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spk01: Good afternoon, ladies and gentlemen, and welcome to the TFF Pharmaceuticals fourth quarter and year-end 2021 financial results conference call. As a reminder, this conference is being recorded. I would now like to turn the call over to your host, Corey Davis of LifeSci Advisors. You may begin your conference at this time.
spk07: Thank you, operator. Hello, everyone, and welcome to the TFF Pharmaceuticals fourth quarter and year-end 21 financial and business results conference call. With me on the line today is Glenn Mattis, President and CEO of TFF, Kirk Coleman, Chief Financial Officer, Dr. Dale Christensen, TFF's Director of Clinical Development, Dr. Bill Williams of the University of Texas at Austin, and Chris Cano, TFF's Chief Operating Officer. The press release announcing our fourth quarter results is available on the TFF Pharmaceuticals website. Please take a moment to read the disclaimer about forward-looking statements in the press release. The earnings released in this teleconference both include forward-looking statements, and these forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially from the statements made. Factors that could cause actual results to differ are described in the disclaimer and in our filings with the U.S. Securities and Exchange Commission, including the risk factors section of our 2021 annual report on Form 10-K filed with the SEC. And now it's my pleasure to turn the call over to Mr. Glenn Mattis.
spk04: Good afternoon and thank you for joining us today to review the company's fourth quarter operations and recent highlights. During this call, I will provide an update on our overall progress. There is a lot to share. After my discussion, I will ask our leader of clinical development, Dr. Dale Christensen, to update us on the progress we are making on our internal clinical programs. Following Dale's remarks, Kirk Coleman, our chief financial officer, will then review the company's financials for the quarter Following Kurt's comments, Dr. Bill Williams of the University of Texas at Austin will provide an update on the latest R&D applications using our thin-film freezing platform technology, which continue to expand as well as opportunities to continue to expand our intellectual property estate. Finally, Chris Cano, our Chief Operating Officer and Head of Business Development, will update our progress in that arena as our thin-film freezing technology continues to generate expanding interest on the part of industry pharma and biotech partners, some of the world's leading academic research institutions, and the government. Without question, 2021 can be best described as a year of significant corporate achievements. Our robust activity on the partnering front, coupled with the advancement of our internal clinical stage pipeline candidates, should provide our shareholders with confidence that we are building significant sustainable growth and value while fully executing our corporate strategy. Obviously, the recent weakness in the capital markets have created conditions that, in our view, do not accurately reflect the progress we have made. Over time, however, we know that building partnerships and generating positive clinical data are important achievements that create value for our shareholders. So despite the current environment, we are more optimistic than ever that our progress on all fronts will be recognized and rewarded. Let me start by briefly describing the progress we've made in our clinical stage pipeline. I'm happy to report that the investments we made in developing our internal pipeline assets have enabled us to advance both of our inhaled boriconazole and inhaled tacrolimus into larger, potentially pivotal Phase II trials that began at the start of the year. In a few minutes, Dale Christensen will describe in more detail these innovative clinical programs, but for now, I'll provide just a brief overview and explain the significant potential of each program. We're applying our thin-film freezing technology to develop an improved formulation of the antifungal voriconazole. Our inhaled voriconazole powder has a target product profile that will improve upon orally administered voriconazole by delivering the drug directly to the infected lung tissue in patients with invasive pulmonary aspergillosis. Our clinical trial is designed to demonstrate efficacy while improving the safety profile of the existing drug, specifically in patients who require more chronic use of Oraconazole, and patients with prophylaxis of infections is advised. In fact, we recently hosted a TFF Science Day last December, featuring a presentation by Dr. Carsten Schwarz, Director of the Cystic Fibrosis Center in Potsdam, Germany. The presentation, which is available on the TFF website under the Events and Presentations section, provides an important KOL-based perspective on the broad potential of TFF borate to support the current use of the oral formulation. As we think about developing internal pipeline candidates, Our main focus is not to just reformulate an existing or novel drug per se, but to rather develop a new formulation that has strong clinical potential to advance the current standard of care. Based upon the clinical data generated to date, the emerging profile of inhaled boriconazole powder has the opportunity to do just that, and we look forward to providing updates on the Phase II program as we move forward. We're equally excited about the potential to improve the current standard of care with our inhaled formulation of tacrolimus. DFS inhaled tacrolimus powder target product profile includes delivering immunosuppressive levels of tacrolimus directly into the lungs following transplantation while reducing the patient's overall systemic exposure. Presently, tacrolimus is administered intravenously to lung transplant patients immediately following surgery to prevent acute rejection of the transplanted lung. Unfortunately, higher doses of tacrolimus are often required to prevent acute rejection, and this can lead to considerable systemic toxicities. By delivering tacrolimus directly to the lung by using our thin-film freezing technology, we hope to achieve sufficient immunosuppression while avoiding these systemic toxicities associated with both the IV and oral delivery currently available. These toxicities are quite limiting and have an extreme negative effect on renal function. In our view, the successful development of inhaled tacrolimus powder offers the potential to significantly improve upon the current standard of care of patients receiving immunosuppression therapy following lung transplant. We are also confident that TFF's inhaled tacrolimus powder will demonstrate similar advantage in patients who have received heart, liver, and kidney transplants as well. The potential of the product can have a profound effect on a significant number of patients. Our internal commercial market forecasts conservatively project sales potential in excess of $1 billion, making TFS inhaled tacrolimus pluriter a blockbuster drug. Now that we are in phase two development for both TFF inhaled tacrolimus and voriconazole, it is important to note that the trials are designed with an interim data analysis. These interim data will be available in the latter part of the third quarter and will serve as a major inflection point for our company. As noted in our corporate presentations, it is our goal to partner these assets with a pharmaceutical company who has the ability to optimize these products in the commercial setting. That process has already begun, and Chris Cano will discuss the approach later on this call. Upon the successful closing of those transactions, we look forward to a meaningful monetization and creation of value for our shareholders. We also made considerable progress with our inhaled niclosamide program. Back in October, we announced Canadian approval for testing niclosamide in humans. And just last month, we announced highly positive data showing the ability of our inhaled niclosamide powder to significantly inhibit viral replications of the Omicron variant of the SARS-CoV-2 virus. These data showed the remarkable potency of this antiviral drug. When delivered directly to the lung at a low concentration, inhaled niclosamide powder produced very strong antiviral activity. Given this level of potency, we believe inhaled niclosamide powder could offer a potential with respect to safety and tolerability over oral delivery. The full Phase I study data set will be available next month. Those