Financial Data and Key Metrics Changes - The company reported a strong financial position with over $300 million in cash, following a public follow-on offering that raised approximately $141 million, expected to fund operations into 2022 [10][11] - Specific financial metrics for Q4 2019 were not detailed in the provided content, but the overall financial health appears robust [10] Business Line Data and Key Metrics Changes - The lead gene therapy candidate, ADVM-022, is advancing with significant clinical progress, particularly in the OPTIC trial for wet AMD, with promising data from Cohorts 1 and 2 showing robust efficacy and a favorable safety profile [8][14][15] - The company plans to explore a second indication for diabetic retinopathy (DR) with an IND submission expected in the first half of 2020 and a Phase 1/2 trial beginning in the second half of the year [8][17] Market Data and Key Metrics Changes - The diabetic retinopathy market is highlighted as a large and underserved area, with an estimated 8 million people affected in the U.S., but only 2 million diagnosed and 1 million treated [17][18] - The prevalence of diabetic retinopathy is expected to increase alongside the growing prevalence of diabetes, indicating a significant unmet need for effective therapies [18] Company Strategy and Development Direction - The company is focused on delivering transformative therapies for patients with serious ocular and rare diseases, positioning itself as a leader in gene therapy [7][9] - The strategy includes advancing the clinical development of ADVM-022 and expanding the pipeline of novel gene therapies using their industry-leading AAV platform [9] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the fluid situation regarding the coronavirus and its potential impact on operations, but reported no specific impacts on the OPTIC trial to date [6][12] - The management expressed excitement about the potential of ADVM-022 as a one-time treatment for wet AMD and DR, emphasizing the commitment to advancing these programs [11][18] Other Important Information - The company has moved to a new headquarters in Redwood City to support growth plans and expand core capabilities [9] - Angela Thedinga was appointed as Chief Technology Officer to lead the manufacturing strategy as the company advances toward later-stage clinical trials [10] Q&A Session Summary Question: Enrollment status for Cohort 4 and potential read-throughs for diabetic retinopathy - Management confirmed active screening for Cohort 4 with strong interest from investigators, indicating rapid enrollment is expected [21][22] - Regarding diabetic retinopathy, management discussed potential read-throughs from AMD data, emphasizing safety and efficacy considerations [23][24] Question: Safety signals and implications for intravitreal therapy - Management highlighted the differences in inflammation types between ADVM-022 and other therapies, noting that ADVM-022 has shown manageable low-grade inflammation [30][33] Question: Status of steroid tapering in cohorts - Management provided insights into the tapering of steroids used in previous cohorts, indicating that inflammation has been low-grade and manageable [48][51]

[PART I](index=3&type=section&id=PART%20I) [Business](index=3&type=section&id=Item%201%20Business) Adverum Biotechnologies is a clinical-stage gene therapy company developing ADVM-022 for ocular diseases and leveraging a proprietary AAV vector platform - Adverum's lead product candidate, **ADVM-022**, is a gene therapy for wet AMD and diabetic retinopathy, administered as a single intravitreal injection using an AAV.7m8 vector[7](index=7&type=chunk) - The company is conducting the **OPTIC trial**, a Phase 1 study of ADVM-022 in wet AMD patients, which has received **FDA Fast Track designation**[7](index=7&type=chunk) - Adverum plans to file an **IND for ADVM-022 in diabetic retinopathy** in the first half of 2020 and initiate a Phase 1/2 trial in the second half of 2020[7](index=7&type=chunk) - The company's manufacturing process utilizes the **Baculovirus Expression Vector System (BEVS)** for high-yield, scalable AAV vector production up to **2000-liter scale**[38](index=38&type=chunk) - In August 2019, development of **ADVM-043 for Alpha-1 Antitrypsin deficiency was discontinued** due to a lack of clinically meaningful protein expression in a Phase 1/2 trial[33](index=33&type=chunk) [Our Product Candidates](index=6&type=section&id=Our%20Product%20Candidates) Adverum's product pipeline includes lead programs for wet AMD and diabetic retinopathy, a rare disease candidate, and a partnered program Product Pipeline Status | Gene Therapy Candidate | Indication | Preclinical | Phase 1 | Phase 2 | Phase 3 | | :--- | :--- | :--- | :--- | :--- | :--- | | **Lead