PDS Biotechnology Corporation (PDSB) Earnings Call Transcript & Summary

Greetings, and welcome to the PDS Biotechnology Fourth Quarter and Fiscal Year 2020 Earnings Call and Webcast. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Deanne Randolph, Investor Relations for PDS Biotechnology. Please go ahead, Deanne.

Good morning, and welcome to PDS Biotechnology's Fourth Quarter and Full Year 2020 Earnings Conference Call and Audio Webcast. With me today are Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Lauren V. Wood, Chief Medical Officer; and Seth Van Voorhees, Chief Financial Officer. Earlier this morning, PDS Biotech issued a press release announcing financial results for the 3 and 12 months ended December 31, 2020. We encourage everyone to read the press release as well as PDS Biotech's annual report on Form 10-K, which will be filed with the SEC later today. The company's press release is available on PDS Biotech's website at pdsbiotech.com, and the annual report will be posted later today. In addition, this conference call is being webcast through the company's website and will be archived there for future reference. Before we begin, I would like to caution listeners that comments made by management during this conference call will include forward-looking statements within the meaning of federal securities laws, including the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve material risks and uncertainties, and the company's actual results may differ materially. For a discussion of these risk factors, including, among others, the risks related to COVID-19; the impact such pandemic may have on the company's business operations, financial operations and results of operations; and the company's ability to respond to the related challenges, including those noted in this morning's press release, please refer to PDS Biotech's SEC filings. Investors, potential investors and other listeners are urged to consider these factors carefully in evaluating the forward-looking statements and are cautioned not to place undue reliance on such forward-looking statements. Following today's prepared remarks -- oh, in addition, the content of this conference call contains time-sensitive information that is accurate only as of the date of the live broadcast, March 18, 2021. Except as required by law, the company undertakes no obligation to revise or update any statement to reflect events or circumstances that take place after the date of this call. Following today's prepared remarks, we will open the discussion for a question-and-answer session. With that, I would now like to turn the call over to Dr. Frank Bedu-Addo. Frank?

