Financial Performance - As of September 30, 2020, the company had an accumulated deficit of $464.9 million and expects to incur substantial expenses and increasing losses from operations in the foreseeable future[48]. - Net loss for the three months ended September 30, 2020, was $27.8 million, compared to a net loss of $16.1 million for the same period in 2019[55]. - Cash and cash equivalents increased to $454.5 million as of September 30, 2020, compared to $166.0 million as of December 31, 2019[61]. - Net cash used in operating activities was $57.1 million for the nine months ended September 30, 2020, compared to $34.3 million for the same period in 2019[64]. - Net cash used in investing activities was $291.7 million for the nine months ended September 30, 2020, primarily for marketable securities purchases[65]. - Net cash provided by financing activities was $355.6 million for the nine months ended September 30, 2020, mainly from the sale of common stock[66]. - The accumulated deficit as of September 30, 2020, was $464.9 million, indicating ongoing financial challenges[61]. Research and Development - The company plans to initiate a pivotal trial for its lead product candidate ADVM-022 in wet AMD in mid-2021 based on promising data from the OPTIC trial[40]. - The OPTIC trial has shown long-term durability beyond 15 months from a single IVT injection of ADVM-022 with zero anti-VEGF rescue injections in the high-dose cohort[40]. - The INFINITY Phase 2 trial is set to enroll approximately 33 patients to evaluate a single IVT injection of ADVM-022 in patients with DME, comparing it to aflibercept[42]. - Future research and development expenses are expected to increase as the company continues to invest in advancing its gene therapy product candidate ADVM-022[57]. Operational Overview - The company has not generated any revenue from product sales to date, relying instead on research, collaboration, and license arrangements with strategic partners[49]. - The company has $454.5 million in cash, cash equivalents, and short-term investments as of September 30, 2020, which is expected to fund operations into mid-2022[48]. - The company is scaling up manufacturing processes from 200L to 1000L to support the future commercial launch of ADVM-022[40]. - The company does not have operational clinical or commercial manufacturing facilities, relying on third-party contractors for clinical manufacturing[48]. - The company has experienced limited impact from the COVID-19 pandemic on its operations and clinical trials to date[43][45]. Revenue and Expenses - Collaboration and license revenue decreased by $250,000 for the three months ended September 30, 2020, compared to the same period in 2019[55]. - Research and development expenses increased by $6.7 million to $16.7 million for the three months ended September 30, 2020, primarily due to higher personnel costs and production costs related to product candidate ADVM-022[57]. - General and administrative expenses rose by $4.0 million to $11.4 million for the three months ended September 30, 2020, mainly driven by increased personnel costs[58].

Financial Data and Key Metrics Changes - The company reported robust treatment response and long-term durability beyond 15 months from a single injection of ADVM-022, with zero rescue injections in patients from Cohort 1 [11][45] - There was a substantial reduction in annualized anti-VEGF injection frequency, with a 100% reduction in the high dose cohort and an 87% reduction in the low dose cohorts [43][45] Business Line Data and Key Metrics Changes - ADVM-022 continues to show a favorable safety profile across all four cohorts, with low-grade inflammation that is manageable with topical steroid eye drops [32][45] - The OPTIC trial has completed enrollment, and the company plans to present additional data from Cohorts 1 to 4 by the end of the year [12][45] Market Data and Key Metrics Changes - The company is preparing to advance ADVM-022 for two significant ocular disease indications: wet AMD and DME, which represent a large global market opportunity [12][46] - The ongoing INFINITY trial for diabetic macular edema is designed to demonstrate superior disease control compared to a single aflibercept injection, addressing a major cause of blindness in working adults [46][47] Company Strategy and Development Direction - The company aims to revolutionize the treatment paradigm for ocular diseases with ADVM-022, focusing on a one-and-done approach to reduce treatment burden for patients [10][11] - Plans are in place to scale up manufacturing capabilities from 200 liters to 1,000 liters to support future commercial product launch [13][14] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of ADVM-022 to change the disease course for patients with neovascular AMD and highlighted the importance of continuous delivery in the context of the COVID-19 pandemic [11][16] - The leadership team is focused on expanding business operations and capabilities, including clinical, regulatory, and manufacturing functions, to prepare for a pivotal trial and potential commercial launch [14][15] Other Important Information - The company has experienced limited impact from COVID-19 on its operations and ongoing clinical trials, successfully completing enrollment in Cohort 4 of the OPTIC trial [16] - The management team emphasized the importance of patient-centric approaches and the emotional impact of treatment on patients and their families [49][50] Q&A Session Summary Question: Efficacy and Safety of ADVM-022 - The management noted that improvements in anatomy and central retinal thickness have been observed, indicating potential efficacy of continuous delivery [52][53] - Concerns regarding posterior inflammation were addressed, with management expressing confidence in the safety profile of ADVM-022 compared to other treatments [54][56] Question: Management of Topical Steroids - Management discussed the experiences of patients when tapering off topical steroids, noting that some patients may experience a rebound effect, but most have been able to discontinue with minimal issues [59][60][64] Question: Inflammation Concerns - The management acknowledged the importance of monitoring inflammation levels and emphasized that the majority of patients have experienced manageable inflammation that responds well to topical steroids [67][68]