Programs** | | | | | | | ADVM-022 | Wet AMD | | ■ | | | | ADVM-022 | Diabetic Retinopathy | ■ | | | | | **Rare Disease** | | | | | | | ADVM-053 (Early Dev) | Hereditary Angioedema | ■ | | | | | **Partnered Program** | | | | | | | GS030 (GenSight) | Retinitis Pigmentosa | | ■ | | | OPTIC Trial Cohort Details | Cohort | Patient Count (n) | Dose (vg/eye) | Prophylactic Steroid | | :--- | :--- | :--- | :--- | | Cohort 1 | 6 | 6 x 10^11 | 14-day oral taper | | Cohort 2 | 6 | 2 x 10^11 | 14-day oral taper | | Cohort 3 | 9 | 2 x 10^11 | 6-week topical taper | | Cohort 4 | 9 | 6 x 10^11 | 6-week topical taper | - As of February 2020, in the OPTIC trial, **6 of 6 patients in high-dose cohort 1 remained rescue injection-free** at a median follow-up of **50 weeks**, while **4 of 6 patients in lower-dose cohort 2 were rescue injection-free** at **24 weeks**[22](index=22&type=chunk) - **ADVM-022** has been **well-tolerated** with no drug-related serious adverse events or dose-limiting toxicities, and low-grade ocular inflammation was responsive to steroid eye drops[22](index=22&type=chunk) - In May 2019, the **FDA lifted a clinical hold on the ADVM-022 IND**, allowing dose escalation up to **2 x 10^12 vg/eye**, though a partial clinical hold remains for **6 x 10^12 vg/eye** doses pending CMC resolution[32](index=32&type=chunk) [Competition](index=13&type=section&id=Competition) The company faces significant competition from established anti-VEGF therapies and emerging next-generation treatments for ocular diseases - **ADVM-022** will compete with established anti-VEGF therapies from major pharmaceutical companies[40](index=40&type=chunk) - Key competitive categories for wet AMD and diabetic retinopathy include biosimilar anti-VEGFs, combination therapies, next-generation anti-VEGFs, and long-acting delivery systems or gene therapies like **RGX-314**[40](index=40&type=chunk) [License and Collaboration Agreements](index=14&type=section&id=License%20and%20Collaboration%20Agreements) The company manages various agreements, including a Regeneron collaboration expiring in 2020, an exclusive license for AAV.7m8, and an ongoing dispute with Virovek - The research collaboration with **Regeneron**, initiated in May 2014, is anticipated to expire on **May 1, 2020**, as Regeneron did not exercise its extension option[41](index=41&type=chunk) - The company holds an **exclusive worldwide license** from the University of California for intellectual property related to the **AAV.7m8 capsid** used in **ADVM-022**[42](index=42&type=chunk) - A dispute exists with **Virovek, Inc.** regarding their notice of intent to terminate a non-exclusive license for AAV manufacturing technology, which Adverum disputes[49](index=49&type=chunk) [Intellectual Property](index=16&type=section&id=Intellectual%20Property) The company protects its technology through over 40 issued patents and 150 pending applications, covering AAV-based delivery and the AAV.7m8 vector - The company owns or licenses over **40 issued patents** and **150 pending patent applications** in the U.S. and foreign jurisdictions[50](index=50&type=chunk) - Company-owned patent families cover AAV-based delivery of anti-VEGF proteins for eye diseases, with patents expected to expire between **2033 and 2039**[51](index=51&type=chunk) - A key exclusively licensed patent family covers the novel **AAV.7m8 vector**, with patents expected to expire in **2032**[54](index=54&type=chunk) [Risk Factors](index=24&type=section&id=Item%201A%20Risk%20Factors) The company faces substantial financial, development, clinical trial, third-party reliance, commercialization, and intellectual property risks, including a history of losses and dependence on ADVM-022 success - **Financial Risk:** The company has a history of significant operating losses and will require additional funding beyond existing cash, which is projected to fund operations into **2022**[79](index=79&type=chunk)[80](index=80&type=chunk)[81](index=81&type=chunk) - **Development Risk:** The business substantially depends on the success of **ADVM-022**, whose IND remains on partial clinical hold for **6 x 10^12 vg/eye** dosing pending resolution of FDA CMC requirements[83](index=83&type=chunk) - **Clinical Trial Risk:** Preliminary and interim data from trials like **OPTIC** may change, and ocular inflammation is a known side effect of **ADVM-022** requiring management[88](index=88&type=chunk)[92](index=92&type=chunk) - **Third-Party Reliance Risk:** Reliance on third parties for preclinical testing, clinical trials, and manufacturing introduces risks of delays, non-compliance, and supply disruptions[94](index=94&type=chunk)[95](index=95&type=chunk)[96](index=96&type=chunk) - **Commercialization Risk:** Significant uncertainties exist regarding market acceptance, pricing, and