Q4 2022 Atea Pharmaceuticals Inc Earnings Call
Speaker 1: Good afternoon, ladies and gentlemen.
Speaker 1: Welcome to the Ataya Pharmaceuticals fourth quarter and full year 2022 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we'll open the call up to your questions.
Speaker 1: To ask a question during the session, you need to press star one one on your telephone. You'll then hear an automated message advising you that your hand is raised. To withdraw your question at any time, press star one one again. Please be advised that today's conference is being recorded. I would now like to turn the call over to Jonae Barnes, Senior Vice President of Investor Relations and Corporate Communications.
Speaker 2: we issued a press release which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the investor section of our website at ir.ateafarma.com. With me from Itea, our Chief Executive Officer and Founder, Dr. Jean Pierre Somadossi.
Speaker 2: Chief Development Officer, Dr. Janet Hammond, Chief Medical Officer, Dr. Ronsha Horga, Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, and our Chief Commercial Officer, John Bavrika. They will all be available for the Q&A portion of today's call.
Speaker 2: Before we begin the call, as outlined on slide two, I would like to remind you that today's discussion will contain forward-looking statements that involve risk and uncertainties. These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read.
Speaker 3: Our actual results may differ materially from what is discussed on the call. With that, I'll now turn the call over to Jean-Pierre. Thank you, Jonay. Good afternoon, everyone, and thank you for joining us. As you will see on slide 3, this year we are forced to continue the meaningful progress made across our advanced clinical development programs.
Speaker 3: We anticipate an interim analysis from the Sunrise Three trial in the second half of this year, followed by completion of involvement by UN.
Speaker 3: We also made meaningful progress advancing our preclinical second generation protease inhibitor program and we anticipate finding an IMD for clinical candidate around the end of the year.
Speaker 3: also made meaningful progress, advancing our pre-Plinical Second Generation Produce and Ibitra Programme, and we anticipate finding a 9D for clinical candidate around the end of the year. With our HCV Programme,
Speaker 3: We completed preclinical and manufacturing work needed for the initiation of a phase two combination trial of Benifosbir and rizazbir in the second quarter. With our dengue program, we conducted two proof of concept studies for AT752, and the results will be shared with you today.
Speaker 3: Let's now move to COVID-19.
Speaker 3: Turning to slide five, Benifazovir is an oral nucleotide for drug that targets viral RNA polymerase, a highly conserved enzyme critical to viral replication and transcription.
Speaker 3: We believe that Benifosvavir profile addresses the key limitations of current therapies. It has low risk of drug-drug interactions and may be co-administered with commonly prescribed drugs for high-risk COVID-19 patients.
Speaker 3: a key limitation of PACS log. Scientific presentations demonstrating beneficial to the lack of drug-drug interaction were presented last week at the Conference on Retroviruses and Opportunistic Infections, also called CORE.
Speaker 3: The US COVID-19 public health emergency is set to expire May 11, and the market dynamics for COVID continue to shift.
Speaker 3: Based on the current variants, there are very limited treatment tools available, which essentially only packs love it for our patients.
Speaker 3: or vocabulary or remdesivir for hospitalized patients.
Speaker 3: The last thing of the public health emergency is going to make it even harder for this patient population to assess diagnostic and treatment.
Speaker 3: This is likely to lead to further morbidity and mortality, particularly in the most vulnerable.
Speaker 3: Moving to slide six, we believe COVID-19 will continue to remain endemic throughout the world and particularly impact the patient population that we are studying in Sunrise Street.
Speaker 3: We believe that all therapeutics will remain a multi-billion dollar opportunity for years to come, and projected annual COVID-19 all anti-viral U.S. demand using Accubia Retail Prescriptions.
Speaker 3: suggests the current estimated annual market opportunity over $10 billion.
Speaker 3: Beyond that, we believe that there is an opportunity to expand this market to patients with drug-junk interactions associated with SPACs lobby that are concerned, promoting and complicating prescribing.
Speaker 3: These include commonly prescribed drugs, such as seizure medications, antipsychotics, anticoagulants, and more.
Speaker 3: Let me remind you that Paxilarvit currently has 90% of the prescription market share and there is still a significant unmet medical need as less than 30% of COVID-19 patients are being prescribed an oral antirap. Going to slide 7.
Speaker 3: As we are moving to a traditional payer market, it is clear that we will have to demonstrate a value proposition of the impact of Beni-Pashevier against carbon.
Speaker 3: This will be achieved by using a primary endpoint of decrease in hospitalization and deaths.
Speaker 3: We believe that this will be the key consideration for drug reimbursement for COVID therapies in the future.
Speaker 3: This is why we are targeting the most vulnerable patient populations in Sunrise 3 who are the greatest risk. This is why we are targeting the most vulnerable patient populations in Sunrise 3 who are the
Speaker 3: for this is progression to severe COVID-19 or mortality, and for whom there are limited treatment options.
Speaker 3: Let's keep in mind that CMS estimates an average cost approaching $22,000 per hospitalization. And approximately 70% of COVID-19 related hospitalizations of hospitalized patients were covered under Medicare.
Speaker 3: Let's keep in mind that CMS estimates an average cost approaching $22,000 per hospitalization. And approximately 70% of COVID-19 related hospitalizations of hospitalized patients were covered in the Medicare. Moving to slide eight.
Speaker 3: Let's now review our innovative Sunrise-3 trial, our phase three registrational trial, which is evaluating Benifosvir as monotherapy and as combination antirheal therapy. Enrollments continue in this global phase three randomized double-blind placebo control study, which will evaluate Benifosvir or placebo.
Speaker 3: administered at the same time as locally available standard of care. Patients will be randomized one-to-one to receive with Benifazovir at 550 mg twice daily or placebo.
