TransCode Therapeutics Inc Aktie

Hello. This is Craig Brelsford with Redchip Companies. Thank you for joining today's event with TransCode Therapeutics, which trades on the NASDAQ under the ticker RNAZ. Joining us today is Philippe Calais, Chairman and CEO of TransCode; Zdravka Medarova, Co-Founder and Chief Scientific Officer; and John Tattory, the Interim CFO.

We will begin with a brief presentation in a moment, and then we will open the event to your questions. Welcome to everyone joining us today on X, YouTube, LinkedIn and other social media platforms.

[Operator Instructions]

Before we begin, please allow me to read the safe harbor statement. This call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements pertaining to future financial and/or operating results, along with other statements about the future expectations, beliefs, goals, plans or prospects expressed by management constitute forward-looking statements. Any statements that are not historical facts should also be considered forward-looking statements. Of course, forward-looking statements involve risks and uncertainties.

Philippe, please go ahead.

Great. Thank you very much, and hello, everybody. It's a pleasure to have the opportunity to describe our company today. And let's jump in right away into the company overview. We really describe ourselves as a rare small cap company with 3 near-term catalysts. First of all, we have a very strong pedigree with some Harvard founders, and Z is one of them. She will be talking later on from Mass General and Harvard Medical School.

The company was founded in 2016, became public in 2021 and has a fairly good financial profile so far with no long-term debt. And we are basically pioneering approaches that are complementary and that aim at redefining the boundaries of advanced cancer. We have three key pillars there. The first of which is the RNA-targeted therapeutics that is prioritized. Then we have vaccine immunotherapy product that mobilize the immune system.

And then we have also immuno-oncolytic agents that directly target tumors. We will focus primarily on the prioritized asset, which are the RNA therapeutics. If we look at our focus, we are targeting an area that is marked by right now, a very strong medical need in the sense that the advanced disease in cancer is the major source of death and reducing significantly the survival of the patient. You have some graphs here highlighting in different diseases, prostate male, female breast, colorectal, lung and melanoma cancer, showing the 5-year relative survival that is significantly reduced as patients are moving into the advanced stages of cancer. This is not only just a major health burden for the patient, but it's also for society and also for the health care system.

If we look at the organization, we are a small company. We have 12 employees. All of them are experts into their own field. And we are also surrounded by a very strong consulting group of experts that are basically a handful of them that are specialized in their own area, whether this is on the clinical side, on the strategic side or on translational science.

Our Board of Directors is comprised of people who have demonstrated strong experience in developing and being successful with exits in the biotech sector. And our Scientific Advisory Board is comprised of one of the co-founder, who was working with [indiscernible], Anna Moore. She is also the Chair of the Scientific Advisory Board, but we have people like Keith Flaherty, Frank Slack, who are well-known leaders in the field of oncology. So very, very strong team there.

If we look at our pipeline, this is a fairly busy slide. But as I said earlier on, we have prioritized the leading assets.

I'm terribly sorry. I'm not seeing the slides being advanced.

Because I see them, sorry. I have them advancing. Sorry about that. How can I resolve that? Now I guess you see the pipeline now, Victor?

Right now, we're seeing innovative and differentiated pipeline, yes.

That's the pipeline.

Right. And if you could move it into presentation mode so that we don't see all the...

That's what I have in front of me. But you don't have that, do you?

I'm not seeing that, right? Okay. Just continue that way, it's okay, Philippe.

All right. Well, I'm sorry about that. Sorry, everyone, for that. So we're going to try to go around that. So as I said early on, we have prioritized TTX-MC138 for the development. We have the cancer vaccine that I mentioned early on. We have a number of additional programs that are at a preclinical stage. And with this, I'm going to turn to Z, who is going to describe TTX-MC138. And do you see right now the cover page for TTX-MC138?

No, we do not.

So there's a real problem there. I don't know because as soon as I move into presentation, then it seems to be stuck.

Please don't be in presentation and just click on the slides on your left-hand side. That would be the way to solve it.

All right. So Z, it's all yours.

So as Philippe mentioned, our lead candidate is TTX-MC138. This is a drug that we originally conceived of and designed at the Massachusetts General Hospital. The whole idea was to design a drug that's going to be broadly applicable to metastatic cancers irrespective of where these tumors originated, whether they're pancreatic, breast, lung, liver cancer, et cetera.

So we looked for a molecule that is critical to the development of metastases from all of these cancers. And we identified the target microRNA-10B as one such molecule that was originally described by Bob Weinberg, a scientist at MIT. To inhibit this target, we designed an antagomir, which is an antisense molecule, an oligonucleotide molecule that binds to microRNA-10B through Watson-Crick base pairing and inhibits it.

In order to deliver this antagomir, we also conjugated it to a platform, which now we call TTX. It's an iron oxide nanoparticle, which we redesigned to make it optimal for delivery to tumors and metastases. These particles were originally developed as contrast agents for MRI. But in our case, they were significantly redesigned for the delivery of nucleic acids. Currently, this drug is in a Phase IIa trial, and we'll present more details to you in the coming slides.

Next slide. So in terms of the clinical development plan for TTX-MC138, we've made quite a bit of progress. We started with a Phase 0 trial. This is a trial in which we injected a microdose, a minuscule dose of the drug radiolabeled with copper 64 and image the delivery of the drug by PET MRI, which is an approach that will allow us to see the bio-distribution of the drug in the body of a human patient.

We enrolled a patient with metastatic breast cancer. And as we'll show you in the coming slides, we confirm delivery to clinical metastases in this patient. We also completed a Phase Ia trial with the main endpoint being the safety of this drug in patients with various advanced solid tumors. We're currently enrolling patients in a Phase IIa trial and we'll speak more about that trial in the coming slides. We're hoping that at the end of the Phase IIa trial, we have sufficient information to then initiate a randomized Phase II trial, which, if successful, could be pivotal and lead to FDA approval.

These are the results from the Phase 0 trial that I already mentioned. In this trial, we enrolled a patient with breast cancer metastatic to bone, lungs and liver. The image on the left is the pre-dose image. The lesions are highlighted by the arrows. So you can see the bone, lung and liver metastases in that patient. On the right is an image obtained 3 hours after dosing with the drug. And what you can see from these images is that indeed, the drug does accumulate in these metastatic lesions.

In addition to accumulation of the drug in metastatic lesions, we also showed that the drug is well tolerated, which is not surprising given that it was injected at the microdose. But this study was important because it allowed us to see what is the bioavailability of this drug in a human patient. This drug was shown to be delivered to metastases in animal models and was shown to also be highly effective in these animal models, leading to complete regressions of metastatic disease in these animals.

So as a first step towards translating this drug in humans, we needed to show that indeed, it accumulates in clinical metastases, and we accomplished that through this Phase 0 trial.

Next slide. In the Phase Ia trial, as I mentioned, the primary endpoint was safety with exploratory endpoints of pharmacokinetics and also preliminary clinical activity. The important conclusion from the Phase IIa trial, which tested 4 different doses of this drug ranging between 0.8 and 4.8 milligrams per kilogram was that the drug was very safe. We had only 3 infusion-related reactions in 2 of the patients that were treated with this drug. This is seen in 16 different patients that received around 86 doses of the drug.

In terms of clinical activity, the median duration, which in this case, equated to progression-free survival was 5 months with the longest duration being 15 doses as of the last public disclosure of our data. We currently still have 3 patients on study as of December 2025. The reason this is important is because these are very heavily pretreated patients that typically, once they fail this therapy go on to palliative care. So these are patients that have failed all other therapies, including other clinical trials with experimental therapeutics, then enter our trial.

So the fact that we're seeing a median progression-free survival of 5 months with some patients lasting for 15 months or longer is a meaningful readout indicating that indeed the drug is clinically active in these patients. This is a list of the different tumor types that were represented in our trial. You can see that we have a wide variety of cancer types. We have pancreatic cancer, we have breast cancer. We have 3 patients with colorectal adenocarcinoma. We have a patient with uterine cancer, kidney cancer and thyroid cancer.

