Item
8.01. Other Events.
On
May 3, 2022, Lineage announced results from the ongoing Phase 1/2a clinical study of OpRegen that support the potential for OpRegen to
slow, stop or reverse disease progression in GA secondary to AMD. Twelve-month primary endpoint data demonstrated that OpRegen was well
tolerated in the study with an acceptable safety profile. We also reported preliminary evidence of visual function and outer retinal
structure improvements observed in Cohort 4 patients with GA and impaired vision. The Phase 1/2a study is an open-label, single-arm,
multi-center, dose-escalation trial evaluating a single administration of OpRegen delivered subretinally in patients with bilateral GA
secondary to AMD. Twenty-four subjects were enrolled into four cohorts. In all subjects, the worse eye based on best corrected visual
acuity (“BCVA”) was selected for OpRegen subretinal delivery and the other eye was untreated. In Cohorts 1-3 (n=12), all
patients were legally blind at the outset of the trial (BCVA: ≤20/200, with a study eye mean of 23.5 letters, or approximately 20/320
(standard deviation (SD): ±11.7; minimum-maximum: 0–39 letters)) and had significant progression of GA (study eye mean GA
area: 12.7 mm2 (SD: ±6.7; min-max: 6–30 mm2)). Cohort 4 (n=12) enrolled patients with impaired vision
(BCVA: ≥20/250 and ≤20/64, with a study eye mean of 44.8 letters, or approximately 20/125 (SD: ±7.5; min-max: 28–54
letters)) and smaller areas of GA (study eye mean GA area: 7.4 mm2 (SD: ±2.9; min-max: 1.4–11 mm2)).
OpRegen was delivered subretinally via pars plana vitrectomy and retinotomy (n=17) or, in Cohort 4 only, via suprachoroidal cannula using
the Gyroscope Therapeutics, Ltd. Orbit Subretinal Delivery System (n=7). We completed enrollment in Cohorts 1-3 in the middle of 2018
and in Cohort 4 in November 2020.
The
primary objective of the study was to evaluate the safety and tolerability of OpRegen as assessed by the incidence and frequency of treatment-emergent
adverse events. Secondary objectives are to evaluate the potential activity of OpRegen by assessing changes in visual function and retinal
structure. The primary objective and the secondary objectives were assessed at 12 months following OpRegen subretinal delivery (“Month
12”) and subjects are followed for up to five years.
Summary
of Safety Results (data cutoff: January 18, 2022)
| |
● |
All
24 treated patients reported at least one adverse event (“AE”) and at least one ocular AE. |
| |
|
|
| |
● |
The
majority of AEs reported with OpRegen were mild (Cohorts 1-3, 87%; Cohort 4, 93%), and the immunosuppressive regimen was well tolerated. |
| |
|
|
| |
● |
The
ocular AEs reported with OpRegen were mainly related to the surgical procedures used for subretinal delivery, with the most common
being conjunctival hemorrhage/hyperemia (n=17) and epiretinal membrane (n=16). |
| |
|
|
| |
● |
One
patient discontinued the study due to an AE that was determined unrelated to treatment. |
| |
|
|
| |
● |
No
cases of rejection following OpRegen subretinal delivery have been reported. |
| |
|
|
| |
● |
No
acute or delayed intraocular inflammation, or sustained intraocular pressure increase following OpRegen subretinal delivery has been
observed. |
Summary
of Activity Results (data cutoff: January 18, 2022)
| |
● |
Preliminary
evidence of improvement in visual function using the Early Treatment Diabetic Retinopathy Study (“ETDRS”) assessment
of BCVA: |
| |
○ |
Cohort
4 subjects (n=12) had an average 7.6 letter gain in the study (treated) eye and an average 1.7 letter gain in the fellow (untreated)
eye at Month 12 compared to baseline. Cohorts 1-3 subjects (n=11) had an average 4.7 letter gain in the study eye and an average
6.0 letter gain in the fellow eye at Month 12 compared to baseline. |
| |
|
|
| |
○ |
Three
subjects in Cohort 4, or 25% of Cohort 4, and one subject in Cohorts 1-3 had a 15 letter or greater gain in the study eye at Month
12 compared to baseline. None of the fellow (untreated) eyes had a 15 letter or greater gain. |
| |
● |
Five
Cohort 4 subjects with OpRegen delivered to most or all of the GA area, including the fovea, had greater gains in visual function
at Month 12 (average 12.8 letter gain) as compared with subjects who did not receive OpRegen in a similar manner to most or all of
the GA area, with evidence for regions of apparent improvement of outer retinal structure as assessed by spectral domain optical
coherence tomography (“SD-OCT”). |
| |
|
|
| |
● |
SD-OCT
imaging analysis of all subjects is ongoing. |
These
data support the potential for OpRegen to slow, stop, or reverse disease progression in GA. Further assessment of the optimal disease
stage for intervention, surgical procedure for subretinal delivery, and target delivery location of OpRegen in a larger, controlled clinical
study is needed to confirm these preliminary findings.
Cautionary
Statement Regarding Forward-Looking Statements
Lineage
cautions you that all statements, other than statements of historical facts, contained in this report, are forward-looking statements.
Forward-looking statements, in some cases, can be identified by terms such as “believe,” “may,” “will,”
“estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,”
“could,” “can,” “plan,” “potential,” “predict,” “seek,” “should,”
“would,” “contemplate,” project,” “target,” “tend to,” or the negative version
of these words and similar expressions. Such statements include, but are not limited to, statements relating to the potential benefits
of treatment with OpRegen in patients with GA, the significance of clinical data reported to date, including the findings of evidence
of visual function and outer retinal structure improvements, from the ongoing Phase 1/2a study of OpRegen. Forward-looking statements
involve known and unknown risks, uncertainties and other factors that may cause Lineage’s actual results, performance or achievements
to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in
this report, including, but not limited to, the risk that positive findings in early clinical and/or nonclinical studies of a product
candidate may not be predictive of success in subsequent clinical and/or nonclinical studies of that candidate; the risk that competing
alternative therapies may adversely impact the commercial potential of OpRegen; the risk that Roche and Genentech may not be successful
in completing further clinical trials for OpRegen and/or obtaining regulatory approval for OpRegen in any particular jurisdiction; the
risk that Lineage may not be able to manufacture sufficient clinical quantities of its product candidates in accordance with current
good manufacturing practice; risks and uncertainties inherent in Lineage’s business and other risks discussed in Lineage’s
filings with the SEC. Lineage’s forward-looking statements are based upon its current expectations and involve assumptions that
may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these
cautionary statements. Further information regarding these and other risks is included under the heading “Risk Factors” in
Lineage’s periodic reports with the SEC, including Lineage’s most recent Annual Report on Form 10-K and Quarterly Report
on Form 10-Q filed with the SEC and its other reports, which are available from the SEC’s website. You are cautioned not to place
undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage 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.