Q1 2024 Inovio Pharmaceuticals Inc Earnings Call

Operator: Clinical and Regulatory Developments and Timing of Clinical Data Readouts, along with Capital Resources and Strategic Matters. All of these statements are based on the beliefs and expectations of management as of today. Actual events or results could differ materially. We refer you to the documents we file from time to time with the SEC, which, under the heading risk factors, identify important factors that could cause actual results to differ materially from those expressed by the company verbally, as well as statements made in this afternoon's press release.

<unk> developments and timing of clinical data readouts, along with capital resources and strategic matters.

All of these statements are based on the beliefs and expectations of management as of today.

Actual events or results could differ materially.

We refer you to the documents we file from time to time with the SEC, which under the heading risk factors identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release.

This call is being webcast live and a link can be found on our website IR dot <unk> dot com and a replay will be made available. Shortly after this call has concluded.

Operator: This call is being webcast live, and a link can be found on our website, ir.inovio.com, and a replay will be made available shortly after this call is concluded. I will now turn the call over to Inovio's President and CEO, Dr. Jackie Shea.

Navios: I will now turn the call over to Navios, President and CEO, Dr. Jackie Shay.

Jacqueline E. Shea: Good afternoon, and thank you to everyone for joining today's call. To begin with, I'd like to discuss our key objectives for 2024. Mike, Mark, and Peter will go into greater detail throughout this presentation, but I feel it's important to emphasize the recent progress we've made in the three main areas that are driving our business forward. Firstly, preparing for the potential approval and commercialization of our first product, INO3107, which is being developed for the treatment of recurrent respiratory papillomatosis. Secondly, advancing other promising candidates in our pipeline, particularly INO3112. And thirdly, strengthening our business as a whole.

Jacqueline E. Shea: Good afternoon, and thank you to everyone for joining today's call.

Jacqueline E. Shea: To begin with today I would like to discuss our key objectives for 2020 full Mike Mark <unk>, who will go into greater detail throughout this presentation, but I feel it's important to emphasize the recent progress we've made in the three main areas that are driving our business forward.

Jacqueline E. Shea: Lastly, preparing for the potential approval and commercialization of our first product <unk> at 31, 7%, which is being developed for the treatment of recurrent respiratory papillomatosis.

Jacqueline E. Shea: Secondly, advancing other promising candidates in our pipeline, particularly <unk> 31 12.

Jacqueline E. Shea: Thirdly, strengthening our business as a whole.

Jacqueline E. Shea: Over the last two years, our strategic focus on these areas has been instrumental in ensuring that we are using our time and resources efficiently to work toward a common goal, to deliver on the promise of DNA medicines to patients. Of utmost importance, we remain on track to file our BLA for 3107 in the second half of this year under the FDA's accelerated approval pathway, and we believe we have alignment with the FDA on our proposed confirmatory trial design based on recent feedback. Our team is energized by the opportunity to deliver the first potential FDA-approved therapy for this devastating disease. And we're now moving to initiate the trial as soon as possible.

Jacqueline E. Shea: Over the last two years, our strategic focus on these areas has been instrumental in ensuring that we are using our time and resources sufficiently to work toward a common goal to deliver on the promise of DNA medicines to patients.

Jacqueline E. Shea: I have utmost importance, we remain on track to file our BLA for 31, 7% in the second half of this year under the Fda's accelerated approval pathway.

Jacqueline E. Shea: And we believe we have alignment with the FDA on our proposed confirmatory trial design based on recent feedback.

Jacqueline E. Shea: Our team is energized by the opportunity to slip at the first potential FDA approved therapy for this devastating disease.

Jacqueline E. Shea: And we're now moving to initiate the trial as soon as possible.

Jacqueline E. Shea: As you'll hear from Mark, we have also been advancing our commercial plans for 3107, establishing key relationships, and putting the building blocks of a successful commercial launch strategy in place. In parallel, our clinical and R&D teams have continued to advance other promising candidates across the pipeline, focusing on later stage assets with high unmet medical need and strong commercial potential. We believe we have reached agreement with the FDA on the Phase 3 trial design for 3112 in combination with Lactorse-E for throat cancer.

Jacqueline E. Shea: As Youll hear from Mark we have also been advancing our commercial plans for $31 seven establishing key relationships and putting the building blocks of a successful commercial launch strategy into place.

Jacqueline E. Shea: In parallel our clinical and R&D teams have continued to advance other promising candidates across the pipeline.

Jacqueline E. Shea: Focusing on later stage assets with high unmet medical need and strong commercial potential.

Jacqueline E. Shea: We believe we have reached alignment with the FDA on the phase III trial design for Phase 112 in combination with <unk> for throat cancer and will focus next on discussing those plans with European regulators.

Jacqueline E. Shea: And we'll focus next on discussing those plans with European regulators. Following feedback from the FDA, we also expect to submit plans for a Phase 2-3 study with INO4201 as an Ebola vaccine booster this quarter. I look forward to a readout of the first clinical data from the Phase 1 trial evaluating the anti-SARS-CoV-2 demab candidates in the second half of this year. Finally, we've continued to strengthen our business, adding key personnel, managing our resources, and strategically strengthening our financial position to support our key objectives.

Jacqueline E. Shea: Following feedback from the FDA. We also expect to submit plans for a phase two three study with INO 40, 201, as an unparallel of vaccine booster in this quarter.

Jacqueline E. Shea: And look forward to the readout of the first clinical data from the phase one trial evaluating the anti <unk> candidates in the second half this year.

Finally, we've continued to strengthen our business, adding key personnel, managing our resources and strategically strengthening our financial position to support our key objectives.

Jacqueline E. Shea: Of particular note, we recently raised approximately $33 million through an offering of common stock and pre-funded warrants in April. We remain committed to financial discipline and operational excellence to achieve milestones, which I believe will continue to be critical to our future success. I'd now like to pass the call over to our CMO, Mike Sumner, who will provide some additional details on 3107 and our other clinical progress across the pipeline.

Jacqueline E. Shea: Of particular note, we recently raised approximately $33 million through an offering of common stock and pre funded warrants in April.

Jacqueline E. Shea: We remain committed to financial discipline and operational excellence to achieve milestones.

Jacqueline E. Shea: Which I believe will continue to be critical to our future success.

Jacqueline E. Shea: I'd now like to pass the call over to our CFO, Mike Sumner, who will provide some additional details from $31 seven and our other clinical progress across the pipeline.

Jacqueline E. Shea: Mike.

Michael Sumner: Thank you very much, Jackie. And greetings, everyone.

Michael Sumner: Thank you very much Jackie and greetings everyone.

Michael Sumner: As Jackie mentioned, we are all focused on advancing INO3107 and excited by the potential to help deliver on the promise of DNA medicine for RRP patients. I'm pleased to share that we remain on target to submit our BLA seeking accelerated approval for INO3107 in the second half of 2024. I'm also pleased to inform you that the FDA has advised us that they have no additional comments on our proposed confirmatory trial design. So we are working to initiate the trial as soon as possible.

Michael Sumner: As Jackie mentioned, we are all focused on advancing <unk> thousand 107, and excited by the potential to help deliver on the promise of DNA medicine for RP patients I am pleased to share that we remain on target to submit a BLA.

Michael Sumner: <unk> accelerated approval for 31% and seven in the second half of 2024.

Michael Sumner: I'm also pleased to inform you that the FDA has advised us that they had no additional comments on our proposed confirmatory trial design.

Michael Sumner: So we are working to initiate the trial as soon as possible.

Michael Sumner: The trial will be randomized and placebo-controlled, involving approximately 100 patients with a history of two or more surgeries in the prior year, with a treatment option for the placebo arm at trial end. The trial is strategically designed to focus on evaluating clinical benefit in reducing surgical interventions for the majority of RRP patients. We believe this approach targets a broader spectrum of RRP diseases while also supporting expansion into the global marketplace. This is based on feedback we have received from European regulators, indicating that they will require a randomized placebo-controlled study for licensure. But perhaps most importantly, we believe our approach reflects what we've heard time and again matters most.

Michael Sumner: The trial will be randomized and placebo controlled involving approximately 100 patients with a history of tool more surgeries in the prior year.

Michael Sumner: With a treatment option for the placebo arm at trial and.

The trial is strategically designed to focus on evaluating clinical benefit in reducing surgical interventions for the majority of RFP patients.

Michael Sumner: We believe this approach targets a broader spectrum of RFP disease, while also supporting expansion into the global marketplace.

Michael Sumner: This is based on feedback we have received from European regulators, indicating that they will require a randomized placebo controlled study for licensure.

Michael Sumner: But perhaps most importantly, we believe our approach reflects what we've heard time and again matters most.

Michael Sumner: Reducing the number of surgeries patients face. That translates into a reduced risk of permanent vocal cord damage and a significant improvement in quality of life. Our plans for this year also include the submission of new immunological data for 3107 to both peer-reviewed publications and key conferences. I look forward to sharing more details on this important work in the year ahead.

