Ladies and gentlemen, thank you for standing by. Good afternoon, and welcome to the BioCardia 2023 Second Quarter Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] After today’s presentation, there will be an opportunity to ask questions.

[Operator Instructions] Participants of today’s call are advised that the audio of this conference call is being broadcast live over the internet and is also being recorded for playback purposes. A webcast replay of the call will be available approximately one hour after the end of the call through November 9, 2023.

At this time, I would like to turn the conference over to Miranda Peto of BioCardia Investor Relations. Please go ahead, Miranda..

Thank you very much. Good afternoon, and thank you for participating in today's conference call. Joining me from BioCardia’s leadership team are Peter Altman, Ph.D., President and CEO; and David McClung, the Company’s Chief Financial Officer.

During this call, management will be making forward-looking statements including statements that address BioCardia’s expectations for future performance and operational results, references to management’s intentions, beliefs, projections, outlook, analogies and current expectations.

Such factors include, among others, the inherent uncertainties associated with developing new products, technologies and obtaining regulatory approvals. Forward-looking statements involve risks and other factors that may cause actual results to differ materially from these statements.

For more information about these risks, please refer to the risk factors and cautionary statements described in BioCardia’s reports on Form 10-K filed, March 29, 2023, and the company subsequently filed quarterly reports on Form 10-Q The content of this time call contains time-sensitive information that is accurate only as of today, August 09, 2023.

Except as required by law, the company disclaims any obligation to publicly update or revise any information to reflect events or circumstances that occur after this call. It is now my pleasure to turn the call over to Peter Altman, Ph.D, BioCardia’s President and CEO. Peter, please go ahead..

Thank you, Miranda, and good afternoon to everyone on the call. BioCardia’s current efforts are focused on advancing its autologous and its allogeneic cell therapy platforms to treat significant unmet cardiovascular and pulmonary diseases, specifically ischemic heart failure, chronic myocardial ischemia, and acute respiratory distress syndrome.

All of our cell-based therapies involve local delivery of the therapeutic to the heart or lungs, where we intend them to act locally. This mission has not changed and all of these programs are still viable. We had a solid second quarter of 2023, and our team delivered on the milestones promised.

For our CardiAMP Autologous Cell Therapy and Heart Failure or BCDA-01, we implemented the adaptive statistical analysis plan with the complete FDA review. We completed our submission in Japan towards approval based on existing data, and we are finally seeing a significant increase in enrollment, including a number of patients from Canada.

For our Cardiac autologous cell therapy for chronic myocardial ischemia, we continue to make progress on enrolling in the rolling cohort in ways that we can enhance the trial. And for our cardio allogeneic cell therapy in heart failure, first patients are about to be enrolled.

BioCardia also closed on a modest financing of $2.6 million in which insiders participated, had a publication with our partner, CellProthera, on the importance of therapeutic delivery had three invited scientific presentations and advanced business development discussions. Q2 was a good quarter.

This third quarter, we were thrown a curve ball when the Data Safety Monitoring Board for the CardiAMP heart failure trial or BCDA-01 recommended we pause enrollment in the study. We have detailed the recommendation in our July 24 press release, and I will read it for you here.

"Based on an analysis of the trial data, the primary FS composite endpoint assessment and a supplemental analysis presented on 7/19/23, unrelated to any emergent safety events, the DSMB recommends pausing new patient enrollment and any potential crossover patient procedures pending an outcomes analysis of patients currently completing the one-year follow-up as well as the patients completing their imminently scheduled treatment.

The DSMB recommends notifying currently enrolled patients completing their treatment sequence that the trial will be paused following their scheduled treatment to assess intermediate study results.

The DSMB recommends the blind not be broken at this time to protect the integrity of the outcomes yet to be collected and to ensure that the study maybe restarted without compromise after completion of the one-year data analysis.” It is confusing to us, as there were no treatment emergent safety issues reported, patients in aggregate appear to be showing clinical improvement and enrollment had accelerated significantly in recent months.

We have followed the Data Safety Monitoring Board recommendation. We continue to randomize and monitor patients enrolled in this clinical study, in which both patients and evaluating physicians are blinded to the treatment group.

We need more information to decide next steps for this program, which could be to restart the trial to initiate a new trial protocol under the same regulatory submission or to abandon the program completely. Today, we don't feel that the DSMB proposal to wait for 14 months to potentially restart the trial makes any sense.

