TFF Pharmaceuticals, Inc.
Q4 2020 Earnings Call Transcript

Published: 10 Mar 2021

[Operator:]

Good afternoon ladies and gentlemen and welcome to the TFF Pharmaceuticals’ 2020 Financial Results Conference Call. As a reminder, this conference is being recorded. I would now turn the call over to your host, Mr. Paul Sagan of TFF Pharmaceuticals Investor Relations. You may begin your conference.

[Paul Sagan:]

Thank you very much, operator. Hello, everyone and welcome to TFF Pharmaceuticals 2020 financial and business results conference call. With me on the line today is Glenn Mattes, President and CEO of TFF; Kirk Coleman, Chief Financial Officer; Dr. Bill Williams of the University of Texas at Austin; Dr. Dale Christensen, TFF’s Director of Clinical Development; and Chris Cano, TFF’s Chief Operating Officer.

[Glenn Mattes:]

Good afternoon and thank you for joining us today to review the company’s third quarter operations and recent highlights. During this call, I will provide an update on our clinical and corporate progress. And then I will ask our Director of Clinical Development, Dr. Dale Christensen to update us on the very significant progress we are making in our internal clinical programs. Then our Chief Financial Officer, Kirk Coleman, will review the company's financials. We're also happy to have with us once again Dr. Bill Williams from the University of Texas at Austin, who will talk about some of the exciting progress and new data; we're seeing the application of our Thin Film Freezing technology to drugs, vaccines, and biologics. And Chris Cano, our Chief Operating Officer, who will update us on business development and operational initiatives for the company. And then we will open up the lines for your questions. While we are reporting on 2020 results, I can say that last year was one with numerous remarkable accomplishments. As we begin 2021, we are on course for a year significant outcomes as we move our internal pipeline forward, capitalize on the transactions already completed, and secure important new partner agreements. As you've seen with the press releases yesterday and today, we continue to build TFF and greatly enhance the value creation of a company. Today, I'll discuss the details of what TFF has accomplished and how these developments has set us up for near, mid, and long-term success. I want to take just a moment to reiterate our Thin Film Freezing technology and company business strategy. This strategy is fundamental to our company and our commitment to sustainable value creation. The first part of our business strategy is the development of an internal pipeline of products. I'm eager to have Dr. Dale Christensen review the progress we've made on the clinical front as well as discussing the path forward for these assets. I am very proud of the clinical development programs as we have executed well on timing, budgets, and results.

[.:]

[Dale Christensen:]

Thank you, Glenn. And good afternoon to everyone who has joined us today. We're very pleased to give you an update on TFFs internal clinical development programs. Despite the effects of the pandemic on trend of clinical trials globally, we've been quite fortunate in that the Phase 1 trials of our two lead programs have had only minimal time delays. Most importantly, we've made great progress and continue to generate exciting clinical data from our human studies. I'm particularly pleased to provide a readout from the final data in our Phase 1 clinical trial of Voriconazole Inhalation Powder for the treatment of Invasive Pulmonary Aspergillosis or IPA. We chose to develop Voriconazole because it is recommended as the first line agent for the treatment of IPA infections. However, it's not well tolerated and up to 20% of the patients discontinue therapy due to adverse events or tolerability issues.

[Kirk Coleman:]

Thank you very much, Dale. For the year ended December 31, 2020 research and development expenses to the company were $10.7 million, compared to $8.8 million for the same period in 2019. The increase in research and development expenses during 2020 was due to the ramp up of research and development activities following the completion of our IPO in October of 2019. The ramp-up includes our preliminary analysis and testing of dry powder formulations of certain drugs and vaccines we believe to have the potential to be become product candidates. General and administrative expenses for 2020 were $8 million compared to $3.2 million in 2019. The company reported the net loss of the year of $18.6 million, compared to a net loss of $11.9 million in 2019. Weighted average common shares outstanding basic and diluted for the year ended December 31, 2020 were 20,425,162, compared with 6,904,983 for the same period in 2019. At the end of 2020, we had total assets of approximately $38.7 million and working capital of approximately $36.2 million. At the end of the year, our liquidity included approximately $35.3 million of cash and cash equivalents. And with that, I'd like to turn the call over to Dr. Bill Williams, who will be talking about some of the groundbreaking work we're doing using our Thin Film Freezing platform in the broad field of small molecule drugs, as well as our work with large molecule biologics. This is an area where our technology is unique in its ability to reformulate these biologics into inhalable dry powder. Bill?

[Bill Williams:]

