ADVM Adverum Biotechnologies Inc

Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases, today announced financial results for the third quarter ended September 30, 2022.

“The third quarter was instrumental for Adverum, as we dosed our first subject in our Phase 2 LUNA trial of Ixo-vec evaluating the 2E11 dose and a new, lower 6E10 dose, along with enhanced prophylactic steroid regimens for the treatment of wet AMD,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “We look forward to sharing interim data from LUNA throughout 2023. We are incredibly excited with our progress in advancing our investigational gene therapy candidate Ixo-vec, which we believe has the potential to transform the treatment paradigm for patients with wet age-related macular degeneration and meaningfully reduce the burden of frequent anti-VEGF injections. The transformational potential of Ixo-vec was recognized by the European Medicines Agency earlier this summer with its granting Ixo-vec with Priority Medicines designation.”

Dr. Fischer continued, “We presented two-year, end of study, safety and efficacy data from our OPTIC trial at the recent Annual Meeting of The Retina Society, indicating that a single IVT injection of Ixo-vec was generally well tolerated and can maintain or improve vision, as well as improve intraretinal and subretinal fluid volume in wet AMD patients. We are encouraged by the data demonstrating that a single intravitreal injection of Ixo-vec can lead to stable and persistent aflibercept protein levels through three years resulting in better fluid control known to be associated with favorable vision outcomes, as well as decreasing treatment burden by an 81-98% reduction in mean annualized anti-VEGF injections. These data strengthen the emerging benefit-risk profile of Ixo-vec as we further evaluate the 2E11 and 6E10 doses in LUNA. We believe Ixo-vec, with its continuous expression of aflibercept over years, can bring immense value to patients with an improved quality of life, caregivers, retinal specialists, payers and the healthcare systems.”

Recent Highlights

• In July 2022, Adverum completed an Investigational New Drug amendment with the U.S. Food and Drug Administration to advance a Phase 2 trial of Ixo-vec in wet AMD.
• In September 2022, Adverum dosed the first subject in its Phase 2 LUNA trial evaluating Ixo-vec at the 2x10^11 vg/eye (2E11) and 6x10^10 vg/eye (6E10) dose levels, with enhanced prophylactic steroid regimens.
• Adverum presented data from the OPTIC trial of Ixo-vec at three key scientific meetings:
  • An oral presentation at the American Society of Retina Specialists detailed an 81%-98% reduction in annualized anti-VEGF injections and demonstrated continuous therapeutic aflibercept protein levels through three years following a single, intravitreal (IVT) injection of Ixo-vec. Ixo-vec was generally well tolerated at the 2E11 dose, along with data demonstrating that mean best-corrected visual acuity and central subfield thickness were maintained or improved in subjects in the OPTIC trial.
  • An oral presentation at the American Academy of Ophthalmology 2022 Annual Meeting detailed anatomical improvements in intraretinal fluid (IRF) and subretinal fluid (SRF). In the 2E11 dose group, there was a 93% and 55% reduction in mean IRF and SRF volume, respectively, from baseline to week 48, following a single IVT dose of Ixo-vec.
  • An oral presentation at The Retina Society’s 2022 Annual Meeting detailed two-year, end of study data for all OPTIC cohorts, including new data documenting that 80% and 53% of the participants in the 6x10^11 vg/eye and 2E11 dose groups, respectively, were supplemental injection free over two years.

Financial Results for the Three Months Ended September 30, 2022

• Cash, cash equivalents and short-term investments were $203.3 million as of September 30, 2022, compared to $305.2 million as of December 31, 2021. Adverum expects the September 30, 2022 cash position to fund operations into 2025.
• Research and development expenses were $23.8 million for the three months ended September 30, 2022, compared to $24.1 million for the same period in 2021. Research and development expenses decreased primarily due lower facilities-related expenses, lower headcount following the restructuring and lower consultant costs; partially offset by restructuring costs and higher clinical trial-related expenses. Stock-based compensation expense included in research and development expenses was $1.4 million for the third quarter of 2022.
• General and administrative expenses were $17.2 million for the three months ended September 30, 2022, compared to $14.5 million for the same period in 2021. General and administrative expenses increased primarily due to reversal of sublease income and restructuring costs; partially offset by lower personnel-associated costs following the restructuring and facilities-related expenses. Stock-based compensation expense included in general and administrative expenses was $3.1 million for the third quarter of 2022.
• Net loss was $40.1 million, or $0.40 per basic and diluted share, for the three months ended September 30, 2022, compared to $38.4 million, or $0.39 per basic per basic and diluted share, for the same period in 2021.

About Wet Age-Related Macular Degeneration

Wet AMD, also known as neovascular AMD or nAMD, is an advanced form of AMD, affecting approximately 10% of patients living with AMD. Wet AMD is a leading cause of blindness in patients over 65 years of age, with a prevalence of approximately 20 million individuals worldwide living with this condition. The incidence of new cases of wet AMD is expected to grow significantly worldwide as populations age. AMD is expected to impact 288 million people worldwide by 2040, with wet AMD accounting for approximately 10% of those cases.

About OPTIC Trial of ADVM-022 in Wet AMD

ADVM-022, ixoberogene soroparvovec (Ixo-vec), is Adverum’s clinical-stage gene therapy product candidate being developed for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach) Ixo-vec has the advantage of being administered as a one-time IVT injection in the office and is designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, optimize patient compliance, and improve vision outcomes for patients with wet AMD.