data will be shared with our partner, Union Therapeutics. Union Therapeutics will then have some time to exercise their option to further develop inhaled niclosamide powder. EFF believes strongly in the antiviral potential of niclosamide in COVID-19 and beyond. We're evaluating additional indications and potential for necrosomies that involve receiving non-dilutive funding to move forward where there is an opportunity. In addition, we are working with our partner, Augmenta Bioworks, on Augmenta 3387. Augmenta 3387 is a potent monoclonal antibody that we're developing to treat SARS-CoV-2. Thus far, in animal testing, we have demonstrated positive data On all the COVID variants, including the Delta variant, we have shown binding to Omicron, and we are assessing the neutralization profile of augmented 3387 on that variant as well. Dale will discuss further in his section. And finally, we continue to work with PLUS products on refining the thin-film freezing formulations of cannabinoids. Very happy to report that we are receiving very positive feedback from PLUS on their consumer testing. Our goal is to launch TFF versions of cannabinoids as a safe substitution for vaping. It is imperative that the TFF formulations meet the preferred product profiles by the users. The target product profiles focus on an easy-to-use inhaled product that delivers a desired experience. We believe that we have now reached that threshold. Plus Products is an excellent partner and has worked closely with TFF to refine our formulations, and test the products with consumers. Plus is in the process of restructuring their company, and we've been told that they are close to announcing a successful outcome. We look forward to partnering with Plus on bringing these products to the marketplace as soon as possible. We're also discussing the TFF cannabinoid opportunities with additional partners. TFF announced our latest collaboration with the global CDMO Catalyst on March 1st. We are very excited about this agreement, as Catalan significantly expands our access to manufacturing capabilities, which has been a major question asked by our potential farmer partners about producing product. This has been especially true in the biologic space, and Catalan clearly addresses this need. Catalan will also offer a thin-film freezing technology to a targeted list of their over 1,000 clients. Catalan has a significant amount of sales resources to enable that effort, and we expect that the TFF portfolio of collaborations will greatly increase as a result of this outreach. Now, I want to address the status of our business development activities. Chris Cannell will greater detail them in a few minutes. The work with potential licensing partners is proceeding very well. Our list of partners continues to grow, as well as the number of open projects We understand that the investor community wants to see TFF sign a number of meaningful licensing transactions. The TFF team very much shares this desire. The company is very confident that this will happen and we will realize the value contribution to the company. Each partnership is different and requires a great amount of work to complete the required experiments to fully demonstrate the value of the thin film freezing technology. Again, this is especially true in the biologic space. We have not been faced with any specific scientific challenge that cannot be addressed. Our partners remain highly engaged and we're working diligently to get to the finish line. We will continue to report progress and when given the go-ahead by the partner, share their names with you. Continuing to focus on our accomplishments, I'm pleased to note that we recently entered into a second cooperative research and development agreement with the United States Army Medical Research Institute of Infectious Diseases, also known as USAMRIT, which is part of the U.S. Army Medical Research and Development Command and the U.S. Army's premier institution and facility for defensive research into countermeasures against biological warfare. And the Geneva Foundation, a nonprofit foundation that supports and advances innovative medical research within the U.S. military. Through this collaboration, TFF Pharmaceuticals and USAMRIT will evaluate the immune response of a dry powder recombinant vascular stomatitis virus severe acute respiratory syndrome coronavirus 2-glycoprotein vaccine using TFF's thin-film freezing technology. The end goal is to develop a single, easily administered and temperature-stable set of countermeasures to protect our warfighters against multiple viral pathogens such as SARS-CoV-2, Ebola, Marburg, and others. This is the second CRADA announcement we've announced over the past two years, and we're very proud to build the government partnerships that are so important in developing effective countermeasures to potential bioterrorist threats and to the future of public health in general. These craters are an addition to the contract we have with Leidos and DARPA to formulate additional countermeasures administered in unique formulations, including the nose, eye, and skin. Also in the government area, I am very happy to announce that our efforts to expand and attract opportunities within the U.S. federal government and build on our ongoing collaborations with USAMRID, DARPA, and other agencies We have been engaging broadly with congressional members to elevate awareness of dry powder approaches with thin film freezing drying that allow for vaccines to be physiochemically stable. We saw this language included in the recently passed fiscal year 2022 government funding bill that was recently signed by President Biden. The language is non-binding, but will elevate the opportunity for securing funding by providing notice to the related agencies, such as HHS, that Congress is interested in monitoring progress on this issue. You will note that in the legislation that the language is specific to thin-film freezing. Moving on in respect to recent corporate developments, I'm pleased to announce the appointment of Brandi Roberts to our Board of Directors. Brandi has over two decades of financial management expertise within the life sciences sector. As we continue to grow and develop more strategic relationships with our existing and future partners, Brandy's expertise and experience will undoubtedly help us navigate larger and potentially more complex partnerships while also bringing us to manage through periods of significant company growth. I welcome Brandy to our board and look forward to working with her for many successful years to come. Today we are also announcing that Dr. Brian Windsor will be stepping down as chief scientific officer and board member to focus exclusively on his role as CEO of Lung Therapeutics. Brian has been with us since our company's founding and has made many significant contributions, both with respect to scientific achievements and as a board member. He was especially helpful as we prepared for and executed our IPO. I'd like to thank Brian for these contributions and wish him the best in his future endeavors. TFF is also proud to announce that Dr. Anthony Hickey will assume the role as Chief Scientific Officer for TFF. Dr. Hickey is a Professor Emeritus in Pharmacoengineering and Molecular Pharmaceutics at the Eshelman School of Pharmacy at the University of North Carolina at Chapel Hill. Dr. Hickey is also an Adjunct Professor of Biochemical Engineering at the University of North Carolina School of Medicine. Tony has also been a member of the TFS Scientific Advisory Board since its inception. Please join me in welcoming and congratulating Dr. Hickey. I also would like to announce the appointments of three senior executives who will bolster our leadership across key areas of our business. Dr. John Kohling has joined as Vice President of Product Development and Manufacturing. Dr. Greg Davenport as Vice President of Government and Strategic Initiatives. and Paul Manley as head of regulatory affairs. Each of these executives has significant experience in their respective fields. And as our partnerships and programs continue to expand, the depth of their scientific knowledge, medical expertise, and relationships will be tremendous assets to help further grow our business. I realize that I just delivered a significant amount of news and likely left out other elements of our progress. Thank you for your attention and patience. Let me now turn the call over to our head of clinical development, Dr. Dale Christensen, who will discuss our clinical programs in greater detail. Dale?