Thank you, Kirk. Good afternoon, everyone. I'm very pleased to give you an update on what has been a very busy and productive quarter for the research team at TFF Pharmaceuticals. In terms of scientific impact to TFF Pharmaceuticals since our last update, we have made significant advancements regarding our programs. To facilitate my summary today, I'd like to break the discussion down into small molecule drugs and biologics. Let's first review our work on small molecules. For our inhale niclosamide dry powder for inhalation program. We recently reported in a bio archive preprint paper, the development of a formulation to reach the lungs as a therapeutic for COVID-19 and other viral infections. This inhale dry powder formulation exhibited sustained niclosamide concentrations, which is very difficult to achieve by other routes of administration due to niclosamide, very low water solubility and high first metabolism. Specifically, we showed that niclosamide inhalation powder prepared by Thin Film Freezing not only proved to be safe after an acute three day multi-dose pharmacokinetics study in rats as evidence by histopathology analysis, but it also achieved excellent lung concentrations above the reported IC50 and IC90 levels for at least 24 hours after just a single dose administration in the a Syrian hamster model. We selected this hamster small animal model, because hamsters are susceptible to SARS COVID infection and thus are a promising candidate as an animal surrogate to model COVID-19 disease. Our studies support the niclosamide dry powder inhalation formulation by Thin Film Freezing for further clinical testing against COVID-19 and other viral infections as mentioned by Dr. Christensen earlier in this call. Regarding our oral niclosamide formulation, we recently reported in a newly published peer reviewed paper on the development of an Amorphous Solid Dispersion produced by Hot-melt extrusion. This is our companion antiviral niclosamide product and improved oral product to complement our dry powder TFF formulation of niclosamide for inhalation that I just discussed. Specifically in our paper. For the first time, we report that the niclosamide Amorphous Solid Dispersion formulation containing a polymer carrier increased the apparent drug solubility by about 60-fold relative to the current state-of-the-art crystalline form of niclosamide. The Amorphous Solid Dispersion niclosamide achieved a more than two-fold increase in oral bioavailability and rats compared to niclosamide and hydrate. These results are highly encouraging for its continued clinical development. Now I would like to discuss our advancements in applications of Thin Film Freezing to biologics. Biologics include mRNA, siRNA and monoclonal antibodies. As Chris Cano will describe TFF Pharmaceuticals has multiple technology validation agreements with pharmaceutical industry partners. Let's first discuss our progress with mRNA and lipid nanoparticles. The applications generally include pulmonary delivery to the lungs to treat diseases such as lung infections, including viral infections and also include applying Thin Film Freezing to convert unstable liquid forms of the mRNA and lipid nanoparticles into stable powder form that can be stored without severe cold chain constraints and then reconstituted back into the liquid form for injection at point of administration to the patient. The problem that Thin Film Freezing is solving for cold chain includes the requirement that presently the liquid form must be stored frozen either at minus 70 degrees C or minus 20 degrees C, achieving only limited shelf life storage. And in fact, the shelf life of either these conditions is relatively short complicating distribution channels. Based on recent work in my laboratory, we are highly confident that Thin Film Freezing can be applied to current mRNA vaccines to successfully formulate a version and that can lessen the need for cold chain distribution and storage. Today, collectively, our studies confirm that the conventional method of slow cell freezing and localization as compared to Thin Film Freezing has failed to successfully convert these liquids into stable dry powder forms. We have been able to achieve this to convert the liquid form of mRNA and lipid nanoparticle into a stable dry powder more stable than a direct side-by-side comparison to conventional localization. In addition, we have also been able to form stable dry powder forms of mRNA and lipid nanoparticles that can be delivered by dry powder inhalation. In comparison, the current state-of-the-art, our liquid forms of mRNA and lipid nanoparticles delivered to the lungs as a liquid, using a nebulizer. Nebulizers have low delivery efficiency when delivering mRNA lipid nanoparticles to the lungs, whereas, we are able to convert the liquid form into a dry powder for inhalation, while preserving the physical properties of the mRNA in liquid nanoparticles. With our work on monoclonal antibodies for multiple partners, we have successfully converted liquid preparations into dry powders, while maintaining the chemical integrity and functionality of the monoclonal antibody. These optimized powders have excellent aerosol performance properties, making them ideal for inhalation delivery to the lungs. We have also found that these monoclonal antibodies can be stored and refrigerated, or controlled room temperatures depending on the specific properties of the monoclonal antibody being studied. Thus an advantage for cold storage requirements. We have also had the opportunity to apply Thin Film Freezing to formulate cytokines and enzymes as dry powders to administer by dry powder inhalation to treat lung diseases, or to reconstitute back to the liquid form for administration to the patient at point-of-use. These protein-based dry powders can be stored at control room temperature. We recently published a peer review paper on applying Thin Film Freezing to the delivery of siRNA in solid lipid nanoparticles. The problem that Thin Film Freezing sought was the very low efficiency of lung deposition when inhaled as a nebulized liquid. We confirmed that Thin Film Freezing transformed the siRNA from a liquid suspension into a dry powder, while preserving the chemical integrity and functionality of the siRNA. We continue to apply Thin Film Freezing to protein antigen based adjuvanted vaccines, including marketed vaccines and vaccines currently in clinical trials intended for immunization by needle-based injection after reconstitution at point-of-use or needle free directly as a dry powder internasally or by inhalation. These protein antigen based adjuvanted vaccines require cold chain storage during distribution. And other methods of converting these liquid forms to their more stable dry powder form have not been successful because their immunogenicity is not preserved; Thin Film Freezing has been successfully used to accomplish this. We also recently reported in a preprint on bio archives, the application of Thin Film Freezing to the formulation of dry powders for inhalation of bacteriophages. The problem we are solving is that presently, bacteriophages are stored and administered as nebulized liquid aerosols. But these liquid forms of bacteriophages have low efficacy when inhaled. Because of CAGR loss and must be stored in a refrigerator to maintain their activity. Each bacteriophages presents its own challenges, and we're using Thin Film Freezing to formulate dry powder bacteriophages one by one. Lastly, our technology validation work on virus vector based vaccines is progressing quite well. Our goal for this work is to provide immunization by needle based injection after reconstitution at point of views or needle free directly as a powder internasally or by inhalation. In our collaborations, we are addressing the required cold chain storage, as well as the lack of mucosal immunity in the respiratory tract, when vaccines are administered by intramuscular injection, and the low efficiency of lung deposition, when vaccines are inhaled as nebulized liquid aerosols. We have successfully transformed these virus vector based vaccines from frozen liquid suspension form to dry powder by Thin Film Freezing with minimal damage to the viruses. We have confirmed that our dry powder has excellent aerosol properties, ideal for pulmonary delivery. I want to acknowledge and thank my colleague, Professor for his significant contributions to our research programs. Lastly, I want to thank you all for your continued support of TFF Pharmaceuticals and the collaboration with the University of Texas at Austin. And now, I'd like to turn the call over to Chris Cano, Chief Operating Officer, who can update you on more of the progress the company is making in its business development and partnership efforts. Chris?

