KS (Buy): Initiate Buy (PT KRW 162,500): Formidable IP, valuation suggests upside (27 March)

• We initiated coverage on ToolGen with a Buy rating and a KRW 162,500 PT, on our view of the company's vastupside potential, driven by its underappreciated chance for CRISPR IP leadership.

• We believe ToolGen has a reasonable likelihood of taking CRISPR-Cas9 IP leadership from the Broad/ Editas.

• In spite of the potential IP advantage that is largely undiscussed in financial markets, ToolGen is substantiallyunder-valued in the CRISPR sector.

SIGHT FP (Buy): Initiate Buy (PT €35): Seeing 5x upside potential on eye-catching GS010 data (30 March)

• We initiated coverage on GenSight Biologics based on the opportunity likely addressed by GS010, a phase IIIAAV-based gene therapy (GT) for a rapidly-progressing form of blindness, Leber's hereditary optic neuropathy(LHON).

• We believe the market is missing critical investment points on GenSight, notably that 1) GS010 in LHON ND4 fitsour predictive Chardan Gene Therapy Framework, 2) a US price of €975,000 (EU:€780,000) for GS010 is justified,3) epidemiology data underestimate GS010's potential, and 4) GenSight, which has pivotal phase III GS010 datadue in 1H18, trades at a discount to relevant peers, some of which are yet to progress beyond phase I/II trials.

Other gene therapy news (26 March-1 April)

VBLT (Buy): Reports 4Q16 and FY2016 financial results and company highlights (27 March)

• VBL Therapeutics announced the interim analysis in the GLOBE pivotal study of adenovirus gene therapy (GT),VB-111, is expected in mid-2017, with top-line data expected in early 2018.

• The company plans to begin enrollment in 2H17 for a phase III VB-111 trial in platinum-resistant ovarian cancer.Critically, platinum-resistant ovarian cancer is distinct from the ovarian cancer population targeted bypolyADP-ribose polymerase (PARP) inhibitors, such as Rubraca from Clovis Oncology (Sell), Zejula from Tesaro(unrated), and Lynparza from AstraZeneca (unrated).

• Recall from our 29 November 2016 note, that we believe signs of continuing efficacy for VB-111 in thyroid cancer,rGBM and ovarian cancer reinforce the drug's disruptive potential in solid cancers.

PRQR (unrated): Appoints David M. Rodman, MD as Chief Development Strategy Officer (27 March)

OXB (unrated): Announces publication in Journal Nature Communications regarding TRiP system (27 March)

ZIOP (unrated): Announces end-of-Phase 2 meeting with FDA for GT product, Ad-RTS-hIL-12 (27 March)

RGNX (Buy): Appoints Olivier Danos, PhD as Chief Scientific Officer (28 March)

• Dr. Danos joined REGENXBIO after holding the position of Senior Vice President, Cell and Gene Therapy at Biogen(unrated).

• At Biogen, Dr. Danos was responsible for executing the partnership with San Raffaele-TIGET and AGTC (Buy). Healso worked with James Wilson and Jean Bennett at the University of Pennsylvania.

RXII (unrated): Receives Japanese patent for RNAi drug, RXI-109, for dermal and ocular fibrosis (28 March)

CRSP (Buy): Announces European patent for CRISPR/Cas gene editing technology (28 March)

• While a somewhat favorable event, the granted European patent grant does not address UC's patent weakness inthe US versus the Broad/Editas and does not address the IP imbalance generated by Broad/Editas in CRISPRnucleases beyond Cas9, such as Cpf1.

SLN.LN (Sell): Reports FY2016 financial results and company highlights (28 March)

SGMO (unrated): Presents in vitro and animal model data reducing tau mRNA using ZFN technology (29 March)

DRNA (Neutral): Reports 4Q16 and FY2016 financial results and company highlights (30 March)

Page 2 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

• Dicerna Pharmaceuticals announced intentions to file an IND submission and/or CTA for DCR-PHXC in late 2017,and initiate trials in 1Q18 for primary hyperoxaluria type 1 (PH1).

• Recall from our 8 August 2016 note, that ALN-GO1 from Alnylam Pharmaceuticals (Buy) has alreadydemonstrated to us superior results in a mouse model of PH1. Moreover, ALN-GO1 is already in clinicaldevelopment, with efficacy studies underway in PH1 patients.

DRNA (Neutral): Secures $70 million in convertible preferred stock (30 March)

RXII (unrated): Reports 4Q16 and FY2016 financial results and company highlights (30 March)

NVS (Buy): Receives Priority Review for BLA submitted for CAR-T, CTL019, for ALL (29 March)

• Novartis AG announced that the Priority Review Designation was based off results from the ELIANA study, where82% of patients infused with CAR-T cells achieved complete remission or complete remission with incomplete bloodcount recovery at three months post CTL019 infusion.

