CLINICAL PIPELINE - pluri-biotech.com

CLINICAL
PIPELINE

PRODUCTS UNDER CLINICAL DEVELOPMENT

PLacental eXpanded (PLX) cells are placenta-derived, mesenchymal-like adherent stromal cells that are expanded ex vivo and are designed to be administered to patients without the need for tissue or genetic matching. This is possible because of the cells’ low immunogenicity and immune-modulatory properties. Accumulated data from multiple in vitro and in vivo experiments indicate that these cells have the capacity to release soluble biomolecules, such as cytokines, chemokines and growth factors, which act in a paracrine and endocrine manner to facilitate healing of damaged tissue. The secreted therapeutic factors reach the target tissue through the bloodstream and initiate the healing process, while the cells remain in the muscle into which they were injected.

PLX-PAD

PLX-PAD for mild to moderate knee osteoarthritis (OA)

PLX-PAD cells exhibit regenerative potential due to their capacity to release factors in response to chemical distress signals from tissues that have been damaged by muscle trauma or inflammation. These therapeutic factors trigger the body’s repair mechanisms and stimulate tissue renewal, differentiation and modulation of immune-mediated inflammation. PLX-PAD cells also rebalance the immune system, which plays a central role in the body’s exacerbated and uncontrolled attack on its own cells and organs in autoimmune diseases.

Pluri completed a global Phase III study of PLX-PAD to treat muscle recovery following surgery for hip fracture. The Hipgen program received € 7.4 million grant from the EU Horizon 2020 program to support Phase III trial
Top results:
* A significant increase in Hip Abduction Strength (HAS) in the injured and uninjured leg compared to placebo up to week 52
* Patients treated with PLX-PAD were able to walk 296 meters versus 266 meters in placebo during 6-min walking test at week 52
* PLX-PAD cell therapy was safe and well tolerated
Pluri conducted a global Phase III study of PLX-PAD to treat Chronic Limb-Threatening Ischemia (CLTI).
. This program (named PACE) received € 7.6 million grant from the EU Horizon 2020 program to support Phase III trial.
Top results:
The study was terminated following interim review, but post-analysis found statistically significant reduction in events of amputation and death in non diabetic or well-controlled patients at 12 months.
Pluri is a partner in PROTO (Advanced PeRsOnalized Therapies for Osteoarthritis), an international EU-funded initiative led by Charité Berlin, with a €7.5M grant from the Horizon Europe program. Under this collaboration a Phase I study of PLX-PAD in patients with mild to moderate knee osteoarthritis is conducted at Charité.
An investigator-initiated Phase I/II trial was conducted with PLX-PAD by Tel Aviv Sourasky Medical Center (Ichilov Hospital) for the treatment of steroid-refractory chronic graft versus host disease (cGvHD).

PLX-R18

PLX-R18 cells release a combination of therapeutic proteins in response to a damaged or poorly functioning hematopoietic system, which plays a key role in protection from infection, uncontrolled bleeding and anemia. PLX-R18 is believed to stimulate the regeneration of damaged bone marrow to produce all blood cells lineages (white, red and platelets)

PLX-R18 is being evaluated for the treatment and as a prophylactic countermeasure against Hematopoietic Acute Radiation Syndrome:

Several studies conducted by U.S. governmental agencies (NIH, DOD) via the FDA animal rule pathway
PLX-R18 was evaluated in the setting of ARS in numerus animal studies with various designs and demonstrated high efficacy in recovering all three-blood cell counts and increasing survival
PLX-R18 is safe in non-irradiated animals
PLX-R18 shows favorable safety in human patients with poor graft function
(Open-label, dose-escalation, Phase I study in the U.S. and Israel, N=21)

The FDA has cleared Pluri’s Investigational New Drug (IND) application for PLX-R18 in the treatment of ARS. The IND allows Pluri to treat victims who may have been acutely exposed to high dose radiation due to nuclear attacks or accident.
R18 cell therapy has received FDA Orphan Drug Designation for the prevention and treatment of ARS.

PLX-R18 was also evaluated in a phase I study for the treatment of Poor Graft Function (Cytopenia) following hematopoietic cell transplantation (HCT).

Top results: first in human study to evaluate the safety and exploratory efficacy in human:

PLX-R18 was well-tolerated with a favorable safety profile
PLX-R18 reduced mortality from 29% to 18%
Statistically significant increase in HGB and platelets at month 6 and 12 with respect to baseline
Increase in Neutrophils with respect to baseline
Statistically significant reduced mean rate of blood transfusion products (Platelets or RBC) per month