Welcome to the Viridian Therapeutics First Quarter 2022 Conference Call. . It is now my pleasure to introduce your host, John Jordan, Vice President of Investor Relations and Corporate Communications at Viridian. Please go ahead, sir..

Thank you, Debbie. Good afternoon, everyone, and welcome to our first quarter 2022 conference call. Today, after the market closed, we issued a press release providing our first quarter 2022 financial results and business updates.

A replay of today's call will be available on our Investor Relations section of our website approximately 1 hour after its completion. After our prepared remarks, we will open up the call for Q&A. Before we begin, I'd like to remind everyone that this conference call and webcast will contain forward-looking statements about the company.

These statements are subject to risks and uncertainties that could cause actual results to differ. Please note that these statements reflect our opinions only as of today. Except as required by law, we specifically disclaim any obligation to update or revise these statements in light of new information or future events.

Factors that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward-looking statements are discussed in greater detail in our most recent filings on Form 10-K and our other reports filed with the SEC.

I would now like to turn the call over to Jonathan Violin, President and Chief Executive Officer of Viridian..

Thanks, John, and good afternoon, everyone. Thanks for joining us on our first quarter 2022 conference call. I'm also joined today by Kristian Humer, our Chief Financial Officer and Chief Business Officer.

We'll begin with a brief update on the business, including recent and upcoming milestones and the progress we're making in advancing our lead candidates for Thyroid Eye Disease or TED. Then Kristian will review our first quarter financial results, then we'll open the call for questions.

First and foremost, I'm excited for the data that we expect to deliver in the coming months. We have multiple data readouts that we expect will confirm the potential of our antibodies to significantly advance the treatment of Thyroid Eye Disease.

After a very productive 2021, we continued our momentum in the first quarter with substantial progress in our Phase I/II proof-of-concept clinical trial for VRDN-001 and the initiation of our first-in-human clinical trial for VRDN-002, both trials are poised to deliver top line data in the third quarter.

We believe these 2 trials will provide the initial evidence to establish VRDN-001 and 002 as meaningful therapeutic advancements in treating Thyroid Eye Disease. I'd like to spend a few minutes reviewing each of our TED programs and the significance of the ongoing trials for each asset, starting with VRDN-001.

Data from previous oncology trials and our preclinical studies indicate that 001 has the same mechanism of action and similar pharmacokinetics in humans as TEPEZZA, the only therapy approved by the FDA for TED. The key difference for VRDN-001 is higher affinity.

Both our own data and previously published data show that VRDN-001 has sub-nanomolar affinity and potency against IGF-1R, the targeted mechanism of action of TEPEZZA. This higher potency may reduce the dose required to deliver efficacy in TED patients.

We see an opportunity to develop 001 as a differentiated intravenous product, addressing the need we've heard from stakeholders for a less burdensome and potentially safer dosing regimen. In December, we announced the dosing of the first subject in a Phase I/II proof-of-concept clinical trial for VRDN-001.

This trial is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics and efficacy of 001. It includes both healthy volunteers and randomized placebo-controlled cohorts of TED patients and is assessing multiple measures of the signs and symptoms of TED, including proptosis, the bulging of eyes, characteristic of TED.

Over the past several months, we completed dose escalation and enrollment of healthy volunteers and continue to enroll TED patients. We expect to deliver top line proof-of-concept data from 2 cohorts of TED patients in the third quarter.

We now have 11 sites active and recruiting similar to the number of sites in the TEPEZZA Phase III trial, and we're working with some of the top enrolling sites from that trial. Though some of the site activation took longer than we initially expected, we continue to see strong engagement from investigators and interest from patients.

Importantly, we've been very pleased that once open, the rate of screening and enrolling patients per site has met our expectations. So we're very confident in our enrollment projections and in sharing top line data in the third quarter.

While we eagerly anticipate reviewing our first data from TED patients, I'm pleased to share today some highly encouraging interim data for the healthy volunteer portion of this trial, which includes 13 subjects receiving 2 doses of placebo or VRDN-001 at 3, 10 or 20 mgs per kg. We're very encouraged by the safety and tolerability seen to date.

