U.S. Markets open in 2 hrs 18 mins

Edited Transcript of BTX earnings conference call or presentation 10-May-18 8:30pm GMT

Thomson Reuters StreetEvents

Q1 2018 BioTime Inc Earnings Call

ALAMEDA May 17, 2018 (Thomson StreetEvents) -- Edited Transcript of BioTime Inc earnings conference call or presentation Thursday, May 10, 2018 at 8:30:00pm GMT

TEXT version of Transcript

================================================================================

Corporate Participants

================================================================================

* Aditya P. Mohanty

BioTime, Inc. - Co-CEO, President & Director

* David Nakasone

* Gary S. Hogge

BioTime, Inc. - SVP of Clinical & Medical Affairs

* Michael D. West

BioTime, Inc. - Co-CEO & Director

* Russell L. Skibsted

BioTime, Inc. - CFO

================================================================================

Conference Call Participants

================================================================================

* Bruce David Jackson

Lake Street Capital Markets, LLC, Research Division - Senior Healthcare Research Analyst

* Keay Thomas Nakae

Chardan Capital Markets, LLC, Research Division - Senior Research Analyst of Therapeutics, Devices and Diagnostics

* Kevin M. DeGeeter

Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research

* Patrick Edward Dolezal

LifeSci Capital, LLC, Research Division - Associate

* Reni John Benjamin

Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst

================================================================================

Presentation

--------------------------------------------------------------------------------

Operator [1]

--------------------------------------------------------------------------------

Good day, ladies and gentlemen, and welcome to the BioTime First Quarter Results Conference Call. As a reminder, this conference call is being recorded.

I would now like to introduce your host for today's conference, David Nakasone of BioTime Investor Relations. David, please go ahead.

--------------------------------------------------------------------------------

David Nakasone, [2]

--------------------------------------------------------------------------------

Thank you, operator, and good afternoon, everyone. Thank you for joining us today for BioTime's investor conference call and webcast to review the company's results for the first quarter of 2018 as well as recent corporate developments.

BioTime issued the first quarter earnings release and accompanying earnings presentation earlier this afternoon, and they are posted and available on our website at www.biotime.com. There will be a replay of this call, which will be available approximately 2 hours after the call's conclusion and will remain available for 7 days. The operator will provide the replay information at the end of today's call.

With us today at corporate headquarters are: Co-Chief Executive Officer Adi Mohanty; Co-Chief Executive Officer, Dr. Michael West; Chief Financial Officer Russell Skibsted; and Senior Vice President of Clinical and Medical Affairs, Dr. Gary S. Hogge. Each executive will make prepared remarks, and then we will take questions from our covering analysts and institutional holders.

Before we get started, we would like to remind you that, during the course of this conference call, the company will make projections and forward-looking statements regarding future events. We encourage you to review the company's filings with the SEC, including without limitation to the company's Form 10-K and 10-Q, which identify the specific factors that may cause actual results or events to differ materially from those described in these forward-looking statements.

These factors may include without limitation risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights.

And with that, I'd like to turn the call over to Adi Mohanty, Co-Chief Executive Officer of BioTime.

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [3]

--------------------------------------------------------------------------------

Thanks, David. Good afternoon, everyone, and thank you for joining our call today. We had a very strong first quarter highlighted by the successful submission of Renevia for CE Mark in Europe and the approval by the DSMB to initiate Cohort 4 of our ongoing clinical trial of OpRegen and dry-AMD.

In the last few weeks, we presented positive clinical data from our ongoing OpRegen trial at the annual ARVO meeting. We also announced the sale of Ascendance. These highlights represent successful execution of our strategy of clinical development, simplification and the locking value for our shareholders.

Since the last time we spoke was only a few weeks ago, I'll keep my comments on the overall business brief to allow more time for Gary to talk about the recent data presented at ARVO. His overview of the data presented at ARVO should help you understand why we are so excited and encouraged by the data presented. During his section, Gary will be referring to some slides presented at ARVO, which are available on our website at www.biotime.com. I would encourage you to pull these up ahead of time since they'll be really helpful to illustrate the points he will be making.

In March of this year, based on the strength and quality of the data seen in the pivotal trial, we submitted Renevia for approval in the EU. We successfully met the primary endpoints in patients with HIV-associated lipoatrophy. The data that we reported last year was quite compelling in that we had 100% retention at 6 months and about 65% retention even out at 18 months. The facial aesthetics market, which is over $4 billion in the U.S. alone, is mostly comprised of synthetic fillers and fat transfers.

Fat transfers are done as a more natural alternative to fillers, especially in larger volumes. However, fat grafts degrade quickly. According to published data, fat grafts retained only about 50% at 6 months.

The European submission of Renevia for CE Mark was filed under a device pathway. Our expectation, which we mentioned in our last call, is still to receive approval of Renevia before year-end. Discussions with the European agencies continue as expected.

In parallel to our discussions with the agencies, we are working diligently on the commercial plans for Renevia. Our current commercial plans include a stand-alone strategy where we would manage all sales and marketing efforts in-house through a targeted approach, a partnership or distributor arrangement or a combination of the 2. As the details of the potential label become clearer, it will help us evolve and finalize our commercial strategy. We look forward to sharing further details with you later this year.

As we have said before, we view the CE Mark submission as an important step to becoming a commercial-ready company and a launching pad into a larger market opportunity within facial aesthetics. Renevia provides patients with facial volume and has the potential to be used in combination with patients' own fat as part of a fat-grafting procedure and/or used by patients who are seeking an alternative through large volume dermal fillers.