So a wide array of patients. And as mentioned with respect to the previous slide, there was quite a meaningful increase in progression-free survival in all of these patients relative to what one would expect typically in a Phase Ia trial.

We met the primary endpoint of safety across all 4 doses that were tested between 0.8 and 4.8 milligrams per kilogram. We had 3, as I mentioned, 3 infusion-related reactions, of which 1 qualified as an SAE and 2 were Grade 2. So this indicates that the drug was indeed found to be very safe in that Phase Ia trial.

Next slide. And this is a more detailed list of the adverse event frequency and nature that was observed in this trial. One thing that I needed to remind you is that most of these adverse events were found to not be drug-related. As I mentioned earlier, the only drug-related adverse events were 3 infusion-related reactions.

In terms of the exploratory endpoint of determining drug pharmacokinetics, these are a couple of graphs that show two things. The first thing, the graph on the left shows that the terminal half-life of the drug is about 24 hours. The drug has biphasic clearance with initial rapid clearance followed by a second slow phase of clearance. This is pretty typical for these sorts of drugs. And in this case, reflects accumulation of the drug in tissue as it leaves the blood and enters the interstitium of various tissues.

The graph on the right represents drug exposure or AUC as a function of dose. And the main point of this graph is that there's a super proportional relationship between dose and drug exposure, meaning that if you increase the dose twofold, you get a more than twofold increase in drug bioavailability in the blood of the patients.

Next slide. These are the preliminary clinical activity data that we obtained. If you look at the graph on the bottom right, that shows the progression-free survival in all of the evaluable patients, irrespective of dose. And you can see that the progression-free survival is quite high. It's found to be 71%. The swimmers plot on the top right then breaks down these by individual patients. And what you can see is that a proportion of the patients actually stayed on treatment for 6 months or more and that a large number of the patients, actually all but 2 of the patients were qualified to have stable disease by RECIST criteria. That constitutes over 80% of the patients that had stable disease.

So what that indicates is that the drug indeed has a very powerful cytostatic effect and it stabilizes disease in a large proportion of the patients irrespective of the cancer type that they have. This is a highlight of the patient with thyroid cancer, which was an interesting case study in that patient, the levels of thyroglobulin increased throughout disease progression, which is thyroglobulin is a biomarker of residual disease. This patient had lung metastases from thyroid cancer. What we saw though was that by cycle 6 of treatment with this drug, thyroglobulin levels went down to undetectable. That patient then was put on a treatment holiday and you could see that thyroglobulin levels rose again, but began to drop off again as we initiated treatment.

So this is, at this point, a preliminary indicator of the powerful effect that the drug has on the levels of this tumor biomarker, presumably by putting the cells into dormancy or stasis. The Phase IIa trial was designed to evaluate the effect of the drug in patients with colorectal adenocarcinoma. These are patients that have been treated successfully through surgery and adjuvant chemotherapy and are free of detectable disease.

However, these patients become ctDNA positive. ctDNA is a tumor marker found in the blood of these patients, which is highly predictive of radiographic recurrence within 12 months. In excess of 80% of patients that have no evidence of visible disease in their body, but are ctDNA positive will actually become radiographically disease positive within 12 months of becoming ctDNA positive.

So that's a very high-risk population of CRC patients, which we are enrolling in our Phase IIa trial. They are being treated with TTX-MC138. The idea is that we're either going to eliminate or reduce the levels of ctDNA in their blood and most importantly, delay or completely prevent radiographic recurrence in these patients, and these are the endpoints of the trial. This trial is done in collaboration with Quantum Leap. This is an academic partner that we have, which has multiple clinical sites throughout the country. We've listed some of these sites in the table on the right.

Using Quantum Leap leverages the established clinical network that they have and is a very efficient and rapid way to progress through this trial by having access to the wide array of clinical sites that they have.

I already alluded to this in the earlier slide. We will select patients or we are selecting patients that are ctDNA positive that have undergone therapy with curative intent. The plan is to enroll 45 patients to treat them with the RP2D established in the Phase Ia trial. We will treat these patients for up to 12 cycles and then monitor ctDNA to see if we're reducing or eliminating ctDNA as a tumor marker from their blood. And importantly, if we are also delaying or preventing disease recurrence.

A few words about the delivery vehicle that we're using in this trial. That's a platform, which we call TTX. We have both in our academic life and currently as TransCode, use this platform to deliver more than simply nucleic acids. It's a highly versatile platform that could be used to deliver peptides, small molecules, tetramers, small proteins, radionuclides, as I mentioned with respect to the Phase 0 trial. So it's a platform that is potentially quite broad and could be partnered out for the delivery of various payloads to tumors and metastases.

Right. Thank you very much. So let's have a quick look at the finance. And first of all, start with the recent corporate development. As a reminder, we acquired Polynoma last October. That's almost a year ago, that's 11 months ago. And we had, at the same time, an investment from CK Life Sciences of $25 million in order to prioritize the funding of the Phase IIa study. In the first quarter of '26, we licensed the immuno-oncolytic portfolio from Unleash Immuno-Oncolytics. And in the second quarter, we entered into an agreement with Yorkville for a $20 million SEPA. So these are the major corporate development over the last year and that allows us to move into the capital structure, and I will turn to John to comment on that.

Sure. Thank you, Philippe. As of our last reporting of actual results as of June 30, at the time, we had approximately 1 million common shares outstanding and a market cap of $6.3 million. Importantly, what's happened since then as a result of shareholder approval, the all Series A, Series B and Series C preferred stock has been converted into common shares. And so on a pro forma basis, we would have had approximately 17 million common shares outstanding as of June.

And based on the latest share price, we have a pro forma market cap of about $28 million. We have no debt. The company has no debt on the balance sheet. And on a pro forma basis, we had $13.1 million as of June. That is $8.4 million of reported cash and $4.75 million of proceeds from a July 2026 convertible note transaction.

Thanks a lot, John. So if we move into the investment thesis, and that will be the last couple of slides that will be presented. We are basically building an innovative and differentiated oncology company that aims at meaningfully improving the treatment of advanced cancer. So filling really a gap in the armamentarium against cancer with different treatment modalities.

Our strategic focus is to develop a balanced and scalable portfolio. This is what I call the 3 shots on goal and with some near-term clinical value creation and platform-driven innovation. From that, because of the limited funds, we have prioritized TTX-MC138 clinical development with a number of catalysts that will happen in the next 18 months surrounding the completion of the Phase IIa study.

And we have a pipeline that is really built for differentiation and scale because the other products are of a different nature. Seviprotimut is an antigen vaccine that targets melanoma. In fact, in some respect, it came under the light recently with the announcement of the positive results of the Moderna Merck study. So that is really very exciting. And also the development of our TTX proprietary delivery engine that could be a very good candidate for partnering, in particular, outside of oncology.

And finally, the development of our engineered adenovirus oncolytic program that has a very strong immunogenicity and targets bladder cancer. So all of this can only happen with quite a lot of capital and organizational discipline in terms of execution. And the recent transaction were structured in order to avoid some heavy upfront financial commitment. And also, we are working on improving the communication for the company. And I think today's webcast is a good example of that.

What are the near-term catalysts and knowing that each of them has the potential to be a good inflection point. In the second quarter, we announced the initiation of the Phase IIa. In the third quarter, we are looking for announcing the enrollment update. Last quarter, we will be looking towards the end of the quarter at the preliminary results of the first patients that entered the study.

In the first half of next year, we will have some initial results that will be of -- sorry, the final results of the Phase Ia that will be announced at a major oncology conference. And we will have an enrollment completion announcement for the Phase IIa. Second half of '27, we will complete the Phase IIa study and have a preliminary readout. And also in parallel, we will have some announcements regarding some preclinical assets we are working on right now, and they should be getting closer to IND. So basically, what TransCode has to offer today is really an exposure to a fully differentiated platform that is built around the 3 shots on goal that I mentioned early on. And we have today, as you have seen, a valuation that remains, let's say, modest to use the best possible term relative to the breadth of our pipeline and the advancement of the program because let's not forget that we have a Phase III ready program. We have a Phase II ongoing right now.