Michael Sumner: Using the number of surgeries patients face that translates into reduced risk of permanent vocal cord damage and a significant improvement in quality of life.

Michael Sumner: Our plans for this year also includes the submission of new immunological data for <unk> 107.

Michael Sumner: To both peer reviewed publications and key conferences.

Michael Sumner: I look forward to sharing more details on this important work in the year ahead.

Michael Sumner: But I can tell you that it supports what we believe to be one of the most important characteristics of 3107, that it reduces the need for surgery in patients by teaching their immune systems to mount an effective response to the underlying HPV infection. Specifically, the team found that treatment with 3107 induces strong immune responses in the airway tissues of patients who are clinically responding to treatment. The types of immune activity we are seeing in these patients are diverse and include activation of antiviral pathways and engagement of both innate and adaptive cells of the immune system.

Michael Sumner: But I can tell you that it supports what we believe to be one of the most important characteristics of $31 seven.

Michael Sumner: That it reduces the need for surgery and patients by teaching their immune systems to Mount an effective response to the underlying HPV infection.

Michael Sumner: Specifically the team has found that treatment with 30, 107, and juices strong immune responses in the airway tissues of patients who are clinically responding to treatment.

Michael Sumner: The types of immune activity. We are seeing in these patients are diverse and include activation of antiviral pathways and engagement of both innate and adaptive cells of the immune system.

Michael Sumner: So moving on to how we think 3107 and our focus on reduction in surgery could make an impact on patient outcomes, I think this quote from a recent paper co-authored by Dr. Simon Best, a laryngologist that specializes in treating RRP, and also an investigator on our completed trial, captures the burden that this disease puts on RRP patients and the real risks they face every time they go in for surgery. The paper emphasizes that while researchers saw cumulative risks for patients who had more than five surgeries, 44% of patients who had less than five surgeries had incurred permanent iatrogenic injury, that is, an injury caused by the surgery itself, not the underlying disease. More simply put, the cumulative risk for injury increases with every surgery. But ultimately, any one surgery could cause permanent damage.

Michael Sumner: So moving on to how we think 30 107, and our focus on reduction in surgery could make an impact on patient outcomes.

Speaker Change: I think this quote from a recent paper co authored by Dr. Simon Best allowing coal just that specializes in treating RFP and also an investigator on a complete the trial.

Speaker Change: Captures the burden that this disease puts on our RP patients and the real risk. They face every time they go in for surgery.

Speaker Change: The paper emphasizes that while researchers saw cumulative risk for patients who had more than five surgeries.

Speaker Change: 44% of patients who had less than five surgeries had incurred permanent iatrogenic injury.

Speaker Change: As an injury caused by the surgery itself not the underlying disease.

Speaker Change: Most simply put the cumulative risk for injury increases with every surgery.

Speaker Change: But ultimately any one surgery could cause permanent damage.

Speaker Change: Consider them that many patients have hundreds of surgeries over their lifetime.

Speaker Change: With 31, seven we aimed to prevent further surgeries before that cumulative risk becomes dangerously high.

Michael Sumner: Consider then that many patients have hundreds of surgeries over their lifetime. With 3107, we aim to prevent further surgeries before that cumulative risk becomes dangerously high. So let's recall what RRP is as a disease, how it's caused, and what drives patients to seek medical treatment. We'll also address why we continue to believe 3107 could be useful for the broadest number of patients. First off, as we've spoken about extensively, RRP is a disease caused by infection with specific strains of the human papillomavirus, HPV6 and HPV11, in the majority of patients.

Speaker Change: So let's recall, what <unk> is as a disease, how is cost and what drives patients to seek medical treatment.

Speaker Change: We will also address why we continue to believe 30 107 could be useful for the broadest number of patients.

Speaker Change: First off.

Speaker Change: As we've spoken about extensively rfps a disease caused by infection with specific strains of the human papilloma virus H.

Speaker Change: <unk>, six and HPV 11, and the majority of patients.

Michael Sumner: The main symptom of the disease that drives patients to seek treatment as adults is the development of papillomas in the airway, especially in the throat and on vocal cords. These papillomas can cause difficulty speaking and breathing, substantially affecting a person's quality of life.

Speaker Change: The main symptom of the disease that drives patients to seek treatment as adults is the development of <unk> in the way of.

Speaker Change: Especially in the throat and on vocal cords.

Speaker Change: These <unk> can cause difficulty speaking and breathing substantially affect tanker persons quality of life.

Michael Sumner: 3107 has been shown to have the ability to generate antigen-specific T-cells with lytic potential targeting both HPV6 and HPV11, which may eradicate HPV-infected cells. Next, what we know about HPV is that it is a very common virus that affects nearly everyone at some point in their life. Most people have the ability to fight off HPV infections without even experiencing symptoms, but those who go on to develop RLP have immune systems that are unable to create an adequate defense.

Speaker Change: 30, 107 has been shown to have the ability to generate antigen specific T cells with lytic potential targeting both HPV six and HPV 11, which may eradicate HBV infected cells.

Speaker Change: Next what we know about HBV is that it is a very common virus that affects nearly everyone at some point in their lives.

Speaker Change: Most people have the ability to fight off HBV infections after them without even symptom development.

Speaker Change: But those who go on to develop RMP have immune systems that are unable to create an adequate defense.

Michael Sumner: For these individuals, we believe D107 has the potential to teach their immune system to mount a response that will help it fight back against the virus and prevent the development of papillomas. This is an excellent example of the benefits of our platform technology. In short, we have designed our proprietary delivery device, Selectra, to optimally deliver DNA medicines to the body cells without the use of chemical adjuvants, lipid nanoparticles, or viral vectors, and without the adverse effects that can be associated with those delivery methods.

Speaker Change: For these individuals we believe <unk> 107 has the potential to teach their immune system to Mount a response that will help it fight back against the virus and prevent the development of <unk>.

Speaker Change: This is an excellent example of the benefits of our platform technology.

Speaker Change: In short we have designed our proprietary delivery device selection to optimally deliver DNA medicines to the body cells.

Speaker Change: Without use of chemical adjuvant, lipid nanoparticles or viral vectors and without the adverse effects that can be associated with those delivery methods.

Michael Sumner: This results in our DNA medicines teaching the immune system to react in an effective way to protect or treat the patient. Finally, the current standard of care for RRP is surgery, which, as I mentioned earlier, can cause greater permanent damage to the vocal cords than the underlying disease itself.

Speaker Change: This results in our DNA medicines teaching the immune system to react in an effective way to protect or treat the patient.

Speaker Change: Finally, the current standard of care for <unk> surgery.

Speaker Change: Which as I mentioned earlier can cause greater permanent damage to the vocal cords than the underlying disease itself.

Michael Sumner: Data from our completed Phase 1-2 trial showed treatment with 3107 resulted in a statistically significant reduction in the number of surgeries in that trial. Treatment with 3107 was observed to be well-tolerated, with the most common adverse events being injection site reactions. As a reminder, this slide shows the results from our Phase 1-2 trial. As you can see here, 81% of patients experienced a reduction in the number of surgeries versus the prior year.

Speaker Change: Data from our completed phase one two trial showed treatment with 31% and seven resulted in a statistically significant reduction in the number of surgeries in that trial.

Speaker Change: Treatment with $31 seven was observed to be well tolerated with the most common adverse events being injection site reactions.

As a reminder, this slide shows the results from our phase one two trial.

As you can see here, 81% of patients experienced a reduction in the number of surgeries versus the prior year, an improvement was seen in patients with a wide range of disease severity.

Michael Sumner: An improvement was seen in patients with a wide range of disease severity, with a median decrease of three surgeries. Furthermore, 28% of the patients required zero surgeries in the year following their first dose. Relative to other phase 1, 2 clinical trials, our protocol required that all surgeries conducted during the dosing window, a 54-day period during which four doses were administered, be counted in the overall result. The protocol for our trial also did not include prescribed laryngoscopy and surgery at week 6 and 12 to maintain minimal residual disease during the treatment window.

Speaker Change: With a median decrease of three surgeries.

Speaker Change: Further 28% of the patients required zero surgeries and the year following the first dose.

Speaker Change: Relative to other phase one two clinical trials a protocol required that all surgeries conducted during the dosing window, a 54 day period during which four doses were administered be counted in the overall results.

Speaker Change: The protocol for <unk> also did not include prescribed laryngoscopy and surgery at week, six and 12 to maintain minimal residual residual disease during the treatment window.

Michael Sumner: As we look to the future development opportunities for INO3107, we plan to capitalize on the product's candidates' clinical and immunological strengths, based on historical data from other DNA medicines programs that involve re-dosing. We believe we will be able to effectively re-dose INO3107 to potentially enhance immune responses in partial and non-responders. We plan on investigating redosing strategies to build on the impressive results I shared on the previous slide and plan to submit a redosing trial design to the FDA in the third quarter.

Speaker Change: As we look to the future development opportunities for <unk> thousand 107, we plan to capitalize on the product candidates clinical and immunological strengths.