spk06: Thank you, Glenn, and good afternoon to everyone who has joined our update call today. Our productivity continued in the fourth quarter, and we continue to make significant progress by advancing our internal clinical development programs. Let me begin the clinical update by discussing our TFF for a connoisseur program. We are developing voriconazole inhalation powder for the treatment of invasive pulmonary aspergillosis, or IPA. IPA is an invasive fungal infection of the lung that causes significant mortality in patients with lung diseases and those with compromised immune systems, including patients on immunosuppressive drugs following transplants and those with severe neutropenia following chemotherapy for leukemia. Last quarter, we completed our Phase 1b trial in asthma patients. As a reminder, this study was performed to allow us to understand if patients with asthma or other hyperreactive airways due to lung disease would experience bronchospasm when the inhaled voriconazole was administered, and this was a necessary step to allowing those patients to be included in the Phase 2 trial. With this study complete, patients with asthma and COPD will be eligible to participate in our future studies. We have also initiated our phase two trial in patients with IPA. The design of this study has been modified from our original study design and is now an open label study that will randomize patients to receive either 80 milligrams of inhaled voriconazole twice a day or to receive oral voriconazole in accordance with the prescribing information. This change is due to the prescribing guidelines for oral voriconazole that provides for increasing the recommended 200 milligram twice daily dose to as high as 300 milligrams twice daily if the patient response to treatment is inadequate, or to reduce the dose to as low as 100 milligrams twice daily if the patient is unable to tolerate treatment at a higher dose. In clinical practice, these dose adjustments have reduced the discontinuation rate due to dose limiting toxicity. but does come with the additional burden of monitoring drug levels in the blood and associated liver enzyme function of the patients in order to identify the appropriate dose for each patient. It is our belief that delivery of the 80 milligram inhaled dose directly to the lung will free these patients and their physicians from the burden of repeated lab tests and dose adjustments to find the Goldilocks zone with high enough drug levels in the blood to be efficacious, but not so much that it is toxic to the liver, eyes, or heart. In our open label design, we will be able to determine the frequency of dose adjustments required to keep patients on oral Voriconazole and compare this to the single inhaled dose. Another important milestone we achieved was that we also began dosing a lung transplant patient with voriconazole inhalation powder in a compassionate use study. This particular patient had previous fungal infections in the lung and experienced significant adverse events while taking oral voriconazole and other antifungals to treat these previous infections. This patient is infected by a non-aspergillus fungal species that is susceptible to voriconazole. Since the presence of non-aspergillus fungal species makes a patient ineligible for our Phase II study in IPA, the treating physician believed that TFFs for aconazole inhalation powder would provide the optimal results for this patient by effectively delivering the Voriconazole directly to the site of the infection. More importantly for this patient, the potential for efficient clearance of the fungal infection is combined with reduced systemic exposure that could otherwise adversely affect the patient due to drug-drug interactions with their immunosuppressive medications that prevent rejection of the allografted lung. I am pleased to report that the patient is doing very well on our Voriconazole inhalation powder And the information received to date supports our treatment and safety hypothesis that underlies the development of this product. We will continue to monitor the efficacy of the voriconazole inhalation power in clearing these less common fungal species while also monitoring the safety of the drug as well as any drug-drug interactions that do arise. We will continue to treat more patients under this compassionate use approach when the appropriate medical need is documented by our network of physicians. In addition to advancing our voriconazole inhalation powder to phase two testing, we've initiated phase two trial activities in Australia with our tacrolimus inhalation powder in lung transplant patients. This study will be performed in patients with stable lung allograft function, but who are also experiencing a level of nephrotoxicity that is causing their physician to reduce their tacrolimus blood levels in order to spare the kidney. These patients face a choice of risking rejection of the lung transplant or losing their kidneys due to tacrolimus-induced nephrotoxicity. And up to 5% of lung transplant patients eventually undergo secondary kidney transplants. Our non-clinical studies demonstrated that when TFF's tacrolimus powder is delivered by inhalation, greater levels of tacrolimus drug are retained in the lung tissue compared to the systemic exposure in the blood, indicating that we can reduce the patient's systemic tacrolimus levels to better protect the kidney while delivering sufficient concentrations of the drug into the lung to maintain the immunosuppression and reduce the risk of transplant rejection. In this study, we will be dosing patients for a sufficient duration to measure potential rejection along with the stabilization or recovery of the kidney function. Next, I'd like to provide an update on the development of our nyclosamide inhalation powder for the treatment or prevention of COVID infections. On our last call, we announced the dosing of the first subjects, and in January, we completed the dosing in this study. We've locked the database and expect to receive the unblinded data in the weeks to come. Delivery of niclosamide inhalation powder directly to the lung represents a highly promising approach for COVID. This was recently confirmed when we announced that our in vitro study showed that niclosamide inhibits replication of the Omicron variant of SARS-CoV-2. The potency of niclosamide derives from the drug's ability to inhibit human cellular targets and respiratory cells that are required for viral replication. This is in contrast to viral targeting drugs because the human host cell machinery is the target. This means that mutation of the virus does not allow for mutational escape from drug efficacy. Our future studies will position inhaled niclosamide for outpatient use so that patients diagnosed with COVID can pick up the drug from a pharmacy and self-administer at home. We believe the lower overall dose and limited systemic exposure will result in reduced adverse events compared to oral COVID targeting antiviral products, a very important differentiator. The leading oral antiviral for COVID is comprised of an antiviral agent known as nirmatrelvir that is paired with ritonavir. The function of ritonavir is to inhibit the cytochrome P450 enzyme CYP3A4 that