Mesoblast developing multiple cell-based products

CEO AND MANAGING DIRECTOR, DR. SILVIU ITESCU

CEO AND MANAGING DIRECTOR, DR. SILVIU ITESCU

Mesoblast (NASDAQ:MESO; ASX:MSB) has leveraged its proprietary technology platform, which is based on specialized cells known as mesenchymal lineage adult stem cells (MLCs), to establish a broad portfolio of late-stage product candidates.

“This technology has the potential to target advanced stages of diseases, with high, unmet medical needs, including cardiovascular conditions, orthopedic disorders, immunologic and inflammatory disorders and oncologic/hematologic conditions,” CEO and managing director, Dr. Silviu Itescu, says in an interview with BioTuesdays.com.

Dr. Itescu explains Mesoblast’s MLCs are rare cells and central to blood vessel maintenance, repair and regeneration, largely via secretion of growth factors, which act on neighboring endothelial cells to promote blood vessel regeneration and function.  

Mesoblast's proprietary technology enables immuno-selection of purified, highly potent cells called mesenchymal precursor cells (MPC), which are the earliest progenitors of all MLCs and give rise to reproducibly homogeneous and highly potent cell therapy product candidates, he adds.

He says MLCs are found around blood vessels and respond to signals associated with tissue damage, secreting mediators, which promote tissue repair and modulate immune responses. MLC products also are allogeneic, meaning cells from one donor may be used in many different recipients without the need for matching.

“Multiple mechanisms of action and proprietary manufacturing processes allow us to make many independent and distinct product candidates,” he adds.

In addition, Dr. Itescu points out that the company has established large-scale expansion of its MLCs to produce a cellular product with “consistent, well-defined therapeutic properties, batch release criteria and established potency assays, with accompanying manufacturing economies of scale.”

Product Delineation Using Mesenchymal Lineage Cells Provides Diversified Pipeline

Product Delineation Using Mesenchymal Lineage Cells Provides Diversified Pipeline

Unlike other categories of stem cells or mature cell lineages, he contends that MLCs do not initiate and facilitate an immune response when administered to unrelated patients.

Dr. Itescu points out that MLCs can be taken from healthy young adult donors and from various tissue sources, including bone marrow, fat tissue and dental pulp.

“The rare MLCs are isolated and expanded to create master cell banks, which are then further amplified to generate thousands of therapeutic doses for use in patients without the need for tissue matching,” he adds. Each allogeneic product candidate is packaged into vials and frozen for later use.

The company’s IP portfolio covers more than 700 patents or patent applications across 72 families, providing, broad commercial protection for our cell-based product candidates.”

Mesoblast’s lead program is MPC-150-IM, which is in a Phase 3 clinical trial across North America in patients with advanced chronic heart failure (CHF).

Dr. Itescu explains that the primary endpoint is a comparison of recurrent heart failure-related major adverse cardiovascular events (HF-MACE) between patients treated with MPC-150-IM and controls. The use of recurrent HF-MACE as a primary endpoint is based on the fact that in the Phase 2 trial, a single injection of MPC-150-IM successfully prevented recurrent HF-MACE over a three-year period.

About half of the 600 patients have been enrolled in the Phase 3 trial and the company plans to release an interim analysis in the first quarter next year to assess the trial’s primary endpoint between cell-treated and control patients, he adds.

Dr. Itescu also notes that the NIH is conducting a 120-patient Phase 2b trial using MPC-150-IM in patients with end-stage CHF that have a heart pump, with a data readout scheduled for the third quarter of 2017.

Mesoblast's proprietary technology enables immuno-selection of purified, highly potent cells called mesenchymal precursor cells (MPC), which are the earliest progenitors of all MLCs and give rise to reproducibly homogeneous and highly potent cell therapy product candidates

Mesoblast's proprietary technology enables immuno-selection of purified, highly potent cells called mesenchymal precursor cells (MPC), which are the earliest progenitors of all MLCs and give rise to reproducibly homogeneous and highly potent cell therapy product candidates

Mesoblast’s pipeline also includes MPC-300-IV, a cell-based product for the treatment of chronic inflammatory conditions, including biologic refractory rheumatoid arthritis (RA).

“The biologic refractory RA population accounts for approximately one-third of all RA patients who have received anti-tumor necrosis factor (anti-TNF) or other biologic agents. They are the hardest to treat and require new therapies that are both effective and safe, without risk of serious infections or malignancies,” Dr. Itescu suggests.

In a Phase 2 trial with 48 patients with active RA, a single dose of MPC-300-IV resulted in dose-related improvements in clinical symptoms, function, and disease activity, without serious adverse events over the 12-week study.

“We believe the safety and efficacy results of this trial provide support for the potential of Mesoblast’s allogeneic MPCs to be positioned as first-line treatment option in RA patients who have previously received a prior anti-TNF or other biologic agents,” he adds.

In a recent research report, Jason Kolbert, an analyst with Maxim Group, said the Mesoblast RA data are impressive and form a solid basis for a pivotal trial.

“We encourage investors to compare the data to other data sets from well-known (blockbuster) drugs in the space. The [Mesoblast] safety profile (critical in RA) is far superior, and the efficacy signals are quite clear,” Mr. Kolbert wrote.

Dr. Itescu says the protocol for a potential Phase 3 program in RA is being developed and the company has started the process to partner MPC-300-IV with pharmaceutical companies.

In a program for chronic low back pain due to degeneration disc disease, Mesoblast is currently enrolling up to 360 patients in a Phase 3 trial across the U.S. with its MPC-06-ID cell-based product. An interim analysis is set for the first quarter of 2017, with enrollment to be completed in the third quarter.

“Most current treatments for chronic low back pain focus on pain relief rather than addressing the underlying degenerative nature of the disease,” Dr. Itescu points out. “We believe MPC-06-ID has the potential to fill an unmet treatment gap for this large patient population.”

In February, Mesoblast’s licensee in Japan, JCR Pharmaceuticals, launched its mesenchymal stem cell product, TEMCELL HS Inj., for the treatment of acute graft versus host disease (aGVHD) in children and adults in Japan. TEMCELL is the first allogeneic cell therapy to be fully approved in Japan.

In patients who have received a bone marrow transplant, donor cells may attack the recipient, causing aGVHD, and resulting in activation of pro-inflammatory T-cells and tissue damage in the skin, gut and liver, which is often fatal.

Tier 1 Product Candidate Deliverables (Calendar Year)

Tier 1 Product Candidate Deliverables (Calendar Year)

In an expanded access program, Dr. Itescu says 241 children in the U.S. were treated with MSC-100-IV for severe, multi-line refractory aGVHD. “Our treatment demonstrated clinically meaningful responses and significantly increased survival in children with this life-threatening disease,” he points out.

To support filing of a biologic license application to FDA for regulatory approval, Dr. Itescu says Mesoblast is conducting a 60-patient, open label Phase 3 trial, using MSC-100-IV as front-line therapy in children with steroid-refractory aGVHD.

After filing a BLA for pediatric approval of MSC-100-IV, he says Mesoblast plans to conduct a further trial to support a product approval of its cell therapy in adults with gastrointestinal or liver aGVHD, the patient groups who have the highest mortality risk.

“We are confident in our competitive position, development capabilities and ability to attract world-class partners,” Dr. Itescu says. “We are entirely committed to transforming our technology into medicines that save and improve lives.”