There have been no drug-related adverse events associated with hyperglycemia, hearing loss or muscle spasms at any dose, including the top dose of 20 milligrams per kilogram. Other adverse events have been generally comparable to placebo. And to date, there have been no infusion reactions or serious adverse events.

In addition to this promising safety profile, we see robust increases in IGF-1 plasma levels, a biomarker for IGF-1R inhibition. Interim data show a rapid sevenfold increase in IGF-1 from baseline to all doses tested, including 3 mgs per kg, suggesting doses as low as 3 mgs per kg are sufficient to achieve maximal IGF-1R inhibition.

Moreover, maximal inhibition was achieved rapidly and was sustained throughout the 2-dose treatment period. No increases in IGF-1 were observed in patients treated with placebo. The robust IGF-1 response at 3 mg per kg is consistent with data for this antibody in oncology patients and suggest this dose could be highly effective in TED patients.

This is important because it could allow us to advance 001 as a self-administered subcutaneous injection in addition to intravenous administration. We've included the preliminary safety and IGF-1 data in our updated corporate presentation, which is available on our website.

This interim healthy volunteer data increases our excitement for our upcoming proof-of-concept results. They confirm our expectations for the safety and potency of our molecule.

And based on these results, we now plan to evaluate an additional cohort of TED patients at a dose of 3 mg per kg following the completion of the proof-of-concept portion of the ongoing trial. So we expect to deliver proof-of-concept data from 2 cohorts in the third quarter and data from the low-dose 3 mg per kg cohort in the fourth quarter.

As a reminder, the proof-of-concept portion of this trial includes 2 cohorts of 8 TED patients each randomized in a 3:1 ratio to receive 001 or placebo. The first cohort will include 2 infusions of 10 mg per kg of 001, and the second cohort will include 2 infusions of 20 mg per kg of 001.

We're assessing multiple efficacy endpoints, and we'll report data at 6 weeks after 2 infusions of 001. We'll report the same endpoints used to evaluate TEPEZZA, focusing on mean change from baseline and proptosis reduction, but we'll also report proptosis responder rate, clinical activity score and diplopia.

Our goal is to see efficacy signals comparable to TEPEZZA at 6 weeks. In particular, we're focused on change from baseline in proptosis for which the 3 TEPEZZA data sets, Phase II, Phase III and Phase III open-label extension showed very consistent changes at 6 weeks with a mean of 1.7 to 1.9 millimeters. So that's the range we're aiming for.

It would confirm that we can recapitulate the rapid improvement in TED symptoms that TEPEZZA has demonstrated and position us to quickly advance our program towards pivotal trials with the goal of being second to market.

Since TEPEZZA is the only entrant in a rapidly growing market already annualizing at $2 billion in the U.S., just 2 years into launch. We believe that showing VRDN-001 proof-of-concept data similar to TEPEZZA would be a major value-creating event for us.

We know we have a compelling product with the potential to be the second entrant in a large, rapidly growing market. And we also would know we have multiple opportunities to differentiate our product profile to enhance our market position.

To this end, we're already preparing 001 for pivotal trials, including manufacturing material at commercial scale, assuming positive proof-of-concept data and we anticipate advancing our program rapidly. We intend to sprint to market with a differentiated 001 product profile and plan to assess multiple dosing regimens in parallel.

Fewer infusions or different routes of administration will be a welcome advancement for TED patients. We look forward to discussing our Phase III plan following our proof-of-concept trial readout. Let's now turn to VRDN-002, our next-generation IGF-1R targeted program.

002 is a humanized monoclonal antibody that incorporates a validated half-life extension technology and is designed to support administration as a convenient, low-volume, subcutaneous injection for the treatment of TED.

Based on the VRDN-001 healthy volunteer data we shared a few moments ago, we're now increasingly optimistic that a low dose of 001 might allow a self-administered subcutaneous dosing paradigm, and we're excited it has the potential to move rapidly and become the first subcutaneous therapy for Thyroid Eye Disease.

VRDN-002 with its half-life extension technology may represent the next-generation best-in-class product, as it has the potential for less frequent subcutaneous dosing than any TED therapy, including VRDN-001. We expect to show the pharmacokinetic benefits of this molecule in our ongoing Phase I first-in-human trial.

We announced dosing of the first subject of this trial in March. The trial is a single ascending dose study to explore safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered 002 in healthy volunteers.