• This is the first CAR-T BLA submission both generally and in particular for relapsed and refractory (r/r) pediatric andyoung adult patients with B-cell acute lymphoblastic leukemia (ALL).

ABEO (unrated): Reports 4Q16 and FY2016 financial results and company highlights (31 March)

KITE (unrated): Completes BLA submission for CAR-T, axicabtagene ciloleucel, for r/r NHL (31 March)

• Recall from our 6 March 2017 industry note, that Kite Pharma announced that axicabtagene ciloleucel, met theprimary endpoint with a single transfusion objective response rate (ORR) of 82% (p<0.0001) in aggressive NHL.

• In the I-O space, we continue to favor Lion Biotechnologies (Buy), which has fewer competitive threats since ittreats solid cancers, which target numerous antigens versus companies like Kite which targets only CD19 as anantigen.

Other companies mentioned in report:

ToolGen, Inc. (199800.KS - KRW47,600.00 - Buy)

Arbutus Biopharma Corporation (ABUS - $3.25 - Neutral)

Adverum Biotechnologies, Inc. (ADVM - $2.70 - Neutral)

Applied Genetic Technologies Corporation (AGTC - $6.90 - Buy)

Alnylam Pharmaceuticals, Inc. (ALNY - $51.25 - Buy)

Arrowhead Pharmaceuticals, Inc. (ARWR - $1.85 - Neutral)

AveXis, Inc. (AVXS - $76.03 - Buy)

Audentes Therapeutics, Inc. (BOLD - $17.04 - )

CRISPR Therapeutics AG (CRSP - $21.77 - Buy)

Dimension Therapeutics, Inc. (DMTX - $1.75 - Neutral)

Dicerna Pharmaceuticals, Inc. (DRNA - $3.40 - Neutral)

Editas Medicine, Inc. (EDIT - $22.32 - Buy)

The Medicines Company (MDCO - $48.90 - Buy)

Intellia Therapeutics, Inc. (NTLA - $14.09 - Buy)

Novartis AG (NVS - $74.27 - Buy)

Spark Therapeutics, Inc. (ONCE - $53.34 - Neutral)

ProQR Therapeutics NV (PRQR - $5.00 - Neutral)

uniQure N.V. (QURE - $5.78 - Buy)

Regulus Therapeutics, Inc. (RGLS - $1.65 - Buy)

REGENXBIO Inc. (RGNX - $19.30 - Buy)

GenSight Biologics (SIGHT FP - €7.20 - Buy)

Silence Therapeutics PLC (SLN.LN - p89.38 - Sell)

Vascular Biogenics Ltd. (VBLT - $5.50 - Buy)

Voyager Therapeutics, Inc. (VYGR - $13.24 - Neutral)

Page 3 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Selected catalysts through mid-2017 in our gene therapy coverage

Date Company Event

Early 2017 ALNY/MDCO Inclisiran: Initiate HoFH phase III trial

Early 2017 ALNY Fitusiran: Initiate phase III trial (ATLAS) in hemophilia A/B

Early 2017 ONCE Voretigene neparvovec: Submit BLA for RPE65-mediated inherited retinal disease (IRD)

Early 2017 ONCE SPK-7001: Report initial efficacy analysis from phase I/II trial in choroideremia

April NTLA,CRSP,EDIT UC deadline to file an appeal of the PTAB ruling at the CAFC

4 April SIGHT FP GS010: Oral presentation and two posters at NANOS

6-8 April ONCE SPK-9001: Report additional data from the phase I/II trial in hemophilia B at HTRS

20 April ARWR ARC-520/ARC-521: Present data on hepatitis B programs at EASL

22 April ABUS ARB-1467: Present data on phase II hepatitis B programs from Cohorts 1-3 at EASL

24-26 April AVXS AVXS-101: Present phase I data in SMA type 1 at AAN (Late-Breaker)

25 April SIGHT FP GS010: Report 78 week phase I/II data in LHON ND4 at AAN

25 April VYGR VY-AADC01: Present phase Ib results from cohorts 1 and 2 in PD at AAN (Late-Breaker)

26 April ALNY Patisiran: Report phase II OLE data in TTR-FAP at AAN

1 May AVXS CMC Type B meeting with the FDA

7-11 May SIGHT FP GenSight will present undisclosed data

June SIGHT FP GS010: Topline release of 96 week phase I/II data in LHON ND4

25-28 June ALNY Givosiran: Report phase I, Part C data for acute hepatic porphyrias at ICCP meeting

