BioCardia, Inc. (Nasdaq: BCDA), a clinical-stage developer of
cellular and cell-derived therapeutics for the treatment of
cardiovascular and pulmonary diseases issued the following letter
to shareholders:
Dear Shareholders,BioCardia is now advancing four novel cell
therapies, with three focused on heart disease, a leading cause of
death and reduced quality of life globally. The Phase III trial of
our lead therapy - CardiAMP® autologous cell therapy for ischemic
heart failure (BCDA-01) – continues to enroll in the U.S. and
Canada, and data published to-date is showing improved functional
capacity and quality of life in treated patients. Most encouraging
is the combined mortality rate across the Phase I, II and III trial
data available, which is <3% per year, exceptional in a
landscape where leading pharmaceutical solutions are showing
mortality that is 3x higher. The FDA has supported this promise by
granting Breakthrough Device Designation to CardiAMP cell therapy
in this indication.
We have embarked on a Phase III trial of CardiAMP autologous
cell therapy in a second indication addressing chronic myocardial
ischemia (BCDA-02), and this year received IND approval from the
FDA to study two allogeneic product candidates, both leveraging
Neurokinin-1 receptor positive (NK1R+) allogeneic mesenchymal stem
cells – BCDA-03 for ischemic heart failure and BCDA-04 for acute
respiratory distress syndrome (COVID-induced ARDS). The NK1R+ cells
are particularly interesting as NK1 is the primary receptor for
Substance P, an important neuropeptide mediator of inflammation
which plays a central role in both heart failure and regenerative
processes following myocardial injury.
No cardiac cell or gene therapy has yet made it to market and we
are aware that this has created a level of skepticism about the
prospects for cardiac cell therapy in general. Why do we believe
BioCardia will succeed where others have failed? 1) our approach
does not rely on stem cells transforming into heart cells and
integrating electrically with the heart cells to enhance
contractile function but instead is designed to leverage the body’s
own healing mechanisms to help the heart recover from damage, 2)
CardiAMP cell therapy incorporates a proprietary screening assay to
identify likely responders based on previous clinical studies,
which is something no other known cardiac cell therapy has
utilized, 3) CardiAMP cell therapy Phase I, Phase II, and Phase III
roll in data has shown strong signals of patient benefit, and 4)
all of our cardiac cell therapies are delivered using our proven
and proprietary Helix™ transendocardial biotherapeutic delivery
system, which publications and internal reports show to be the
safest and most efficient delivery system for cell therapy delivery
to the heart, and in use preclinically and clinically by other
leading cell, gene and protein-based biotherapeutic programs to
deliver their therapies.
Your support of BioCardia has enabled our work and I am pleased
to provide you with an update on our progress in 2022 and our
perspective on what is ahead for 2023.
2022 ACCOMPLISHMENTS
One year ago, we set out important milestones across our four
therapeutic programs for 2022 and accomplished most of what we set
out to do:
Program |
2022 Milestone |
Status |
BCDA-01 CardiAMP Autologous Cell Therapy in Ischemic Heart
Failure |
Successful Data Safety Monitoring Board reviews in February and
August. |
Achieved |
BCDA-02 CardiAMP Autologous Cell Therapy in Chronic Myocardial
Ischemia |
First safety data. |
First patient has been enrolled and is seeing significant
improvement. Three additional patients have recently been
consented. In screening we are seeing a high exclusion rate
hindering enrollment and are planning to modify the protocol to
improve this before going into the randomized
phase. |
BCDA-03 NK1R+ Allogeneic Mesenchymal Cell Therapy IND in Ischemic
Heart Failure |
FDA Investigational New Drug Application Approval. |
Achieved |
BCDA-04 NK1R+ Allogeneic Mesenchymal Cell Therapy in Acute
Respiratory Distress |
FDA Investigational New Drug Application Approval. |
Achieved |
A year of regulatory successes While BioCardia
is a small company, we have had positive momentum this year with
the Food and Drug Administration (FDA), the Center for Medicare and
Medicaid Services (CMS) and the Office of the Inspector General at
Health and Human Services (OIG HHS).
