Navidea Biopharmaceuticals, Inc. (NYSE:NAVB) Q2 2022 Earnings Conference Call September 8, 2022 4:00 PM ET
Company Participants
Michael Rosol – CMO
Alex Cappello – Vice Chair
Erika Eves – VP, Finance & Administration
Conference Call Participants
Michael Okunewitch – Maxim Group
Fred Zaino – Keystone
Michael Okunewitch – Maxim Group
Operator
Greetings. Welcome to the Navidea Quarter Two 2022 Earnings Call and Business Update. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] And please note that this conference is being recorded.
I will now turn the conference over to Dr. Michael Rosol. Thank you, sir. You may begin.
Michael Rosol
Thank you, and thank you all for joining us here today. This call is being webcast live on our website, ir.navidea.com, and a replay will be made available. There is an accompanying slide deck that is also being displayed. Following prepared remarks, we will be conducting a live question-and-answer session. Navidea’s Chair of its Board of Directors, Mr. Alex Cappello, it’s Vice Chair, Mr. Kim Scott and its Vice President of Finance and Administration, Erika Eves, are joining me on the call today.
During the course of this conference call, we will be making forward-looking statements regarding future events and the future performance of the company. These events relate to our business plans to develop Navidea’s molecular diagnostics and immunotherapeutics, which include clinical and regulatory developments and timing of clinical data readouts, along with capital resources and strategic matters, as well as the impact of the COVID-19 pandemic on Navidea’s business operations. All of these statements are based on the beliefs and expectations of management as of today. These statements involve certain assumptions, risks and uncertainties and could cause actual results to differ materially. We assume no obligation to revise or update forward-looking statements, whether as a result of new information, future events or otherwise. Investors should read carefully the risks and uncertainties described within the safe harbor section of our website, as well as the risk factors included in the company’s most recent quarterly and annual filings with the SEC.
With that, let’s begin our update. During the second quarter of 2022 and since, we continue to work on financing for the company. We closed on $2.5 million bridge loans from the company’s Vice Chair of the Board of Directors, Mr. Scott. And last month, the company completed a rights offering with the investment banking arm of Maxim Group.
The company received aggregate gross cash proceeds of approximately $6.2 million in the rights offering. If exercised, additional gross proceeds of up to $11.6 million may be received through the exercise of warrants issued in the offering. The warrants are exercisable immediately, expire 5 years from the date of issuance and have an exercise price of $0.50 per shar.
We also received an accelerated reimbursement payment of $800,000 for certain research and development expenses from a strategic partner. We continue to plan for additional capital raise in the coming months.
We have advanced our clinical trials in rheumatoid arthritis, as well as our pipeline and other diagnostic indications and in therapeutics. Overall, we’ve made good progress on our Phase IIb trial in rheumatoid arthritis, or RA, comparing imaging to biopsy, and we announced promising preliminary results and our ability to distinguish the fibroid pathotype from the non-fibroid in our first 11 evaluated patients. These strong early results support our hypotheses and provide great data and support of fulmanocept imaging is a biomarker of CD206 expression in joints of patients with RA.
We also continue to enroll into the RA Phase III and have recently opened up an additional 9 sites for a total 12 now open. We are also advancing our therapeutics and imaging applications through collaborative relationships with various well-known institutions and investigators across the globe, and we are growing and diligently maintaining the company’s intellectual property. The team here works extremely hard and efficiently and I’m very proud to be associated with this outstanding group of individuals.
You may have seen our recent release about the termination of the Jubilant memorandum of understanding. This memorandum carried with advising terms of exclusivity, such that we could not entertain discussions or offers from other parties for the rights to our potential commercial product in RA. From the time of the original signing of the MoU to now, we have continued to advance tilmanocept in RA into the Phase IIb and Phase III trials currently underway. The ending of the exclusivity period is a significant opportunity to speak to potential partners with advanced data in hand.
In the Capital Royalty Group case, we announced a ruling awarding CRGs attorney fees on their breach of contract claims against Navidea and Macrophage Therapeutics. We are disappointed in the court’s ruling and do not believe the law and the facts presented at the trial support this ruling. We are discussing our best course of action to pursue in response to this ruling. As we’ve said in the recent past, there are many things we are working on behind the scenes, and we will provide you with updates as soon as we are able and as appropriate.
Now I’d like to provide more detail around the clinical updates. I’ll begin with progress in our rheumatoid arthritis program. We continue to enroll into our Phase III trial in RA. As I just mentioned, we recently announced that we have opened up 9 new sites at the end August and have enrolled 30 subjects to date. We’ve done this with about 16 total site months of enrollment. So our per site, per month enrollment rate is significantly greater than the average.
The indications we are going forward in RA once again, are one, early prediction of treatment response to a new or first-time anti-TNF alpha therapy and two, identification of RA patients with low level of localization of tilmanocept to are less likely to respond to anti-TNF alpha therapy.
As we have discussed previously, there is a large unmet need for reliable early predictor of whether or not a therapy is working in a patient with RA because if a drug is not working, the patient’s disease is not being treated, and this can lead to long-term health consequences along with unnecessary high drug costs for ineffective therapies that bring with them possible side effects.
