Q4 2022 Jaguar Health Inc. Earnings Call
Speaker 2: Good morning. Before I turn the call over to management, I would like to remind you that management may make forward-looking statements relating to such matters as continual growth prospects for the company, uncertainties regarding market acceptance of products and the impact of competitive products and pricing, industry trends and product initiatives.
Speaker 2: including projects in the development stage which may not achieve scientific objectives or meet stringent regulatory requirements. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially than those contemplating and such forward-looking statements.
Speaker 2: These statements are based on currently available information and management's current assumptions, expectations, and projections about future events. While management believes its assumptions, expectations, and projections are reasonable in view of currently available information, you are questioned not to place undue reliance
Speaker 2: of the company's form of 10-K for the year of 2022, which was filed March 24, 2023, and its other filings with the SEC, which are available on the Investor Relations section of Jaguar's website.
Speaker 2: Except as required by law, Jaguar undertakes no obligation to update or revise any forward-looking statements contained in this presentation to reflect new information in future events or otherwise. Additionally, please note that the company's
Speaker 2: Supplements is condensed consolidated financial statements presented on a GAAP basis by providing non-GAAP EBITDA and non-GAAP recurring EBITDA. Jaguar believes that the disclosed items of those non-GAAP measures provide investors with additional information that reflects the
Speaker 2: the basis upon which the company's management assesses and operates the business. These non-GAAP financial measures should not be viewed in isolation or as substitutes for GAAP net sales and GAAP net loss, and are not substitutes for GAAP net loss.
Speaker 2: for or superior to measures of financial performance in conformity with GAAP. Today's conference is being recorded. At this time, it is now my pleasure to turn the conference over to Lisa Conte, Jaguar Health's founder, president, and chief executive officer. Lisa, the floor is yours. Thank you very much, and welcome to all.
Speaker 2: As you just heard, my name is Lisa Conti and I am the founder, president, and CEO of Jaguar Health and our wholly owned subsidiary in the United States.
Speaker 2: NAPO pharmaceuticals. Sometimes we use NAPO and Jaguar names interchangeably.
Speaker 2: I'm also a member of the board of Napo Therapeutics, the corporation we established in 2021 in Milan, Italy, which is focused on expanding access to profilomer in Europe , in particular for rare disorders. I'm also a member of the board of Napo Therapeutics, the corporation we established in 2021 in Milan, Italy, which is focused on expanding access to profilomer in Europe , in particular
Speaker 3: I'm going to begin today by letting you know we will highlight shortly the key events that we expect in 2023 will be transformative in terms of value generation for all our stakeholders, including patients and shareholders.
Speaker 3: Moving late-stage pipeline opportunities towards revenue-generating reality. This is an important theme that you will hear infused throughout today's call.
Speaker 3: Right now, I will review the key top-line results for the fourth quarter of 2022. Prescription product net revenue was approximately $11.9 million for the year ended December 31, 2022.
Speaker 3: versus approximately $4.3 million for the previous year and in December 31st, 2021, an increase of 178.7%. We are quite pleased with the growth trajectory of our current prescription drug business.
Speaker 3: which for my testes is currently limited to the approved specialty market indication of HIV related diarrhea. As I often say specialty often typically means a relatively small market opportunity.
Speaker 3: Regarding the company's cash position,
Speaker 3: The company had cash of approximately $15.3 million as of March 24, 2023, just a couple of days ago. The filing date of Jaguar's annual report on foreign 10K for the year 2022. I'm going to repeat that. Cash of approximately $15.3 million.
Speaker 3: as I speak this morning, an important and meaningful subsequent event in our 10K filing that I'm often asked about. Thank you for listening.
Speaker 3: Following my updates, please check up to the intensely testing Monica
Speaker 3: Carol Liza, Jaguar's Chief Financial Officer, will provide a recap of the key financial results for 2022. And then we'll hear from Ian Wendt, Jaguar's Chief Commercial Officer. Ian will speak to updates on my testing-related commercial initiatives to continue to educate and serve the HIV community.
Speaker 3: and about ongoing commercial efforts underway for cannalivia CA1, our prescription drugs for the treatment of chemotherapy-induced diarrhea in dogs.