CardiAMP autologous cell therapies - BCDA-01 and BCDA-02
- The FDA Center for Biologics Evaluation and Research (CBER)
granted the CardiAMP Cell Therapy Breakthrough Designation to
BCDA-01 after a review of all our clinical data, effectively
agreeing that this therapy has potential to be a significant
advance for patients with ischemic heart failure.
- The OIG HHS agreed with our position to provide support for
patient required co-payments in the CardiAMP Phase III Trial. We
implemented this because it was the right thing to do for our
patients, particularly those with limited financial means.
- Health Canada granted approval of an Investigational Testing
Authorization (ITA) for the CardiAMP Heart Failure trial and
provided us with a “No Objection Letter” on a Clinical Trial
Authorization (CTA) to expand the trial into Canada.
- CMS granted a reimbursement code for CardiAMP autologous cell
therapy (encompassing both BCDA-01 and BCDA-02 therapies) to cover
procedure and product costs up to $20,000 in both of our Phase III
clinical trials for heart failure and chronic myocardial ischemia.
We sought this to provide our clinical partners with an easier
pathway to reimbursement from CMS that allows them to focus their
efforts on the clinical aspects of the study rather than on getting
cases covered.
NK1R+ MSC allogeneic cell therapies - BCDA-03 and BCDA-04
- FDA CBER approved our Investigational New Drug (IND)
Application for our allogeneic Neurokinin-1 receptor positive
(NK1R+) mesenchymal stem cell therapy for the treatment of Acute
Respiratory Distress. These are “off the shelf” cells from younger
donors intended to be expanded to produce many doses for many
patients.
- FDA CBER also approved our IND to study our allogeneic NK1R+
MSC to treat heart failure patients ineligible for CardiAMP therapy
in the CardiALLO Phase III Trial. Physicians have expressed
enthusiasm at the prospect of a cell therapy procedure that is
easier to perform than autologous therapy and utilizes “off the
shelf” cells from young, healthy donors rather than an older
patient’s own cells. We view this allogeneic therapy as a promising
option for the 30% of heart failure patients whose cells are
ineligible for autologous CardiAMP therapy.
In addition, in December, European Council members expressed
support for a proposal to the European Commission to delay the
transitional deadlines for medical devices under the Medical
Devices Regulation (MDR). This is good news for BioCardia as it is
expected to extend the commercial availability of our CE Marked
Helix biotherapeutic delivery platform as we work to transition to
the MDR.
Certification for Cell Therapy and Device
Manufacturing Throughout the course of the year other
government agencies, both local and federal, certified our new
medical device manufacturing and cellular therapy manufacturing
facilities in our new Sunnyvale location. BioCardia is now licensed
to manufacture both devices and drugs in this new facility and is
currently manufacturing allogeneic cell therapy in preparation for
our trials. This capability underlies our clinical stage programs
and reduces our operational cost.
Phase III CardiAMP Heart Failure Trial Remains a
Focus Although our number-one priority is always patient
safety, patient enrollment in our lead heart failure program is a
very close second. In 2022, we saw encouraging activity intended to
positively impact enrollment moving forward.
- Data looks good - The August 2022 DSMB review
of 115 enrolled and 10 crossover patients was positive, noting no
safety issues. Available aggregated blinded results showed patients
having meaningful improvements on average across both treated and
control patients, which is remarkable in a trial where patients
typically decline over time. Aggregate survival rate for patients
reaching one-year follow-up, including both treated and control
patients, was observed to be greater than that seen in a recent
large pivotal trial of a new approved heart failure
drug.
- Canadian sites gearing up - Three of the four
trial sites initially targeted in Canada have completed their site
initiation visits and we are looking forward to their contribution
to enrollment ahead. Note that Canada does not have the
reimbursement requirements we have in the U.S. so we will not
experience reimbursement-related barriers in these sites that we
faced to-date.
- Patient education expanded – Clinical sites
have faced challenges enrolling the trial as patients are eager to
receive CardiAMP therapy and are not enthusiastic about the
potential of being randomized to the control group. We have
enhanced our patient education portal - www.CardiAMP.com – to
better explain the opportunity for control patients to crossover to
CardiAMP treatment at two years and to feature actual trial
patients and investigators sharing their positive experiences. We
are thankful for each of these voices of experience. Everyone who
knows someone with heart failure can visit this website and
understand our efforts better.
