Aldeyra Therapeutics, Inc. (ALDX) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by. And welcome to the Aldeyra Therapeutics conference call. [Operator Instructions] At this time, I would like to turn the call over to Mr. Joshua Reed, the company's Chief Financial Officer. Please go ahead, sir.

Thank you. And good morning, everyone. On the call with me are Dr. Todd Brady, Aldeyra's President and Chief Executive Officer; Dr. James Gow, Senior Vice President of Clinical Development; and Adam Brockman, Director of Nonclinical Development. Please turn to Slide 2. This morning's conference call contains forward-looking statements regarding future events and the future performance of Aldeyra. Forward-looking statements include statements regarding the timing of planned clinical trial initiations, Aldeyra's possible or assumed future results of operations, expenses and financial position, business strategies and plans, research, development and commercial plans or expectations, trends, market sizing, competitive position, industry environment and potential growth opportunities, among other things. These statements are based upon the information available to the company today. As a result of the COVID-19 pandemic, clinical site availability, staffing and patient recruitment have been negatively affected, and the time lines to complete our clinical trials may be delayed. Aldeyra assumes no obligation to update these statements as circumstances change. Future events and actual results could differ materially from those projected in the company's forward-looking statements, including the current and future impact of the COVID-19 pandemic on our business, results of operations and financial position. Additional information concerning factors that could cause results to differ materially from our forward-looking statements are described in greater detail in the company's press release issued this morning and our filings with the SEC. Now please turn to Slide 3 as I introduce Dr. Todd Brady, our President and Chief Executive Officer.

