ENGLEWOOD, Colo., June 2, 2022
/PRNewswire/ -- Ampio Pharmaceuticals, Inc. (NYSE American: AMPE),
a biopharmaceutical company focused on the advancement of
immunomodulatory therapies for the treatment of pain resulting from
osteoarthritis in the knee and potentially other articular joints,
today released the following letter to stockholders from its Chief
Executive Officer, Mike Martino.
Dear Fellow Stockholders,
On behalf of the board and management team, we appreciate the
support and patience you have demonstrated over the last several
weeks. The purpose of this letter is to answer the questions we can
currently answer in the context of our previously announced process
to evaluate strategic alternatives for Ampion™ and Ampio. It is
important to note that we won't comment about the earlier
announcements regarding personnel and governance changes.
Additionally, this letter does not address the previously announced
internal investigation, which is ongoing. We know these questions
are top of mind for many investors, but we simply cannot speak
about these issues at the present time.
I would like to start with AP-013, a randomized,
saline-controlled, double-blind Phase 3 clinical study evaluating
the efficacy of an intra-articular injection of Ampion™ in adults
with pain due to severe osteoarthritis of the knee ("AP-013") and
key steps we are taking to determine if it's appropriate to conduct
an additional trial or set of trials. Let's start with the evidence
we have reviewed from the trial results. Compared to baseline,
Ampion-treated patients have shown clear evidence of reduction of
pain and improvement in function as early as 2 weeks after dosing
which lasted up to 24 weeks. However, the saline control that
Ampion was evaluated against in AP-013 and earlier trials is an
active control, not a placebo, and it showed benefit as well. As a
result, the pre-specified intent-to-treat population analysis of
AP-013 did not demonstrate a statistical benefit of Ampion when
compared with saline on either pain or function over the 12-week
efficacy analysis period. According to the agreed upon Special
Protocol Assessment ("SPA") with the United States Food and Drug
Administration ("FDA"), the AP-013 trial was required to
demonstrate a statistical benefit of Ampion when compared with
saline on both endpoints (i.e., pain and function).
Additionally, while the per-protocol analysis of AP-013 was
initially encouraging, additional scrutiny of the data and
methodology supporting the analysis showed that the per protocol
analysis was flawed. In particular, that analysis
disproportionately captured the best performers from the
Ampion-treated population and the worst performers from the
saline-treated population. This is purely the result of applying
the major protocol deviation criteria included in the protocol.
However, the resulting per protocol analysis cannot be used as a
basis for submission of a biologics license application to FDA.
On the positive side, we have reconfirmed that the AP-003-A
trial, which reflected an enrollment of 329 symptomatic
moderate-severe osteoarthritis of the knee (OAK) patients,
demonstrated a statistically significant decrease in pain at 12
weeks compared to saline (p=0.004). Additionally, Key Opinion
Leaders we've consulted with remain optimistic about the potential
for designing a clinical trial that can show a beneficial effect,
but there are obviously challenges that will need to be evaluated
and weighed against other potential strategies available for Ampion
and Ampio as a company.
We now have data in more than 1,500 Ampion-treated participants,
and a like number of saline-treated patients, and we are merging
all the data into a meta-analysis to inform potential designs for
any future trial that we may conduct. We believe this will increase
the probability of designing a trial in which Ampion may achieve a
statistically significant benefit, and all design elements of the
trial are currently under review, including endpoints, the
statistical analysis plan, inclusion/exclusion criteria, improved
subjective methods for evaluating pain at baseline, and trial
monitoring and reporting elements.
It is also important to remember that AP-013 was intended as a
confirmatory trial to AP-003-A. If our trial design is
substantially different from our previous trials, we may be
required to perform two pivotal trials.
Additionally, the trial may need to be conducted under a Special
Protocol Assessment (SPA) with FDA, with an agreed to statistical
analysis plan. Until we gain more regulatory clarity, partnership
discussions are understandably on hold. However, several potential
partners have indicated their willingness to re-engage once we gain
that clarity. The potential need for two pivotal trials, the
regulatory pathway, and partner interest are among the top factors
that we are considering as we evaluate our strategic
alternatives.
Moving on to the COVID-19 program. As reported in May, we have
found no clinically meaningful treatment effect signals from the
Company's three COVID-19 clinical trials; AP-017, AP-018 and
AP-019. In other words, we were unable to detect a statistically
significant difference between Ampion and placebo for the primary
endpoints of the trials, which were mortality and time to
mechanical ventilation. Signs of potential Ampion benefit were seen
in a few prespecified secondary endpoints. However, most of the
secondary endpoints did not show a treatment benefit.
