Greetings. Welcome to Panbela Therapeutics Fourth Quarter 2023 Earnings Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] Please note this conference is being recorded.

I will now turn the conference over to your host, James Carbonara, Investor Relations. James you may begin..

Thank you, operator. With me on the call are Jennifer Simpson, Chief Executive Officer; and Sue Horvath, Chief Financial Officer. Before I turn the call over to Dr. Simpson, please note that statements made on this call that are not historical facts may be forward-looking statements.

Significant risks and uncertainties that could cause actual results to differ from those expressed or implied in the forward-looking statements are detailed in the company's annual report on Form 10-K and supplemented by subsequently filed reports on Form 10-Q as well as in other reports that the company has filed with the SEC.

Any forward-looking statements made on this call are made only as of today's date, and the company does not undertake any obligation to update or supplement any such statements to reflect subsequent developments. Now, I would like to turn the call over to Jennifer Simpson CEO of Panbela. Jennifer please proceed..

Thank you, James, and thank you everyone for joining. I will begin the call with a review of our clinical development program, recent accomplishments and upcoming milestones. Sue will then follow with a review of the financial results and then we will open it up for Q&A.

So let's start with our Phase 3 initiatives specifically the ASPIRE global clinical trial. ASPIRE is a global randomized double-blind placebo-controlled study designed to assess ivospemin or SPP-101, in conjunction with gemcitabine and nab-paclitaxel for patients with untreated metastatic pancreatic ductal adenocarcinoma.

During Q4, the independent Data Safety Monitoring Board or DSMB completed its second pre-specified review of safety data for treated patients, which included the first 214 patients in the trial. The DSMB has recommended that the study continue without modification.

Then in January, we surpassed 50% enrollment for the ASPIRE trial moving faster than originally projected. As we have reached the full complement of sites open and enrolling we have seen a steady cadence of enrollment, expecting full enrollment to be completed by the first quarter of 2025.

We are looking forward to the interim data analysis based on overall survival. We originally projected this to occur in mid-2024. However, we have not seen enough depth at this time. With patients living longer we are evaluating the data and working to update the expected timing for the interim analysis.

There also has been positive movement in the metastatic pancreatic cancer treatment landscape. Based on the NAPOLI3 trial, ONIVYDE was approved in February for use within the NALIRIFOX regimen for first-line metastatic pancreatic cancer.

This approval was based on a 1.9-month median overall survival benefit, 11.1 months in the treatment arm versus 9.2 months for the control arm, which was gemcitabine and abraxane. This approval is significant to Panbela for a number of reasons. It is the first approval in first-line metastatic pancreatic cancer in approximately 11 years.

The 1.9-month survival benefit is similar to the approval of gemcitabine and abraxane versus gemcitabine in the IMPACT trial.

Additionally for the ASPIRE trial it helps to validate the assumed median survival of the control arm, which has not changed greatly since its original approval 11 years ago with a median survival of 8.5 months in the IMPACT trial.

With enrollment of the ASPIRE trial moving faster than anticipated, we look forward to the overall survival interim analysis and the completion of the trial in the hope that our product may be a potential option for patients in the future.

Turning to familial adenomatous polyposis or FAP, Panbela remains committed to collaborating with the FDA, EMA and the FAP community to move this program forward, with the goal of bringing a novel treatment option for FAP patients.

Once we obtain consensus on a global registration plan among the FDA and EMA, we plan to advance this initiative while upholding our established cost model. Concurrently, we intend to explore ways to maximize the value of this asset.

Moving on to the PACES trial our Phase 3 double-blind placebo-controlled study of Flynpovi aim to prevent the recurrence of high-risk adenomas and second primary colorectal cancers in patients diagnosed with stage zero to three colorectal cancer.

As a reminder, the PACES trial receives funding from the National Cancer Institute or NCI and is being run by the Southwest Oncology Group also known as SWOG. This study successfully cleared a planned futility analysis and enrollment is complete. We expect data by the second half of 2026. Shifting gears to Phase 2 studies.

In July, we announced an agreement with US WorldMeds to divest assets from the Eflornithine Pediatric Neuroblastoma Program for non-dilutive payments of up to $9.5 million.

Panbela has already received an initial upfront payment of $400,000 and stands to receive further payments as US WorldMeds achieved key milestones related to Eflornithine's clinical advancement, regulatory approval and commercial sales.

