ALDX - NASDAQ

Good morning and to welcome to the Aldeyra Therapeutics Third Quarter 2019 Financial Results Call. My name is Andria, and I will be your operator today. [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.

Good morning, everyone. With me today is Dr. Todd Brady, Chief Executive Officer. Todd will begin today's call with an overview of our strategy and recent highlights. I will discuss our Q3 results, Todd will make some concluding comments and then we will be happy to take your questions. Please note that this morning's conference call contains Forward-Looking Statements regarding future events and the future performance of Aldeyra. Forward-looking statements include statements regarding 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, and 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. 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 earlier this morning containing financial results for the third quarter of 2019, and the Company's filings with the SEC. Now I will turn the call over to President and Chief Executive Officer, Dr. Todd Brady.

Thank you, Josh, and thank you all for joining us today. Aldeyra continue to make great progress across our novel clinical programs and immune-mediated diseases during the quarter. As you heard last week, we reached an agreement with the FDA on the innovative design of our invigorates Phase 3 clinical trial in allergic conjunctivitis, which we plan to initiate in the first half of 2020. In addition to discussing our recent accomplishments and upcoming milestones this morning, I would like to highlight an area that a number of investors have asked us to expand on as we move into next year, which is our strategy and vision for Aldeyra. As many of you know, Aldeyra is an immunology-focused biotechnology Company, developing novel pharmacotherapies to treat immune-mediated diseases. We are advancing a broad pipeline of drug candidates designed to down-regulate pro-inflammatory signaling that is linked to serious medical conditions not adequately addressed by current treatments. By inventing, developing, acquiring and commercializing next generation therapies, our goal is to reduce the burden of disease and help patients lead healthier lives. Our growth strategy is anchored by three pillars. First, researching, discovering and acquiring first-in-class compounds that target large markets as well as orphaned indications. Second, building and developing an innovative pipeline of clinical stage drug candidates with novel mechanisms that focus on the regulation of immune cell activation or proliferation; and third, advancing multiple late-stage programs that have significant advantages over current standard-of-care and ready and goes programs for commercialization. Much of our late-stage clinical work to-date has focused on anterior ocular inflammatory disease with reproxalap, the lead assets in our platform. Reproxalap is designed to target and inhibit pro-inflammatory molecules called RASPs, which are elevated in a range of diseases, including dry-eye disease and allergic conjunctivitis, where we have Phase 3 programs underway. To give you some context for the size of these markets, according to a recent study from current opinion and allergy and clinical immunology, the anterior ocular inflammatory disease affects more than 40% of the population in the U.S. alone, and last year accounted for nearly $11 billion in prescription drug expenditures. Based on our reproxalap’s favorable therapeutic profile and highly differentiated activity versus standard-of-care. We believe, it has the potential to be the next novel entrant in dry-eye disease, and also the next novel entrant in allergic conjunctivitis for the approximately 30 million allergic conjunctivitis sufferers in United States, who do not respond adequately to or are dissatisfied with anti-histamines. The safety and efficacy profile is topical ocular reproxalap is well established. To-date more than 1,000 patients have been dosed across 12 clinical trials with no observed safety concerns. Reproxalap has demonstrated a clinically significant and durable response and allergic conjunctivitis in broad and clinically relevant improvement in symptoms and signs of dry-eye disease. As a result, our pipeline of ocular disease therapy has generated strong interest and attention from ophthalmologists, optometrists, researchers and other key opinion leaders. In October, we presented at the Ophthalmology Innovation Summit and at The American Academy of Ophthalmology Annual Meeting in San Francisco. At AAO, our chief medical officer Dr. David Clark presented the results of our ALLEVIATE Phase 3 clinical trial and allergic conjunctivitis, the primary and secondary endpoints of alleviate were highly statistically significant and clinically relevant. Last week, we released expanded results from our completed allergen chamber clinical methods trial of topical ocular reproxalap in allergic conjunctivitis. Consistent with the positive results of ALLEVIATE reproxalap demonstrated highly statistically significant and clinically relevant improvement over vehicle for ocular itching, the approvable endpoints in allergic conjunctivitis, as well as for ocular redness and tearing, all of which in aggregate, comprise the primary symptoms and signs in patients suffering from allergic conjunctivitis. In addition to sharing the results, we discuss the design and primary endpoint for upcoming INVIGORATE Phase 3 clinical trial in allergic conjunctivitis. As in the earlier clinical methods trial, ocular itching and INVIGORATE will be assessed in an allergen chambers, an innovative and rigorous method that we believe is optimal for testing drug activity and allergic conjunctivitis. Combining the real world exposure of a field trial with the controlled allergen exposure of directly administering allergen to the eye. The primary endpoint of INVIGORATE will be achieved at statistically significant reduction in ocular itching between drug and vehicle is demonstrated at a majority of 11 time points in a pre-specified range from 110 to 210 minutes following chamber entry. In the completed allergen chamber trials reproxalap was statistically superior vehicle at every time point to be pre-specified INVIGORATE. And other reason highlights part one of our adaptive Phase 3 RENEW clinical trial in dry-eye disease remains on-track for completion this quarter, at which time we expect to report on the endpoints, dosing regimen and sample size planned for Part 2 of the trial. Dry-eye disease which afflicts an estimated 34 million patients in the United States is a persistently disturbing condition that represents one of the largest markets and ophthalmology and physicians and patients agree that currently available therapies are inadequate. From the front of the eye, we are expanding our ocular disease pipeline into the posterior segment with the initiation of the GUARD Phase 3 clinical trial of ADX-2191 and proliferative vitreous retinopathy, or PVR. PVR is a rare inflammatory disorder of the retina that leads to severe retinal scarring and blindness, occurring most commonly following retinal detachment repair surgery or ocular injuries. Approximately 4000 patients per year are diagnosed with PVR in the United States, and nearly double that number in Europe and Japan. There is no approved treatment for PVR that is highlighted by the FDA’s recent decision to grant Fast Track designation for ADX-2191. The Fast Track designation allows us to engage in regular communications with the FDA about the development plan, and qualifies ADX-2191 for priority review, enrolling new drug applications submission. The GUARD trial will compare recurrence rates of PVR rated retinal detachment across patients treated with a ADX-2191 or standard of care following surgical repair of retinal detachment. Initiation of patient enrollment for Part 1 of the trial is expected this quarter. Beyond the eye we are advancing novel immune mediated systemic portions of our pipeline on multiple fronts. Phase 1 clinical testing is underway for ADX-629. A novel orally administered RASP inhibitor for the treatment of systemic autoimmune disease, a class of conditions that in aggregate affects an estimated 50 million Americans. In addition, Phase 2 clinical testing of the chaperone inhibitor ADX-1612 is planned to start later this quarter in patients with post-transplant lymphoproliferative disorder, a rare and potentially fatal immunological disease that can occur following solid organ transplant. Now I will turn the call over back to Josh for the financial Review. After which I will close to the look of our anticipated clinical milestones and upcoming events, Josh.