If we initiated a new trial protocol, there are changes we would like to include to simplify the performance of the trial and there are changes that the FDA has expressed interest in, including specifically a change to a different functional capacity measure for the third tier of Finkelstein Schoenfeld composite endpoint.

If there are interesting signals in the trial that support a new trial protocol with a different endpoint, our sense is we could implement this very quickly. A second trial, if it makes sense, would also address the FDA saber desire to have two separate trials for an approval.

One of our first actions on receiving the Data Safety Monitoring Board recommendations was to confirm that the Data Safety Monitoring Board review materials were correct.

The only data in the trial at this interim analysis that has been well monitored or cleaned is that for the primary composite endpoint, the survival data, the major adverse cardiac event data and the functional capacity by six-minute walk data.

We engaged independent experienced data analysis and clinical consultants to review the primary endpoint analysis and secondary outcome measures. They will be able to see the information that the DSMB reviewed as well and assess whether a follow-up meeting with the DSMB is warranted.

We have been advised to stay blinded during this process to preserve options should the data set be better with respect to the primary end points. Soon thereafter, BioCardia may have a segregated team, review the primary endpoint based on the monitor clean data and the secondary endpoints based on the available unmonitored data.

Additional sub-analyses on this interim data set will also likely take place to inform next steps. New material information will be shared publicly as appropriate.

On June -- our June submission of the CardiAMP Cell Therapy system to Japan's Pharmaceutical and Medical Device Agency, or PMDA, for a first formal consultation towards approval for the indication of ischemic heart failure with reduced ejection fraction was based on existing safety and efficacy data.

The submission was reviewed and accepted by the PMDA for formal consultation with some clarifying questions which have been addressed. The PMDA consultation could take up to four months to schedule for their normal review process although dates in September have been requested. Subsequent interactions with PMDA are expected.

To our knowledge, we have a great deal more safety and efficacy data than other cardiac cell therapies approved or reported to be seeking approval soon in Japan.

We have 185 procedures performed to-date in the Cardiac Phase 1, 2 and 3 programs with good support for efficacy from the 63 patients where we have complete visibility into the data and apparently good safety from the additional 122 procedures to which we are still blinded.

There are other compelling reasons for PMDA to support approval and that the elements of the system already have first world regulatory approvals in Japan, EU, and/or USA and the procedure is minimally invasive where other CardiAMP Cell Therapy offerings in Japan requires surgical open chest access to the heart.

If approved, the CardiAMP Cell Therapy system has potential to be the first minimally invasive catheter-based cell therapy available in Japan.

PMDA has confirmed that should we be approved other developers of cell therapies in Japan could also be unable to use our delivery systems if we authorize it ahead, such that an approval of CardiAMP Cell Therapy could be in advance to the field as a whole.

As we work through the process of gathering more information to decide next steps for the BCDA-01 program and consult with PMDA, we expect important milestones for our other clinical programs.

The CardiAMP Cell Therapy trial for chronic micron ischemia or BCDA-02 is a Phase 3 multicenter randomized double-blinded controlled study intended to include up to 343 patients at up to 40 clinical sites.

The company expects to complete enrollment in the rolling cohort of five patients in the fourth quarter of 2023 and begin the randomized phase of the trial. A number of leading investigators, including both principal investigators in this trial, believe this to be the most compelling indication for this therapy.

Planning for the randomization phase is already underway based on promising experience in the patients treated to date, strategies of using the cell population analysis as a means to set patient dosing as opposed to excluding patients and means to include more patients based on modifying baseline exclusion criteria are under consideration to enable more rapid enrollment.

Six additional centers are actively being onboarded. The company's CardiALLO allogeneic cell therapy for ischemic heart failure or BCD03 program is a Phase I/II clinical trial encompassing 69 patients.

Clinical-grade cells have been manufactured at BioCardia are ready for use with the company's proprietary delivery system, also manufactured at BioCardia. The first clinical center has finalized its clinical study agreement and received conditional IRB approval.

Cellular preparation test runs at the clinical site and the site activation vision are scheduled for this month. Patient enrollment is expected to begin in the third quarter.

This study builds on three previous trials of mesenchymal stem cells in ischemic heart failure using the company's proprietary Helix Delivery System, encompassing 93 patients treated with no treatment-emergent serious adverse events. Previous trial results showed compelling early signals for benefit.