Speaker 3: We expect to enroll at least 1,500 high-risk patients with mild or moderate COVID-19. Two study codes defined by the type of standard of care the patients receive will be studied.
Speaker 3: The first call is a monotherapy cohort that will be comprised of patient receiving supportive care, which represent the primary analysis population. The second call is a combination and Tival cohort that will be comprised of patients who are receiving a compatible antivow against COVID-19.
Speaker 3: as part of the spandrel care. The primary endpoint of the study is all-cause hospitalization of deaths through day 29 in at least 1,300 patients from the Monotherapy Corps.
Speaker 3: You will recall that we have already evaluated hospitalization in the Morning Sky trial and been forced to be assured that 71% reduction.
Speaker 3: in hospitalization versus placebo. And importantly in addition, the subgroup analysis showed an 82% reduction in patients over 40 years old.
Speaker 3: The study is expected to have a large global footprint with up to 300 clinical sites in 25 countries and 50 countries.
Speaker 3: including the United States, Europe , Japan and the West of the world.
Speaker 3: Moving now to our Epitide C program, which we believe has the potential to become a best in class combination. For more information, visit www.epitide.com
Speaker 3: with the potential to improve upon the current standard of care by offering a shorter duration for the health and the freedom of free treatment for patients with HCV.
Speaker 3: to improve upon the current standard of care by offering a shorter duration, PRA-DS inhibitor-free treatment for patients with HCV.
Speaker 3: I outlined our phase two open label study of beneficial and in HCV patients. The study will involve approximately 280 HCV infected direct acting anti-viral naive patients across all genotype
Speaker 3: including a lead and course of approximately 60 patients. Patients will be administered 550 milligrams Benifazovir in combination with 180 milligrams visit via once daily for eight weeks.
Speaker 3: The primary endpoints of the study are safety and sustained biological response or SVR at week 12 post-street.
Speaker 3: Other virologic endpoints include virologic failure, SVR at week 24 post-treatment, and Saline resistance
Speaker 3: Regular submissions for the initiation of the trial are ongoing, and dosing of patients in this clinical trial is expected to begin during the second quarter. Initial data from the leading cohort of approximately 60 patients is anticipated around the end of the year.
Speaker 3: Turning to slide 12, I will now provide an update on our program for AT752 intervention against dengue. incarceration press
Speaker 3: We have been a pioneer in the development of a neuro-active-alteremputic for dengue. Our proof of concept study, DEFEND-2, demonstrated that AC-752 treatment is a
Speaker 3: led to a faster resolution of fever, which is the demajor clinical sign of Dengue.
Speaker 3: However...
Speaker 3: The FedTru also highlights the need for better diagnostics to identify patients earlier in the course of the disease, and also the need for a large sample size to account for the high variability for treatment and for prophylaxis as well.
Speaker 3: To address these factors, robust phase two studies would require long clinical timelines with major associated costs, which has led to the business decision to deprioritize the dengue program.
Speaker 3: To address these factors, we will bust phase two studies. We will require long clinical timelines with major associated costs, which has led to the business decision to deprioritize the DANGY program. Turning to slide 13.
Speaker 3: As you may recall, we have been conducted two studies to assess the efficacy of AT752 in the treatment and prevention of dengue field.
Speaker 3: we have been conducted two studies to assess the efficacy of AT752 in the treatment and prevention of dengue fever. For
Speaker 3: First, the Defend 2 Phase 2 clinical trial was randomized placebo control and conducted in dengue endemic areas. It involved patients with dengue fever within 48 hours of the inserta fever.
Speaker 3: and the diagnosis of dengue confirmed with a positive NS1 antigenemia test. The primary endpoint of this trial was changed in dengue viral load from baseline with exploratory analysis looking at the change in viremia, NS1 level and fever.
Speaker 3: In the first cohort of DEFEND2, we enrolled 21 patients in India, Thailand and the Philippines.
Speaker 3: We have also been conducting a human infection challenge trial under a US IMD. The healthy subjects were treated on day one with 8752 of the SIBO and then injected with a live, attain-ended strain of Dengit Type I on the following day.
Speaker 3: subject with those with AT752 of placebo for a total of 14 days.
Speaker 3: subject will then monitor for symptoms, viremia, and that's one level in safety. Let's move to slide 14.
Speaker 3: This schematic depicts our understanding of the time course of dengue illness. As you can see, there is a lag between infection and viremia. And viremia precedes the development of symptoms and time.
Speaker 3: Our study was designed to enroll patients around day six of infraction. Based on the data that we will now review, patients likely presented later in the course of the disease had enrollment. On slide 13, you can see that the viral load changes over time.
Speaker 3: through day seven as measured by PCR. Placebo patients are depicted in red and AT752 patients on the right in blue. Please notice that the study involved patients with all four several types of dengue.
Speaker 3: and it is well known that the viral kinetics of each serotype are quite different. At enrollment, patients presented late in the quarter of the disease with high variability and low viremia level at baseline.
Speaker 3: particularly in the placebo arm, which adds three patients with viremia levels below the lower level of quantification.
Speaker 3: particularly in the placebo arm, which adds three patients with viremia levels below the lower level of quantification. As a consequence...
Speaker 3: The primary endpoint of change in variable decline, as you can appreciate from baseline, is unaviable. Moving to slide 16.
Speaker 3: Placelists are a biomarker of dengue progression. You can see in this slide the trajectory of placeless counts from baseline to day seven for both the AT752 treatment arm and placebo.
Speaker 3: Consistent with the VIMIA data and baseline, platelets who were already low are below the lower limit of normal.
Speaker 3: In the majority of patients further demonstrating late presentation of disease at enroll.