Thank you, Josh. And good morning, everyone. I'm thrilled to update you on the advancement of our second immune-modulating therapy with the potential to target COVID-19. ADX-1612, our novel HSP90 inhibitor, targets viral replication and infection. And as we announced this morning, ADX-1612 has demonstrated nanomolar potency similar to or greater than that of remdesivir in an in vitro model and to our knowledge represents one of the most potent antiviral drugs described for the SARS-CoV-2 virus to date. ADX-1612 may also downregulate pathological host immune responses, especially immune cell proliferation that leads to pulmonary congestion. What's particularly exciting is that we now have 2 distinct mechanistic approaches for the treatment of COVID-19. ADX-1612 complements ADX-629, our novel and orally available immune-modulating RASP inhibitor, which targets the aberrant and elevated host cytokine response that leads to respiratory compromise, including the requirement for mechanical ventilation and other forms of morbidity in COVID-19 patients. On Slide 5, the antiviral mechanism of ADX-1612 relative to that of other antivirals is illustrated. Viruses contained 2 general components: nucleic acids and proteins. And while most antiviral compounds, including remdesivir, target nucleic acid replication, ADX-1612 represents a distinct and, therefore, potentially synergistic approach that targets the viral proteome. Together, compounds that target nucleic acids and compounds that target proteins may represent a more effective antiviral treatment strategy than either type of drug alone. In in vitro experiments of SARS-CoV-2 infected transformed human cells, ADX-1612 was demonstrated to be at least as potent as and potentially substantially more potent than remdesivir in inhibiting viral growth and preventing cell death. Following treatment with ADX-1612, protection of infected cell viability was observed between 80 and 312 nanomolar, representing highly potent antiviral activity. ADX-1612 is a highly selective inhibitor of heat shock protein 90 or HSP90, which facilitates protein folding and, therefore, controls the activity and persistence of hundreds of client proteins, known collectively as the protein chaperone. As is shown on Slide 6, HSP90 is a well described antiviral target and is required for viral replication, host cell lysis and exit and cell infection. Other less potent HSP90 inhibitors have also demonstrated nanomolar potency against a variety of different viruses, including influenza, respiratory syncytial virus and hepatitis C. Importantly, a comprehensive genomic expression profile of the SARS-CoV-2 virus was recently completed and published online on May 5. The principal target highlighted in the analysis was HSP90, as can be seen on Slide 7. A low potency HSP90 inhibitor was tested against SARS-CoV-2 in vitro, demonstrating significant in dose-responsive reduction in viral load. The expression profiling results emphasize the uniqueness of HSP90 as an antiviral target and highlight the critical role of HSP90 and viral infection with SARS-CoV-2. The authors conclude that testing potent HSP90 inhibitors in COVID-19 represents a potentially important therapeutic strategy. Slide 8 presents clinical evidence for the antiviral activity of ADX-1612. A patient with an Epstein-Barr virus transformed T-cell lymphoma that was resistant to standard of care medications was treated with ADX-1612. The treatment resulted in a reduction in circulating EBV positive cells, approximately 50%, a finding that was supported by ex vivo activity of ADX-1612 against cells with viral infection. It's important to note that ADX-1612 has been clinically tested in over 1,600 patients in aggregate, and the pharmacokinetics, safety and tolerability of ADX-1612 have been well characterized. The protein chaperone is also critical for the proliferation of immune cells, elevated levels of which can lead to pathologic inflammation and disease. Slide 9 represents a case report of a patient with chronic refractory vasculitis and autoimmune condition before and after a single dose of ADX-1612, which resulted in substantial clinical improvement. The clinical findings are consistent with the activity of ADX-1612 in animal models of autoimmune disease, which demonstrate the activity of drug in reducing immune cell count. Thus, in addition to the potential antiviral activity, ADX-1612 has the potential to partially mitigate aberrant immune responses that lead to the morbidity and mortality of COVID-19. The planned trial design, which is subject to regulatory review and feedback from government agencies, is summarized on Slide 10. Consistent with other antiviral protocols, severe COVID-19 patients are intended to be enrolled. The treatment regimen is expected to be 2 doses of ADX-1612 over 3 days. Pending regulatory review, extension of dosing at investigator discretion may be possible. Standard clinical endpoints, including time to discharge, days in the intensive care unit, days in hospital and global clinical scores, are expected to be assessed. The ADX-1612 drug substance manufacturing process is well-characterized and optimized currently at a multi-kilogram scale. ADX-1612 is manufactured via a 3-step synthetic process, and current supply is expected to be sufficient to support the proposed Phase II trial and potentially subsequent Phase III trial. The ADX-1612 drug product is manufactured as a concentrate solution for intravenous infusion. The expected development milestones and clinical plans for ADX-1612 are listed on Slide 11. A Coronavirus Treatment Acceleration Program application, or CTAP, is expected to be filed this month with IND submission expected shortly after regulatory feedback, and clinical trial initiation is planned for the third quarter of this year. As many of you know, ADX-1612 is also being tested in the investigator-sponsored Phase II EUDARIO trial in ovarian cancer, which is expected to complete enrollment in June of this year. Moving to Slide 13. As we announced earlier this month, ADX-629, a novel, orally available RASP inhibitor, is in development for the prevention of cytokine release syndrome and other forms of aberrant inflammation that lead to severe respiratory compromise in COVID-19 patients. RASP are pre-cytokine modulators of inflammation. And by inhibiting RASP, ADX-629 and other RASP inhibitors, such as reproxalap, which is now in Phase III clinical trials for dry eye disease and allergic conjunctivitis, may prevent elevation of cytokine levels. In an animal model of cytokine storm, ADX-629 demonstrated broad and highly statistically significant reduction in cytokine levels, including TNF alpha, interferon gamma and IL-17, while upregulating the key antiinflammatory cytokine, IL-10. The data suggests that RASP inhibitors have the potential to represent immunological switches that may broadly modulate immune systems from pro-inflammatory states to antiinflammatory states. The planned trial design for ADX-629, which now reflects FDA regulatory review and feedback from other governmental agencies, is summarized on Slide 14. COVID-19 patients recently admitted to the hospital are intended to be enrolled. The treatment regimen is expected to be up to 28 days of ADX-629, administered orally twice per day. The proportion of patients on mechanical ventilation, time-to-discharge and other clinical outcomes in addition to cytokine profiles are expected to be assessed. As with ADX-1612, the ADX-629 drug substance manufacturing process is well-characterized and optimized at a multi-kilogram scale. ADX-629 is synthesized via a 5-step process. And Aldeyra believes that sufficient supply to support the proposed Phase II trial and potentially subsequent Phase III trials is available. The ADX-629 drug product is manufactured as either a tablet or capsule or as a powder for reconstitution for oral administration. The expected clinical milestones for ADX-629 are listed on Slide 15. Based on feedback from the FDA via CTAP, IND filing is expected midyear and clinical trial initiation planned for the third quarter of this year. In addition, following application to BARDA's CoronaWatch program, ADX-629 has been accepted for a CoronaWatch presentation with BARDA. The COVID-19 clinical program is 1 of 3 trials designed to systematically assess the immune-modulating potential of ADX-629 across the 3 major forms of inflammation: allergic disease representing TH2 type cytokine disease to be tested in atopic asthma; autoimmune disease representing TH1 type cytokine inflammation to be tested in psoriasis; and cytokine release syndrome, a combination of TH1, TH2 and TH17 cytokine inflammation, to be tested in COVID-19. Phase II trials in atopic asthma and psoriasis are expected to begin later this year. In summary, we are advancing 2 mechanistically distinct approaches that we believe have significant potential to modulate numerous targets associated with COVID-19. And we look forward to updating you on the potential developed milestones in the quarters ahead. Now we'll be happy to take your questions. Operator, please open the line.