Our Phase III trial will establish the ability of technetium 99m tilmanocept imaging to serve as an early predictor of treatment response in RA patients switching to an anti-TNF alpha therapy, addressing this unmet medical need.
In NAV3-32, our comparison study of tilmanocept imaging biopsy, this trial remains in active recruitment. As we’ve announced and discussed previously, the preliminary results of this trial are promising. Our aim is to recruit patients with each of the three pathotypes of RA to obtain comparative imaging and pathology results and the trial is designed so that we enroll a minimum of four subjects in each of these three pathotypes of RA, fibroid, diffuse myeloid and lymphoid myeloid. So overall trial size has been expected to range between 12 to 24.
To date, we have achieved the minimum or more in two out of three of the passive type buckets with patients having at both our imaging and joint biopsies completed. The primary objective of the study is to assess the relationship between joint-specific tilmanocep uptake values and the pathobiology of RA involved joint tissue.
Knowledge of an individual RA patients pathotypes may be clinically important because it may predictto which RA therapy a patient is likely to respond. There is a growing body of literature suggesting that those patients with the fibroid type of RA are much less responsive to the anti-TNF alpha drugs. And so a means of determining whether or not a patient has this particular pathotypeis is seen as extremely important to a number of key opinion leaders in rheumatology.
As of this time, there is no reliable way of assessing a patient’s pathotype of RA other than by doing an invasive biopsy. And we have hypothesized that tilmanocep could provide this information.
We previously discussed those preliminary results that I mentioned on the first 11 patients. These results indicated that tilmanocep uptake in RA inflamed joints is able to discretely differentiate patients with the fibroid pathotypes i.e., those with low macrophage involvement from those having either the diffuse myeloid or the lymphomyeloid pathotypes of RA, i.e., those with high macrophage involvement.
7 of the subjects had relatively low levels of tilmanocep uptake. All 7 of these subjects were found to have the the fibroid pathotypes. Of the remaining 4 subjects, 3 have the diffuse myeloid pathotypes and one had the lympho myeloid. Furthermore, those subjects with either one of these 2 pathotypes had on average, more than 3 times the tilmanocep uptake as the average subject with the fibroid pathotype. So we have been able to clearly classify patients as either fibroid or non-fibroid based on our imaging results taken before the biopsy in those 11 cases.
These data also provide support for one of our indications in the Phase III trial, the ability to predict from a baseline scan alone, whether a patient is likely to receive a meaningful clinical benefit from an anti-TNF alpha therapy. Since as I mentioned, there’s increasing evidence that if a patient has a fibroid pathotype of RA they are less likely to receive significant clinical benefit from anti-TNF alpha therapy.
You might recall in our previously completed Phase IIb study, NAV 331, that contained the pilot arm looking at the efficacy of tilmanocep imaging at early prediction of treatment response, those patients exhibiting a low level of tilmanocep uptake in their joints on their baseline scan had an almost 90% non-response rate to anti-TNF alpha therapy using a clinical gold standard assessment. You can look for these preliminary results to be presented at an upcoming conference, along with full study results from this previous Phase IIb study NAV 31.
Finally, these biopsy trials are notoriously slow recruiting, but in fact, our recruitment rate overall number of sites is faster than what our lead PI indicated he would expect. Specifically, in our planning phase, were told that if we could open 10 sites for recruitment, we could achieve our enrollment figures in about 18 months. Due in large parts of resources, as well as COVID and site reopening issues, we have only been able to open 3 to date for enrollment from the opening of our first of 3 sites to now is 18 months. As usual, the clinical team has done a great job at exceeding expectations where we’ve almost completed enrollment in the same time period with roughly a third of the sites.
We continue to make very good progress in automating the image quantification as well, which will have significant benefit for the commercial product. We have the letter of intent and continue to work closely with MIM software on the full agreement for them to be our commercial partner for image quantification of tilmanocept imaging in RA.
Once again, MIM is a leading medical image software company based in Cleveland with a large footprint in the nuclear medicine space. They completed a pilot study using data from our trials demonstrating that they can develop a fully automated application that can robustly reproduce our quantitative imaging results using our proprietary algorithm.
This will be important for rollout of a commercial product. The ability to perform the quantitative reads rapidly and reproducibly and at large scale through automated means is critical to large-scale use of tilmanocept for rheumatoid arthritis.
Keep in mind that all of this, the imaging analysis methodology, as well as the data upon which it is built, including the normative database you’ve heard us discos before, is not only critical to driving the most accurate and sensitive objective read of our images, but it also serves as a significant barrier to entry to possible competitors in this space. We will continue to work with MIM to finalize the terms of the partnership and we’ll make an announcement when done.
In other areas of our diagnostics pipeline development in cardiovascular disease, the group at Massachusetts General Hospital in Boston, has published the results of the investigator-initiated atherosclerotic plaque imaging study that we help to support, the data are promising in terms of localization of tomato [ph] center to sites of atherosclerotic plaque and were in line with what was reported in the pilot study we co-published with them previously. We press released the publication, and you can find reference to it there.
