Participants
- PropThink
- Dr. Michael Chancellor, KOL
- Jonathan Kaufman, Lipella CEO
PropThink
Good afternoon everyone, welcome to PropThink’s Digital Conference. My name is Deniel Mero, Editor of PropThink. I will be hosting today’s event. PropThink Digital Conferences is a platform designed to give you access to subject-matter experts, including prominent investors, executives, KOLs, and others with unique insights into the healthcare space.
Before we jump into the discussion, just as a reminder for the audience that there will be forward looking statements made, which are based on assumptions. We are not registered investment advisors so nothing in this presentation should be construed as investment advice. Always consult a professional before making any [investment] decisions.
That said, let’s get into the agenda and the speaker today. We’ve invited a renowned urologist to discuss the hot bladder-cancer space and share his insights on this current surge of interest and talk about a large unmet need from one of the lasting side effects that many cancer survivors face, called hemorrhagic cystitis (“HC”).
Today’s expert urologist is Dr. Michael Chancellor, Chief Medical Officer of Lipella Pharmaceuticals (NASDAQ: LIPO). He has served as a professor and research director at the William Beaumont School of Medicine since 2008 and has been a been principal investigator in more than 75 clinical trials. Dr. Chancellor has authored hundreds of publications regarding the treatment of urinary bladder dysfunction, has received more than 90 awards in connection with his work with urinary bladder dysfunction, and is generally considered an international key opinion leader (“KOL”) in the industry.
Dr. Chancellor is a board-certified urologist, previously holding the positions of instructor at the College of Physicians and Surgeons Columbia University, associate professor at Jefferson Medical College, and professor at University of Pittsburgh School of Medicine.
Dr. Chancellor, welcome! That is quite the long list of accomplishments. I'm looking forward to the discussion today.
Dr. Michael Chancellor, KOL
Thank you for having Lipella. Deniel, I'm really excited and looking forward to talking with you and PropThink.
PropThink
Perfect. Let’s start off with the recent surge of interest in the space. There not only seems to be a surge of interest, but also progress being made in bladder cancer treatments. CG Oncology (NASDAQ: CGON) had the first IPO of the year in 2024, with their oncolytic virus immunotherapy called cretostimogene. That IPO was priced at $19, opened at $29 and is now trading over $40. Another program from Janssen released promising late-stage data for their TAR-200, which releases chemo gemcitabine in a controlled manner into the bladder.
As a urologist, do you view these as big steps forward for the field?
Dr. Michael Chancellor, KOL
Yes, I think these are big steps forward. Bladder cancer has tremendous unmet need.
It is the sixth most common cancer, but it doesn't quite get the recognition of lung cancer or prostate cancer. The most unique thing about bladder cancer is that 80% of the patients will have tumor recurrence. That happens on the inner surface of the bladder. And to have recurrence that often, it really makes it perhaps the single most expensive cancer disease to treat. So we're sort of stuck on how we treat the cancer. We instill chemo or BCG immune therapy in the bladder, but they're pretty toxic, and the success rate is not good enough. If it was, four out of five patients wouldn't have tumor recurrence.
The dangerous part is if the localized bladder cancer, non-muscle invasive, grows into the bladder muscle and metastasizes, you're talking about a cystectomy, removing the bladder and wearing a urine bag or making a neobladder or systemic chemotherapy. The threshold of keeping this cancer superficial in the bladder lining is high and has a very high rate of recurrence.
The advances of putting gene therapy directly in the bladder or using the immune modulator, the checkpoint inhibitor, in the bladder itself, is really an ideal way to maximize efficacy while minimizing systemic toxicity. That's Lipella’s core competency -- a localized bladder drug delivery platform.
PropThink
Are these therapies seen as the eventual treatments that replace the toxic standards of care like radiotherapy and chemotherapy for bladder and other pelvic malignancies?
Dr. Michael Chancellor, KOL
Perhaps. Right now, the only way to diagnose bladder cancer, is to look in the bladder with a cystoscope; it's very much like seeing a polyp during colonoscopy. Once you see it, you must scrape it away, and try to remove it all, and stage it. Currently, you're giving mitomycin, chemo or BCG in the bladder and watch out for recurrence. If there is recurrence, you have got to give the systemic oncology treatment. So, an effective localized treatment, be it to block the gene that induces cancer or treat it with the proven success of the checkpoint inhibitors, but placing it directly in the bladder is very attractive, and it could be the standard of care within or over the next few years. This is even an area that Lipella is working on in developmental work because it’s a great unmet need for the 10,000 urologists and the tens of thousands of patients who have bladder cancer and are worried about the recurrence of this disease.
