Eli Lilly and Company is preparing to make a major splash in the ophthalmic arena after the company announced it will acquire Adverum Biotechnologies.
Big news! But first, a look at these players.
We’ll start with Lilly.
Originally founded in 1876, the Indianapolis, Indiana-based global pharmaceutical company researches, develops, and manufactures an extensive range of medicines—with major investments in biotech and genetic medicine.
Among its therapeutic areas of focus: cardiovascular and endocrine/metabolic conditions; dermatology and allergy/inflammation; diabetes and endocrinology; immunology; neuroscience; and oncology.
- In the last few years, Lilly’s portfolio has included major GLP-1 drugs such as Mounjaro and Zepbound (tirzepatide) for type 2 diabetes and obesity, respectively.
I notice ophthalmology hasn’t been a focus …
Indeed, it has not (and hence this new expansion into the ophthalmic space).
Talk about Adverum now.
Previously known as Avalanche Biotechnologies before changing its name in 2016, the clinical-stage gene therapy company is headquartered in Redwood City, California.
Its therapeutic focus: Establishing gene therapy candidates—specifically: durable, single-administration therapeutics—as the new standard of care for debilitating ocular diseases.
- Among those targeted diseases: Wet age-related macular degeneration (AMD), geographic atrophy (GA), and retinitis pigmentosa (RP). See its full pipeline.
So what technology has Adverum developed to target these diseases?
An adeno-associated virus (AAV) transgene vector technology known as AAV.7m8.
What it does: This vector capsid is designed to encode retinal cells to “become biofactories that provide robust, sustainable amounts of therapeutic proteins throughout the retina.”
- To note: Therapeutic protein biofactories are genetically engineered (biologically derived) to produce therapeutic proteins for medicinal use—and to treat diseases.
Go on…
A peptide loop within the platform also enables AAV.7m8 to:
- Be delivered via an intravitreal(IVT) injection
- Cross the inner limiting membrane (ILM) following injection
- Transduce and improve retinal cells
And the resulting effect: The targeted delivery of a therapeutic payload at the location of the specific retinal disease.
- See here for a more detailed rundown on this platform.
So, what investigational therapy has utilized this technology?
That would be Ixoberogene soroparvovec (Ixo-vec), Adverum’s lead gene therapy candidate under clinical evaluation for the treatment of wet AMD.
What to know: Ixo-vec is a vectorized aflibercept (an anti-vascular endothelial growth factor [VEGF]) coding sequence that uses AAV.7m8 to carry an aflibercept coding sequence controlled by a proprietary expression cassette (a specialized DNA sequence).
- Importantly: This expression cassette is optimized exclusively for IVT injection.
And more simply?
Essentially, Ixo-vec incorporates AAV.7m8 to provide aflibercept as a therapeutic protein throughout the retina—all to enable the delivery of long-term VEGF inhibition.
And keep in mind: This process is intended to be conducted as an in-office treatment option (reportedly cost-effective), according to Adverum.
What makes this unique from other treatments?
Ixo-vec has the potential to replace the standard repeated IVT injection schedule for retinal diseases such as wet AMD with a one-time—one-and-done—therapy.
Any clinical findings on its performance yet?
Indeed, there is. The candidate has already received FDA Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations and is currently undergoing evaluation in the phase 3 ARTEMIS study.
While no data is available yet (as screening has just concluded), we did previously report on 52-week findings from the phase 2 LUNA study as well as 4-year findings from the OPTIC clinical program.
And the gist of that data?
- Ixo-vec was generally well tolerated and demonstrated a favorable safety profile
- Patients had an 86% reduction in annualized anti-VEGF injections through year 4
- Almost 50% of patients were injection-free through 4 years after treatment
See here for specifics on this.
Now let’s talk about this acquisition.
Per the agreement: Lilly will acquire all outstanding shares of Adverum’s common stock
- For a per share price of $3.56 per share in cash payable at closing, plus
- One non-transferrable contingent value right (CVR) entitling a shareholder to receive up to an additional $8.91 per CVR in cash—but only if and when two milestones are reached—for a total potential per share consideration of up to $12.47.
And those two milestones?
The deal’s CVR will provide additional payments for Adverum’s shareholders upon:
- U.S. approval of Ixo-vec prior to the seventh anniversary of the deal’s closing date
- The payment: up to $1.78 per CVR in cash
- The first achievement of annual worldwide net sales of Ixo-vec by Lilly, its affiliates, or its licensees, surpassing $1 billion prior to the 10th anniversary of the deal’s closing date
- The payment: up to $7.13 per CVR in cash
That’s quite the deal. Anything else?
Yup. See here for another stipulation.
And also: The companies entered into a Promissory Note, which secured all of Adverum’s assets—intellectual property rights included.
What this means: Adverum can receive a loan of up to $65 million from Lilly (in four installments) to support ongoing clinical trials and registrational development activities or Ixo-vec prior to the deal closing.
- But take note: If the transaction is called off, Adverum will owe that money.
Has Adverum commented on this yet?
Adverum President and CEO Laurent Fischer, MD, noted the opportunity this deal presents for the company—particularly as it seeks to advance xo-vec toward potential regulatory approval.
He emphasized both companies’ shared focus on “healthy aging and genetic medicine innovation.”
- (Lilly’s) scientific depth and global reach offer the opportunity to accelerate our vision to deliver a transformative “one-and-done” therapy that can potentially restore and preserve vision for millions of patients living with (wet) AMD,” Dr. Fischer stated.
Last question: When is this deal expected to close?
Q4 2025 (as in, sometime between now and Dec. 31).