Preclinical studies on Gallium 68 tilmanocept for PET imaging and related next-generation manifest imaging agents have progressed significantly through internal work at Navidea and through extramural collaboration with researchers at the University of Alabama at Birmingham or UAB. We have completed work on our NIH-funded preclinical studies for evaluating Gallium 68 tilmanocept and various new imaging agents similar to tilmanocept in a mouse model atherosclerosis.
We’re on another important set of preclinical imaging studies was completed and presented at a recent Society of Nuclear Medicine and Molecular Imaging meeting and the manuscript is currently in peer review. This work looked at a method to increase the localization of our imaging agent to target tissues, while additional technology was designed to block off-target imaging agent localization to the liver, which is the major site of localization when tilmanocept is administered intravenously.
These studies were highly successful, showing that we can dramatically increase localization of a new tilmanocept like imaging agent to tumors, while simultaneously significantly blocking off-target localization to the liver.
On the therapeutic assets front, we are advancing our candidates in the oncology and anti-inflammatory spaces in preclinical studies. Work on new drug delivery constructs and new targeted payloads has progressed. These new constructs carry new drug payloads that may be more effective than doxorubicin for beneficially altering the immune status of tumor macrophages, for example. Results in mouse models have demonstrated that when administered alone or in combination with another cancer drug, these therapeutic constructs significantly reduce the rate of tumor growth.
Some of these covering new bisphosphonate payload constructs were recently presented at the Tumor Myeloid Directed Therapy Summit meeting as well. This work is about advancing to a lead candidate for macrophage phenotype altering drugs for oncology indications.
In vitro studies examining the ability of our dexamethasone constructs for inflammatory indications have shown positive results as well, demonstrating macrophage phenotype change. These constructs will soon be tested in preclinical models.
Preclinical studies are also ongoing in Leachman ISS [ph] Leachman ISS is a vector borne chronic disease caused by a protozoa parasite that replicates in CD206-positive macrophages. It is transmitted to humans through the bite of infected sandlifound found in parts of the tropics, subtropic and Southern Europe. Leachman ISS is rare in the U.S., but in more tropical countries where the sandflies vectors are found, it is a common serious and potentially life-threatening disease.
We published work in 2017, demonstrating that high CD206 expressing macrophages play a role in the dominant form of the disease. And recently, we have renewed preclinical studies with one of the world leaders in this area and then promising early results from 2 preclinical studies. A third replication study is currently underway. And so our therapeutic pipeline is robust and moving forward.
That brings me to our overall intellectual property front. We received notification of issuance of patents from the U.S. PTO for our patent application covering a Manocept-based therapeutic for Leachman ISS. We continue to submit new provisional applications and work on our pending applications as well. We have filed two new provisional patent applications, one describing a new degradable linker for dexamethasone in paclitaxel-containing Manocept therapeutic constructs and the other describing bisphosphonate containing Manocept construct using studies I mentioned a few minutes ago.
These constructs are being evaluated preclinically for effects on macrophages and in animal model of oncology and inflammatory indications. We have filed five new provisional patents in total since December 30, 2021.
We also received a decision of grants for patent application in Japan for claims related to targeted delivery of a wide range of therapeutic payloads attached to Manocept platform-based constructs using a degradable hydrophone [ph] Linker. So we have an active IP protection strategy that we will provide needed protections and rights to both our current diagnostic and therapeutic agents, as well as to our next-generation molecules and disease indications.
Now on the drug manufacturing and supply front for both Lymphoseek and the RA product, we have been and continue to work with a new active pharmaceutical ingredient or API supplier, as well as the final drug product supplier. We will keep you up to date as this progresses. But as of this time, we are advancing towards completion of these and readiness for clinical and commercial supply going forward.
On the Lymphoseek Europe and Rest of the World front, you might have seen our recent press release announcing publication of a manuscript by an Australian investigator using tilmanocept. This was the first study coming out of Australia and this investigator and his colleagues are enthusiastic about using Lymphoseek in Australia going forward.
We are also in early discussions about potentially licensing Lymphoseek Europe with possibilities long-term relationship with other diagnostic pipeline products as well. Prior challenges to penetrating that market were pricing and competition, but with appropriate pricing in a number of studies demonstrating the strengths of Lymphoseek and sentinel lymph node indications, we feel there is an excellent opportunity there for the writing partner.
These are just some of the highlights of the last quarter that we wanted to touch on for this update. We remain largely focused on the RA pipeline, specifically the Phase IIb imaging the biopsy trial and the Phase III, while we also continue to support and push for progress on our other diagnostic and therapeutic indications.
As always, I want to thank the team here for their tireless efforts to keep things moving and our network of clinical trial sites and academic research collaborators for all of their hard work. Our strategy remains to advance our pipeline products to key inflection points and seek appropriate partnerships for commercialization and marketing.
So thank you. With that, I’d like to turn the call over to Erica for the financial updates. Erika?
Erika Eves
Thanks, Mike. So a brief review of second quarter results. Total net revenues for the second quarter of 2022 were $57,000 compared to $261,000 for the same period in 2021. Total net revenues for the first half of 2022 were $57,000 compared to $385,000 for the same period in 2021.