metabolizes the antiviral compound. Inhibition of CYP3A4 ensures that enough of the antiviral drug circulates in the blood to reach effective antiviral levels. However, ritonavir is contraindicated with many critical drugs that are used by patients with complicated conditions. These conditions put them at risk for increased severity and death from COVID. This means that many of the most at-risk patients cannot take this medication. Niclosamide is not burdened by the same issues, and the levels we are delivering to the lung would not suffer from similar drug-drug interactions. so that it could be administered therapeutically and potentially prophylactically to these high-risk patients. Finally, as the Omicron and now Omicron BA.2 wave has hit, the utility of monoclonal antibody therapies has essentially evaporated, with the Regeneron and Lilly antibodies proving ineffective against Omicron and the Veer, GSK, and AstraZeneca products being ineffective against BA.2. We have found that our lead monoclonal antibody, AUG3387, that we have been developing with Augmenta Bioworks, binds to the Omicron spike protein with high affinity. However, along with our colleagues at Augmenta, we continue to assess our 3387's neutralization data while determining the specific path forward for this asset. These discussions also include involvement with members of our scientific advisory board. And with that update, I'd like to turn the call over to our Chief Financial Officer, Kirk Coleman, for a review of the financials. Kirk?
spk03: Thank you, Dale. For the three months ended December 31st, 2021, Research and development expenses for the company were 6.9 million compared to 3.1 million for the same period in 2020. The increase in research and development expenses during 2021 was due to increased preclinical activity related to the niclosamide and increased clinical activity related to inhaled 4-conazole and tacrolimus programs. The ramp up also includes our preliminary analysis and testing of dry powder formulations of several drugs and vaccines that we believe have the potential to become product candidates. For the full year 2021, research and development expenses were $21.3 million compared to $10.7 million in 2020. The increase in research and development expenses during 2021 was mainly due to increased manufacturing costs, clinical and preclinical expenses related to niclosamide, boriconazole, and tricholomus programs, increased payroll and related expenses, and increased stock-based compensation. The increase in research and development expenses also includes our preliminary analysis and testing of dry powder formulations of several drugs and vaccines owned or licensed by third parties that we believe may lead to the out-licensing of our TFF technology for the development of dry powder product candidates. General administrative expenses for three months into December 31, 2021 were $3.2 million compared to $2.9 million in 2020. For the full year 2021, general administrative expenses were $10.6 million compared to $8 million for 2020. The company reported a net loss for the fourth quarter of $10 million compared to a net loss of $5.9 million in 2020. For the full year 2021, the net loss was $31 million versus a net loss of $18.6 million for 2020. Weighted average common shares outstanding, basic and diluted for the three months into December 31st, 2021, were $25,371,781 compared with $22,759,329 for the same period in 2020. As of December 31st, 2021, we had total assets of approximately $40.7 million and working capital of approximately $36.9 million. At the end of the fourth quarter, our liquidity included approximately $33.8 million of cash and cash equivalents. And with that, I'd like to turn the call over to Dr. Billy Williams, who will talk about some of the groundbreaking work we're doing using our thin film freezing platform, particularly with large molecule biologics and how our technology is unique in its ability to successfully transform these complex molecules into an inhalable dry powder.
spk02: Thank you, Kirk, and good afternoon, everyone. I am pleased to report that we have had another productive quarter on many fronts for expanding the thin film freezing technology platform and differentiating it from other technologies. We have published in high-impact journals important new research on several aspects of thin film freezing, including on the preparation of dry powder for inhalation containing monoclonal antibodies made by thin film freezing. This new research confirms that the aerosol properties of an anti-PD-1 monoclonal antibody made by thin-film freezing were significantly better than powder prepared by conventional shelf freeze drying. Also, when stored at room temperature for 10 weeks, the anti-PD-1 monoclonal antibody in the powder was stable, whereas the same formulation stored as a liquid was not. It is evident that the antibody is not stable when stored as a liquid at room temperature on a shelf. Thin-film freezing solves that limitation. With respect to heat stability, we reported that the addition of a pharmaceutically acceptable excipient in the formulation was able to significantly raise the glass transition temperature of the powder, a key metric to predict storage stability, which is expected to further increase the storage stability of the monoclonal antibody. Importantly, the PD-1 binding activities of the anti-PD-1 monoclonal antibody before and after thin-film freezing were not different. Lastly, we showed that another monoclonal antibody, an anti-TNF-alpha, could also be converted to a dry powder by thin-film freezing. For comparison, it was reported that when infliximab, the anti-TNF-alpha monoclonal antibody contained in the product Remicade, When it's processed by a spray drying process, its binding ability was reduced by over 20%, which is an unacceptable reduction. So applying thin-film freezing to the anti-TNF-alpha in our study had superior results compared to spray drying another antibody based on the infliximab paper. We concluded that thin-film freeze drying can be applied to produce stable, aerosolizable dry powders of monoclonal antibodies for pulmonary delivery. As Glenn noted earlier in this call, it is clear that thin-film freezing applications are now viable across an expansive range of molecular structures, including biologics. And we continue to grow the number of projects in development utilizing thin-film freezing for next-generation monoclonal antibodies fusion proteins, and many other biologics. Next, we have successfully applied thin-foam freezing to formulation of dry powder vaccines containing the adjuvants MF59 or Ativax, which is a similar adjuvant to MF59. So why is this significant? Vaccines containing these important adjuvants are difficult to formulate and stabilize. These adjuvants, like MF59, are nano-emulsion-based vaccines that are now used in seasonal and pandemic influenza vaccines. However, these adjuvanted vaccines require a cold chain for storage and are sensitive to accidental freezing. Our new studies confirm that thin-film freezing can be applied to convert vaccines containing MF59 or Ativax from liquid to a more stable dry powder while maintaining the immunogenicity of the adjuvanted vaccine. Based