Adverum Biotechnologies Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Pipeline Highlights and Corporate Updates

Rhea-AI Summary

Adverum Biotechnologies, Inc. reports positive preliminary data from the ongoing LUNA Phase 2 trial of Ixo-vec in patients with wet AMD, showcasing potential best-in-class reduction in anti-VEGF injections and encouraging safety profile. The company completed a $127.5 million private placement financing to extend cash runway into late 2025. A 1-for-10 reverse stock split is set to be effective on March 21, 2024, with the approval of the Board of Directors. Key appointments and milestones for 2024 were also highlighted.

Positive

• Positive preliminary data from the LUNA Phase 2 trial of Ixo-vec in patients with wet AMD at the Macula Society Annual Meeting.
• Completion of a $127.5 million private placement financing to extend cash runway into late 2025.
• Approval of a 1-for-10 reverse stock split effective March 21, 2024.
• Appointment of Romuald Corbau, Ph.D. as Chief Scientific Officer.
• Anticipated milestones for 2024 include continued regulatory interactions, LUNA 26-week interim analysis in mid-2024, and initiation of Phase 3 trial in the first half of 2025.
• Financial results for the fourth quarter of 2023 showing cash, cash equivalents, short-term investments, research and development expenses, general and administrative expenses, and net loss.

Negative

• None.

Insights

Biotech Equity Analyst

The recent update from Adverum Biotechnologies regarding their LUNA Phase 2 trial of Ixo-vec for wet AMD has significant implications for the company's valuation and investor sentiment. The reported reduction in anti-VEGF injections and the percentage of patients not requiring supplemental injections suggest a strong efficacy profile. This could position Ixo-vec as a competitive product in the wet AMD market, which is currently dominated by frequent and costly injections. The safety profile appears favorable, which is critical for patient compliance and market acceptance.

The completion of a $127.5 million private placement financing is a positive signal to the market, indicating institutional confidence in Adverum's pipeline. The financing at a 20% premium to the volume-weighted average price also reflects the perceived value of the company's assets. This cash injection extends the company's runway, reducing near-term financial risk and allowing investors to focus on the clinical development milestones.

The approval of a 1-for-10 reverse stock split is a strategic move often aimed at increasing the stock price to meet exchange listing requirements and improve perception. However, it can also dilute existing shareholders and may not have the desired long-term effect if the underlying business concerns are not addressed.

Medical Research Analyst

The preliminary data from the LUNA trial suggests that Ixo-vec could be a transformative treatment for wet AMD, potentially reducing the treatment burden significantly. The 90% and 94% reductions in annualized anti-VEGF injections are particularly noteworthy, as current treatments can be burdensome for patients. Maintaining or improving mean Best Corrected Visual Acuity (BCVA) and Central Subfield Thickness (CST) are key indicators of efficacy in ocular therapies and will be closely monitored by clinicians.

Long-term data from the OPTIC trial showing sustained aflibercept levels and reduced injection frequency over three years provide additional support for the durability of Ixo-vec's effect. This could lead to a paradigm shift in treatment, moving from chronic management to a more sustained approach, potentially improving patient quality of life and reducing healthcare costs.

The absence of serious adverse events related to Ixo-vec is encouraging, but it is important to remain cautious until more comprehensive safety data are available. Intraocular inflammation is a known risk with ocular gene therapies and being responsive to corticosteroids is a positive sign, but long-term surveillance will be key to understanding the full safety profile.

Healthcare Financial Analyst

The financial results show a decrease in research and development expenses, which can be attributed to more efficient trial management and possibly a strategic narrowing of focus within the company's pipeline. The reduction in general and administrative expenses, through decreased facilities costs and increased sublease income, indicates a leaner operation, which is often welcomed by investors seeking efficient capital allocation.

