Because we expect sales of vonapanitase, if
approved, to generate substantially all of our product revenues for the foreseeable future, the failure of vonapanitase to gain
market acceptance would harm our business and would require us to seek additional financing.
Vonapanitase or any additional product candidates, if approved,
may face significant competition and our failure to effectively compete may prevent us from achieving significant market penetration
The biotechnology and pharmaceutical industries
are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. We face
potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical, biotechnology and
medical device companies, academic institutions, governmental agencies and public and private research institutions. While we believe
that vonapanitase’s features, safety and efficacy will differentiate it from any competitive products that may become available
in the future, we expect to face potential competition from many different sources, including larger and better-funded pharmaceutical,
specialty pharmaceutical and biotechnology companies and medical device companies, as well as from academic institutions and governmental
agencies and public and private research institutions that may develop potentially competitive products or technologies.
Some of our competitors have significantly greater
financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials,
obtaining regulatory approvals, marketing and selling approved products than we do. Smaller or early stage companies may also prove
to be significant competitors, particularly through collaborative arrangements with large and established companies.
The key competitive factors affecting the success
of vonapanitase, if approved, are likely to be its efficacy, safety, convenience, price, and the availability of reimbursement
from government and other third-party payors. Our commercial opportunity could be reduced or eliminated if our competitors develop
and commercialize products that are safer, more effective, more convenient or less expensive than any products that we may develop.
Our competitors may also obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for
We are not aware of products approved in the
United States or Europe that would compete with vonapanitase for the improvement of secondary patency and fistula use for hemodialysis.
We are aware of companies with therapies in development including Vascular Therapies, Enceladus Pharmaceuticals, Symic Biomedical,
Aplagon, and Athera Biotechnologies, as well as companies developing vascular access technologies, including BioConnect Systems,
Avenu Medical, Phraxis, Brookhaven Medical, Laminate Medical Technologies, Stent Tek and TVA Medical. Other technologies in development
include new synthetic grafts, including those that may be developed by companies that currently compete in the graft market, such
as W.L. Gore, C.R. Bard and Maquet, as well as tissue engineered grafts, including those in development by Cytograft and Humacyte.
Finally, vonapanitase’s commercial success could be affected by the development of technologies to improve the outcomes of
interventions to restore patency, including stents, stent grafts and drug-coated balloons.
Vonapanitase, or any additional product candidates for which
we seek approval as biologic products, may face competition sooner than anticipated.
The enactment of the Biologics Price Competition
and Innovation Act of 2009, or BPCIA, as part of the ACA, created an abbreviated pathway for the approval of biosimilar and interchangeable
biological products. The abbreviated regulatory pathway establishes legal authority for the FDA to review and approve biosimilar
biologics, including the possible designation of a biosimilar as “interchangeable” based on its similarity to an existing
brand product. Under the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12 years after the
original branded product was approved under a BLA. Certain changes, however, and supplements to an approved BLA, and subsequent
applications filed by the same sponsor, manufacturer, licensor, predecessor in interest, or other related entity do not qualify
for the 12-year exclusivity period.
The BPCIA is complex and is still being interpreted
and implemented by the FDA. ACA is also facing increased scrutiny by legislators. As a result, the ultimate impact, implementation,
meaning and continued effectiveness of BPCIA are subject to uncertainty. While it is uncertain when such processes intended to
implement the BPCIA may be fully adopted by the FDA or whether any aspects of BPCIA may change, any such processes or changes could
have a material adverse effect on the future commercial prospects for our biological products.