Thank you, Deanne, and thank you all for joining us this morning. During the year 2020, the PDS Biotech management team advanced numerous key initiatives supporting continued development of our Versamune platform-based products. The Versamune platform was designed to activate multiple immunological processes that are necessary to promote in vivo generation of antigen-specific CD8 killer T-cells. During the year, we continued to progress our oncology and infectious disease programs despite the challenges posed by the COVID-19 pandemic. In the second quarter of 2020, we initiated the first of 3 Phase II clinical trials of our flagship oncology candidate, PDS0101, which is being developed to treat advanced HPV-associated cancers such as anal, cervical, head and neck, penile, vaginal and vulvar cancers. The additional 2 clinical trials of PDS0101 were initiated during the fourth quarter. We also successfully added $30 million of cash to our balance sheet during the year, providing the company with sufficient capital resources to achieve key value-enhancing milestones in 2021 through 2022. Since we last spoke to you on our third quarter call, significant advancements have been made in both our oncology and infectious disease pipelines. In our oncology pipeline, first, the National Cancer Institute-led Phase II trial evaluating a triple combination of PDS0101 with 2 of EMD Serono's clinical stage immunotherapies in advanced HPV-associated cancers achieved its preliminary efficacy benchmark. This benchmark required that 3 or more of the first 8 patients achieve an objective response to treatment. And this, therefore, triggers full enrollment in that study. Secondly, the M.D. Anderson-led Phase II trial evaluating a combination of PDS0101 with chemoradiotherapy in locally advanced cervical cancer is actively enrolling patients. And third, the PDS-initiated VERSATILE-002 study of PDS0101 in combination with Merck's blockbuster immunotherapy, KEYTRUDA, for patients with recurrent or metastatic HPV-associated head and neck cancer is also active and open to enrollment. With our COVID-19 program, PDS0203, significant progress was also made. In conjunction with our Brazilian partner Farmacore, during the fourth quarter, we expanded the consortium for development of a Versamune-based COVID-19 vaccine with the addition of Blanver, a leading Brazilian pharmaceutical company focused on the development, manufacture and commercialization of innovative pharmaceutical products. In addition to this, we recently announced the commitment of funding of up to approximately USD 60 million by the MCTI, which is the Brazilian Ministry of Science, Technology and Innovation, to fund clinical development and commercialization of our Versamune-based COVID-19 vaccine in Brazil with our Brazilian consortium partners, Farmacore and Blanver. In addition to these achievements, on January 1, our new Chief Financial Officer, Seth Van Voorhees, officially joined us here at PDS Biotech. Seth is an accomplished CFO with a broad background, including experience in corporate finance, capital markets, investment banking and licensing. He's rapidly become an integral part of the team and will introduce himself more fully later on this call. Now I'll provide some more depth on our oncology pipeline. As I mentioned, there are currently 3 ongoing Phase II clinical trials of PDS0101, which are all being conducted in partnership with world-renowned leaders in oncology, including the National Cancer Institute, or NCI, Merck and the M.D. Anderson Cancer Center. The NCI and M.D. Anderson trials are investigator-initiated trials, meaning they are being run by those institutions. As a reminder, PDS Biotech retains 100% ownership of PDS0101 and all other Versamune-based products. Our strategy is to combine PDS0101 with state-of-the-art treatments like checkpoint inhibitors and clinical-stage immunotherapies as well as with standard of care in order to maximize our potential to deliver improved outcomes to a broader population of HPV-associated cancer patients. I'll start with the NCI-led trial. The furthest progress of our PDS0101 clinical trials is the NCI-led Phase II trial evaluating a novel triple combination of PDS0101 with 2 clinical-stage immunotherapies from EMD Serono: bintrafusp alfa, which is also called M7824, this is the first-in-class bifunctional checkpoint inhibitor; and NHS-IL12, an antibody conjugated cytokine designed to facilitate entry of the cytokine, IL-12, into tumors to enhance local T-cell responses. This novel combination is being studied in patients with several types of advanced HPV-associated cancers. Any patient with an advanced HPV-associated cancer, including anal, cervical, head and neck, penile, vaginal and vulvar cancers whose cancer has returned or spread after treatment, is eligible to enroll in this trial. On February 3, we announced that this trial had achieved its preliminary efficacy benchmark of 3 or more objective responses in the first 8 patients, meaning that a minimum objective response rate of about 40% was required to perform the full trial. This result was achieved ahead of the full enrollment of the initial 8 patients, and the trial has, therefore, been opened up to recruitment of 45 patients. Now the highest objective response rate in this specific population of patients who have failed prior treatment but not yet been treated with a checkpoint inhibitor, meaning that they were checkpoint inhibitor naive, is about 30%. This result was achieved with M7824 monotherapy, and the study was published in October 2020 in the Journal for ImmunoTherapy of Cancer. The 40% threshold was selected as it is a 30% improvement over the highest objective response rates to date in this specific patient population. The trial has now been opened up to full enrollment and is studying the effect of the triple combination in 2 distinct populations of advanced HPV-positive cancer patients. In the first group, the objective response rate is being evaluated in checkpoint inhibitor-naive patients. In the second group, the objective response rate is being evaluated in patients who have failed checkpoint inhibitor therapy. These are the checkpoint inhibitor refractory patients. We expect to present more interim data on this program next quarter. Excellent preclinical synergy between the 3 immunotherapeutic agents was reported by the National Cancer Institute in the Journal for ImmunoTherapy of Cancer in June of 2020. We believe that if the trial is successful, and safety and efficacy is demonstrated, that