So we believe that TransCode is really targeted for investors who seek exposure to technology with multiple inflection points in the near future. With this, we are completing our corporate presentation, and we would be very happy to answer any questions.

[Operator Instructions]

What is the expected time line for an initial data readout from the Phase IIa PRE-I-SPY colorectal trial? And would that be an interim or a full data set?

We are looking at an announcement, as I mentioned previously in the slide, towards the end of this year, beginning of next year with the first patients that will have entered the trial and will have a few months exposure. We can certainly identify some trends very early in the process because the biomarker that we are using from Natera, which is ctDNA is being done on a monthly basis. So that will allow us to monitor the level of positivity of that test. And then once we have fully enrolled all the patients, we are looking at an initial readout of the final results by the end of '27.

Thank you, Philippe. Are there any additional indications? For example, glioblastoma, given the preclinical publication, where TransCode plans to file an IND or begin dosing in the near term?

I will turn to Z to answer that one.

Yes. We are actively working towards advancing this drug in glioblastoma in collaboration with Henry Ford and Michigan State University, we are working towards a clinical trial to try to answer the question. The main question, which is delivery to glioblastoma tumors. So there are plans to advance this asset into glioblastoma.

How has the Phase II trial been enrolling so far? And when you report results, what would you consider success from the Phase II readout?

Right now, as we announced previously, we have initiated the trial, and that was right before summertime. So as you can imagine, things have been a little bit slow during the summer period. So we hope to be able to make an announcement on the enrollment in the near future, but this has not happened as yet. So we will do that in the near future.

And positive readout of the study would be, first of all, would be to confirm the safety in that patient population and also to see the trends in the ctDNA measurements. So from being positive to being negative, we have a very interesting point of reference in the recent announcement, in fact, last week from AstraZeneca that got their product, Etcamah that was approved in breast cancer using ctDNA. So we are at the forefront of the science here and the changes that were observed in ctDNA in that patient population were within a few months of exposure to the treatment. So this is really one of the key points that we will be looking forward in that study.

I have been investing with TransCode Therapeutics for over 3 years now, a small personal investor here. First of all, really, really, really love the science. I wish you all the best luck and fortune in getting this drug through all the trials. World needs your medicine. My question pertains to CVRs that were awarded to investors purchasing shares last year. Can you provide any clarification on this matter?

Well, I'm not that familiar with it, Philippe, having just started this morning. I apologize. I would happy to take a question through e-mail. The individual would like to send it, I'm happy to respond to the e-mail. I apologize.

Let's not forget that John joined -- in fact, started only yesterday. So his second day on the job. So we will give him a little time to brief, but we will be happy to answer by e-mail if that investor wouldn't mind sharing his e-mail.

Or he could just write us at [email protected]. We will then forward to the C-suite of TransCode.

What are the relevant biomarkers for the MC-138 trial? And how do you expect to use these to guide your future trial design?

Z, do you want to have a go at this one?

I mean, as we mentioned, ctDNA is the primary biomarker that is going to allow us to very quickly assess whether the patients that are enrolled in our trial are actually responding to therapy. CtDNA is emerging as a very, very sensitive biomarker in a lot of trials. And in my personal view is likely to become mainstay diagnostic as we continue to prove its value in patients. But it is a lot more sensitive than radiographic detection. So it allows the clinician to detect disease recurrence much earlier, months earlier than traditional approaches.

And so for that reason, using ctDNA to guide our treatment decisions is going to be extremely valuable, not only in the ongoing Phase IIa trial, but also in future trials that we are conducting on the response of patients to our therapy. CtDNA is also consistent with the mechanism of action of the drug. We have shown that the drug not only inhibits the ability of cancer cells to grow, proliferate and metastasizes, but also affects there's stemness for those of you that have a little bit of a biology background.

Stemness is the capacity of a tumor cell to regenerate itself and to generate a tumor. Most tumor cells in the body actually die or stay dormant, they cannot spontaneously repopulate an entire microscopic tumor. Stemness is the capacity of these cells to do that. And one of the mechanisms of action of TTX-MC138 is to inhibit that capacity in these tumor cells. So even if a person has tumor cells in their body, these tumor cells cannot turn into an overt microscopic tumor.

So for that reason, using ctDNA as an early biomarker of recurrence and disease progression is likely to be a very sensitive biomarker of the efficacy of our drug.

And just to add to what Z said and regarding the importance of ctDNA, the example that I mentioned early on of AstraZeneca's drug approval a week ago is really showing a major shift in the management of that patient population that is at high risk of recurrence and for which no treatment exists. When we think about the size of the population, just in colorectal cancer, we have about 150,000 new diagnosis every year. And we know that about 40% of those patients will relapse after treatment. So this is really a very important population that is at risk and for which today, there is no other treatment than waiting for the metastasis to come back and then to have the heavy burden of additional surgery and heavy treatment.

So there is really a vacuum, a need for such a therapy as the one we are offering today that will really answer the medical need. That's to put things into perspective. And the approval from the FDA has shown a significant shift in the recognition of ctDNA as a viable biomarker.

Does management anticipate presenting updated data at any major oncology conferences, for example, ASCO, ESMO, AACR in the next 12 months?

Yes, all of the above. We routinely present each year at ESMO, ASCO GI, ASCO and AACR. So we do anticipate that.

And in addition to that, I must say because Z will not mention it, that we have a number of publications also that she is working on together with our Head of the Scientific Advisory Board so with Anna Moore. So there's a number of publications that are coming on a regular basis about advancing. And I think that early on, we were referring to the GBM, Anna Moore study. So there is a lot of publication. I think we've had numerous publications in the last few years, and we keep the flow coming.

Is there a regulatory catalyst on the horizon such as Fast Track, Orphan Drug or Breakthrough Therapy Designation being pursued for TTX-MC138?

This is definitely -- I will have a go at this one. This is definitely our goal to follow this path. Now obviously, the FDA will not jump into giving those categories and those kind of awards for a biotech until we complete and we advance our clinical development and demonstrate also how unique and how well we fulfill a medical need. So we need to wait for the completion of the Phase IIa, prepare for the Phase II, present it to the FDA, and then the FDA will be able to provide those fairly unique accelerated review awards.

And final question. In the Phase IIa ctDNA positive colorectal cancer trial with Quantum Leap, what specific efficacy endpoints will determine whether the trial is considered a success?

Z, do you want to have a go?

Well, so FDA approvable endpoints at this point are delay or an increase in event-free survival. So if we show a delay or prevention of radiographic recurrence, that's going to really be the most important endpoint.

And the study also is having a number of traditional endpoints. So there's ctDNA on one hand, but we also have the traditional endpoints that are recognized by the FDA from the overall response rate to the partial response, the complete response, the remission. So all of these are part of the study, knowing also that the study being developed in collaboration with Quantum Leap that is a very important and well-recognized academic network organization allows us to have access to the most prestigious clinical sites in oncology.

So usually, those sites are early adopters. A successful study will be supported by top academicians and the sites are -- for example, we have University of Texas, MD Anderson. We've got University of Alabama, Chicago. We've got several Mayo Clinics also around the country. So that will allow us to be recognized by early adopters in the field.

Thank you, everyone. For more information on TransCode Therapeutics, reach us at 1-800RedChip or e-mail us at [email protected]. Please visit the information page created by RedChip for TransCode Therapeutics, it's redchip.com/stocks/rnaz. There, you can view and download the investor presentation and fact sheet and register for news alerts on TransCode Therapeutics. Watch Small Stocks, Big Money, RedChip's program featuring exciting small-cap companies every Saturday night at 7:00 p.m. Eastern on Bloomberg USA and every Sunday at 11:00 a.m. U.S. Eastern on CNBC.