- Adaptive statistical analysis recommended by
DSMB - The DSMB recommended implementing an adaptive
statistical analysis plan (SAP), which attempts to determine the
appropriate number of patients needed in a clinical trial to meet
the primary endpoint based on the data within the trial itself as
opposed to data from a previous trial. This data
reviewed by the DSMB is based on an ongoing study and has not been
fully monitored or verified. Should a future DSMB review include an
adaptive statistical analysis plan, it could result in the DSMB
being able to recommend the trial enrollment be stopped early for
anticipated success with fewer patients or confirmation the study
should continue as planned to the next DSMB review. Our Phase II
results showed that the Phase III CardiAMP Cell Therapy in Heart
Failure trial would have a 90 percent chance of meeting its primary
endpoint with 86 patients1. However, the Phase III was designed
with 250 patients randomized to address potential greater
variability in clinical measures in a larger trial, potential loss
of patients to follow-up, and to provide sufficient safety data to
support FDA approval. We have observed from the available aggregate
unmonitored blinded data at the recent DSMB review that there was
less variability than we have seen in the Phase II trial at
important baseline measures, and few patients appear to have been
lost to follow-up. Should we meet the primary endpoint with fewer
patients, the FDA Breakthrough designation granted to this program
may reduce the need to have a significant additional number of
patients to demonstrate safety prior to market approval and allow
BioCardia to obtain additional safety data post market
approval.
Closing of $3.6 Million Financing BioCardia
successfully closed a $3.6 million financing in December. The
financing included insider participation alongside new and existing
life sciences institutional investors enthusiastic about what lies
ahead for the company in 2023. This financing extends our runway in
advance of anticipated 2023 progress.
2023 PLANS
CardiAMP Phase III Trial DSMB Review Has Potential for
Significant Impact An adaptive SAP design is well underway
using a Bayesian approach and we anticipate looking at the
operating characteristics for the design in early January with an
FDA “sprint discussion” afforded under the breakthrough designation
to follow. In parallel, we anticipate all data that contributes to
the primary efficacy endpoint in the study submission to have been
monitored by our very capable clinical research staff verifying all
clinical data required for interpretation. While we expect this
will all be in place for a DSMB review in Q2 2023, there are also
no guarantees we will be able to implement such a plan or that
implementation of such a plan will result in an early end to the
clinical trial for efficacy at of the future DSMB
review.
Potential for CardiAMP Heart Failure Trial Enrollment
Improvements We expect 2022 work on the regulatory and
reimbursement fronts, activation of the trial in Canada, and
enhanced patient education efforts to have a positive impact on
enrollment in 2023. We also intend to publish and present new data
from the CardiAMP HF Trial designed to further influence referrals
to the trial among heart failure specialists. To this point, we
have seen some reluctance among these specialists concerned about
losing control of patients to physicians in the trial, expressing
the aforementioned skepticism about cell therapy, and feeling that
the new heart failure drugs available will adequately serve their
patients. We feel that the following peer-reviewed data will
further support enhanced enrollment:
- A presentation entitled: “Cardiac Remodeling After
Intramyocardial Autologous Bone Marrow Mononuclear Cell Therapy for
Ischemic Cardiomyopathy: 2-year Echocardiography Results from the
CardiAMP Cell Therapy Heart Failure Trial Open-Label Roll-In
Cohort” has been accepted for presentation at the American College
of Cardiology annual meeting in March 2023.
- Clinical manuscripts in the works designed for publication in
peer reviewed journals: (1) two-year results from the roll-in
cohort of the CardiAMP Heart Failure Trial previously presented at
Heart Failure Society of America conference, (2) an explanation of
our clinical results relative to current therapies and why this
supports our FDA Breakthrough Designation, and (3) a review of the
clinical trials to date on intramyocardial autologous mononuclear
cell therapy, showing consistent benefits for patients with
ischemic cardiomyopathy on average, despite the fact that many of
these results did not reach statistical significance.
Regulatory Efforts for CardiAMP Cell Therapy in
Japan In 2023, we intend to submit for regulatory approval
of CardiAMP cell therapy in Japan. We plan to prioritize pursuit of
a petition for a special designation as a highly needed medical
therapy from a leading Japanese clinical society to the Ministry of
Health Labor and Welfare to support enhanced reimbursement and
regulatory approval. Should the special designation not be granted,
we will pursue regulatory approval through a traditional
pathway.