this novel combination involving other PDS pipeline products could be applied to a broad range of advanced cancers. Moving on now to the PDS Biotech-initiated VERSATILE-002 trial. VERSATILE-002 is a multicenter, open-label, single-arm, nonrandomized trial of approximately 100 patients, evaluating the combination of our Versamune-based PDS0101 with the anti-PD1 checkpoint inhibitor pembrolizumab also known as KEYTRUDA. This combination is being evaluated for first-line treatment of recurrent or metastatic head and neck cancer. Our partner, Merck, is providing the drug and also sits on the joint steering committee for the trial, while PDS Biotech has responsibility for the day-to-day management and financing of the study. We believe that the combination of PDS0101 and standard-of-care KEYTRUDA has the potential to provide significantly improved clinical benefit to recurrent or metastatic head and neck cancer patients compared to treatment with KEYTRUDA alone in the first-line treatment setting for recurrent disease. This means that patients whose cancer has returned or spread following initial treatment will be able to take this chemotherapy-sparing combination using 2 immuno-oncology agents, an approach that may be very appealing to patients. Published preclinical studies suggest that Versamune-based immunotherapies, including PDS0101 and KEYTRUDA, may work synergistically to enhance antitumor responses. The in vivo tumor-attacking killer T-cell responses induced by PDS0101, combined with the ability of KEYTRUDA to better expose the tumors to T-cell attack, may improve the overall response rate achieved with KEYTRUDA alone in these advanced cancer patients. Patients are actively being screened and enrolled at multiple sites in the United States. And we anticipate that interim data will potentially be available late in the fourth quarter of 2021 or during the first half of 2022. Similarly to the triple combination trial, a successful trial of KEYTRUDA with PDS0101 that confirms the published preclinical data could justify the evaluation of several of our pipeline products with checkpoint inhibitors. And moving on to the third trial, the IMMUNOCERV trial. The M.D. Anderson-initiated IMMUNOCERV trial is a Phase II trial of PDS0101 in combination with standard-of-care chemoradiotherapy, or CRT, for the treatment of locally advanced cervical cancer. The study will investigate the safety and preliminary efficacy outcomes of this combination. We announced the initiation of the study in October. The study is also actively recruiting and enrolling patients. And we anticipate that preliminary data will be available during the fourth quarter of 2021 or during the first quarter of 2022. Dr. Lauren Wood, our Chief Medical Officer, will provide additional details about our ongoing clinical trials shortly. Now our clinical development strategy of combining PDS0101 with standard-of-care treatment is designed to mitigate risk in our proof-of-concept Phase II trials while also demonstrating the potential for enhanced clinical benefit to patients over the standard of care without compounding toxicity. If we achieve these goals, we believe that we will have a clear path towards commercialization of PDS0101. After initial commercial approval, our strategy of combining PDS0101 with standard of care also positions us for rapid market penetration and expansion. As some of you already may know, the HPV cancer market is large and is expected to remain robust for the next several decades despite the use of preventive HPV vaccine first introduced in 2006. There are currently about 43,000 new incidences of these cancers every year in the United States alone. HPV-associated head and neck cancer has been described as a silent epidemic due to the rapidly increasing incidence of this cancer, and anal cancer incidence has also been steadily increasing. Also, as you might have noticed, our evaluation of PDS0101 in combination with multiple types of cancer treatment is intended to better understand the synergies between Versamune, a potent in vivo T-cell activating technology, and various leading cancer treatments. If this is successful, it presents an opportunity to rapidly and strategically expand and develop our oncology pipeline. Now I'll move on to our pipeline product, PDS0103. In April of 2020, we announced the expansion of our Cooperative Research and Development Agreement, or CRADA, with the National Cancer Institute to include studies of PDS0103, which combines Versamune with novel peptides derived from the cancer-associated protein known as MUC1. These novel, proprietary and highly immunogenic peptides were developed by the Lab of Tumor Immunology and Biology at the National Cancer Institute. MUC1 is expressed in a wide range of solid tumor types, including ovarian, breast, colorectal and lung cancers. Expression of MUC1 is often associated with poor disease prognosis due in part to drug resistance. In preclinical studies conducted at PDS Biotech, PDS0103 demonstrated the ability to generate powerful in vivo MUC1-specific CD8 killer T-cells. Our hypothesis is that in humans, due to Versamune's ability to effectively promote important immunological processes and to activate type I interferons, that we will see a similar result, allowing the immune system to better recognize such cancers and to treat MUC1-expressing tumors. As part of our collaboration with the National Cancer Institute, the Institute is performing preclinical combination studies of PDS0103 with other immunotherapeutic agents ahead of the planned human clinical study. We expect that the results of their preclinical work will be available by the fourth quarter of this year. Moving on now to our infectious disease pipeline. Last week, we announced the commitment of funding by the MCTI, the Brazilian Ministry of Science, Technology and Innovation, of up to approximately USD 60 million to our Brazilian consortium, including partners Farmacore and Blanver. These funds are to support the full clinical development of our Versamune-based second-generation COVID-19 vaccine, along with the development of the commercial scale manufacturing process. This award was made contingent upon receiving the go-ahead from the Brazilian drug regulatory agency, Anvisa, to progress the vaccine into human clinical trials. In our third quarter earnings call in November, we announced that Farmacore had an initial meeting with Anvisa to discuss the preclinical and clinical development plans. A pre-IMPD package was submitted to Anvisa in February of 2021, and