[Operator Instructions] Your first question comes from Louise Chen of Cantor.

Congratulations on the strong data. My first question for you is, if these 2 products are approved for COVID, where would they fit in the treatment paradigm for COVID since there are a lot of drugs in development, and I think it would be helpful to understand where it fits here? Second question is, obviously, manufacturing, development will cost money. Do you plan to partner your COVID candidates with anybody, or are you going to go it alone? And then last question I have for you is, will there be any economic benefit for your COVID projects? Or do they help validate your science?

Louise, thanks for the questions. 629 and 1612 represent 2 very different treatment approaches that have roles in different parts of the treatment paradigm for COVID-19. ADX-1612, like other antivirals such as remdesivir, would be used for severe infection. These are patients that have intravenous lines and where severe respiratory compromise and other morbidities of COVID-19 are already apparent. In contrast, ADX-629 would be administered theoretically prior to severe COVID disease. And as I mentioned on the call today, the protocol potentially could specify if [Technical Difficulty] be enrolled for testing with ADX-629 immediately after admission to the hospital. So I think of 629 as being more prophylactic and preventative with regard to severe disease and 1612 like remdesivir to be more geared towards the treatment of severe COVID-19. In terms of your other questions about partnerships, we're always open to partnerships. My guess is as the treatment pipeline for COVID-19 evolves across the industry, there will be many partnerships. I think the ability to get a COVID-19 therapy in our company or other companies will likely depend on broad-based collaboration. So I think partnerships are certainly something that will be critical across the industry. In terms of economic benefit, too early to tell. I will say, though, with any company, not just Aldeyra that's working on COVID-19 treatments, there is a strong feeling of altruism. I think one of the benefits of being involved in biotechnology is the outcome of our work potentially has the potential to help patients across a variety of different diseases. And COVID-19 is just the latest of many diseases that we think would benefit from our therapies. Both 1612 and 629 are broadly applicable. Our company, Aldeyra, is based on systems-based approaches. That is we focus on drugs that have the potential to modulate numerous targets and thus would apply to many different diseases. So in the case of 1612, I mentioned the Phase II program in ovarian cancer. 1612 also has the potential to modulate other immune diseases that are characterized by immune cell proliferation. And I think of 629 likewise has the potential to apply to a broad-based series of immune-mediated diseases, and that's why we're testing it in the 3 different forms of inflammatory disease that I mentioned this morning, Louise.

Your next question comes from Adam Walsh with Stifel.

This is Edwin on for Adam. Congrats on the progress. First one on ADX-1612. Before an IND submission in the third quarter, do you need to do more studies and provide more data to the FDA? And also, do you know if there are any other HSP90 inhibitors are going to be tested in COVID-19 as well? Then I have a follow-up.

We're not aware, Edwin, of other HSP90 inhibitors there could be. We're not aware of any. I will say, as I pointed out in the presentation that HSP90 is a well-known antiviral target, not just for SARS-CoV-2, but for viral disease in general. Viruses generally require the host system for protein synthesis and folding, which means that for viruses to replicate nucleic acids, for them to exit the cell via exosomes, for them to lyse the cell for viruses to infect new cells. All of that is HSP90 dependent for many viruses, again, not just for SARS-CoV-2. So I wouldn't be surprised if there are other HSP90 developed -- programs in development. I'm not aware of any at the present time. Remind me of your first question, Edwin?

Do you need to do more studies before the IND submission between now to third quarter? Yes.