PropThink
Let’s talk briefly about Hemorrhagic cystitis, a complication from radiotherapy or chemo that is characterized by uncontrolled urinary blood loss. Talk about this condition, how it impacts life for cancer survivors and what strategies are being applied to manage the bladder damage?
Dr. Michael Chancellor, KOL
Yes, in my career, there's been tremendous improvement in surgery, robotic and immune therapy, the checkpoint inhibitors. We are a lot better at curing and controlling cancer, but thereby the consequences of chemo or radiation treatment for cancer survivors is an increasing unmet need. The better we are at curing cancer, the more we have to deal with the collateral damages that may happen with radiation and chemotherapy.
Hemorrhagic cystitis is just the worst thing for urologists and for men with prostate cancer, women with cervical and uterine cancer, and men and women with colon cancer, that get radiation and certain chemo. It may treat the cancer, but the damage from the radiation starts after a year or two and it gets worse. They survive the cancer, but the sequela of the treatment just progressively adds on. We have no current effective treatment for hemorrhagic cystitis.
At Lipella Pharmaceuticals, we identified this, we went to the FDA and we received the first orphan disease designation in cancer survivorship for the use of tacrolimus, a drug to put in the bladder for the treatment of hemorrhagic cystitis.
PropThink
Newer approaches to bladder cancer are now either reaching late-stage trials or already approved. Immunotherapies like Keytruda and the oncolytic virus immunotherapy from CG Oncology. There is also the gene-therapy adstiladrin from Ferring Pharma approved just over a year ago. Do you see the increased adoption of these therapies lowering the incidence of HC?
Dr. Michael Chancellor, KOL
No. The straight answer is that HC really occurs after prostate cancer, gynecologic cancer and colon cancer. It really doesn't happen that much with bladder cancer. The use of radiation in combination with immunotherapy and chemotherapy is increasing every year in order to obtain optimized care. The risk of hemorrhagic cystitis, especially today, since there's no current approved treatment, it's going to increase despite these advances in bladder cancer.
You can see from the figure on the left side of the screen that the current treatments are all over the place – if the patient has radiation damage, if they're bleeding -- you're talking about old school, flushing the bladder through a catheter to get rid of the clot to using laser to fulgurize all the pinpoint bleeding. You try to give them HBOT -- hypobaric oxygen therapy – essentially you take them to a scuba diving tank, go to two and a half atmosphere for 60 sessions over three months. We’ve even done injecting Botox in the bladder. If they're really bad, you're talking blood transfusion and surgery, so there is very limited treatment. We envision this being the first in class treatment that a physician can give in their office or in the emergency room that can quickly stop the bleeding in somebody who's had radiation or chemo damage to the bladder.
PropThink
You’ve published papers showing how a liposomal tacrolimus formulation for intravesical bladder administration can treat hemorrhagic cystitis (HC). This formulation, now called LP-10, is being tested in Phase 2. Tacrolimus has historically been used as an immunosuppressant for organ transplants. How is it working to treat HC?
Dr. Michael Chancellor, KOL
It was really a very ingenious idea our CEO, Jon Kaufman, and I, came up with. Tacrolimus is probably the single best transplant rejection drug. It’s mostly because of tacrolimus that since the 1980s that patients with heart transplants, liver transplants, kidney transplant, can live a very long, high quality of life. It is the most effective and very quickly blocks the inflammation due to cytokine release that causes transplant rejection.
But what's special here is tacrolimus is a very potent drug, and it does not dissolve in water or saline. What it does is it causes an acute small vessel constriction, vasal constriction. If you give too much tacrolimus by a pill or intravenously, it shuts your kidney down; it causes kidney damage due to the vasal constriction.
We figured out that if we put a high dose of tacrolimus in the bladder where the bleeding and the inflammation is, we can use its anti-inflammatory property to treat the disease and we can use its Achilles heel, the side effect of vasoconstriction to stop these hundred points of little blood vessel bleeding in the bladder. We can get a high dose in the bladder while minimizing the systemic side effects. That's the rationale for using the liposomal formulation of tacrolimus. Liposome delivery and body cavities are our core competence. We manufacture CMC within Lipella and the tacrolimus is really a good use of this drug, localized to treat this disease.