[Chris Cano:]

Thanks, Bill and good afternoon, everyone. Thank you for joining us today. As I have previously shared, the TFF business development team is laser focused on three key areas of growth for the company. These three areas are. One, growing the TFF pipeline with internal development program, two, our pharma partnering efforts, and three, our government contracting efforts. We continue to make great strides in each of these key areas. As Dale discussed, we continue to expand our pipeline beyond our existing products, including Voriconazole Inhalation Powder, Tacrolimus Inhalation Powder, and TFF micro somite. We are now actively collaborating on the joint development of a monoclonal antibody for COVID with our partners, Augmenta Bioworks. We continue to aggressively progress this project to early stage development. The TFF BD team continues to hunt for new assets, compounds that have specific formulation and delivery challenges that would benefit from the TFF dry powder technology. And that would generate the differentiated and value added products for patients, physicians and payers. In addition, I want to update everyone on all of our former partnerships and the collaborations we're working on. As Dr. Williams has described, TFF is very active in the mRNA space. We have multiple active mRNA programs underway. We are working with a large pharma partner formulating their proprietary mRNA into the TFF dry powder for delivery directly to the lung. We are also working with a mid-cap pharma company, delivering their proprietary mRNA directly to the lung, via the TFF dry powder technology. No two mRNAs are the same, but they do have similar delivery challenges. We're able to overcome these challenges with our innovative technology. Announcing feasibility agreements is not TFFs standard corporate practice, but given the collaborative nature of our partner, the current events of the pandemic, the timing of this work and applicability to real time events, TFF has agreed to disclose certain aspects of the new partnership. We recently entered into a new feasibility and material transfer agreement with GreenLight Biosciences, an mRNA company, in order to formulate the mRNA COVID vaccine. As you as you may have seen in our recent announcement dated March 9, we are working with GreenLight Biosciences to formulate their mRNA vaccine for COVID into a dry powder, which will be quickly reconstituted on site for injection. Therefore, generating a more stable formulation which removes cold chain storage and transportation challenges faced by many, if not all, of the current mRNA competitive products. In addition, we are working on other mRNA programs and we are actively engaged in meaningful discussions with the leading mRNA vaccine companies. We strongly believe that our Thin Film Freezing technology will play an important role in formulating second generation COVID-19 vaccines. To the best of our knowledge, we are the only technology able to formulate a dry powder of mRNA and our TFF dry powder maintains particle size, has superior aerosol properties, has an encapsulation efficiency of greater than 90% and maintains the activity level of the mRNA. As previously mentioned, announcing feasibility agreements is not TFFs standard corporate practice, but staying in the COVID space and given the collaborative nature of our partner and the current events of the pandemic TFF has agreed to announce another project, TFF is working with NeuroRx on their product candidate ZYESAMI, which is Aviptadil, a synthetic form of a naturally occurring peptide found in the lung called vasoactive Intestinal Peptide, or VIP. This product is currently in late stage clinical trials for critically ill COVID patients. And based on the results of these trials, the hope is to file and receive Emergency Use Authorization. By formulating a TFF dry powder version of VIP, it would offer patients and physicians an alternative route of administration of VIP for treating the disease state much earlier, which would be a tremendous value to COVID stricken patients. Also, as Dr. Williams discussed, we are very active in the monoclonal antibody space. We have multiple active monoclonal antibody or MAD programs underway. As we disclosed back on February 19, we are working very closely with Dr. John Dye of USAMRIID, formulating their mAbs. Based on recent in vitro testing, we are very pleased to announce that the TFF technology was able to generate dry powder forms of USAMRIID mAbs, that maintain the same activity as the initial liquid formulation. This is a very exciting accomplishment. It validates our technology and clearly supports pursuing the next steps of development. That next step of development is in vivo testing. And if successful, TFF would seek non-diluted funding to move the vaccines forward in development. In addition, we are working with another government agency on their proprietary mAbs, generating the dry powder that exhibits very favourable aerosol properties while maintaining high activity levels. These mAbs are in development as a COVID therapeutic to be delivered directly to the lung. We are also engaged with a large pharma company, and we are currently formulating their proprietary mAbs for delivery to the lungs. We are preparing for initial in vitro testing. To round out our mAbs programs, we continue to progress our joint collaboration and development arrangement with Augmenta Bioworks. In addition to these programs, we are actively engaged in discussions with other leading mAb companies. Again, to the best of our knowledge, we're the only technology able to formulate a dry powder monoclonal antibody that maintains the activity and integrity of the mAb and has superior aerosol properties. To complete our form of partnerships, we are currently formulating our partner’s siRNA, plasmid DNA, oligonucleotides, B peptides, cytokines, AAV and VSV product candidates, along with many small molecules. Also, we recently entered into a collaboration agreement with a second leading academic institution where we are formulating their VSV vaccines into dry powder. This arrangement is very new, but holds tremendous opportunity for TFF. We hope to provide updates on this collaboration, as in vitro testing gets underway and testing results are achieved. In addition, we are -- we continue to work very closely with our partners at UGA. We are pursuing the advancement of the universal influenza protein based product candidate that we announced our positive results on back on October 27. We are pursuing additional protein based universal influenza vaccine candidates from our University of Georgia colleagues. Last week, we were honored to present to the CIVICs group. CIVICs stands for the Collaborative Influenza Vaccine Innovation Centers. We presented to an audience of over 80 participants, which included key opinion leaders and decision makers at numerous academic institutions and government agencies. We were privileged to share with this group our innovative technology and the exciting projects and programs we are working on. Our strategy is to engage with key academic centres and researchers, positioning Thin Film Freezing as the formulation partner, and then securing tech transfer and or licensing those assets to TFF. Lastly, Glenn mentioned the government contract in his opening remarks. We hope to be able to share additional details on this arrangement in the near future. We're very excited about this contract, which now establishes TFF as an approved contractor in the government arena. It opens doors for more opportunities for TFF to apply its Thin Film Freezing technology to different products for partnering opportunities with these government agencies and for additional value creation for TFF Pharma. In summary, the TFF BD team has been making tremendous progress in our partnering efforts. We currently have over two dozen pharma partners that we are collaborating with, and that list is growing. In each of these partnerships and arrangements, we are taking our partners proprietary compounds, and formulating these compounds in our TFF technology. These different compounds are being formulated, optimize, tested in our labs and being shipped to partners for testing. First, the dry powder samples are run through specified in vitro testing by our partner to confirm viability and activity. Then these samples are run through in vivo testing by our partner to confirm knockdown and activity in animal testing. Upon successful in vivo results, we then expect to engage with these partners in a full blown collaboration in a licensing agreement. While I have this opportunity, I think it is extremely important to thank our most valued collaborator, and partner. All of these business development efforts are supported by the tireless efforts and support of our collaboration partners at the University of Texas at Austin. With the continuing support of Dr. Bill Williams and his research team, we continue to expand the applications of the Thin Film Freezing technology into new and innovative areas of drug delivery. In closing, from a BD perspective, we are very excited about the growth opportunities of our technology and of our company. We believe we have only scratched the surface of the many applications of the Thin Film Freezing technology. We are highly confident, as we have said repeatedly that TFF will close at least two signature development transactions in 2021. We are laser focused on accelerating that outcome. Thank you for your time today. I will now hand it back over to Glenn.