However, the reported net loss of $23.7 million underscores the high costs associated with biotech R&D and the importance of the recent financing in maintaining operational stability. The pro forma cash position suggests a healthy buffer for the company, but it is critical for investors to monitor the burn rate and the progress of clinical trials to gauge the likelihood of additional financing needs or a potential partnership or acquisition.

- Preliminary LUNA data presented at the Annual Meeting of the Macula Society support potential best-in-class clinical activity and an encouraging safety profile in patients with wet AMD -

- Completed $127.5 million private placement financing with new and existing institutional investors -

- Cash runway expected into late 2025 –

- 1-for-10 reverse stock split to be effective March 21, 2024 -

REDWOOD CITY, Calif., March 18, 2024 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company pioneering the use of gene therapy as a new standard of care for highly prevalent ocular diseases, today reported financial results for the fourth quarter and full year 2023. The company also provided recent pipeline highlights and corporate updates.

“We have made tremendous progress during 2023 and in 2024 to date in our development of Ixo-vec as a durable potential gene therapy treatment for the millions of patients suffering from wet AMD,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “We were pleased to present at Macula Society preliminary data from our ongoing LUNA Phase 2 trial of Ixo-vec, which demonstrated potentially best-in-class clinical activity at both the 2E11 and 6E10 doses of Ixo-vec, with the data trending similar to, or better than, the data in our first-in-human OPTIC trial. Importantly, the preliminary data demonstrated that Ixo-vec was generally well tolerated. We look forward to presenting the 26-week interim analysis of our LUNA Phase 2 program in mid-2024.”

Dr. Fischer continued, “In the lead-up to the data presentation at Macula Society, Adverum completed a $127.5 million private placement financing with new and existing investors that we expect to meaningfully extend our cash runway into late 2025, well beyond the anticipated presentation of topline 52-week data from our ongoing LUNA Phase 2 trial. In parallel, we are continuing to interact with regulators in the U.S. and E.U. to inform Phase 3 development of Ixo-vec, which we plan to initiate in the first half of 2025.”

Ixo-Vec Program Highlights:

• Preliminary Ixo-vec LUNA Trial Data at Macula Society 2024:
  • In February 2024, we announced positive preliminary efficacy and safety data from the ongoing LUNA Phase 2 trial of Ixo-vec in patients with wet AMD at the 47^th Annual Meeting of the Macula Society in Palm Springs, California.
  • LUNA patients treated with either the 2E11 or 6E10 dose of Ixo-vec experienced potentially best-in-class reduction in annualized anti-vascular endothelial growth factor (VEGF) injections and the percentage of patients receiving no supplemental injections through 26 weeks.
    • Patients at the 2E11 and 6E10 doses had mean 90% and 94% reductions, respectively, in annualized anti-VEGF injections.
    • 85% and 68% of patients at the 2E11 and 6E10 doses, respectively, received no supplemental injections through 26 weeks.
  • Maintained or improved mean BCVA and mean CST at both dose levels.
  • Ixo-vec continued to be generally well tolerated, with cases of intraocular inflammation responsive to local corticosteroids.
  • No Ixo-vec related serious adverse events, episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony were reported.
• Long-Term Ixo-vec OPTIC Trial Data at AAO 2023:
  • In November 2023, the company announced 3-year data from the OPTIC extension study of patients with wet AMD during the Retina Subspecialty Day at the American Academy of Ophthalmology (AAO) 2023 Annual Meeting in San Francisco, California.
  • Patients in the OPTIC extension trial continue to experience long-term benefit from Ixo-vec through 3 years of follow-up, including maintenance of vision, durability of anatomic improvements and sustained reduction in anti-VEGF treatment burden.
    • Patients at the 2E11 dose had an 84% reduction in annualized anti-VEGF injections, with 53% of the participants at the 2E11 dose receiving zero supplemental injections through three years.
    • Aflibercept protein levels have been sustained through follow-up, which is up to 4.5 years post-treatment.
    • BCVA was maintained and CST was improved through 3 years.
  • Ixo-vec was generally well tolerated, with the most common adverse event being dose-dependent inflammation that was responsive to topical corticosteroids.
    