Speaker 3: Turning to slide 17, as I have mentioned, the fever is the major clinical sign of danger. This slide demonstrates the time to resolution of fever defined as the temperature of the fever.
Speaker 3: of 37 degrees Celsius or less, sustained for 24 hours, and maintained through day five. In a pre-specified exploratory endpoint,
Speaker 3: in patients who presented with body temperature above 37 degrees Celsius. The median time to fever resolution was four days in the AT752R.
Speaker 3: and greater than five days in the placebo arm.
Speaker 3: greater than five days in the placebo arm. Slide 18.
Speaker 3: shows the change in body temperature for those patients who presented with a temperature of more than 37 degrees Celsius at baseline.
Speaker 3: In a post hoc analysis, there was a difference in body temperature change from baseline of 0.9 degrees Celsius at day three in favor of the 80......
Speaker 3: as compared to the placebo. Also, at day three, 100% of patients were presented with baseline body temperature above 37 degrees Celsius, as a reduction in body temperature below the baseline levels in the AT752 arm versus only 33% of patients.
Speaker 3: the placebo. Moving to slide 19.
Speaker 3: The safety profile of AT752 was favorable in the study, and there were no drug-related SAEs, and adverse events were largely mild to moderate and occur at similar frequency with those in the placebo group.
Speaker 3: Two non-drug related SAEs which were hospitalization due to thrombocytopenia and disease progression to severe dengue occur. One out of seven in placebo and one out of 14 in the AT75UR.
Speaker 3: Although non-serious adverse events were mostly mild and moderate, self-limiting, and occurred in comparable frequency inactive and placebo-1.
Speaker 3: Turning to slide 20. The human infraction channel study was also a randomized double-blind placebo control trial evaluating 8752 dose of 750 milligrams TID.
Speaker 3: where dozing was initiated prophylactically, 24 hours ahead of subject receiving an injection of acetenated live Teng-Yuan virus.
Speaker 3: The available results in five healthy volunteers were uninterpretable due to the high variability observed in telogryomia, antigenemia, and the onset and severe radio symptoms.
Speaker 3: In addition, there were much lower drug exposures than those observed in phase one with normal volunteers and in defend two study with treatment patients who were very likely due to a lack of treatment.
Speaker 3: of those in compliance. For this type of study, it is clear that a much larger sample size of greater than 50 healthy volunteers would be needed to account for this high variability. I will now turn the call to Andrey Fokrone. I will see a photo review. I will find an Todd Shilotit.
Speaker 4: Thank you, Jean-Pierre. As Journe mentioned in her introductory remarks, earlier today we issued a press release containing our financial results for the fourth quarter and full year 2022. Those statements of operations and balance sheet can be found on Slides 22 and 23. Our balance sheet remains strong with cash, cash equivalents and market.
Speaker 4: and full year 2022, respectively, compared to $57.8 million and $167.2 million for the corresponding period in 2021. The decrease in R&D expense was primarily due to the elimination of the cluster arrangement with ROSE. In addition, in Q4-21,
Speaker 4: we recorded a $25 million expense due to the upfront payment related to our in-license of Rusevir from Merck.
Speaker 4: G&A expenses remained relatively consistent at $12.4 million and $48.7 million for the fourth quarter and full year 2022, compared to $13.2 million and $45.8 million for the corresponding period in 2021. Interest income and otheritech stock market in? NG street gone bulk Difficulty market mutant 3 Marketplace to China
Speaker 4: was $5.6 million and $11.2 million for the fourth quarter and full year 2022, compared to less than $0.1 million and $0.2 million for the same period in 2021. The increase was primarily the result of investing in higher yield marketable securities and higher interest rates.
Speaker 4: For 2023, our R&D spans will be driven principally by spending on clinical trials, including primarily our Sunrise 3, Phase 3 clinical trial for COVID-19 and our Hepatitis C, Phase 2 study of the combination of phenyphosphir and rusevir. And closing.
Speaker 4: Due to the deprioritization of our program for dengue, we are extending our cash guidance into 2020 SACS.
Speaker 3: I'll now turn the call back over to Jean-Pierre for closing remarks. Thank you, Andrea. In closing, on slide 25, we have a busy year ahead of us as we continue to advance our antiviral programs to fight serious viral diseases, especially for patients with limited treatment options. For more info, If you like to see more of our
Speaker 3: Importantly, we are well capitalized to fund our program to key inflection points and beyond. To the finish line with an extended cash runway now until 2026, due to depriotization of our DANGY program.
Speaker 1: With that operator, we will now open the call up to your questions. Thank you. At this time, we will conduct a question and answer session. As a reminder, to ask your question, you will need to press star 1-1 on your telephone and wait for your name to be announced.
Speaker 1: To withdraw your question, press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from Matthew Harrison of Morgan Stanley . Your line is open. Please go ahead. Hi, this is Steve from Matthew. Thanks for taking my question. So I want to ask, would you consider to license our authentic program?
Speaker 1: since you did prioritize this one. Thanks. I'm sorry, can you repeat the question? Oh, sure. Would you consider to license out your dengue program? Well, look, as you know, there is some nonprofit agency and government agency and other sub-parlies as well.
Speaker 3: that are the potential to be interested in the collaboration partnership. We are not giving our guidance on and on if this could happen, but certainly we are trying to keep the collaboration in together and find everything in discussing with sir Paoli's
Speaker 5: Thank you one moment for our next question. Our next question comes from Tim Lugo of William Blair. Your line is open. I stand foroonjche
Speaker 6: Hi, this is John on for Tim. Thanks so much for taking our questions, so maybe two from us. So I'm wondering if you can maybe just give us some color commentary on your confidence and enrollment of the Sunrise Study. I mean, obviously we're seeing a lot more apathy towards COVID and there's less reporting that's going on. This is seeming to show, you know, it seems like trends are going in our favor, but sometimes it's a little hard to tell with the lower reporting.