Thank you, Todd. Turning to our Q3 results, we reported a net loss for the quarter of approximately $18.7 million, compared to a net loss of approximately $10.8 million for the third quarter of 2018. Basic and diluted net loss per share was $0.69 for the quarter, compared to $0.52 per share for the same period last year. Losses have resulted from the cost of research and development programs, as well as from our general and administrative expenses. Research and Development expenses were $16.2 million for the third quarter of 2019 compared to $7.9 million for the same period in 2018. The increase of $8.3 million is primarily related to the increase in clinical and pre-clinical development costs, manufacturing personnel costs and non-cash compensation costs related to a portion of upfront acquisition considerations that is subject to vesting based on continued surface. General and administrative expenses were $2.8 million for the third quarter of 2019, compared to $3.1 million for the same period last year. The decrease of $300,000 is primarily related to a decrease in consulting costs. In the third quarter of 2019 total operating expenses were $19 million, compared to $10.9 million in the prior year. Cash, cash equivalents and marketable securities at September 30, 2019 were $76.2 million which includes $15 million drawn from our debt facility in September of 2019. Based on our current operating plan, we expect our current cash, cash equivalents and marketable securities will be sufficient to fund our operations into 2021. Now, I will turn the call over to Todd for concluding remarks prior to opening the call for questions.