We've completed dose escalation and expect to announce top line data from this trial in the third quarter, either concurrently with or following shortly after our VRDN-001 proof-of-concept readout.

We expect that the results of this trial will demonstrate how well half-life extension technology improves pharmacokinetics compared to a traditional IGF-1R antibody. And these data will inform the dose and dosing frequency of a low-volume subcutaneous product.

We're on track to have a subcu drug product ready in early fourth quarter, and we expect to be ready to initiate a subcutaneous proof-of-concept trial in TED patients shortly thereafter. With our 001 and 002 programs, we believe we have a compelling TED portfolio with intravenous and subcutaneous options that can compete across all settings of care.

I'm grateful for the excellent work that Viridian team has done to advance our programs and also for the investigators, volunteers and patients who are participating in our trials. Moving to our programs beyond TED.

We're expanding our pipeline by discovering and developing more convenient next-generation antibodies for indications in which proof of concept for the targeted mechanism of action already exists.

For both our VRDN-004 and 005 programs, we see opportunities to advance patient care and involve treatment paradigms with a new best-in-class entrant, and we continue to progress these programs in discovery stage. We'll provide updates as these programs mature. For now, we remain laser-focused on delivering on our TED portfolio opportunity.

I'll now turn the call over to Kristian, who will discuss our financial results for the first quarter.

Kristian?.

Thank you, Jonathan. Good afternoon, everyone. I want to open up our comments by stating that we ended the first quarter with $175 million in cash, cash equivalents and short-term investments as of March 31, 2022.

This puts us in a strong financial position to fund the advancement of multiple programs in TED, while expanding our discovery pipeline and operations into 2024. Subsequent to the end of the first quarter, we entered into a credit facility with Hercules for up to $75 million.

Upon closing of this facility, we withdrew only $5 million an additional $20 million is available at the company's request through June 15, 2023, with an additional $25 million available upon the company's achievement of certain milestones. The remaining $25 million is available subject to lender approval.

The company is under no obligation to draw funds in the future. We believe this credit facility further increases our financial strength by reducing our dependence on capital markets, which provides us added strategic and operational flexibility to advance our programs. Turning to expenses.

We reported research and development expenses of $17.7 million for the quarter ended March 31, 2022 compared with $13.8 million for the same period last year. The increase in research and development expenses was primarily driven by personnel-related costs, license fees and clinical trial costs for VRDN-001 and VRDN-002.

These increases were offset by expenses related to manufacturing and IND-enabling studies for VRDN-001 and VRDN-002 that were incurred in the first quarter of 2021. The General and administrative expenses were $8.4 million during the first quarter of 2022 compared with $6.2 million for the same period last year.

The increase in G&A expenses was driven by increases in personnel-related costs, including severance, share-based compensation changes and consulting expenses. The net loss was $25.7 million for the first quarter of 2022 compared with $18.5 million for the same period last year.

The increase in net loss was driven by increased operating costs as well as lower revenue from our collaboration with Zenas in the first quarter of 2022 compared to 2021.

As of March 31, 2022, Viridian had approximately 42.9 million shares of common stock outstanding on an as-converted basis, which included 27.2 million shares of common stock outstanding and approximately 15.7 million shares of common stock issuable upon the conversion of shares of Series A and Series B.

With that, I'll ask the operator to open the call for questions..

. The first question comes from Chris Howerton with Jefferies..

Congratulations on the clinical progress thus far. For my questions, I think, pretty simple. In terms of the first question, just wanted to clarify on the healthy volunteers data. I'm color blind, and I can't see everything all that well, but it looks like the error bars are not consistent across throughout the line plots.

So I'm just wondering if there's -- is it a sparse data set in that, like there's only 1 patient at certain time points or I guess just a little more color in terms of what constitutes the data representing that graph. And then the second question, again, I think is just a relatively simple clarification.

When you think about the dosing between 001 and 002, do you think of them as being equipotent, it does a 3 mg and equal 3 mg in 002..

Sure. Thanks, Chris. So with respect to the IGF-1 question, keep in mind, this is an interim analysis. In the slide preceding -- the slides you're referring to, we discussed the stage of the trial. The top dose cohort, the 20 mg per kg cohort is ongoing. And so we don't have data from later time points there.