reimbursement for a single-administration gene therapy, alongside competition from established and developing therapies[107](index=107&type=chunk)[118](index=118&type=chunk)[112](index=112&type=chunk) - **Intellectual Property Risk:** Reliance on licensed patents and an ongoing dispute with **Virovek** over a manufacturing technology license pose risks to product development[141](index=141&type=chunk) [Unresolved Staff Comments](index=54&type=section&id=Item%201B%20Unresolved%20Staff%20Comments) The company reports no unresolved staff comments - Not applicable[176](index=176&type=chunk) [Properties](index=55&type=section&id=Item%202%20Properties) In January 2020, the company relocated its corporate headquarters to an 81,000 square foot facility in Redwood City, California, under a ten-year lease - The company's new corporate headquarters is an **81,000 square foot facility** in Redwood City, California, under a **ten-year lease** that commenced in January 2020[177](index=177&type=chunk) [Legal Proceedings](index=55&type=section&id=Item%203%20Legal%20Proceedings) The company reports no legal proceedings - Not applicable[178](index=178&type=chunk) [Mine Safety Disclosures](index=55&type=section&id=Item%204%20Mine%20Safety%20Disclosures) The company reports no mine safety disclosures - Not applicable[178](index=178&type=chunk) [PART II](index=56&type=section&id=PART%20II) [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=56&type=section&id=Item%205%20Market%20for%20Registrant%27s%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock trades on Nasdaq under "ADVM", has approximately 15 record holders, and has never paid cash dividends, nor does it anticipate doing so - The company's common stock is listed on the **Nasdaq Global Market** under the ticker symbol **\"ADVM\"**[180](index=180&type=chunk) - The company has never declared or paid cash dividends and intends to retain all future earnings for business development[182](index=182&type=chunk) [Selected Financial Data](index=56&type=section&id=Item%206%20Selected%20Financial%20Data) The company is not required to provide this information as it qualifies as a smaller reporting company - The company is not required to provide this information as it qualifies as a smaller reporting company[184](index=184&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=57&type=section&id=Item%207%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) For 2019, the company reported a net loss of **$64.5 million**, an improvement from 2018, with **$166.0 million** in cash and investments, supplemented by a **$140.8 million** February 2020 offering, expected to fund operations into 2022 Results of Operations (2019 vs. 2018) (In thousands) | (In thousands) | 2019 | 2018 | Change | | :--- | :--- | :--- | :--- | | Collaboration and license revenue | $250 | $1,612 | $(1,362) | | Research and development | $40,419 | $50,133 | $(9,714) | | General and administrative | $28,376 | $24,560 | $3,816 | | Impairment of goodwill and intangible assets | $0 | $5,000 | $(5,000) | | **Operating loss** | **$(68,545)** | **$(78,081)** | **$9,536** | | **Net loss** | **$(64,486)** | **$(72,627)** | **$8,141** | - **R&D expenses decreased by $9.7 million** in 2019, primarily due to a **$7.9 million reduction** in manufacturing costs for **ADVM-022** and **ADVM-053**[209](index=209&type=chunk) - **G&A expenses increased by $3.8 million** in 2019, driven by higher consulting, professional services, and facilities costs[210](index=210&type=chunk) - As of December 31, 2019, the company had an accumulated deficit of **$385.0 million** and cash, cash equivalents, and short-term investments totaling **$166.0 million**[188](index=188&type=chunk)[215](index=215&type=chunk) - In February 2020, the company raised an additional **$140.8 million** in net proceeds from a public stock offering, with the total cash position expected to fund operations into **2022**[215](index=215&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=65&type=section&id=Item%207A%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is not required to provide this information as it qualifies as a smaller reporting company - The company is not required to provide this information as it qualifies as a smaller reporting company[221](index=221&type=chunk) [Financial Statements and Supplementary Data](index=65&type=section&id=Item%208%20Financial%20Statements%20and%20Supplementary%20Data) The consolidated financial statements for 2019 and 2018 are presented, showing 2019 total assets of **$222.7 million**, total liabilities of **$47.8 million**, and a net loss of **$64.5 million**, reflecting the adoption of Topic 842 Consolidated Balance Sheet Data (as of Dec 31) (In thousands) | (In thousands) | 2019 | 2018 | | :--- | :--- | :--- | | Cash