The company's allogeneic cell therapy trial for acute respiratory distress syndrome or BCDA04 has been deprioritized to focus current financial resources on the other programs. This decision was based on the greatly reduced population of patients with acute respiratory distress secondary to COVID.

When resources permit, BioCardia intends to expand the current indication to a broader population beyond COVID-induced ARDS and to other pulmonary indications. BioCardia's Helix Biotherapeutic Delivery System or Helix delivers therapeutics into the heart muscle with a penetrating helical needle from within the heart.

It enables local delivery of cell- and gene-based therapies, including BioCardia's own cell therapies. It remains the safest, easiest to use and most efficient means for the delivery of cells, genes and proteins to the heart muscle.

The delivery platform includes proprietary approved steerable guide systems, approved delivery catheters and investigational imaging navigation. Business development is active around our Helix Biotherapeutic Delivery System and in other areas, and we are working to close meaningful deals by the end of the year.

These deals have potential to enable us to avoid financing. Underlying our programs is extensive intellectual property. In June, the company announced that the Japan Patent Office granted a patent titled Radial and endocardial delivery catheter, with a patent term that will expire in 2034.

The patent describes interventional biotherapeutic delivery catheters to deliver biologics to specific target sites within the heart chamber. The allowed claims covered by BioCardia’s helical needle tip catheter technology platform in existing products and in future products in active development with enhanced features.

Also in June, the European Patent Office issued an intention to grant for a patent titled Site Selection entry and update with automatic remote image annotation.

The patent application describes techniques to bring previously obtained high-resolution, 3-dimensional images of patients' heart, such as from a magnetic resonance image or MRI into the cardiac catheterization procedure suite and to merge this image with the X-ray images that the physician uses to navigate during the procedure.

This approach has been compelling in preclinical studies and is expected to further enhance targeting ease of procedures and data collection compared to our current procedures. In summary, we have four significant compelling clinical programs and strategic assets around our three platforms of great value.

We recognize that the market share price does not reflect this. We recognize that there's disappointment and confusion from the DSMB response, but there is a wealth of data and active programs generating more data and products are built on data.

We have significant near-term catalysts ahead from each of our three cardiac programs, as well as our business development activities. I will now pass the call to David McClung, our CFO, who will review our Q2 2023 results.

David?.

Thank you, Peter, and good afternoon, everyone. Revenues were approximately $43,000 for the three months ended June 2023, comparable to approximately $975 million for the first three months ended March 31, 2022, primarily due to the timing of collaboration agreement revenues. Expenses quarter-over-quarter were remarkably similar.

Research and development expenses were approximately $2.3 million for the three months ended June 2023 and for the three months ended June 2022. And selling, general and administrative expenses remained at approximately $1.2 million in the second quarter of 2023 comparable to the same amount in the second quarter of 2022.

Our net loss was approximately $3.4 million in Q2 2023, as compared to $2.5 million in Q2 2022, primarily due to the fluctuation in collaboration revenues. Net cash used in operations during the quarter was approximately $3.2 million, as compared to approximately $2.6 million in the second quarter of 2022.

In BioCardia ended the quarter with approximately $4.3 million in cash and cash equivalents, which provides runway into November without additional capital or funding from the business development and other activities that Peter mentioned earlier. This concludes management's prepared comments, and we're happy to now take questions.

Thank you. At this time, we will open up the call to questions. [Operator Instructions] Today's first question comes from Joe Pantginis with H.C. Wainwright. Please proceed..

Hi, everybody. Good afternoon and thanks for taking the question. So, Peter, I want to focus on the DSMB review, because obviously, like you said, I mean, this somewhat of a really unique situation. And I guess I want to reconcile something even though you don't have the answers yet and then look forward a little bit.

So if the DSMB comes out and says that unblinded data are not likely to meet the primary endpoint, usually, you would be in trial wind down activities right now and the study would be essentially done. But it's not, and that's the very unique aspect.

So I guess, from that standpoint, how do you reconcile that comment with the study still ongoing and the -- that you've seen blinded improvements in patients? And then the second aspect of that question is, which I think is important for listeners is then for patients that will be followed in a blinded fashion to the one-year benchmark.

You know what are the benchmarks that we and investors should be looking for with regard to deltas and treatment effects?.

Well, thank you, Joe for the question on the DSM review and some of the nuances. I guess on the first part, I don't have great clarity and so I can only hypothesize. As I noted in our prepared comments, we are also a little confused, but we assembled the DSMB and it's a very solid group.