So I think what you're seeing mostly reflects that but we have completed the 3 in the 10 mg per kg cohort. And then the second question was 002 versus 001 and comparative potency. So these molecules have similar affinity for receptor where we're expecting to differ is in the pharmacokinetics.

So to remind everyone, VRDN-001 has a very similar pharmacokinetics to teprotumumab and other first-generation entrants in this class. But with the inclusion of half-life extension, we believe VRDN-002 will have a substantially longer half-life as we've seen in our preclinical data.

And so the question that the ongoing study will begin to answer is with a similar dose, let's say, 3 mg per kg dose, if we can get sustained exposure we may not be able to give -- we may not have to give as big a dose over time.

So the question of equivalent dosing is really not just the affinity for the receptor, but very largely driven by the pharmacokinetics. And that's why we're so excited about VRDN-002. We know that VRDN-001 is sub-nanomolar affinity.

And in fact, we believe, based on the old oncology data that as you lower the dose much below 3 mgs per kg, it becomes PK limited improving affinity further is not likely to help. What we think is going to help us improving the pharmacokinetics of that is with dose limiting again so we're so excited about VRDN-002.

I'm looking forward to seeing the first-in-human data next quarter..

Okay. Very good. I mean I guess I'll ask it. The -- so your competitor Horizon has also announced that they are developing what they call a high concentration subcutaneous formulation as well.

How do you anticipate this changing your strategy in the near term, if at all?.

Yes. So let's review what that might mean, right? So TEPEZZA is approved at -- well, the loading dose is 10 mgs per kg and then 7 ensuing doses of 20 mgs per kg. And we know that the average patient size receiving TEPEZZA is 75 milligrams. So that's 1.5 gram of drug every 3 weeks. The current marketed formulation is 50 mgs per ml.

So 150 milligrams of 50 mgs per ml, that's 30 milliliters, 3-0. So that's a large volume, right? That would be a large infusion to get the subcu. So what might one be able to achieve with a high concentration formulation. Now a typical target to shoot for would be about 150 mgs per ml. Not all antibodies can get there can. Some can.

In fact, both 001 and 002, we've been able to formulate to 150 mgs per ml without precipitation, good viscosity. So that's a kind of standard threshold for high concentration. There are 2 products that have got higher than that 280 and 200 mgs per ml, Actemra. So that would be sort of an upside.

So let's say we can get -- we see Tepro at 150 mgs per ml, that takes the volume to 10 mls and maybe if it manages to meet the best ever of 200 mgs per ml, it could get down to 7.5 mls. So that's still a pretty substantial volume. And it's not -- that's not something that's a single low-volume injection.

For that, we think the threshold is 2 mls and we can point to commercial products had been very successful with 2 mls or lower as an injection. So we're looking still at the approved dosing in TEPEZZA, even assuming success of a high concentration formulation at an infusion or a large number of injections.

And so that's why we think that getting a lower dose and then the lower volume can enable us to deliver a compelling product with a low volume and less frequent subcutaneous product..

The next question is from Thomas Smith with SVB Leerink..

Congrats on the initial data here. Just maybe start with one on the healthy volunteer data for 001. Safety looks really clean. Is there any additional color you can add on the hypertension or hyperglycemia events? I know both deemed unrelated to study drug. But just wondering if there's anything else you can add to that..

Yes. So the hyperglycemia who was in a patient -- who had hyperglycemia baseline. It was mild, continue to be mild. And that's why it's deemed unrelated to study drug. And then hypertension, I mean, these are kind of typical mild variations one often sees in a Phase I study.

And again, they were mild and really deemed unrelated by study drug and not of concern to either the mass investigator or to us..

Okay. Makes sense. And then on the proof-of-concept, TED cohorts, any additional color on patient enrollment here? Are there any specific headwinds you're coming up against in terms of site activation or patient enrollment? And then I guess maybe a follow-up to that.

Any early read on the types of TED patients that your investigators are enrolling into the study? Are these patients that are more on the milder or severe end of the active disease spectrum, where the investigators indicating the greatest degree of interest at this point?.