The OPTIC trial is designed as a multi-center, open-label, dose-ranging, safety, and efficacy trial of Ixo-vec in participants with wet AMD who have demonstrated responsiveness to anti-VEGF treatment. Patients in OPTIC are treatment-experienced, and previously required frequent anti-VEGF injections to manage their wet AMD and to maintain functional vision.

About LUNA Trial of Ixo-vec in Wet AMD

Ixoberogene soroparvovec (Ixo-vec) is Adverum’s clinical-stage gene therapy product candidate being developed for the treatment of wet AMD. Ixo-vec utilizes an engineered, proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec has the advantage of being administered as a one-time IVT injection in the office and is designed to deliver long-term efficacy and reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance, and improve vision outcomes for patients with wet AMD.

The LUNA trial is a multicenter, double-masked, randomized, parallel-group Phase 2 study evaluating two doses of Ixo-vec, including the 2x10^11 vg/eye (2E11) dose and a new, lower 6x10^10 vg/eye (6E10) dose, in wet AMD. The trial will randomize up to 72 participants equally across two doses and four prophylactic steroid regimens in 40 sites in the U.S. and Europe. The primary endpoints include the mean change in best-corrected visual acuity (BCVA) from baseline to one year and the incidence and severity of adverse events.

About Adverum Biotechnologies

Adverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases with the aspiration of developing functional cures for these diseases to restore vision and prevent blindness. Leveraging the research capabilities of its proprietary, intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. By overcoming the challenges associated with current treatment paradigms for these debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit www.adverum.com.

Forward-looking Statements

Statements contained in this press release regarding events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to statements regarding the potential benefits of Ixo-vec, the timing of preliminary data from the LUNA trial evaluating the same, as well as cash runway to fund operations into 2025. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverum’s novel technology, which makes it difficult to predict the timing of commencement and completion of clinical trials; regulatory uncertainties; enrollment uncertainties; the results of early clinical trials not always being predictive of future clinical trials and results; and the potential for future complications or side effects in connection with use of Ixo-vec. Additional risks and uncertainties facing Adverum are set forth under the caption “Risk Factors” and elsewhere in Adverum’s Securities and Exchange Commission (SEC) filings and reports, including Adverum’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2022 filed with the SEC on August 11, 2022. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Corporate & Investor Inquiries

Anand ReddiVice President, Head of Corporate Strategy, External Affairs and EngagementAdverum Biotechnologies, Inc.T: 650-649-1358E: areddi@adverum.com 

Media

Megan TalonAssociate Director, Corporate CommunicationsAdverum Biotechnologies, Inc.T: 650-649-1006E: mtalon@adverum.com 

Adverum Biotechnologies, Inc.
Consolidated Balance Sheets
(In thousands)
		September 30				December 31
			2022				2021
		(Unaudited)					(1)
Assets
Current assets:
Cash and cash equivalents		$	84,430			$	34,195
Short-term investments			118,834				270,993
Lease incentive receivable			-				5,709
Prepaid expenses and other current assets			9,979				6,248
Total current assets			213,243				317,145
Property and equipment, net			36,579				33,060
Operating lease right-of-use assets			79,882				86,000
Restricted cash			2,503				2,503
Deferred rent receivable			-				769
Deposit and other long-term assets			155				250
Total assets		$	332,362			$	439,727
Liabilities and stockholders' equity
Current liabilities:
Accounts payable		$	846			$	1,387
Lease liability, current portion			11,236				1,886
Accrued expenses and other current liabilities			16,539				18,047
Total current liabilities			28,621				21,320
Lease liability, net of current portion			94,464				101,108
Other noncurrent liabilities			940				1,114
Total liabilities			124,025				123,542
Stockholders' equity:
Common stock			10				10
Additional paid-in capital			980,156				964,965
Accumulated other comprehensive loss			(1,953	)			(714	)
Accumulated deficit			(769,876	)			(648,076	)
Total stockholders' equity			208,337				316,185
Total liabilities and stockholders' equity		$	332,362			$	439,727
(1) Derived from Adverum's annual audited consolidated financial statements.

Adverum Biotechnologies, Inc.
Consolidated Statements of Operations
(In thousands except per share data)
		Three months endedSeptember 30,								Nine months endedSeptember 30,
			2022				2021				2022				2021
		(Unaudited)
License revenue		$	-			$	-			$	-			$	7,500
Operating expenses:
Research and development			23,849				24,069				77,078				66,657
General and administrative			17,188				14,453				46,117				52,546
Total operating expenses			41,037				38,522				123,195				119,203
Operating loss			(41,037	)			(38,522	)			(123,195	)			(111,703	)
Other income, net			923				160				1,450				572
Net loss before income taxes			(40,114	)			(38,362	)			(121,745	)			(111,131	)
Income tax provision			(17	)			-				(55	)			-
Net loss		$	(40,131	)		$	(38,362	)		$	(121,800	)		$	(111,131	)
Net loss per share — basic and diluted		$	(0.40	)		$	(0.39	)		$	(1.23	)		$	(1.13	)
Weighted-average common shares outstanding - basic and diluted			99,475				98,126				99,027				97,966