Correct. Right. No, that's a good question. The COVID-19 regulatory process is interesting. And I am extremely impressed with the FDA in terms of the efficiency and quality of their feedback that we've received for ADX-629. I expect the same thing for ADX-1612. So what's required going forward before IND or before clinical testing is to be discussed with not only FDA but other regulatory agencies. I will say that ADX-1612 has been in over 1,600 patients. So as I mentioned on the call, the safety, the tolerability, the pharmacokinetics, all of that has been well-characterized in a variety of different kinds of patients, including patients with hepatic compromise or renal compromise or pulmonary compromise. So I think we have a very good head-start in terms of Phase I type of data before entering the clinic for COVID-19.

Great. My second question is a big picture strategic question. We understand that you recently announced the company will prioritize the late-stage program in eye disease. Now we have 2 assets, 629 and 1612, to be tested in COVID-19, which is great. And we also know that you are looking for opportunities in psoriasis, atopic asthma and cancer. So my question is, are you considering to make a strategic change now? And how do you balance your current financial and human resources in these different therapeutic areas going forward?

The short answer is no. We're not making strategic changes, but I do think we're being nimble and reactive given COVID-19. As I mentioned, there is some altruism there, but it also helps us to accelerate the testing of our compounds in a clinical disease where there is severe inflammation. We are still very focused on reproxalap, which, as I mentioned in the call, is now in Phase III clinical trials for dry eye disease and allergic conjunctivitis. We remain optimistic about the prospects for reproxalap as it continues to advance towards NDA filing. We continue to support our retina program, the Phase III GUARD trial in proliferative vitreoretinopathy. Our mission all along in developing systems-based immune-mediating products has been to advance products in the eye initially as we recently announced and then progress towards retinal disease and systemic disease. I think the COVID-19 pandemic has accelerated that progression, and that's what you're witnessing here in the last -- at Aldeyra in the last couple of months.

Your next question comes from Justin Kim of Oppenheimer.

Congrats on the intriguing findings. Just wanted to drill down a little bit on the target patient population. As you look to signal generation for 629 and 1612, the device population seem to be quite broad. Just wondering, are there specific ideal patients that would be great for identifying such a signal for these respective agents?

I think that's a key point, Justin, and one that I attempted to elucidate a bit with Louise's question as well. And that is that the antivirals, I believe, will be used for severe disease. And so if you look at the proposed synopsis slide in the deck for 1612, the patient population looks and feel a lot like that, which is suggested for remdesivir. These are patients that already exhibit severe morbidity associated with COVID-19. The patient population for 629 is quite different. Because 629 is orally administered, because at least in animal model 629 has shown the ability to prevent or mitigate cytokine storm, the notion with 629 is to enroll patients just after admission to the hospital for respiratory compromise, so as to prevent escalation of the immune system, to prevent cytokine release syndrome and thereby prevent the requirement for mechanical ventilation and other heroic efforts to treat patients with severe disease. So that's how, Justin, I would bifurcate the 2 patient population. 629 is really geared towards earlier stages of disease. And like remdesivir, I think, 1612 would be geared towards the later stage of the disease.

Yes. I mean, that's an interesting point. Maybe just the follow-up on 629. There's been some hesitance to use sort of anti-inflammatories upfront. We've kind of seen sort of those immune-blocking agents use more sort of in the backlog. I'm just wondering what the differences mechanistically 629 might have that sort of give you confidence to use the agent more upfront in the paradigm?

I'm thrilled to talk about the mechanism of 629. Broadly, most immune-modulating agents that we have today target specific mediators. I think of anti-cytokine drugs targeting specific cytokines, JAK kinase drug targeting specific enzymes. The problem with that approach is toxicity and severe dysregulation of the immune system. So when you target a specific factor, you have a digital response on or off, like a light switch. And I think that leads to immune system dysregulation, which can, in theory, potentiate infection. So treating the immunological response to infection is a fine line, too much and the infection persists or exacerbates, too little and the host immune response becomes pathologic and leads to morbidity and mortality. I think the beauty of 629 mechanistically, at least, is that there's not one single target RASP or a family of targets, which, as I mentioned in the call on describing the cytokine results that are in the deck for 629, seem to represent a broad-based immunological switch or as we like to call it a dimmer switch, which allows for analog modification of the immune system. So we're not just shutting down one target. We're modulating the system broadly, which I think, in theory, allows for better adjustment of that fine line that I talked about when attempting to treat immunological disease associated with infection. It's not too much so as to allow persistence or exacerbation of infection and not too little so as to allow pathologic consequences of the immunological response.