2Q17 AVXS Provide update/minutes from CMC Type B meeting

2Q17 AVXS AVXS-101: Initiate phase I trial in SMA 2

2Q17 AVXS AVXS-101: Initiate SMA type 1 pivotal trial in the US

2Q17 RGLS RG-012: Completion of the MAD study in Alport syndrome

2Q17/3Q17 AVXS AVXS-101: End-of Phase I meeting with the FDA

2Q17/3Q17 AVXS Conduct a comprehensive clinical program review with the EMA

1H17 ADVM ADVM-022: Initiate IND-enabling toxicology and biodistribution studies in wet AMD

1H17 ADVM ADVM-053: Engage discussions with the FDA for HAE

1H17 ONCE SPK-9001: Update on phase I/II data in hemophilia B

1H17 PRQR QR-110: Initiate first in human clinical trial for LCA10

1H17 RGNX RGX-111: File an IND for a phase I/II study in MPS I

8-13 July ALNY Fitusiran: Report phase II OLE data in hemophilia A/B at ISTH

September ALNY Patisiran: Report top-line results from phase III APOLLO trial in TTR-FAP Mid-2017 AGTC XLRS: Release data on dose escalation phase I/II trial

Mid-2017 ALNY/MDCO Inclisiran: Initiate phase III ASCVD trial

Mid-2017 ALNY ALN-HBV: Initial data from phase I/II trial in HBV

Mid-2017 EDIT Initiate Leber congenital amaurosis 10 (LCA10) natural history study

Mid-2017 ONCE SPK-8011: Report phase I/II data in hemophilia A

Mid-2017 PRQR QR-010: Report additional date from phase Ib trial in CF

Mid-2017 RGNX RGX-314: Initiate phase I trial for wet AMD

Mid-2017 RGNX RGX-121: File an IND for a phase I/II study in MPS II

Mid-2017 VBLT VB-111: Report interim results from the phase III GLOBE study in rGBM

Mid-2017 VYGR VY-AADC01: Open-label phase Ib results from cohort 3 in Parkinson’s disease

Source: Corporate reports, Chardan.

Figure 1: Key selected catalysts through mid-2017 include the AVXS pivotal trial initiation (2Q17) and ALNY phase III patisiran data (September)

Page 4 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Weekly gene therapy market movements: 31 March 2017 vs. 24 March 2017

Source: Corporate reports, FactSet, Chardan. Note: All mentioned stocks are unrated unless otherwise stated. Other public (unrated unless stated) gene therapy companies include: Benitec Biopharma, Fibrocell, Marina Biotech, Oncosec Medical, Oxford BioMedica, RXi Pharmaceuticals, Lysogene, and Vascular Biogenics (Buy).

Figure 2: Selected price movements in the week ended 31 March 2017—In vivo GT was up 4.2%, with in vivo gene editing up 18.9%.

Week-over-week performance: In vivo gene therapy 4.2% (AAV 1.4%, small RNA -1.3%, in vivo gene editing 18.9%)

INDICES & BASKETS TICKER RATING CCM PT UPSIDE CLOSE CHANGE % CHANGE MC ($MM) CASH %

S&P 500 SP50 2362.72 18.74 0.8%

Nasdaq COMP 5911.74 83.00 1.4%

Drugs DRG 508.85 -0.94 -0.2%

Biotech NBI 3069.35 33.15 1.1%

Chardan Gene Therapy (cap wtd) 4.2% 24,846.3 28.7%

Chardan Gene Therapy (in vivo ) (cap wtd) 4.2% 13,627.5 36.0%

Chardan Gene Therapy (ex vivo ) (cap wtd) 4.3% 11,218.8 20.0%

AAV-BASED GENE THERAPY TICKER RATING CCM PT UPSIDE CLOSE CHANGE % CHANGE MC ($MM) CASH %

Voyager Therapeutics VYGR Neutral $13.00 -1.8% $13.24 $1.68 14.5% 354.2 46.8%

Abeona Therapeutics ABEO NR NR NR $5.00 $0.20 4.2% 201.3 37.5%

Applied Genetic Technologies Corporation AGTC Buy $10.00 44.9% $6.90 $0.25 3.8% 124.6 127.5%