Thank you Josh. In summary, Aldeyra continue to make great progress in Q3 and advancing our immunology platform toward the goal of reducing the burden of disease and helping patients lead healthier lives. Looking ahead, this quarter, we expect to achieve several key milestones, including completion of part one of the RENEW Phase 3 clinical trial and dry-eye disease, followed by announcement of the endpoints, dosing regimen and sample size planned for Part 2. Initiation of Part 1 of GUARD Phase 3 clinical trial of ADX-2191 and PVR and initiation of the Phase 2 clinical trial of ADX-1612 for post-transplant lymphoproliferative disorder. In addition I want to let you know about a couple of upcoming events we will be presenting and hosting one-on-one meetings at the Stifel Healthcare Conference in New York on Tuesday, November 19th, and at the Jefferies Healthcare Conference in London on Thursday, November 21st. For those is attending. We look forward to meeting with you. Now, we would be happy to take your questions. Operator, please open the line.

[Operator Instructions] You have a question from Yigal Nochomovitz of Citigroup.

Hi Todd and Josh thanks for taking the questions. With respect to the renewed Phase 3 trial in dry-eye and specifically with respect to Part 1, could you just help bracket the scenarios for how Part 1 could complete? You mentioned endpoints dosing regimen and sample size plan for Part 2 ? but could you just comment a little bit more specifically in what you see is the most likely outcome for Part 1, and additionally what one might represent an upside case with respect to those variables? Thank you.

Right, good morning Yigal. Yes. So far, I think, sufficiently outlined the goal of Part 1, which is to clarify the dosing regimen and the endpoints and the sample size for Part 2. As you recall, Part 1 has really two trials intended within one trial that is a four times a day dosing regimen versus a four times a day vehicle regimen, and a four times a day regimen tapered down to twice a day regimen versus a corresponding vehicle control. So the goal of the trial primarily is not only to confirm the primary endpoint for the pivotal section of the trial, that is Part 2, but also to clarify the dosing regimen, which will advance. So one of those dosing regimens that I described will advance to Part 2 and that will certainly be disclosed this quarter in the next few weeks. I will say that there are a variety of scenarios in any clinical trial. Adaptive clinical trials are particularly interesting, because the first parts of those trials in this case, RENEW Part 1 are really designed to power the subsequent parts of the trial in this case RENEW Part 2. There is always the possibility that an endpoint can be hit, but I think the expected outcome of RENEW one is that we will proceed to Part 2 and that the nature of Part 2 will be described.

Okay great, and then just one question on vitreoretinopathy. As you mentioned you have the fast track designation. Do you believe that having breakthrough would be additionally beneficial, have you applied for breakthrough? Are you sort of satisfied with how the FDA is positioning this Fast Track approach?

We are obviously pleased about the FDA granting breakthrough status for ADX-2191 and PVR. It is easy to understand how that came about. There is no approved therapy for PVR. There is no treatment that is widely used for PVR aside from repeat surgeries, which lead to further instances of PVR. I think breakthrough therapy is often and extension of Fast Track and as we receive a data from the GUARD trial, which is also an adaptive trial, I expected applying for breakthrough would be a possibility.

Great. Thank you very much Todd.

Thank you.

Your next question comes from the line of Louise Chen of Cantor Fitzgerald.

Yes. Hey this is Sudan Loganathan in for Louise. Thanks for taking your questions, I have a few. So wanted to touch on the systemic disease indications for reproxalap. Are we still expecting to initiate on the Sjögren Larsson Syndrome after discussion with regulatory authorities and when do you expect that the timing for that to occur. And what other indications in the systemic is that making diseases are you very interested in for reproxalap going forward. And then secondly, I wanted to ask on the cash runway, are there any other abilities in 2020 to access more cash or how do you see that going forward as you push through these clinical trials in Phase 3 development? Thanks guys.