Speaker 2: Maybe you could just tell us something about what you're seeing coming through, especially in the higher-risk populations. Yep. Janet? Thank you, John . Yes. Enrollment is continuing in Sunrise, and we're making good progress. We filed our clinical trial in all targeted countries for regulatory approval. We are continuing to see enrollment, but we're not going to provide specific numbers at this point.
Speaker 6: And we will continue to pull for the data through. Maybe just one more from us. So I'm seeing some articles now coming out that viral rebound is more common than we initially might have thought. Regardless of treatment with an antiviral, such as pet flow, very
Speaker 6: I'm wondering if you maybe have any updated thoughts about this or the time course is just too short. Is this maybe fixed with a combination and maybe how you're thinking about this longer term? Janice, you want to address the question?
Speaker 2: Yes, thank you. Yes, we've been watching the reports also with some interest, and there seems to be a variety of theories, I think. So, really, you'd have to call them as to what the cause for viral rebound may be. And it's something that we're certainly watching in our study. We're going to be collecting information about the cause for viral rebound.
Speaker 2: and also continuing to watch patients for symptoms of rebound as well as just plain viral rebound as we conduct the study. And so we hope to get some further clarity and information on that. But I think the jury is probably still out as to exactly what happens here, whether it's variant-specific, whether it's dependent on viral load and a much higher viral load, and perhaps needing longer times to clear.
Speaker 3: it's still something that I don't think we fully understand. But thank you for the question. If I may just add, it sounds like in some postdoc analysis or some trial, there is a rebound, ID dependent on the age of the patients. And so we hope that with our...
Speaker 3: high-risk patient population, actually, mostly in the elderly, we are going to really evaluate, as Janet indicated, those potential rebounds and the impact of the combination.
Speaker 5: Okay, thanks. Very helpful. Thank you very much. As a reminder, to ask a question, you need to press star one one on your telephone and wait for your name to be announced.
Speaker 5: One moment for the next question. This question comes from Rana Rees of SBB Securities. Your line is open. Go ahead.
Great, thanks. Afternoon everyone. I appreciate you walking us through the Denge results. So I'll start there. I was curious if you could clarify which factors seem to contribute the most to the unavailable results for defend to sourcing different things like I made possibly trial execution. Maybe there are some.
I have indicated, and I'm going to let Aransa, that let's not forget that fever is the major clinical sign of dengue. So, Aransa, why don't you address the question, please?
Yes, thank you. Thank you for the question. So, I guess that my home to be the true the, the very low to be unevaluable. I think that the main reason is that the patients tend to come later in the course of the disease. And as you can see in the slide, a lot of them, particularly in the placebo.
have already either low or undetectable violence by the time they come to you. And they come to you later. It's not unusual. We mandate a 48-hour fever criteria. But patients sometimes have a hard time identifying really when the fever started exactly. And so they probably came later, presented later, by the time, you know, we were able to involve them.
Another factor is that the tests that we use for involvement, the NS-1 antigen, is an antigen test. And as you've seen with COVID, antigen tests are not often very sensitive. They're not as sensitive as PCR, but sites don't have PCR available. So we will need to develop better, more sensitive diagnostic tests if we want to advance programs like this. So those are contributing factors. And with regards to the efficacy question, I think what we have seen in this data…
is a resolution of fever that is factoring more rapidly in the active. And as you know, fever is the main clinical sign for dengue. In fact, it's called dengue fever. And so we think that the resolution, past the resolution of fever, even considering such a small data set, is quite interesting and promising a signal in this trial.
Got it. Thanks for clarifying. Another question on the COVID program. Could you remind us what you want to see in the Sunrise III interim to encourage you to move forward? If we fast forward and get positive final results, do you still think EUA is on the table with the FDA? Janet? Yes, and I have shared so much information with all the fuckers about my My Our STRUGGLING
So, we're planning to do an interim analysis when we achieve enrollment of 60 percent of the patient population in the study. And, as you know, the primary endpoint is the proportion of patients who require hospitalization. So, we're looking to see something to suggest that we're going to an overall hospitalization rate inpatient population of ideally 4 to 6 percent of what we're anticipating. And we still think that, actually, in the patient population that we're going after in the study, that this is not an unreasonable number, and there have actually been some recent articles coming out, I think, in support of that.
Where we can plan to be that. Okay, great. Thanks a lot. Thank you. One moment for our next question. This question comes from the line of Umar Rafat of Evercore ISI. Your line is open. Hi, this is Jessica Huayon for Umar. Just one question. We're trying to reconcile the Sunrise 3 study design with that of a competitor, oral COVID antiviral, especially in light of the announcement last month that the COVID public health emergency will end in May. Specifically, the FDA took issue with a placebo controlled study in the US.
So I just want to confirm that in the Sunrise III trial, the randomized monotherapy population will still include U.S. patients, and you don't expect the FDA to want you to change your trial design. The short answer is no, but Janet, what is the extent of my answer? Sure. Yes, the answer is no. The FDA has endorsed and reviewed our phase III clinical trial, and I think as we described, patients are being randomized to drug or placebo on top of what is the available standard of care for the patient where they are. And actually, I think as Jean-Pierre mentioned in his remarks, there actually are a significant number of people, and actually, particularly unfortunately, in the most vulnerable patient population.
people who are unable to take past COVID because of drug interaction. And so for patients such as these, our drug is administered on standard of care, which would not include a direct vaccine antiviral. We do allow patients to have access to direct vaccine antivirals, monoclonal antibodies, if those were to be considered to be effective, and patients are allowed to be vaccinated also. But many patients, we believe, will actually not be taking anything other than our drug or procedure because of these circumstances.