And so as we try to read the proverbial tea leaves, there could be -- I'll just rehash it so folks who are not entirely aware, we have a very low mortality rate in the trial relative to what we've seen in the latest clinical trial setting for the latest guideline directed therapy in the New Journal of Medicine.

And we appear to have a very low major adverse cardiac event rate. And those are two components of the primary Finkelstein-Schoenfeld three-tiered end point. The third element is six-minute walk. And so I can hypothesize that maybe there's something wrong with the six-minute walk distance measure in as this primary endpoint.

We have -- because the levels are so low with respect to mortality and MACE events, the six-minute walk likely has a larger impact in this trial than we may have expected. And the nuance of how it's incorporated in the Finkelstein-Schoenfeld endpoint may have implications as well. And so that data, as I mentioned, is being analyzed.

It actually already has been analyzed by a separate group and we're confirming that the data that was provided to DSMB is the conclusions that they're drawing are from a substantially correct data analysis.

The other thing that we're doing is we have a clinical adviser, external to the company that we are going to have a look at all of the materials and assess whether or not a follow-on conversation as appropriate with DSMB to clarify potentially altering the recommendation.

I think right now, our sense is that the restart in 14 months, as I've detailed, does not make a lot of sense today to management. And so -- but we've been advised to stay blinded ourselves to the data to maximize potential going forward. Our expectation is that will evolve after these next steps. And so that's just where we are.

Now your second question, I think, was on trial wind down and.

No, more of benchmarking – sorry. Forgive me that margin one year, yeah..

Yes. So as far as trial wind down, the information we receive from this will impact the data that we have. So we are still randomizing patients today. And because all of the data supports that this is safe and all the past data that we see supports this is efficacious, we're still bullish on the direction that we're going.

And so those patients will be randomized, expectation is all the outstanding patients will be randomized in the next six weeks to eight weeks. And then we'll follow them for a period of a year before we get to the true data readout from this trial.

The interim readout that we may have, if data is viewed, we'll have the challenges that many of the endpoints have not yet been monitored, and so they will be looking at that. What I would expect to look for here is I follow the primary endpoint. I mean, the mortality data is going to be important.

I mean, if we're losing on that for some reason that I can't explain, that would be a surprise. The MACE data will be this next thing to look at. And if we're losing on that, that will also be interesting to look at.

But I think the primary feature since those two are so low already in this treated population; I don't expect either of those to have any interesting signals. Again, I'm not privy to the data. So I'm providing you my best guess work here all. And my expectation is that if there's something, it's the six-minute walk is problematic.

When we look at the other pre-specified endpoints, quality of life, all of the extensive echo data we have from our core laboratory at Yale, there may be some interesting observations in there that enhance our comfort level.

And then also two-year data follow-up, we haven't really looked at two years, but understanding how these patients are doing long-term is also going to be really important.

And I would, again, I look at the survival data, I look at the MACE data and then I look at the functional endpoints of six-minute walk, quality of life, and all the -- actually all of the echocardiography data such as LV ejection fraction, LV end diastolic dimensions, the end systolic dimensions.

And those are really important endpoints and are quite objective, and we'll see where we go from there. I think right now, it's interesting. I mean, we don't have clarity on why they would pause it.

If they don't think we're going to hit the primary endpoint, maybe their perception is these guys pause this and stopped this trial and restarted with another variable other than six-minute walk, maybe they'll be successful, I don't know. It's all guesswork. But we're being prudent as we're moving forward.

We are stewards of the value that this trial has in it for all of our shareholders and for patients, and so we have to take the steps that we're taking and the order we're taking, and we're doing it with world-class folks, so that we'll get to the right answers hopefully sooner rather than later..

Peter, thanks a lot. I appreciate the color and the speculation for this pretty unique situation and looking forward to the outcomes. Thanks a lot..

Yeah, appreciate the question, Joe..

At this time, we are showing no further questioners in the queue, and this does conclude our question-and-answer session. I would now like to turn the conference back over to Peter Altman for any closing remarks..

I want to thank all of you for participating in today's call and for your interest in BioCardia and our primary mission to treat heart disease. We look forward to sharing our continued progress, and as I always say, stay healthy, be kind and have a wonderful day. Thank you..

The conference has now concluded. Thank you for attending today's presentation and you may now disconnect..