on our studies to date, thin-film freezing can be used to prepare dry powders of multivalent universal influenza vaccines as well. We are very excited about these results, which again point to the versatility of the thin-film freezing technology and its potential to enhance vaccine formulation development. So, these highlight just two of our most recent published research papers from our group on thin-film freezing. And we also plan on publishing additional research very shortly, including a publication that will describe the development of powder formulations of the liposomal adjuvant AS01B containing vaccines using thin film freezing. This adjuvant, AS01B, is important since it is the adjuvant used in the FDA-approved Shingrix vaccine for herpes zoster and shingles, and it is used as the adjuvant in malaria vaccines that are being tested in Phase II clinical studies now. Finally, we will present five key papers at the upcoming Respiratory Drug Delivery Conference, which is being held in Orlando, Florida, in early May. The theme of our talks will be to provide this influential audience with our most recent data on applications of BIMFILM freezing to stabilize and deliver biologics, to differentiate thin film freezing from other technologies for proteins, and to discuss applications of artificial intelligence to facilitate the drug development process for products made by thin film freezing. In closing, I want to acknowledge my colleague, Professor Zhenrong Cui, and our team of dedicated researchers at the University of Texas at Austin for their significant contributions and collaboration. I also want to thank Dr. Tony Hickey for agreeing to serve as Chief Scientific Officer. Tony is internationally recognized for his expertise in drug delivery and drug therapies, and this will greatly complement our efforts. Thank you for your continued interest and support, and I'll now turn the call over to Chris Cano, Chief Operating Officer and Vice President of Business Development for TFF Pharmaceuticals.
spk09: Chris? Thanks, Bill. And good afternoon, everyone. Thank you for joining us today. The TFF business development team is focused on three key areas of growth for the company. These three key areas are, one, growing the TFF pipeline of internal development programs, two, our pharma partnering efforts, and three, our government and academic contracting efforts. We continue to make tremendous progress in each of these key areas. For today's call, I will be focusing on our lead collaboration efforts with both our pharma partners and our academic collaborators. First, with our pharma partners, TFF continues to be very active in the biologic space. Our biologic projects are steadily advancing as key experiments get us closer to satisfying the requests by our partners for the data they need to execute licensing agreements. We also continue to increase the number of partnerships each quarter. Lastly, we are in continuing discussions with a number of new potential partners discussing additional feasibility projects. These biologic projects include, but are not limited to, different phages, monoclonal antibodies, FADs, siRNA, oligos, mRNA, plasma DNA, peptides, proteins, BSV, lentivirus, and nanobodies among many other classes of complex biologics. TFF continues to work with its partners in two key applications of the TFF dry powder technology for biologics. The first application is formulating our partner's proprietary biologic into a stable dry powder for inhaled delivery directly to the lungs for certain respiratory diseases. The second application involves taking our partner's proprietary biologic vaccines and formulating a stable dry powder version for reconstitution and injection, which is not subject to cold chain storage. Our experiences have shown that every biologic drug substance that we receive from a partner is unique and has its own set of challenges. In other words, there is no one-size-fits-all solution. In fact, a tremendous amount of formulation work and testing takes place for each biologic product. Through numerous rounds of formulation work and testing, TFF is able to fine-tune our technology and our processes to discover and optimize a unique and innovative dry powder formulation for that specific biologic drug substance. These efforts are all performed in a direct, interactive, and collaborative manner with all of our partners. As an example, we have multiple mRNA programs with numerous different formula partners. Across the board, our TFF dry powders have shown exceptional physical attributes, which include very favorable particle size, polydisparity, or PDI, and very high encapsulation efficiency rates. Beyond the physicochemical testing attributes, TFF is also testing the integrity of these mRNA products by a capillary electrophoresis, or CE, testing. Our CE testing shows that following the application of our TFF dry powder process, the integrity and activity of the mRNA shows minimal loss or is equivalent to the original mRNA, which is a critical measurement in determining the retention of the compound's physical, chemical, and biological properties. We have shipped our TFS mRNA dry powder samples to multiple partners. For some partners, we are awaiting transfection assay testing results. For others, we are awaiting confirmatory physicochemical and molecular integrity testing to be completed by the partner. For others, we are awaiting results from stability testing of the mRNA dry powder at various temperatures and time points. And for some other partners, we are conducting animal studies. These efforts do take time, and for each partner, across all our different biologic projects, on a case-by-case basis, partners are requesting different stages of testing and or different data sets in order to commence licensing negotiations. In many cases, the partner funds the work that has gone beyond what was planned in the original NTA statement of work. Rest assured that in all cases, TFF continues to take a very aggressive approach with its partners to reach our goal of entering into collaboration and licensing agreements with each of these partners. Now, let me provide some brief updates on some recent partnering activity. As recently disclosed on our website, we are very pleased to be collaborating with Pfizer on multiple projects. This work is moving along very well, and TFF is generating positive data on these projects. Pfizer continues to review and evaluate the data in real time, and we continue to aggressively move these projects forward. Also, as we just disclosed on our website, we are now partnering with Astellas on a specific product where we are applying, processing, formulating, and testing the TFF dry powder technology to formulate a dry powder version of a specific Astellas product. Being sensitive to the confidential nature of this project, We cannot disclose any further details at this time, but hope to be able to provide more color as this project evolves and we receive the proper disclosure approvals from Astellas. As Glenn previously mentioned, we are very pleased to be partnering with Catalan. This partnership will provide TFF with the opportunity to work with Catalan in expanding our access to scale up manufacturing capabilities, while