Okay. Great. Maybe just a last question. I know you talked a little bit about through what the opportunity in COVID-19 is and sort of the intent behind developing these 2 agents. Is it right then to sort of maybe think about ARDS like infection complications as sort of an opportunity maybe that this might help give you that signal for sort of maybe in the way that the upcoming program for 629 are also sort of somewhat signal generating as well?

Correct. And I know we've had discussions with you about this in the past. And we agree with the notion that all drugs in development for COVID or most drugs, assuming they're not vaccines, but drugs or -- are, in a sense, advancing medical science in several different ways. But most therapeutics are not specific to SARS-CoV-2. And thus your notion about broader applications is absolutely correct. I think in developing these drugs, not just at Aldeyra, but across the industry, we're learning more about the biology of viruses, not just SARS-CoV-2. We're allowing for the development of therapeutics that could address future pandemics, if not the second and/or third waves of COVID. And finally, as you point out, success in COVID infection from an antiinflammatory standpoint portends success in viral pneumonias broadly and perhaps in ARDS and other forms of severe respiratory compromise. ARDS has been a problem for decades and still really has no good solutions. And I think one of the benefits, if you will, of the COVID-19 pandemic is that the biotechnology industry broadly is developing therapies that could be applied to ARDS and other severe forms of morbidity that you typically see in the intensive care unit, for which we have few therapeutic options today.

Your next question comes from Yigal Nochomovitz of Citigroup.

Todd, just I had a question on the virus neutralization assay. Can you just clarify, are these 2 assays that you use for your comparing remdesivir to 1612 the same assay or slightly different assays? And also, you mentioned the range was 80 to 312 nanomolars. The slide say 80 to 160. So could you just clarify?

Yes the cell-based assays, which are typically used to measure antiviral activity, are semi-quantitative and are qualitative. So generally, companies will give ranges for antiviral activity. And it depends on how the test is interpreted exactly. What we do know from the test is that it was run head-to-head versus remdesivir. So we have an idea in our own test of the potency of remdesivir, at least in terms of a range. And we have an idea of the potency of our own drug, at least in terms of a range. The potency of remdesivir has also been listed in the FDA fact sheet on remdesivir. So from a couple of different angles, I think, we're able to estimate where the potency of remdesivir is versus our own compound.

Okay. And the range that you cite, the 80 to 160, that -- is that EC50 as well?

Adam, would you like to comment? Adam Brockman is our Head of Preclinical. Would you like to comment on the assay cell?

Sure. Yes. So this is a measurement of cytopathic effect. And at this time, we don't have an exact read on EC99 or EC50. The simple fact is that the cells were protected at concentrations above 80 nanomolar and that protection was conserved up into higher concentrations without seeing any cytotoxicity.

Okay. Got it. And Todd, just going back to your comments around where you would deploy 1612, you said in the more severe infections and 629 more as a prophylactic. I'm just wondering, given the activity potentially against CRS, is there no role for 629 potentially even in more severe disease in view of combating CRS? Clearly, that would be a problem for the severe patients as well.

Yigal, the answer is yes. I do think there could be a role in the treatment of cytokine release syndrome. And certainly, the preclinical data suggests the potential of ADX-629 in that regard. The clinical trial, though, was designed to assess both prophylaxis and treatment. So the way the trial has been designed is that patients are at hospital enrollment begin treatment orally on 629. And because it's oral and because in this trial 629 will be administered via powder in a bottle for reconstitution, it can be administered via nasogastric tube if patients are intubated. So to get to your question about the treatment of severe disease, even with patients that require mechanical intubation, we'll be able to continue to administer ADX-629 through the course of the hospital stay and potentially, as patients are discharged down to the hospital floor and hopefully discharged from the hospital entirely.

Okay. That make sense. And then I think you mentioned that 1612 was an IV infusion. And how complicated or easy would it be to make an oral?

We have no plans right now to investigate oral administration of 1612. I do think, though, that one investigation we might take is the analoging of 1612 to generate compounds that may be orally available. But at this time, 1612 remains IV.

