Lomecel-B significantly decreased biomarker Tie-2 in Aging Frailty subjects at 270 days compared to placebo
Significant, dose-dependent decrease in Tie-2 at Day 270
Oral presentation today at the International Conference for Frailty & Sarcopenia Research
MIAMI, Sept. 29, 2021 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN)
("Longeveron" or "Company"), a clinical stage biotechnology company
developing cellular therapies for chronic aging-related and
life-threatening conditions, announced preliminary top line results from
ongoing biomarker analysis from the Company’s Phase 2b trial of
Lomecel-B investigational cell therapy in Aging Frailty subjects.
Biomarker
analysis, which is considered exploratory in this trial, revealed that
administration of Lomecel-B was associated with a statistically
significant reduction in serum levels of soluble TIE-2 (sTIE-2)
in a dose-dependent fashion at Day 270 compared to placebo. The levels
fell by -243.13 ± 1073.21 pg/mL for the combined Lomecel-B arms (95% CI
-519.69, -93.61; p=0.0051) at 270 days as compared to an increase of
356.03 ± 1018.95 pg/mL in the placebo group (95% CI -4.06, 786.87;
p=0.0524). The difference between the placebo and high dose Lomecel-B
(200 million cells) is -936.85 pg/mL (95% CI -1640.27, -233.43;
p=0.0095). It is known that reductions in sTIE-2 correlate with
anti-inflammatory and pro-vascular effects [1, 2], while elevated levels
of sTIE2 have been observed in patients with peripheral arterial
disease (PAD) [3].
TIE-2 is a cell surface receptor tyrosine
kinase that can activate biochemical pathways to promote vascular (blood
vessel) health [1, 2, 4]. This receptor is present on cells that line
blood vessels, and protects against vascular leakage and inflammation
[5, 6]. However, TIE-2 can be cleaved from the cell surface, which
increases the levels of sTIE-2 in the blood stream [7]. As such,
increased levels of sTIE-2 in the blood stream may be indicative of poor
vascular health [3] and endothelial dysfunction [8, 9]. Since poor
vascular health and endothelial dysfunction are associated with the
onset and development of frailty in older adults [10, 11], the finding
that Lomecel-B can reduce sTIE-2 suggests that improving vascular and
endothelial function may be a potential mechanism of action of this
product. This is the first time that a cell therapy has been associated
with a reduction in sTIE-2 in the blood stream.
The Company plans to further explore the Tie-2 changes in additional subject populations with Aging Frailty.
Virtual Presentation Jorge
Ruiz, M.D., Associate Director for Clinical Affairs at the Geriatric
Research, Education and Clinical Center (GRECC), Miami Veterans Affairs
Healthcare System, and lead investigator in the trial, will present the
results from the trial titled: A Phase 2b, Randomized, Blinded and
Placebo-Controlled Trial to Evaluate the Safety and Efficacy
of Lomecel-B Infusion in Patients With Aging Frailty (the “Phase 2b trial”) at the 2021 11th Annual International Conference for Frailty & Sarcopenia (ICFSR).
Today’s
slide deck will be available on the Company’s “Events &
Presentations” page and the webcast of the presentation will be made
available on the Company’s website after the conference.
About the Phase 2b Trial
The
Phase 2b trial, which was partially funded by a Small Business
Innovation Research (SBIR) grant from the National Institute on Aging
(NIA), evaluated the safety and efficacy of a single peripheral
intravenous infusion of four different doses of Lomecel-B cell therapy
(25 million (n=37), 50 million (n=31), 100 million (n=34) and 200
million (n=16) cells. The primary objective of the study was to assess
the effect of Lomecel-B treatment on exercise tolerance and endurance
via the six-minute walk test (6MWT).
Results
showed that frail subjects (average age of 75.2 years) with impaired
mobility could walk nearly 50 meters further 180 days after a single
infusion of Lomecel-B (200 million Lomecel-B group; p=0.0065). This
increase persisted through 270 days (200 million Lomecel-B group change
from baseline 47.9 meters; p=0.0115, and p=0.0077 compared to placebo).
By comparison, the placebo-treated subjects change from baseline at 180
days and 270 days was 8.0 meters (p=0.5371) and -15.5 meters (p=0.2728),
respectively. Additionally, results showed a clear, statistically
significant dose-response curve at day 180 using the 6MWT endpoint.