Dimension Therapeutics DMTX Neutral $2.25 28.6% $1.75 $0.05 2.9% 43.8 203.4%

Adverum Biotechnologies ADVM Neutral $3.50 29.6% $2.70 $0.05 1.9% 113.6 208.1%

Audentes Therapeutics BOLD NR NR NR $17.04 $0.23 1.4% 370.2 36.8%

AveXis AVXS Buy $100.00 31.5% $76.03 $0.89 1.2% 2,104.2 11.7%

Spark Therapeutics ONCE Neutral $55.00 3.1% $53.34 $0.37 0.7% 1,655.9 19.0%

GenSight Biologics SIGHT-PAR Buy €35.00 386.1% €7.20 -€0.02 -0.3% 148.4 34.4%

uniQure QURE Buy $11.99 107.4% $5.78 -$0.03 -0.5% 147.1 126.3%

REGENXBIO RGNX Buy $35.00 81.3% $19.30 -$0.85 -4.2% 582.4 41.1%

Mean 2.3% 531.4 81.2%

Median 1.4% 201.3 41.1%

Total (wtd) 1.4% 5,845.5 32.5%

SMALL RNA GENE THERAPY TICKER RATING CCM PT UPSIDE CLOSE CHANGE % CHANGE MC ($MM) CASH %

Dicerna Pharmaceuticals DRNA Neutral $3.50 2.9% $3.40 $0.77 29.3% $70.7 98.2%

Regulus Therapeutics RGLS Buy $5.00 203.0% $1.65 $0.25 17.9% $87.3 105.5%

Silence Therapeutics SLN-GB Sell £0.72 -19.4% £0.89 £0.02 2.7% £62 80.6%

Arbutus Biopharma ABUS Neutral $3.00 -7.7% $3.25 $0.05 1.6% $178.8 85.5%

Arrowhead Pharmaceuticals ARWR Neutral $2.00 8.1% $1.85 -$0.02 -1.1% $138.0 97.3%

Alnylam Pharmaceuticals ALNY Buy $97.00 89.3% $51.25 -$1.22 -2.3% $4,408.2 27.0%

Mean 8.0% 976.6 82.4%

Median 2.1% 138.0 91.4%

Total (wtd) -1.3% 4,883.0 33.6%

IN VIVO GENE EDITING TICKER RATING CCM PT UPSIDE CLOSE CHANGE % CHANGE MC ($MM) CASH %

ToolGen 199800-KON Buy KRW 162,500 241.4% KRW 47,600 KRW 11,400 31.5% $247.3 5.1%

Sangamo Therapeutics SGMO NR NR NR $5.20 $1.10 26.8% $368.5 108.5%

CRISPR Therapeutics CRSP Buy $23.50 7.9% $21.77 $3.89 21.8% $866.7 36.4%

Editas Medicine EDIT Buy $65.00 191.2% $22.32 $3.06 15.9% $908.9 39.6%

Intellia Therapeutics NTLA Buy $19.00 34.8% $14.09 $1.02 7.8% $507.6 53.8%

Mean 20.8% 579.8 48.7%

Median 21.8% 507.6 39.6%

Total (wtd) 18.9% 2,899.0 46.9%

Page 5 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

REGENXBIO is our top pick, and AveXis is the largest target holding, in our AAV-based gene therapy portfolio

Source: Corporate reports, FactSet, Chardan. Note: All mentioned stocks are unrated unless otherwise stated. *In order to calculate public sector data, the ABEO and BOLD target market caps are modeled to be the same as the current market cap. ** Refers to the partnered product with Lysogene. RGNX's RGX-501 (HoFH) is in phase I/II trials; RGX-314 (wet AMD), RGX-111 (MPS I), and RGX-121 (MPS II) are expected to enter phase I/II trials in 2017.

Figure 3: Selected public AAV-based gene therapy companies—We prefer AVXS (Buy) and RGNX (Buy) for greater potential to drive upside for the AAV-based GT space

Target Target

CCM Phase of Price ($) CCM CCM Dil. MC Percent CCM MC percent 52-wk 52-wk Cash % 1st year

Company Ticker rating develop. 03/31/2017 PT ($) PT $ in mm of sector $ in mm of sector high high share of profit

Abeona Therapeutics* ABEO Unrated I/II $5.00 Unrated Unrated 184.3 3.3% 184.3 2.4% $9.44 53.0% 37.5% Unrated

Adverum Biotechnologies ADVM Neutral Preclinical $2.70 $3.50 29.6% 112.7 2.0% 146.2 1.9% $6.31 42.8% 208.1% >2025

Applied Genetic Technologies Corporation AGTC Buy I/II $6.90 $10.00 44.9% 126.9 2.2% 183.9 2.4% $19.86 34.7% 127.5% 2024

Audentes Therapeutics* BOLD Unrated Preclinical $17.04 Unrated Unrated 370.2 6.5% 370.2 4.8% $20.74 82.2% 28.5% Unrated

AveXis AVXS Buy Pre-III $76.03 $100.00 31.5% 1,966.4 34.8% 2,586.4 33.8% $85.98 88.4% 11.7% 2020

Dimension Therapeutics DMTX Neutral I/II $1.75 $2.25 28.6% 43.7 0.8% 56.2 0.7% $10.47 16.7% 203.4% 2024