Corporate Updates:

• Approval of 1-for-10 reverse stock split: On March 8, the Board of Directors approved a 1-for-10 reverse stock split of the Company’s common stock. The Company's common stock will begin trading on a reverse stock split-adjusted basis on March 21, 2024. Following the reverse stock split, there will be approximately 20.8 million shares of the company’s common stock outstanding.
• $127.5 Million Private Placement Financing: In February 2024, the Company completed a private placement of 106.25 million shares of common stock (or pre-funded warrants in lieu thereof) to a select group of institutional and accredited healthcare specialist investors at a price of $1.20 per share, representing a premium of approximately 20% to Adverum’s 30-day volume-weighted average price. The financing was led by TCGX with participation from new and existing investors including 5AM Ventures, Commodore Capital, Frazier Life Sciences, Logos Capital, Samsara BioCapital, Venrock Healthcare Capital Partners and Vivo Capital, as well as two large investment management firms. The financing is expected to extend Adverum’s cash runway into late 2025.
• Appointment of Romuald Corbau, Ph.D. as Chief Scientific Officer: In January 2024, the company announced the appointment of Romuald “Romu” Corbau, Ph.D. as Chief Scientific Officer. Dr. Corbau brings over 25 years of experience in drug development, including leading Spark Therapeutics’ translational R&D for Luxturna^®, a subretinal injection gene therapy product for Leber’s congenital amaurosis, an inherited vision loss disease that routinely results in blindness
  

Anticipated Milestones

• 2024: Continued FDA and EMA formal and informal regulatory interactions
• Mid-2024: LUNA 26-week interim analysis
• H1 2025: Initiation of Phase 3 trial
  

Financial Results for the Three Months Ended December 31, 2023

• Cash, cash equivalents and short-term investments were $96.5 million as of December 31, 2023, compared to $117.1 million as of September 30, 2023, and $185.6 million as of December 31, 2022. Including proceeds from the February 2024 private placement financing, pro forma cash, cash equivalents and short-term investments was $223.8 million. Adverum expects its cash, cash equivalents and short-term investments to fund operations into late 2025.
• Research and development expenses were $15.3 million for the three months ended December 31, 2023, compared to $22.2 million for the same period in 2022. Research and development expenses decreased due to lower clinical trial related expense, lower material production and bioanalytics, lower stock-based compensation expense, lower license fees, and lower outside research and development services. Stock-based compensation expense included in research and development expenses was $1.0 million for the fourth quarter of 2023.
• General and administrative expenses were $10.9 million for the three months ended December 31, 2023, compared to $11.7 million for the same period in 2022. General and administrative expenses decreased due to lower facilities expense due to fewer premises leased in the current period and higher sublease income and lower depreciation expense. Stock-based compensation expense included in general and administrative expenses was $3.1 million for the fourth quarter of 2023.
• Net Loss was $23.7 million, or $0.23 per basic and diluted share, for the three months ended December 31, 2023, compared to $32.7 million, or $0.33 per basic and diluted share for the same period in 2022.

About Wet Age-Related Macular Degeneration
Wet AMD, also known as neovascular AMD or nAMD, is a VEGF driven advanced form of AMD affecting approximately 10% of patients living with AMD associated with the build-up of fluid in the macula and the retina. Wet AMD is a leading cause of blindness in people over 65 years of age, with approximately 20 million individuals worldwide living with this condition. New cases of wet AMD are 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. Additionally, wet AMD is a bilateral disease, and incidence of nAMD in the second eye is up to 42% in the first two to three years. The current standard of care requires frequent life-long repeated bolus injections of anti-VEGF in the eye. IVT gene therapy has the promise to preserve vision and reduce most or all injections for the life of the patient by delivering stable therapeutic levels of anti-VEGF to control macular fluid.

About Ixo-vec in Wet AMD
Adverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, 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 is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec has also received PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD.