[Glenn Mattes:]

Thank you very much, Chris. And thanks to the rest of the TFF team who participated today. I realized that we presented you with a lot of very detailed information on today's call. Well, there's quite a bit to discuss and share. I trusted you have a strong sense of the level of excitement in TFF. The excitement for the future is what everyone involved is feeling and working towards every day. Our goal is to build a strong and formidable foundation, while accelerating the positive outcomes. Today we share with you the positive progress we're making with our internal pipeline. We completed clinical trials of TFF Voriconazole and TFF Tacrolimus confirmed the target product profile and set us up for meaningful pivotal trials. In addition, monoclonal program is off to a strong start, as is the co-development of the Augmenta monoclonal antibodies. In addition, we were tracking well in our collaboration with Felix in the macrophage space and PLUS product is moving ahead to a commercialization with Thin Film Freezing versions of cannabinoids. Bill Williams discussed the newest data he and his colleagues at UT have generated, most importantly the drug theory of data in the biologics arena has grown significantly since the last time we spoke. And Chris Cano has given a strong update on the current status of our business development activities with pharmaceutical company partners, academia and the government. The agreements announced earlier this week with GreenLight and NeuroRx, along with the important recently signed government provider agreement are truly significant. We are laser focused on growing the portfolio of signature development agreements. As I said in the opening of the call, the achievements of 2020 and the beginning of 2021 are just the tip of the iceberg. I believe we are on a steady trajectory of meaningful growth as a company. We have planted great seeds in fertile soil, the harvest should be bountiful. As always, we appreciate the support of our investors and partners. And we look forward to speaking with you next quarter. And with that, I will turn the call back to the operator and open it up to questions. Operator?

[Operator:]

Our first question comes from line of Jonathan Aschoff with ROTH Capital Partners. Your line is now open.

[Jonathan Aschoff:]

Thank you. Hi guys. I was wondering

[Glenn Mattes:]

Jonathan, we can barely hear you. Could you possibly repeat that question?

[Jonathan Aschoff:]

Yes. Can you hear me now?

[Glenn Mattes:]

Yes. It's much better. Thank you, Jonathan.

[Jonathan Aschoff:]

Okay. Great. So can you give me any more specifics about the effort at PLUS products? Why did you partner with them and how you expand in cannabinoids because they are a fairly significant part of the model?

[Glenn Mattes:]

Yes. Thanks for the question, Jonathan. So, as I said in the call, first of all, as you know, we have an intermediary company, RTR, that's run by Rob Romero, who is a Managing Director of Connective Capital. So he is in direct contact with PLUS. And actually, we have folks out there this week that are beginning to produce product, and one of the PLUS facilities. We believe that PLUS has a great plan for commercializing. They're testing a bunch of different formulations as we speak. They're doing great science. They have great market penetration in California, as you probably know what their edibles products. And once they get into the market PLUS has given me some very robust commercial forecasts that are well north of $100 million, almost $200 million. And we get a very significant royalty on those sales, once PLUS is in the California market, we plan on expanding and PLUS an RTR plan on expanding the penetration nationally, either through PLUS or through other partnerships. So we believe that this is going to be a very lucrative endeavor for PLUS and through RTR, and a very meaningful contributor revenue to TFF in the very, very near future, very exciting.

[Jonathan Aschoff:]

Thank you, Glenn. And my next one's about Tac. I mean, that data looks pretty strong. And I was curious if you could get nearly bioequivalence approval outside of lung.

[Glenn Mattes:]

Okay. To answer that question can I turn it over to Dr. Christensen? Dale, do you answer that, please?

[Dale Christensen:]

Yes. Thank you, Glenn. So it is -- let me take one step back, it is possible that there would be what is essentially a matching exposure level, because ultimately, there's widely varying PK among individual subjects, and each subject they do dose adjustments to reach a -- the therapeutic drug level. And so what -- so it's not just a straightforward dose with one dose of oral dose with an equivalent dose of inhaled and show that they give an equal exposure. So, there's a little more to it than a normal BE that would be required. And so that is something that we are certainly evaluating what it would take to get there with the FDA.

[Jonathan Aschoff:]

Okay. And I didn't see that much on the Vori asthma trials. Can you tell me anything about that?

[Glenn Mattes:]

Dale again.

[Dale Christensen:]

Yes. Yes. Thank you, Glenn. Ultimately, we are continuing to enroll subjects and I can say that to-date, there's been no bronchospasm, but, again, we're just continuing to enroll patients -- asthma patients in the study and we look forward to completing that study in the next couple months.

[Glenn Mattes:]

Just quickly -- the reason we're doing that we want to be able to include asthma patients in the pivotal IPA trial for Voriconazole and the FDA required to be able to see that we have caused a bronchospasm in these patients with twitchy airways and so far, the data is supportive of everything we've seen in all the clinical trials that we've done for Vori and Tac, et cetera. Thanks Jonathan.

[Jonathan Aschoff:]

Thanks Glenn.