Okay, thank you. One moment for another question. We have another question from Rana Ruas of SVB Securities. Your line is open. Hey, yeah, thanks for taking the extra question. I just want to circle back about the possibility of an EUA for Bendithosivir. Do you have any updated thoughts on that? Janet? I'm so sorry. I realized as soon as I finished that I hadn't answered your question completely. Yes. So we believe that emergency use authorization is still possible. I think it's at the discretion of the Health and Human Services to allow for EUAs even with the passing of the – or the lapsing of the pandemic health emergency. So we believe it will be data-driven and depending on what we see as to whether contracting might be possible, but we believe it is.
Still possible should we have good results, even at the interim analysis. OK, great. Thanks. Thank you. That concludes our Q&A segment. I'll now turn it back over to the Attea Pharmaceuticals team for any closing remarks. Again, thank you all for joining us today. And thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
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Good Afternoon, ladies and gentlemen. Welcome to the Atayah Farmaceuticals, Fourth Quarter and Full Year 2022 Financial Results and Business Update Conference call. At this time, all participants are in a listen-only mode. Following the formal remarks, we'll open the call-up to your questions.
To ask a question during the session, you need to press star 1 1 on your telephone, but then hear an automated message advising you that your hand is raised. To withdraw your question at any time, press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to turn the call over to Jonay Barnes, Senior Vice President of Investor Relations and Corporate Communications at Attea Pharmaceuticals. Ms. Barnes, please proceed. Thank you, operator. Good afternoon, everyone, and welcome to Attea Pharmaceuticals' fourth quarter and full year.
2022 Financial Results and Business Update Conference Call. Earlier today, we issued a press release which outlines the topics we plan to discuss. You can access the press release as well as the slides that we'll be reviewing today by going to the investor section of our website at ir.ateafarma.com. With me from Itea are Chief Executive Officer and Founder, Dr. Jean Pierre Semidosi, Chief Development Officer, Dr. Janet Hammond, Chief Medical Officer, Dr. Ron Chahorga, Chief Financial Officer and Executive Vice President of Legal, Andrea Corcoran, and our Chief Commercial Officer, John Davrika. They will all be available for the Q&A portion of today's call. Before we begin the call, as outlined on slide two, I would like to remind you that today's discussion will contain forward-looking statements that involve risk and uncertainties.
These risks and uncertainties are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which we encourage you to read. Our actual results may differ materially from what is discussed on the call. With that, I'll now turn the call over to Jean-Pierre. Thank you, Jonay. Good afternoon, everyone, and thank you for joining us. As you will see on slide three, this year we are forced to continue the meaningful progress made across our advanced clinical development programs following strong execution in 2022. Clinical advocacy results from the Morning Sky trial informed our Phase III Sunrise III trial of Beniposvivir for the treatment of COVID-19, which was initiated in the fourth quarter of 2022. We anticipate an interim analysis from the Sunrise III trial in the second half of this year, followed by completion of enrollment by year-end. We also made meaningful progress in the second half of the year, followed by complete implementation of the Padre
Advancing our pre-plinical second-generation produce inhibitor program, and we anticipate filing a 9D proclinical candidate around the end of the year. With our HCV program, we complete pre-clinical and manufacturing work, needed for the initiation of a phase 2 combination trial of any positive and a result of the year in the second quarter. With our DANGY program, we conducted two proof-of-concept studies for 87.52 and the results will be shared with you today. Let's now move to COVID-19. Turning to slide 5, Benny Fossivier is on all nuclear-type quadriple. The target file I have in the polymerase, a highly conserved enzyme critical to valve replication and transcription. We believe that Benny Fossivier profile addresses the key limitations of current therapies.
It has low risk of drug drug interaction and may be core administered with commonly prescribed drugs for high risk COVID-19 patients, a key limitation of backlog. Scientific presentation demonstrating Bini-Polta-Villac of drug drug interaction were presented last week at the conference on RetroValuses and Opportunistic Infections, also called COAR. The US, the US COVID-19 Public Health Emergency, is set to expire May 11 and the market dynamics for COVID continues to show. The US, based on the current variance.
There are very limited treatment tools available with essentially only packs of it for our patients or VAC-VIRY or WEM-DISIVIA for our hospitalized patients. The last thing of the Public Health Emergency is going to make it even harder for this patient to assess diagnostic treatment.
This is likely to lead to further mobility and mortality, particularly in the most vulnerable. Moving to slide 6, we believe COVID-19 will continue to remain endemic throughout the world, and particularly impact the patient population that we are starting in sunrise 3.
We believe that all therapeutics will remain a multi-billion dollar opportunity for years to come, and projected annual COVID-19 all-antivoweled U.S. demand using Accuvia Retail Prescriptions suggests a current estimated annual market opportunity over $10 billion.
Beyond that, we believe that there is an opportunity to expand this market to patients with drug drink interactions associated with back flow with our concern, limiting and complicating prescribed. These include commonly prescribed drugs such as seizure medications, anti-psychotics, anti-coragulants and more.
Let me remind you that Paxilar with currently has 90% of the prescription market share and there is still a significant unmet medical need as less than 30% of COVID-19 patients are being prescribed an all-empty route.
Turning to slide 7, as we are moving to a traditional payer market, it is clear that we will have to demonstrate a value proposition of the impact of many parts of the vehicle against carbon. This will be achieved by using a primary endpoint of decrease in hospitalization and death.
We believe that this will be the key consideration for drug reimbursement for COVID therapies in the future. This is why we are targeting the most vulnerable patient populations in Sunrise 3 who are the greatest risk for disease progression to severe COVID-19 or mortality and for whom there are limited treatment options.