Financial Performance - As of June 30, 2020, the company had an accumulated deficit of $437.1 million and expects to incur substantial expenses and increasing losses in the foreseeable future[42] - The net loss for the six months ended June 30, 2020, was $52.1 million, an increase of $22.7 million compared to a net loss of $29.4 million for the same period in 2019[49] - The accumulated deficit as of June 30, 2020, was $437.1 million, indicating ongoing financial challenges since inception[53] - Net cash used in operating activities for the six months ended June 30, 2020, was $30.5 million, compared to $24.8 million for the same period in 2019[57] - Net cash provided by financing activities for the six months ended June 30, 2020, was $151.4 million, primarily from the sale of common stock[59] Revenue Generation - The company has not generated any revenue from product sales to date, relying instead on research, collaboration, and license arrangements with strategic partners[44] Cash Position - The company had $280.1 million in cash, cash equivalents, and short-term investments as of June 30, 2020, which is expected to fund operations into 2022[43] - As of June 30, 2020, the company had $280.1 million in cash, cash equivalents, and short-term investments, up from $166.0 million as of December 31, 2019[53] Research and Development - Research and development expenses increased by $10.2 million to $19.2 million for Q2 2020 compared to Q2 2019, primarily due to increased production costs and personnel-related expenses[50] - The company expects research and development expenses to continue increasing as it invests in advancing its gene therapy product candidate ADVM-022 and other research programs[50] Administrative Expenses - General and administrative expenses rose by $3.5 million to $10.6 million for Q2 2020 compared to Q2 2019, driven by higher personnel costs and facility-related expenses[51] - The company anticipates that general and administrative expenses will rise in future periods to support its gene therapy programs and organizational growth[51] Clinical Trials and Product Development - The OPTIC trial for ADVM-022 has shown long-term durability beyond 15 months from a single IVT injection with zero anti-VEGF rescue injections in the high-dose cohort[35] - The INFINITY Phase 2 trial has been initiated to evaluate ADVM-022 in patients with diabetic macular edema, with plans to enroll approximately 33 patients[35] - The company is scaling up manufacturing processes from 200L to 1000L to support the future commercial launch of ADVM-022[35] - The FDA granted Fast Track designation for ADVM-022 for the treatment of wet age-related macular degeneration[35] Manufacturing and Operations - The company does not have operational clinical or commercial manufacturing facilities, relying on third-party contractors for clinical manufacturing[43] - The company has licensed the right to use AAV.7m8 to GenSight Biologics for their product candidate GS030, currently in clinical development[37] - The company has experienced limited impact from the COVID-19 pandemic on its operations and clinical trials to date[39] Internal Controls and Governance - As of June 30, 2020, the company's disclosure controls and procedures were deemed effective by the Chief Executive Officer and Chief Financial Officer[61] - There were no changes in internal control over financial reporting during the three months ended June 30, 2020 that materially affected internal controls[61] - The management acknowledges that disclosure controls and procedures cannot prevent all errors and fraud, providing only reasonable assurance[62] - The design of the control system must consider resource constraints and the cost-benefit ratio of controls[62] - The company recognizes the inherent limitations in all control systems, which may not detect all control issues or instances of fraud[62] Funding and Financial Strategy - The company plans to seek additional funding through equity or debt financings to support its development and commercialization efforts[54]