Farmacore and Anvisa met on March 5 and agreed on the path forward for official submission of the final data package and the combined Phase I/II human clinical trial protocol. Over the past several weeks, the consortium has made significant progress toward advancing this novel Versamune-based vaccine into the clinic. Blanver Farmoquímica, a leading Brazilian pharmaceutical and manufacturing company, joined the consortium to commercialize PDS0203 in Latin America. Blanver will manufacture, promote, distribute and commercialize PDS0203 across Latin America. In late February, Farmacore submitted a data package to the Brazilian regulatory agency, outlining the clinical trial protocol and the proposed clinical manufacturing process. Farmacore received positive feedback from Anvisa on March 5, where they agreed on the path to clinical development. The consortium will continue to address information requests from Anvisa as those discussions continue in the pursuit of a full innovative medicinal product dossier on IMPD, which is required to proceed into human clinical trials. Based on the initial discussions with Anvisa, Farmacore has begun working with a top clinical research organization to prepare to initiate clinical trials in Brazil during the second or third quarter. All funding, as expected, is contingent on the availability of financial resources within the MCTI. And the Secretary for Research and Scientific Training of the MCTI has committed to making every effort to finance all clinical and development stages of the program. As we have discussed in the past, the Versamune technology is engineered and designed to overcome what we believe is a critical limitation of cancer immunotherapy and vaccine technology, which is the in vivo induction and promotion of high levels of powerful CD8 T-cells, including long-lasting memory T-cells. This characteristic of Versamune was successfully demonstrated in a Phase I human clinical trial. Based on emerging scientific COVID-19 data, it is becoming more and more evident that T-cell responses and CD8 T-cells, in particular, play an important role in conferring immunity and protection against infection. It is also reported that T-cell induction may correlate with longer-term protection. We have already reported on the positive CD8 and CD4 T-cell responses generated with PDS0203 in preclinical studies. We also recently reported on a publication in the December 2020 issue of the leading peer review journal vaccines by a team at the Mount Sinai Icahn School of Medicine, which demonstrated superior preclinical induction of neutralizing antibodies when their SARS-CoV-2 antigen was administered in a Versamune-based vaccine. The preclinical study also demonstrated effective protection against challenge with the virus after vaccination. As I have said on numerous occasions, our goal with the COVID-19 vaccine program was not to race to be one of the first vaccines to be commercialized but rather to design and develop a vaccine that possesses the critical characteristics necessary to be a globally successful COVID-19 vaccine. We believe this means that the vaccine must induce neutralizing antibody responses against the virus. And the vaccine must have the potential to induce a greater breadth of immune responses, including killer T-cells and helper T-cells, which specifically recognize conserved and nonmutating regions of the virus. Such a vaccine may provide improved protection against multiple variants of SARS-CoV-2. This ability to recognize and to target regions of the virus that are less likely to mutate is quite important, especially considering our current knowledge regarding the virus' propensity for mutation. We also believe that virus-specific memory T-cells are important for robust, long-term protection against infection. For commercial success, the vaccine should also be safe, simple, capable of production at commercial scale and should demonstrate long-term stability, thereby eliminating the need for ultra-cold chain storage. PDS0203 is being developed with a goal of exhibiting each of these qualities. We believe that if PDS0203 is confirmed in the upcoming clinical studies to effectively induce not only antibodies, but also to promote effective induction of potent virus-recognizing killer T-cells in vivo, that this could be an important development in our understanding of Versamune's potential role in combating viral diseases. Not only would this relate to develop -- development of an effective COVID-19 vaccine, but it may also be important in the development of a more effective and broadly acting Versamune-based flu vaccine that may provide protection against multiple strains of influenza viruses, including pandemic strains. We anticipate that the planned combined Phase I/II trial will begin in Brazil in the second or third quarter. There are 2 main reasons why Brazil presents a suitable location for clinical studies. First, to date, Brazil has relatively low vaccination rates, which therefore provides a suitable, steady population. Secondly, we know that there are several COVID variants circulating in Brazil, which will give us an opportunity to test PDS0203's effectiveness against multiple strains. We expect that the full clinical development process will last about 1.5 to 2 years and that the vaccine may be commercially available in 2023. Now although several vaccines are now available in the United States, Latin America is still significantly underserved. We believe that should clinical development be successful, PDS0203 could be competitive with a near-term multibillion-dollar market opportunity in Latin America. I'll move on now to PDS0202, which combines Versamune with novel influenza vaccine antigens in a developmental universal flu vaccine. We announced last year that PDS Biotech's collaborator, Professor Jerold Woodward, of the University of Kentucky School of Medicine was awarded a grant from the NIAID to support preclinical development of this program. Dr. Woodward initiated those studies earlier this year in partnership with the Collaborative Influenza Vaccine Innovation Centers network of the NIH to develop a more durable, broadly protective and longer-lasting vaccine effective against multiple strains of influenza, specifically including pandemic strains. We anticipate results from those studies will be available by the end of the calendar year. Now I'd like to pass the call to Dr. Lauren Wood, who will provide more comprehensive clinical updates, and review the details of the clinical plan for PDS0203. Lauren?