To that end in December US WorldMeds received FDA approval of its New Drug Application or NDA for eflornithine marking the first FDA approval of an NDA for any polyamine-targeted therapy in a cancer indication. As mentioned, Panbela benefits financially from this continued advancement of the program.

Additionally, this approval validates the role polyamines complain cancer therapy as we look forward to data from our ongoing programs that we are discussing today in metastatic pancreatic cancer, colorectal cancer, non-small cell lung cancer and prostate cancer as well as the advancement of preclinical programs in ovarian cancer and multiple myeloma.

Continuing with Phase 2 trials. In September, we entered into a clinical trial agreement for a Phase 2 trial in castration-resistant metastatic prostate cancer or CRPC leveraging preclinical models that demonstrate a potential role for polyamines in androgen-resistant prostate cancers.

This clinical trial will determine if the addition of eflornithine to the treatment regimen will demonstrate further efficacy in these difficult-to-treat patients. The study is actively enrolling.

Staying with Phase 2 investigation, the Phase 2 trial for CPP-1X or eflornithine is led by Indiana University School of Medicine and financially supported by the Juvenile Diabetes Research Foundation or JDRF.

Results show that DFMO or eflornithine treatment may preserve beta cell function reflected by C-peptide levels in patients with Type 1 diabetes through the modulation of urinary polyamines in particular putrescine.

There is a pressing need for the development of safe and effective treatment addressing the underlying cause of early-stage disease, and we are thrilled to champion this initiative with JDRF and the Indiana University School of Medicine. This trial continues to enroll patients.

As a reminder, the study referred to as the Paclitaxel [ph] study is a multicenter double-blind placebo-controlled 2:1 random assigned Phase II trial for individuals with recent onset Type 1 diabetes. The study is enrolling approximately 70 patients and an interim analysis is anticipated next year.

In Phase 1 development, we have three programs that we plan to initiate. We are currently engaged in a clinical trial collaboration with Moffitt Cancer Center for a Phase 1/2 program designed specifically for patients with STK11 mutant non-small cell lung cancer.

In the Phase 1 trials initial stages our objective is to determine the maximum tolerated dose of eflornithine in conjunction with pembrolizumab, while simultaneously evaluating its efficacy. Following this phase, our intention is to advance into a Phase 2 trial to further assess effectiveness.

This study is open and screening patients, and we anticipate enrolling our first patient in the first half of this year, with plans to initiate the Phase 2 trial in the latter half of the year. Our second Phase 1 program scheduled to begin in the first half of this year.

We'll focus on evaluating ivospemin in the platinum-resistant ovarian cancer population. This endeavor underscores the ongoing collaboration between the company, and John Hopkins University School of Medicine.

Third, we are also engaged in an ongoing collaborative research initiative with the University of Texas MD Anderson Cancer Center focusing on evaluating polyamine metabolic inhibitor therapies along CAR T cell therapies and bispecific monoclonal antibodies in preclinical models.

Recently, we announced the acceptance of an abstract detailing research on SBP-101, or ivospemin and CPP-1X or eflornithine in multiple myeloma cell lines for online publication at the American Society of Hematology meeting or ASH meeting, and it was included in the November supplemental issue of the journal Blood.

Panbela's new programs placed focus on the modulation of the immune system by polymenes. Our initial clinical proof of concept involves the timing targeted therapy combined with a checkpoint inhibitor for patients with STK11 mutant non-muscle lung cancer.

We are excited about expanding this research collaboration to explore the potential benefits of polyamines in immune modulation for hematologic malignancies. Finally, we are currently engaged in collaborative efforts with key opinion leaders to start the neoadjuvant pancreatic investigator initiative.

We are in the advanced stages of securing the necessary institutional approvals, to initiate the trial in the first half of this year. Turning briefly to our intellectual property or IP efforts. We strengthened our portfolio by announcing the issuance of new patents in China, Australia and Europe.

These patents cover claims of a novel process for the production of SBP-101, a product developed in collaboration with Syngene International Ltd. In closing, our unyielding commitment is to advance our development program for the benefit of patients worldwide.

To summarize our projected milestones, we expect in the first half of 2024 to open the neoadjuvant pancreatic cancer trial, enroll our first patient in the non-small cell lung cancer Phase 1 trial to open the Phase 1 ovarian trial to announce gastric cancer prevention Phase 2 results, publication of the final Phase 2b metastatic pancreatic trial data, and the overall survival interim analysis of the Phase 3 ASPIRE trial which we originally projected for the middle of 2024.