Speaker 3: As a reminder, our commercialized human drug product is named Mytesi. The generic name is Krofelimer.
Speaker 3: It's a first-in-class anti-secretary agent approved initially in the United States for the specialty indication of HIV-revited diarrhea, very specifically the symptomatic release of non-infectious diarrhea in adult patients with HIV-AIDS on anti-retroviral therapy.
Speaker 3: As I mentioned, the relatively small market disindication was fast tracked by the FDA, and that's why HIV diuret is the first approved indication for Krofelemer.
Speaker 3: As I frequently state, what is really powerful about Crophelimer is that it is a pipeline within a product. And what I'm going to focus on today are our key clinical milestones. Again, what we believe are potentially transformative events in 2023 in support of the company taking Crophelimer from pipeline opportunities.
Speaker 3: Two, with the potential of important and significant clinical trial results this year, tangible revenue generating patient-benefitting, shareholder stakeholder-benefitting product indications.
Speaker 3: Our ongoing pivotal phase three trial on target trial called the on target trial of Crofellamer for cancer therapy related diarrhea. And I may refer to that as C.T.D.
Speaker 3: is our flagship development program.
Speaker 3: This trial is being conducted with the same dose and formulation of R-MITESC products.
Speaker 3: course, already commercialized in the United States for HIV-related diarrhea. The same...Now we have an hour in Virginia The whoever are against it has a scores
Speaker 3: Same product, same dose, same formulation.
Speaker 3: The on-target trial is evaluating the effectiveness of Kofelemer's novel mechanism of action.
Speaker 3: the modulation of two chloride ion channels in the gastrointestinal tract to mitigate or substantially reduce CTD in a prophylactic setting.
Speaker 3: It is a study that aims to expand the approved indication of my testee from the current limited HIV-related diarrhea to the potential blockbuster needs of prophylaxis in patients with cancer therapy-related diarrhea. Our efforts over the past year to expand the untargeted trials to...
Speaker 3: and international sites with trial sites now active in Eastern Europe in both Georgia and the Republic of Serbia as well as in Argentina and Taiwan have significantly accelerated patient enrollment. Enrollment is now at approximately, it's actually at over 80%.
Speaker 3: and target trial enrollment of 256 patients is expected to complete early in the second quarter of 2023, which is literally just around the quarter.
Speaker 3: We do feel that the on-target trial will be transformative for value and value recognition at Jaguar. DiWia is the most common side effect associated with cancer therapy as many as 50 to 100% of patients experienced diarrhea.
Speaker 3: In addition to addressing patient comfort and dignity, which is so important.
Speaker 3: With approximately 40% of patients changing or stopping their life-saving cancer therapy due to diarrhea, there is a clear, unmet medical need for a focused, paradigm-shifting biological approach.
Speaker 3: Our expectation is that the placebo controlled on target trial will provide evidence that diarrhea associated with targeted cancer therapies is chronic.
Speaker 3: Impacts the patient's ability to remain on their targeted cancer therapy regimens, approved doses for better outcomes, better outcomes in their cancer treatment, and that addressing CTD reduces overall healthcare costs such as required hospitalization.
Speaker 3: and rehydration of implications of chronic and or severe diarrhea.
Speaker 3: Remember, profilmer has a safety profile in support of its current approval, thus providing a potential opportunity for a paradigm shift for both prophylaxis.
Speaker 3: and management of CTD for which there are no current approved or tested anti-diarrhea reagents.
Speaker 3: for which antimotility drugs such as the modium and l-paramod, which are primarily opioids, have constipating risks.
Speaker 3: which is totally inappropriate and again untested and unapproved for chronic administration.
Speaker 3: Prophile America is not an opioid and does not have that constipating risk associated with opioids.
Speaker 3: Each year, according to the CDC, more than 1 million cancer patients receive chemotherapy or radiation in an outpatient oncology clinic in the United States.
Speaker 3: Treatment can last for a month to years.
Speaker 3: in both the curative and metastatic situations.
Speaker 3: These targeted therapies of which are about 70 now.
Speaker 3: which are used on a chronic basis, often for the rest of the patient's life, work for the most part.