Your next question comes from Yale Jen of Laidlaw & Company.

Congrats on one more new compound into the study. Just a few quick ones. The first one, I just want to continue the previous one to confirm the virus neutralization assay level is at 80 to 160 or 80 to 330?

So the correct range is 80 to 320-or-so. Above that, we haven't fully tested the compound. And below 80, I think, there's so little drug that it's less likely to be active. But the range in terms of the cytoprotection data that Adam described is -- the broad range is 80 to 320. Again, these assays are semiquantitative. So what you do have is an idea of the range, especially relative to other compounds. In terms of EC50 and EC99, that requires a more complex series of experiments that we'll undertake in the future.

Okay. That's very helpful. Another follow-up here is that you mentioned that 1612 has certain level of anti -- or suppressing the immunity to some extent, relatively speaking. So would that be counter to the sort of desire for patient to build up their immune response or antibodies and T-cell response to fight out the infection later on? Was there any potential contradiction there?

So what's interesting is that in the 1,600 patients that have been tested so far, primarily cancer patients, we have seen no evidence of myelosuppression, at least not at the doses we would intend to test clinically with COVID. So I don't think that at the level we would intend to use for COVID treatment, we'll see any downregulation of the immune system that in turn turns out to be pathologic. As I mentioned before, there is always this fine line between too much immune systems downregulation and too little. In the clinic and again in lots of patients, we really haven't seen evidence of immune system dysregulation. It's an empirical question as to what dose do we see antiviral activity, at what dose do we see immune-modulating activity. I think we'll have to work that out in the clinic. My guess is we'll start with doses that are antiviral. As I just mentioned with Yigal's question, those levels are very, very low in the nanomolar range. We may not see immune-modulating activity until higher levels of drugs. But again, I think it will be an empirical question as to how to titrate the dose to maximize the antiviral activity and at the same time potentially prevent immune cell proliferation and other aberrant immune responses.

Okay. That's very helpful. Maybe 2 quick ones. The first one is in terms of the first study you proposed, would there be a dose so the ranging part of the -- for 1612? Or is it simply select 1 or 2 dose -- 1 or 2 doses?

The 2 comments I would make there, Yale, is that we have a very good idea of the maximally tolerated dose for this compound. So I think we know where to start. We have a very good idea of what levels are needed for viral inhibition. Certainly, the range -- ranges that we've talked about this morning. Whether there is dose titration or dose-ranging initially, whether that occurs in later trials, I think, is subject to FDA commentary. Certainly, we're open to all those trial designs. And my guess is at some point in the COVID-19 development plan there will be some dose ranging.

And maybe the last question here is that if the things work well, would you consider or maybe partner -- to consider production at risk before all the study ends? Or you will wait until more certain about the outcome before thinking about the mass production?

As we said this morning, I -- we have enough drug, we believe, to cover Phase II testing, for sure, for both 1612 and 629. Both compounds are optimized in terms of process, characterized at up to kilogram scale. So I think for the time being, clinical supply is readily available, potentially for Phase III clinical testing as well. That really depends on the size and timing of Phase III, which really depends on regulatory agency feedback and feedback from other government agencies as well. In the future, I think, we may look to manufacturing and supply partnerships. But all of that, I think, depends on the initial clinical data from the trials we've outlined today, Yale.

Your next question comes from Esther Hong of Janney.

So first, on ADX-1612, can you speak about safety and tolerability observed to date? And then second, when could we potentially see data from 1612 and 629?

Esther, 1612 is generally administered in cancer trials at 150 milligrams per meter squared. That turns out to be the optimal dose after many, many patients in Phase II and even a Phase III clinical trial following dose-ranging in Phase I. The dose-limiting toxicity in cancer is GI, gastrointestinal distress. And again, we have not seen the other typical anticancer side effects at the doses we intend to use clinically, including myelosuppression. Our starting dose for COVID may be at 150 milligrams per meter squared. It may be lower. I think that all depends on regulatory feedback. It probably also depends, per Justin's question, on the exact nature of the patient population we intend to enroll. But the good news is the drug from a safety and tolerability standpoint is extremely well characterized. In terms of the timing for data, I think, that's all to be determined, partially because we need to await for -- await INDs. We also need to see how the COVID landscape evolves. As you know, the therapeutic options in terms of investigational therapeutic options for COVID-19 are rapidly expanding. I think there is probably some competition for patients. However, I do not expect a severe shortage of patients, especially if there are future waves of COVID infection, which I think most experts would argue will occur. So -- but timing, if we begin in the third quarter for both of these compounds as we expect, timing could be anywhere from the end of the year to early next year, depending again on the size and nature of the trials that will be elucidated with regulatory feedback.