[Operator:]

Our next question comes from Ram Selvaraju with H.C. Wainwright.

[Boobalan Pachaiyappan:]

Hi, this is Boobalan dialing in for Ram Selvaraju. Can you hear me okay?

[Glenn Mattes:]

Yes.

[Boobalan Pachaiyappan:]

All right. Awesome. So, few questions. So, just to start out, I know you're running asthma trial and you're obviously planning to start a Phase 2 study for TFF Vori in the near future. So, I'm just trying to understand a sort of sense of what are the similarities and differences between these two trials? And what new information you're planning to obtain from the asthma study that will not be a focus of the upcoming Phase 2 study?

[Glenn Mattes:]

So as I just said and Dale spoke, we decided at the urging of the FDA to run a study in asthma patients to be sure we can include them in the trial that as looking at TFF for powder in the Phase 2 trial. So, this is a way to enhance the patient population of the next trial.

[Boobalan Pachaiyappan:]

Okay, all right. Thanks. And with respect to the upcoming Phase 2 study, how do you define success in this study? And what specific metrics will be given importance?

[Glenn Mattes:]

So the trial will be powered for non-inferiority and efficacy, and we will mine the data for pure efficacy. This doesn't mean that we don't expect to see better efficacy, but the power will be non-inferiority and efficacy, and -- at a better adverse event profile.

[Boobalan Pachaiyappan:]

Okay. So, with respect to your TFF Tac, so we understand delivering breath to the lungs for treating lung indications. But with respect to like, what is the rational again delivering drugs to the lungs for treating non-lung indications such as kidney disease? So, on what kind of challenges one could potentially anticipate during this route? And what are the possible ways to attack these challenges?

[Glenn Mattes:]

Dale, could you give a brief answer and then I'd like to move on to other questions. I have a lot of people in the queue. Thank you.

[Dale Christensen:]

Yes. So, briefly, Tacrolimus has widely differential bioavailability based on if somebody is eating a high fat meal, it is poorly absorbed in someone if they eat a high fat meal, because it's very fat soluble and not water soluble. And so it stays in the GI tract. There are also wide variations in Tarcrolimus bioavailability, based on other drugs that are taken orally. And so, when it's delivered via the lung, you bypass all of that gastrointestinal, the interaction drug interactions that would occur there, and that gives you a more defined, tighter PK range from a single dose or from a given dose. And so we think that, that's going to be the advantage. And ultimately, it will be balancing the lung levels and potential for any toxicity in the lung versus system or, the advantages gained by safety versus any potential for localised toxicity in the lung. So we're addressing that from our toxicology studies.

[Glenn Mattes:]

Thank you. I will be happy to…

[Boobalan Pachaiyappan:]

All right.

[Glenn Mattes:]

… talk to Boobalan and you on other further calls. I just want to be sure that we get some more questioners on the line.

[Boobalan Pachaiyappan:]

All right.

[Glenn Mattes:]

So, thank you so much for your understanding.

[Operator:]

Our next question comes from Mayank Mamtani with B. Riley Securities.

[Mayank Mamtani:]

Hi. Good afternoon, team. Congrats on the progress. So many friends and the new government contract announced today and thanks for the comprehensive update. I appreciated the question. So maybe, starting with Dale here, so great to see you can go with a higher dose 80mg, versus 40mg. I'm just curious if you think about the FDA dialogue, like when they want you to also pursue a lowest therapeutic effective dose. So in other words, would you have two different those arms in your in your pivotal study? A - Dale, again, just if we can have a brief answer, we're running out of time. And there are a lot of folks in the queue.

[Dale Christensen:]

Yes. Good question. But ultimately, for anti infective, they want you to be at the highest tolerated dose that doesn't induce toxicity, so that you can avoid the potential for development of resistance. And so, there's no requirement to go to a minimally efficacious dose, because that's where you would see resistance develop.

[Mayank Mamtani:]

Understood. And then, maybe for Chris, quickly on the, -- I think in the last update, you had said there was a partnership with an RNA, top 10 kind of player. I'm just curious, the kind of work that is progressing on that front and, trying to kind of also visualise the work, obviously a different modality that you're doing a lot of mRNA. How should we think about, one of these partnerships getting to a meaningful inflection point? Any update, you could provide? Also in light of a publication you had the siRNA modality?

[Glenn Mattes:]

Chris, you can answer that?

[Chris Cano:]

Yes, sure. Thanks, Glenn. And thanks for the question, Mayank. So we're really excited about our work. As you mentioned, we did speak, last quarter, about a top 10 Pharma company. And that work continues. As I've shared with everyone, it's a process, right. And so when we received the materials, formulating the materials, optimising in vitro, in vivo, and so it does take time, we're continuing to pursue that partnership that continues very well. As well as I had earlier mentioned, we're dealing with over 24 different partners. And so we're flowing everyone successfully to our pipeline. And as I closed in my comments, we expect to do at least two signature transactions this year. That's our goal. And I'm obviously laser focused on exceeding that goal.

[Glenn Mattes:]

Mayank, I could add just a brief color on that.

[Mayank Mamtani:]

Go ahead.

[Glenn Mattes:]

With the bigger companies, they want, we're doing really outstanding data, the data is very supportive, they'll come back with another round of experiments they want us to do. And all of these are coming out positive, where we're moving everything very steadily towards the end of the experimentation. But we want the listeners to really understand, we have so many jobs on go. I have this big whiteboard in my office with all the companies that we're working with. And that's the only way we can really keep track of where we're at. So, we, more than anybody, want to get these things to the finish line, we know they will get to the finish line. We're moving -- we've done so much already. And just this is at the tip of the iceberg. I think we're getting very close and --

[Mayank Mamtani:]

Okay. Just -- I really appreciate the color and maybe Glenn, another time, I'll push you on how many CDAs and NDAs you have in place. But I do want to respect, we have Bill with us. Just quickly, Bill, if I may, can you share some data that -- any qualitative color on lyophilization versus Thin Film for mRNA? And I'm also, not just looking at stability and cold chain storage benefit, but also this point about mucosal immunity, very important to investors, as we think about transmission and sterilizing immunity. Could you could you maybe comment on that? And maybe if any color, how mRNA might be different from, again, a stability standpoint when you think about other protein based vaccine approved? Because you kind of tested it all?