PropThink
I assume that you can't just use a Prograf, for example, from Astellas, to go after the same intravesical administration?
Dr. Michael Chancellor, KOL
Yes, two points there. First, we have the orphan disease designation protection for all tacrolimus in the bladder for hemorrhagic cystitis. We have seven-year exclusivity, and second, as I mentioned, tacrolimus is one of the most hydrophobic drugs there is. It just does not dissolve in water or saline. If you take it by the same formulation, the capsule and pill, you just can't put it in the bladder. It won't dissolve -- even the IV formulation. It's actually in the range of castor oil, and you have to dilute it out in a liter IV bag before you can put it in somebody's vein and you just can't put that in the bladder. This is in addition to our liposomal patent protection. We have the orphan designation for all tacrolimus to treat hemorrhagic cystitis.
PropThink
Let’s talk about what the LP-10 Phase 2a data showed?
Dr. Michael Chancellor, KOL
After we received the orphan designation, we appealed to the FDA and we received the IND and they told us we can go directly to a multicenter dose-escalation Phase 2a clinical trial. This was carried out in the US at five centers where a total of 13 subjects were treated, each receiving up to two installations of LP-10.
This is the first-in-human trial. As a clinician, and I know the FDA feels this way, it's safety first. We demonstrated that [LP-10] was well tolerated. It doesn't cause any burning, and nobody needed a pain pill narcotic. There weren’t any product-related adverse events. We also showed that because we can measure tacrolimus in the whole blood, the whole blood tacro level. We know that we had a high dose in the urine, but there was only a minimal increase in tacro level in the blood and only for an hour or two. We achieved a high local concentration while really minimizing the temporary local exposure. Moreover, we achieved a good signal of efficacy that really, I think means that we achieved the goals of this phase two trial. And before we move on to the next slide, we finished the trial, it's published in peer-reviewed literature, and now we're talking to the FDA about the Phase 2b trial.
Lipella is in a very exciting place with our lead product for hemorrhagic cystitis. Moreover, we received an IND to start clinical Phase 2 development of our pipeline product, a mouthwash, an oral rinse of LP-10 for a disease called oral lichen planus. This is an autoimmune disease in the inside lining of the mouth that's very painful. The pain causes difficulty eating plus it has a risk for malignant transformation to squamous cell cancer. We have IRB approval to start a multicenter Phase 2a trial with oral lichen planus. Lastly, we received orphan designation for tacrolimus, as a mouth rinse for the treatment of oral graft vs. host disease. This is a rare and very serious disease that occurs in patients who have a hematologic stem cell transplantation. We have an IND in the queue with the FDA currently.
PropThink
What impact did LP-10 show in bleeding and other metrics in the Phase 2a data?
Dr. Michael Chancellor, KOL
Looking at it from the top line, hemorrhagic cystitis is bleeding in the bladder, and there are a number of ways to look at bleeding in the bladder. Panel A [slide deck] is for the urologist to look in the bladder, and you can see the number of bleeding sites. What else can you do? Well, you can count the number of blood cells in the urine on microscope in the laboratory. As in the doctor's office where you can dip the urine for a urine pregnancy test, you can also see if there's hemoglobin, blood, in the urine. Lastly, you can see if there's blood in the urine, if patients are bothered because they’re having urinary leakages. The bars [slide deck] on the left show the results before treatment; the bars on the right show the results after treatment. The deep dark green is bad, meaning there's a lot of bleeding, and the light blue is good, meaning there's no bleeding. When you can see the transformation, the improvement that we've noticed on multiple parameters, including looking at blood in the urine from before and after, it's just visually apparent to anybody.
PropThink
So talk about the approval pathway here. What sort of studies, in addition to the Phase 2b that is being planned, does the FDA want to see for approval? As for the benchmarks for these approvals, what is the FDA looking for?
Yes, we've had a conversation that they want a treatment for this disease. The FDA granted an orphan designation. So, we had a positive Phase 2a study, now we're going on to a Phase 2b. That's going to be the gold standard; double-blind placebo-controlled trial. We're going to consider the two doses of LP- 10 to optimize what is the minimal effective dose, and we're going to compare it against placebo in a one-to-one randomization.
In talking with the FDA, we're going to look at the number of bleeding from baseline to week four as the primary outcome with the usual statistical measurement that the FDA requires. The FDA really likes patient-reported outcomes. What does the patient say?