Speaker 3: By mechanism that induces the type of secretory diarrhea that crofelominalizes.
Speaker 3: Again, on target is a prophylactic study, which tells you a lot about how important it is to prevent the onset and the impact of diarrhea during cancer treatment with targeted therapy drugs.
Speaker 3: CTD is not the mild loss of bowel control that we've all invariably experienced with perhaps the mild flu, a bad meal. This is diarrhea that computations in the hospital cause organ shutdown and has even contributed to death in some patients.
Speaker 3: to have been studied in targeted cancer agent manusatius clinical trials.
Speaker 3: To project the potential global market opportunity for CTD, since Kropellin would be the first drug to be approved for this indication.
Speaker 3: To project the potential global market opportunity for CtD, since Kropellin would be the first drug to be approved for this indication, we're looking at an analogous market.
Speaker 3: Well, we don't put out financial, specific financial guidance and forecasts. The value of the global chemotherapy induced noisy and vomiting markets, CINV.
Speaker 3: is projected to reach $23.9 billion by 2022, according to report published by market research from healthcare analysts.
Speaker 3: And CINB agents are typically only used for about the first three to five days in traditional cytotoxid chemotherapy, and many of these agents are generic, which
Speaker 3: So, somewhat lowers with the projections, financial projections can look like for proprietary drugs.
Speaker 3: with the projections financial projections can look like for proprietary drugs. With Ctd,
Speaker 3: We are talking about diarrhea that can persist on the chronic faces for months or years. That's the paradigm shift.
Speaker 3: We are very excited about our CTD program, the successful completion of patient enrollment in the on target pivotal trial, which as I mentioned, is targeted for early in the second quarter of 2023. Will we expect lead to a primary endpoint readout in Q3?
of this year.
and then to a supplemental new drug application filing for the same formulation of crocelamer as the currently commercialized drug mitesci.
My testee is already approved for chronic use in people living with HIV-AIDS and it has a full FDA-compliant supply chain in place from the rain forest.
to our distribution network with specialty pharmacies across the United States.
And as a reminder, safety and manufacturing are the two most common reasons that new drug applications fail, and these activities are completed for my testes from a regulatory perspective.
Hence, we spent much care and engaged in extensive communication with the FDA in the design and execution of this final clinical and regulatory step to support bringing co-fellomers to cancer patients suffering from diarrhea and or the risk of diarrhea.
on a profile act of spaces from their prescribed therapy. In preparation for the expected commercial launch and co-pellarmor of the CTD, we're increasing our focus on patient advocacy initiatives in the United States. In support of this goal, we're very pleased that Dr. Kelly Shanahan
a former clinician herself and a obstatic breast cancer patient who is now a full-time independent patient advocate has joined the Jaguar Scientific Advisory Board as both a healthcare provider and cancer patient.
She shares our deep commitment to patient comfort and dignity, especially to the importance of preventing and ameliorating CTD on a chronic basis and in both a curative and metastatic settings.
and to support a care-in-case cancer patients in general.
We are so pleased to hear Dr. Shanna Hens voice and perspective on how successful supportive care management is a key component to successful cancer treatment outcomes.
She brings a unique and welcome perspective to the community, including industry that will all meant our efforts to bring about a paradigm shift to address the very high and neglected comorbidity of C-T-D as novel targeted agents and approaches are addressing long-term management and potential cures for cancer.
We support a full community approach to holistic patient care and complete to support life and support quality of life.
I'm now discussed by two prioritized rare disease target indications for the pro-pelinder
I'll now discuss my two prioritized rare disease target indications for a crofelomer, short bowel syndrome.
which I referred to as SPS, the intentional failure in adults. And microbialists include inclusion disease, MVID, and ultra rare pediatric congenital diarrhoea disorder.
This year, Jaguar and the company we established in Europe , Napo Therapeutics, are planning to support third-party and we are supporting third-party investigator-initiated proof-of-concept studies of Crofelanin in patients with SBS with intestinal failure or pediatric patients with MDID focused on obtaining...
Proof of concept data showing reduction of requirements of parental support, including parental nutrition and or IV fluids.