How did we go from "positive results" for inhaled Ampion in the
40-patient AP-014 trial to "no signal" in these trials? In general,
small exploratory studies may show a large treatment effect because
of the small denominator and should always be viewed as hypothesis
generating rather than definitive. Historically, across all drug
development categories, only a minority of phase 2 trials can be
confirmed in larger phase 3 trials. This is the reason why FDA
requires two successful pivotal phase 3 trials. Specific to Ampion,
the AP-019 trial enrolled 129 participants and could not show a
beneficial effect of Ampion compared with placebo as only 3 deaths
or progression to respiratory failure occurred (the original
primary endpoint). The AP-017 trial which studied intravenous
Ampion compared with placebo enrolled only 35 participants and had
a very slow enrollment rate. We determined that the evolving
treatment landscape combined with the reduced incidence and
severity of COVID had significantly curtailed our ability to enroll
the required 200 subjects and, as such, the trial was closed
because of the projected time to completion and financial
commitment. AP-018 was a small Phase 1 study to document safety
that enrolled 32 patients and failed to show a benefit.
Given these results and the changing Covid treatment landscape,
we believe it would be an unwise use of investor funds to continue
the COVID-19 program at this time. As a reminder, AP-017 and AP-019
were initiated on the premise they might support an Emergency
Medical Use Authorization (EMUA) in what was then a bleak landscape
for Covid treatments. However, several treatments have recently
been approved for the treatment of COVID-19, including antibodies
that inactivate the SARS-cov-2 virus that causes Covid, as well as
drugs that prevent viral replication, and corticosteroids that have
demonstrated a reduction in the severity of the disease.
Additionally, the prevalence of vaccines and multi-shot vaccination
protocols and the diminishing severity of emerging variants of
Covid-19, such as Omicron, have all converged to confer immunity
and reduce the number of ICU patients requiring respiratory
support. These developments make Covid prevention and treatment a
very crowded competitive space in which Ampion simply hasn't
demonstrated sufficient benefits to be competitive.
I would like to highlight the following positive takeaways which
should not be minimized. We now know that nebulized (inhaled)
Ampion has an excellent safety profile, which can potentially open
up additional target indications that involve lung inflammation
which are potentially more promising than COVID-19. Additionally,
we have been issued four significant patents in the space. If, how
or when we continue to pursue development of Ampion for treatment
of respiratory inflammation has yet to be determined; although, I
can say it is not a near term project or priority.
Turning briefly to the financials, as of March 31, 2022, we had $28.8 million of cash and cash equivalents. We
will be burning $1.2-$1.3 million per month through September 2022 primarily due to required
close-out costs for all prior trials, both OAK and COVID-19
related. After September 2022, we
project a burn rate of approximately $1.0
million per month, which we will seek to trim further
(though as previously mentioned, Ampio is a very lean
organization). Based on our current cash position and projection of
operating expenses and capital expenditures, we believe we will
have sufficient liquidity to fund operations into the second half
of 2023. However, this estimate does not include the cost of
funding new trials or programs or any other strategic alternatives
nor any expense reductions. Rest assured we will be taking a very
hard look at any additional expenses prior to committing to
them.
To conclude, we are working diligently to evaluate all options
to deliver value for stockholders, including but not limited to,
additional trials for Ampion, evaluating other opportunities in our
pipeline, leveraging our bioprocessing capability, and considering
business development opportunities. We look forward to providing
you future updates as our evaluation of these alternatives
continues.
About Ampio Pharmaceuticals, Inc.
Ampio Pharmaceuticals, Inc. is a biopharmaceutical company
primarily focused on the advancement of immunology-based therapies
for the potential treatment of multiple inflammatory conditions
(e.g., osteoarthritis of the knee (OAK) and other articular
joints). Ampio's lead drug is Ampion™.
Forward-Looking Statements
This press release contains forward-looking statements that are
made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995. Any statements contained
in this press release that are not statements of historical fact
may be deemed to be forward-looking statements. Without limiting
the foregoing, words such as "may," "will," "expect," "believe,"
"anticipate," or "estimate" or comparable terminology are intended
to identify forward-looking statements. Forward-looking statements
are subject to various risks and uncertainties that could cause
actual results to differ materially from those expressed or implied
in such statements.
Such forward-looking statements include, for example, statements
about Ampio's projection of operating expenses, capital
expenditures and future liquidity. The risks and uncertainties that
could cause actual results to differ materially from those
expressed or implied in these forward-looking statements include
the risk factors described in the Ampio's Annual Report on Form
10-K for the year ended December 31,
2021, and other factors set forth in Ampio's filings with
the Securities and Exchange Commission, including Ampio's Quarterly
Report on Form 10-Q for the quarter ended March 31, 2022.
The forward-looking statements in this press release speak only
as of the date of this press release. Except as required by law,
Ampio assumes no obligation to update or revise these
forward-looking statements for any reason, except as required by
law.
Investor and Media Contacts:
Tony Russo or Nic Johnson
Russo Partners
info@ampiopharma.com
tony.russo@russopartnersllc.com
nic.johnson@russopartnersllc.com
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SOURCE Ampio Pharmaceuticals, Inc.