We're going to have essentially a standardized app, a voiding diary. Every time a patient has a leak or has hematuria, they will enter it into the voiding diary. So, the patient report of bleeding in the urine will be compared between LP-10 and placebo from baseline and at week four, which would be the primary efficacy outcome.
PropThink
For the Phase 2b trial, what are the costs going to be to run something like that? Lipella had $2.4 million in cash as of September 30th. You'll need to find that money somewhere. What financing routes are you considering to not only fund this Phase 2b, but also the subsequent trials that that will come afterward?
Jonathan Kaufman, Lipella CEO
We anticipate the Phase 2b costing approximately $6.5 million, and $2.4 IS correct for EO3Q, and we then had approximately $4 million in hand after our issuance of equity last November. And yes we are actively exploring both equity financing and partnership pathways regarding the LP-10 phase-2b clinical trial.
The LP-310 clinical trial, for oral lichen plannus is moving forward with our existing cash.
Regarding equity financing, we are exploring a combination of options while balancing the interests of existing shareholders. There is significant insider ownership; consider that Michael and I have a little bit over 35% of the outstanding common stock.
PropThink
We’ll now start the Q&A portion of the event. You may submit a question using the text box at the bottom right corner of your screen. Let’s just wait. I see one has already come in. The first question here talks about LP-10, is there a need for two Phase 3 studies, or will the upcoming study serve as one of the two Phase 3s?
Dr. Michael Chancellor, KOL
I can answer this part. Yes, we believe it will be the second part since the Phase 2b is a well-controlled, double-blind placebo controlled trial, that I think if we achieve the efficacy, we will work with the FDA to potentially use an accelerated pathway to approval. So, therefore, just one additional Phase 3 study, will get us to an NDA application.
PropThink
Who is the natural buyer of the company for a product like this? If it does end up getting approved, is it a midsize pharma? is it a big pharma, or would you need to self-commercialize?
Jonathan Kaufman, Lipella CEO
All options are available for this indication. We have ongoing dialogs with multiple companies interested in the LP-10 asset. These include European as well as domestic companies both with a global marketing presence. Viable partnership candidates all have unique strategic interests, be that alignment with existing urology program, and/or expertise in 505(b)(2) product development.
PropThink
For the HC trials, would you need to run studies for each different type of chemo-affected cancer, or is this Phase 2b, or a follow-on Phase 3, act as a blanket for multiple cancers?
Dr. Michael Chancellor, KOL
Yes, I really like this question. It's something we thought about because it does affect men and women, radiation and chemo. So, fortunately in our first trial, although all of the patients treated were men, there was a woman who screened. It wasn't just all male prostate cancer, but that would be the largest group.
There were people that developed HC after chemotherapy. As of right now, one trial will be inclusive of men and women radiation and chemo. I think that's most strategic for Lipella moving forward.
PropThink
Are more doctors relying on chemo as a result of BCG shortages that have been going on for five years now? If so, meaning more doctors relying on chemo instead of BCG, do you see this impacting, the rates of the HC, currently or in the near future?
Dr. Michael Chancellor, KOL
Yes, it definitely could. With the chemo related HCs due to cyclophosphamide and ifosfamide, and you're absolutely right, BCG is in great shortage. That's why I think we're all interested in potentially placing PD-1 in the bladder also.
Moreover, radiation is actually used more and more across the board for pelvic cancer. Men don't like to have their prostate removed. The radiation associated HC, I believe is an increasing problem moving forward, and especially as survival is increasing with pelvic cancer treatment.
PropThink
The next question here talks about whether the company has applied for breakthrough therapy designation.
Jonathan Kaufman, Lipella CEO
Sure, I can take that one. Breakthrough therapy designation is certainly something that we're considering for this development program, especially since an effective new product for HC would meet all three orphan designation requirements. We have communicated with the FDA on this topic in 2023 and our current intention is to include the upcoming Phase 2b data in the final application. We look forward to announcing if/when we receive the designation.
PropThink
The next question asks, how does MESNA stack up as a treatment for HC? Would it protect bladder against toxic chemo and result in fewer rates of HC, if used been in tandem with chemo?
Michael Chancellor, Lipella CMO
MESNA has been around a long time, first of all. So, there’s nothing new about it and you have to give it before you give somebody chemo, and it could decrease the risk of that. So as a treatment, if somebody is peeing blood from radiation or chemo, MESNA would have no therapeutic effect.