and cash equivalents | $65,897 | $154,949 | | Short-term investments | $100,138 | $50,130 | | **Total assets** | **$222,727** | **$213,495** | | **Total liabilities** | **$47,770** | **$12,328** | | **Total stockholders' equity** | **$174,957** | **$201,167** | Consolidated Statement of Operations Data (Year ended Dec 31) (In thousands) | (In thousands) | 2019 | 2018 | | :--- | :--- | :--- | | Collaboration and license revenue | $250 | $1,612 | | Total operating expenses | $68,795 | $79,693 | | **Operating loss** | **$(68,545)** | **$(78,081)** | | **Net loss** | **$(64,486)** | **$(72,627)** | | Net loss per share | $(1.01) | $(1.18) | - The company adopted the new lease accounting standard (**Topic 842**) on January 1, 2019, recording a right-of-use asset of **$23.1 million** and a lease liability of **$24.7 million**[259](index=259&type=chunk) - As of December 31, 2019, the company had federal net operating loss carryforwards of approximately **$159.5 million** and federal R&D tax credit carryforwards of **$4.6 million**, subject to ownership change limitations[295](index=295&type=chunk) [Changes in and Disagreements with Accountants on Accounting and Financial Disclosure](index=85&type=section&id=Item%209%20Changes%20in%20and%20Disagreements%20with%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure) The company reports no changes in or disagreements with its accountants on accounting and financial disclosure - None[299](index=299&type=chunk) [Controls and Procedures](index=85&type=section&id=Item%209A%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2019, a conclusion affirmed by Ernst & Young LLP - Management concluded that as of December 31, 2019, the company's disclosure controls and procedures were effective[300](index=300&type=chunk) - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2019, based on the **COSO 2013 framework**[301](index=301&type=chunk) - The independent registered public accounting firm, **Ernst & Young LLP**, issued an unqualified opinion on the effectiveness of the company's internal control over financial reporting as of December 31, 2019[304](index=304&type=chunk) [Other Information](index=88&type=section&id=Item%209B%20Other%20Information) This section details the company's 2020 Annual Meeting of Stockholders, scheduled for June 23, 2020, including proposal deadlines - The **2020 Annual Meeting of Stockholders** is scheduled for **June 23, 2020**[310](index=310&type=chunk) [PART III](index=89&type=section&id=PART%20III) [Directors, Executive Officers and Corporate Governance](index=89&type=section&id=Item%2010%20Directors%2C%20Executive%20Officers%20and%20Corporate%20Governance) The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2020 Annual Meeting of Stockholders - Information is incorporated by reference from the definitive proxy statement[312](index=312&type=chunk) [Executive Compensation](index=89&type=section&id=Item%2011%20Executive%20Compensation) The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2020 Annual Meeting of Stockholders - Information is incorporated by reference from the definitive proxy statement[313](index=313&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=89&type=section&id=Item%2012%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2020 Annual Meeting of Stockholders - Information is incorporated by reference from the definitive proxy statement[314](index=314&type=chunk) [Certain Relationships and Related Transactions, and Director Independence](index=89&type=section&id=Item%2013%20Certain%20Relationships%20and%20Related%20Transactions%2C%20and%20Director%20Independence) The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2020 Annual Meeting of Stockholders - Information is incorporated by reference from the definitive proxy statement[315](index=315&type=chunk) [Principal Accountant Fees and Services](index=89&type=section&id=Item%2014%20Principal%20Accountant%20Fees%20and%20Services) The information required by this item is incorporated by reference from the company's definitive proxy statement for its 2020 Annual Meeting of Stockholders - Information is incorporated by reference from the definitive proxy statement[316](index=316&type=chunk) [PART IV](index=89&type=section&id=PART%20IV) [Exhibits, Financial Statement Schedules](index=89&type=section&id=Item%2015%20Exhibits%2C%20Financial%20Statement%20Schedules) This section provides an index of financial statements and exhibits filed with the Form 10-K, with consolidated financial statements located in Item 8 - This section contains the index of financial statements and exhibits filed with the Form 10-K[318](index=318&type=chunk)[319](index=319&type=chunk) [Form 10-K Summary](index=91&type=section&id=Item%2016%20Form%2010-K%20Summary) The company reports no Form 10-K summary - None[322](index=322&type=chunk)