And finally, join RedChip's next webinar with FibroBiologics on Tuesday, September 22, at 4:15 p.m. U.S. Eastern. Register for all RedChip webinars at redchip.com/events. Thanks again to our many participants today. And thank you, Philippe, Z and John.

Good morning, everyone, and thank you very much for joining us for this first ever webcast to cover our company research and corporate strategy. I'm Philippe Calais, the Chief Executive Officer and Chairman of the Board of Directors. Having an extensive experience in pharma and biotech, I joined as the first independent Board member right after the company inception in 2018, then became the Chairman of the Board in 2021 as we completed our first public offering and more recently, became the Chief Executive Officer last October.

It has been quite a ride since 2018, and we hope that this webcast will give you a better idea of what we have achieved so far of our strategy and our plans going forward.

First of all, our usual disclaimer. And then who really are we? Our company was founded by two Harvard faculty members, Professor Anna Moore and Dr. Zdravka Medarova from the Massachusetts General Hospital and the Harvard Medical School. Their goal was to identify and develop new therapeutics to target advanced tumors.

Since our first public offering in 2021, approximately $100 million were invested through financing, but also through government-funded non-dilutive grants. We aim at redefining the boundaries of advanced cancer care by pioneering different but complementary approaches that we describe as our three shots on goal strategy.

First of all, RNA-targeted therapeutics that precisely reach tumors with TTX-MC138 being our prioritized and lead program. Then we pursue vaccine immunotherapies, mobilizing the immune system to recognize and destroy cancer cells. Thirdly, and more recently, immuno-oncolytic agents directly targeting tumors while at the same time, stimulating systemic immune responses.

It is well established that over 90% of cancer deaths are due to advanced forms of the disease. There are numerous challenges to successful treatments in advanced cancer, the most important ones being the dissemination to distance sites, the immune evasion and the resistance.

On the right-hand side, you can see the dramatic reduction in relative survival rates in different forms of cancer when comparing to the advanced -- when comparing the advanced forms, represented by the green line; against the earlier forms, on the orange line. The market opportunity is enormous and untapped. The American Cancer Society estimates the global market to be in the $120 billion to $250 billion range by 2032, and this is only just 6 years away.

Here is a snapshot of the management team that is driving this innovation. We have 12 full-time employees and 4 fractional consultants. You will get to know several of our managers that will be presenting today. However, Sue Duggan, our Senior VP, Clinical Operations and Manufacturing; as well as Tania Montgomery, our VP, Business Development and IR; will not be presenting today, but they both play a critical role in our organization.

Our Board is comprised of four independent members with extensive biotech experience, all founders or currently leading biotech companies. Tom, our CFO; and myself, complete the Board.

Our Scientific Advisory Board is headed by our Co-Founder, Dr. Anna Moore from Michigan State University, where we have recently started an R&D collaboration that was announced last April. The collaboration gives us access to state-of-the-art facilities and the equipment that allow us to timely execute on our preclinical projects. Other members are all Board members -- all world leaders in their field, as is Keith Flaherty, who will speak in a minute.

To finish this introduction, let's have a look at our well-staged truly innovative and differentiated pipeline. TTX-MC138 is our lead and prioritized compound. TTX-MC138 is an antaglomer targeting microRNA-10B that is currently in Phase II for colorectal cancer in ctDNA-positive patients.

Seviprotimut-L, a Phase III-ready compound, was acquired from Polynoma last October. Seviprotimut-L is a cancer vaccine for Stages IIb and IIc melanoma. Our versatile proprietary TTX drug design engine has yielded two new programs, TTX-siPDL1 and TTX-RIGA.

Finally, last March, we licensed a full pipeline from a niche immuno-oncolytics, thus adding a new generation oncolytic immunotherapy platform. As you can see, in the last 6 months, we have diversified our pipeline with two new treatment modalities. However, we remain laser-focused on our core priority with TTX-MC138, and we will pursue other programs of our pipeline as funding is made available.

So now that the scene is set, please allow me to introduce Professor Keith Flaherty, our longer-standing adviser, who has provided his highly valuable guidance since the company was formed. Keith, the floor is yours.

Thanks, Phil. It's a pleasure to join you and the rest of the team members today. As you said, I've been around the company since inception, but in fact, a little longer than that. So I've been at Massachusetts General Hospital now for 16 years. And Dr. Moore and Medarova came to my office sometime in the mid-2010s, having worked on sort of the core technology behind MC-138 for years at that point, really dialing in the particle characteristics and demonstrating the delivery of the particle systemically in animal models to tumors at various sites and had also deliberated on what might be the most impactful cargo, specifically thinking about microRNA directed therapeutics as really great unmet need scientifically and where we thought clinical impact also could be quite significant.

And so it's been an absolute pleasure to first watch the company come into inception to translate this science to medicine and to watch how this program has matured. Later in the discussion, I'm going to revisit the topic of the very large unmet need that you alluded to in your opening comments that MC-138 is ultimately aiming to address, how we've really deliberated on a very broad opportunity with this agent and narrowed down to what we think would be the most impactful demonstration of proof of concept with this agent in patients with cancer.

And I'll highlight the rationale for that, again, a little bit later and lastly, touch on both the Phase Ia results from my perspective in terms of how it is that, that corroborates this agent's credentials, this agent really for further development and touch again upon the Phase IIa design that we've landed on.

So quite excited about where 138 stands and as you said, a whole pipeline now that is elaborated behind it. So looking forward to participating in the discussion.

Well, hello. My name is Daniel Vlock. I am a consulting oncology clinician for TransCode, and I want to take you through the clinical development of our lead compound, TTX-MC138.

So as Keith mentioned, this is an iron oxide nanoparticle platform, which allows the delivery of RNA therapeutics to tumors. And this basically outlines the key components of that. It is specifically designed to promote tumor uptake.

And we -- and the initial lead is to focus on inhibiting miR-10B, which, as you can see from the figure over there on the right is a key component that is a regulator of metastatic cancer and has an impact downstream not only on immune invasion, but tumor cell motility, apoptosis and also proliferation.

And so it is a key target to go after that way. And by inhibiting that, we're hoping to have an impact not only in relapsed/refractory disease, but also in microscopic disease as well, too.

So let me show you where we are with the program and how we are planning to develop it. This is the clinical development plan for MC138, where the first is a Phase 0 and a Phase Ia, which have been completed already, and we are now beginning the dose expansion in micro metastases, and that will hopefully be our first indication.

Let me show you the data that we have with those beginning with the Phase 0 program -- study, I mean. This was the Phase 0, which was basically to demonstrate the underlying mechanism of action that these nanoparticles can truly target metastatic disease.

So this was in a patient with metastatic breast cancer with bone, liver and lung metastases. And in this case, a radiolative microdose of MC138 was given to this patient on day 1. And then PET scanning was done to look at where it basically tracked to in the tumor. And what you can see here is that with those arrows that you can see on the right figure that PET MRI showed accumulation of the drug in the metastatic lesions.

At the small dose, it was well tolerated as well, too. But what it documented is what we have seen in animal models that these nanoparticles were actually able to track to the areas of interest and therefore, at least have a therapeutic impact in those areas.

Based on those studies, we began a Phase I trial. And this is a Phase I trial looking at safety of therapeutic doses of MC138. And the main endpoint on that is to basically see whether there is any toxicities that we need to worry about and then to look at it in terms of secondary endpoints, which will be response rates as well, too.

A total of 16 patients have been treated, around 86 doses to date. The duration has been up to 5 months with patients being out a lot longer than that, and we believe that is significant, and there are still 3 patients that are on study with this trial as well, too. We ended the toxicity portion of this at the end of last year, but are continuing to follow patients because patients do still remain on study.

This is the tumor types that were treated. This is typical for a Phase I study where you get patients that have exhausted other therapies and are, therefore, available to be treated for these kinds of tumors, and it is a wide range, certainly with breast cancer, sarcomas and then a variety of unusual tumors as well, too, which is typical for this kind of an initial study.

This is the safety endpoints that we looked at this way. So you can see over there that we began with the dose escalation study where we began with 0.8 milligrams per kilogram and then gradually escalated up to 4.8 milligrams per kilogram, which was the top dose that we gave here.