GenSight Biologics SIGHT-PAR Buy III €7.20 €35.00 386.1% 169.3 3.0% 823.2 10.8% €10.82 66.5% 34.4% 2020

REGENXBIO RGNX Buy PII/III** $19.30 $35.00 81.3% 511.0 9.0% 926.7 12.1% $24.55 78.6% 41.1% 2022

Spark Therapeutics ONCE Neutral BLA $53.34 $55.00 3.1% 1,646.3 29.1% 1,697.5 22.2% $65.99 80.8% 19.0% 2019

uniQure QURE Buy Market $5.78 $11.99 107.4% 148.1 2.6% 307.3 4.0% $15.00 38.5% 126.3% 2021

Voyager Therapeutics VYGR Neutral IB $13.24 $13.00 -1.8% 379.3 6.7% 372.5 4.9% $18.25 72.5% 46.8% 2023

Sector 35.3% 5,658.4 100.0% 7,654.2 100.0% 73.1% 32.4% 2022

High 386.1% 1,966.4 34.8% 2,586.4 33.8% 88.4% 208.1% 2024

Mean 79.0% 514.4 9.1% 695.8 9.1% 59.5% 80.4% 2022

Median 31.5% 184.3 3.3% 370.2 4.8% 66.5% 41.1% 2022

Low -1.8% 43.7 0.8% 56.2 0.7% 16.7% 11.7% 2019

Selected private AAV-based gene therapy companies

Esteve, Freeline Therapeutics, Horama, MeiraGTx Limited/Athena Vision, NightstaRx, SolidGT

Page 6 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Alnylam is our top pick in sRNA gene therapy; we see more uncertainty elsewhere in the space

Source: Corporate reports, FactSet, Chardan. Note: All mentioned stocks are unrated unless otherwise stated.

Figure 4: Selected public small RNA therapy companies—We prefer ALNY (Buy) for greater potential to drive upside for the small RNA GT space

Target Target

CCM Phase of Price ($) CCM CCM Dil. MC Percent CCM MC percent 52-wk Cash % 1st year

Company Ticker rating develop. 03/31/2017 PT ($) PT $ in mm of sector $ in mm of sector high share of profit

Alnylam Pharmaceuticals ALNY Buy III $51.25 $97.00 89.3% 4,399.5 89.0% 8,326.8 92.2% 64.0% 14.2% 2020

Arbutus Biopharma ABUS Neutral IIA $3.25 $3.00 -7.7% 178.2 3.6% 164.5 1.8% 59.3% 73.3% 2023

Arrowhead Pharmaceuticals ARWR Neutral Preclinical $1.85 $2.00 8.1% 132.2 2.7% 142.9 1.6% 22.5% 77.3% N/A

Dicerna Pharmaceuticals DRNA Neutral Preclinical $3.40 $3.50 2.9% 70.6 1.4% 72.6 0.8% 32.5% 134.4% 2021

Regulus Therapeutics RGLS Buy II $1.65 $5.00 203.0% 87.3 1.8% 264.6 2.9% 18.5% 105.5% 2021

Silence Therapeutics SLN-GB Sell Preclinical £0.89 £0.72 -19.4% 78.0 1.6% 62.8 0.7% 66.2% 80.6% N/A

Sector 82.7% 4,945.7 100.0% 9,034.3 100.0% 57.9% 22.2% 2021

High 203.0% 4,399.5 89.0% 8,326.8 92.2% 66.2% 134.4% 2023

Mean 46.0% 824.3 16.7% 1,505.7 16.7% 43.8% 80.9% 2021

Median 5.5% 109.7 2.2% 153.7 1.7% 45.9% 78.9% 2021

Low -19.4% 70.6 1.4% 62.8 0.7% 18.5% 14.2% 2020

Selected private small RNA therapy companies

ADViRNA, Arcturus Therapeutics, Quark Pharmaceuticals, Silenseed, Sirnaomics, SomaGenics, Sylentis

Note: Benitec Biopharma, Marina Biotech, Mirna Therapeutics, and RXi Pharmaceuticals are additional unrated public companies

Page 7 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

In vivo gene editing: We see greater upside potential for Editas (Buy) and ToolGen (Buy)

Source: Corporate reports, FactSet, Chardan. Note: All mentioned stocks are unrated unless otherwise stated. *To calculate public sector data, Sangamo’s target market cap is modeled to be the same as the current market cap.