[Bill Williams:]

Yes, yes. Thanks, Mayank. Excellent question. So I have recently in my research lab, we've looked directly for the first time at one of the two mRNA vaccines that are approved for emergency use for COVID. So I actually have looked at those vaccines from pre-freezing, one of those vaccines and we've done a side by side comparison with conventional lyophilization. And our Thin Film Freezing powder maintained the encapsulation of the mRNA and the lipid nanoparticle. It produced a dry powder that to-date has been stable as a dry powder at room temperature for several weeks now. So -- and we've done this and we compared to conventional lyophilization where that was not able -- that process was not able to produce the original nanometer particle size upon reconstitution. So I am highly confident Thin Film Freezing works with mRNA lipid nanoparticles; especially in one of the two vaccines that are approved for COVID right now. And then with guards to inhalation, yes, several of the partners that we're working with, they've designed their mRNA lipid nanoparticle for lung delivering, for mucosal immunity. And again, even if the conventional lyophilization happened to work with their particular mRNA lipid nanoparticle modality, they could not -- they couldn't -- it's not a powder that's amenable to inhalation, dry powder inhalation. So Thin Film Freezing is and it's working for those applications. So, hopefully, that answered your really good question, Mayank.

[Mayank Mamtani:]

And about --

[Glenn Mattes:]

Mayank, we move on to other questions, we can always have a way of catching up and by the way, all of you on the line …. Q – Thank you.

[Glenn Mattes:]

All of you on the line, we will stay on the line as long as you have questions. So we're so excited about the fact that you're all interested in have questions here. So we're not looking at the clock here.

[Operator:]

Our next question comes from Jason McCarthy with Maxim Group.

[Unidentified Analyst:]

Hi, this is Michael Quintavalla on the line for Jason McCarthy. Thanks for taking the question. So I figure we are coming up on time, so I'll just keep it to a troll on we can always circle back at another time. But like this gave us any color on the kind of trial sizes needed for the pivotal studies of Vori and Tac, especially as we're heading towards those studies as early as late this year.

[Glenn Mattes:]

Yeah. If I can, we have not been public with analyzing the number of patients in those pivotal trials. Based upon this receiving the Vori final report and waiting on the Tac report, we were so looking at specific for those trials. Well, we'll let you and Jason know as soon as we we've got those numbers. I mean, at last look, I will tell you the first view we had of the Vori pivotal was about 140 patients, which is pretty consistent with what we've been thinking all along. But if you give us a little more time to zero in, the out conducting some advisory boards with some really notable investigators to help us craft that and we are going to meet with the agency to run our protocols by them.

[Unidentified Analyst:]

All right. Thank you. And then just one more, if you don't mind, I'd like to see if you could discuss in just a bit more greater detail. What exactly that subcontractor license means and what that allows you to do with the US government that would have been more difficult before?

[Glenn Mattes:]

Well, I'm really glad you asked -- really glad that you asked that question. Because we are so unbelievably excited about this opportunity, I can tell you that we really hope to be able to go into great detail on what we're doing here. We had a kickoff meeting yesterday and we're waiting to hear just how classified this government agency feels this information is. So we're really at the mercy as you can understand of the government agency to allow us and the other subcontractors, and the primary contractor to make an announcement. What I can tell you is that we've we started talking with the contractor. Almost honestly, almost a year and a half ago, I probably alluded to the potential of a government contract coming to some of you on one-on-one conversation. We went through an incredible diligence process where we were compared to other potential formulators. And we also -- based on his work are in a position to look at not only inhalation to the lungs, but intranasal and specific in this arena, topical formulations and formulations to given to the eye. So what does this do for TFF? Number one, great opportunity. We can't disclose the financial terms at this point. But we are now set up to systematically -- systemically be a contractor to the government. So we're -- we've been talking to government other potential opportunities, we've organized here internally, we know how to work the system, the contractor we're working with is very experienced in this arena. So I really hope that all of the investors that are listening to this call, although we can't be really open about the terms and what's happened here, as we'd like to be appreciate for a significant opportunities, not only in the government arena, but in all of our outreach and all of our partnerships. So unless asked, I wasn't going to say this, and I hope you can hear in our voice and on behalf of team, what tremendous work we've done and what a great position and testament is it to just how disruptive this technology is.

[Unidentified Analyst:]

Lots of exciting stuff. Thanks for taking the questions.

[Glenn Mattes:]

Yeah. Thank you so much for the question.

[Operator:]

Our next question comes from Daniel Carlson with TW Research Group.

[Daniel Carlson:]

Hey, guys, thanks for taking my question. I’ll try to be quick and early run over time. Regarding RNA modalities, you've seem to be -- you're seeing good activity. What gives you the confidence that you can formulate mRNA, siRNA, RNA et cetera into an inhalable dosage formulation?

[Glenn Mattes:]

Dr. Williams could you answer it for Daniel?

[Bill Williams:]

Sure. Hey, Daniel. Great question. So, fortunately, we have experienced in our research group with probably five different mRNA lipid nanoparticle formulations from different partners. And I mentioned a minute ago, most recently, we've -- I've used in the research group, the Thin Film Freezing technology to work directly with one of the two approved mRNA lipid nanoparticle COVID-19 vaccines. And so the powder produced from those, we have characterized those powders and they have characteristics that are amenable to inhale delivery by dry powder inhalation. So we've done it, we know it can be done. And what we do is we focus on the parameters, each mRNA lipid nanoparticles a different composition that's coming, and it presents its own unique properties. And that's what part of the -- of our technology validation studies, that's what we're coming up with the best approach to use on each individual one. Thanks for the question.