Speaker Change: Based on historical data from other DNA medicines programs.

Speaker Change: Which involve re dosing, we believe we will be able to effectively re dose 30, 107 to potentially enhance immune responses for partial and non responders.

We plan on investigating re dosing strategies to build on the impressive results our share on the previous slide and.

Speaker Change: And plan to submit a re dosing trial design to the FDA in the third quarter.

Michael Sumner: We are also continuing our conversations with regulators in Europe to help frame clinical development efforts for ex-U.S. markets, which we believe will be expedited by utilizing a placebo-controlled study design for our U.S. confirmatory trial. Our strategy in Europe is supported by the Orphan Drug Designation, granted by the European Commission last year, and the previously granted CE mark for S-Electrodevice, which indicates that it meets certain European health and safety Turning now to another late stage candidate, I'd like to provide some important updates on INO3112.

Speaker Change: We are also continuing our conversations with regulators in Europe to help frame clinical development efforts for ex U S markets.

Speaker Change: Which we believe will be expedited by utilizing a placebo controlled study design for our U S confirmatory trial.

Speaker Change: Our strategy in Europe is supported by the orphan drug designation granted by the European Commission last year.

Speaker Change: And the previously granted CE Mark for our electric device, which indicates that it meets certain European health and safety requirements.

Speaker Change: Turning now to another late stage candidates I would like to provide some important updates on INR 31 12.

Michael Sumner: As you may recall, we announced a clinical collaboration and supply agreement with Coherus Biosciences in the first quarter of this year to investigate 3112 as a potential treatment for HPV 16 and 18 related loco-regionally advanced high-risk throat cancer when used in combination with Loctorzi, an anti-PD-1 monoclonal antibody recently approved for the treatment of nasopharyngeal carcinoma. In combination, this therapeutic approach is designed to leverage the antigen-specific T cells elicited by 3112 and the ability of Loctorzi to re-engage T cells to boost the immune response against cancer cells.

Speaker Change: As you May recall, we announced a clinical collaboration and supply agreement with <unk> Biosciences in the first quarter of this year to investigate 31 12 as a potential treatment for HPV 16, and 18 related local or regionally advanced high risk throat cancer.

Speaker Change: When used in combination with <unk>.

Speaker Change: An anti PD, one monoclonal antibody recently approved for the treatment of nasopharyngeal carcinoma.

Speaker Change: In combination. This therapeutic approach is designed to leverage the antigen specific T cells are listed by 31, 12, and the ability of lock towards E to Reengage T cells to boost the immune response against cancer cells.

Michael Sumner: We're excited about the potential for this novel combination therapy and believe it could meet the high unmet need within this rapidly growing patient group. The incidence of HPV-positive throat cancer is on the rise in high-income countries and has surpassed cervical cancer as the most common HPV-related cancer diagnosed in the United States.

Speaker Change: We're excited about the potential for this novel combination therapy and believe it could meet the high unmet need within this rapidly growing patient group.

Speaker Change: The incidence of HPV positive throat cancer is on the rise in high income countries and.

Speaker Change: And has surpassed cervical cancer as the most common HPV related cancer diagnosed in the United States.

Mark Twyman: We previously submitted a study package for our phase 3 trial to the FDA in the first quarter and recently received feedback giving us confidence that we can move forward with our phase 3 trial to evaluate the ability of 3112 in combination with Loctorzi, with the aim of increasing event-free survival. Our goal is to conduct a multi-centre study in North America and Europe, and our next steps are to discuss the trial design with European regulators.

Speaker Change: We previously submitted a study package for a phase III trial to the FDA in the first quarter and recently received feedback, giving us confidence that we can move forward with our phase III trial to evaluate the ability of <unk> hundred 12 in combination with <unk>.

Speaker Change: With the aim of increasing event free survival.

Speaker Change: Our goal is to conduct a multicenter study in North America, and Europe, and our next steps are to discuss the trial design with European regulators.

Mark Twyman: We are also continuing to drive progress with some of our earlier stage candidates, including INO4201, which is being studied as a heterologous boost to the FDA-licensed Ebola vaccine Avivone. We recently generated some encouraging new antibody response data from our previously reported Phase I study by utilizing the FANG assay. This assay, which is often used in this disease space and more accurately allows us to benchmark our data against other primary vaccines on the market, indicates that 4201 elicits a strong antibody response comparable to the Avivo primary vaccination.

Speaker Change: We are also continuing to drive progress with some of our earlier stage candidates, including INR 40 201.

Speaker Change: Which is being studied as a heterologous boost to the FDA licensed Ebola vaccine of Evo.

Speaker Change: We recently generated some encouraging new antibody response data from our previously reported phase one study by utilizing the Fang assay.

Speaker Change: This assay, which is often used in this in this disease space and more accurately allows us to benchmark had data against other primary vaccines on the market.

Speaker Change: Indicates that 40 201 elicits a strong antibody response comparable to the vivo primary vaccination.

Mark Twyman: We are planning to publish this data in a peer-reviewed journal, and based on productive feedback from the FDA and discussions with KOLs and collaborators, we are moving forward and aim to submit our revised protocol for the Phase 2-3 clinical trial with 4201 this quarter. We are aiming to conduct the trial in tandem with a non-human primate study to allow immunobridging of protective antibody levels in the non-human primate challenge study to human titus.

Speaker Change: We are planning on publishing this data in a peer reviewed journal and based on productive feedback from the FDA and discussions with Kols and collaborators. We are moving forward and aim to submit a revised protocol for the phase III clinical trial with $42 <unk> this quarter.

Speaker Change: We are aiming to conduct the trial in tandem with our nonhuman primate study to allow immuno bridging of protective antibody levels in the nonhuman human Primate challenge study to human titers.

Mark Twyman: And finally, from our work on next-generation DNA medicines, we look forward to sharing a readout of the first clinical data from the DARPA-funded phase 1 trial evaluating the anti-SARS-CoV-2 DMAB candidates in the second half of 2024. For those not familiar with this innovative technology, we're using a core DNA medicines platform to evolve traditional monoclonal antibody therapeutics by encoding the DNA sequence for a specific We believe our DMAB technology has transformative potential, enabling functional monoclonal antibodies to be directly produced within the body. With that, I'll turn the call over to Mark to provide an update on our commercialization efforts for 3107. Mark? Thanks, Mike, and hello.

Speaker Change: And finally from our work on next generation DNA medicines, we look forward to sharing a readout of the first clinical data from the DARPA funded phase one trial of <unk>.

Speaker Change: Valuate, a Z anti Sars Covid two <unk> candidates in the second half of 2024.

Speaker Change: For those not familiar with this innovative technology, we are using our core DNA medicines platform to evolve traditional monoclonal antibody therapeutics by encoding the DNA sequence for specific monoclonal antibody and a DNA plasmid.

Speaker Change: We believe <unk> technology has transformative potential enabling functional monoclonal antibodies to be directly produced within the body.

Speaker Change: With that I'll turn the call over to Mark to provide an update on our commercialized commercialization efforts for <unk> 107, Mark Thanks, Mike and Hello, everyone I'd like to start today by taking a moment to highlight what's really driving our efforts to bring 31, 7% market patients.

Mark Twyman: Thanks, Mike, and hello, everyone. I'd like to start today by taking a moment to highlight what's really driving our efforts to bring 3107 to market, patience. RP patients are desperate for a treatment that will provide relief from the physical and emotional burdens of surgery, and we are focused on bringing a potentially game-changing treatment option to market for them. Listening to patients allows us to continue to add to our understanding of their journey and the impact the disease has on their lives to enable us to best serve them. The quotes listed on this slide come from actual patients we've spoken to about RRP and how it has affected them. I can tell you that that is the case with all rare diseases.

Mark: Patients RFP.

Mark: RP patients are desperate for a treatment that will provide relief from the physical and emotional burdens of surgery and we are focused on bringing in potentially game changing treatment option to market for them.

Mark: Listening to patients allows us to continue to add to our understanding of the journey and the impact of the disease has on their lives to enable us to best serve them.

Mark: The court listed on this slide come from actual patients we've spoken to you about RFP and how it has affected them.

Mark: I can tell you.

Mark: That is the case with all rare diseases for those living with RFP. The impact is real and can be life altering to the point that they can't work in their desired profession or enjoy their friends and family like they used to.

Mark Twyman: For those living with RRP, the impact is real and can be life-altering to the point that they can't work in their desired profession or enjoy their friends and family like they used to. I would like to thank patients, healthcare providers, and patient advocacy groups for assisting us in ensuring that we develop 3107 to best meet patient needs. While Mike laid out what we see as the clinical advantages of 3107, they were just one part of our foundation for commercial success.

Mark: I would like to thank the patients health care providers and patient advocacy groups, who are assisting us and ensuring that we develop <unk> thousand 107 to best meet patient needs.

Mark: While Mike laid out what we see is the clinical advantages of <unk> thousand 107. There are just one part of our foundation for commercial success as I highlighted last quarter that foundation also includes a critical understanding of the patient and healthcare provider landscapes and building a deep bench of expertise on our commercial team.