Figure 5: In vivo gene editing—We broadly expect outperformance for the CRISPR sector, with higher potential for performance for EDIT (Buy) and ToolGen (Buy)

Target Target

CCM Phase of Price ($) CCM CCM Dil. MC Percent CCM MC percent 52-wk Cash % 1st year

Company Ticker rating develop. 03/31/2017 PT ($) PT $ in mm of sector $ in mm of sector high share of profit

CRISPR Therapeutics CRSP Buy Preclinical $21.77 $23.50 7.9% 864.7 31.3% 933.4 18.2% 87.1% 36.4% N/A

Editas Medicine EDIT Buy Preclinical $22.32 $65.00 191.2% 797.5 28.8% 2,322.5 45.3% 51.3% 39.6% N/A

Intellia Therapeutics NTLA Buy Preclinical $14.09 $19.00 34.8% 486.2 17.6% 655.6 12.8% 46.3% 53.8% N/A

Sangamo Therapeutics* SGMO Unrated I/II $5.20 Unrated Unrated 367.8 13.3% 367.8 7.2% 68.4% 38.8% Unrated

ToolGen 199800-KON Buy Preclinical KRW 47,600 KRW 162,500 241.4% 248.9 9.0% 849.7 16.6% 100.0% 5.1% N/A

Sector 85.5% 2,765.1 100.0% 5,129.1 100.0% 63.1% 37.9% N/A

High 241.4% 864.7 31.3% 2,322.5 45.3% 100.0% 53.8% N/A

Mean 118.8% 553.0 20.0% 1,025.8 20.0% 70.6% 34.7% N/A

Median 113.0% 486.2 17.6% 849.7 16.6% 68.4% 38.8% N/A

Low 7.9% 248.9 9.0% 367.8 7.2% 46.3% 5.1% N/A

Selected private in vivo gene editing companies

Caribou Biosciences, Casebia Therapeutics, eGenesis Bio, Excision BioTherapeutics, Exonics Therapeutics, Feldan Therapeutics, Homology Medicines, Poseida

Therapeutics, Precision BioSciences, Recombinetics

Page 8 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Important Research Disclosures

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

10,000

20,000

30,000

40,000

50,000

2014 2015 2016 2017

03/27/17I:B:NA

Rating and Price Target History for: ToolGen, Inc. (199800/KS) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

8

16

24

32

2014 2015 2016 2017

05/16/16I:S:$3.25

06/16/16N:$3.25

07/08/16S:$2.75

08/08/16S:$3

10/14/16N:$3

11/30/16B:$4

12/13/16N:$3

Rating and Price Target History for: Arbutus Biopharma Corporation (ABUS) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

15

30

45

60

75

2014 2015 2016 2017

02/19/15I:N:$40

06/16/15S:$20

06/23/15N:$20

07/27/15N:$17.5

08/17/15B:$17.5

10/26/15B:$12.5

03/01/16B:$9

03/28/16B:$7.5

06/08/16N:$5

Rating and Price Target History for: Adverum Biotechnologies, Inc. (ADVM) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

8

16

24

32

40

2014 2015 2016 2017

07/21/15I:B:$25

03/18/16B:$22.5

03/28/16B:$25

09/19/16B:$15

02/09/17B:$10

Rating and Price Target History for: Applied Genetic Technologies Corporation (AGTC) as of03-30-2017

Created by BlueMatrix

Page 9 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

30

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90

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150

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04/04/16I:B:$93

05/26/16B:$115

10/06/16B:$77

11/09/16B:$73

11/30/16B:$89

12/19/16B:$69

01/09/17B:$97

Rating and Price Target History for: Alnylam Pharmaceuticals, Inc. (ALNY) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

4

8

12

16

20

2014 2015 2016 2017

05/19/16I:B:$12

07/08/16B:$11.5

08/10/16B:$10

11/10/16B:$8

11/30/16N:$2

Rating and Price Target History for: Arrowhead Pharmaceuticals, Inc. (ARWR) as of 03-30-2017

Created by BlueMatrix

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100

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03/28/16I:B:$60

08/17/16B:$65

11/02/16B:$85

01/25/17B:$100

Rating and Price Target History for: AveXis, Inc. (AVXS) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q112

14

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18

20

22

2014 2015 2016 2017

Rating and Price Target History for: Audentes Therapeutics, Inc. (BOLD) as of 03-30-2017

Created by BlueMatrix

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Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q19

12

15

18

21

24

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03/27/17I:B:$23.5

Rating and Price Target History for: CRISPR Therapeutics AG (CRSP) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

4

8

12

16

2014 2015 2016 2017

11/02/15I:N:$13

03/24/16N:$12.5

03/28/16N:$11.5

08/18/16N:$10

01/31/17N:$4

Rating and Price Target History for: Dimension Therapeutics, Inc. (DMTX) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

8

16

24

32

2014 2015 2016 2017

04/04/16I:N:$5

06/30/16N:$4

08/08/16N:$3.5

Rating and Price Target History for: Dicerna Pharmaceuticals, Inc. (DRNA) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q18

