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![Page 1: Commercialisation of Allogeneic Mesenchymal Precursor c.ymcdn.com/sites/ · PDF fileCommercialisation of Allogeneic Mesenchymal Precursor Cells Dr Kilian Kelly Director, Regulatory](https://reader031.vdocuments.us/reader031/viewer/2022022504/5ab731a57f8b9a1a048ea6ae/html5/thumbnails/1.jpg)
Commercialisation of Allogeneic Mesenchymal Precursor Cells
Dr Kilian KellyDirector, Regulatory and Clinical
17th Annual ISCT MeetingRotterdam, Netherlands, 21 May 2011
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Agenda
About Mesoblast
Mesenchymal Precursor Cells
Nonclinical considerations
Key issues for allogeneic use in humans
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About Mesoblast
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About Mesoblast
Global HQ in Melbourne, Australia
Offices in New York and Austin, USA, including wholly-owned subsidiary Angioblast
Listed on ASX (MSB)
Primarily focussed on development of adult stem cells (Mesenchymal Precursor Cells; MPCs)
Development at an advanced stage for a wide range of indications
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Mesenchymal Precursor Cells
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We own the intellectual property on MPCs
US manufacturing process patent granted
Products for eye diseases
Products for cardiac diseases and diabetes
US composition patent granted
Global use patents file
Culture-expanded cellsIsolated cells
Bone marrow + antibody
Magnetic beads
Magnet
Products for orthopaedic diseases
MPC highly-expandable + non-immunogenic
Bone
Cartilage
Heart muscle
Pancreas
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Our industrial scale manufacturing process
Homogeneous cell population
Well-controlled cell expansion
Efficient large-scale expansion
Lower costs of cell culture process
Batch-to-batch consistency
Stringent release criteria
Greater potency of expanded product
Bone marrow plus MPC-binding antibody
Magnetic beads
Magnet
Final product
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“Off-the-shelf” product portfolio
Lead products
Bone marrow transplantation
Congestive heart failure
Spinal fusion
Knee osteoarthritis
Long bone fracture repair
Acute myocardial infarction
Intervertebral disc repair
Eye disease (AMD)
Diabetes
Neurodegenerative diseases
Pre-clinical Phase I Phase II Phase III
IND clearance
FDA approval
Partnered with Cephalon
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Very promising clinical efficacy data: heart failure
Interim results after average 18 month follow-up
Event MPC treatment (N=45)No. patients with event (%)
Controls (N=15)No. patients with event (%)
p value
Any Serious Adverse Cardiac Event (SAE)
20 (44.4%) 14 (93.3%) 0.001
Any Major Adverse Cardiac Event (MACE¶)
3 (6.7%) 6 (40%) 0.005
Cardiac deaths 0 (0.0%) 2 (13.3%) 0.059
All cause deaths 2 (4.4%) 2 (13.3%) 0.26
MACE¶ or any hospitalization for heart failure
6 (13.3%) 6 (40%) 0.056
Interim data analysis December 2010, after all patients have reached 6 months follow-up (average 18 months)¶MACE defined as composite of MI, revascularization, or cardiac death
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Very promising clinical efficacy data (2)
In patients with non-healing fractures:– Significant new bone growth observed in all fractures– Clinical & radiographic union of fractures observed in >80%
In patients with haematological malignancies:– Composite efficacy endpoint of 100 day survival with
sustained engraftment of both neutrophils and platelets– 80% transplanted with MPC-expanded cord blood met this
endpoint, c.f. 38% in controls– Incidence of severe graft-versus-host disease lower in those
transplanted with MPC-expanded cord blood
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Allogeneic Cell Therapy:Nonclinical considerations
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Nonclinical considerations (1)
Standard regulatory guidance (inclICH) often not applicable
Availability of relevant and/or feasible animal models for human derived cells?
Safety studies may need to be conducted in animal disease models rather than healthy animals
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Nonclinical considerations (2)
Human cells would elicit a xenogeneic response in immunocompetent animals
Use of nude mice etc is an option, but has limitations
Studies with allogeneic animal cells can be more informative
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Key issues for allogeneic use in humans
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Donor selection (1)
Need clearly defined criteria to select suitable donors
Must meet relevant regulatoryrequirements, e.g.:
– 21 CFR Part 1271 (US)
– Directive 2006/17/EC (EU)
In addition, may want to specify additional criteria – e.g. age, race?
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Donor selection (2)
Selection process will typically involve detailed medical history, physical exams & lab tests
Samples should be retained for retrospective testing
Full traceability from donor to recipient is essential, without compromising anonymity of donor
Comparability between donors also important
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Donor selection (3)
Typical exclusions:
– Malignancy
– Current systemic infection
– Positive test for HIV, Hep B/C, HTLV I/II, Treponema pallidum, CMV
– High risk of infection with communicable diseases
– Known/suspected TSE
– Autoimmune diseases
– Unexplained health issues
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Immunogenicity
Crucial regulatory and commercial consideration for allogeneic use
Mesoblast has demonstrated that MPCs do not initiate an immune response in unrelated recipients
This facilitates “off the shelf” use just like classic pharmaceutical drugs
Prior to first in human – risk assessment/nonclinical data
In clinical trials – monitor for immune response
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Logistical considerations (1)
Fresh-released products have very short shelf life: requires either manufacturing close to point of use or cryopreservation
Need to establish that cryopreservation does not adversely affect cells
May need to demonstrate safety of cryoprotectant for human use
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Logistical considerations (2)
Cryopreserved products have special storage, distribution and handling requirements
Investigational sites likely to need specific training
Re-labelling of product difficult if not impossible
However, if appropriate procedures are put in place, supply worldwide from a single manufacturing facility is feasible
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Thank you.
Questions?
This document was accompanied by an oral presentation, and is not a complete record of the discussion held.
No part of this presentation should be used elsewhere without prior consent from the author.
For more information, please contact [email protected]