This was extremely well tolerated. There was one that would be technically determined to be a serious adverse event, which was an infusion reaction. The reason that it was looked at that way, even though it was a low grade, is that because of out of an abundance of caution when this patient presented several hours later with a rash, it was felt to be safer to admit the patient to the hospital, which is why it then got graded that way.

But frankly, this was well tolerated. The patient did well and was discharged the next morning. So we have been able to escalate up through 4.8 milligrams per kilogram without any dose-limiting toxicities, and it was extremely well tolerated.

This gives a an overview of the toxicity that we saw. And again, the vast majority of these were really Grade 1. The one area where we saw something that was at least initially deemed as higher was in iron overload. This is an iron nanoparticle. We were certainly focused on that. But really on review of this, although it says this was a Grade 3, which would be considered to be a more serious toxicity, that was only based on elevated serum ferritins, toxicity with iron overload is based on evidence of organ toxicity, we saw none of that here.

And so although we are seeing increased iron levels in these patients, there really has not been any organ toxicity based on that. And so we believe that this is still extremely well tolerated. And any kind of significant events were really rare and did not raise the question of any kind of safety concerns.

This is the pharmacokinetics that we saw with the study this way. And as you can see over there on the left is that cohort by cohort, basically, we saw dose levels that would behave in a dose-dependent fashion with higher levels being achieved at the higher doses.

What's important to point out here as well, too, is that the pharmacokinetics really matched quite nicely what has been seen in the animal studies here shown in rats and dogs. So it basically is consistent with what we have seen in preclinical data. So the animal models appear to be consistent with what we're seeing in the human models, and that gives us greater comfort in terms of what we're going to see in terms of pharmacokinetics and hopefully with efficacy as well, too.

This is the efficacy analysis that we saw. We have known that this is -- this drug leads to basically disease stabilization. It is not designed to basically have -- is cytostatic as opposed to basically tumoricidal in this particular case. And so therefore, what was expected to be seen was disease stabilization, which we saw in 60-plus percent of the patients there. And that's a long period of time to have people on that.

So 9 out of the 14 evaluable patients had disease stabilization, which again is consistent with the mechanism of action of the drug. That is shown over here in what's called the swimmers plot where we draw wide at 6 months. And as you can see, a considerable number of individuals were out much longer than that 3 patients remain on study. And that's what you also see with the progression-free survival, which is shown on the Kaplan-Meier curve there on the lower right of this as well, too.

I wanted to share this one patient with you because it points to what we think is basically the cytostatic nature of what we're observing. This is a patient with metastatic thyroid cancer with lung metastases. This patient has remained on study. Although we have not seen a regression of the tumor nodules, we have basically -- they have not progressed as well too.

What was also noted, although it was not initially -- we were not drawing these levels as part of the study, but it was done clinically; is thyroglobulin levels. And this is associated with increased tumor burden. And what you can see here is that this patient had rising levels of thyroglobulin, which is indicative of increased tumor burden.

But after the patient was begun on study, as you can see there, the thyroglobulin levels dropped to 0. Despite the fact that we saw tumor nodules radiographically, the evidence of tumor burden was basically down to that particular point.

Because of concerns about iron overload, the drug was held on cycle 7 and 8, at which point we saw the thyroglobulin levels basically go up again. Drug was restarted. And as you can see, it began to go back down again as well, too. And so this would be indicative of a drug that is having a cytostatic in terms of holding the tumor in place, although not seeing the same regressions and it's consistent with the disease stabilization that we have seen with the vast majority of patients on this study.

Let me now move on to where we want to go next with the drug, and that is using MC138 in colorectal cancer and targeting minimal residual disease. And we believe there's an opportunity here to address a major unmet medical disease, which is basically going after patients with microscopic disease.

This field has changed quite dramatically in that with liquid biopsies, looking at ctDNA, we are now able to detect microscopic disease far in advance of when it becomes radiologically evident. And that becomes important in terms of an intervention at that point, which was up until a few years ago, something that could not happen.

This gives us an opportunity to have an agent like MC138 in that microscopic disease setting. And so we are going to be treating patients with micrometastases who are at a high risk of recurrent. This is individuals who have undergone therapy for their disease, in this potation colorectal cancer with curative intent where they have had their surgery followed by adjuvant therapy, but then it appears that their disease has come back.

At present, there is no therapeutic option available for these patients. And we know that if they are ctDNA positive that they are going to have almost a near certainty that their disease is going to come back.

And so to have a therapy such as what we have that is well tolerated and that can be given to -- that is specifically designed for these kind of microscopic diseases is a unique opportunity for MC138. And that is what we are doing is to take these individuals after conventional therapy and adjuvant therapy has been given with curative intent and then to basically treat that patient population.

To do this study, we have done -- we have developed a collaboration with Quantum Leap Healthcare Collaboration. This is a multi-institutional collaboration that has involved -- the planned sites that you can see on the right. It is a collaboration that involves major clinical cancer sites around the country.

And as you can see, the Mayo Clinic, University of Minnesota, et cetera, major cancer centers that have basically collaborated together to develop novel therapeutics. So these are leading cancer centers that are collaborating with us to basically help develop new standards of care.

So we view this not only as an excellent opportunity, but also as a validation of the science that we are doing. By working with Quantum Leap, we are able to basically use their platform to rapidly have the study up and running with accelerated timelines and cost savings and patient enrollment as well, too.

This is the trial design for this initial Phase IIa trial and that we will take individuals who have had curative intent standard therapy with metastatic -- with colorectal cancer who are then ctDNA positive. We plan on treating 48 patients at the top dose that we have seen. And we will basically follow them with ctDNA positive. And the endpoint will be not only clearance of that, but also the evidence of basically preventing radiologic response.

This will happen relatively quickly. We think that this is a unique window of opportunity that we can follow these patients and look for evidence of basically a reduction in relapse-free survival in this high-risk group of individuals.

At this particular point, that's where we're going with the studies. Let me now move on and introduce you to Lou Brenner, who will be talking about the cancer vaccine program that we're doing. Lou, all yours, please.

Thanks, Dan. It's a pleasure to have the chance to talk about the company and its programs. Similar to Dan, I'm an adviser to the company. I've been working with this company for the past couple of years. I myself am a clinician and have had the chance in my industry career to work on both iron oxide nanoparticles as therapeutics and diagnostics as well as immunotherapy for cancer.

And so the elements of this platform, including the approach to go after significant unmet needs in advanced metastatic cancer is something that was quite attractive to me. I'll focus briefly with some commentary on another aspect of the company's portfolio, the Seviprotimut-L cancer vaccine.

Next slide, please. So this program came about as part of a partnership with CK Life Sciences. It is a vaccine to go after patients who still have unmet needs due to metastatic or advanced cases of melanoma. This is a polyvalent vaccine. As many would know that the immunotherapy approach in metastatic melanoma has been quite successful with key important drugs that have really been significant advances in the industry and for the benefit of patients, including KEYTRUDA and Opdivo. These checkpoint inhibitors are used for the treatment of advanced melanoma.

However, they're not universally effective or universally well tolerated in patients, and it does leave an opportunity for additional approaches that leverage some of the scientific understanding that's been developed to provide another technological approach, in this case, a vaccine rather than a checkpoint inhibitor.

The side effects in a vaccine have the potential to moderate some of the immune-related toxicity associated with checkpoint inhibitors. The patient eligibility, some patients are just unable to tolerate or unable to be treated with checkpoint inhibitors. And the ability to have this administered potentially in the dermatologist or the oncologist office might have an opportunity. In addition, there's potential for combination or sequential therapy.

The drug has gone through -- Seviprotimut has gone through an initial Phase III study called the MAVIS study, which I'll cover in a moment. It's had very good and active dialogue with the regulatory body at the FDA to try to advance this towards what could be a planned pivotal Phase III study.