In accordance with the guidelines of specific European Union countries, publications of data from proof of contact trials could support early patient access programs to Grafell and for SPS within testnal failure or MDID.
potentially in 2024 through programs in the Eastern European countries, Italy, France, UK, perhaps Spain as well.
Early access programs do not exist in the United States. Are revenue generating?
and reimbursable for participating patients, while the indicated product is continuing through clinical development for full approval in the EU. Let me describe from a moment the catastrophic medical situation for people with short bowel syndrome. Normal, small intestine is 20 to 25 feet in length.
In short bowel syndrome, the patient's mobile could be less than five feet for congenital reasons or as a result of surgery due to cancer inflammation or an accident. As you can imagine with a very short gut, it's like a cittance. What goes in comes right out.
The bottom line is that it's not a enough intestinal real estate, a enough surface area for the SPS patient to absorb the nutrients of life.
carbohydrates, protein, fat, vitamins and minerals. So what happens is that such espionage-? aten....
That's having testinal failure. Often end up on parental nutrition, the intravenous feeding of liquid nutrients for up to 20 hours a day, seven days a week.
Obviously, this has a significant negative impact on patients' quality of life, and there are multiple adverse events, infections, and other complications associated with parenteral nutrition quite common.
And parental nutrition is expensive, costing hundreds of thousands to a million dollars a year to manage an individual patient, including the myriad of associated complications with high morbidity, high mortality.
The global SDS market is projected to reach
$5 billion by 2027, according to reports and research reports. This again is for an orphan indication of about 40,000 patients around the world, but a classic orphan rare disease business model.
Although parental nutrition is considered the standard of care,
There is a drug product to prove for SPS called to-to-to-dubu-tides and it's a GLP-2 analog. It's essentially growth hormone intended to grow the real estate of the gut slightly. So there's a little bit more time for absorption of the nutrients of life. It's administered as an injection and is estimated to be utilized in less than 10% of the SPS.
population, again, is not standard care. To do with the glybosyfarch pronounce, to do the glybos has a range of side effects, including liver disorders.
and is not tolerated by many patients on a chronic situation.
The primary endpoint in the trial for the approval of tibetide was the reduction in the time required to be on parenteral nutrition by about 20%.
What we're looking to do with Crophelimer is to reduce the time on torrential errone nutrition as the primary endpoint as well. That pathway has already been utilized and provide better stool consistency and the quality of life measurement. We are working to design a global phase.
to short bowel syndrome study of crocalomar that harmonizes with the requirements of both the FDA and the European Medicines Agency, EMA, which is the regulatory agency of the EU.
Jaguar is also planning to submit an investigation on new drug application and IND to the FDA for MVID in the second quarter of 2023. Again, another milestone just around the corner.
So, to recap, early Q2, 2023, literally just a couple of days away to get into Q2, we expect to have completion of enrollment in our phase 3 trial of prophylaxis of cancer therapy related diarrhea. That's the on-target trial.
with a primary endpoint readout expected in Q3 of this year.
And within the same time frame, we're targeting our first proof of conflict evidence for patients with either SBS within testinal failure and or for MVID in support of potential early access program participation, revenue generating participation.
in certain European countries.
This pathway could bring in meaningful revenues. Well, Prophellumer continues to go through the process for full approval not only in the EU on a global basis for these two rare disease educations.
I'm not going to discuss our other development stage programs at this time.
We are prioritizing for 2023 these two late-stage clinical development programs with key near-term milestones, with the potential to be transformative in value recognition for Jaguar, particularly with the current financial market conditions for emerging biotech companies, which has not spared Jaguar either.
And I do want to recap our current cast mission.
$15.3 million, relevant to achieving these important clinical milestones. Before I hand the discussion over to our CFO , Carolina, I want to let you know that anybody participating today that we will have a brief Q&A segment at the end of the webcast to address questions if there are any.
submitted in writing and that we have time for. Questions can be submitted via the webcast link for today's event that appears on the events and presentations page of the investor relations section of Jaguar's website. The URL for Jaguar's website is jaguar.el. We will now move along to key financial results for the fourth quarter of 2022.
million for the year ended December 31.
2022 versus approximately $4.3 million for the year ended December 31, 2021.
An increase of 178.7%.
prescription product net revenue of approximately $3.3 million.
dollars in Q4 2022 increased 3.4% over the third quarter in 2022.
and increased approximately 57% over prescription product net revenue in the fourth quarter of 2021.
My TESI total prescription volume was approximately 5,947 in the year 2022.
Due to the transition to limited distribution specialty pharmacy model in 2022,
The company cannot accurately compare prescription volume from
2021 to 2022, as there are significant differences in reporting methodology from these distributions
2022 as there are significant differences in reporting methodology from these distribution models.
In the future, the company will be able to accurately reflect growth in prescription volume using 2022 as the new baseline.
My Tessie total prescription volume decreased slightly by approximately 2% in the fourth quarter of 2022 over the third quarter of 2022.
Description volume differs from invoice sales volume.
which reflects among other factors varying buying patterns among specialty pharmacies.
in the closed network as they manage their inventory levels.
The loss from operation decreased by $6.3 million.
From $40.7 million in the year 2021,
to $34.4 million in 2022.
Largely, due to the aggregate improvement in net revenue of $7.6 million,
decreased cost of sales and marketing expenses of 400,000 and warrant inducement expenses of $1.6 million in 2021 and non-recorded in 2022.
These were offset by the aggregate increase in R&D and G&A expenses of $3.3 million.
Nam Gap, EBITDA, for the year 2022 and the year 2021, we're in that loss of $28.1 million.
and net loss of 37 and a half million dollars, respectively.
Net loss attributable to common shareholders decreased by approximately $5.1 million.
from $52.6 million in 2021 to $47.5 million in 2022.
In addition to the loss from operations, interest expense increased by 4.3 million from 8.4 million in the year 2021 to 12.7 million.
In 2022, primarily due to the additional interest expense incurred on loyalty interest agreements as a result of the change in the timing of payments due to exchanges in a new loyalty interest purchase agreement. The loss and the extinguishment of debt.
Increased by $1.4 million.
from $800,000 for the year 2021 to $2.2 million in 2022.
Due to the extinguishment laws from the exchange of the outstanding balance of a royalty agreement for shares of the company's common stock.
Change in fair value of financial instruments and hybrid instruments designated a fair value option or FBO decreased.
by $1.9 million from a loss of approximately $2 million in the year 2021.
to a loss of about $21,000.
of about $21,000 for the year 2022.
primarily due to fair value adjustments in liability classified warrants and notes payable designated.
to fair value adjustments in liability classified warrants and notes payable designated as FBO.
Other income or expenses increased $1.7 million from approximately 800,000.
And other expenses for the year, 2020, 2021. So approximately 1Million dollars.
and other incoming 2022 due to write-off of extinguished liabilities as a result of legal release and reversal of long outstanding pools with reasonable uncertainty to not be incurred.
Well, that concludes my recap of high-level financials for the fourth quarter and the full year of 2020-22.
I will now hand the discussions over to Ian Wint, Jaguar's Chief Commercial Officer.
Thank you, Carol, and good morning to all. Q4 2022 is the sixth consecutive quarter of growth in my testing at revenue which we're quite pleased about.
As previously announced, the transition we completed in January 2022 to a limited distribution network of specialty pharmacies resulted in a meaningful reduction in mitosis distribution costs as well as a higher average net price.
I'm very pleased to report that we significantly outperform the industry grossed in that average in the fourth quarter of 2022 as we did in the four previous quarters
for sales of our human prescription product. For comparison, according to prescription drug data and analytics firm SSR Health, the rolling four quarter average gross to net discount rate in Q3 2022 was 48.9% for all US prescription branded products.
In 2022, the total gross net discount for my TESI was approximately 20%.
The transition to specialty pharmacy distribution also assists in the preparation of the company's U.S. commercial distribution network for potential future indication and expansion of prophylmer to other populations of patients with complex medical needs, such as CTD, inflammatory bowel disease and SBS.
I'm also pleased to report that our innovative recently launched programs that further support patients' connections to care and medication and access services are continuing as planned. Our telehealth initiative, which went live in May 2022, enables patients seeking help with their HIV-related diarrhea to be linked immediately to a provider for assistance with their medical needs.
This capability prevents patients from having to wait until their next scheduled doctor visit to get help with what is an urgent problem.
Additionally, as announced March 13th, we are excited to be developing an artificial intelligence-powered web portal for U.S. healthcare professionals to support patient access to myTESI.
We remain committed to reducing access and reimbursement barriers for mitosis patients. One key challenge we often hear from patients and their healthcare providers is that payers and insurance companies frequently require prior authorization to approve medication reimbursement. Artificial intelligence, AI technology, like OpenAI's You are absolutely right!
to help make this otherwise burdensome process easier and faster for healthcare providers to navigate in a compliant way.
Leveraging AI technology in support of the prior authorization process is expected to help a significant number of Lactase patients start on their medically appropriate and necessary medication quicker and be able to stay on their prescribed regimen helping ensure they spend fewer days separating needlessly from HIV related diarrhea. Turning to the animal health side of our business, Canalevia CA1.
our FDA conditionally approved drug for the treatment of chemotherapy-induced diarrhea, or CID in dogs, became commercially available to veterinarians across the United States at the end of April 2022.
Since that time, we have succeeded in pushing Canalevia CA1 into broad distribution with the leading veterinary distribution centers. Canalevia CA1 net revenue was approximately $24,000 in the fourth quarter of 2022, representing an increase of 100% over Canalevia CA1 net revenue in the third quarter of 2022, which totaled approximately $12,000. Health activities for the drug remained underway and reception of Canalevia CA1 was completed.
about all of our important activities underway in 2023 and beyond with a very, very sharp strategic focus on these key clinical milestones in 2023, which I just cannot say enough, which we feel will be transformative for some value recognition.
for a company whose value and industry has been hit hard in the past months and year. I do want to say in closing,
You deeply about Jaguar. This past Tuesday was International Day of Forest, and I want to take a moment to express how proud we are to be collaborating and interdependent with the people and tropical forest ecosystems of Peru from where we sustainably support source.
the latex of dragon's blood tree, the plant also known as Croton Lechelery, from which Crofelomer is isolated and purified. It is clear that the cultural and ecological health of people and forests are intertwined at multiple levels, and we wish to express our gratitude to our partners and communities in the rainforest for their support. Thank you for your attention. Thank you for your attention.
who've been working with us and teaching us for several decades how to sustainably manage this valuable medicinal plant within their ecosystems in support of our mission to expand cofilomer access to all patient populations in need around the globe.
I do also want to remind everybody that Crofalomer-Mytesi is a natural product. It's organic, as I mentioned, sustainably harvested fair trade, and it is the only oral drug approved by the FDA under botanical guidance.
And under botanical guidance, there's no practical pathway to bring a generic to market. And so while we have well over 100 patents issued and many more that are being filed on a regular basis, as you do in the pharmaceutical industry, we essentially have exclusivity forever, which is a valuable and additional valuable asset and characteristic of this product.
as we go into business development discussions and negotiations.
So this concludes our formal webcast for today. And I'm going to now look at some of the questions and we will do a few Q&A as we have a little bit of time left. Give me a moment here to pull those up. Okay.
are from a webcast for today. And I'm going to now look at some of the questions, and we will do a few Q&A as we have a little bit of time left. Give me a moment here to pull those up. And.
Okay.
Looks like there are a few questions in there. Okay.
So, is the primary completion date still this month? March 2023 for Came with European Disit
So, as I mentioned, I'm just going to recap timing here.
We expect to complete enrollment early in the second quarter. So early in the second quarter is
April , beginning of May, we are standing behind that. And then that's completion of enrollment. The primary endpoint is after three months of treatment.
So you can count forward, let's say you go May, June , July , so the end of July , beginning of August . And then typically in the industry, you would have about eight weeks plus or minus.
to freeze the database upon which you get the primary endpoint released. And so that's the timeframe that you can look at and gives us what we mentioned that we expect to and are targeting the primary endpoint in the third quarter of this year. So you can see the cascade of events.
from completing patient enrollment. Again, what we're looking for here is the statistical significance as negotiated with the FDA, and there was a lot of discussion with the FDA on this trial in a positive sense, on that primary endpoint because we are talking about the expansion.
of the indication for supplemental NDA for my testing already on the market. Same dose, same formulation, literally the same bottle. My testee already on the market already approved for chronic indication. So for example, chronic safety studies, carcinogenicity studies have already been completed and supported that chronic indication.
And obviously we have a full supply chain regulatory compliant in place to take the product from Peru to a bottle in essentially any specialty pharmacy that we're working with in the United States. So manufacturing is completed as well. Two most common reasons why new drug applications get pushed back.
So I can tell you that we, well, what I think the most important thing that I can tell you is what I did tell you already that are, and what's in the public domain here, $15.3 million in the bank right now with this key clinical activities that we're looking for, which we feel can be transformative in value.
in targeted for the third quarter of this year.
So, I think that addresses the.
I think that addresses the sentiment behind that question.
Okay. I'm just going to touch my head. Okay.
Let's see, the question is, with Phase III enrollment largely complete in the second quarter.
and the switch to specialty pharmacy for Mitessi complete.
expenses to significantly decrease going forward. Carol, why don't you make any comments that you would like on that. But let me point out that.
expenses to significantly decrease going forward. And Carol, why don't you make any comments that would you like on that? But let me point out that the six.
The significant expenses in the company right now are associated with the clinical work to expand the indications and to get to new populations for pro-pheloma. And those clinical trials are still ongoing. And in fact, as you come towards the end of clinical trials, you have additional activity from statisticians, quality operations to make sure that you clean up and you freeze those databases in an accurate way. But Carol, did you want to make any additional commentary?
Sure, we did save around the distribution costs compared to 2021 and 2022. So those were the big cost savings right there and of course the net revenue significantly increased.
For R&D, yes, there will be some increases there because of the clinical trials surrounding our main indications at FOCUS, which is CTD, and the SBS group. I think there's anoon for questions, so bear with me and talk to me.
Those are the key savings that we had for 2022 and 2021. Thanks, Carol. So, here's a question that I appreciate to bring up this topic. Someone was wondering if there's still future plans of attaining Fast-Track Voucher for cholera.
So the collar program is very important and exciting program. The collar mechanism of diarrhea is the pure clinical manifestation of the mechanism by which crofelomer works and our second anti-secretory agent.
known affectionately right now as NP-300. We do have an approved IND for NP-300. What this is referring to is that product is being developed with the financial return that is being targeted by us of a certain amount of time.
tropical disease priority review voucher. And what that is is sort of a prize that you get from the FDA that provides incentives to develop products for certain tropical diseases, certain rare diseases, and cholera is on that list. And so you get this prize, this voucher, when you have a successful
towards in six months or less. So it provides certainty in some sense, greater efficiency and speed in reviewing a new drug application. And that voucher is transferable in sales, and you can sell them. And there is a market for them. And they sell anywhere from the lowest ever with something like $67 million. I think the highest ever was 300 and something million dollars.
in recent years.
So we're pursuing that the key is that that voucher is only available for the first indication for which a product is approved. Profelomer is already approved.
But our second generation anti-secretory, NP300, is also an anti-secretory agent, we feel is a distinct product under botanical guidance and comes from the same plant, Croton Lurch 3, Dragon's Blood, and works by the same mechanism of action.
In earlier years, we had done clinical work in cholera with Profelimer that is published, posters are published that showed...
statistical significance in a key endpoint for the reduction of dehydration. And what kills a cholera patient is not the cholera infection, it's the dehydration that typically occurs between 6 and 18 hours after infection, so often considered the death zone. And that's where we saw the significant reduction in the dehydration. So we'll be following the same clinical pathway, in fact, the same principal investigator, and we'll be following the same principal investigator.
the same clinical trial site with MP300. Why did I not talk about it? Because, again, with the industry and the valuation of Jaguar and other companies in the industry hit so hard this year, we are focusing on what I talked about. Those key, what we feel are transformative clinical events that move us.
from pipeline to revenue generation. And the cholera program wouldn't do that in 2023. So it's a longer term before we do we get to that revenue generating or voucher generating situation. So it is on hold just for 2023.
And as we get through these milestones and get some value recognition in this company, God bless, we will be able to turn that very, very important program on. And it's not as long a program as CTD or even HIV was, because these are acute clinical trials. So they are two to three days of drug administration. So the trials move much faster.
So thank you for that question. Somebody asked about cantilever for exercise induced diarrhea in dogs.
So, Kenilevia CA1 is a conditionally approved product, and in a second, Ian, I'm going to let you talk about what that means specifically and how that affects our ability to educate and promote that product. And a second conditional approval, exercise-induced diarrhea.
is in discussions with the Center of Veterinary Medicine at the FDA right now. So what's being discussed and negotiated is their desire for us to do some clinical work specifically in that patient population, though it is for a conditional approval, which often gives you a lot lower.
BAR for clinical work. Again, it falls in that same category as Colorado. Where are we going to put our dollars and resources in 2023 to make a revenue generating difference in the near term? So that's still under discussion with the Center of Veterinary Medicine.
Ian, do you want to talk about some of the limitations of a conditionally approved product, but the excitement of what we're seeing with chemotherapy-induced diarrhea in dogs? And by the way, chemotherapy-induced diarrhea in dogs is highly predictive and analogous to the situation in humans. So it gives us, again, another reason to be highly confident about our on-target trial in humans.
So go ahead Ian. Yeah happy to thanks Lisa. Yeah the CA1 or conditional approval designation that you see for Candlevia right now is a easier pathway to approval. You have to show reasonable expectation of effectiveness and doesn't require necessarily a full
Effectiveness trial that you might in the designated population that you might see for traditional approval So it allows you to get to market faster and for less cost
But it does come with some limitations and a couple of them just to just so you understand what those might be are that it cannot be used off label. So there's a federal law in place that for CA1 designated medications, prescription medications, they have to strictly adhere to the label as indicated.
And you might be aware that on the veterinary community, they write off-label medications all the time, and he would help the physicians do as well. But in this case, for C1, there is that limitation. There's also a limitation in the size of the market. So right now...
You can only seek this in the canine arena for indications that would dose no more than 70,000 dogs. So there are some limitations there. And then it comes with some requirements to complete the full effectiveness trial for traditional approval within a five-year timeframe of your initial approval. So we're working on that and ultimately we will end up, we anticipate.
having full approval in the future. We're working with the CBM on that clinical development program. But we are seeing great uptake of Candlevia CA1, especially among veterinarian colleges, which are our primary target audiences. We engage with them in a variety of ways. In fact, I'm off in a couple of weeks of the Great Cancer Society meeting.
we'll have a chance to further educate that important customer group on the benefits of Canalee VCA1. Thanks, Ian. Okay, we have time for one more question here. We're coming upon the witching hour. We're trying to keep this to an hour.
Does it, which I assume is talking about corfelomer, also work on IBS? There are so many potential indications that reference to a pipeline within a product. There is published Phase II data for IBS, irritable bowel syndrome.
with Crofelmer, and we couldn't do everything. So there are target pipeline indications of Crohn's disease, inflammatory bowel disease. There are investigator-initiated trials going on right now in functional diarrhea, in IBS, as well. Of course, we have short bowel syndrome and CDD.
So there are other indications, other important patient populations to go after in the future, which is a very risk-mitigated future drug development strategy for this company because, again, it would be indications of its mitosis where we already have the safety, we have the chronic adverse Deus if the Mos.
Right now, we are very focused, can't say it enough, on cancer therapy-related diarrhea, short bowel syndrome, and MVID, and other indications in other territories in the future. So with that, I know there's some other questions there. I can't get to all of them, and some of them we've already referred to.
Again, the sentiment behind the question and the comments that we've made. Thank you all very much for listening. Thank you very much for your support for Crophelimer, Mytesi, Jaguar, Napo, Napo Therapeutics. We're going to get back to work here. It's going to be a very, very important year for all the stakeholders. We're really looking forward to what will be uncovered in the next six, seven, eight, nine months at this company.
Thank you. I'll conclude now. Thank you. This will conclude today's webcast. You may disconnect at this time. Thank you for your participation.
I.