The decrease was primarily due to the 2021 partial recovery of the debts previously written off in 2015. The 2021 receipt of reimbursement from Cardinal Health of certain R&D costs, decreased grant revenue related to grants from the NIH supporting Manocept developments and decreased license revenue from transitional sales of timanocept in Europe.
Research and development expenses for the second quarter of 2022 were $1.7 million compared to $1.5 million for the same period in 2021. R&D expenses for the first half of 2022 were $2.9 million compared to $2.7 million for the same period in 2021. The increase was primarily due to increased employee compensation, including incentive-based awards and increased recruiting fees, offset by decreases in drug project expenses and regulatory consulting expenses.
Selling, general and administrative expenses for the second quarter of 2022 were $1.3 million compared to $1.4 million for the same period in 2021. SG&A expenses for the first half of 2022 were $3.1 million compared to $3.7 million for the same period in 2021.
Decreases in employee compensation, including the fringe benefits and incentive-based awards travel, investor relations, general office expenses, facilities costs and franchise taxes were offset by increases in insurance, director fees and losses on the abandonment of certain intellectual property and legal and professional services.
Navidea’s net loss attributable to common stockholders for the second quarter of 2022 was $3 million or $0.10 per share compared to $2.7 million or $0.09 per share for the same period in 2021. Navidea’s net loss attributable to common stockholders for the first half of 2022 was $6 million or $0.20 per share compared to $5.6 million or $0.20 per share for the same period in 2021.
Navidea ended the second quarter of 2022 with $328,000 in cash and cash equivalents. As Mike mentioned previously, the company received aggregate gross cash proceeds of approximately $6.2 million in the recent rights offering. And this exercised additional gross proceeds of up to $11.6 million may be received through the exercise of warrants issued in the rights offering. The company estimates that it currently has enough cash to continue operations into the first quarter of 2023.
And finally, as previously disclosed, the company is not currently in compliance with the NYSE American’s continued listing requirements related to stockholders’ equity. The NYSE American has accepted the company’s plan to regain compliance and the company continues to provide quarterly updates to NY&C as required under the plan. The company has until July 28, 2023, to regain compliance with the stockholders’ equity requirements.
And now I’d like to turn it back over to Mike.
Michael Rosol
Thank you, Erika. So we’re now going to open it up for questions. Let me remind you that you have myself, the Chief Medical Officer, Michael Rosol; Erika Eves, VP of Finance and Administration, as well as our Chairman of the Board; Alex Cappello and our Vice Chair of the board Mr. Kim Scott on the line and as well as our Investor Relations person, Jeff Smith.
Question-and-Answer Session
Thank you. [Operator Instructions] Our first question comes from the line of Michael Okunewitch with Maxim Group. Please proceed with your question.
Q – Michael Okunewitch
Hey, guys. Thank you for taking my question. So I guess, first, I’d like to see, maybe just discuss a little bit about your commercial plans in light of the termination of the MoU with Jubilant and how the value of the program may have been impacted by the additional Phase IIb data, as well as the market analysis, which has both emerged in the time since that was signed?
Michael Rosol
Thanks, Michael. Appreciate the question. I think your answer embedded within the question, as I think you probably know, very good. So we’ve advanced the program as we’ve said and you just reiterated significantly since the original signing of that agreement. So that agreement was signed a couple of years ago, and we were, if I recall correctly, in the early stages of our first Phase IIb study.
So we had the hypothesis with limited data in hand. And as such, the terms that were initially outlined, while beneficial, of course, to the company, we’re nowhere near what we’d be expecting to get at this stage of the program development. So since that time, we’ve completed that Phase IIb that data were supported to move into the Phase III. We met with the FDA and they concurred with this assessment.
We also as mentioned, begun and have announced the preliminary positive results to the Phase IIb study, giving us proof points for our mechanism of action of localization of tilmanocept to macrophages in the joints of patients with RA, as well as being able to identify two distinct classes of pathotypes at least, which helps us along the way towards having a true biomarker of the rheumatoid arthritis a non-invasive biomarker or a virtual biopsy.
So with the advances that we’ve done, we think we’re in a much better position to have discussions and reading the concomitant benefits of having advanced the program significantly as we discuss our partnership with possible players or players in the field and possible partnerships.
So with that exclusivity we have, we were able as you know, to even entertain discussions with other partners who have been following us as we advance our program. So now we’re in a position where we can have those discussions, entertain those. And since we’ve advanced further, we’ve derisked the program significantly.
And the further we go, the more we derisk it, assuming things keep going on the trajectory that they are going, looking very positive. So that doesn’t mean we turn away an offer now. But if we can keep going towards NDA submission, the further we go, the better we are for where we might be in terms of the negotiations.
So looking back on Lymphoseek, for example, the deal with Cardinal was struck after approval of Lymphoseek in North America, as well as in the EU, although Cardinal is not in the EU or at least they’re not a player in this space in the EU market. But since we advanced it so far to approval and were ‘actually running it, doing the commercialization in the United States on our own we were able to get a heavy inflator and great value for Lymphoseek in North America in those negotiations. So we see something similar to that happening in the RA space. So I gave you a long-winded answer, hopeful there’s something in there that’s meaningful.