[Glenn Mattes:]

One thing I want to add before, Daniel, if you have any other questions, but we will have a TFF Science Day, we're looking at sometime in late May or early June. So we'll be announcing that as, and the reason we're picking that time is we'll have more some more mature data, and at that point, maybe some more partnerships in the academic space. So stay tuned for a specific announcement on that. I'm sorry Daniel to interrupt. There are others.

[Operator:]

Our next question comes from Bill Morrison with National Securities.

[Bill Morrison:]

Hi, guys, thanks for taking the questions. I'm trying to write fast as I can, lots of good stuff going on. But did you say there was 20 -- greater than a couple of dozen partners in biologics, or both biologics and small molecules?

[Glenn Mattes:]

Yeah. Hi, Bill, good to hear from you. Hope you're doing well. So we’re trying not to count specifically, it's north of 24. And I think Chris did a really good job of giving the graph of the different opportunities we're working on. He mentioned, monoclonal, mRNA, SRNA, phages, peptoids, VSV vaccines, we do have a couple of partners, actually we're doing work with for quite some time. They are just, sort of, formulation, new chemical entity plays, in fact, one of the first companies we mentioned without specifics was a top five company where we actually now are working on three of their compounds, they've actually asked us to do GMP materials for in vivo testing, they won't let us use their name yet. But we hope that's in the near term offering that will probably experience some revenue from that transaction just for manufacturing. So it really stands and every week it just kind of grows in each of categories. And I think Bill, you understand we don't want to say it's 25, this week 28, next week 32. We're going to kind of keep doing the 24 and above. So we're not having to check ourselves on numbers. But the funnel, the funnel is really full on a whiteboard, Chris is probably chuckling because he comes in and we erase some bad names. And so far we haven't raised any, we just keep adding names. So it's -- I don't know if you ever saw and the guy was juggling seven plates at one time that kind of like what we're doing here. But it's fun. It's unbelievable.

[Bill Morrison:]

Yes, it seems so. And then just on UNION, any update on the upfront?

[Glenn Mattes:]

Yeah. So Dale and Bill mentioned that the upfront is going to be triggered by the conclusion of our first inhuman trial and those trials are initiating. So I would look for something definitive here in the latter part of the year.

[Bill Morrison:]

Beautiful. Thanks, guys. Great job.

[Glenn Mattes:]

Thanks, Bill.

[Operator:]

So our next question comes from Dick Williams with Williams Resource.

[Unidentified Analyst:]

Hi, Glenn. I'd like to firstly say congratulations to you and the medical professionals on your team that you guys have done a phenomenal job year-to-date as well as last year. I know this is annual, but I'm more interested in the current times and I was in the prior times. But you guys have done a wonderful job. So I just have one question. And I'm sure a lot of investors have been disappointed with the results of our stock in the marketplace in the last day or so, with the last two announced that were out. And of course, we all have to realize one thing that we are microcap in the biotech sector, and that the biotech sector itself in the marketplace ran out of favor, I guess, weeks ago, and took a hit of I don't know what it was 30%, but significant, and we were just a part of that. So we have to just live with those kinds of things. But I wanted to relate to NeuroRx and the announcement you made yesterday. I think there was some things in there that went totally unnoticed, because I felt this was very significant. Firstly, the management team of that company is superb. They're very, very high level executives from big pharma and biological companies. And in the release, we talked about what we're doing for them and that's fine. But I think this particular opportunity is very close, it's not the norm of what we have in our pipeline. They are in a process with that, I'm probably going to pronounce this wrong ZYESAMI. And a trial that the FDA dictated to them should be for 28 day endpoint to achieve what they're achieving with this product to do something with I forget the name of the cell that controls a lot of the oxygen/blood in the body and is extremely important. And with COVID that cell gets damaged and that's one of the plots that cytokine and whatever else occurs thereafter. So they have started to have success with this trial. And I don't know how many people are currently in it. But they were discovering early on in the trial that the results; A, were good. And that they were starting to achieve more than they thought they would and that it would continue to be achieved beyond 28 days. So they went back to the FDA and said, hey, guys, this really should be a 60 day endpoint, not a 28 day endpoint, and the FDA in the last several days, agreed with them and extended it to the 60 days. So my question is if you can add some color as to how we fit in there with a powder and how quickly we can determine if we're doing it to that particular drug, how we can determine that it could be applicable to be used in that trial or an extension to that trial. But obviously, they are ready at the end of 60 days assuming results to ask for an emergency use authorization from the FDA. So my question is, does anyone appreciate how close this all is? And how we fit into that if at all?

[Glenn Mattes:]

Okay, first of all, thank you for the question. I think you've done a great job fully understanding why we're -- so it was such an important transaction for both new RX and the company. Chris is the closest to this. He gets so much of the credit for bringing this forward. So Chris you want to comment on this question. I just so before you do, I think this is a very analogous situation to some of the early work we did a build it on remdesivir with the hope that wouldn't be different definitely would have been effective, which is I guess we're still wondering about, we would have been the ability to take that product earlier on into the less severe COVID patients, but your appreciation are close. This is you really grasp the real value here. Chris Cano, I know is curious to clear about - could you comment please?

[Chris Cano:]

Yeah, absolutely. And thank you Dick for the question and thank you for your support. When it comes to neuro RX, we're really excited about it. You know, being able to formulate that right and deliver it as a dry powder to treat COVID frisking patients is really exciting for us, right? Right now they're treating critically ill patients, right. And so we've always viewed, if we can create a dry powder, we can treat patients earlier in the sickness or disease state. So you're correct that this is really at the goal line, there -- I'll just call it their lead asset. This is still it -- we're going to be doing feasibility work. And this I view as kind of a second generation of their lead product. So hopefully, I addressed your question satisfactorily.

