In the future we intend to pursue additional
indications such as the application of vonapanitase in brachiocephalic fistula creation and/or patients undergoing placement of
an arteriovenous graft and/or patients with symptomatic PAD. As a result, we may forego or delay pursuit of opportunities with
other product candidates or for other indications that may prove to have greater commercial potential. Our resource allocation
decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending on
current and future research and development programs and product candidates for specific indications may not yield any commercially
viable products. If we do not accurately evaluate the commercial potential or target market for a particular product candidate,
we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases
in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate.
Even if we obtain and maintain approval for vonapanitase or
additional product candidates from the FDA, we may never obtain approval for vonapanitase or additional product candidates outside
of the United States, which would limit our market opportunities and adversely affect our business.
Even if we obtain approval of a product candidate
in the United States from the FDA, such approval does not ensure approval of that product candidate by regulatory authorities in
other countries or jurisdictions, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities
in other foreign countries or by the FDA. Sales of vonapanitase or any additional product candidates outside of the United States
will be subject to foreign regulatory requirements governing clinical trials and marketing approval. Even if the FDA grants marketing
approval for a product candidate, comparable regulatory authorities of foreign countries must also approve the manufacturing and
marketing of the product candidate in those countries. Approval procedures vary among jurisdictions and can involve requirements
and administrative review periods different from, and greater than, those in the United States, including additional preclinical
studies or clinical trials. In many countries outside the United States, a product candidate must be approved for reimbursement
before it can be approved for sale in that country. In some cases, the price that we intend to charge for our products, if approved
for sale, is also subject to approval. Moreover, the failure to obtain approval in one jurisdiction may negatively impact our ability
to obtain approval in another jurisdiction.
Based on additional data including the data
from our Phase 3 clinical trials and assuming sufficient funds become available, we plan to commence a clinical trial of vonapanitase
in Europe for patients undergoing creation of radiocephalic fistulas. Prior to enrolling our first patient in Europe, we plan to
formally seek guidance from the EMA regarding its requirements for regulatory approval. If a clinical trial of vonapanitase in
Europe is necessary for regulatory approval, we expect results from this trial to be available two to three years after the first
patient is enrolled. If results of this European trial successfully meet its primary endpoint and depending on the guidance obtained
from the EMA, we would expect to submit a Marketing Authorization Application, or MAA, following our receipt of the trial results.
Obtaining an approval is a lengthy and expensive process and the EMA has its own procedures for approval of product candidates.
Even if a product candidate is approved, the EMA may limit the indications for which the product may be marketed, require extensive
warnings on the product labeling or require expensive and time-consuming clinical trials or reporting as conditions of approval.
Regulatory authorities in countries outside of the United States and Europe also have requirements for approval of product candidates
with which we must comply prior to marketing in those countries. Obtaining foreign regulatory approvals and compliance with foreign
regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction
of vonapanitase or any additional product candidates in those countries.
Advertising and promotion of any product candidate that obtains
approval in the United States will be heavily scrutinized by the FDA, the Department of Justice, the Department of Health and Human
Services’ Office of Inspector General, state attorneys general, members of Congress and the public.
While the FDA does not restrict physicians from
prescribing approved drugs and biologics for uses outside of the products’ approved labeling, known as off-label use, pharmaceutical
manufacturers are prohibited from promoting and marketing their products for such uses. Violations, including promotion of our
products for off-label uses, are subject to enforcement letters, inquiries, investigations, civil and criminal sanctions by the
government, corporate integrity agreements, debarment from government contracts, debarment and exclusion from participation in
federal healthcare programs. Additionally, comparable foreign regulatory authorities will heavily scrutinize advertising and promotion
of any product candidate that obtains approval outside of the United States.