Thanks for the questions. I will let Josh answer the cash question in a moment. But let me comment on reproxalap. Obviously reproxalap continues to excel in ocular surface disease, which represents they describe I have described in the call today. Massive, underserved markets, not only in the United States but also worldwide. In terms of Sjögren Larsson Syndrome we have disclosed that we are in the process of discussing with regulatory authorities not only in the United States, but also in Europe, about the path for subsequent advancements. And the timings thus is unpredictable and will depend on the nature of those discussions. I do not envision other indications for reproxalap at this point, given the late stage - as I have described it in terms of ocular surface disease. We are obviously very excited though about other systemic applications of the RASP platform. And as I mentioned today, we have begun of Phase 1 clinical testing of ADX-629, which is a novel orally administered RASP inhibitor that has we think broad applicability to a variety of diseases systemically. Autoimmune disease is one of the most common classes of diseases worldwide. And even further inflammation and inflammatory signaling is prominent in many, if not most diseases that afflict human being. So we are obviously excited about the potential for ADX-629 in other novel RASP inhibitors that I think you will hear about shortly when administered orally or otherwise systemically. Josh I will turn it over to you talk about cash.

Sure thanks Todd. Thanks Sudan . Our cash position is strong. As I noted earlier, based on our current plan, we have got enough cash and marketable securities to take us into 2021 and pay for the RENEW GUARD and INVIGORATE trials. This does not include access to additional capital under our credit facility or the ATM. But the vehicle along with potential non-dilutive financing from partners provides flexibility if needed.

Awesome. Thanks guys.

Your next question comes from the line of Esther Hong of Janney.

Hi, good morning. So my questions on PVR. Can you talk a little bit more about the current standard of care and discuss any other therapies or approaches that are in development for PVR. And then also will 2191 only be used in patients after the first instance of detachment or kind of be used to patients who have failed retinal detachment surgery, thanks.

Thank you Esther. PVR is a terrible situation for patients in today's market. There is no approved therapy for PVR that we are aware there are no products in development for PVR, which represents clear unmet medical need. The sort of pathogenesis of PVR relates to retinal detachment. So, in patients either for idiopathic reasons or due to trauma, the retina will detach from the posterior segment of the eye that reattaching the retina is generally not a problem surgically either air, oil can be inserted into the into the eyes to hold the retina back on the ocular surface or the back of the posterior segment. The problem comes in a minority of patients that develop scarring as a result of that and as you mentioned, we think there are about 4,000 patients in the United States every year and about double that number outside the U.S. that develop PVR. The PVR causes scarring, it is aberrant fibrogenesis, it leads to further retinal detachments. There are two issues with the scarring, one is you cannot see through a scar. And the second is, the scarring pushes the retina back off the posterior segment of the eye, leading to other retinal detachment surgeries and the cycle continues. In our trial, to your question, we are enrolling patients that have had one retinal detachment due to PVR. And the other group that we are enrolling are patients that have suffered open globe injury, that has resulted in rental detachment, those patients are at high risk for PVR. The endpoint as I mentioned on the call is recurrence, that is the recurrence of retinal detachment due to PVR and we will be monitoring that end point over six months.

Great. Thank you.

[Operator Instructions] Your next question comes from the line of Adam Walsh of Stifel.

Hey guys, thanks for taking my questions this morning and we look forward to having you at our conference as well Todd. In terms of the RENEW Phase 3 clinical trial designed in dry-eye disease in the data that are coming up from Part 1, how important is it for you, Todd do you think to get a BID dosing regimen, obviously you are doing a tapering arm in the trial, so I'm curious to know how important you think that is if it all some docs that we have talked to have suggested that in dry-eye disease that perhaps as a QID dosing regimen is actually potentially for preferred. And then on the tapering schedule, it looks like you go QID for weeks one to four and then BID for weeks five to 12. How did you come up with that? And then the final question is on the FORMULATION trial that you are running to increase resilience time in the eye, will those data be put out at the same time as the RENEW Part 1, and are those data gaiting for a Phase 3? Thanks.

Thank you and thanks again for invitation to the conference, we look forward to seeing you there. The Part 1 of RENEW is really designed to assess two different dosing regiments for a couple of reasons. Number one, we are big believers in the loading dose, maintenance dose concept. And for those of us with medical backgrounds, this is a very familiar pharmacologic mechanism. I will say the QID dosing that is increasing the dosing early on could be a very beneficial thing for many of these patients that reports a physicians in more or less and exacerbated state. And so, typically with diseases, not just ocular diseases, you will often treat patients with a higher dosing frequency initially to control symptoms. But patients don't always require that increased dosing frequency overtime. And that is exactly what you have described with the QID to BID taper arm in RENEW Part 1. We also noticed that in the Phase 2b trial, a lot of self-tapered, meaning that after their symptoms improved, they tended to take less drug overtime. And I think that is quite reflective of the real world. We have done a considerable amount of market research not only with physicians, but also with patients. And with any ocular service disease, whether it be allergic conjunctivitis or dry-eye disease, but what we find is practically in the real world, many patients dose as needed, almost on a PRN basis. So RENEW Part 1 is really designed to get that all these concepts and, but frankly, we would be thrilled to have either dose arm work. The key for us really is an early on-set of activity, which gets at the loading dose, maintenance dose concept. A problem in today's market with a currently available therapies, is they often take weeks or months to work. And so to put a patient on a drug to ask that patient to deal with persistently disturbing symptoms over weeks to months, just to see if a therapy is active seems a fairly untenable and difficult position. We hope with reproxalap to solve that issue where such that we can generate systematic improvement early. Yes, I’m talking about your FORMULATION trial question. The FORMULATION trial is ongoing. And you can read more about it on clinicaltrials.gov. We will not disclose results from the FORMULATION trial with Part 1. To the extent that we disclose anything, I would expect that would be a first half of 2020 event.

And Todd, I mean, obviously you are going to be launching another study, is the FORMULATION gaiting for the pivotal?

No. Absolutely not. We are always opportunistic not only in terms of FORMULATION, but different trial approaches and different molecules and different mechanisms. I think the FORMULATION trial represents one of those opportunistic approaches to modestly modify the FORMULATION to residence time and drug in the front of the eyes. Topical ocular administration is challenging, because as human beings we are good at getting rid of foreign substances in front of our eyes. We blink, we tier, drug often runs down then there is a lacrimal duct and any efforts that drug formulators can make to increase ocular resonance residence time I'm sure would be well received from patients and physicians alike.

Great. Thanks very much.

Your next question comes from the line of Matthew Cross of JonesTrading.

Hey guys, and nice to hear from you all again so soon. A couple I wanted to ask about the new non-ocular trial initiations that have just been started or on the verge of doing so. So I guess starting with the Phase 1 trial of ADX-629 and systemic autoimmune disease. Clearly a big step here to beginning into the systemic usage of RASP and wanted to get a sense for what we may see from this trial on two fronts. First, Am I correct that this is expected to be sort of an all comers trial for various autoimmune and metabolic indications. And if so, could you maybe describe what you are hoping to see from this Phase 1 outside of safety in order to measure success? Specifically, are there particular RASP related biomarkers you will be looking for to gauge activity or do you look for something more general, like regulatory T-cell or cytokine behavior?

Matt I'm glad you asked that question. I hope you can feel our enthusiasm about our systemic RASP program. To our knowledge, this is the first time ever that a RASP inhibitor has been tested in humans at a systemic basis. So we are thrilled to be right at the vanguard of exploiting this novel mechanism for autoimmune and inflammatory disease, which I mentioned on the call, it is probably a component of most diseases. So I think our potential indication are broad here, as you point out in your question. This is a Phase 1 trial with ADX-629. So there are no diseased patients, in particular these are normal healthy human volunteers. Obviously with Phase 1 trials, the goal is to assess pharmacokinetics safety and tolerability. And we are obviously looking at a variety of outcomes and not only standard PK and safety, tolerability end points, but biomarkers. The RASP mechanism, as you pointed out allows for the assessment of a variety of different parameters, not only RASP, but also the downstream effects of RASP immunologically, which would include standard things such as cell counts, inflammatory cell counts and cell activity and so forth. So I think what you could expect to hear as a result of the Phase 1 trial I hope in the first half of next year, is a variety of different I would say pharmacodynamic outputs from the trial, and then from there, I think based on those outputs along with safety, tolerability PK we will decide what Phase 2 programs to pursue.