I think MESNA is a neutral and it's not something that is considered in Lipella’s development plan.
PropThink
What do you see as the most important catalyst for the company this year? Whether that's internal data or external data anticipated?
Jonathan Kaufman, Lipella CEO
There'll be first patients treated in likely in two clinical trials this year. One will be the Phase 2a for the LP-310 for oral and then another will be for this asset sometime in the second half of 2024.
These are important milestones for us because it means that we've got all the T'S crossed and the I’s dotted in terms of making progress in the clinic.
The oral lichen planus trial is open label, so, after recruitment begins, we'll have an opportunity to look at that data as it moves forward. There'll be numerous news events on that program.
The LP-10 trial, as Michael described, is placebo-controlled and double blind. The DSMB, the Data Safety Monitoring Board, will be able to take a look at the data periodically, but most news will be recruitment progress, and when the trial is complete and the randomization is unblinded, we'll have the possibility of the most significant catalyst: the LP-10 phase-2b clinical results.
PropThink
The next question I think this is for you Michael. Which treatment in development are you and your peers most excited about. Mitomycin gel from UroGen? The device from JnJ that delivers gemcitabine? Oncolytic virus immunotherapy from CG Oncology?
I think you might have touched a little bit on this earlier on in the call, but which of these treatments do you think provide the most excitement for urologists?
Dr. Michael Chancellor, KOL
I have no personal knowledge of the conflict with any of them. I'm just speaking of urologists had for 20, 30 years. So mitomycin is okay. The degree of efficacy is only modest. If a better delivery certainly makes it more tolerable, but there's really no strong evidence over the last 20 years that it works better than BCG. The use of a checkpoint inhibitor, PD-1 has just been so revolutionary across every cancer that urologists see and other fields.
Given some of our interests that the hint that a localized PD-1 could work, is just scientifically most exciting. Lastly, I think gene therapies across the field, I'm just personally interested in. I think that's where I stand, but it is just my opinion.
PropThink
Jon, this question is for you. It's a continuation of the prior question on the catalyst. What will those first patients treated mean for the company? Is that sort of an interim data read or more validation of safety?
Jonathan Kaufman, Lipella CEO
For Lipella and for most any pharmaceutical company, if you're looking at a clinical program and making progress, having a first patient treated is signal announcement, almost as good as FDA IND approval announcement. This is because it proves the accomplishment of a lot of non-trivial, convergent requirements, including but not limited to: obtaining the FDA IND approval, then obtaining central IRB approval, creating and effectuating a data safety monitoring board (DSMB), contracting a CRO, selecting sites, negotiating site contracts, scheduling site start-up, site trainings, and finally site IRB approved recruitment - all non-trivial. Having the first patient treated, is proof that all if this is complete. It's when the clock starts ticking toward trial completion.
PropThink
These are all the questions that I see in the queue right now. Michael, would you like to add any final remarks?
Dr. Michael Chancellor, KOL
Speaking as a CMO and as a clinician too I feel very strongly that we're doing good and that we're focusing on diseases that have unmet needs. We're repositioning a drug and a delivery method that's well known to the regulatory. I'm excited to hopefully contribute to medicine and healthcare. Thank you for the opportunity, Deniel.
PropThink
Everyone thank you for your time. The event obviously proved to be very insightful. This concludes the presentation and the Q&A portion. This event was sponsored by Lipella Pharmaceuticals, if you’re interested in getting in touch with the company you may do so via their website lipella.com. If you’re interested in learning more about PropThink, you can visit our website at propthink.com or follow us on Twitter with the handle @propthinker. Thank you for attending and I hope to see everyone again.
Disclaimer:
PropThink Digital Conferences are organized and marketed by PropThink LLC ("PropThink" or "we") with the aim of connecting subject matter experts with investors. This Digital Conference is sponsored by Lipella Pharmaceuticals, Inc. (the "Company") which has paid fifteen thousand dollars for PropThink to conceptualize, market and host a Digital Conference featuring the Company. PropThink is not a registered investment advisor in any jurisdiction. We do not publish investment advice and remind readers that investing involves considerable risk. PropThink urges all readers to carefully review the Company's regulatory filings and consult with an investment professional before making any investment decisions. Please read our full disclaimer at https://propthink.com/disclaimer
Access This Content Now
Sign Up Now!