16

24

32

40

48

2014 2015 2016 2017

03/27/17I:B:$65

Rating and Price Target History for: Editas Medicine, Inc. (EDIT) as of 03-30-2017

Created by BlueMatrix

Page 11 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q110

20

30

40

50

60

2014 2015 2016 2017

11/04/15I:B:$50

03/21/16B:$65

10/06/16B:$57.5

11/07/16B:$65

03/07/17B:$80

Rating and Price Target History for: The Medicines Company (MDCO) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q15

10

15

20

25

30

2014 2015 2016 2017

03/27/17I:B:$19

Rating and Price Target History for: Intellia Therapeutics, Inc. (NTLA) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q145

60

75

90

105

120

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09/19/16I:B:$95

10/10/16B:$92

Rating and Price Target History for: Novartis AG (NVS) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

20

40

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2014 2015 2016 2017

12/23/15I:N:$45

03/17/16N:$35

08/12/16N:$50

08/18/16N:$55

11/07/16N:$47.5

03/29/17N:$55

Rating and Price Target History for: Spark Therapeutics, Inc. (ONCE) as of 03-30-2017

Created by BlueMatrix

Page 12 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

8

16

24

32

2014 2015 2016 2017

06/20/16I:N:$4.5

Rating and Price Target History for: ProQR Therapeutics NV (PRQR) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

8

16

24

32

40

2014 2015 2016 2017

04/24/15I:B:$40

08/27/15B:$35

09/30/15B:$40

03/28/16B:$35

08/08/16B:$25

08/15/16B:$20

11/15/16B:$12

Rating and Price Target History for: uniQure N.V. (QURE) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

5

10

15

20

25

2014 2015 2016 2017

04/13/16I:B:$15

06/07/16B:$20

06/28/16B:$13.5

07/22/16B:$14.5

07/25/16B:$12

12/07/16B:$5

Rating and Price Target History for: Regulus Therapeutics, Inc. (RGLS) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

8

16

24

32

2014 2015 2016 2017

10/20/15I:B:$33

12/30/15B:$33

01/07/16B:$35

03/28/16B:$28

05/10/16B:$35

Rating and Price Target History for: REGENXBIO Inc. (RGNX) as of 03-30-2017

Created by BlueMatrix

Page 13 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q16

7

8

9

10

2014 2015 2016 2017

Rating and Price Target History for: GenSight Biologics (SIGHT FP) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

80

160

240

320

2014 2015 2016 2017

03/31/16I:S:$0.8

06/24/16S:$72

Rating and Price Target History for: Silence Therapeutics PLC (SLN/LN) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

4

8

12

16

20

2014 2015 2016 2017

09/21/15I:B:$25

10/23/15B:$27.5

04/18/16B:$20

Rating and Price Target History for: Vascular Biogenics Ltd. (VBLT) as of 03-30-2017

Created by BlueMatrix

Q1 Q2 Q3 Q1 Q2 Q3 Q1 Q2 Q3 Q10

8

16

24

32

2014 2015 2016 2017

12/09/15I:S:$20

01/25/16N:$15

03/04/16N:$12.5

03/28/16N:$11

03/15/17N:$13

Rating and Price Target History for: Voyager Therapeutics, Inc. (VYGR) as of 03-30-2017

Created by BlueMatrix

Page 14 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

Distribution of Ratings/IB ServicesChardan Capital Markets

IB Serv./Past 12 Mos.

Rating Count Percent Count Percent

BUY [BUY] 60 65.93 17 28.33HOLD [NEUTRAL] 26 28.57 3 11.54SELL [SELL] 4 4.40 0 0.00NOT RATED [NR] 1 1.10 1 100.00

Regulation Analyst Certification ("Reg AC") — Gbola Amusa, MD, CFA

ANALYST(s) CERTIFICATION: The analyst(s) responsible for covering the securities in this report certify that theviews expressed in this research report accurately reflect their personal views about “Company” and its securities. Theanalyst(s) responsible for covering the securities in this report certify that no part of their compensation was, is, or willbe directly or indirectly related to the specific recommendation or view contained in this research report.

DISCLOSURES

Within the next 3 months Chardan expects to receive investment banking income from the issuer.

Within the last twelve months, Chardan Capital Markets has received compensation for investment banking servicesfrom Arrowhead Pharmaceuticals, Inc., AveXis, Inc., REGENXBIO Inc. and Vascular Biogenics Ltd.. This researchcontains forward looking statements made pursuant to the safe harbor provision of Private Securities Litigation Act of1995.

Within the past 12 months Chardan Capital Markets has managed or co-managed a public offering for AveXis, Inc. andREGENXBIO Inc..