Mark Twyman: As I highlighted last quarter, that foundation also includes a critical understanding of the patient and healthcare provider landscapes and building a deep sense of expertise on our commercial team. At a strategic level, for some time now, we've been clear on what the key strategic drivers of commercial success will be and have made significant progress to date against each of them. As examples, we've secured a temporary CPT code for administration of 3107, selected a 3PL partner, and have identified potential specialty distribution and pharmacy partners that we believe can best support our intended channel strategy.

Mark: Strategic level for some time now we've been clear on what the key strategic drivers of commercial success will be that have made significant progress to date against against each of them as.

Mark: As examples we've secured a temporary CPT code for administration of 31, 7% selected as retail partner and have identified potential specialty distribution and pharmacy partners that we believe can best support our intended channel strategy.

Mark Twyman: Based on a comprehensive claims database analysis, we are in the final phases of locking down our geographic field footprint in the HCP payor deployment strategy and supporting non-field-based HCP inpatient engagement strategy. We also plan to submit the proposed brand name for 3107 to the agency for review in the near term. We're moving fast, but remain grounded in a very thoughtful, methodical approach that I believe will carry us forward successfully.

Mark: Based on a comprehensive claims database analysis, we are in the final phase of locking down our geographic footprint and ACP payer deployment strategy and supporting non field based HCP and patient engagement strategies.

Mark: We also plan to submit the proposed brand name for 31, 7% of the agency will review in the near term.

We're moving fast but remain grounded in a very thoughtful methodical approach that I believe will carry us forward successfully.

Mark: Okay.

Mark Twyman: With the potential to be the first therapeutic treatment for RRP in the first DNA medicine approved in the U.S., 3107 could be groundbreaking from a scientific perspective. But a product like the recently approved Narragasistat serves an important reminder of why treatment options for rare diseases like RRP are necessary. Narragasistat has many similar characteristics to 3107. Neurogastrocyte is the first FDA-approved treatment for adults with desmoid tumors, a rare disease characterized by non-cancerous growth found in connective tissue that, much like papillomas, is rarely fatal but places an incredible physical and emotional burden on patients, reducing their quality of life.

Mark: With the potential to be the first therapeutic treatment for RFP in the first DNA medicine approved in the U S. Turning 107 could be groundbreaking from a scientific perspective, but a product like the recently approved near Airgas. A stat serves an important reminder of our treatment options for rare diseases like RFP are necessary.

Mark: <unk> has many similar characteristics to 31 seven.

Mark: <unk> is the first FDA approved treatment for adults with Desmoid tumors are rare disease characterized by noncancerous growth founded connective tissue that much like papilloma are rarely fatal replace an incredible physical and emotional burden on patients reducing their quality of life.

Mark Twyman: Like RRP, the standard of care for desmoid tumors is surgery, which doesn't address the underlying disease or eliminate the probability of recurrence, and of itself places significant physical, Approved for marketing by the FDA in late 2023, niragastast offers a desperately needed non-surgical treatment option to patients who might otherwise face the risk of damage to local soft tissue and joints, very much in the same way that we hope 3107 will prevent the need for surgery for RFP patients.

Mark: Like RFP the standard of care for Geismar tumors is surgery, which doesn't address the underlying disease or eliminate the probability of recurrence in of itself places significant physical and emotional burden on patients.

Mark: Proof of marketing by the FDA in late 2023, neuro gases that offers a desperately needed nonsurgical treatment option to patients who might otherwise face the risk of damage to local soft tissue enjoys very much in the same way that we hope for a 107 to prevent the need for surgery for RP patients.

Peter D. Kies: I'll now turn the call over to our Chief Financial Officer, Peter Kies, for an overview of our first quarter financial results.

Mark: I'll now turn the call over to our Chief Financial Officer, Peter Keys for an overview of our first quarter financial results here.

Peter D. Kies: Thank you, Mark. Today, I'd like to provide an overview of Inovio's operational highlights and financial condition for the first quarter of 2024. As Jackie noted earlier, we continue to strengthen our financial position by working to advance 3107 and other promising candidates. We are pleased to announce a completed offering of common stock and pre-funded warrants in April 2024 with net proceeds from the offering of approximately $33.2 million after deducting underwriter discounts and commissions and operating expenses. These additional funds will help support our commercialization efforts for 3107 and support progress across our pipeline.

Peter D. Kies: Thank you Mark today I'd like to provide an overview of <unk> operational highlights and then financial condition for the first quarter of 2024.

Peter D. Kies: As Jackie noted earlier, we continue to strengthen our financial position, while working to advance 30, 107 and other promising candidates.

Peter D. Kies: We are pleased to announce a complete completed offering of common stock and pre funded warrants in April 2024, with net proceeds from the offering of approximately.

Peter D. Kies: $33 2 million after deducting underwriter discounts and commissions and offering expenses.

Peter D. Kies: These additional funds will help support our commercialization efforts for 30, 107 and support progress across our pipelines.

Peter D. Kies: We have again reduced our total operating standards, dropping from 44.1 million in the first quarter of 2023 to 31.5 million in the first quarter of 2024, a 29% decrease. Breaking down our operational spend further, our R&D expenses in the first quarter of 2024 totaled $20.9 million, compared to $30.2 million for the same period in 2023. The year-over-year decrease in R&D expenses was primarily the result of lower drug manufacturing, clinical trial expenses, outside services, and expense inventory related to INO4800 and other COVID-19 studies, and lower Employee and Consultant Compensation, including stock-based compensation, among other variants.

Peter D. Kies: We have again reduced our total operating spend dropping from $44 1 million in the first quarter of 2023 to $31 5 million in the first quarter of 2024 or 29% decrease.

Peter D. Kies: G&A expenses for the first quarter of 2024 were $10.6 million compared to $13.9 million for the same period in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including non-cash employee and consultant stock-based compensation, and a decrease in other legal expenses, among other variants.

Peter D. Kies: Breaking down our operational spend further.

Peter D. Kies: Our R&D expenses in the first quarter of 2024 totaled $29 million.

Peter D. Kies: Compared to $30 2 million for the same period in 2023.

Peter D. Kies: The year over year decrease in R&D expenses was primarily the result of lower drug manufacturing.

Peter D. Kies: Clinical trial expenses outside services and expense inventory related to INR 4800, and other COVID-19 studies and lower employee and consultant compensation, including stock based.

Peter D. Kies: Compensation among other variances.

Peter D. Kies: G&A expenses for the first quarter of 2024 were $10 6 million compared to $13 9 million for the same period in 2023.

Peter D. Kies: The decrease in G&A expenses was primarily related to a decrease in employee compensation, including noncash employee and consultant stock based compensation.

Peter D. Kies: And a decrease in other legal expenses among other variances.

Peter D. Kies: Inovio's net loss for the quarter was $30.5 million, or $1.31 per share, basic and dilutive, compared to a net loss of $40.6 million, or $1.89 per share, basic and dilutive, for the first quarter of 2023. During the quarter, we paid the remaining balance of our convertible notes of $16.9 million and have no further debt. We finished the quarter of 2024 with $105.6 million in cash, cash equivalents, and short-term investments, compared to $45.3 million as of December 31, 2023.

Peter D. Kies: <unk> net loss for the quarter was $30 5 million or $1 31 per share basic and dilutive compared to a net loss of $46 million.

Peter D. Kies: $1 89 per share basic and dilutive for the first quarter 2023.

During the quarter, we paid the remaining balance of our convertible notes of $16 9 million and have no further debt.

Peter D. Kies: We finished the quarter of 2024 with $105 6 million in cash cash equivalents and short term investments compared to $45 3 million as of December 31, 2023.

Peter D. Kies: Inovio estimates that its cash runway, including the net proceeds of $33.2 million raised in April 2024, to extend into the third quarter of 2025. This projection includes an operational net cash burn estimate of approximately $30 million for the second quarter of 2024. These cash runway projections do not include any further capital raising activities that Inovio may undertake.

Peter D. Kies: <unk> estimates of cash runway.

Peter D. Kies: Including the net proceeds of $33.2 million raised in April 2024 to extend into the third quarter of 2025.

This projection includes an operational net cash burn estimate of approximately $30 million for the second quarter of 2024.

Peter D. Kies: These cash runway projections do not include any further capital raising activities that are novo may undertake.

Peter D. Kies: As a reminder, you can find our full financial statements in this afternoon's press release as well as in our Form 10-Q filed today with the SEC. Now, with that, I'll turn the call back over to Jacqueline. Thanks, Pete.

Peter D. Kies: As a reminder, you can find our full financial statements in this afternoon's press release as well as in our Form 10-Q filed today with the SEC now with that I'll turn the call back over to Jacky.

Jacqueline E. Shea: Thanks, Peter. I'd now like to open up the call to answer any questions you might have. Operator?

Jacky: Thanks Peter.

Jacky: Now I'd like to open up the call to answer any questions you might have operator.