Thank you, Frank. And once again, thanks to all of you for joining us this morning. As Frank just detailed, we have made significant progress in both our infectious disease and oncology pipelines since our third quarter call. I'll begin with our ongoing oncology clinical trials. The investigator-initiated study of PDS0101 in combination with bintrafusp alfa, also known as M7824, a first-in-class bifunctional checkpoint inhibitor and NHS-IL12, an antibody conjugated cytokine designed to facilitate entry of the cytokine IL-12 into the tumor to enhance the local T-cell response was initiated in June with encouraging and faster-than-projected initial accrual to date. This NCI-led study was the result of independent preclinical animal studies performed at the National Cancer Institute, which showed strong synergy between the 3 agents. The triple combination resulted in enhanced anti-tumor activity when compared to treatment with the individual agents or with dual combination. The details and findings of these preclinical studies were published in the June 17 issue of the Journal for ImmunoTherapy of Cancer, also known as JITC. This investigator-led study recently achieved its initial safety benchmark, meaning that fewer than 2 dose-limiting toxicities were observed in the first 6 patients who received the triple combination. Furthermore, as Frank mentioned, the trial recently met its initial efficacy benchmark: the observation of objective response in 3 or more of the initial 8 patients that had been enrolled. And the trial will now progress to full enrollment. We anticipate that additional data from this trial will be available during the second or third quarter of this year. Now on to the PDS-sponsored VERSATILE-002 study. As Frank discussed during his remarks, activation of sites and enrollment in VERSATILE-002 continues to progress. As a reminder, the primary endpoint of VERSATILE-002 is the objective response rate, or ORR, at 9 months following initiation of treatment. There will be a leading cohort of 12 patients to assess the safety of the combination and a formal planned interim analysis evaluating response to treatment in the first 38 patients. We estimate that interim data of the initial 12 subjects for safety to be available sometime between the fourth quarter of 2021 or the first half of 2022. The study's lead principal investigator, Dr. Jared Weiss, who serves as the section chief of Thoracic and Head and Neck Oncology at the University of North Carolina School of Medicine Lineberger Comprehensive Cancer Care Center, and we are thrilled to have Dr. Weiss involved in this study. Moving now to the M.D. Anderson-led Phase II clinical trial of PDS0101 in combination with standard-of-care chemoradiotherapy for treatment of locally advanced cervical cancer. This study is also known as IMMUNOCERV. This study will enroll approximately 35 patients and investigate the combination of safety and preliminary oncologic outcomes as well as explore immune timing by PDS0101 and other biomarkers of immune response, importantly, in both blood and tumor tissue. We believe that PDS0101's demonstrated ability to activate the immune system and induce tumor-targeting killer T-cells may provide improved outcomes to patients with cervical cancer. The earliest possible readout of clinical data from this study is also the second half of 2021. This study is being conducted by Dr. Ann Klopp, M.D., Ph.D., an Associate Professor of Radiation Oncology at the M.D. Anderson Cancer Center. Moving now to the planned clinical trial of our COVID-19 vaccine. In agreement with Anvisa, the randomized placebo-controlled Phase I/II study of PDS0203 will evaluate safety, immunogenicity and preliminary efficacy of PDS0203 in approximately 360 healthy adults. Patients in the study will receive 2 doses of PDS0203 administered 3 weeks apart. Study participants will be divided based on age, with an 18 to 55 age group and a greater than 56 years of age group. A low-dose and high-dose vaccine or placebo will be tested in each of these age groups. Initial evaluations of efficacy will be conducted starting 14 days following receipt of the second dose of vaccine. Specifically, we are seeking to characterize safety, reactogenicity and validate the induction of SARS-CoV-2-specific antibodies as well as CD4 helper T-cells and CD 8 killer T-cells against SARS-CoV-2. Our co-development partner, Farmacore, will be meeting on a regular basis with regulatory officials from Anvisa to review ongoing data from this Phase I/II trial in an effort to react as quickly as possible to results. If the Phase I/II study successfully establishes both safety and efficacy, we are prepared to quickly move into a Phase III trial to confirm PDS0203's effectiveness in preventing COVID-19 infection. One of the planned analyses in the Phase III design is the assessment of efficacy against variants of the virus. As Frank mentioned, the robust T-cell induction by Versamune may provide protection not only against wild-type virus, but also potentially against currently circulating variants of concern of the virus since PDS0203 is being designed to induce an immune response against conserved regions present in SARS-CoV-2. Conserved regions of the virus are those that remain stable despite ongoing viral mutation. I would now like to turn the call over to our CFO, Seth Van Voorhees, to review our full year 2020 financials. Seth?

