Clinical Evidence for Immune Reprogramming with Extracorporeal Mesenchymal Stromal Cell TherapyBarcia, Rita N., PhD1, Nguyen, Sunny, BS1, Brian O’ Rourke , PhD1, Igo, Peter, BS1, Tilles, Arno W., MD, MSBE1, Elizabeth Lapointe1, Chris Gemmiti, PhD 1, Brian LK Miller, MS, MBA1, Parekkadan, Biju, PhD1,2,3
1Sentien Biotechnologies, Inc. 99 Hayden Ave, Suite 140, Lexington, MA 02421 2 Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey 08854 3Center for Surgery, Innovation, and Bioengineering, Massachusetts General Hospital, Boston, MA 02114 3Harvard Stem Cell Institute, Cambridge, MA 02138
An interim analysis was performed on the low dose cohort (n=4 in each group).
Product Concept: Sentien is developing a combination product (SBI-101) that integrates allogeneic MSCs within an extracorporeal, bloodcontacting device to fundamentally change the administration route. Instead of bringing MSCs to the blood, our product brings blood to the MSCs.
Bioactive molecules secreted by MSCs are the primary source of activity of these therapeutically promising cells. We have engineered a systemto maximize delivery of therapy from MSCs to circumvent the half-life issues that have hindered MSC transplantation. This system overcomesthe dosing constraints of IV infusion and potentiates a broad range of biological responses unparalleled in single molecule therapeutics.
The Sentien Approach: Bringing blood to the MSCs
Ex-vivo MSC therapy using SBI-101 technology shows promise for severe COVID-19Grant Funding Agencies:NIDDK 5R44DK085766NHLBI 4R44HL128659
SBI-101 Clinical Data in AKI Reflects Broad Immunomodulation
Phase I/II: Double blind, randomized, controlled, study at 2 doses to establish safety and pharmacologic POC (NCT03015623) Miller et al., Kidney Int Rep. 2018
SBI-101 Acute Kidney Injury (AKI) trial
2. MSCs secrete therapeutic molecules creating concentrated, sustained microenvironment in SBI-101
3. SBI-101 modulates immune cells leading to a systemic anti-inflammatory response
1. Blood is continuously exposed to MSCs in SBI-101
SBI-101
8-10 US based clinical sitesCRRT only (control)CRRT + 250M cells (low dose)CRRT + 750M cells (high dose)
Endpoints:1: Safety2: Renal specific efficacyExploratory: PK/PD biomarkers
Monocytes
T cells
B cells
Accelerated Kidney Repair
MSC Secreted Factors à Systemic Immunomodulation à Immune Cell Reprogramming
Therapeutic Hypothesis of MSC-Mediated Blood
Reprogramming
All patients were on Continuous Renal Replacement Therapy (CRRT)
SBI-101 AKI Results are Consistent with Immune Reprogramming
*Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; published online Jan 24.
TNF-⍺, MCP-1, and IFN-y are all highly increased in COVID-19 ICU patients*
COVID-19Patient data
Scree
n B
Pre-D
ose
End of T
x
Day 1
Day 3
Day 7
0.0
0.5
1.0
1.5
2.0
Cha
nge
over
pre
trea
tmen
t
TNFa
24hr 250M
Sham
Tx
SBI-101 AKI Patient
data
Scree
n B
Pre-D
ose
End of Tx
Day 1
Day 3
Day 7
0
1
2
3
4
Cha
nge
over
pre
trea
tmen
t
IFNy
24hr 250M
PLTx
Scree
n B
Pre-D
ose
End of T
x
Day 1
Day 3
Day 7
0.0
0.5
1.0
1.5
Cha
nge
over
pre
trea
tmen
t
MCP-1
Tx
Low dose SBI-101
Sham
Immunomodulation observed in SBI-101 AKI Clinical Data Supports Therapeutic Hypothesis in COVID-19
**ZHOU, et al., Aberrant pathogenic GM-CSF+T cells and inflammatory CD14+CD16+monocytes in severe pulmonary syndrome patients of a new coronavirus,
pre print
Healt
hy co
ntro
l (n=
10)
ICU
(n=
12)
Non-
ICU
(n=
21)
Scree
n B
Pre-D
ose
End of T
xDay
1Day
3Day
70
1
2
3
Fold
Cha
nge
from
Pre
-Dos
e
Total MonocytesSham LD 24hrTx
Inflammatory monocytes have positive correlations with severe pulmonary
syndrome in patients infected 2019-nCoV**
SBI-101 Sham
*
InhibitedActivated
* Septic subject that got better has pathway profile similar to SBI-101 treatment
Phase 1b data suggests that SBI-101 broadly inhibits immune-mediated inflammatory pathways, including:
• T cell response• Maturation of lymphocytes• Activation of lymphocytes• Immune response of leukocytes• Quantity of leukocytes• Inflammation of Organ
Known MSC biology is very well suited to address the hyper-inflammation associated with severe COVID-19. By addressing a broad array of immune-mediated inflammatory pathways, MSCs can simultaneously address multiple aspects of the inflammatory cascade.
SBI-101 therapy allows for extended delivery of MSC
secreted factors, harnessing the potential of MSC therapy for
systemic inflammatory diseases such as COVID-19.
Adapted from From Li, et al. Molecular immune pathogenesis and diagnosis of COVID-19, Journal of Pharmaceutical Analysis, Pre proof
MSCs Therapy Ideally Suited for Severe COVID-19