Adverum Biotechnologies Completes Enrollment of Phase 2 LUNA Trial in Wet AMD and Reports Second Quarter 2023 Financial Results
10 Agosto 2023 - 10:05PM
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 provided an update
on its ongoing Phase 2 LUNA trial evaluating ixoberogene
soroparvovec (Ixo-vec) for the treatment of wet age-related macular
degeneration (wet AMD) and reported financial results for the
second quarter ended June 30, 2023.
“We are pleased to announce completion of enrollment in our
Phase 2 LUNA trial,” stated Laurent Fischer, M.D., president and
chief executive officer of Adverum Biotechnologies. “The LUNA study
design allows us to evaluate efficacy and safety of two Ixo-vec
doses, while optimizing the prophylactic steroid regimens. This
double-masked, randomized trial includes a primary cohort of
approximately 60 subjects enrolled in the United States. We are
maintaining the option to enroll an additional cohort of
approximately 12 subjects that may provide further data to inform
our global development plan. The totality of data from the OPTIC
and LUNA trials, which will include approximately 90 subjects dosed
with Ixo-vec, is the largest gene therapy pre-phase 3 dataset in
wet AMD with subjects to be followed out to five years. This should
give us confidence to proceed with a significantly de-risked global
pivotal trial strategy.”
“We are extremely grateful to the investigators, study
coordinators and other site staff for their partnership in the
design and conduct of the LUNA trial and to all the patients who
are taking part in the study,” said Star Seyedkazemi, PharmD, chief
development officer of Adverum Biotechnologies. “We believe
Ixo-vec, with its previously demonstrated continuous expression of
aflibercept over 3 years following a single, in-office intravitreal
injection, has the potential to bring immense value to patients,
caregivers, retinal specialists, payers, and healthcare
systems.”
The primary LUNA cohort is evaluating the efficacy and safety of
Ixo-vec in approximately 60 subjects randomized equally between the
2x10^11 vg/eye (2E11) and 6x10^10 vg/eye (6E10) doses. Subjects are
also randomized across four prophylactic regimens. Approximately 40
patients will receive one of two local ocular corticosteroid
regimens. The remaining 20 subjects will receive one of the local
ocular corticosteroid regimens, plus oral prednisone to inform the
decision of whether to include an oral prophylactic in future
trials.
Recent Highlights
- Innovation Passport: In April 2023, the United Kingdom’s
Medicines and Healthcare Products Regulatory Agency granted Ixo-vec
an Innovation Passport under the Innovative Licensing and Access
Pathway (ILAP). This designation is intended to accelerate the
regulatory and market access interactions in the United Kingdom. To
date, Adverum is the only ocular gene therapy company in wet AMD to
have been granted Fast Track Designation by the U.S. FDA, PRIME
designation by the European Medicines Agency and most recently the
Innovation Passport under ILAP.
- Ixo-vec Nonclinical Data: Adverum presented an oral
presentation of nonclinical data supporting Ixo-vec’s clinical
development at the ASGCT 2023 Annual Meeting.
- Ixo-vec Bilateral Dosing: Adverum presented data outlining the
rationale for staggered, bilateral administration of Ixo-vec in
patients with bilateral disease. Up to 42% of wet AMD patients
experience neovascularization in the second eye in the first two to
three years following diagnosis in the primary eye, indicative of
an unmet need for many wet AMD patients globally.
- Ixo-vec was administered to one eye, then two months later to
the fellow eye of NHPs. Following the second, staggered
administration of Ixo-vec, the fellow eye demonstrated aflibercept
protein levels within the targeted therapeutic range.
- Staggered, bilateral intravitreal (IVT) administration of
Ixo-vec was well tolerated, with encouraging therapeutic activity,
as well as no increase in intraocular inflammation levels.
- These data demonstrate for the first time that the ocular
humoral response in NHP is compartmentalized to the eye dosed with
AAV capsid.
- Ixo-vec Dosing at 2E11 and 6E10 Human Equivalent Doses: In an
oral presentation of nonclinical data, Adverum demonstrated
consistent aflibercept protein levels across the 2E11 and 6E10
doses in NHPs, indicating that the 6E10 dose may offer similarly
robust levels of efficacy as the 2E11 dose with the potential of an
improved inflammation profile.
- Ixo-vec Biodistribution: In a poster presentation, Adverum
presented data on an evaluation of intraocular per cell
biodistribution of Ixo-vec vg and aflibercept mRNA via in-situ
hybridization in NHP eyes at the human equivalent dose of 2E11 and
6E10.
- Additional Pipeline Programs: Adverum unveiled IVT gene therapy
programs for the treatment of Geographic Atrophy (GA) and for
optogenetics at the ASGCT 2023 Annual Meeting.