Adverum Biotechnologies, Inc. (NASDAQ:ADVM) Q3 2019 Earnings Conference Call November 7, 2019 4:30 PM ET Company Participants Myesha Lacy - Vice President of Investor Relations & Corporate Communications Leone Patterson - Chief Executive Officer Aaron Osborne - Chief Medical Officer Conference Call Participants Tyler Van Buren - Piper Jaffray Emma Nealon - Cantor Fitzgerald Phil Nadeau - Cowen & Company Joon Lee - SunTrust Patrick Dolezal - LifeSci Capital Myesha Lacy Thank you, and welcome, everyone. Today ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2019 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | --- | --- | --- | --- | |---------------------------------------------------------------------------------------|-----------------------------------------------------------------|------ ...

Financial Data and Key Metrics Changes - The company is focused on developing ADVM-022 for treating VEGF-driven retinal diseases, particularly wet AMD and diabetic retinopathy, which are significant causes of vision loss [6][9] - The company has achieved significant clinical and regulatory milestones with ADVM-022, with plans to present 24-week data from the Phase I OPTIC trial at an upcoming meeting [8][21] Business Line Data and Key Metrics Changes - ADVM-022 is being developed as a single intravitreal injection approach, which could provide a more durable treatment option compared to current therapies that require frequent injections [6][13] - The company has discontinued the gene therapy program targeting A1AT deficiency and has moved the program for Hereditary Angioedema back into early development [9][10] Market Data and Key Metrics Changes - Approximately 1.2 million individuals in the US are affected by wet AMD, and the prevalence of diabetic retinopathy is also increasing, indicating a growing market for ADVM-022 [7][19] - The company plans to submit an IND for ADVM-022 in diabetic retinopathy in the first half of 2020, highlighting the potential expansion of its market reach [20] Company Strategy and Development Direction - The company aims to scale up its manufacturing process to support later-stage development and commercial use, with a new corporate headquarters to enhance in-house capabilities [10] - The focus remains on developing ADVM-022 for AMD and diabetic retinopathy, while exploring opportunities in other VEGF-driven diseases [9][20] Management's Comments on Operating Environment and Future Outlook - Management believes that gene therapy can be transformative for patients and is committed to advancing their development pipeline [6][11] - The company is optimistic about the upcoming data presentations and the potential impact of ADVM-022 on treatment burdens for patients [21][65] Other Important Information - Recent corporate updates include the retirement of board member Mitch Finer and the transition of President and Chief Scientific Officer Mehdi Gasmi to the Board of Directors [10] - The company is expanding its talent pool with recent senior management additions to support its mission [11] Q&A Session All Questions and Answers Question: Can you provide clarity on the types of patients being enrolled in the OPTIC trial? - The protocol stipulates that patients must have had at least two injections in the previous four months, ensuring they require frequent anti-VEGF injections [23][24] Question: Can you elaborate on the criteria for rescue injections in the trial? - Rescue injections are based on OCT and vision criteria, with stringent protocols to ensure patients only receive them when necessary [27][29] Question: What is the rationale behind using prophylactic oral steroid dosing in the study? - The use of tapering doses of prednisone is to manage expected immune responses following gene therapy [30][31] Question: How do you view the acceptable level of inflammation for less frequently administered intravitreal gene therapy? - A balance is expected, where some immune response is acceptable if it leads to a significant reduction in the need for rescue injections [33][34] Question: What was the reasoning for the decision to lower the dose in the second cohort? - The decision was based on observing robust preliminary anatomical responses and not due to safety concerns [36][38] Question: Can you clarify the relationship between anatomical responses and the need for additional anti-VEGF injections? - Robust anatomical responses are assessed through OCT, and the goal is to reduce the number of rescue injections required [63][64]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2019 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-36579 Adverum Biotechnologies, Inc. (Exact name of registrant as specified in its charter) Delaware 20-5258327 (State or other jur ...