This would obviously be a larger, more significant study, and the company is considering its options in terms of how to pursue manufacturing and what would objectively be a large study, several hundreds of patients, the kind of which would potentially be transformative, but also would require a significant commitment of resources. It does provide significant optionality for the company as it thinks about carrying forward its platform of advanced cancer therapeutics.

Next slide, please. So just to briefly cover the study that's already completed and has been published in the Journal of Immunotherapy for Cancer in 2021. This is the MAVIS study looking at Seviprotimut versus placebo, an adult population with advanced but resected forms of melanoma. The dosing starts relatively quickly after the first dose. It's done with an intradermal injection.

This was a significant study in that it had 55 sites in the United States and Canada. You see on the right, both the recurrence-free survival and the overall survival and the hazard ratio of 0.65 and 0.37. This puts it in the potential ballpark of some of the other therapies that have been approached.

However, acknowledging that this study at 100-something patients is a little bit smaller than other studies that have been done in the past, so it is definitely hypothesis generating, and it does allow the company to think through what options it might have, including potentially looking at patients with advanced disease that haven't been treated before or have not been able to be treated with traditional checkpoint inhibitor therapy.

And so as we think about the portfolio more broadly, having this cancer vaccine for melanoma is something that adds to the MC138 story. In addition, there's additional parts of the portfolio for treatment of bladder cancer.

And with that, I'll introduce my colleague, Michel Janicot, to talk about our other platform for immunotherapy in bladder cancer.

My name is Michel Janicot. I'm a PhD in molecular and cellular biology. I have about 35 years' experience in oncology R&D, and I'm supporting TransCode as acting Head of Translational Medicine, which, in other words, I'm helping the company to strengthen the two-way bridge between preclinical and clinical development.

The following set of slides illustrate an interesting and very complementary addition to TransCode R&D pipeline with the recent acquisition of Unleash immuno-oncology and consequent integration of an oncolytic virus platform in the company portfolio.

Oncology viruses are designed to selectively target and replicate in tumor cells, which induce significant tumor cell lysis or killing, which in turn generates tumor antigen released in the tumor microenvironment, which are then used by the host patient as signaled for broad antitumor immune response.

Specifically, our lead candidate, UIO-524 represents a rationally designed next generation of oncolytic virus, which is based on adenovirus type 5, which in real life is responsible for mild symptoms of regular cold. Among other genetic elements, very important elements, UIO-524 consists of a target recognition motive, namely the [ fiber 5/3 ], which targets [ Desmoglein-2 ], a receptor known to be expressed in malignant cell. And this motive is actually sort of piloting the virus to tumor cell.

The second important element is a tumor microenvironment sensitive hybrid promoter, namely [ KHSpark ], which in real life, regulate the expression of key matrix cellular glycoprotein involved in extracellular matrix remodeling and tumorigenesis, and that is highly active in malignant cell and [ cancer ] associated stromal compartment. This promoter senses hypoxia and inflammation in tumor microenvironment and therefore, driving selective virus -- efficient virus replication.

And last but not least, the virus also contains 3 highly relevant immunostimulatory factors intended to activate dendritic cells, T cells, natural killer cells. And those agents are CD40 ligand, which is also known as [ CD154 ], which is a protein primarily found on activated T cells, which act as a critical communication bridge between the immune system.

The second immunostimulatory factor is the 4-1BB ligand, also known as CD137L, which is a transmembrane cytokine and immune checkpoint molecule that binds to 4-1BB receptor, found primarily on antigen-presenting cells, which are the dendritic cells and provide crucial costimulatory signal to promote T-cell activation, proliferation and antitumor immunity.

The third element is interleukin-21, IL-21, which is a cytokine that coordinate the transition between innate and adaptive immunity. So all these elements concur to the fact that this virus will replicate efficiently in -- selectively in tumors and create an environment very, very adequate for reaction of the host immune system.

It is of note that UOI-524 is currently in preclinical development stage halfways to IND, but we have also additional alternative in discovery phase. With this virus, an initial clinical proof of concept has been achieved in experimental human tumor-bearing immunodeficient mice. Those mice are used to allow human tumor growth and development.

As you can see on the top left of this slide, briefly, the human cells were injected under the skin of the animal to form subcutaneous tumors. And when those tumors were established, either vehicle control in gray or UOI-524 in green was injected intravenously 3 times during the first week. And then the tumor size was measured over time and is what you see on the top left.

Clearly, results demonstrated that at well-tolerated dose, systemic administration of UOI-524 were shown to induce promising significant inhibition of tumor growth, which, in this case, is essentially due to oncolytic activity as this experimental model were performed in immune-deficient mice, leaving the immune system component of the reaction to the virus majorly out. And this was compared to the vehicle control arm. And you see clearly a good efficacy of that particular virus.

On the top right, the company initial focus for clinical evaluation is proposed to treat adult patient with low-grade muscle invasive bladder cancer, which represents an unmet medical need. Muscle invasive bladder cancer account for about 25% of all bladder cancer diagnosed and carries a high risk of spreading to other parts of the body.

As you can see in the very, very naive scheme in the insert that you see that the tumor starts at low grade in the wall -- in the intra wall of the bladder. And then progressively, the tumor is developing, start to invade muscles and it's where you start to have the metastatic property with a dreadful outcome.

Talking about bladder cancer and muscle invasive bladder cancer, from a health economic perspective, bladder cancer represents the ninth most common cancer globally with over 600,000 new cases worldwide diagnosed annually. The market size for muscle invasive bladder cancer alone is currently about $2 billion and according to the expert analyst, is projected to progress to more than $3 billion by 2035 with an expected compound annual growth rate of about 5% over the next decade.

Using intravesical administration of the virus, which, if eventually necessary, further increase the safety profile of this drug class, we strongly believe that UIO-524 represents a valuable addition option to the therapeutic armamentarium to treat patients with bladder cancer and certainly beyond bladder cancer in solid tumor indication.

And for the following section of this presentation, I leave the floor to my colleague, Zdravka Medarova, who's going to lead you to the next section.

My name is Dr. Zdravka Medarova. I'm Chief Scientific Officer of TransCode. I also co-founded TransCode along with Anna Moore and Michael Dudley back in January of 2016 based on technology that we developed at Harvard Medical School. I'm also Associate Professor of Radiology at Harvard Medical School and one of the investigators at the Massachusetts General Hospital.

When we first started Transcode, we envisioned the company as a platform company. And it's a platform company based on two properties. The first one is the fact that we develop nucleic acid-based drugs for cancer. And because of the modularity of the genetic code, one can develop drugs that are purely modular.

The advantage of that is that currently, only 20% of cancer-causing genes are druggable using traditional approaches such as small molecules or monoclonal antibodies, whereas using the genetic code as a target, essentially any cancer-causing gene will be druggable, which will then open up the remaining 80% of cancer-causing genes for the design and development of drugs. And as you can imagine, this is going to open a huge pipeline of cancer drugs if it winds up being successful.

The second property of TransCode's technology that makes it platform-based is the use of the TTX drug design engine. And TTX is essentially a nanoparticle, as mentioned earlier, which is modular in terms of its synthesis. And because of that modularity, we can use this particle to develop a wide variety of drugs, specifically towards cancer, but also towards macrophage-related diseases.

And the chemistry behind this particle allows us to tune the delivery of these drugs to various tissues and cell types such as we can, for example, achieve controlled release in terms of time, in terms of the microenvironment. We can achieve the delivery not only of nucleic acids, but also peptide small proteins, which will then allow us to develop targeted versions of these drugs. So these are all potential directions that we could take using this platform-based technology.

So as part of TransCode's pipeline, we have developed a couple of therapeutics for cancer. The first one is a novel immune checkpoint inhibitor, which we call TTX-siPDL1. And that inhibitor is essentially the TTX platform conjugated to a small interfering RNA against PD-L1. PD-L1 is a target for immune checkpoint inhibitors.

