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 ours.
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, Fist Assist, 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.
We believe that vonapanitase,
or any additional product candidates approved as a biological product under a BLA, should qualify for the BPCIA’s 12-year
period of exclusivity. However, there is a risk that BPCIA will be repealed or amended, or the FDA will not consider vonapanitase
or any additional product candidates to be reference products for competing products, potentially creating the opportunity for
generic competition sooner than anticipated.
period of regulatory exclusivity does not currently apply to companies pursuing regulatory approval via their own traditional BLA,
rather than via the abbreviated pathway. Moreover, the extent to which a biosimilar, once approved, will be substituted for any
one of our reference products in a way that is similar to traditional generic substitution for non-biological products is not yet
clear, and will depend on a number of marketplace and regulatory factors that are still developing. It is possible that payers
will give reimbursement preference to biosimilars even over reference biologics absent a determination of interchangeability.