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 to restore vision and prevent blindness. Leveraging the 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. Additionally, by overcoming the challenges associated with current treatment paradigms for 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 as a one-time IVT injection for the treatment of wet AMD, including its potential to improve vision outcomes, the potential best-in-class clinical activity of Ixo-vec, and anticipated timing of preliminary and interim data from the Phase 2 LUNA trial and initiation of a Phase 3 trial, and statements associated with the Company’s cash sufficiency and runway, and other statements containing the words “anticipates,” “believes,” “expects,” “intends,” “plans,” “target,” “will” and similar expressions. 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: risks associated with market conditions. 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 most recent Annual Report on Form 10-K filed with the SEC, as updated by any subsequent reports on Form 10-Q. 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, except as required by law.

Corporate, Investor and Media Inquiries
Adverum Biotechnologies, Inc.
E: ir@adverum.com

Adverum Biotechnologies, Inc.
Selected Consolidated Balance Sheet Data
(In thousands)
	December 31,				December 31,
	2023				2022
Cash and cash equivalents, and marketable securities	$	96,526	1		$	185,589
Total assets		173,010				308,372
Total current liabilities		24,914				32,246
Total liabilities		89,541				126,854
Total stockholders' equity		83,469				181,518
(1) Cash, cash equivalents, and marketable securities exclude approximately $127.8 million in net proceeds from Adverum's February 2024 private placement

Adverum Biotechnologies, Inc.
Consolidated Statements of Operations
(In thousands except per share data)
	Three months ended December 31,								Years ended December 31,
		2023				2022				2023				2022
	(Unaudited)								(1)
License revenue	$	—			$	—			$	3,600			$	—
Operating expenses:
Research and development		15,278				22,199				77,676				99,277
General and administrative		10,880				11,741				49,915				57,858
Total operating expenses		26,158				33,940				127,591				157,135
Operating loss		(26,158	)			(33,940	)			(123,991	)			(157,135	)
Other income, net		1,311				1,223				5,748				2,673
Net loss before income taxes		(24,847	)			(32,717	)			(118,243	)			(154,462	)
Income tax benefit (provision)		1,133				(19	)			1,078				(74	)
Net loss		(23,714	)			(32,736	)			(117,165	)			(154,536	)
Net loss per share — basic and diluted	$	(0.23	)		$	(0.33	)		$	(1.16	)		$	(1.56	)
Weighted-average common shares outstanding - basic and diluted		101,213				99,915				100,824				99,251
(1) Derived from Adverum's annual audited consolidated financial statements.

FAQ

What positive data was presented at the Macula Society Annual Meeting regarding ADVM's LUNA Phase 2 trial?

Positive preliminary efficacy and safety data from the ongoing LUNA Phase 2 trial of Ixo-vec in patients with wet AMD were presented, showing potentially best-in-class reduction in anti-VEGF injections and encouraging safety profile.

How much was the private placement financing completed by ADVM?

Adverum completed a $127.5 million private placement financing with new and existing investors to extend cash runway into late 2025.

What is the effective date for the 1-for-10 reverse stock split approved by ADVM's Board of Directors?

The 1-for-10 reverse stock split approved by ADVM's Board of Directors will be effective on March 21, 2024.

Who was appointed as Chief Scientific Officer by ADVM in January 2024?

Romuald Corbau, Ph.D. was appointed as Chief Scientific Officer by ADVM in January 2024.

What are the anticipated milestones for ADVM in 2024?

Anticipated milestones for ADVM in 2024 include continued FDA and EMA regulatory interactions, LUNA 26-week interim analysis in mid-2024, and initiation of Phase 3 trial in the first half of 2025.

What were ADVM's financial results for the fourth quarter of 2023?

ADVM reported cash, cash equivalents, and short-term investments of $96.5 million as of December 31, 2023. Research and development expenses were $15.3 million, and general and administrative expenses were $10.9 million for the same period.