Let's keep in mind that CMS estimates an average cost approaching $22,000 per hospitalization and approximately 70% of COVID-19 related hospitalizations of hospitalized patients were covered under Medicare. Moving to slide eight, let's now review our innovative Sunrise III trial, our phase three registrational trial, which is evaluating Benifosvivir as monotherapy and that's combination anti-viral therapy.
Enrollment continues in this global phase three randomized double-blind placebo control study, which will evaluate beneficial placebo, administer at the same time as locally available standard of care. Patients will be randomized one to one.
to receive video of Benifazovir at 550 milligrams twice daily of placebo. We expect to enroll at least 1500 high-risk patients with mild or moderate COVID-19. Two study codes defined by the type of standard of care the patients we see would be studied.
The first cohort is a monotherapy cohort that would be comprised of patients receiving supportive care, which represents the primary analysis population. The second cohort is a combination antiviral cohort that would be comprised of patients who are receiving a compatible antiviral against COVID-19 as part of the sprenal care. The primary endpoint of the study is all-cause hospitalization of deaths, through day 29, in at least 1,300 patients.
from the monotherapy cohort. You will recall that we have already evaluated hospitalization in the Morning Sky trial and been forced to be assured that 71% reduction in hospitalization versus placebo. And importantly in addition, the subgroup analysis showed that 82% reduction in patients over 40 years old. Sunrise 3 were focused on high risk patients that are the greatest risk for disease progression to severe COVID-19 or mortality. The study is expected to have a large global footprint with up to 300 clinical sites in 25 countries, including the United States, Europe .
Japan, and the rest of the world. Moving now to our Epitide C program, which we believe has the potential to become a best-in-class combination, with the potential to improve upon the current standard of care by offering a shorter duration, pro-adhesive inhibitor-free treatment for patients with HCV. Slide 10 outlines our Phase II open-label study in 24th VeVIA and Wiss-Wiss VIA in HCV patients.
The study will involve approximately 280 HCV-infected direct-acting anti-viral-naive patients across all genotypes, including a lead-in cohort of approximately 60 patients. Patients will be administered 550 mg Benifazovir in combination with 180 mg Resas-VL once daily for eight weeks. The primary endpoints of the study are safety and sustained biological response, or SVR, at week 12 post-treatment.
Other virologic endpoints include virologic failure, SVR at week 24 post-treatment, and resistance. Regulatory submissions for the initiation of the trial are ongoing, and dosing of patients in this clinical trial is expected to begin during the second quarter. Initial data from the leading cohort of approximately 60 patients is anticipated around the end of the year. Turning to slide 12, I will now provide an update on our program for AT752 intervention against Zangi.
We have been a pioneer in the development of our neuro-antibiotic therapeutic for dengue. Our proof of concept study, DEFEND2, demonstrated that AC752 treatment led to a faster resolution of fever, which is the major clinical site of dengue. However, DEFEND2 also highlights the need for better diagnostics to identify patients earlier in the course of the disease, and also the need for a large sample size to account for the high variability for treatment and for prophylaxis as well. To address these factors, robust phase two studies would require long clinical timelines with major associated costs, which has led to the business decision to deprioritize the dengue program. Turning to slide 13, as you may recall, we have been conducting two studies to assess the efficacy of AC752 in the treatment and prevention of dengue fever.
and a pioneer in the development of our normal anti-viral therapeutic for dengue. Our proof of concept study, DEFEND-2, demonstrated that AC752 treatment led to a faster resolution of fever, which is the D major clinical site of dengue. However, DEFEND-2 also highlights the need for better diagnostics to identify patients earlier in the course of the disease, and also the need for a large sample size to account for the high variability for treatment and for prophylaxis as well. To address these factors, robust phase two studies would require long clinical timelines with major associated costs, which has led to the business decision to deprioritize the dengue program. Turning to slide 13, as you may recall, we have been conducted two studies to assess the efficacy of AC752 in the treatment and prevention of dengue fever. For more information, visit www.aclu.org
First, the DEFEND-2 Phase II clinical trial was randomized placebo control and conducted in dengue endemic areas. It enrolled patients with dengue fever within 48 hours of the onset of fever and the diagnosis of dengue confirmed with a positive NS1 antigenemia test. The primary endpoint of this trial was changed in dengue viral load from baseline with exploratory analysis looking at the change in viremia, NS1 level and fever. In the first cohort of DEFEND-2, we enrolled 21 patients in India, Thailand and the Philippines. We have also been conducting a human infection challenge trial under a USIMD.
The healthy subjects were treated on day one with AT 752 of placebo, and then injected with a live attenuated strain of dengue type 1 on the following day. Subject were those with AT 752 of placebo for a total of 14 days. Subject were then monitored for symptoms, viremia, and S1 level and safety. Let's move to slide 14.
This schematic depicts our understanding of the time course of dengue illness. As you can see, there is a lag between infection and viremia. And viremia precedes the development of symptoms and time.
Our study was designed to enroll patients around day six of infraction. Based on the data that we will now review, patients likely presented later in the course of the disease had enrollment. On slide 13, whencharging Sun HIP C democratization Running to around Bidens Woods
You can see that the viral load changes over time through day seven as measured by PCR. Placebo patients are depicted in red and 87.52 patients on the right in blue.
Please notice that the study involved patients with all four serotypes of dengue, and it is well known that the viral kinetics of each serotype are quite different.
Please notice that the study in more patients with all four stereotypes of Dengue, it is well known that the volcanetics of each stereotype are quite different. At enrollment.
Patients presented late in the quarter of the disease with eye variability and low pyrimia level at baseline. Particularly in the placebo arm, which adds three patients with pyrimia levels below the lower level of quantification. As a consequence, the primary endpoint of change in viral decline, as you can appreciate from baseline is unavoidable. Moving to slide 16. Placeless are biomarker of Dengie progression.