at the same time, giving TFF access to a very large customer base to evaluate the applications and benefits of the TFF technology. We believe this collaboration can ultimately lead to additional licensing partnerships for TFF, providing us with a potentially meaningful source of revenue over time. At TFF, there are many applications of the TFF dry powder technology. We continue to aggressively explore and expand into new areas and or applications of our dry powder technology. Most recently, TFF entered into a new feasibility arrangement with a new undisclosed partner. We are moving forward on a new initiative, the concept of formulating the TFF dry powder for use in an intranasal device. TFF along with our partner are exploring the applicability of a specially formulated TFF dry powder in our partner's proprietary intranasal device. If these initial experiments prove successful, we believe the unique attributes of the TFF dry powder can be expanded to include additional routes of administration, which, depending on the compound and the disease state, can be very advantageous for both patients and prescribers. As Glenn mentioned earlier, we have finalized a new credo with Usamerid. This is our second credo with Usamerid. With our partners, we will be evaluating the immunogenicity and protective efficacy of the TFF tri-powder version of a VSV vaccine for COVID. We are very excited to progress this animal work with our partners and continue to advance this asset through the next stages of development. We also continue to make very good progress with our academic partnerships. In collaboration with the University of Georgia, late last year, we filed a publication related to the application of the TFF technology to formulate certain adjuvants. These were adjuvants utilized in our mouse immunogenicity study, which we reported on back in October of 20. Also with our partners at UGA, we received favorable efficacy data in our recent ferret study. We are now in discussions with UGA on clearly defining next steps on advancing the TFF version of UGA's universal influenza HA recombinant vaccine. With the Albert Einstein College of Medicine, we are now moving our VSB program into both animal studies and stability testing. And with Dr. Drew Weissman at the University of Pennsylvania, we have completed our initial mRNA formulation work, and we have finalized our protocols for animal testing. And we are scheduling the delivery of our TFF dry powder samples to Dr. Weissman to commence these studies. As it relates to our internal programs, we have recently engaged Torreya partners as our financial advisor to lead the partnering process of both our lead assets, TFF Mori and TFF Tech. We have prepared virtual data rooms in advance of this process, and we currently have interested commercial partners performing extensive due diligence exercises. As mentioned earlier, upon receiving the phase two interim data, TFF will be actively engaging in asset acquisition and licensing negotiations. In summary, the TFF BD team has been making tremendous progress in our partnering efforts. We continue to grow the number of collaborations with pharma partners and academic collaborators, as well as we continue to grow our government contracting efforts, all in a strategic effort to expand the applications of our thin film freezing technology. In closing, I would like to thank our partners at the University of Texas at Austin. With the continuing efforts and 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. Thank you for your time today. Enjoy your evening. I will now hand it back over to Glenn.
spk04: Thanks to Dale, Kirk, Bill, and Chris. And I apologize for the length of the call. We're always faced with a time challenge in order to selectively communicate the breadth of our work and opportunities. As I mentioned in my earlier remarks, TFF is continuing to execute across all facets of our business. And while the current market conditions make it challenging to reflect the progress in our share price, I want to assure our shareholders that validation of our core drug delivery technology only continues to grow. and is shown by the continued expansion of our partner programs, coupled with the success we are demonstrating in advancing our internal clinical stage assets, which are rapidly approaching the opportunity to partner and monetize. EFF has achieved significant recognition and validation, with the light brightly shining on the thin film freezing platform by the pharma industry, academia, and government. The opportunity to work with Catalan is also a significant boost to our capabilities and potential. As we continue to execute on our business strategy, we believe a closer alignment between the growing value of our technology platform and our company valuation should eventually be realized. I thank all of the TFF employees and key consultants for their contributions to the company, and the board and I thank our shareholders for your support. And with that, I'll turn the call back to the operator and then open it up to questions. Operator?
spk01: At this time, we'll be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation cell will indicate your line is in the question queue. You may press star 2 to remove your question from the queue. For participants using speaker equipment, it may be necessary for you to pick up your handset before pressing the star keys. One moment while we poll for questions. Our first question comes from the line of Jonathan Ashworth with Roth Capital Partners. You may proceed with your question.
spk10: Thank you, guys, and good afternoon. I was wondering if you could first tell us the significance of the recent niclosamide data. More specifically, how do you directly correlate in vitro drug correlations with what to expect to achieve in the first trial in humans, which is kind of a very different microenvironment?
spk04: Thanks for the question, Jonathan. This is Glenn. Dale, could you answer Jonathan's question, please?
spk06: Yes, thank you, Jonathan, for the very good question. So we have done a number of things to help make that correlation. One is that we have published data where we administered the TFF niclosamide powder directly to the lungs of hamsters and rats, and we were able to quantify the amount of niclosamide in the lungs in the lung tissue as well as the epithelial lining fluid, the fluid that lines the lungs. And there we saw that we would be delivering far more than the one micromolar concentration. Also, you know, we are delivering a clinical dose where we saw safety at six milligrams delivered twice daily. With that six milligram dose and an estimated volume of approximately 50 milliliters of fluid in the lung, that gives us a concentration of niclosamide in the lung lining fluid of greater than 100 micromolars. So, When we saw a one micromolar concentration effectively inhibiting complete viral replication, we know that by delivery of our dry powders, we are exceeding that concentration throughout the testing both in the hamsters and rats in vivo as well as with what we would expect from the humans.
spk10: Thanks, Dale. What do you guys think that Union needs to see from the Phase 1 niclosamide trial to elect to conduct Phase 2?