References 1. Ghosh, C.C., et al., Gene control of tyrosine kinase TIE2 and vascular manifestations of infections. Proc Natl Acad Sci U S A, 2016. 113(9): p. 2472-7. 2. Han, S., et al., Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med, 2016. 8(335): p. 335ra55. 3. Findley, C.M., et al., Plasma
levels of soluble Tie2 and vascular endothelial growth factor
distinguish critical limb ischemia from intermittent claudication in
patients with peripheral arterial disease. J Am Coll Cardiol, 2008. 52(5): p. 387-93. 4. Maisonpierre, P.C., et al., Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science, 1997. 277(5322): p. 55-60. 5. Augustin, H.G., et al., Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol, 2009. 10(3): p. 165-77. 6. Kelly-Goss, M.R., et al., Dynamic, heterogeneous endothelial Tie2 expression and capillary blood flow during microvascular remodeling. Sci Rep, 2017. 7(1): p. 9049. 7. Reusch, P., et al., Identification of a soluble form of the angiopoietin receptor TIE-2 released from endothelial cells and present in human blood. Angiogenesis, 2001. 4(2): p. 123-31. 8. Idowu, T.O., et al., Identification of specific Tie2 cleavage sites and therapeutic modulation in experimental sepsis. Elife, 2020. 9. 9. Thamm, K., et al., Molecular Regulation of Acute Tie2 Suppression in Sepsis. Crit Care Med, 2018. 46(9): p. e928-e936. 10. Alonso-Bouzon, C., et al., Association between endothelial dysfunction and frailty: the Toledo Study for Healthy Aging. Age (Dordr), 2014. 36(1): p. 495-505. 11. Amarasekera, A.T., et al., Does vascular endothelial dysfunction play a role in physical frailty and sarcopenia? A systematic review. Age Ageing, 2021. 50(3): p. 725-732.
About Lomecel-B
Lomecel-B
is a proprietary allogeneic product comprised of medicinal signaling
cells (MSCs) from the bone marrow of adult donors and culture-expanded
in Longeveron’s current good manufacturing practice (cGMP) cell
processing facility.
About Longeveron Inc.
Longeveron
is a clinical stage biotechnology company developing cellular therapies
for specific aging-related and life-threatening conditions. The
Company’s lead investigational product is the LOMECEL-B™ cell-based
therapy product (“Lomecel-B”), which is derived from culture-expanded
medicinal signaling cells (MSCs) that are sourced from bone marrow of
young, healthy adult donors. Longeveron believes that by using the same
cells that promote tissue repair, organ maintenance, and immune system
function, it can develop safe and effective therapies for some of the
most difficult disorders associated with the aging process and other
medical disorders. Longeveron is currently sponsoring Phase 1 and 2
clinical trials in the following indications: Aging Frailty, Alzheimer’s
disease, the Metabolic Syndrome, Acute Respiratory Distress Syndrome
(ARDS), and hypoplastic left heart syndrome (HLHS). The Company’s
mission is to advance Lomecel-B and other cell-based product candidates
into pivotal Phase 3 trials, with the goal of achieving regulatory
approvals, subsequent commercialization, and broad use by the healthcare
community. Additional information about the Company is available at https://www.longeveron.com/.
Forward-Looking and Other Statements
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statements in this press release that are not historical facts are
forward-looking statements that reflect management's current
expectations, assumptions, and estimates of future performance and
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events, circumstances, or effects. Moreover, forward-looking statements
in this release include, but are not limited to, statements about the
ability of our clinical trials to demonstrate safety and efficacy of our
product candidates, and other positive results; the timing and focus of
our ongoing and future preclinical studies and clinical trials; the
size of the market opportunity for our product candidates, the
beneficial characteristics, safety, efficacy and therapeutic effects of
our product candidates; our ability to obtain and maintain regulatory
approval of our product candidates, our plans and ability to obtain or
protect intellectual property rights, including extensions of existing
patent terms where available and our ability to avoid infringing the
intellectual property rights of others. Further information relating to
factors that may impact the Company's results and forward-looking
statements are disclosed in the Company's filings with the SEC. The
forward-looking statements contained in this press release are made as
of the date of this press release, and the Company disclaims any
intention or obligation, other than imposed by law, to update or revise
any forward-looking statements, whether as a result of new information,
future events, or otherwise.
BioFlorida is the voice of Florida's life sciences industry, representing 8,600 establishments and research organizations in the BioPharma, MedTech, Digital Health and Health Systems that collectively employ nearly 107,000 Floridians. Source: TEConomy/BIO (released 2022)
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