Business Development Keeps MovingOn the heels
of our 2022 deal with BlueRock Therapeutics to provide our Helix
delivery system for their therapeutic development efforts, we are
discussing partnerships with leading biopharmaceutical firms where
BioCardia may benefit from licensing fees and milestones during
development, as well as a percentage of sales once those therapies
enabled by our delivery products are commercial. In parallel to our
efforts to achieve regulatory approval in Japan, we are in
discussions with potential distribution partners in Japan which, if
finalized, could lead to commercial revenue.
Allogeneic Cell Therapy Clinical ProgramsNow
that we have both INDs approved by FDA and clinical-grade cells
manufactured in our facility, the next milestones for our
allogeneic NK1R+ mesenchymal stem cell indications of heart failure
(BCDA-03) and acute respiratory distress (BCDA-04) involve treating
the first patients in these studies. For the acute
respiratory distress indication, we are actively completing the
clinical site start-up phase of aligning on patient informed
consent, clinical study agreement, and budget which we anticipate
completing for at least one site in the weeks ahead. Even as we
make progress on these new programs, our priority is our BCDA-01
CardiAMP cell therapy program based on the positive data we are
seeing and the Breakthrough designation that has potential to
accelerate our regulatory and commercial efforts.
I am tremendously proud of the BioCardia team and its clinical
partners for the regulatory, reimbursement and clinical progress we
have made over the last year. The coming year offers the potential
for catalysts that could dramatically improve our prospects,
timetable, and attractiveness as a business. We are excited about
what the future holds and are grateful for the opportunity in front
of us to create an entirely new class of heart failure treatments
and transform cardiovascular and pulmonary care. Thank you for your
continued support, which makes everything we do possible.
Sincerely yours,
Peter A. Altman, Ph.D.
President and Chief Executive Officer, BioCardia, Inc.
Forward Looking Statements This press release
contains forward-looking statements that are subject to many risks
and uncertainties. Forward-looking statements include, among other
things, references to regulatory discussions in Japan, additional
sites participating in the Company’s clinical trials, the efficacy
and safety of our products and therapies, preliminary conclusions
about new data, the achievement of any of the anticipated upcoming
milestones, statements regarding our intentions, beliefs,
projections, outlook, analyses or current expectations. Such risks
and uncertainties include, among others, the inherent uncertainties
associated with developing new products or technologies, regulatory
approvals, unexpected expenditures, the ability to raise the
additional funding needed to continue to pursue BioCardia’s
business and product development plans, the ability to enter into
licensing and partnering arrangements, and overall market
conditions. We may find it difficult to enroll patients in our
clinical trials due to many factors, some of which are outside of
our control. Slower than targeted enrollment could delay completion
of our clinical trials and delay or prevent development of our
therapeutic candidates. These forward-looking statements are made
as of the date of this press release, and BioCardia assumes no
obligation to update the forward-looking statements.
We may use terms such as “believes,” “estimates,” “anticipates,”
“expects,” “plans,” “intends,” “may,” “could,” “might,” “will,”
“should,” “approximately” or other words that convey the
uncertainty of future events or outcomes to identify these
forward-looking statements. Although we believe that we have a
reasonable basis for each forward-looking statement contained
herein, we caution you that forward-looking statements are not
guarantees of future performance and that our actual results may
differ materially from the forward-looking statements contained in
this press release. As a result of these factors, we cannot assure
you that the forward-looking statements in this press release will
prove to be accurate. Additional factors that could materially
affect actual results can be found in BioCardia’s Form 10-K filed
with the Securities and Exchange Commission on March 29, 2022,
under the caption titled “Risk Factors.” BioCardia expressly
disclaims any intent or obligation to update these forward-looking
statements, except as required by law.
Media Contact: Anne Laluc,
MarketingEmail: alaluc@BioCardia.comPhone: 650-226-0120
Investor Contact: David McClung, Chief
Financial OfficerEmail: investors@BioCardia.comPhone:
650-226-0120
_________________________________
1 Raval 2018.
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