PART I—FINANCIAL INFORMATION [Item 1. Financial Statements (unaudited)](index=3&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) The company's unaudited Q1 2019 financials show a net loss of $14.5 million and total assets of $221.0 million [Condensed Consolidated Balance Sheets](index=3&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets grew to $221.0 million due to a new lease asset, while liabilities also increased accordingly Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2019 | December 31, 2018 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $144,107 | $154,949 | | Short-term investments | $45,381 | $50,130 | | Total current assets | $193,137 | $208,754 | | Operating lease right-of-use asset | $22,592 | $— | | **Total assets** | **$221,047** | **$213,495** | | **Liabilities & Equity** | | | | Total current liabilities | $10,610 | $10,719 | | Lease liability, non-current | $22,078 | $— | | **Total liabilities** | **$32,904** | **$12,328** | | Accumulated deficit | $(335,032) | $(320,543) | | **Total stockholders' equity** | **$188,143** | **$201,167** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The company reported a Q1 2019 net loss of $14.5 million, an improvement from the prior year due to lower R&D expenses Condensed Consolidated Statements of Operations (in thousands, except per share data) | Metric | Three Months Ended March 31, 2019 | Three Months Ended March 31, 2018 | | :--- | :--- | :--- | | Collaboration and license revenue | $— | $216 | | Research and development | $10,131 | $12,794 | | General and administrative | $5,576 | $5,368 | | **Operating loss** | **$(15,707)** | **$(17,946)** | | **Net loss** | **$(14,489)** | **$(17,200)** | | Net loss per share | $(0.23) | $(0.30) | [Condensed Consolidated Statements of Stockholders Equity](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders%20Equity) Stockholders' equity declined to $188.1 million, primarily driven by the quarterly net loss - Total stockholders' equity decreased by **$13.1 million** during the first quarter of 2019, mainly due to the **net loss of $14.5 million**[8](index=8&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operations was $13.2 million, contributing to a total cash decrease of $10.8 million for the quarter Condensed Consolidated Statements of Cash Flows Highlights (in thousands) | Cash Flow Activity | Three Months Ended March 31, 2019 | Three Months Ended March 31, 2018 | | :--- | :--- | :--- | | Net cash used in operating activities | $(13,217) | $(12,984) | | Net cash provided by investing activities | $2,745 | $25,383 | | Net cash provided by (used in) financing activities | $(370) | $69,798 | | **Net (decrease) increase in cash** | **$(10,842)** | **$82,197** | - The significant difference in financing activities between Q1 2019 and Q1 2018 is due to **$70.2 million in net proceeds from common stock sales in 2018**, which did not recur in 2019[61](index=61&type=chunk) [Notes to Condensed Consolidated Financial Statements](index=7&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Key notes cover the company's clinical-stage status, adoption of a new lease standard, and collaboration agreement updates - The company is a clinical-stage gene therapy company with an **accumulated deficit of $335.0 million** as of March 31, 2019, but believes it has sufficient funds to continue operations into 2021[14](index=14&type=chunk) - On January 1, 2019, the company adopted the new lease accounting standard (Topic 842), recording a **lease liability of $24.7 million** and a **right-of-use asset of $23.1 million**[16](index=16&type=chunk) - The collaboration agreement with Editas generated no revenue in Q1 2019, as the remaining performance obligations were completed in 2018[25](index=25&type=chunk)[26](index=26&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operation](index=13&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operation) Management discusses the clinical hold on its lead product, ADVM-022, and financial results, including a reduced net loss - The company's lead product candidate, ADVM-022 for wet AMD, is in a Phase 1 OPTIC trial; however, the **FDA placed the IND on clinical hold** in April 2019[41](index=41&type=chunk) - Development of ADVM-043 for A1AT deficiency was discontinued based on data from the ADVANCE trial[41](index=41&type=chunk) - R&D expenses decreased by **$2.7 million**, primarily due to a **$3.3 million reduction** in costs from discontinuing the ADVM-043 program[53](index=53&type=chunk) - As of March 31, 2019, the company had **$189.5 million in cash**, cash equivalents, and