spk04: Yeah, so we have been getting really nice feedback from Union on all of the work that we've been doing, Jonathan. We think the work we've done and what we'll see in the final tables of the Phase 1 data will certainly meet and clear the hurdles of what union is expecting. What we don't know is what the union current overall strategies are, but from what we've done in terms of the data generation, what we've promised them that we would do, we've done everything that we think should get them to exercise the option. So we're positive about that. They will have time to assess that after Dale produces the final tables. Certainly, we want Union to exercise the option, and we would go on from that point.
spk10: Okay. You guys just, you know, said that you were very keen on partnering the non-biologics that you have, the TAC and the VORI. And I was kind of wondering, you know, when will we see Phase II TAC and VORI data that, you know, would be the kind that would be enough to drive someone to partner?
spk04: Yeah. So we think the latter part of the third quarter. Jonathan will have meaningful interim analyses to share with the partners that are lining up in Chris's process with TREA. So these are open-label studies. So we think certainly by, I would say, the latter part of the quarter, we will have enough data for them to decide. You never know. I mean, these partners could decide to make an offer before they see data. If I were them, I wouldn't. So we're preparing to do this the right way and have the data be sort of the final, you know, piece that they need to make us offers. Everything else that we've done, all of that's in data rooms of our patent information. So they should be ready to make offers as soon as those data are made available.
spk10: Okay, thank you. And just one fast last one. Is your latest CROTA... developing multi-pathogen prophylactic products or, you know, single-pathogen prophylactic products?
spk04: Dale, could you handle that one?
spk06: Yes. So the current CRADA covers a single product initially that is a proof of concept for the approach that will then lead to additional testings against other pathogens.
spk10: But you can make a product where, I mean, you intend to make a product where they can take one hit, be protected against many things, and, you know, get back to shooting.
spk06: That is ultimately the goal. But, yes, it is establish the first one, and then we can make the multivalent after that.
spk10: Okay. Thank you, guys. That's all. Thanks, Jonathan.
spk01: Our next question comes from the line of Mayank Mantani with B Riley Securities. You may proceed with your question.
spk08: Hi, team. This is actually William on for today. Really appreciate the update and all the progress that you've been making. Two questions here from us. First being, do you think you could provide a bit more detail on how investors should think about the path to monetization for each of the crowders entered with the exam read? And then it would also be good to understand the significance of the government's subcontractor designation and some of the barriers to entry, which confer a competitive advantage to TFFB.
spk04: Yeah, so we look – first of all, thank you for the questions, and thanks for standing in for my regards to him. So the creatives give us a great opportunity to develop products that ultimately have an inherent – customer in the government. And as those creators work, then beyond any sales to that customer, we would be able to look at other commercial opportunities through that work. It also gives us the non-dilutive opportunities to further expand the utilization of the technology in these very, very important biologic areas. On the DARPA program, We are subcontracted through Leidos and all commercial terms and sales of anything that comes out of that work with DARPA on countermeasures also will have a monetization effect and a revenue generation effect for TFF. So a lot of the devils in the details and what the data are and how quickly we can get these things through the development cycle But we do see that as sort of, you know, you've got the government as a customer. And then, of course, anything beyond the government sector, TFF would benefit from sales there as well.
spk08: Excellent. Makes sense. And then, additionally, is there any extra color you could provide on how you plan to create value from the external programs, including the universal influenza vaccine with the PTA? technology and the plus product relationship following the restructuring?
spk04: Sure. So passive to head for us with UGA is first of all to finish up the data. Ideally, TFF would like to secure the exclusive rights to the tech transfer of that technology from UGA. And just like we've done, for example, in the case with Augmented Bioworks where we've invested in the asset through a phase one trial. We would either do that alone or seek non-dilutive financing. And at that point, once we've demonstrated safety through phase one, find a partner to take that forward. That's one of the reasons why we've brought Greg Davenport on board to really work with the grant side of things. work all the different departments of government, including, you know, beyond DARPA, but looking at BARDA and IAD, et cetera. And we've been pretty active in making them aware of all the work that we're doing there. So once we have the animal data, then we'll make the effort to secure the tech transfer and move that asset along. Since you asked about cannabinoids, we're really feeling... very good about where we stand right now. We learned a lot, and PLUS has been a terrific partner in helping us refine our formulations and do commercial testing. What we did discover, and I think as you're aware, we're positioning the TFF cannabinoids as a substitute for vaping, a healthy substitute for vaping. Basically, this is direct inhalation of the TFF formulations either through our capsule or or direct inhalation through some other devices that we've worked up with our friends at Ed Plus. And what we did discover that when you inhale THC directly to the lung, albeit you get a very nice experience, you also, THC seems to be an irritant. You get a little bit of cough, feel a little bit of tingle in your chest. And our resident formulation, expert John Colling has really refined those formulations. I don't feel at liberty to share you what we've done to modify the formulation successfully. Those have met with really extremely positive commercial response. And now as we look forward, you know, we're doing some more testing. Plus is hopefully in the process of finishing up their restructuring. and moving the product into a commercial launch. We do have some backups there. We've certainly been talking to other companies about our technology, but we feel that Plus has been a loyal partner. They've been along with us the whole way. They've helped us really get to the point where I think we're ready to enter the marketplace in a very, very meaningful way. The other thing we've learned is that it's a tough market. It's highly competitive. a lot of price pressure. But, again, that's why we've taken the time to really refine these formulations to the point where we've gotten the feedback from the marketplace that these can be and will be a very desirable product. So, look, it's taken a little longer than we thought. We learned some things formulaically that we've been able to address. We've been through multiple, multiple iterations, a lot of work, a lot of creativity. And now I think we're at a pretty important inflection point. We'll see where PLUS lands in the next, hopefully, few days or weeks.
spk08: Understood. Appreciate the color, and I appreciate you answering our questions. And really, congratulations again on all of the great work. Thanks.
