On
May 3, 2021, Lineage announced updated interim results from its ongoing, 24-patient Phase 1/2a clinical study of its lead product
candidate, OpRegen. OpRegen is an investigational cell therapy consisting of allogeneic retinal pigment epithelium (RPE) cells
administered to the subretinal space for the treatment of dry age-related macular degeneration (AMD) with geographic atrophy (GA).
The
patients in the ongoing clinical study are 50 years of age or older, whose dry AMD has advanced to the GA stage, with absence
of additional concomitant ocular disorders. The eye in which the disease has progressed the most is treated, while their other
eye serves as a measure of disease progression. Following injection, the patients are followed for 12 months at specified intervals
to evaluate the safety and tolerability of OpRegen. Following the initial 12-month period, patients are evaluated at longer intervals
for up to an additional five years following administration. A secondary objective of the clinical study is to examine the ability
of transplanted OpRegen to engraft, survive, and modulate disease progression in the patients. In addition to thorough characterization
of visual function, several vision tests are used to quantify stabilization or improvements in visual function. Anatomical evaluation
imaging is also performed to assess the restoration of the structure of the retina.
The
updated interim results included additional data on 24 patients enrolled in the study, including all 12 patients treated in Cohort
4, which have better baseline vision and smaller areas of GA than earlier cohorts, and included a minimum of 4.5 months
of follow-up in all 24 patients treated with OpRegen. Nine of twenty-four patients were treated with the “thaw and inject”
formulation of OpRegen, two via a standard pars plana vitrectomy (PPV) and seven utilizing the Orbit™ Subretinal Delivery
System (Orbit SDS).
Overall,
10/12 (83%) of the Cohort 4 patients’ treated eyes were at or above baseline visual acuity at their last assessment, based on per
protocol scheduled visits ranging from 4.5 months to approximately 3 years post-transplant. Improvements in best corrected visual acuity
(BCVA) for Cohort 4 patients reached up to +19 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. In contrast,
10/12 (83%) of the patients’ untreated eyes were below pre-treatment baseline values at the same time points. Among the newly reported
data, three (50%) of the more recently treated Cohort 4 patients exhibited marked improvements in BCVA ranging from +7 to +16 letters
at their last scheduled assessments of at least 4.5 months. Two additional Cohort 4 patients experienced a gain of 2 letters from their
baseline values. One Cohort 4 patient measured 7 letters below baseline. Previously reported structural improvements in the retina,
decreases in drusen density, and a trend toward slower GA progression
in treated compared to untreated eyes continued. Overall, OpRegen has been well tolerated with no unexpected adverse events or serious
adverse events, and evidence of durable engraftment of OpRegen RPE cells have extended to more than 5 years in earliest treated patients,
supporting the potential for OpRegen to be a one-time treatment.
A
Cohort 4 patient with evidence of retinal restoration and confirmed history of GA growth, which was first reported 9 months following
treatment, continues to demonstrate areas of retinal restoration as of their last assessment, approximately 3 years after treatment.
Below
are highlights of the updated interim results (as of April 16, 2021):
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In
Cohort 1-3 patients (all legally blind at baseline), visual acuity reductions occurred as expected due to progressive GA;
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In
Cohort 4 patients, which collectively had smaller areas of GA and higher baseline BCVA as compared to Cohort
1-3 patients, improved or sustained BCVA has been observed in 10/12 (83%) patients as of their last visit prior to this update
(range of -7 to +19 letters on the ETDRS chart);
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OpRegen
continues to be well-tolerated in all treated patients (N = 24);
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The
majority of adverse events were mild (87%);
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Sustained
subretinal pigmentation continues to suggest multi-year durability of OpRegen transplants;
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Improved
anatomy and function continue to be observed in some patients, including:
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Reduction
in drusen;
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Photoreceptor
and RPE layer restoration;
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Localized
slowing of GA progression in treated areas;
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Better
visual acuity via ETDRS scores and reading speed; and
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Improved
National Eye Institute Visual Function Questionnaire (VFQ-25) scores.
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Post-treatment
surgical interventions occurred in four cases (5 events in 4 patients):
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Three
epiretinal membranes (ERM) were surgically peeled. Mild to moderate ERM were observed in an additional 12 out of 17 PPV operated
patients. Most ERMs were
clinically insignificant.
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Retinal
detachment (RD) was observed in 2 out of 17 patients, neither of which appears to be attributable to OpRegen or any study
related medications:
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The
first case of RD, which occurred in a Cohort 3 patient, was an unsuccessful repair of a post-surgical retinal tear; visual
acuity did not regain baseline levels; and
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The
second case of RD, which occurred in a Cohort 4 patient, was successfully repaired; post-surgical visual acuity has remained
higher than baseline.
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Choroidal
neovascularization (CNV) was observed in 3 out of 7 patients receiving OpRegen via the Orbit SDS, all of whom received treatment
with an approved anti-VEGF;
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As
previously reported, one PPV operated patient developed CNV, which was identified
more than two years following treatment.
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As
part of an ongoing effort to administer the minimally effective dose and duration of immunosuppressive therapy, immunosuppression
was utilized only during the perioperative period of approximately 3 months in Cohort 4 patients. One patient received a modified
immunosuppressive regimen at baseline, which included no tacrolimus and only mycophenolate mofetil. One patient was diagnosed
with COVID-19 shortly after treatment for whom all immunosuppression was halted and reinstated once the patient was asymptomatic.
Both patients showed no signs of acute or delayed inflammation or rejection of OpRegen cells with 4.5 months of post-transplant
follow up. Other than the reduced regimens described above, immunosuppressants have been discontinued as scheduled, typically
within 90 days post-operatively, and no cases of acute or delayed rejection or inflammation due to OpRegen have been reported
in any patients treated with OpRegen.
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,” “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 expected clinical
outcomes of treatment with OpRegen in dry AMD patients with GA. 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 press release, including risks
and uncertainties inherent in Lineage’s business and other risks in Lineage’s filings with the Securities and Exchange
Commission (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 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.