[Q – Unidentified Analyst:]

Okay, so we won't, we can't be involved in essence in the 60 day window. But it would be a secondary product to add on or come in at a later date. Because if it's approved at the end of 60 days that it works, they're going to file for a EUA and they're going to be out with the product obviously –

[Glenn Mattes:]

We think that the follow-on would be right behind it. So, a lot of this will come around discussions with the FDA on how quickly the work can be done. And we've got a lot of experience and thinking through, these sort of transitions from – the existing product to the powder version, they'll probably still need to be some – Dale would be able to comment, but on – on some pre-ground, some toxicity work. And then the amount of bridging you have to do in the clinical arena is to be determined. But I know we use the word exciting a lot, we will have to find another word here. But it is a very terrific opportunity for us.

[Unidentified Analyst:]

Well, I'll use the word exciting. I'm able to do that. And thanks for the answer to that. I think you gave it a color that I was looking for, and congratulations on that deal. It's terrific.

[Glenn Mattes:]

Thanks.

[Operator:]

Our next question comes from Steven Glassman , Private Investor.

[Glenn Mattes:]

I guess, your name wrong, Steve.

[Unidentified Analyst:]

That's okay. Glenn, can you talk about how you plan on monetizing the work you're doing on the universal flu vaccine? What's the strategy there?

[Glenn Mattes:]

Sure. So, Steve, what we're hoping to do is be as engaged as we possibly can with all of the leading flu vaccine academic researchers and tie up the detect transfers from the academic institutions to TFF. And then as these individual flu vaccines or antigens are developed, we will hope to find non-dilutive funding to bring those forward. And then it kind of becomes, Steven, if you can imagine a bake-off or a beauty caucus, one or two of those will emerge, right? And as they emerge to be the leading potential universal flu vaccine, we then will be able to in the work that we're doing, take those forward and more than likely find a commercial partner to take them into further development. So we're trying to be, again, this word sort of ubiquitous around partnering and that was really the purpose of this civics presentation we gave, which was enabled by Dr. Ted Ross, at UGA where we presented I think there are 84 participants on the line where we will – the technology will expose, you know, Bill and Dale and John presented, and we have a second academic institution that is agreed to do work with us, we're actually just working on a material their internal policy is not going to let us announce that until the first data are generated. So that's two months away. And then there are actually two other academic institutions that are on the Mount Rushmore, if you will, of universal flu vaccine. Researchers, we hope to have engagements with them and others that are interested. So once we have those done in a transfer, we think we're have a high likelihood of getting the non-dilutive financing and then monetizing them through partnerships.

[Unidentified Analyst:]

180 million doses per year in this country that's a very big opportunity.

[Glenn Mattes:]

Well, yes, especially with new vaccine.

[Unidentified Analyst:]

Yeah. Exactly. Yes, it'll be much more ubiquitous because a tripod it was a young, young children injury, old frail people take it as well plus, we'll be way more effective so less resistance.

[Glenn Mattes:]

And think Steve about all the parts of the world that can't, you know, access vaccines for a number reasons, especially, if they need to be refrigerated. Right? So if there's any place -- any place at all, where this technology plays, is in the ability to bypass Cold Chain and either have may needleless vaccine to the powder or reconstituted vaccines. So, you know, I am glad these questions are coming because it gives us an opportunity to really talk about just how big these opportunities are.

[Unidentified Analyst:]

Very exciting, and I’ll now use that word.

[Glenn Mattes:]

Okay.

[Unidentified Analyst:]

Question for Dale, if I may. Has there been any problems inhaling the powder, in VIVO, in human trials for any substances, adverse reactions?

[Dale Christensen:]

Thanks, . That is a good question. So far in both -- in all of our clinical trials, in asthma patients and healthy normals for Voriconazole, there have been a few patients that have experienced headache, a few that seem to have, you know, mild lightheadedness that appears to be most likely due to the inhalation and some of that practice. But in general -- and this goes across the board, the -- there are no experiences of costs for either Tacrolimus or reports of costs following inhalation of either Tacrolimus or Voriconazole, and even more important, there has been no reported drops in FEV1 that's the ability to inhale. That is indicative of the induction of bronchospasm and an adverse effect on the lung. So to-date in all trials, all healthy normals as well as patients, there's been no pulmonary function testing that has shown any abnormalities.

[Unidentified Analyst:]

Excellent. Thank you, Dale. Thank you, everybody.

[Dale Christensen:]

Welcome.

[Operator:]

We have follow-up question from line up Daniel Carlson with TW Research Group.

[Daniel Carlson:]

Yes. Hi. Dr. Bill just to follow-up on the COVID vaccines. I know that there's internal programs, there's other technologies out there. Do you see any other technology is being competitive with TFF on this?

[Bill Williams:]

Not that I'm aware of. No. I mean, the question at the end of the day is whether conventional lawfulisation will work if it's a product for reconstitution to back to a liquid for injection at the point of use. But for inhalation, and for a lot of these products, conventional lawfulisation as I mentioned earlier, it's too slow, a freezing process. And so you get damage to the to the lipid nanoparticle, which causes degradation of the mRNA. And that's a type of data that we're finding because we do that comparison in our studies. That's our -- that's like our control to understand that. So, yes, great.

[Daniel Carlson:]

Gentlemen, if I could just follow-up one more question. You said you have run one of the vaccines the COVID vaccines. I'm wondering if that was done under an MTA or if that was done, as you did with Remdesivir, just going out and getting it on your own? If you can?

[Glenn Mattes:]

Yes, I'll answer that Daniel. Still ran it as a researcher. That's all I can say at this point.

[Daniel Carlson:]

Okay. Thanks, guys. Great progress. Appreciate it.

[Paul Sagan:]

Yes. Thank you.

[Operator:]

That concludes today's question-and-answer session. I’d like to turn the call back to Glenn Mattes for closing remarks.

[Glenn Mattes:]

Well, for all of you that have stayed on with us for the entire call, it's greatly appreciated. For those of you that know me, I'm -- we're highly accessible. We'd love to talk about what we're doing here. Those of you who don't know me, we are very accessible, and we'd love to answer your questions. So thank you for your support. I hope you all a well and stay well and we look forward to updating you on our progress as we move forward. Thank you very much.

[Operator:]

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.