You can see in this line the trajectory of places counts from baseline should they suffer for both the 8750 treatment of and placebo. Consistent with the value of the verimiodata at baseline, place lets we are already low a billar to lower the limit of normal.
in the majority of patients further demonstrating late presentation of disease as in Rome. Turning to slide 17, as I have mentioned,
The fever is the major clinical sign of day. This slide demonstrates the time to resolution of fever defined as a temperature of 37°C or less sustained for 24 hours and maintained to day five. In a pre-specified exploratory endpoint.
In patients who presented with body temperature above 37 degrees Celsius, the median time to fever resolution was four days in the AT752R and greater than five days in the placebo R.Biopopnar type 18 shows the change 22 hours in
In body temperature, for those patients who presented with a temperature of more than 37 degrees Celsius, add baseline. In a post-all canal,
temperature for those patients who presented with a temperature of more than 37 degrees Celsius at baseline. In a post hoc analysis, there was a difference in the temperature of the patient's blood temperature by roofs out to police.
in body temperature change from baseline of 0.9 degrees Celsius at day 3 in favor of the 80 faster of the 80 7 5
as compared to the placebo arm. Also, at day three, 100% of patients were presented with baseline body temperature above 37 degrees Celsius, at the reduction in body temperature below the baseline levels in the AT752 arm, versus only 33% of patients in the placebo arm.
compare to the placebo. Also, at day three, 100% of patients who presented with baseline body temperature above 37 degrees Celsius, had a reduction in body temperature below the baseline levels in the 87.5 to arm versus only 33% of patients in the placebo. Moving to slide 19.
The safety profile of 87.52 was favorable in the study and there were no direct related essays. And adverse events were largely mild to moderate and occur a similar frequency with those in the placebo group.
Two non-drug related SAEs which were hospitalization due to thrombocytopenia and disease progression to severe dengue occur. One out of seven in placebo and one out of 14 in the AT75
Although non-cellular adverse events were mostly mild and moderate, self-limiting, and occurred in comparable frequency inactive and placebo-1. Turning to slide 20, the human infraction channel study was also a randomized, double-blind placebo control trial evaluating AT752 dose of 750 mg TID.
where dosing was initiated prophylactically, 24 hours ahead of subject receiving an injection of adtenuated live-dangu-wan virus. The available result in five healthy volunteers were uninterruptible due to the high variability observed in cello-vibramia, antigenemia, and the onset and severity of symptoms. In addition, there were much lower drug exposures.
Then those observed in the phase one with normal volunteers and in defense two study with treatment patients who are very likely to do a lack of those in compliance. For this type of study, it is clear.
that a much larger sample size of greater than 50 healthy volunteers would be needed to account for this eye variability. I will now turn the call to Andreypokrone. I will see a photo review. I will find an update. Thank you, Sample here.
As Johnnay mentioned in her introductory remarks earlier today, we issued a press release containing our financial results in fourth quarter and full year 2022. Those statements of operations and balance sheet can be found on slides 22 and 23.
Our balance sheet remains strong with cash, cash equivalents, and marketable securities at $646.7 million at December 31, 2022, compared to $764.4 million at December 31, 2021. R&D expenses were $27.5 million and $81.9 million for the fourth quarter and full year 2022, respectively, compared to $57.8 million and $167.2 million for the corresponding period in 2021. The decrease in R&D expense was primarily due to the elimination of the cost share arrangement with Roche.
In addition, in Q4-21, we recorded a $25 million expense due to the upfront payment related to our in-license of Rusevier from Merck. J&A expenses remained relatively consistent at $12.4 million and $48.7 million for the fourth quarter and full year 2022, compared to $13.2 million and $45.8 million for the corresponding period in 2021. In-house income and other was $5.6 million and $11.2 million for the fourth quarter and full year 2022, compared to less than $14.5 million for the second quarter and full year
0.1 million and 0.2 million for the same period in 2021. The increase was primarily the result of investing in higher yield marketable securities and higher interest rates. For 2023, our R&D spends will be driven principally by spending on clinical trials, including primarily our Sunrise 3, phase 3 clinical trials for COVID-19 and our Hepatitis C phase 2 study of the combination of phenyphosphir and rusevir. In closing, due to the deprioritization of our program for dengue, we are extending our cash guidance into 2026.
I'll now turn the call back over to Shumpir for closing remarks. Thank you Andrea. In closing on slide 25, we have a busy year ahead of us as we continue to advance our anti-vowel programs to find serious viral diseases, especially for patients with limited treatment options. Importantly, we are well capitalized to fund our program to key inflection points and be on.
to the finish line with an extended cash runway now until 2026, due to depriotization of our DANGY program. With that operator, we will now open the call up to your questions. Thank you. At this time, we'll conduct a question and answer session. As a reminder, to ask your question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, press star 11 again. Please stand by while we compile the Q&A roster.
Our first question comes from Matthew Harrison of Morgan's family. Your line is open. Please go ahead. Hi, this is B for Matthew. That's what I'm taking my question. So I want to ask, would you consider to license out your Dandenberg program? This is your D Prioritize, this one. Thanks.
I'm sorry, can you repeat the question? Oh, sure. Would you convener to license out your then gave program? Well, look, as you know, there is some nonprofit agency and government agency and other short policies as well that are the potential to be interested in the collaboration partnership.
We are not giving our guidance on at one if this could happen, but certainly we are interesting in discussing with third parties.
Thank you. One moment for our next question. Our next question comes from Tim Lugo of William Blair. Your line is open. Hi. This is John on for Tim. Thanks so much for taking our questions.
but sometimes it's a little hard to tell with the lower reporting. You could just tell us something about what you're seeing coming through, especially in the higher risk populations. Yeah. Janet.