However, with not enough events or deaths at present, we are working to evaluate the data that we may update the projected timing. And in the second half of 2024, we anticipate to obtain feedback from the FDA and EMA for global registration in FAP and to open the non-small cell Phase II trial -- non-small cell lung cancer Phase II trial.

In summary, the fourth quarter and year-to-date have marked significant strides for Panbela. We are enthusiastic about the ongoing creation of value for our shareholders as we progress in 2024. I will now turn it over to Sue..

Thank you, Jennifer. General and administrative expenses were $0.9 million in the fourth quarter of 2023 compared to $1.7 million in the fourth quarter of 2022. This decrease is the result of lower professional fees in 2023 versus 2022.

Research and development expenses were $6.1 million in the fourth quarter of 2023 compared to $3.5 million in the fourth quarter of 2022. The increase is primarily due to the increased activity in the ASPIRE trial.

All share and per share amounts of our common stock presented here and in our report 10-K have been retroactively adjusted to reflect the reverse stock split completed in January of 2024 as well as those that occurred in 2023.

Net loss in the fourth quarter of 2023 was $6.5 million or $65.90 per diluted share compared to a net loss of $4.7 million or $344.61 per diluted share in the fourth quarter of 2022. Total cash was approximately $2.6 million as of December 31, 2023, which does not include proceeds from the $9 million public offering we closed in January.

Total current assets were $3.1 million and current liabilities were $12.3 million as of the end of the quarter on December 31, 2023. Total non-current assets, consisting primarily of cash deposits held by our contract research organization, were $8.7 million.

As a result of the CPP acquisition in Q2 of 2022, we added debt and accrued interest to our balance sheet. During the quarter ended December 31, 2023, no debt or interest payments were due or paid.

The principal balance remaining on the notes is $5.2 million and there was approximately $238,000 of accrued interest -- accrued and unpaid interest as of that date. The current portion of $1 million plus the accrued interest was paid per the terms of the note earlier this month. Looking to the cap table.

First a reminder, all shares have been retroactively restated for the reverse split that occurred on January 18. As of December 31, 2023, we had approximately 480,000 common shares outstanding. And including shares reserved for options and warrants, we were at a total of approximately 826,000 shares.

The shares reserved number includes all outstanding equity awards including stock options, which were held primarily by insiders and all warrants to purchase common stock. Our cash used in operations for the year ended December 31, 2023, totaled approximately $25.2 million.

Cash used in operations for the year ended December 31st, 2023 included approximately $3.7 million in payments necessary to secure a supply of standard-of-care chemotherapy agents for the ASPIRE trial as well as $2 million in the total payments made to increase those deposits held by our CRO for future clinical trial costs.

On December 2nd, 2023 and December 21st, 2023, the company induced certain warrant holders to exercise their warrants for cash. Gross proceeds received from this exercise totaled approximately $1.9 million and $2 million respectively.

In January of this year, we closed a $9 million public offering consisting of 4,375,000 shares of its common stock or prefunded warrants in lieu thereof and two classes of warrants to purchase up to an aggregate of 8,750,000 shares of common stock at a purchase price of $2.06 per share plus the associated warrants.

Those warrants will have an exercise price of $2.06 per share are exercisable upon issuance and will expire five years following the date of issuance. The net proceeds of this offering was approximately $8.2 million.

Panbela's common stock is listed on the NASDAQ Stock Market Exchange under the symbol PBLA, but it is currently trading on the OTC Pink Sheets under that same ticker. The company is currently pursuing a new listing of its common stock on a national securities exchange.

Operator, can you please open the phone lines now for Q&A and poll for questions?.

Certainly. At this time, we'll be conducting a question-and-answer session. [Operator Instructions] And the first question today is coming from Jonathan Aschoff from ROTH MKM. Jonathan your line is live..

Thank you. Hello Jennifer and Susan. Good afternoon. I have a few questions.

What's the FAP trial going to cost you think?.

Hi Jon. Good afternoon. I'm sorry, which trial, I apologize I didn't hear that one..

The FAP.

The Phase 3 FAP trial that you need to get regulatory guidance and clearance on?.

Got you. Got you. So, for the FAP trial that is a program that once we have agreements on the global registration path most likely we'll be seeking a partner for that program. So, for us, we are trying to remain cost neutral on that one while moving the asset forward..

Okay, that's definitely clear.

Can I ask you if eflornithine approved, so could you elaborate on the financial -- the actual direct financial benefit to Panbela for that?.

Yes. So, with the approval to the -- obviously, the first approval was in the neuroblastoma program that we divested to US WorldMeds.