Chardan Capital Markets intends to seek compensation for investment banking services from all companies underresearch coverage. Chardan Capital Markets or its officers, employees or affiliates may execute transactions insecurities mentioned in this report that may not be consistent with the report’s conclusions.

RATINGS

Buy: Expected to materially outperform sector average over 12 months and indicates total return of at least 10% overthe next 12 months.

Neutral: Returns expected to be in line with sector average over 12 months and indicates total return betweennegative 10% and 10% over the next 12 months.

Sell: Returns expected to be materially below sector average over 12 months and indicates total price decline of atleast 10% over the next 12 months.

FORWARD-LOOKING STATEMENTS: This Report contains forward-looking statements, which involve risks anduncertainties. Actual results may differ significantly from such forward-looking statements. Factors that might causesuch a difference include, but are not limited to, those discussed in the “Risk Factors” section in the SEC filingsavailable in electronic format through SEC Edgar filings at www.SEC.gov on the Internet.

COMPENSATION OR SECURITIES OWNERSHIP: The analyst(s) responsible for covering the securities in this reportreceives compensation based upon, among other factors, the overall profitability of Chardan Capital Markets includingprofits derived from investment banking revenue and securities trading and market making revenue. The analyst(s) thatprepared the research report did not receive any compensation from the Company or any other companies mentionedin this report in connection with the preparation of this report. The analysts responsible for covering the securities inthis report currently do not own common stock in the Company, but in the future may from time to time engage intransactions with respect to the Company or other companies mentioned in the report. Chardan expects to receive, orintends to seek, compensation for investment banking services from the Company in the next three months.

GENERAL: This report is provided for informational purposes only. It is not to be construed as an offer to buy or sell asolicitation of an offer to buy or sell any financial instruments or to particular trading strategy in any jurisdiction. Theinformation and opinions in this report were prepared by registered employees of Chardan Capital Market. Theinformation herein is believed by Chardan Capital Market to be reliable and has been obtained from public sourcesbelieved to be reliable, but Chardan Capital Market makes no representation as to the accuracy or completeness ofsuch information. Opinions, estimates and projections in this report constitute the current judgment of the author as ofthe date of this report. They do not necessarily reflect the opinions of Chardan Capital Market and are subject tochange without notice. In addition, opinions, estimates and projections in this report may differ from or be contrary to

Page 15 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017

those expressed by other business areas or group of Chardan Capital Market and its affiliates. Chardan Capital Markethas no obligation to update, modify or amend this report or to otherwise notify a reader thereof in the event that anymatter stated herein, or any opinion, projection, forecast or estimate set forth herein, changes or subsequentlybecomes inaccurate.

Chardan Capital Market does not provide individually tailored investment advice in research reports. This report hasbeen prepared without regard to the particular investments and circumstances of the recipient. The securitiesdiscussed in this report may not suitable for all investors and investors must make their own investment decisionsusing their own independent advisors as they believe necessary and based upon their specific financial situations andinvestment objectives. Estimates of future performance are based on assumptions that may not be realized.Furthermore, past performance is not necessarily indicative of future performance.

Chardan Capital Market salespeople, traders and other professionals may provide oral or written market commentaryor trading strategies to our clients that reflect opinions that are contrary to the opinions expressed in this research.

Electronic research is simultaneously available to all clients. This report is provided to Chardan Capital Market clientsand may not be redistributed, retransmitted or disclosed, in whole or in part, or in any form or manner, without theexpress written consent of Chardan Capital Market. Receipt and review of this research report constituted youragreement not to redistribute, retransmit, or disclose to others the contents, opinions, conclusion or informationcontained in this report (including any investment recommendations, estimates or target prices) without first obtainingexpress permission from Chardan Capital Market.

This report is not intended for distribution to, or use by any person or entity in any jurisdiction or country where suchdistribution or use would be contrary to local law or regulation.

For investors in the UK: In making this report available, Chardan Capital Market makes no recommendation to buy, sellor otherwise deal in any securities or investments whatsoever and you should neither rely or act upon, directly orindirectly, any of the information contained in this report in respect of any such investment activity. This report is beingdirected at or distributed to , (a) persons who fall within the definition of Investment Professionals (set out in Article19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (the “Order”)); (b)personsfalling within the definition of high net worth companies, unincorporated associations, etc. (set out in Article 49(2) of theOrder); (c) other persons to whom it may otherwise lawfully be communicated (all such persons together being referredto as “relevant persons”). This report must not be acted on or relied on by persons who are not relevant persons.

Page 16 of 16Chardan Capital Markets, LLC

Biotechnology & PharmaceuticalsIndustry NoteApril 2, 2017