And in this table, we're outlining some of the advantages of TTX-siPDL1 with traditional checkpoint inhibitors, which are monoclonal antibodies. And I'd like to draw your attention to the safety and potency advantages that TTX-siPDL1 holds. Because TTX-siPDL1 uses an RNA-based approach that silences the gene for PD-L1, it is potentially a much more powerful inhibitor of PD-L1.

The analogy that could be used is traditional checkpoint inhibitors mop up the floor in the case of a flood, whereas the siRNA-based approach would effectively turn off the faucet. So you can imagine based on this analogy, how much more powerful siRNA-based approach would be than a traditional monoclonal antibody. So that's in terms of potency.

A second element related to potency is the potential of the siRNA component to convert cold tumors into hot, which is a necessary signal that needs to be present in addition to the immune checkpoint inhibitor in order to have an effective response against cancer. So with the TTX-siPDL1 platform, we could actually achieve both inhibiting the checkpoints, but also converting a cold tumor into a hot tumor. So again, increased potency compared to traditional checkpoint inhibitors.

In terms of safety, because of the tunable release that could be achieved using the TTX platform, we could lower the systemic exposure or if we can tune the systemic exposure to the checkpoint inhibitor in effect then lowering systemic immune activation and minimizing the potential for undesired side effects.

So these are some of the advantages of TTX-siPDL1. And here, we're showing some preliminary results in a mouse model of pancreatic cancer in which we treated these mice either with TTX-siPDL1 or an inactive drug called TTX-si scrambled. We used 2 doses of TTX-siPDL1, a low dose and a high dose.

And what you can see from the graph on the left is that with the high-dose TTX-siPDL1, we can achieve a profound delay in tumor progression relative to the control treatment, which translates into quite significant enhancement in survival, as you can see from the graph on the right.

So in effect, what happened was that in this animal model, we increased survival very dramatically compared to the controls to 67% at 12 weeks, which in this animal model is quite a dramatic improvement.

A second drug that we are developing as part of our pipeline is TTX-RIGA, and that's a pattern recognition receptor agonist. Pattern recognition receptor agonists have been of interest for a while, not only because they can lead to regression of preexisting tumors, but also because they can help build lifelong immunity against rechallenge with these tumors.

So in patient terms or in human terms, what that would mean is if a patient responds to a therapy with a pattern recognition receptor agonist, they would effectively be assured the absence of recurrence because of immune activation against the tumor antigens.

So here is a table outlining some of the advantages of our approach relative to traditional pattern recognition receptor agonists. And it relates a lot to safety.

Traditional pattern recognition receptor agonist hold the potential for cytokine-related toxicity because the target is present not only in tumor cells, but also in healthy cells. For that reason, typically, pattern recognition receptor agonists are injected intratumorally to avoid systemic exposure.

The way the TTX-RIGA is designed, it will permit systemic administration of the drug and targeted activation only in the tumor microenvironment. And the reason why that's important is because, as we know, cancer is a systemic disease, it's not a local disease.

Therefore, systemic delivery of the drug in the context of tumor-targeted activation will then increase the potency while also increasing the safety of this drug compared to traditional pattern recognition receptor agonist.

And here's an example of a study that we did in mice with melanoma. I'd like to draw your attention to the graph in the middle. That graph depicts the growth of the tumors over time for up to 22 days after treatment. These tumors are secondary tumors. So essentially, what was done is mice were implanted with melanoma tumors. They were treated at that point, they were rechallenged at the end of treatment with secondary tumors to mimic cancer recurrence.

And what you can see in the red line is that the animals treated with TTX-RIGA in this case, failed to progress their secondary tumors, where the control group did progress their tumors grew. And what that indicates is that we have successfully built systemic immunity against the tumor antigens and are preventing the growth of secondary tumors.

So that's an interesting result that remains to be replicated in additional animal models, but potentially illustrates the value of this technology in this particular drug.

So to summarize, we believe that TransCode holds the key to a really broad pipeline of cancer therapeutics because of the modularity of the design of the drugs that we're developing. We have the unique advantage of being able to deliver nucleic acids to cancer, which has so far slowed down the development of these technologies or the translation into clinical practice.

And believe -- therefore, we believe that with the illustrated examples of TTX-siPDL1 and TTX-RIGA, we are just at the beginning of kind of an exponential growth curve in terms of drug development.

And with that, I'd like to introduce Tom Fitzgerald, our CFO, who will talk about our corporate finance.

Thanks very much, , and thank you, everybody, for joining this morning. We're thrilled to have you here and thrilled to share the story.

As you can see and you've heard, we've -- since the IPO in just about 5 years ago, we've made substantial progress on a number of fronts. Clinically, as you've heard a lot of the details about from prior speakers, organizationally, the team that we've assembled here over the past few years is just extraordinary. Some of the best people that one could ever hope to have in the oncology area.

And then most recently, strategically, which is just summarized here, so in addition to moving forward in the clinic with the TTX program, we've gotten -- added additional shots on goal, as Philippe had described earlier. one of those being the [ semiprotomate ] program for cancer vaccines and the immuno-oncolytic program for immunotherapy.

In Q4 of '25, it was October '25, we did the acquisition of Polynoma, and that involved issuing to CK Life Sciences, which was the ultimate owner of Polynoma, Series A convertible preferred shares. So when you see those on our balance sheet, that's what that went to.

And at the same time, concurrent with the acquisition of Polynoma, we also received a $25 million investment in common stock from CK Life Sciences, and that was represented with Series B preferred shares. There were also issued 83,000 common shares to CK in connection with the Polynoma acquisition. So you'll see that on our cap table as well.

And then in March of this year was when we did the exclusive worldwide licensing of the oncolytic portfolio from Unleash Immuno Oncolytics, and that involved us issuing Series C convertible preferred shares to the Unleash entity.

And then in April of '26 of this year, just a couple of months ago, we entered into a financing arrangement with Yorkville Advisors, a standby equity purchase agreement, or SEAPA, that provides for up to $20 million of financing under a variety of conditions, fairly common to those kind of programs.

Uncommon to those programs that involved the issuance of up to $6 million of convertible notes. And we've taken down $1 million of the face amount of those convertible notes and are on track to receive the additional $5 million of face value of convertible notes shortly after our shareholder meeting, which is coming up on July 2 of this year.

Once shareholders approve the convertibility of the Series A, B and C shares and all the shares that are potentially issuable to Yorkville Advisors, all of those will become part of our cap table on an as-converted basis.

So here's a summary of our capital position right now. This is using the share price of a few days ago, $5.69 a share. Prior to any of the convertibility that I described with the Series A, B and C shares and the Yorkville shares, we've got about 950,000 shares outstanding, giving us a market cap of $5 million -- just over $5 million, which we think is -- doesn't fully reflect the company's potential or accomplishments to this point.

On a pro forma basis, assuming conversion of all the shares that I've talked about, we'll have about 18.6 million shares outstanding, and that would give us a pro forma market cap of a little bit over $100 million.

We have no long-term debt. The only short-term debt that we have are the convertible notes to Yorkville that I mentioned. And as of March 31, the date of our latest 10-Q filing, we had just under $13 million of cash, and we anticipate receipt of additional cash over the course of the next 30 to 45 days so that we'll have -- we'll be in a good position to go into 2027 and hopefully beyond that.

So with that, I'll turn it over -- turn it back to Philippe Calais, who will provide some concluding remarks. And again, thank you all for being here.

Thank you very much, Tom. That's so far a very, very interesting and enlightening presentation from everyone. If we look at the investment thesis, our mission is really to build an innovative and differentiated oncology company that will meaningfully improve the treatment of advanced cancer by developing breakthrough treatment modalities that are acting on metastatic cancer and enhancing the power of the immune system.

We believe that the power of innovation is at the intersection of three elements: the targeted delivery, the immune activation and the tumor biology; all three serving to unlock the next wave of innovative cancer drugs with marked clinical impact for the patient.

We're building a balanced and scalable portfolio, the famous three shots on goal that came back a few times today, that combine near-term value creation, platform-driven innovation and long-term pipeline sustainability. This approach allows us to advance promising drug candidates and technology platforms today while continuously generating differentiated programs for the future.