Thank you, Lauren, and good morning, everyone. As this is my first conference call as CFO, I'd like to take a moment to discuss my view of the company and why I decided to join PDS earlier this year. When I was interviewing with the -- for the CFO position, I saw a company that was developing an exciting platform capable of inducing killer CD8 T-cells in the right quantity, in the right quality, in the right location, and doing all these incredible things with a strong safety profile, providing with an opportunity to develop a broad range of therapies for cancer and infectious diseases. I was impressed by the validating partnership it established with market-leading institutions such as the National Cancer Institute and the M.D. Anderson Cancer Center. These organizations felt so highly of Versamune's potential that they initiated 2 of the 3 Phase II combination studies currently underway. Thus, based on these validating partnerships, the company's 3 Phase II trials, its deep product pipeline in preclinical development, combined with an exciting pipeline in infectious disease candidates, my decision to join PDS was an easy one. I'm excited to be part of the PDS team as we seek to develop this potential to create value for you, our shareholders, and to improve therapeutic care for all. Finally, as we move forward together, please feel free to contact me if I can be of assistance now or in the future. Now I'd like to turn our discussion to a review of our financial results for the 12-month period ending December 31, 2020. In addition, I would also like to touch on the financial implications of our recently announced commitment from the Brazilian government to fully fund the clinical program for PDS0203. For fiscal year 2020, our loss from operations was approximately $14.9 million versus a loss of approximately $21 million during the same period in 2019. When factoring in other income and expenses primarily related to the merger in 2019, our net loss was approximately $14.9 million in fiscal 2020 or a net loss of $0.89 per basic and diluted share compared to a net loss of negative $7 million or $1.44 per basic and diluted share for fiscal 2019. Research and development expenses totaled approximately $7.9 million in fiscal 2020 as compared to $6.1 million for fiscal 2019, an increase of approximately $1.8 million or 30%. Most of this increase was a result of higher levels of Versamune-related developmental expenditures. For fiscal 2020, general and administrative expenses were approximately $7 million compared to approximately $11 million for fiscal 2019, a decrease of approximately $4 million or 37%. Most of this decrease related to higher levels of reverse merger expenditures in 2019 that did not reoccur in 2020. From a cash flow perspective, we started 2020 with approximately $12 million of cash and raised approximately $30 million from the issuance of equity in 2020. That was offset by approximately $13 million of cash that was used in our operations in 2020, leaving us with a cash balance at the end of the year of approximately $29 million. Now I'd like to discuss the implications of our announcement last week regarding funding by MCTI of up to BRL 330 million, which equates to approximately USD 60 million for the development of a Versamune-based COVID vaccine. The announcement both validates our confidence in the Versamune platform and provides the funding to support PDS0203 into a fully commercialized product. Upon approval by the Brazilian drug regulatory agency, Anvisa, funding will be released to support an initial combined Phase I/II trial, and assuming that trial is successful, the release of full financial support for a registration-enabling Phase III trial. The government funding will also support the scale-up of manufacturing of the PDS0203 product. A portion of the committed funding will be paid to PDS for the support activities it will provide to this program, which will have a positive impact on our cash burn rate. If successful, the Brazilian market represents a potential multibillion-dollar revenue opportunity based on its population of 213 million people and reported COVID-19 vaccine pricing of approximately $20 to $74 for a 2-dose regimen. Outside of Brazil, our development partner, Farmacore, also has the rights to commercialize PDS0203 throughout Latin America, which increases this market potential by approximately 3x based on the population. In summary, this announcement has 2 important financial implications for PDS. First, it provides near-term financial support for our clinical and scale-up activities for PDS0203. And second, it represents a significant revenue potential starting in 2023 based on the commercialization of PDS0203 if the planned clinical trials are successful. Thank you for your time today. And I'd like to now turn the call back to Frank for final remarks.