Michael Okunewitch
Okay. No, no, I appreciate as much color as you can give. I’d like to follow up on that point without getting into anything that you’re unable to disclose, I’d like to see if you could just review some who are some of the potential commercial partners that might be a fit. Obviously, they are the big nuclear pharmacies like Cardinal and Jubilant, but are there any other players in that space? Or is there potentials for other companies, maybe those in inflammatory disease or diagnostics, who would make them a viable partner for the product?
Michael Rosol
Yeah. Great question. So indeed, you’ve hit up on two of those, of course, in the nuclear pharmaceutical space in addition to the two you mentioned, for example, there’s Curium that has wide reach. There’s also Lantheus medical imaging. And there are several as well. But also, as you mentioned, we certainly would not close the door on something with a large pharma player who has traction in the inflammatory space domain and in rheumatoid arthritis specifically or an interest in that area. And as you said, I can’t reveal things, but of these are possible opportunities for partnerships for us in one way or another.
Michael Okunewitch
Yes. All right. Thank you very much. I appreciate you taking my questions. And I’ll hop back in the queue.
Michael Rosol
Sure. Thank you.
Operator
And our next question comes from the line of Fred Zaino with Keystone. Please proceed with your question.
Fred Zaino
Okay. How are you? Just a couple of quick questions. The $800,000 payment that you received from that third party. Is there more to come? And if so, how much? And then I believe there’s a sales milestone, Cardinal payment somewhere in the $10 million. I’m just curious if you could shed any color on that/
Michael Rosol
Yes. Without breaking confidentiality, I think I can say that there are – so this was an accelerated payment and there is the potential for another milestone-based payment in our R&D development related to that agreement. So that is something that could be coming down the road.
And in terms of the Cardinal milestone. We do receive our annual sales figures for Lymphoseek, we are not at liberty to disclose those, but there is the potential if and when they hit the $100 million in sales, net sales in one of their fiscal years that we would get a $10 million milestone. And that remains a possibility. And that’s about all I can say right now.
Fred Zaino
Right. On the – any plans to hire a CEO?
Michael Rosol
Yes. So what our strategy has been was to – in consultation with search firm that we had hired was to wait until the company was sufficiently capitalized to recruit a CEO of a caliber that could then take us into the next level. So with where we are now, the board arwill be having discussions and determine if that should be opened up now or what the next step should be.
Fred Zaino
One final question. I appreciate everything. The cash gives you the runway in Q1 2023. Do you think there’s any substantial or meaningful catalysts that you’ll be able to achieve in that time frame, maybe final results from 332 or something there that allows you to raise more capital?
Michael Rosol
Yes, exactly. I think you’ve hit upon one of the big ones. So potentially, the closeout of 332 with the results there milestones in the recruitment in the Phase III, of course. And additionally, some milestones in the development of the therapeutic assays. But the two big ones are likely the NAV 332 results and the advancement of the Phase III, maybe the first 50 or 100 patients as we go more towards completion.
Fred Zaino
Great. Thanks so much. Great job.
Michael Rosol
Thank you.
Operator
Thank you. [Operator Instructions] And our next question comes from the line of Mike Rachel with a private investor. Please proceed with your question.
Unidentified Analyst
Yes. Thanks, And Erika for all your hard work and your staff. It’s really appreciated. Dr. Rose, [ph] you said there have been 30 people in the Phase II-33 already. And they [indiscernible] they also started the 213 day assessment?
A – Unidentified Company Representative
Yes. A handful of those, pardon the Mike, by the way, thanks for the question. A handful of those are still – are finalizing the screening, but they’re enrolled, the majority of those have been imaged and are proceeding. We have several of those this month are reaching their 6-month milestone. And so that’s a big event. And there are something on the order of 13 who’ve achieved the 12-week or 3-month milestone. So things are progressing.
Unidentified Analyst
All right. And a follow-up question on that. Do you see with opening those 9 additional sites? Will that give you a right way, assuming where the funding is there, obviously to still be on your targets of mid-2023, early 2024/
A – Unidentified Company Representative
Yes, that’s a great question. We’re always – we have a very – me aside, we have a very high performing team, and we have great sites that we’ve chosen for very good reasons. So as I’ve mentioned and alluded to in the past, our recruitment rate is several fold, 1 to 2 – I’m sorry, 2 to 3 times what the normal recruitment rate is for RA trials. And in some cases, it’s been 4 times at individual sites.
So we know what we’re doing. We can open up the right sites and they’re motivated to get patients. It’s always been for us about resources and that filters down to how many sites we can open.
With that said, we’re pushing the envelope here, but the opening these 12 sites if we can maintain these very high recruitment rates that we’ve seen in the Phase III in our first 3 sites. And already, we know that several of those sites we’ve just opened identified in some cases, 5 or 6 patients they’re going to bring in in the next month if those sites can ramp up quickly as it looks like they can because they’ve been preparing and recruit at an accelerated rate. We could still be on target for those – for that guidance.
Optimally, we’d like more funding in order to more sites because that is – that’s how we build that model. But we can – we have the sites that are over performing. And if they continue to do it, right now, that is still achievable. Don’t – our miles may vary, right? But we will do our but it’s still within the ballpark with these 12 sites, especially if they keep going the way they look like they’re starting.