Sure. Yes. So in terms of enrollment, you need 2 things, right? You need to get site active and then you need to get patients enrolled at the sites. And we -- we now have 11 sites open. The majority of those have been in recent weeks. So we were expecting an uptick in site activation a little earlier.

Now that we have these sites open, some of them have been open for a few months. We've got a pretty nice track records to see what the enrollment rate looks like. And it really is matching what we had expected our priority. So the hurdles we have been getting in the sites activated which are for a variety of factors.

We think we're past, solved the issue and now the enrollment rate is performing just as we'd hoped. So that's why we're very comfortable with our third -- third quarter guidance.

With respect to types of patients, we designed the study to ensure that we were not going to be enrolling patients that were less likely to show a benefit, right? So we really mimicked the TEPEZZA Phase III IV criteria.

And we're working with sites very experienced in the space and of course, keeping close oversight to make sure that no one outside of IV criteria are slipping in. So the study is really designed to ensure we're enrolling a similar patient population. And been really happy with the engagement we've seen from sites, the interest from patients.

And keep in mind that TEPEZZA is not often quickly available. A lot of patients either don't have access or it takes them a while. So whatever the reason we're seeing really good interest and are pleased with the moment achieving so far..

Okay. Got it. And then just one last question on the plans to add the 3 mgs per kg cohort for TED patients. Like really interesting to think about the prospects of this in a subcutaneous formulation.

I guess just how much formulation work have you done to date around 001? And how difficult would it be to advance the subcu form? And how quickly could you potentially get this into the clinic?.

Yes. So we -- actually, very quickly, we shared this at some point last year, we were very quickly able to get 001 and 002, for that matter to our target concentration of 150 mgs per ml. And that's with good viscosity -- and meaning that it would be amenable to subcutaneous products. So we don't see anything blocking us.

In terms of timing, to when could that advance forward, really, the key question is, when the 3 mg per kg dose work. So stay tuned for an update on our plans, but it's something that we're increasingly excited about and don't see any hurdles on the formulation front that would keep us from getting there..

And congrats again on the initial data..

Next question is from Laura Chico with Wedbush. ..

I'm getting one from investors that I just wanted to clarify on. With respect to 002, the timing is moving out to the third quarter and maybe that's just a narrowing.

But I guess I'm kind of curious if the initial dosing is complete, I guess, are the remaining data items to process there on the 002 readout, just kind of clarifying the timing change on that? And then with respect to 001, I might have missed this, apologies if I did. I don't see any of the pharmacokinetic data released.

When might we get a little bit more visibility on that aspect of the healthy volunteer data. I think there was some question before about kind of half-life differences with TEPEZZA in different type of patient populations. So I'm curious if you have any color there..

Sure. Thanks, Laura. So for 002, we're narrowing the guidance. We'd said midyear, meaning 2Q, 3Q, and we're clarifying that it's third quarter. We did say dose escalation is completed. So that means we got up to the top dose.

But keep in mind that with half-life extension, you need a sample for a while to understand how well the half-life extension technology is working. So we just need to wait. But we're very pleased with how the study has gone and everything has gone quite well. With respect to 001 PK, again, we're still collecting data at the top dose cohort.

But what we've seen so far, very consistent with the oncology data, actually really excellent PK. So we see no signs of target-mediated clearance, which is something that we have to watch out for, but it looks great even at the low dose. No evidence of antidrug antibodies.

Again, that was true back in the oncology dangerous molecule, but wonderful to see that again in our hands. And then with respect to -- are there differences in across patient population? So just to remind everyone, we think about 001 versus Tepro. These are both IgG1 antibodies. So they're very similar.

They have indistinguishable pharmacokinetics in nonhuman primates, also in oncology trials when both of these antibodies were oncology studies -- and -- but Tepro has never been in healthy volunteers.

And so when we look at the PK and thyroid eye disease patients, instead of individual PK, which is how we prefer to think about pharmacokinetics and when I cited the oncology data and the nonhuman primate data, that's individual PK. But TED PK is really population PK based on standpoint.

That's really a different model and you can't really do an apples-to-apples comparison. What I can say is based on the preliminary data, we don't see any obvious differences with between 001 and Tepro. And so we think we're going to have a very similar PK when we get to TED patients..