Operator: Ladies and gentlemen, we will now begin the question-and-answer session. Should you have a question, please press star followed by the number one on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press star followed by the number 2. If you are using a speakerphone, please lift the handset before pressing anything. Your first question is from the line of Hartaj Singh from Oppenheimer. Your line is now open.

Speaker Change: Ladies and gentlemen, we will now begin the question and answer session should you have a question. Please press star followed by the number one on your Touchtone phone, you'll hear a prompt that your hand has been raised.

Speaker Change: Should you wish to decline from the polling process. Please press star followed by the number too.

Speaker Change: If you are using a speaker phone please lift the handset before pressing any keys.

Speaker Change: Your first question is from the line of harsh Taj Singh from Oppenheimer. Your line is now open.

Hartaj Singh: Great, thank you. I have got a couple of questions. One broad and one just kind of specific to the P&L. Just on the broad question, you know, we've had some investors kind of ask us what the effect of HPV vaccines is. I know they've been around for a while, Jackie, Mark, but, you know, Australia, they published a 2020 perspective saying that, you know, RP rates have been going down there. Can you just give us your thoughts there on how you view vaccines, in the context of RP, and then, secondly, just an expert Peter, if you can just give us an idea that, you know, would be phase 3 advancing for 31, for INO 3112. Would you expect the burn to start moving up over the next few quarters?

Speaker Change: Oh, great. Thank you.

Hartaj Singh: Got a couple of questions one broad and one just kind of specific to the P&L.

Hartaj Singh: Just on the broad question.

Hartaj Singh: Had some investors kind of ask us what the effect of HPV vaccines, I know they've been around for a while Jackie mark but.

Hartaj Singh: I guess, Australia, they publish a 2020 perspective, saying that RP rates have been going down there. So can you just give us your thoughts there on how you view ETE vaccines, a context of RP.

Hartaj Singh: And then secondly, just on Opex burn Peter if you can just give us an idea of that.

Hartaj Singh: With the phase III is advancing.

Hartaj Singh: For 31.

Hartaj Singh: Sure.

Hartaj Singh: Great.

Peter D. Kies: Friday 31, 12 would you expect the burn to start moving up over the next few quarters and thank you for the question.

Jacqueline E. Shea: And thank you for the question.

Jacqueline E. Shea: Hi Hartaj, nice to hear from you. So yes, HPV vaccines are a very important, very important question here. So HPV vaccines were launched in 2006 and 2009, first of all targeting girls and then moving on to boys as well. Another very critical point to bear in mind is the fact that RLP has three main age peaks. So, paediatric RRP tends to peak at around age 7, and then there's a peak in adulthood in the 30s, and then a further peak in the early 60s.

Speaker Change: Hi, <unk> nice to hear from you. So yes, HPV vaccines very important very important question here. So HPV vaccine launched in 2006 and 2009 first of all targeting girls and then moving into this fall.

Speaker Change: And what we've seen is that the HPV vaccines is certainly starting to have an impact on pediatric levels of RFP in countries that have achieved very high explanation right. So countries like Australia. For instance, you mentioned plans they have seen a significant impact in reduction in our Op Inc.

Speaker Change: But I think an important thing to notice.

Speaker Change: <unk> vaccination levels have really stalled in many high income countries.

Speaker Change: For instance, in the U S HPV vaccination rates during that 60% full for girls and women and.

Speaker Change: Slightly lower than that for the men in sort of high 50% set as the significant proportion of the population that remains on vaccinated and therefore unprotected against RFP.

Speaker Change: And another very critical point to bear in mind is the fact that RFP has three main H peaks, so pediatric RFP tends to peak at around <unk> seven and then there's the pekin adulthood.

Speaker Change: The third and then a further pekin.

Speaker Change: Yearly six states.

Jacqueline E. Shea: And for people in those sort of peak adult age groups, many of those people have not yet been vaccinated or were not vaccinated or are not eligible for vaccination, given the relatively recent rollout of the HPV vaccine. And then lastly, RRP is a disease that disproportionately affects boys and men. And these are the proportion, and these are the parts of the population that are least likely to have received the HPV vaccination. So taken all together, whilst I think we are seeing encouraging progress in terms of HPV vaccines, which do protect against infection with HPV 6 and 11, providing some protection in the juvenile population, we're still not really seeing that come through yet in the adult population. So unfortunately, RRP is going to be with us for decades to come.

Speaker Change: For people in those.

Speaker Change: Sort of peak adult age groups many of those people have not yet been vaccinated.

Speaker Change: Well were not vaccinated, who were not eligible for vaccination.

Speaker Change: Given the relatively recent rollouts of the HPV vaccine.

Speaker Change: And then lastly.

Speaker Change: <unk> is a disease that.

Speaker Change: Disproportionately affects points in men and these are the propulsion and needs of the part of the population that's at least likely to have received HPV vaccination.

Speaker Change: Taken altogether, whilst I think we are seeing encouraging progress in terms of HPV vaccines, which do protect against infection with HPV six and 11.

Speaker Change: Providing some protection in the <unk> population, we're still not really seeing that come through yet in the adult population. So unfortunately, RFP is going to be with us for decades to come.

Michael Sumner: Mike, anything you'd like to add to that?

Speaker Change: Mike anything you'd like to add to that.

Michael Sumner: You hit every major point.

Mike: You made your point.

Mike: Yes.

Peter D. Kies: And then, moving on to your question about OPEC sperm, we are, as Mike mentioned during the call, our next step for 3112 will be to conduct discussions with the European regulators because we're looking to conduct this trial in both North America and Europe. And it's going to take us a little bit of time to go through those interactions. But I'll hand over to Peter, and he can provide some further color on the financials. Peter?

Speaker Change: And then moving on to your question around Opex spend we are as Mike mentioned during the call. Our next step for 31 12 will be to conduct discussions with the European regulators, who has been looking to conduct this trial in both North America and Europe.

Mike: And.

Mike: It's going to take us a little bit of time to go through those interactions.

Mike: But I'll hand over to Peter and he can provide some further color on the financials Peter.

Peter D. Kies: Thank you, Jackie. Yes, Hartaj.

Peter D. Kies: Thank you Jackie we asked her to us So we did increase our estimated burn this quarter by $4 million.

Peter D. Kies: Do expect that to be fairly consistent.

Peter D. Kies: So, you know, we did increase our estimated burn this quarter by $4 million. I do expect that to be fairly consistent. And, you know, we've given guidance that we have cash into the third quarter 2025. So a lot of that's related to that increase right now is related to our commercial activities, accelerating our commercial activities after our fundraising. But once we dive into 3112 more and get that launched, we could see some potential increases after that. Great. Thank you, Jackie.

Peter D. Kies: And.

Peter D. Kies: Given that we've given.

Peter D. Kies: Guidance that we have cash.

Peter D. Kies: In the third quarter of 2025.

Peter D. Kies: So a lot of that's related to that increase right now is related to our commercial accelerated our commercial activities after our fund raising.

Peter D. Kies: But once we dive into 31 12 more in depth that launched where you could see some potential increase was after that.

Operator: Great. Thank you, Jackie. Thanks, Peter. Thanks, Mike.

Speaker Change: Great. Thank you Jackie Thanks, Peter Thanks, Mike.

Operator: Your next question is from the line of Roy Buchanan from JMP. Your line is now open.

Speaker Change: Your next question is from the line of Roy Buchanan from JMP.

Roy Buchanan: Line is now open.

Roy Buchanan: Hey, thanks for taking the questions. Just a few on 3107. This one's pretty nice, but just what are the device aspects of the BLA? What do you need to do to get that submitted in terms of the devices?

Roy Buchanan: Hey, Thanks for taking the questions I just a few on 30 107.

Roy Buchanan: I just wanted to pretty naive, but just what are the device aspects of the BLA, what do you need to do to get that submitted in terms of the device itself.

Yeah, Great question Ryan.

Jacqueline E. Shea: Yeah. A great question, Roy.

Jacqueline E. Shea: So, as people may be aware, INO3107 in the U.S. is regulated as a combination product. So, that means we need to submit on both the drug component as well as the device component. And I'll hand over to Mike to talk about our regulatory interactions around this combination with the FDA. Mike? Thank you, Jackie.

Roy Buchanan: People might be aware INR 31, it's happened in the U S is regulated as a combination product.

Ryan: So if that means we need to to submit some by the drug component as well as the device component.

Ryan: And I'll hand over to Mike to talk about our regulatory interactions around this combination with the FDA might thank you Jackie.

Michael Sumner: So, I mean, obviously, devices are a living, breathing element. And so, basically, our file is really updating, making sure we're aligned with all the latest regulations that relate to the device. But I would remind you that the 5-PSP device has been used in two phase three studies before. We have significant experience with it, so we have a very good idea of how it performs in the clinical setting. So, really, it's just updating the device to bring it up to meet all the current standards for the BLA.

I mean, obviously devices are living breathing.

Ryan: Element.

Mike: So basically our filings really updating making sure we are aligned with all the latest regulations.

Mike: That relate to the device.

Mike: But I would remind you that the <unk> PSP devices being used in two phase III studies before we have significant experience with it. So we we have a very good idea of how it performs in the clinical setting.

Mike: So really it's just updating the device to <unk>.

Mike: Bring it up to <unk>.

Mike: Meet all the current standards for the BLA.

Michael Sumner: Okay, great. And then, I know this is hard to say until you actually start enrolling it, but can you just give us any kind of sense on how long it might take to enroll the confirmatory trial? And then for the immunology presentations you mentioned in the second half, can you point us to any conferences we should be particularly looking at? And then I have one on 31-12. Thanks.

Speaker Change: Okay, Great and then I know this is hard to say until you actually start enrolling it but can you just give us any kind of sense on how long it might take to enroll the confirmatory trial and then for the.

Speaker Change: For the immunology presentations, you've mentioned in the second half can you point us to any conferences, we should be.

Speaker Change: <unk> really looking at and then I have 131 12.

Michael Sumner: Yeah, Mike. Do you want to talk about the confirmatory trial and what we're thinking about in terms of the enrollment timeline?

Speaker Change: Yeah, Mike do you want to talk about the confirmatory trial and what we're thinking about in terms of enrollment timeline.

Michael Sumner: Certainly. I mean, we said on the call today that we're targeting approximately 100 patients. We were able to recruit the 32 patients in the Phase I-II study across eight clinical sites within approximately a year time period. We are going to be expanding beyond the eight clinical sites significantly. So we're targeting roughly the same recruitment period because, obviously, we're hoping that there'll be a commercial product available, and so we want to recognize that patients will be wanting to access that as soon as possible. With regard to immunology, we haven't indicated what conferences we're going to target or publications at the moment, but we will do so as soon as we know.

Mike: So I mean, we have said on the call today that we are targeting approximately 100 patients we were able to recruit the 32 patients in the phase one two study across eight clinical sites within approximately a year time period, we are going to be expanding beyond.

Mike: On the eight clinical sites significantly. So we are we're targeting roughly around the same recruitment period.

Mike: Because obviously, we are hoping that there'll be.

Mike: Our commercial product available. So we want to recognize that patients will be wanting to access that as soon as possible.

Mike: With regards to the immunology.

Mike: We haven't indicated what.

Mike: Conferences, we go into target or publications that moment, but we will do so as soon as.

Mike: We know.

Jacqueline E. Shea: If I can just add sort of one additional point, with regard to the confirmatory study, the FTAs have advised us that we just need to start that study before we can submit our BLA. So, you know, whilst we'll be looking to complete that study as quickly as possible, we just need to start it before we can. Before we submit that BLA. Right, okay. Do they have any requirements for enrollment, like 10 patients in or anything, or not at all?

Speaker Change: Okay and then just.

Speaker Change: Sorry.

Speaker Change: If I if I can just absolute one additional point with regards to the confirmatory study. We just the Fda's have advised us we just need to start that study before we can submit our BLA. So whilst we'll be looking to complete that study as quickly as possible.

Speaker Change: We just need to start it before we can.

Speaker Change: Before we submit that BLA.

Speaker Change: Right. Okay did it have any requirements on enrollment.

Speaker Change: 10 patient fan or anything or not at all.

Michael Sumner: No, they have not given us any targets. I mean, as you can expect, we believe it is to make sure that we are meeting our obligation of performing that confirmatory study, and we will definitely be able to demonstrate that to the FDA.

Speaker Change: No they have not given us any targets.

Speaker Change: As you can expect we believe it is to make sure that we are meeting our obligation of performing that confirmatory study and we will definitely be able to demonstrate that to the FDA.

Michael Sumner: Got it. Okay. And then 3112, you may have answered this, but have you reached out to the EU regulators and scheduled a meeting or just any sense of timing for that? Thank you. And we have not...

Speaker Change: Got it Okay and then.

Speaker Change: 31, 12, you may have answered this but.

Speaker Change: Have you reached out to the to the EU regulators and scheduled a meeting or just any sense on timing for that thank you.

Michael Sumner: We have not reached out yet. We will, now that we have had our meeting with the FDA and got alignment and have a pathway forward, we aim to get that submission in as fast as possible. So I would imagine there'll be some time during quarter three.

Speaker Change: We have not reached out yet.

We will be now that we have.

Speaker Change: Had a meeting with the FDA and global alignment and.

Speaker Change: And have a pathway forward, we aim to get that submission in as fast as possible.

Speaker Change: So I would imagine it will be sometime during quarter three.

Speaker Change: Okay. Thank you.

Operator: Your next question is from the line of Gregory Renza from RBC Capital Markets. Please go ahead.

Your next question is from the line of Gregory <unk> from RBC capital markets. Please go ahead.

Anish Nikhanj: Hi guys, it's Anish on for Greg. Thanks for the color on today's call and for taking our questions.

Gregory: Hi, guys its a niche on for Gregg. Thanks for the color on today's call and for taking our questions. I just wanted to ask on <unk> 107, and more on the clinical use side and considering the competitive landscape and with prestige and utilizing a sub Q route of administration. What are you hearing from Kols physicians and even patients on the use of the select your device is another relative layer.

Jacqueline E. Shea: I just wanted to ask on 3107 and more on the clinical use side, in considering the competitive landscape and with Precision utilizing a sub-key route of administration. What are you hearing from KOLs, physicians, and even patients about the use of the selector device as another relative layer or step for drug administration? And how do you feel about this position 3107 and the opportunity ahead just in thinking about if it could be better suited for certain clinics, practitioners, or even patients? Thanks so much.

Speaker Change: Or step for drug administration, and how do you feel this positions $31 seven and the opportunity ahead, just in thinking about if it could be better suited for certain clinics practitioners or even patients. Thanks. So much.

Jacqueline E. Shea: Yeah, that's a great question. So for people who are not familiar with our devices, as Mike mentioned earlier in the call, this is a device that we've used previously in two other phase three studies. We've used the device in clinical trials in, I believe, more than 30 countries now, and what we uniformly hear back from physicians and patients is that the device is very effective in administration of DNA medicines via the device is very tolerable for patients.

Speaker Change: Yeah. That's a great question. So for people here, who are not familiar with our devices as Mike mentioned earlier on that Nicole. This is the device that we've used previously and into other phase III studies, we've used the device.

Speaker Change: And in clinical trials and I believe more than 30 countries now and what we uniformly hear back from fulfill.

Speaker Change: Physicians and patients if the device is Barry administration of DNA medicines part the devices very tolerable for patients and it's quick and easy to use for health care providers.

Jacqueline E. Shea: And it's quick and easy to use for healthcare providers. So we really see the device as an important part of our delivery and that it's enabling targeted and localized uptake of our DNA medicines. And so we see it as a core component of that. And we're really not seeing it as a barrier compared to sub-Q administration. Mark, do you want to talk about that?

Speaker Change: So we really see the devices is an important part of our delivery and thats, enabling targeted and localized uptake about DNA medicines and so we see it as a core component that we're really not seeing it as a.

Speaker Change: As a barrier.

Speaker Change: Compared to sub Q administration.

Speaker Change: Mark do you want to talk about it just to be a little bit more specific.

Mark Twyman: Yeah, I mean, just to be a little bit more specific, your comments were spot on, that we've done primary market research with physicians, and they've said exactly what Jackie said. Their device is not an obstacle. It's easy to use. In fact, laryngologists are the device. Right. They use devices sort of every day. If you go to one of their conferences, that's pretty much what's on the conference floor. So, you know, again, the results of the and the input from the market research suggest that it won't be an obstacle for use either in their practice or in the OR. So we're pretty confident about that.

Mark: Comments were spot on but we've done primary market research with physicians and they said exactly what Jack said.

The device is not an obstacle is easy to use in fact laryngologist device physicians right now may use devices sort of everyday as you go to one of their conferences, that's pretty much what's on the conference floor zone.

Mark: Again, the results of the and the input from the market research suggests that it won't be an obstacle for use either in their practice should they decide to use the device in their practice are in or in the or so were pretty confident about that.

Jacqueline E. Shea: Great, thanks so much, and I look forward to seeing you at our conference this week. Yeah, I look forward to seeing you.

Speaker Change: Great. Thanks, so much and look forward to senior at our conference this week.

Anish Nikhanj: Yeah, I look forward to seeing you as well, Anish.

Speaker Change: Yes look forward to seeing news violence.

Operator: Your next question is from the line of Roger Song from Jeffries. Please go ahead.

Roger Song: Your next question is from the line of Roger song from Jefferies. Please go ahead.

Roger Song: Great. Thanks for the update and taking our questions. There may be a couple of questions related to 3107 in the confirmatory study. One is in terms of the control arm treatment option at the site end. I'm just curious how heterogeneous we are talking about here, particularly as you expand this trial into global clinical sites. And also, for the 100 patients in the sample size, what is the powering assumption there, particularly related to the effect size, how much reduction you are powering for the study to show that understanding you probably alluded to one less, one fewer surgery can be clinically needed for those patients. I'm just curious, and want to confirm what the powering assumption, the effect size assumption, you have for the confirmatory study. Thank you.

Roger Song: Yes.

Roger Song: Great.

Roger Song: Thanks for the update and to your question will be a couple of questions related to certain wells.

Roger Song: Thank you, Roger. So your line's not terribly clear, but I think what we heard you asking was around the sample size and the powering for the confirmatory trial and what we're thinking of there, and also around the clinical trial sites, how heterogeneous they are, and what the potential implications of that could be for a global rollout. Does that capture your question?

Roger Song: I'll now confirmatory study.

Roger Song: One of the control arm Jim option at this time.

Ann: Hi, Ann.

Ann: Just curious to how heterogeneous.

Ann: Thank you Paul.

Speaker Change: In this trial.

Speaker Change: <unk> global.

Speaker Change: Clinical side and also for the logic why in your patients.

Speaker Change: The sample size or what is the powering assumption.

Speaker Change: Related to the.

Speaker Change: In fact, how much reduction you are powered for the study to shell.

Speaker Change: Mccormick you probably alluded at one one last.

Speaker Change: Once your dream, Kent clinically meaningful patient just curious.

Speaker Change: What's the powering assumption.

Speaker Change: Option you have.

Speaker Change: <unk> for the.

Walter: Walter study thank you.

Jacqueline E. Shea: That's correct. Sorry about that.

Roger Song: Okay. Thank you Roger.

Speaker Change: Your line is not terribly clear, but I think what we heard you asking what's around the sample size and the powering for the confirmatory trial.

Roger Song: We're thinking of there and also around the clinical trial sites, how heterogeneous stale.

Roger Song: The potential implications of that could painful for a global rollout does that capture your question.

Speaker Change: That's correct and sorry about that.

Jacqueline E. Shea: The connection here. Yes. Those are the questions. So, we are.

Speaker Change: Yes, yes, no the other question.

Michael Sumner: All right, so Mike, would you like to talk about the sites we've used to date, the sites we're thinking of using going forward, and why we think actually, you know, having already been to eight sites is actually very helpful for us.

Speaker Change: Alright, So Mike would you like to talk about the.

Mike: The sites, we've used to date the sites, we're thinking of using going forward and why we think actually having already been in eight sites, it's actually very helpful for them.

Michael Sumner: And precisely that fact, I mean, we conducted the Phase I-II study across eight academic sites primarily. And we obviously looked from an analysis point of view to see if there was any variability from site to site, and we did not see that. As you can imagine, in the United States, RRP is based on sites that are able to do clinical trials are academic in nature. So as we expand beyond the original eight sites, we really do not expect to see any impact from the site characteristics. And we are aiming to perform this study within the United States at this stage. As you mentioned, we have spent some time with European KOLs.

Mike: And precisely that.

Mike: Frank I mean, we have conducted the phase one two study across eight academic sites primarily.

Mike: And we obviously looked from analysis point of view to see if there was any variability from site to site and.

Mike: And we did not see that as you can imagine in the United States RFP.

Mike: Based on sort of sites that are able to do clinical trial or academic in nature. So as we expand beyond the original eight sites, we really do not expect to see any impact from the site characteristics.

And we are aiming to perform this study within the United States.

Mike: At this.

Mike: Stages as you mentioned, we have spent some time with European Kols. The disease, while is treated surgically. They don't necessarily have access to the same surgical equipment. So we've kept that level of heterogeneity in.

Michael Sumner: The disease, while it is treated surgically, they don't necessarily have access to the same surgical equipment. So we've kept that level of heterogeneity in mind as we've designed both the study and our planned rollout. With respect to effect size, we obviously haven't detailed that, but what I will say is that we will be using a two-to-one randomization because we want to limit the number of patients that do not receive active

Mike: In mind is we've designed both to study and in our.

Mike: Planned rollout.

Mike: With respect to the effect size, we obviously havent detailed that but what I, what I will say is that.

Mike: We will be using a two to one randomization.

Mike: Because we want to limit the number of patients.

Mike: Do not receive active treatment.

Michael Sumner: If you remember, as we released both cohorts from the Phase I-II study, both of those cohorts individually were statistically significant. And we, as part of the study, also collected three-year data for patients coming into that study. And so we really used that data to try and estimate the placebo effect. And we've got a very nice safety margin, we believe, in terms of how we've powered the study. So we're very confident, based on what we've seen in our Phase I-II study and what data we have, that we have an appropriate effect size and statistical sample.

Mike: If you remember as we released both cohorts from the Phase one two study both of those cohorts individually was statistically significant.

Mike: And we as part of the study we also collected three year data.

Mike: For patients coming into that study and so we really use that data to try and estimate what the placebo effect.

Mike: And we've gone we've got a very nice safety margin. We believe in terms of how we've powered the study so we're very confident.

Mike: Just on what we've seen in our phase <unk> study and what data we have that we will.

Mike: We have an appropriate effect size and statistical sample.

Jacqueline E. Shea: Yeah, and if I can just add here, Mike, one of the reasons why we've gone down this path of conducting a placebo-controlled confirmatory trial is that there are a couple of sort of real key reasons underpinning this. First of all, the median number of surgeries for RRP patients is approximately four per year, and therefore, there are a lot of patients who are having less than four surgeries a year, and so it's important for us to be able to address that population of RRP patients as well, ideally before they start experiencing significant damage to their vocal cords.

Speaker Change: If I can just add him Mike one of the reasons why we've gone down this path of conducting a placebo controlled confirmatory trial. If there were a couple of sort of real key reason underpinning This festival.

Speaker Change: The median number of searches for ARLP patient since approximately four per year and therefore, there are a lot of patients who are who are having less than four et cetera, and so it's important for us to be able to address that population of RP patients with smile ideally before they start experiencing significant Dom.

Jacqueline E. Shea: And then also in discussions with the European regulators, they've also made it very clear that they see the path forward in Europe as potentially requiring a placebo-controlled trial. So we think conducting a placebo-controlled trial in the U.S. will be very helpful as we start to think about how we move 3107 into Europe. Mike, anything else you want to add to those aspects? No, I think we've covered all that.

Speaker Change: And to that vocal cords.

Speaker Change: And then also in discussions with the European regulators Staples have made it very clear that they see the path forward.

In Europe.

Speaker Change: Steve requiring a placebo controlled trial.

Speaker Change: So we think conducting a placebo controlled trial in the U S.

Speaker Change: Be very helpful. As we start to think about how we move.

Speaker Change: 31, <unk> seven into Europe.

Speaker Change: Uh huh.

Speaker Change: Mike anything else you want to add to those aspects now I think we've covered all the relevant points.

Michael Sumner: No, I think we've covered all the relevant points. Bye.

Speaker Change: Thanks.

Roger Song: Great, thank you. Thank you again.

Speaker Change: Great. Thank you. Thank you again.

Operator: Your next question is from the line of Yi Chen from HC Wainwright. Please go ahead.

Speaker Change: Your next question is from the line of E. Chen from H C. Wainwright. Please go ahead.

Yi Chen: Thank you for taking my questions. With respect to the target patient population in the confirmatory trial, what percentage of those patients do you expect to be different from the existing, the completed trial? And do you expect that to alter, potentially alter the efficacy readout in the future?

Yi Chen: Thank you for taking my questions.

Yi Chen: With respect to the <unk>.

Yi Chen: Patient population will be confirmed.

Yi Chen: Hum.

Yi Chen: What percentage.

Those patients do you expect to be correct.

Yi Chen: The completed trial do you expect that to alter.

Yi Chen: Initially ordered the efficacy readout in the future.

Yi Chen: Okay.

Michael Sumner: No, I think one of the things we were very pleased about was that the data set we saw from our phase 1, 2 was highly representative of the RRP population. And the inclusion-exclusion criteria are not changing in any significant points. So we would hope, again, that we would have a population of greater than two surgeries in the previous year and be representative of the true RRP population that's out there.

Speaker Change: No I think one of the things we were.

Speaker Change: Very pleased about was the data set we saw from our phase one two was highly representative of the <unk> population.

Speaker Change: And the inclusion exclusion criteria are not changing on any significant.

Speaker Change: So we would hope again that we will have a population of greater than two surgeries in the.

Speaker Change: The previous year and be representative of the true RFP population that's out there.

Jacqueline E. Shea: And just as a reminder, we enroll people in the Phase 1-2 study who've had from between 2 and 8 surgeries the prior year, people who have both 6 and 11 positive disease as well as people with mixed disease. So we really do believe that that patient population is representative of the population we want to treat.

Speaker Change: And just as a reminder, we enroll people in the phase one two study who'd had from between two and eight surgeries. The prior year people have had.

But it's $6 11 positive disease as well as people with mixed disease. So we really do believe that that patient population is representative of the population we want to trade.

Michael Sumner: So when you say a broader spectrum of RRP disease, what exactly does that mean?

Speaker Change: So when you see a broader spectrum of disease, what exactly does that mean for the confirmatory trial.

Michael Sumner: This relates to the fact that we are allowed to recruit patients who have had two surgeries. The FDA made it very clear to us that if we wanted to do a single-arm study, we could only go down to three or more surgeries. And as Jackie mentioned earlier in the call, that isn't fully representative of the RRP population. So that was one of the driving forces behind us picking a placebo-controlled design.

Speaker Change: This relates to the fact that we are allowed to recruit patients with two surgeries. The FDA made it very clear to us.

Speaker Change: If we wanted to do a single arm study, we could only go down to three or more surgeries.

Speaker Change: As Jackie mentioned earlier in the coal that is fair.

Fully representative of the RFP population. So that was one of the driving forces behind us picking a placebo controlled design.

Michael Sumner: Okay, so if for the confirmatory trial, there are a lot of two surgeries patients enrolled, could that potentially change the readout?

Speaker Change: Okay.

So if you if political politically kernel.

Speaker Change: There are a lot of two surgeries patient population could be.

Speaker Change: That potentially changing rebuilt.

Michael Sumner: I don't think we have any reason to believe that the population we recruit will be any different than what we saw in the Phase 1-2 study. I would fully expect we will have that full range that we saw in the previous study, starting at 2, but going up to 8, and maybe more surgeries. It's difficult to say. Based on the RRP Foundation data that they say, they note a median of four surgeries a year in this patient population, which was exactly what we hit. As we expand our clinical trial sites, I'm sure they will treat a very similar population.

Yes, I don't think we have any reason to believe that the population we recruit will be any different.

Speaker Change: Then what we saw in the phase one two study I would fully expect we will have that full range that we saw in the previous studies, starting at two but going up to eight and maybe more surgeries, it's difficult to say.

Speaker Change: Sure.

Based on the RFP Foundation data that they say they've they note a median of four surgeries a year in this patient population, which was exactly what we hit.

Speaker Change: As we expand our clinical trial sites I am sure they treat a very similar population.

Speaker Change: Okay. Thank you.

Speaker Change: Yeah.

Operator: Your next question is from the line of Sudan Loganathan from Stevens. Please go ahead.

Speaker Change: Your next question is from the line of Sudan LOE guidance then from Stephens. Please go ahead.

Sudan Loganathan: Yes, thank you for taking the time to answer my questions. Sorry if I'm hopping on a little late. I just wanted to ask really quickly just in terms of the BLA submission being on track for INO3107, you know, with the accelerated approval pathway, would there be the ability, you know, if not for the accelerated approval pathway, is there still a chance to get on the market by 2025? Or, you know, are there any assurances from the FDA regulators that you can get to, you know, just make sure that you're on track for that for 2025?

Sudan: Yes. Thank you for taking my questions sorry for hopping on a little late.

Sudan: Wanted to ask really quickly just in terms of the BLA submission be on tract, Brian out 3107.

Speaker Change: With <unk>.

Sudan: Under the accelerated approval pathway.

Sudan: Would there be the ability.

Not for the accelerated approval pathway, there is still a chance to get it under our regular.

Sudan: Approval processes in the market by 2020 fiber is there any assurances from the FDA regulators that you can get to.

Sudan: Just make sure that.

Sudan: You're on track for that for 2025.

Michael Sumner: So, I mean, as part of our pre-BLA meeting with the agency, we will obviously request priority review, which is one of the advantages of breakthrough designation, based on everything that the FDA has said to us about, you know, their recognition of the significant impact on these patients' quality of life. We are very hopeful that we will be granted priority review, which would substantially contract the review period.

Sudan: So I mean as part of a pre BLA meeting with the agency. We will obviously request priority review, which is one of the advantages of breakthrough designation.

Sudan: Based on everything.

The FDA has said to us about their recognition of the.

Sudan: And as a significant impact on these patients' quality of life.

Sudan: We are very hopeful that we will get granted priority review, which would substantially contract.

Michael Sumner: So, you know, obviously, I can't talk on behalf of the FDA, but we are on track to submit our BLA in the second half of this year. So, with priority review, we would hope that would mean a six-month review period once the file has been accepted.

Sudan: Few periods so.

Speaker Change: Obviously I can't talk on behalf of the FDA, but we.

Speaker Change: We are on track to submit our BLA in the second half of this year. So with priority review, we would hope that would mean a six month review period. Once the file has been accepted.

Michael Sumner: And then secondly, real quick, in terms of the initiation of the confirmatory trial, with the feedback that the FDA may provide for that trial, are any of the outcomes of that trial going to be necessary or needed for a full approval or any part of the approval process going forward with the priority review, or just how is the timing going to line up between the two?

Speaker Change: Great and then secondly real quick.

Speaker Change: In terms of the initial initiation of the confirmatory trial.

Speaker Change:

Speaker Change: With the feedback there.

Speaker Change: May provide.

Speaker Change: That trial.

Speaker Change: The outcomes of that trial is going to be.

Speaker Change: Necessary or needed for full approval or.

Speaker Change: Any part of the approval process in all kind of going forward with.

Speaker Change: The prior year viewer and just how the timing going to line up between the two.

Michael Sumner: So with respect to the BLA filing under the accelerated approval process, none of the confirmatory study data will be required. The only thing the FDA has asked us to do is commence that trial. And based on our previous work with CROs, we are already engaging with clinical trial sites to get that process moving as fast as possible. So we do not anticipate that that will hold up our filing.

Speaker Change: Yes, so with respect to the BLA filing under the accelerated approval process, none of the confirmatory study.

Speaker Change: Data will be required the only thing the FDA have asked us to do is commence that trial.

Speaker Change: And based on our previous work with <unk>, we are already engaging with clinical trial sites to get that process moving as fast as possible.

Speaker Change: So we do not anticipate that that will hold up finally.

Michael Sumner: And then we will need the full data from the confirmatory trial for full approval.

Speaker Change: Then we will need the full data from the confirmatory trial for full approval.

Speaker Change: Got you and is there like a.

Michael Sumner: [inaudible] any guidance on like when you could expect to have the full data for the confirmatory trial or is it, could we look back at the trial so far and how long it's taken to get data to extrapolate to how long it may be also to get that final confirmatory trial data?

Speaker Change: Any guidance on like how when.

Speaker Change: When you could expect.

Speaker Change: All data collected from a trailer is could we look at back at.

Speaker Change: Trial, so far and how long it's taken to get data to extrapolate to how long. It may be also to get that final confirmatory trial data.

Jacqueline E. Shea: Yeah, so as Mike said, we will be making further details about the trial available when we start it. We are looking to try and get this trial started as soon as possible, and as Mike said, we're looking to recruit around 100 patients. We're going to expand the number of clinical sites that we go across, and we'll look to try and recruit the participants as quickly as possible. For the Phase I-II trial, we actually recruited faster than we initially thought, and the trial was fully enrolled in less than a year. Great

Speaker Change: Yes. So this is <unk>.

Speaker Change: We will be making further details about the trial available when we started the trial.

Speaker Change: We are looking to try and get this trial started as soon as possible and as Mike said, we're looking to recruit around 100 patients. We can expand the number of clinical sites that the gang across and we'll look to try and recruit.

Speaker Change: The participants as quickly as possible.

Speaker Change: For the phase one two trial, we actually recruited faster than we initially thought in recruitment with the trial was fully enrolled.

Speaker Change: Yeah.

Sudan Loganathan: Great. Thank you so much. That's all my questions. Thanks for squeezing me in.

Speaker Change: Great. Thank you so much that's all my questions. Thanks for squeezing me in here.

Speaker Change: Nice to talk with you.

Jacqueline E. Shea: There are no further questions at this time. I would now like to hand the call back to Jacqueline Shea, President and CEO, for closing remarks. Please go ahead.

Jacqueline E. Shea: There are no further questions at this time I would now like to hand, the call back to Jackie shape, President and CEO for closing remarks. Please go ahead.

Jackie: Thank you.

Jacqueline E. Shea: As I outlined at the opening of this call, we have set an ambitious agenda for the year, but with a strengthened balance sheet and a strategic focus on the BLA submission and other important catalysts ahead, we are continuing to deliver on our key objectives. And with our commitment to deliver on the promise of DNA medicine for patients and minds, we're committed to keep the momentum going.

Jackie: As I outlined at the opening of this call. We have set an ambitious agenda for the year, but with a strengthened balance sheet and our strategic focus on the BLA submission and other important catalysts ahead, we are continuing to deliver on our key objectives.

Jacqueline E. Shea: And with our commitment to deliver on the promise of DNA medicines for patients in mind, we're committed to keep the momentum going.

Jacqueline E. Shea: With that, thank you again for your attention. Have a good evening, everyone. Good night.

Speaker Change: Thank you again for your attention have a good evening everyone Goodnight.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you very much for your participation. You may now disconnect.

Speaker Change: In addition, gentlemen. This concludes today's conference call. Thank you very much for your participation you may now disconnect.

Speaker Change: Okay.

Speaker Change: [noise].