Your next question comes from Matthew Cross with JonesTrading.

Congrats on the steps forward here for 1612 and 629. I was wondering a few things about 1612. So first off, I guess, I was glad to hear that HSP90 was highlighted as a target for treatment of COVID-19 in this recent paper. But could you maybe speak to a couple of points here? One being the kind of relatively low positive correlation that was listed here between HSP90 mRNA and SARS-CoV-2 viral load. And then maybe also how effective this less potent HSP90 inhibitor that was described in the paper was in terms of reducing viral load in order to kind of contrast 1612's potency with this other HSP90? I'm trying to get a better sense of how much more potent 1612 needs to be relative to some of these results that we're seeing in order to be reasonably effective in this setting? And maybe taking into account that it may also be used as part of a combination.

Right. The combination, Matt, is fascinating because all of these tests are done with monotherapy. And as we know, in the clinical world, especially with COVID-19, there's unlikely to be monotherapy and for good reason because drugs can work additively or synergistically. So all of our comments today and the data that we've discussed are really all about monotherapy. And I think that empirically in the clinic we'll have a better idea of how these drugs behave in setting a polypharmacy as time goes on. The paper released on May 5 was particularly fascinating. First of all, a whole genome expression analysis was performed. I note that really the only target that's exclusively highlighted in that paper is HSP90, which is why the authors took the extra step of testing an HSP90 inhibitor. Now the inhibitor they used is a first generation HSP90 inhibitor of low potency as the authors point out, which is why they concluded that HSP90 inhibitors that are currently being clinically tested that represent the second-generation of compound is worth investigating for COVID-19. I think you correctly point out that the potency of the inhibitor used by the authors in that paper is in the hundreds of nanomolar. But we found that actually quite encouraging because it's certainly in the nanomolar range and confirm activity of HSP90 inhibitors as antivirals. And it also confirms the ranges we cited this morning, which are obviously lower [Technical Difficulty] authors reported with a lower potency HSP90 inhibitor.

Got it. Okay. That's very helpful, Todd. And then I had another question about kind of extrapolating from the results that 1612 was generated in EBV-infected patients. I guess, how much overlap would you say there is in the pathology of EBV and SARS-CoV-2 from what we know so far? And secondly, it looks like after producing more than a 50% reduction, if I'm reading the chart right here, in the number of infected cells, there was a bit of a resurgence over time. So I was wondering how we should interpret that finding? If this is related to kind of the number of patients involved in that analysis and just noise in data or something more serious like viral adaptation to the treatment?

I think it's noise in data. These -- the EBV-infected patient represents a single patient that was tested. So I don't know that we can draw conclusions quantitatively over time in terms of response. But your first point is absolutely correct, in that HSP90 is broadly used by viruses. All viruses in a way behave in the same manner. They infect host cells. They replicate their nucleic acids, either RNA or DNA. They form protein by hijacking the host protein synthesis system. And those proteins are designed to infer more nucleic acid replication and to build viral protein coats and other things. And then HSP90 is used for cells -- for viruses to exit cells and lyse cells. And then finally, HSP90 is important in the cellular infection process as viruses enter other cells. And that's true pretty much across all viruses. If you go to the literature, it's easy to find other nanomolar like potencies with HSP90 inhibitors for other viruses, and rubella is one that comes to mind. So I think the data we have in the deck, plus the data and the literature, plus the interest sort of broadly in the scientific community about using HSP90 as a broad-based antiviral approach, really supports the notion of investigating the 1612 in COVID.

Great. Okay. No, I think that all logically follows. Looking forward to seeing the results or the initiation of the trials at the very least in the second half of the year.

There are no further questions at this time. I will now return the call to Dr. Brady.

I want to thank you all again for joining us today for this important announcement. And as always, we look forward to keeping you updated on our progress.

This concludes today's conference call. You may now disconnect.