Financial Data and Key Metrics Changes - The company ended Q1 2020 with $297 million in cash, cash equivalents, and marketable securities, which is expected to finance operations until 2022 [11] - The financial results for the first quarter of 2020 were reported alongside the announcement of the new INFINITY trial for ADVM-022 [5] Business Line Data and Key Metrics Changes - The ongoing OPTIC Phase I trial for ADVM-022 has shown promising data, demonstrating long-term durability beyond one year with zero rescue injections in patients treated in Cohort 1 [9][14] - The INFINITY Phase 2 trial for diabetic macular edema (DME) is now open for patient enrollment, with the FDA having approved the IND for diabetic retinopathy [10][15] Market Data and Key Metrics Changes - Approximately 30 million people in the U.S. are impacted by diabetes, with about 1.5 to 2 million patients likely suffering from DME, representing a significant market opportunity [15][42] - The current standard-of-care therapy for DME requires frequent anti-VEGF intravitreal injections, which presents a challenge for patient compliance [16] Company Strategy and Development Direction - The company aims to position itself as a leader in gene therapy, focusing on developing a pipeline of novel gene therapies beyond ADVM-022 [10] - The INFINITY trial is designed to demonstrate superior control of disease activity following a single injection of ADVM-022 compared to aflibercept [17] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the impact of COVID-19 on operations but emphasized the commitment to advancing clinical trials and maintaining patient safety [7][12] - The company remains focused on developing transformative one-time treatments for patients with wet AMD and DME [20] Other Important Information - The collaboration with Regeneron has been terminated, allowing the company to explore new indications and targets [77] - The company has implemented remote study monitoring and precautionary measures at study sites due to COVID-19 [7][12] Q&A Session Summary Question: Can you clarify the DME trial design and the criteria for rescue injections? - Management confirmed that the criteria for rescue injections in the INFINITY trial are stringent, with expectations that more than half of aflibercept patients would require rescue by week 16 [24][34] Question: What are the implications of the trial design for future registrational studies? - Management indicated that the trial design is robust and aims to show superiority over current standard care, with potential for creative approaches in future studies [29][66] Question: How does the company plan to address the dosing for DME patients? - The same two doses used in wet AMD trials will be applied, with flexibility to adapt based on interim analysis results [66] Question: What is the expected timeline for data from the INFINITY trial? - Management stated that data will be shared once patients are enrolled and treated, with further guidance on timelines to follow [69] Question: Can you discuss the inflammation kinetics observed in the OPTIC trial? - Inflammation is expected to peak early post-injection, with steroid eye drops effectively managing it [72][74] Question: What are the next steps following the OPTIC trial? - The company plans to analyze data from Cohort 4 before determining the design of future studies [48][68]

Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME) Market Overview - Over 30 million people in the U S are living with diabetes, all at risk of DR[6] - DR affects approximately one in three (33%) adults with diabetes[6] - DME affects approximately 5% of people with diabetes[7] - The global sales for approved anti-VEGF therapies is $11 billion[6] - Standard-of-care therapy for DME is anti-VEGF intravitreal injections, which require frequent and long-term administration[6] ADVM-022 Gene Therapy - ADVM-022 is a one-time intravitreal injection for durable expression of therapeutic protein[7] - It produces codon-optimized aflibercept for efficient VEGF and PlGF inhibition[7,8] INFINITY Phase 2 Trial - The INFINITY trial is a Phase 2 clinical trial of ADVM-022 in Diabetic Macular Edema (DME)[2,9,10] - The trial will enroll approximately 33 patients and is designed to demonstrate superior disease control compared to a single aflibercept injection[10] - The primary objective is to assess the time to worsening of DME disease activity[9]

Financial Performance - As of March 31, 2020, the company had an accumulated deficit of $407.9 million and expects to incur substantial expenses and increasing losses from operations in the foreseeable future[42] - The company reported total operating expenses of $23.791 million for Q1 2020, an increase of $8.084 million compared to $15.707 million in Q1 2019[48] - The net loss for Q1 2020 was $22.906 million, compared to a net loss of $14.489 million in Q1 2019, representing an increase in loss of $8.417 million[48] - The company has not generated any revenue from product sales to date, relying instead on research, collaboration, and license arrangements[43] - Net cash used in operating activities was $13.6 million for the three months ended March 31, 2020, compared to $13.2 million for the same period in 2019[56] - The company has not generated positive cash flow or net income from operations since inception[52] Research and Development - Research and development expenses for Q1 2020 were $14.751 million, up from $10.131 million in Q1 2019, reflecting an increase of $4.620 million[48] - The company expects research and development expenses to increase in future periods as it continues to invest in advancing its gene therapy product candidate ADVM-022[49] - The OPTIC trial for ADVM-022 has shown long-term durability beyond 1 year with zero rescue injections in Cohort 1[34] - The INFINITY Phase 2 trial will enroll approximately 33 patients to evaluate ADVM-022 in patients with diabetic macular edema (DME)[36] Cash and Investments - The company had $297.1 million in cash, cash equivalents, and short-term investments as of March 31, 2020, sufficient to fund operations into 2022[42] - As of March 31, 2020, the company had an accumulated deficit of $407.9 million and $297.1 million in cash, cash equivalents, and short-term investments, up from $166.0 million as of December 31, 2019[52] - Net cash provided by financing activities for the three months ended March 31, 2020, was $148.6 million, primarily from the sale of common stock[58] - The company sold 10,925,000 shares of common stock for $140.9 million in net proceeds in February 2020[53] Administrative Expenses - General and administrative expenses rose to $9.040 million in Q1 2020 from $5.576 million in Q1 2019, an increase of $3.464 million[48] - General and administrative expense rose by $3.5 million to $9.0 million for the three months ended March 31, 2020, from $5.6 million in the same period of 2019[50] - General and administrative expenses are anticipated to rise in future periods to support the advancement of gene therapy programs[50] Future Funding - Future funding will be required for development, commercialization, and internal research programs, with potential reliance on equity or debt financings[53]