Unidentified Analyst
Okay. Third question, then I’ll come back in the queue. On the 332 of the last conference call, there was 11 completed and there were several potential any of those potential progress yet to the biopsy stage? Or are you still screening on 323?
A – Unidentified Company Representative
Yes. No, we have more. I just – I debated giving the numbers on those that it becomes a kind of an accounting game. And of course, we have to think about when we release the data carefully, both related to kind of breaking the seal of the trial. Usually, you do these defined time points. And then I don’t want to speak too much on the data itself because, one, it’s not finalized and validated yet. And two, to actually publish these data.
And so the more you talk about the data, the less – the more difficult it becomes to publish or at least in principle, you’re not supposed to be publishing data that you’ve discussed in great detail. So anyway, said we have advanced some of those patients have been recruited into the trial and imaged and biopsy. So we have more patients.
In terms of the buckets, as I mentioned, we need to fill out one more of the pathotypebuckets. And then the plan is to look at those data and determine what we have found, can we discriminate between the 3 pathotypes or is it a fibroid non fibroid, which is very important. And then we’ll look at the correlations of the macrophage number and density across all those subjects with our imaging signal and the more data we have for that the better.
Unidentified Analyst
On the LS, you said that you couldn’t disclose the sales for the Cardinal agreement. But in your presentation, you had about — there been about 600,000 injections — do you still see that number accelerating at a reasonable rate on the number of injections in the U.S.
A – Unidentified Company Representative
The number is above that now. We do know where that is. It’s not greatly above that number now, but it is – it has gone up. It’s hard to say what that’s going to happen with the trajectory just from my looking at it. There were things going and COVID and supply chain issues that impacted the medical field at large, not just the nuclear medicine field or sense assessment field, although it did implicate those or impact those. So with all that said, it looks like the trajectory is good. They have a good percentage of the market share, but it’s hard to predict. Is it plateauing? Or is it going up? And I’ve probably said as much as I can say.
Operator
Thank you. And our next question comes from the line of Michael Okunewitch with Maxim Group.
Michael Okunewitch
Hey, thank you for getting back to me. I just had one more. I’d like to follow up on the on the enrollment side for the Phase III. If I’m interpreting from your slides correctly, it seemed like there’s a decent bit of variability in the total number. I think it was 198 to 672. Could you discuss what factors would contribute to the total size of the trial is related to how the phenotypes break down during your enrollment?
Michael Rosol
Great question. What it relates to is the number of responders and nonresponders to the anti-TNF alpha therapeutics. So we need – if you look at sensitivity and specificity, NPV and PPV truth tables, you can model these out the number of samples you need in each one of those and your boxes and your power of the study if you fill those boxes in with a certain number of patients. All of that is independent of whatever we’re doing here, our diagnostic but relative to our diagnostic, what’s important is the number of anti-TNF alpha responders and nonresponders.
We need about 100 in each of those those 2 buckets. We need 100 nonresponders and 100 responders. The reason there’s such – and that’s why the bottom of it is 198. If we have a breakdown where we’re at about 100 of each, it’s obviously, it’s not exactly 100 that’s why it’s not 200, but it’s close.
So if we have about 100 and 100 and we have no dropouts, then we’re done, and we can analyze the data. If the breakdown of the nonresponders to the responders is more like we’ve seen in our previous Phase IIb trial or like some of the literate there are many more nonresponders to the anti-TNF than responders than trial size will need to grow. So we modeled out kind of the worst case ratio, and that’s how we get to 672. And on top of that, there’s a 10% to 15% dropout rate baked into that.
So the worst case is if have maybe the worst ratio that has been seen for nonresponders to responders we’d have a trial size of 672. Best case is 100 to 100 for a total of 200. If you look across in rheumatoid therapeutic with anti-TNF alpha therapies and the ACR50 response level, you get about a 40% on average responder rate and a 60% nonresponder.
So that dropouts give us about a 300-person trial. So I said a lot, but the range is in there for those reasons. And what we’re doing, Michael is we’re looking – as we go, we have the clinical outcomes, right? So we’re looking at the 3-month clinical outcome to give us an idea of where our trajectory is going to give us an idea of where we are and how the trial size is going to look at the end of the day. How many do we need to keep collecting recruiting.
We’re looking at the 3 months as a surrogate of the 6 months outcomes so that we can stop recruiting into the trial earlier rather than later. When we know or think we know we’ve recruited enough of responders and nonresponders. So really, it’s all about the responders. We need to have about 100 responders and single those out because more patients than are not responders to anti-TNF alpha So we’re at the mercy of the drugs themselves, but – and we’re going to monitor it as we go.
Michael Okunewitch
All right. Thank you. I really appreciate the additional insight on that.
Michael Rosol
Yawh. You are welcome.
Operator
And our next question comes from the line of Adi English a Private Investor. Please proceed with your question.
Q – Unidentified Analyst
Thanks for taking my call. And congratulation to the team for your progress. I want to go back – my question goes back to some comments that were made in April of this year on the finance call that we had some there were some very encouraging and positive comments made about work that was going on with the investment banker and potentially having the collateral that the company needed to make a loan to achieve the long-term and large financing that we need to go forward.
And then we had the S1, which really fell short of the $35 million that I believe is closer to the figure that’s needed for the long-term financing of all your projects and pipeline. I wonder if you could tell me what has happened since April that’s now changed your funding strategy of a larger loan and our larger capital being brought into the company?
Michael Rosol
Sure, Eddie. Thanks for the question. I’m going to – I’ll tackle it and then I’ll open up the line to our Board members as well if they want to chime in. So indeed, our – what the Board and management did as well, we’re a high level of due diligence, working closely with our investment banks.
And looking at all possibilities for raising sufficient funds to have the capital to get us across the goal line. The long and the short of it is for various reasons, including the market. And some of this I’m relating to you from what we’ve been told by our investment bankers, we are where we are now. And so what the board has to do is now work with our investment bank and close out of the rest of capital raise, raise the rest of the money so that we can have the resources to get our where we need to be. So that we’ll be in a great position to not just advance these products to make big business partnership deals and get the return on the investments that folks like you deserve.
So the Board, I know, has gone through a great deal of due diligence working with the investment bank and the forces at play. And this is where we are now. And they are now working closely, having many meetings and discussions about what are the next steps. So with that said, maybe if you want just say, Alex, if you’d like to chime in and then maybe Kim up to you.
Alex Cappello
I’ll let Kim respond because he’s been dealing with the – all 3 investment banks, whereas I have not.
A – Unidentified Company Representative
Thanks, Alex. Yes, this is Kim. I have been running with financing and working with different banks to try and get $35 million, which is totally funded all the way through the period of time to get the NDA submitted.
There has been a number of problems. There were a number of problems since April. Market, other things that have happened that we probably can’t really express right now. But at this point, we have the commitment of Maxim to finish out what they started and get us – get us the additional funding. We are – those talks will be ongoing and moving forward, but it was a good start to get $6.2 million. And hopefully, we’ll get the balance of it in the near future.
Alex Cappello
Thanks, Kim.
Q – Unidentified Analyst
Thank you. I have another question, if I may, going to the third-party assessment on the RA product and the revenue charts. Those charts show that it’s possible to receive $41 million of revenue in 2024 in that program, other charts that were published in July with your time line on the RA is the IND for the product won’t get filed until late in 2024. So has that revenue projection shifted due to some of the delays in the 333/
A – Unidentified Company Representative
I mean it could. By the way, I wouldn’t call those delays in 333. It’s also – it’s an NDA submission. I mean the plan is to – has been – or the guidance has been to have full in 2023, there’s a 6-month tail on the trial folks, right? So once they we follow them for 6 months up to a maximum of 213 days as Mike pointed out.
And then what we need to do then is right off the final data. This depending on the team size and the resources we can throw at if this takes anywhere from 3 to 6 to get all that together and to file for the NDA and then you have the NDA process.
So there’s a little bit of flex in there because if things maybe push a quarter or so here and there or — but as we’ve made these projections, we’ve had our best back foot forward in terms of predicting. And if there are discrepancies in those, they came about over some time and based on when we thought we could ramp up opening of the trial site. So that would get to your delay comments, opening up the maximum number. So yes, there’s some flex in those. If they don’t exactly align, it’s because over time, things might shift a little only because we haven’t had the full amount of money to fully fan the flames as you pointed out.
A – Unidentified Company Representative
Eddie, this is Kim again. I just want to make it crystal clear that the Board is committed to finish the Phase II trials in the Phase II trial in the Phase III trial. And that’s where our focus is and our — majority of our money is going. And we continue to watch our or pennies and we continue to find money where we can find money like that $800,000 that came in. Mike worked really hard on that. And so I think that with the money this to shell pass, and we will look at this as just a little blip on the back end from a standpoint of getting the Phase III trial going all the way to NDA and approval of the trial related arthritis.
Q – Unidentified Analyst
Got it. Got it. One more question, if I could, Mike. The July prospect as had the time line on it, it suggested that the 332 would complete in the third quarter, which that’s just a few weeks from that — and I noticed that the Queen Mary side still recruiting. Are you still on track to complete 332 this month?
Michael Rosol
Yes. No, It’s a good question. At that stage, again, based on the trajectory. So that was where things were looking. But again, these things can vary over time. recruitment can wax and wane. And then we can’t control who walks through the door. So we still want to fill in all those buckets. We’ve also discussed, frankly speaking, we’ve discussed internally over whether a sufficient number has already been accrued so that we could stop the trial and make do with the data we have because we already have a compelling story, we think. — in order to meet the full objectives of the trial. And we think this is important for several reasons, including discussions we’re having with possible partners.
We think it’s important to complete the trial as originally intended. And so we just need to keep it going until we get all those people we need to get walking through the door. It’s really hard to map these trials out. We not only can you not control recruitment, but you don’t know who you got until you get them, right? And so that’s the tricky part. So we’re doing our best to enroll as rapidly as we can. I work with the sites. So does Rachel Hersey, our lead of our clinical trial offices in constant communication.
We ran with the PIs of these sites recently to talk about recruitment and how it’s looking and what we can do. And as you mentioned, the Queen Mary site I mentioned way back when, when we were told that, that site could be opened up quickly — it turned out — and this was — this is not an excuse, it was — it is out of our hands. There were internal milestones and processes that they had to put in place that they’re still working on finishing up. And sometimes with academic sites with their own — and I’m not throwing them under the bus, but their own internal processes are such that they have delays they didn’t even anticipate. So that site has been delayed for longer than I’d like. Because the processes. And again, maybe too much info here, but I remember working at Novartis and even here at Navidea. — there have been academic sites that have taken us 1.5 years — and at Novartis, actually, there were a couple of very famous sites we stopped working with because we could never open them up. And isn’t that amazing. But in any we’re working hard with the Queen Mary. I’d like to get them open. So we we can, and we’re asking them if we can do anything more. So we’re going to keep running that trial until we finish it, and I think it’s going to pay dividends for the company and for investors like yourself. So please be patient with us.
Operator
Thank you And our next question comes from the line of Mike Rachel a Private Investor. Please proceed with your question.
Q – Unidentified Analyst
Yeah. This is follow up. Can you provide any more color or depth on the 2 oncology related to preclinical trials ongoing that you’re currently planning 2024 earlier INDs. When is is the M1 M2 and – can you provide any more color on those?
Michael Rosol
Sure. What we’re doing is we’re doing – right now, we’re doing preclinical studies to select our lead candidates to move first towards IND for first in human studies. And so you’ve heard me mention various new payloads, new constructs. We have the doc construct that has some promising preliminary results, there are reasons to believe that some of our other newer therapeutic payload constructs would have and will have superior efficacy.
And so we’ve been advancing those as well preclinically. And we’re getting very close to a phase where we can say, this is our lead and these are our other candidates that we will also continue to advance behind those. So things are moving. We’ll be looking to do some investigator-initiated studies to help us advance towards IND and in possibly investigator-initiated INDs. So we’ll work closely with research collaborators well institutions who can help us get these into humans more rapidly and do those first human studies rapidly as well.
And then on the inflammatory side, for inflammatory indications, we’ve worked quite hard to time the dexamethasone containing constructs, so that we can then put those into animal model and advance those towards INDs as well. So — and in addition, there’s the leishmaniasis. So again, we have I want to be clear that we’re very focused on our strategy. We develop our lead candidates by going through chemistry, in vitro, in vivo towards human. We’re doing that in the oncology space. We’re doing it in parallel in the inflammatory space, and we have our studies ongoing, as I mentioned, in the leishmaniasis space, for example. And so that may also go towards an IND in the next 1 or 2 years as well, depending on how these studies that we’re currently carrying out — so when that slide was crafted, it was really about taking an anti an immunotherapy for cancer to IND as well as an anti-inflammatory.
And at the end of the day, optimistically, it might be more than one immunotherapy with give or take a year between the 2 and anti-inflammatory and maybe leashmeniasis. There’s quite a bit of potential with this molecule and what we can do with it. right? It’s adaptable. We target this key player, the macrophage. We’ve shown we can the phenotype of the macrophages and ways that can have significant consequences for therapeutic benefit. We’ve shown this in the preclinical world.
We continue to do it. As you know and others — in general, the macrophage domain is a hot area and growing and big and small pharma are starting to pay more attention to the macrophage as a key player in disease in a wide variety of diseases. And the cool thing is, we’re this little company in Ohio that is really at the forefront of this hot area of medicine. What we need are the resources to keep us at the forefront and move us so that we can get to the goal line the way we’d like to
Yes, I think that’s great. And to me, having been a total novice but studying this the potential is so strong. And like you said, the external world is starting to wake up to it, no matter where you look all the way from ratioing to mine of targeting. But would you think that is positioning you to have people start knocking on your door if not already in the near future
Speaker 8
Yes. So when I first started video race we couldn’t focus on them quite as much as we wanted to or as much as we wanted to because of ongoing litigation. Over the last couple of years, we’ve been in a much better position where we can release the great potential of our teams on to those — the potential of the molecule in in the therapeutic domain broadly. So what’s been happening is that we’ve been accumulating data. We’re starting to have our coming out parties where we’re presenting abstracts now. We’re having conversations. I can’t get into details with with players in the space. And indeed, there are — there is a growing recognition not just the macrophage port for the macrophage, but can do in the domain of the macrophage as a company with our molecule. So that’s happening, and it may not happen as quickly as any of us would like, but it is happening. And I think if we can keep our momentum going and ramp it up, big things will happen sooner rather than later. That’s just my personal opinion.
Qaend
Operator
Okay. At this time, we have reached the end of the question-and-answer session. And I would now like to turn the call back over to Dr. Rosol for any closing remarks.
Speaker 1
Operator
Thank you. I’d like to thank you all for taking the time to participate in today’s call. And to ask for those of you who asked questions, thank you for the questions. The team remains dedicated to getting things done here moving forward — we’re working closely with our Board of Directors, and we look forward to next discussions as the month — the days and months ahead to proceed. So thanks again. And with that, we’ll close the
Operator
Thank you, everyone. This does conclude today’s conference. You may now disconnect your lines at this time. Thank you for your participation, and have a great day.+
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