And so with that program there was a $400,000 upfront payment and then there's a total of another $9.1 million in non-dilutive milestones, mostly tied to the commercial sales, both US and Europe, as well as there's an ongoing trial in the Children's Oncology Group in the first line setting of neuroblastoma.

So just as a quick reminder, the first approval was in the maintenance setting. And so as that current trial moves forward which went to US WorldMeds as part of our agreement, there are regulatory milestones around that trial as well.

So, we are anticipating that probably between the end of second half of this year and first half of next year, we will start to see some of those milestone payments come in probably to the tune of $0.5 million to $1 million to start and then they ramp up as sales continue..

Okay. That's very helpful. Thank you.

Given the R&D level fluctuations, can you help us out with how the R&D looks over 2024?.

In terms of program of financials, I was going to say that will be a two questions..

Yes.

So are we going to stay in 6s and go higher?.

Right now, we're projecting that between 6% and 6.5% per quarter for the total burn for the company. So that would include the modest spending, we do on G&A and then the balance is R&D and almost all of that really is the ASPIRE trial.

The other thing that affected us last year was the need to secure standard of care chemotherapy agents for the trial that wasn't expected. That will also continue. We have to determine at what level that will impact the numbers..

Yes. I think Jonathan if I might add just one more thing too. I think it's really important. The ASPIRE trial as Sue mentioned, it's the primary driver of our cash needs is the ASPIRE trial. It is 600 patient -- approximately 600-patient trial randomized double-blind placebo-controlled.

The other programs that we went through, it's quite an extensive pipeline. We are very fortunate to have funding for almost all those programs from other sources. So I think that's an important distinction.

A lot of times when you have a company with so many programs, the cash needs are split across those programs and we really have a main driver and are fortunate to have all these other programs in conjunction with funding from other sources..

Okay. That was helpful. And lastly, can you tell us about the exchange that you might go to given the delisting? It doesn't have to be the Pink sheets.

Isn't there a far more favorable option perhaps?.

Sue, do you want me to take that? Or do you want to take it?.

Yes, I can take it. Yes. Certainly, I mean the Pink sheets are a temporary place for us to be likely even the OTCQB will be not necessarily a long-term solution either. We need to be on a national exchange.

So there's -- we're looking at all of the others that we might be able to uplift to -- that might include the CBOE American with the NYSE are a couple of the options that we're looking at..

What seems to maybe provide the most -- the potential for the most liquidity you think? You think the CBOE is the best of -- between that and AMEX?.

In our research what we found is that the volume on the CBOE tends to be very close to what's seen on NASDAQ. So if that's the primary driver for our decision that might be the right place to go..

Okay. Thank you very much..

Thank you so much, Jonathan..

Thank you. And the next question is coming from Joe Pantginis from H.C. Wainwright. Joe, your line is live..

Thank you. Hi. This is Josh on for Joe. I just had two quick questions. So for the first one, I believe last quarter it was maybe said that we would potentially see some data in 2024 for the Phase 1 STK11 trial.

I was just wondering, now with the first patients being enrolled in the first half of 2024, do we still expect that? Or would that potentially be pushed back? And then just quickly, I think I missed it about the Phase 1 study in Platinum-Resistant Ovarian Cancer. I was just wondering if you could reiterate when that is set to begin..

Yeah. Absolutely. And thanks so much, Josh. So for the STK11 mutant, Phase 1, since the trial is open and screening for patients now, we would most likely have data towards the end of this year and that would then feed into the start of the Phase 2 portion. As of right now that is our current projection.

We're going to have to see how the enrollment goes. As a reminder, the STK11 mutant population of Non-Small Cell Lung Cancer, depending on which stores you look at ranges between 10% and 30% of lung cancers. But I will say market's been actively screening. And so as enrollment starts we will keep everyone updated on the progress.

But our hope right now is data from that by the end of the year. For the Ovarian Cancer, we have been working very closely with The Johns Hopkins University School of Medicine and looking to finalize that protocol and have that Phase 1 program opened by the first half of this year.

And it's interesting because we're looking at a number of trial designs. It could end up being a Phase 2, instead of a Phase 1, depending on which path we take. But we have a very engaged team. So we look forward to finalizing that and updating everyone accordingly..

Perfect. Thank you, for answering my questions. And thank you, for the update..

Sure. Thank you so much..

Thank you. This does conclude the Q&A session and also concludes today's conference. You may disconnect your lines at this time, and thank you for your participation..