Thank you, Seth and Lauren. Before we begin our question-and-answer session, I would like to thank all of our fantastic team members here at PDS Biotech and all of our clinical partners for their dedication. Were it not for their ability to navigate through the unprecedented challenges posed by the COVID-19 pandemic, we would not have 3 active PDS0101 Phase II clinical trials nor would we have achieved the financial support of the MCTI. We anticipate generating significant data from our ongoing clinical trials that will allow us to apply the Versamune technology to the next generation of cancer immunotherapies as well as novel vaccine that may induce a broader range of protection against infectious diseases. That concludes our prepared remarks. Operator, please begin our question-and-answer session.

[Operator Instructions] Our first question today is coming from Joe Pantginis from H.C. Wainwright.

My question really revolves around the NCI study. And I guess it sort of have a couple of parts there. So the first part of the question is maybe can you give a little more perspective around the patient population and their underlying demographics and why you can be encouraged, even more encouraged about the responses that you're seeing early on? And then second, I think this talks to the broader theme. As you see the immunotherapy landscape continue to expand, there's always going to be questions and ongoing questions about how do you tease out the individual contributions of each of the therapies within the regimen? Now obviously, the JITC journal article, I think, goes far in explaining that. But I think that's part of the main question. And then lastly that I hope would look to answer that -- the overall question is the type of work that NCI and you are doing with regard to translational data and looking at the actual impact of T-cell activation.

Thank you very much, Joe. Lauren, I'll hand over that question to you.

Okay. Good morning, Joe, and thank you for your question. So I'll try and address each of your questions systematically. Regarding the patient population, the individuals that are in the patient population are those that we would expect to have HPV-related recurrent metastatic disease. They include individuals with cervical cancer, anal cancer, vaginal/vulvar cancer as well as head and neck cancer. So that is the representative population that is targeted by this triple combination and that we are seeing as it relates to enrollment. The other aspect that you said was further clarification about the 2 populations in the study. The study was focused and targeted on delivering this triple combination therapy to checkpoint inhibitor-naive individuals based on the preclinical data that we noted that was published in the June 20 JITC article. However, we also know that since immunotherapy has become the fourth cornerstone of cancer treatment that there are now a lot of patients with checkpoint refractory disease. We know that only about 20% on average, 15% to 20% depending upon the agent of patients respond to checkpoint inhibitor therapy. And so there is an emerging and growing population of checkpoint refractory patients who have failed prior exposure to this class of drugs. Investigators at the NCI were interested in also exploring in a preliminary manner whether or not this triple combination would also have activity in the checkpoint refractory population. So those are the 2 cohorts for the NCI study. Your point is very well taken regarding when you deliver triple combinations or dual combinations of any agent, whether it's immuno-oncology agents, whether it's immuno-oncology in chemotherapy or radiotherapy, what is the specific contribution of each of the agents? We clearly know that from the preclinical studies, the triple combination was superior to any of the dual combinations, and all of the dual combinations were superior to any of the monotherapy combinations. How we would tease this out in additional subsequent potentially randomized Phase II studies might be to give the triple combination versus the best dual combination that was observed in the preclinical studies. Again, it would really depend on the clinical data that we observe with the triple combination in both the checkpoint inhibitor naive as well as refractory populations because you might want to be exploring differences in combination when you're trying to figure out and tease out what is the most important component in the regimen or the relative contributions. Your third question regarding the type of translational work and data that's being done, this is a critical question, and it's one of the reasons why we're really thrilled to be partnering with Drs. Schlom and Gulley and Dr. Strauss at the NCI and their group because it's critically important for us to be able to not only confirm whether or not we see this potent induction of HPV16-specific CD8 T-cells, but also whether or not we have evidence that these T-cells track into tumors. And so there is the plan for patients who may undergo subsequent surgical resection or biopsy to characterize those responses. There's going to be intensive interrogation of not only the T-cell repertoire, but also whether or not the HPV16-specific responses that are induced, their quantity as well as their potency as it relates to polyfunctional activity. Did I get everything for you?

No, you certainly did. I know I threw a lot in there in 1 seemingly run-on sentence.

Thank you, Joe. Thank you, Lauren. And Joe, just to add a little bit to what Lauren said. One of the reasons why we set that bar at 40% approximately is in this patient population, if PDS0101 is actually inducing these in vivo killer T-cells and the state of the art, the highest response rate was approximately 30%, we -- our projection was that if these T-cells are actually being induced even in these patients with somewhat weakened immune systems, we would expect to see at least a 30% increase over what M7824 have shown in the clinical trials. And so that was another reason why we wanted to see that bump up of about 30% to say, "Okay, this appears to be doing what we hope it would do. Therefore, let's go ahead and enroll the full trial."

[Operator Instructions] Our next question is coming from Trevor Allred from Oppenheimer.

I wanted to ask about the regulatory process for Brazil and how that might differ from the U.S., if at all? And then how might that potential Brazilian approval, how might that impact commercialization across Latin America? Will they require any further regulatory trials beyond Brazil? Or will emergency use enable broad use?

Lauren, we'll start with you.

Okay. Trevor, and thanks for that question. So as many people are aware, Anvisa is the regulatory authority for Brazil regarding pharmaceutical products, devices and other interventions and equivalent to the U.S. FDA. Their process is very similar to the FDA in that sponsors are able to submit pre-IMPD packages. In the United States that would be a pre-IND package where the sponsor is able to have preliminary discussions with the regulatory agencies regarding their platform, their product and the proposed study of that product in first-in-human clinical trials. After the submission out a full IMPD, as Frank mentioned during the call, which is equivalent to the U.S. IND, which we submit to the FDA, that is then reviewed. And the regulatory agency provides the go-ahead to initiate studies of PDS0203 in human subjects. Importantly, once a trial is initiated, there is very frequent communication between sponsors and the regulatory agencies regarding safety, reactogenicity as well as efficacy outcomes. And we know that these are significantly accelerated as it relates to all COVID-19 vaccine platforms. Same thing happens in Brazil with very prompt review, evaluation and communication that is ongoing. Now regarding the regulatory process for the rest of Latin America and whether or not an EUA-authorized vaccine that is manufactured in Brazil and approved by Anvisa, how rapidly it would be taken up by other regulatory agencies in Latin America is a question that really resides with each of the regulatory agencies of those countries. As everyone is aware, there are 3 vaccines that are approved for COVID-19 in the U.S. There are also vaccines approved in Europe as well as the U.K., but individual health authorities have also elected to review COVID-19 vaccine packages based on their individual countries' priorities. And the presumption is that's exactly what would happen as well in other countries in Latin America.

We have reached end of our question-and-answer session. I would like to turn the floor back over to management for any further or closing comments.

Well, thank you very much to all for your continued interest in PDS Biotechnology. We believe that 2021 will be an exciting year for the company. We have multiple ongoing clinical trials of PDS0101 in oncology, and also the anticipated initiation of clinical trials for our second-generation COVID-19 vaccine. These studies should deliver proof-of-concept data for our lead asset, PDS0101, and should also provide validation of our Versamune T-cell activating platform more broadly. We appreciate your ongoing support in this pursuit. For more information about the company and our ongoing clinical trials, please visit our website at pdsbiotech.com. Thank you very much once again.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.

Thank you very much.