That's very helpful, John. And maybe one last one, if I can sneak it in there. With the proof-of-concept data coming in 3Q, will we have full data at both the 6-week and the 12-week time points..

Sure. We're really focused on the 6-week time point because, again, we're mimicking the TEPEZZA dosing paradigm through week 6. So we dose on day 1, we dose on day 21 and then we're measuring efficacy on day 42 at week 6. There is a near-term follow-up at week 12, but we're not dosing between week 6 and week 12.

And so in terms of doing the kinds of cross-trial comparisons that we all are interested in really have to look at the 6-week time point and not the 12-week. Lots of interest in information will come out of the 12-week follow-up, but we're not guiding to include that in the top line readout release.

As soon as we have the 6-week data on both the 10 mg per kg and 20 mg per kg cohorts, we'll have a rich data set that we'll be excited to share..

Next question is from Rami Katkhuda with LifeSci Capital..

Congrats on the early data. Just going off a previous question.

If the 3 mg per kg dose 001 is shown to be efficacious in a subcu therapy, I guess does that affect your development plan with 002 at all? Or is it too early to tell?.

Yes. Well, what we like about our approach here is we have lots of options, lots of shots on goal. If we can get 001 to subcu, I mean that 3 mg per kg cohort works and 001 can move forward in the subcu product presentation and a subcu injection, right? We're trying to get to a low-volume injection as opposed to a larger volume infusion.

The nice thing about that is that there's potential that can move very quickly and could be the first subcu entrant in Thyroid Eye Disease. With 002 with half-life extension, there's an opportunity to reduce the frequency and come up with the most convenient possible product presentation.

And so we -- I think we'd be interested in moving that forward as well, which is that, right? So it's the only IGF-1R antibody with half-life extension in the market. So it could be really hard to beat..

Definitely makes sense. I guess another question, if you don't mind.

Can you remind us if plasma levels of the IGF-1 biomarker generally correlate with clinical efficacy in TED?.

Well, because Tepro was never dose-ranged we can't point to a dose response relationship. So really, what we can do is look back at all the IGF-1R antibodies in the past. So very consistently and based on the underlying biology, when you inhibit IGF-1R when you bind and block the receptor, plasma levels of IGF-1 go up.

So it's a marker for target engagement. Doesn't tell us anything specifically about the pathophysiology. So we can't draw either mechanistic or quantitative length. But the fact that we're seeing a maximum response with a same high rate of onset of the increase in all these doses.

And given the fact that we have sub-nanomolar affinity and we're well above 10 micrograms per ml exposure, if you look back at the old oncology data for this drug, it's very reasonable to hypothesize that we're saturating the receptor and could deliver full efficacy at this dose.

That's really what drove our excitement for announcing that we'll be starting a 3 mg per kg cohort with that in the fourth quarter..

. Our next question is from Jason Butler with JMP Securities..

This may be one that you still need to see more data from, but any thoughts based on the data you have today and whether dosing frequency with the 3 mg per kg subcu formulation would be? Would it be the same 2, 3 weeks? Or could it be different than that? And then just at this point, is at least one of the scenarios for 001 that you conduct a registration study or studies that incorporate both the subcu and the IV formulations you've got a FDA in parallel with both formulations..

Yes. So I think it's a little too early to answer both questions declaratively, right? We need to see some more data. But there's a trade-off, right? But when you think about a subcu product, you can -- there's a trade-off between volume and frequency. So you can have a lower volume more frequently or a larger volume less frequently.

And when we see data from the 3 mg per kg cohort, we'll have some interesting decisions to make as to what we will study going forward.

Now of course, when we think about how can we get this approved, right? The goal, as I said, would be to get this to market as fast as possible, and that will very much feed into our thinking as to what kind of dosing frequency will do and what level of evidence is required to get the subcu product approved.

So stay tuned, but we're really excited that there's potential that this could move forward quickly..

Congrats on the progress and the data..

This concludes our question-and-answer session. I would like to turn the conference back over to Jonathan Violin for any closing remarks..

Thank you, and thanks, everyone, for joining us today. As I hope you've heard, we're very excited about both the ongoing progress that we're making across our TED programs and the multiple upcoming data readouts. So we look forward to updating you as our programs advance. And with that, we'll close the call..

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect..