Orthobiologics Activity Signals Collaborations and Clinical Data Essential for Company Growth

By Julie A. Vetalice

ORTHOWORLD estimates that global orthobiologic product sales account for ~10% of the orthopaedic market’s revenue, overall. In 2016, that translated to just over $4.9 billion, an increase of 3% vs. 2015. For this year and into 2019, we’re projecting similar growth.

Supporting this growth will be patients who continue to seek non-surgical alternatives for joint repair, and continued growth in the use of synthetics and stem cell-based products. Collaborations will remain attractive in the space as companies choose orthobiologic-focused partners to get products to market, and universities partner with companies on licensing and development. Robust clinical and economic data will be a requirement for product clearance and adoption. These strategies were among our stated market observations in THE ORTHOPAEDIC INDUSTRY ANNUAL REPORT®, and activity thus far in 2017 reaffirms our stance.

We’ve compiled year-to-date activity through the second week of October 2017—M&A, collaborations, funding, data—to show how your competitors and customers have responded to market demands.

Exhibits 1 and 2 illustrate who acquired or partnered with whom so far, this year.
Exhibit 1: Merger & Acquisition Activity

 Acquirer  Acquired Description
 Kuros Biosurgery  Xpand
Biotechnology
Kuros gained access to MagnetOs synthetic bone graft putty, which in 3Q17
received FDA 510(k) clearance as an autograft extender in the
posterolateral spine.
 Stability Biologics’
stockholders
 MiMedx’s
Stability
Biologics assets
After acquiring Stability in 1Q16, MiMedx leadership determined in 3Q17
that the portfolio was not a strategic fit with its new focus on becoming a
biopharmaceutical company and returned the company to previous
stockholders. MiMedx will retain access to Stability sales reps via private
label distribution agreement.
 Organogenesis  NuTech Medical NuTech’s portfolio includes Affinity fresh amniotic allograft; NuShield
dehydrated terminally-sterilized allograft and NuCel and ReNu
cryopreserved allografts. NuTech will continue existing operations as a
division of Organogenesis, focused on surgical biologics.
 Tissue Regenix
(TRX)
 CellRight
Technologies
Combined, the companies will offer products for bone and soft tissue
regeneration based on CellRight’s human-derived bone grafts and TRX’s
dCELL decellularization platform. Purchase price $30.0MM.

 

Exhibit 2: Collaboration Activity

 Parties  Description of Collaboration
 AlloSource, Stryker Stryker will distribute AlloSource biologic products in the U.S. for use in sports medicine
procedures.
 Amend Surgical,
Univ. of Florida
Amend Surgical will exclusively license patents for the development of Biomimetic Bone.
 ARTOSS,
Owens & Minor
Artoss entered into a Defense Acquisition Purchasing Agreement with Owens & Minor and
gained U.S. Department of Defense access to NanoBone bone graft.
 Bioventus,
MEDSERVICE
Bioventus selected MEDSERVICE to distribute DUROLANE single-injection joint fluid in
Russia.
 Bioventus, Premier Premier is now offering Bioventus’ full surgical orthobiologics product portfolio to its U.S.
membership, comprising 3,750 hospitals and >130,000 provider organizations.
 Bone Biologics, UCLA Bone Biologics entered into an exclusive license agreement with UCLA for global
application of NELL-1 protein, with an initial focus as a bone graft substitute for
spine fusion.
 Bone Therapeutics,
Asahi Biomet
Asahi Kasei will exclusively develop and commercialize PREOB autologous bone cell
therapy in Japan for the treatment of osteonecrosis of the hip and potential future
orthopaedic applications.
 BONESUPPORT,
Zimmer Biomet
An extended U.S. distribution agreement allows Zimmer Biomet to continue its exclusive
rights for CERAMENT BONE VOID FILLER products for orthopaedics, trauma and
foot/ankle indications.
 DePuy Synthes,
Orthocell
Under terms of a research collaboration agreement, a joint multi-center Australia study
of Ortho-ATI stem cell treatment for tendon and ligament regeneration commenced
in 1Q17.
 LifeLink Tissue Bank,
HCT Regenerative
LifeLink Tissue Bank will provide allografts to treat sports, orthopaedic and spine injuries
to HCT Regenerative, for distribution in Taiwan. HCT, established in 2016, is the first
company in Taiwan to process human tissue into regenerative biomaterials for
clinical use.
 Seikagaku, Ono
Pharmaceutical
Co-development and marketing collaboration in Japan for SI-613 for the treatment of
osteoarthritis.
 Vericel, Orsini
Pharmaceutical
Two-year renewable agreement for distribution of Carticel and MACI in the U.S. and
Puerto Rico.
 Vericel, Innovative
Cellular Therepeutics
 Innovative Cellular Therapeutics gained exclusive rights to develop and distribute Carticel
and MACI in Southeast Asia.

 

Of the 34 transactions that we’ve reported to date this year, orthobiologics were involved in eight. Exhibit 3 shows where dollars were spent.
Exhibit 3: Funding Activity

 Amend Surgical Funding agreement with The Florida Institute for the Commercialization of Public
Research addressing newly-licensed technology developed at the University of
Florida, in support of products for the bone graft substitute market.
 ASC Biosciences Partnered with Stem Cell Development Fund to receive $1.5MM to support
development and marketing of its Multipotent Adult Stem Cell platform.
 BONESUPPORT  Commenced trading as BONEX on Nasdaq Stockholm following completion of its
IPO.
 Carmell Therapeutics  Closed a $4MM Series B financing in support of Phase III clinical development of
its Bone Healing Accelerant.
 Cerapedics  Closed a $20MM senior secured term loan that will support commercialization of
i-FACTOR bone graft for ACDF and fund an FDA study on its application in TLIF.
 DiscGenics  Closed a $14MM Series B financing to support regulatory approvals and
manufacturing ramp-up for Phase III clinical and commercial production
of its cell therapy for treatment of degenerative disc disease.
 Hyalex Orthopaedics  Raised $16MM in a Series A financing. Hyalex is developing HYALEX synthetic
polymer that is designed to mimic hyaline cartilage, to potentially replace only
diseased areas of joints while sparing healthy bone.
 Providence Medical Technology  Closed a $10.5MM debt agreement that will support distribution of cervical fusion
technology in U.S. and ex-U.S. markets.

 

Clinical data on the cost/benefit of orthobiologic treatments is required to gain product clearance and adoption. This last section details clinical trials and studies.

Hip/Knee

Andrews Institute for Orthopaedics & Sports Medicine and the Andrews Research & Education Foundation are facilitating a randomized, multi-center Phase II U.S. FDA-observed clinical trial evaluating use of a patient's own stem cells to regenerate knee cartilage. This is reportedly the first time that stem cells will be evaluated in a clinical trial for the ability to regenerate cartilage in massive knee cartilage injuries. The 6-year study may end early if results indicate statistical significance.

Studies indicate that Anika Therapeutics’ HYALOFAST scaffold + autologous adult MSCs present a viable option to treat knee cartilage lesions, regardless of patient age.

Phase III study results demonstrated that Anika’s CINGAL provided superior immediate and short term OA pain relief after injection vs. hyaluronic acid alone, and superior relief at 26 weeks vs. saline.

Bone Therapeutics completed patient recruitment for interim analysis in its Phase III trial of PREOB for the treatment of hip osteonecrosis.

Results from Phase I and Phase II study indicate that Histogenics NeoCart tissue-engineered implant is a safe, effective treatment for articular cartilage lesions through 5-year follow-up.
Spine

Results from ovine study of Bio2 Technologies’ Vitrium bioactive glass demonstrated the device’s capability to support interbody fusion.

Interim results in a Phase IIA trial with Bone Therapeutics’ ALLOB showed evidence of successful spinal fusion and statistically significant improvements at 12 months.

Burst Biologics received IRB approval for a U.S. prospective clinical study of BioBurst cellular allograft in spinal fusion.

Follow-up data from an IDE clinical trial of Cerapedics’ i-FACTOR bone graft indicated statistical superiority to autograft in ACDF.

FDA accepted DiscGenics’ Investigational New Drug Application for a clinical study of its cell therapy product candidate to treat degenerative disc disease.

Medtronic launched a long-term global clinical study to collect prospective data on INFUSE bone graft in posterolateral and transforaminal lumbar interbody fusion.

Studies suggest that a single injection of Mesoblast’s Mesenchymal Precursor Cells resulted in meaningful improvements in chronic low back pain and function that were durable for at least 3 years.

SpinalCyte announced the first injection in a clinical trial of CybroCell fibroblasts for spinal disc regeneration.
Trauma

Bone Therapeutics reported positive interim efficacy results and early conclusion of the Phase I/IIA study of ALLOB allogeneic bone cell therapy in the treatment of delayed-union fractures. Given the close relationship between the delayed-union and non-union indications, the company will also cease recruitment in the PREOB non-union trial to focus resources on ALLOB.

BONESUPPORT enrolled the first patient in the pivotal Investigational Device Exemption trial of CERAMENT G in the surgical repair of open diaphyseal tibial fractures.

Carmell Therapeutics will launch a Phase III clinical study for Bone Healing Accelerant, its first Plasma-based Bioactive Material product/indication, designed to treat fractures.

Interim results from study of PolyPid’s BonyPid-1000 bone substitute in the treatment of open tibial fractures indicate that the product met performance and safety endpoints in first patients at 6 months.
Soft Tissue Repair

MiMedx commenced a Phase III study to evaluate AmnioFix Injectable allograft vs. placebo in the treatment of Plantar Fasciitis.

Orthocell announced recruitment of the first patient in a clinical trial investigating Ortho-ATI to treat rotator cuff tendinopathy.

Six-month results from Phase I/II study indicate that RepliCel’s RCT-01 fibroblasts demonstrated product safety and clinical potential for tendon regeneration and healing.

Interim study results indicate that patients receiving Rotation Medical’s Bioinductive Implant to treat rotator cuff disease reported statistically significant improvement at six months. Earlier results indicated inducement of new tissue formation in all study participants with large and massive rotator cuff tears.
Julie A. Vetalice is ORTHOWORLD’s Editorial Assistant. She can be reached by email.

Tags: M&A