- Complement Factor I Program for Dry AMD / Geographic Atrophy:
In a poster presentation, Adverum introduced its GA program
delivering complement Factor I (CFI), a fundamental component and
rate-limiting enzyme of the complement cascade, as a payload
utilizing two IVT capsids: 7m8 and LSV1. Both the 7m8 and LSV1
capsids packaged with AAV-CFIco yielded robust intraocular human
CFI levels in NHPs, and both proprietary capsids were well
tolerated in non-human primates (NHPs).
- CaMeRaOpsin Program for Optogenetics: In a poster presentation,
Adverum presented data on an optogenetic program utilizing an
engineered melanopsin mutant that could serve as a therapeutic
transgene for optogenetic vision restoration in indications with
photoreceptor loss such as advanced GA.
- Ray Therapeutics License: In June 2023, Adverum announced that
it granted a non-exclusive, royalty-bearing license of its AAV.7m8
IVT vector capsid to Ray Therapeutics.
Anticipated Milestones
- Late Q3 2023 –Anticipate aflibercept protein
levels for percentage of cohort with a minimum of 14 weeks of
follow-up as of data cutoff.
- Q4 2023 – Anticipate LUNA preliminary efficacy
and safety data for percentage of cohort.
Financial Results for the Three Months Ended June 30,
2023
- Cash, cash equivalents and short-term
investments were $141.5 million as of June 30, 2023,
compared to $185.6 million as of December 31, 2022. Adverum expects
the June 30, 2023 cash position to fund operations into 2025.
- Research and development expenses were $20.6
million for the three months ended June 30, 2023, compared to $30.3
million for the same period in 2022. Research and development costs
decreased due to lower compensation, material production and
bioanalytics, license fees, impairment of long-lived assets,
laboratory expenses, and consulting and contractor expenses. These
decreases were partially offset higher facilities related expenses.
Stock-based compensation expense included in research and
development expenses was $1.4 million for the second quarter of
2023.
- General and administrative expenses were $12.5
million for the three months ended June 30, 2023, compared to $13.8
million for the same period in 2022. General and administrative
costs decreased due to lower compensation, professional services
and insurance costs, partially offset by higher facilities related
expenses. Stock-based compensation expense included in general and
administrative expenses was $3.1 million for the second quarter of
2023.
- Net Loss was $31.5 million, or $0.31 per basic
and diluted share, for the three months ended June 30, 2023,
compared to $43.8 million, or $0.44 per basic and diluted share,
for the same period in 2022.
About Wet Age-Related Macular DegenerationWet
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 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.
About Ixo-vec in Wet AMDAdverum 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 LUNA Trial of Ixo-vec in Wet AMD The LUNA
trial is a double-masked, randomized, Phase 2 trial being conducted
at approximately 40 sites in the U.S. and Europe. LUNA trial will
evaluate Ixo-vec in subjects with wet AMD who are 50 years or older
and have demonstrated a response to anti-VEGF treatment. Up to 72
subjects will be enrolled, with approximately 60 subjects in the
primary LUNA cohort randomized equally between the previously
evaluated 2E11 vg/eye and new, lower 6E10 vg/eye doses. Subjects
will also be randomized across four prophylactic regimens.
Approximately 40 patients will receive one of two local ocular
corticosteroid regimens. The remaining 20 subjects will receive one
of the local ocular corticosteroid regimens, plus oral prednisone
to inform the decision of whether to include an oral prophylactic
in future trials. The corticosteroid regimens in LUNA were designed
to cover the period of peak immunogenicity observed in non-clinical
studies and in the Phase 1 OPTIC study.
The LUNA trial primary endpoints are mean change in best
corrected visual acuity (BCVA) from baseline to one year, as well
as the incidence and severity of adverse events. Important
secondary endpoints include, the mean change in central subfield
thickness (CST) from baseline to one year and assessing the
effectiveness of prophylactic corticosteroid regimens on minimizing
inflammation. Additionally, LUNA will assess aflibercept protein
levels starting at Week 14 and include an interim analysis at Week
26. LUNA participants will have the option to be evaluated for
safety and efficacy as part of the long-term extension of the
study.