short-term investments, which is believed to be sufficient to fund operations into 2021[43](index=43&type=chunk)[56](index=56&type=chunk) Results of Operations Comparison (in thousands) | Line Item | Q1 2019 | Q1 2018 | Change | | :--- | :--- | :--- | :--- | | Collaboration and license revenue | $— | $216 | $(216) | | Research and development | $10,131 | $12,794 | $(2,663) | | General and administrative | $5,576 | $5,368 | $208 | | **Operating loss** | **$(15,707)** | **$(17,946)** | **$2,239** | | **Net loss** | **$(14,489)** | **$(17,200)** | **$2,711** | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=18&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is exempt from this disclosure as a smaller reporting company - The company is not required to provide quantitative and qualitative disclosures about market risk because it qualifies as a **smaller reporting company** under SEC rules[64](index=64&type=chunk) [Item 4. Controls and Procedures](index=18&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of the quarter-end - The CEO and CFO concluded that as of March 31, 2019, the company's **disclosure controls and procedures were effective**[65](index=65&type=chunk) - **No material changes** were made to the company's internal control over financial reporting during the first quarter of 2019[65](index=65&type=chunk) PART II—OTHER INFORMATION [Item 1. Legal Proceedings](index=19&type=section&id=Item%201.%20Legal%20Proceedings) The company reports no material legal proceedings for the period - Not applicable[68](index=68&type=chunk) [Item 1A. Risk Factors](index=19&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant financial, developmental, commercial, and operational risks - **Financial Risk:** The company has a history of significant operating losses, with an **accumulated deficit of $335.0 million** as of March 31, 2019, and will require substantial additional funding[70](index=70&type=chunk) - **Development Risk:** The **FDA placed the IND for lead candidate ADVM-022 on clinical hold** in April 2019; failure to lift the hold would harm the business[73](index=73&type=chunk)[74](index=74&type=chunk) - **Commercialization Risk:** ADVM-022, if approved, will compete with well-established anti-VEGF therapies like **Lucentis® and EYLEA®**, requiring market acceptance and adequate reimbursement[104](index=104&type=chunk) - **Reliance on Third Parties:** The company depends on third parties to conduct clinical trials and manufacture its product candidates, introducing risks related to performance and supply chain continuity[81](index=81&type=chunk)[83](index=83&type=chunk) - **Intellectual Property Risk:** The business relies on licensed patents and proprietary technology, and the inability to maintain or protect this IP could materially harm the company[125](index=125&type=chunk)[126](index=126&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=48&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This item is not applicable for the reporting period - Not applicable[162](index=162&type=chunk) [Item 3. Defaults Upon Senior Securities](index=48&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports no defaults upon senior securities - None[162](index=162&type=chunk) [Item 4. Mine Safety Disclosures](index=48&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company's operations - Not applicable[162](index=162&type=chunk) [Item 5. Other Information](index=48&type=section&id=Item%205.%20Other%20Information) The company reports no other material information for the period - Not applicable[162](index=162&type=chunk) [Item 6. Exhibits](index=49&type=section&id=Item%206.%20Exhibits) This section lists all exhibits filed with the Form 10-Q, including officer certifications - Exhibits filed include the Employment Agreement with CFO Thomas Leung, CEO and CFO certifications (Rule 13a-14(a) and Section 906), and XBRL interactive data files[163](index=163&type=chunk)[164](index=164&type=chunk) [Signatures](index=50&type=section&id=SIGNATURES) [Signatures](index=50&type=section&id=Signatures) The report is duly signed by the Chief Executive Officer and Chief Financial Officer - The Form 10-Q was signed on **May 8, 2019**, by Leone Patterson (CEO) and Thomas Leung (CFO)[166](index=166&type=chunk)[167](index=167&type=chunk)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2018 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 | --- | --- | |---------------------------------------------------------------------------------------------------|--------------------------------------------------| | | | | For the transition period from t ...