Perfect, no that is very helpful to frame things. And I guess kind of building on your point about this being first study of RASP and obviously systemically and focus on PK here. Can you comment on your expectations maybe for bio availability of ADX-629. I know back in the days discussing the [indiscernible] mechanism. You have raised the point that RASP needs to be targeted with something like a one-to-one ratio of inhibitor to [indiscernible]. So I’m wondering what kind of exposure level is reasonably expected to the active or more generally how 629 may differ from the reproxalap Formulation to achieve the kind of PK you are looking for systemically?

So we will certainly comments on pharmecokinetics at the end of phase one, you are correct silky metrically there is a one-to-one ratio between the RASP inhibitor and the RASP. What that means, though, I think, can only be answered empirically in diseased patients. The pharmacologic half life of RASP inhibitors has proven to be quite long. An example is our Phase 3 ocular programs. Where we have demonstrated long pharmacologic clinically relevant activity that obviously greatly exceeds pharmacokinetics for our RASP inhibitors. We will have to see in Phase 2 how various dosing paradigms affect disease, but because RASP are so proximal and so upstream and so early in the inflammatory cascade, one could expected that RASP inhibition has many long-term persistent downstream effects that would last much longer than drug residents.

Got it. Okay, fair enough, and look forward to ultimately seeing those results to kind of address some of these conclusions for Phase 2. I just want to squeeze in one more quick one on ADX-1612 that kicks off here shortly. Is there any update you have received on the mesothelioma and ovarian cancer ISTs, maybe just guidance on when you are hoping to have more to say on those programs? And as you start your own Company sponsored trial in PTLD, are there any learnings from your investigators' experience with ADX-1612 in these first two indications that you feel may be applicable to PTLD, despite the fact that these are obviously rather different indications?

Right, so the cancer programs, and ovarian cancer, and mesothelioma were inherited from the previous developer of ADX-1612. We are obviously not a cancer company, but we do see significant potential value. If our programs in mesothelioma and ovarian cancer workout. The ovarian cancer trial is called EUDARIO that has begun enrolling patients that has an investigator-sponsored trial that run in Europe. The mesothelioma trial, we also expect to begin next year, that is also an investigator-sponsored trial. So the timing of that depends on the investigator. One reason that we shifted those programs to investigator-sponsored trial was to conserve resources and focus on our immunological programs that we have internally. Both of those programs is really a synergy that has been observed pre-clinically between a chaperome inhibition and DNA-damaging agents. So both the ovarian cancer and mesothelioma programs are testing the combination of ADX-1612, which is a chaperome inhibitor and DNA-damaging agents in this case Platons [Ph]. The reason why there is a presumed synergy there is because Platons which damage DNA will require DNA repair, which itself requires the chaperome. So without proper chaperome activity which is inhibited by ADX-1612, is difficult to repair DNA, which is the main mode of action of DNA damaging agent such as Platon and both of those trials features that combination clinically. Are there any learnings from PTLD? Probably not. I don't think that - I think these are vastly different diseases. To begin with PTLD is not necessarily frank cancer. PTLD is an aberrant proliferation of immune cells that follow a transplant. And in some cases, PTLD can evolve into lymphoma, but we view ovarian cancer and mesothelioma as pathologically distinct from PTLD. That doesn't mean we are not excited about PTLD, we are really with ADX-1612 attempting to focus on immune diseases where there is an aberrant proliferation of immune cells, which is featured in a lot of immune diseases as our bodies mounts immune responses. One way we do that is to increase inflammatory cell proliferation. That can go haywire on diseases such as PTLD, where there are excessive amounts of immune cell replication and that is exactly what ADX-1612 is targeting in PTLD and potentially other diseases.

Great. Now I appreciate the detail here and the overall update today. So looking forward to the update on RENEW and thanks again Todd.

Thanks Matt.

Thank you. I will now turn the call back to Dr. Brady for any closing comments.

Thank you, operator and thank you all for joining us again today. As always, we look forward to keeping you informed of our progress and advancing our late stage-pipeline and product candidates for the treatment of immune mediated disease.