We have prioritized TTX-MC138 as our lead asset and are laser-focused on the clinical program execution. We see 3 potential catalysts in the next 18 months, the Phase IIa enrollment completion, the preliminary data readout and the final data. Our next clinical program is Seviprotimut-L, is Phase III ready. Both clinical programs serve as fundamental assets for combination strategies.

Behind those clinical programs is a deep and expanded preclinical pipeline anchored by three core engines of innovation. We plan to evaluate the combination of TTX-MC138 and Seviprotimut-L in a preclinical program to explore potential strategies between both modalities to address metastatic disease in melanoma and capitalize on the roles of miR-10B in the target.

Our proprietary delivery engine, TTX, you've heard about that one from Z, has already yielded two in-house programs with siPDL1 and RIGA. In addition, the TTX delivery engine enables the use of diverse and flexible payloads leading to different therapeutic modalities that aim at improving precision and targeting platforms. TTX is available for partnering.

Through our newly acquired Unleash immuno-oncology platform, we will be developing agents that directly target tumors while simultaneously stimulating systemic immune response. This platform expands our reach into a novel mode of action and enables the creation of differentiated next-generation cancer therapies. We will initially focus our efforts on muscle invasive bladder cancer.

So together, those programs and platforms provide a scalable framework for project pipeline expansion, allowing us to generate multiple product candidates for either internal development or for partnering. And in order to meet those challenges as an organization, we focus on execution. It's all about execution, execution and execution.

We also operate under a strict capital discipline. This capital discipline applies to all levels of the organization. For example, we optimize our research operations through our R&D collaboration with Michigan State University. We benefit from a unique pool of researchers and state-of-the-art equipment that would be difficult to acquire by ourselves.

We also elected to collaborate with Quantum Leap to manage TTX-MC138 Phase IIa clinical trial with significant benefits expected as compared to a traditional CRO model. Finally, both Polynoma and Unleash transactions were, by design, structured to avoid upfront financial commitment.

We also believe that communication with all our stakeholders and investors will promote a better understanding of our mission and ultimately help fill the evaluation gap. Today, our first webcast is the best example of how we implement this strategy.

So I hope that you appreciated today the extent of the work that has been done by the absolutely amazing team that we have gathered at TransCode Therapeutics, and I thank them really for their contribution and their dedication. This is not small work. It is extensive, and we have gone for such a long way since 2018.

So talking about the execution, let me show you a brief slide of the near-term catalysts, most of which are related to TTX-MC138 and each has a potential to be a significant inflection point.

In the second quarter of '26, and we are in that second quarter, we expect to have the enrollment initiation in the Phase IIa. In the third quarter, we will have an update on the enrollment. And in the fourth quarter of this year, we will look at preliminary results.

The first half of 2027 will lead to the Phase Ia results being released at a major oncology conference and also Phase IIa enrollment completion. The second half of '27, we see the Phase IIa completion and the preliminary readout that is associated with the completion. And for the other programs, we will advance those -- some preclinical assets towards IND as obviously available funding is made available, and that includes government grants. So that's nondilutive grants.

As we are reaching the end of our webcast, please allow me to turn back to our scientific adviser, Professor Keith Flaherty, for a few concluding remarks.

Thanks, Phil. I've been a clinical investigator now for 26 years at Mass General for 16 of those now and met the TransCode founding team back in the inception of the company in the mid-2010s and have watched this story evolve in a way that I think is really maintains all of the novelty and potential unique impact that was potential within view based on preclinical data now several years back.

I think the unmet need that MC138 potentially addresses, I think, is really quite substantial. A couple of ways to describe that. But I think probably first and foremost, the ability to halt the progression -- metastatic progression of cancers and further dissemination even once cancers have initially metastasized, I think, is quite a real value proposition.

But the fundamental premise really does start from the preclinical data, extensive preclinical data suggesting that if you can deliver miR-10B to tumors systemically, you can have a sort of diverse mechanistic effect ultimately leading to halting progression of metastatic disease.

As we've deliberated on translating the preclinical data into clinical development strategy, we really focused on kind of these two aspects: One is the ability to halt progression of metastatic disease when it is microscopic. And as this audience is well aware, in recent years, we've been able to develop technologies that allow us to find those patients with far greater reliability, largely leveraging circulating tumor DNA detection methods, which have become increasingly sensitive.

So we now have a very large fraction of the solid tumor population who undergo definitive surgery, followed by radiation as appropriate. And then when tested with the circulating tumor DNA detection assays can basically be found at a state where they have microscopic metastatic disease only, so not visible on radiographic scans and certainly not symptomatic.

We think that's a point in disease evolution where this approach can be very impactful, again, based really directly on the preclinical data. And this is an emerging area of clinical investigation in the field where we're deploying established therapies now in this so-called MRD-positive solid tumor setting, but also investigational agents that have a particular mechanistic rationale as this one does.

And reflecting on the Phase Ia data, basically, in my experience as an early phase clinical trial investigator, we're always looking to try and understand the degree to which we can connect the dots from preclinical data and our expectations based on preclinical efficacy studies as well as toxicology, pharmacokinetics and the like.

And basically, I would say the Phase Ia data really affirms what had been seen preclinically in terms of ability to deliver doses, achieve exposures that are very, very well tolerated as they were in preclinical species. So absolutely no surprises on that front. And so this product appears to be behaving as expected in terms of ability to administer it systemically.

We're going to have an increasing focus, of course, in shifting to the Phase IIa study in terms of trying to corroborate the ultimate mechanism of action, as alluded to in the MRD-positive setting where we think we'll be able to take patients who are detected to have circulating tumor DNA, monitor that circulating tumor DNA on therapy and basically aim to suppress the progression of metastatic disease in that setting.

We know that patients who are MRD positive are essentially certain to relapse and generally within a matter of months' time. And so we will need not follow this population for very long to have a sense of whether this agent as monotherapy is able to suppress the further progression of disease and true radiographic or clinical relapse. So that's ultimately the goal.

And in deliberating on the various tumor types where we have a reason to believe miR-10B plays a substantial role based on extensive preclinical data generated by the company and by others in the field, colorectal cancer is one indication. that we think really sort of is at the center of this opportunity in terms of taking patients who are MRD-positive and demonstrating that we can suppress the progression to metastatic disease over metastatic disease.

Ultimately, this platform technology in terms of the delivery strategy, this very unique nanoparticle that had been derisked even before the development of this program as a core that can be used to deliver contrast agents for radiographic studies really represents quite a unique platform for delivering therapeutics beyond miR-10B.

This is for the life cycle of the company thus far, been the lead program and product, but establishing proof of concept with this agent will really open the door to substantially expand the pipeline and use this unique delivery platform to achieve systemic delivery in a way that we've not been able to in prior years when trying to achieve target delivery with RNA therapeutics in particular.

So again, I think we're quite pleased with the progress of the program so far. It's the agent's graduation from Phase Ia just clearly supports its further investigation in Phase IIa. And again, we think are the most profound proof of concept would be the ability to suppress progression of metastatic disease in patients who are MRD positive.

In future studies, we also expect to follow preclinical data leads in terms of combining this agent with other standard therapies where we have preclinical evidence of synergy and deploy those standard therapy-based combinations in patients with overt metastatic disease where we have reason to believe we can achieve more deep and durable responses with a combination of conventional agents combined with MC138.

So progression of studies to be done and establish essentially two-pronged version of clinical proof of concept. But as I said from the outset, this is an agent that was highly novel at the time that was first conceived and developed preclinically remains really truly unique in the field in terms of its potential.

With that, back over to you, Phil.

Thank you very much, Keith. We hope that we were able to convey our vision and our passion for our company as we are fully anchored on our laser focus on TTX-MC138, as you have heard from Keith, the development and the execution in the context of our three shots on goal against advanced cancer. Our team is fully committed on executing on our goal to serve the needs of the patients, also our stakeholders and investors. So thank you very much, and have a great rest of the day.