spk04: Bye. Thanks. Thanks for those kind words. Appreciate it.
spk01: Our next question comes from the line of Daniel Carlson with TW Research Group. You may proceed with your question.
spk05: Yeah, thanks, Glenn. Lots of interesting tidbits from your call. Just a couple quick questions. I see you added Estella, as you said, to the slide deck. I know you can't comment much about that, but maybe you can comment about what the criteria is for adding any of these major pharma partners to your slide deck.
spk04: Yeah, so thanks, Daniel, and I hope you're doing well. So the first thing that I guess I should share is very, very few of the partners we have been working with or work with really want to give us an opportunity to share that we're working with them. And, you know, in many cases, I think as Chris articulated well, you know, if you know that a company is working with TFF on dry powder formulations, it's not hard. to figure out what we're working on, right? And a lot of these situations, you know, it becomes a concern over, you know, competitive advantage. Now, you know, these companies understand that we're not working with them exclusively in these spaces, but they're really hesitant to go ahead and, you know, share with us. Now, a lot of these companies we've been working with for a long time, and the work has matured quite nicely. to the point where I think they feel and we feel it's a good time and it makes sense for us to share the name of the company. Clearly, it's very selective. We only want to share those companies that we think will be meaningful to our investor audience. I think hopefully, maybe Wednesdays and Tuesdays, you'll see more and more of these show up. on our list. And at the same time, those companies that are on the list, you know, we'll close transactions with them. So, yeah, I take it as a good sign, you know, certainly if things weren't going well, you know, they would not want us to share their name, but don't take it as if it's not going well when companies don't want us to disclose. So it's, you know, we're happy to when we can, when we think it's going to, you know, be meaningful to an investor to see that we're making progress.
spk05: Gotcha. Thanks. I found it very interesting that you're doing compassionate use and VORI, especially in a different indication. So kind of a multi-part question here, just how broad are the indications here for compassionate use? Where's that interest coming from and how does this impact the overall program?
spk04: Dale, do you want to answer that, please?
spk06: Yes. Thanks, Daniel. Very good question. So the interest is coming for this particular patient that we started. So I'll talk about the current patient, and then I'll talk about the overall plans. The current patient is someone who already has a history of fungal infections that were treated with antifungals. And the patient, when they were given oral or IV, the doses that would be used systemically, the patient had very severe tolerability issues. And there were other contraindications that made it so that the patient could not take boriconazole orally because it is the best drug to treat the fungus that's growing in his lungs. the physician felt like this inhaled route and delivery of the drug right to the site of infection would be best or the best way to approach it and have the lower systemic levels. That has translated to, again, this is a lung transplant patient where the subject is on tacrolimus and other immunosuppressive drugs. So drug-drug interactions are a problem, and in fact, this patient has had minimal drug-drug interactions that require dose adjustments of tacrolimus. So it really does support our hypothesis that we can potentially, you know, we'll get some, you know, single-case data for efficacy out of this, but it does support that we deliver lower systemic concentrations that require fewer dose adjustments for drug interactions with the others. Going forward for other patients that we might take into the trial, again, we would be predominantly looking for subjects who fit this general criteria you know, thread where they would not be somebody who, you know, they're not occurring in a location that, you know, in a country where we're operating sites for our clinical phase two clinical trial, uh, they would not be people who, you know, who, or have drug, drug interactions that would complicate their treatment otherwise. And who in a, you know, um, especially lung transplant, heart transplant, kidney transplant, that type of patient that ends up with these infections. That's kind of who we're thinking about for this type of study. But it is really a one-off, you know, case-by-case basis, looking at the data for the individual patients and making sure that this is the right drug to treat their infections.
spk05: Thanks, Dale. It seems like great validation for the program, so congrats on that. And then, Glenn, one last question. You mentioned in the omnibus package a specific language within film freezing, which makes it almost seem like it's tailored for you guys. Can you just provide any more comment about that whole situation?
spk04: Yeah. So, Daniel, there's a lot of things that we do here that we're not public about. In fact, if we were public about everything that we do, these calls would take two hours, not one hour. In fact, we apologize for the length. But we have been working on a lot of different levels when basically this whole issue of cold chain stores started to gain attention to our technology. And one of those arenas, you know, we kind of viewed it at the time, I think Kirk's term is a lottery ticket, right? But, you know, we brought some people in that didn't know how to do this kind of work and clearly the technology offers a lot of value to everybody in the government, everybody in the commercial world and clinical development world. So to make a long story short, we were able to present the technology to people that are in a position to move things like this forward in government appropriations. And as a result of that work, and the perceived benefit of the technology, we were able to have this language added to the omnibus legislation, which just so happens specifically uses the language of thin film freezing powers. They misspelled powders, but it's powders. And, you know, we're really excited about that. And, you know, so it's basically no guarantee of funding. This is a, in the 22 fiscal year budget for HHS to pursue, and they have noticed to be able to fund activities here. And now it's our job to go after those, right? And we have lots of really interesting ideas about how they can help us. So, you know, it's an amazing technology. You know, the company's really had a terrific year, you know, We have a lot of news. We'll have a lot of news coming up, partnerships to come, and this is just another way that we could create value for patients and our shareholders.
spk05: Gotcha. Well, you do have a lot of balls in the air, Glenn, so congrats on all the accomplishments so far.
spk04: Keep up the good work, and I'll jump back. Okay. Thanks. Do we have, Operator, anybody else in the queue?
spk01: We do not. I'd like to turn it back over to you for closing remarks.
spk04: Okay. Well, thanks to all the questioners, all the listeners. As you know, I'm always available to add some color to what we've been able to describe to you this afternoon. I want to thank my team. They are really remarkable in what they do, and we're really looking forward to where this is all headed in the coming days, weeks, and months, and we look forward to our next earnings period and earnings call. I wish you all well. Stay healthy and happy, and we'll talk to you soon. Appreciate it. Bye.
spk01: This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation, and enjoy the rest of your day.
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