Yes, so in Rome is continuing in sunrise and we're making good progress. We filed our clinical trial in all targeted countries for regulatory approval and we are continuing to see in Romans that we're not going to provide specific numbers at this point and that we will continue to report as the year goes through.
Maybe just one more from us. So I'm seeing some articles now coming out that viral rebound is more common than we initially might have thought, regardless of treatment with an antiviral such as PEX-LOVID. Wondering if you maybe have any updated thoughts about this, or the time course is just too short. Is this maybe fixed with a –
rebound may be. And it's something that we're certainly watching in our study. We're going to be collecting virological samples and also continuing to watch patients for symptoms of rebound as well as just playing on viral rebound as we...
conduct the study until we have to get some further clarity and information on that. But I think the jury probably still allows us to exactly what happens here, whether it's very specific, whether it's dependent on bowel load and a much higher bowel load and perhaps meeting longer times to clear. It's still something I don't think we fully understand. But thank you for the question.
If I may just add, it sounds like in some talk analysis or some trial, there is a rebound ID dependent on the age of the patients. We hope that with our high risk patient population, actually...
Mostly in the elderly, we are going to really evaluate as a Janet indicated those potential rebounds and the impact of the combination. Okay, thanks very helpful.
Thank you very much. As a reminder, to ask a question, you need to press star 11 on your telephone and wait for your name to be announced. One moment for the next question. This question comes from Rana Rees of SBB Securities. Your line is open. Please go ahead.
Great, thanks. Afternoon everyone, appreciate you walking us through the dengue results. So I'll start there. I was curious if you could clarify which factors seem to contribute the most to the unevaluable results for DEFEND-II. I started seeing different things like possibly trial execution.
As I have indicated, and I'm going to let Irensa, that let's not forget that fever is the major clinical sign of dengue. So, Irensa, why don't you address the question, please? Yes, thank you. Thank you for the question. So...
I think the main reason is that the patients tend to come later in the course of the disease. And as you can see in the slide, a lot of them, particularly in the placebo, are not
had already either low or an acceptable value by the time they come to you. And they come to you later. It's not unusual. We mandate 40-hour fever criteria. But patients sometimes have a hard time identifying really when the fever started exactly.
And so they probably came later, presented later, by the time we were able to involve them. Another factor is that the tests that we use for involvement, the NS-1 antigen is an antigen test. And as you've seen with COVID, antigen tests are not often very sensitive. They're not as sensitive as PCR, but sites don't have PCRs.
available, so we will need to develop better, more sensitive diagnostic tests if we want to advance programs like this. So those are contributing factors. And with regards to the efficacy question, I think what we have seen in this data is a resolution of fever that is factoring more rapidly in the active. And as you know, fever is the main clinical sign.
for Dengue, in fact it's called Dengue Fever. And so we think that the resolution, past the resolution of Fever, even considering such a small data set is quite interesting and promising as we think now in this trial.
Got it. Thanks for clarifying. And another question on the COVID program. So could you remind us what you want to see in the Sunrise 3 interim to encourage you to move forward? And if we fast forward and get positive final results, you do still think EUA is on the table with the FDA.
Janet? So, we're planning to do an interim analysis when we achieve enrollment of 60% of the patient population in the study. And, as you know, the primary endpoint is the proportion of patients who require hospitalization. So, we're looking to see something suggested by going to the overall hospitalization rate in the patient population of ideally 4 to 6% is what we're anticipating. So, we're planning to do that.
Thank you. One moment for our next question. This question comes from the line of Umar Rafat of Ebercore ISI. Your line is open.
Hi, this is Jessica, just one question. We're trying to reconcile the Sunrise 3 study design with that of a competitor oral COVID antiviral, especially in light of the announcement last month that the COVID public health emergency will end in May. Specifically, the FDA took issue with a placebo controlled study in the U.S.
I don't know what was the extent of my answer.
So yes, the answer is new. The FDA has endorsed and reviewed our phase 3 clinical trial. And I think as we described, patients are being randomized to drug-opercyber on top of what is the available standards of care for the patient where they are. And actually I think as John Tiam mentioned in his remarks.
There actually are a significant number of people and actually, particularly unfortunately, in the most vulnerable patient population, people who are unable to take past COVID because of drug interactions. And so for patients such as these, our drug is administered on standard of care, which would not include a direct-acting antiviral. We do allow patients to have access to direct-acting antivirals.
monoclonal antibodies if those were to be considered to be effective, and patients are allowed to be vaccinated also. But many patients we believe will actually not be taking anything other than our drug or procedure because of these circumstances. Okay, thank you. One moment for another question.
We have another question from Ron Arroz of SVB Securities. Your line is open. Hey, thanks for taking the extra question. I just want to circle back about the possibility of an EUA for being the FOSSEVIR. Do you have any updated thoughts on that?
We have another question from Rana Ruas of SVB Securities. Your line is open. Hey, yeah, thanks for taking the extra question. I just want to circle back about the possibility of an EUA for Bendith Fossevere. Do you have any updated thoughts on that? Janet?
I'm so sorry, I realized that soon as I finished that I hadn't gone into your question completely. Yes, so we believe that an emergency use authorization is still possible. I think that's the discretion of the Health and Human Services to allow four EUAs, even with the passing of the or the lasting of the of the pandemic health emergency. So we believe it will be data driven and depending on what we see.
as to whether such a thing might be possible. But we believe it is still possible should we have good results, even at the interim analysis. OK, great. Thanks. Thank you. That concludes our Q&A segment. I'll now turn it back over to the Attea Pharmaceuticals team for any closing remarks. Again, thank you all for joining us today.
And thank you for your participation today's conference. This does conclude the program. You may now disconnect.