About Adverum BiotechnologiesAdverum
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 StatementsStatements 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 in the treatment of wet AMD, the
design of and enrollment in the LUNA trial, including the
prophylactic corticosteroid regimens, anticipated preliminary and
interim data from the LUNA trial and pipeline programs. 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 March 31, 2023 filed with the SEC on May 11, 2023. 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 and Media InquiriesAnand
ReddiVice President, Head of Corporate Strategy, External Affairs
and EngagementAdverum Biotechnologies, Inc.T:
650-649-1358E: areddi@adverum.com
Adverum Biotechnologies, Inc. |
Consolidated Balance Sheets |
(In thousands) |
|
|
|
|
|
|
|
June 30 |
|
December 31 |
|
|
|
2023 |
|
|
|
2022 |
|
|
|
(Unaudited) |
|
|
(1) |
|
Assets |
|
|
|
|
Current assets: |
|
|
|
|
Cash and cash equivalents |
|
$ |
111,187 |
|
|
$ |
68,431 |
|
Short-term investments |
|
|
30,266 |
|
|
|
117,158 |
|
Prepaid expenses and other current assets |
|
5,690 |
|
|
|
5,006 |
|
Total current assets |
|
|
147,143 |
|
|
|
190,595 |
|
Property and equipment, net |
|
|
32,041 |
|
|
|
34,927 |
|
Operating lease right-of-use asset |
|
|
58,287 |
|
|
|
78,934 |
|
Restricted cash |
|
|
2,650 |
|
|
|
2,503 |
|
Deposit and other long-term assets |
|
|
1,308 |
|
|
|
1,413 |
|
Total assets |
|
$ |
241,429 |
|
|
$ |
308,372 |
|
|
|
|
|
|
Liabilities and stockholders' equity |
|
|
|
|
Current liabilities: |
|
|
|
|
Accounts payable |
|
$ |
1,418 |
|
|
$ |
2,238 |
|
Accrued expenses and other current liabilities |
|
|
17,704 |
|
|
|
16,767 |
|
Lease liability, current portion |
|
|
25,396 |
|
|
|
13,241 |
|
Total current liabilities |
|
|
44,518 |
|
|
|
32,246 |
|
Lease liability, net of current portion |
|
|
65,756 |
|
|
|
93,561 |
|
Other noncurrent liabilities |
|
|
- |
|
|
|
1,047 |
|
Total liabilities |
|
|
110,274 |
|
|
|
126,854 |
|
Stockholders' equity: |
|
|
|
|
Common stock |
|
|
10 |
|
|
|
10 |
|
Additional paid-in capital |
|
|
994,929 |
|
|
|
985,651 |
|
Accumulated other comprehensive loss |
|
|
(606 |
) |
|
|
(1,531 |
) |
Accumulated deficit |
|
|
(863,178 |
) |
|
|
(802,612 |
) |
Total stockholders' equity |
|
|
131,155 |
|
|
|
181,518 |
|
Total liabilities and stockholders' equity |
$ |
241,429 |
|
|
$ |
308,372 |
|
|
|
|
|
|
(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 ended June 30, |
|
Six months ended June 30, |
|
|
|
2023 |
|
|
|
2022 |
|
|
|
2023 |
|
|
|
2022 |
|
|
|
(Unaudited) |
|
|
|
|
|
|
|
|
|
License revenue |
|
$ |
- |
|
|
$ |
- |
|
|
$ |
3,600 |
|
|
$ |
- |
|
|
|
|
|
|
|
|
|
|
Operating expenses: |
|
|
|
|
|
|
|
|
Research and development |
|
|
20,599 |
|
|
|
30,265 |
|
|
|
41,658 |
|
|
|
53,229 |
|
General and administrative |
|
|
12,466 |
|
|
|
13,760 |
|
|
|
25,246 |
|
|
|
28,929 |
|
Total operating expenses |
|
|
33,065 |
|
|
|
44,025 |
|
|
|
66,904 |
|
|
|
82,158 |
|
Operating loss |
|
|
(33,065 |
) |
|
|
(44,025 |
) |
|
|
(63,304 |
) |
|
|
(82,158 |
) |
Other income, net |
|
|
1,576 |
|
|
|
283 |
|
|
|
2,776 |
|
|
|
527 |
|
Net loss before income taxes |
|
|
(31,489 |
) |
|
|
(43,742 |
) |
|
|
(60,528 |
) |
|
|
(81,631 |
) |
Income tax provision |
|
|
(21 |
) |
|
|
(19 |
) |
|
|
(38 |
) |
|
|
(38 |
) |
Net loss |
|
|
(31,510 |
) |
|
|
(43,761 |
) |
|
|
(60,566 |
) |
|
|
(81,669 |
) |
Net loss per share — basic and diluted |
|
$ |
(0.31 |
) |
|
$ |
(0.44 |
) |
|
$ |
(0.60 |
) |
|
$ |
(0.83 |
) |
Weighted-average common shares outstanding - basic and diluted |
|
|
100,768 |
|
|
|
99,000 |
|
|
|
100,537 |
|
|
|
98,799 |
|
|
|
|
|
|
|
|
|
|
Grafico Azioni Adverum Biotechnologies (NASDAQ:ADVM)
Storico
Da Mag 2024 a Giu 2024
Grafico Azioni Adverum Biotechnologies (NASDAQ:ADVM)
Storico
Da Giu 2023 a Giu 2024