Our interactions with the FDA continue as planned. We expect to share more detail on U.S. registration in the coming months and continue to expect to begin the trial before year-end 2018.

Turning now to the sale of Ascendance. This is an example of one way we could monetize our noncore assets. The sale of Ascendance was a good step in the right direction to simplify BioTime and unlock value. In roughly 2 years, the BioTime group of companies converted this noncore asset into a meaningful amount of cash. The portion of cash AgeX received was approximately $3.2 million for its interest in Ascendance. We continue to work on some other assets that can provide similar or better benefits to BioTime.

Now before I turn the call over to Gary, as I mentioned earlier, please refer to our earnings presentation under the Events & Presentation section of our website to follow along as Gary walks you through the OpRegen program and the data presented at ARVO. Now let me turn the call over to back to Dr. Gary Hogge, our Senior Vice President of Clinical and Medical Affairs.

--------------------------------------------------------------------------------

Gary S. Hogge, BioTime, Inc. - SVP of Clinical & Medical Affairs [4]

--------------------------------------------------------------------------------

Thank you, Adi. Earlier this year, the independent Data Safety Monitoring Board, commonly referred to as the DSMB, approved in parallel this expansion of Cohort 3 and the initiation of Cohort 4 of our ongoing OpRegen Phase I/IIa clinical trial dry-AMD, otherwise known as age-related macular degeneration.

The approval of Cohort 4 is a significant milestone because the patients in Cohort 4 will have much better vision than the patients in the first 3 cohorts. As a reminder, patients in the first 3 cohorts were legally blind with an average best corrected visual acuity, or BCVA, of 2,200 or worse. These patients were in the very late stages of their disease, and performing a battery of functional assessments on these patients is challenging, given their lack of vision and ability to adequately perform many of these assessments.

Along with patients with better vision, the patients in Cohort 4 will likely be in an earlier stage of the disease, allowing our investigators and teams the ability to perform an expansive spectrum of functional assessments and evaluate patients in our eventual target patient population. Enrollment for Cohort 4 has begun, and we expect the first patient of this cohort to be treated soon with the second patient to follow approximately 30 days after the first patient due to DSMB-mandated time to evaluate safety.

Following treatment and monitoring the second patient in a similar manner as determined by the DSMB, we plan to enroll the next 7 patients immediately following approval of the DSMB so that we can treat the first 9 patients in Cohort 4 within the next 3 to 4 months. With regards to the last 3 patients of Cohort 4, we intend to incorporate any potential learnings, enhancements and/or efficiencies before treating the last 3 patients in this cohort.

As a reminder, this is an open-label trial. The preliminary data from the first 2 patients of Cohort 4 should be available before the year-end. If accepted for presentation, we expect an interim update will be provided at the American Academy of Ophthalmology meeting, AAO, later this year in Chicago.

Two weeks ago, positive data from our ongoing OpRegen trial in dry-AMD were presented at the annual Association for Research and Vision and Ophthalmology meeting, or ARVO, as it is commonly referred to. ARVO is one of the world's most respected ophthalmology meetings, where experts and company representatives from around the globe meet to discuss and learn about recent advances in the field. The positive OpRegen data presented was from the first 9 patients in the first 3 cohorts for this Phase I/IIa clinical trial. There were no serious adverse events noted. And importantly, the data we presented suggest positive signals of structural improvement in the retina.

So why do we believe these data are meaningful? To answer this question, it might be helpful to have a little background on dry-AMD. At this point, would you please turn to Slide 3? Retinal pigment epithelial cells, also known as RPE cells, form a thin layer which is found beneath the photoreceptor cells. RPE cells are important to the eye because they obtain nutrients and oxygen in the choroid and transport them to the photoreceptor cells. They also carry away waste products from photoreceptor cells for disposal to the choroid. Additionally, RPE cells recycle proteins and other components involved in the phototransduction process and provide other survival proteins to the retina.

When we look at dry-AMD a little more closely, we can more fully appreciate the data we presented, in particular the data related to the structure of the retina. As you can see from both pictures on the slide, dry-AMD is characterized by deterioration of the RPE layer over time. As RPE cells weaken and lose function, there's often a formation of excess accumulated waste products of the retina, known as drusen, which forms underneath the retina. These deposits can grow in size over time. The depth and deterioration of RPE cells is often associated with the loss of function of the photoreceptors, which are critical to sight. Photoreceptors are essential to vision because they convert light into signals, they can stimulate biological processes through changes and cells' membrane potential.

Now that we have a better understanding of the disease, let's talk about our cell replacement program with OpRegen. We have a proprietary process that drives the differentiation of human pluripotent stem cells to generate RPE cells of extremely high purity. They're injected into the back of the eye through a subretinal injection upon a surgical procedure known as a vitrectomy. OpRegen is also xeno-free, meaning that no animal products are used at any point in the derivation and production process.

The avoidance of the use of animal products eliminate some potential safety risk and concerns. We started this program with exhaustive preclinical work in animals. Studies in mice, rats and pigs have shown a single subretinal injection of OpRegen, the cells can rapidly organize into a natural monolayer structure in the subretinal space where they're surgically delivered and survives another course of the experiment as evidenced by immunohistochemical staining and analyses with the human OpRegen results.

Importantly, the rats also demonstrated an increase in vision function through optomotor tracking assessment. Optomotor tracking is designed to evaluate the vision of rats and mice to determine if they can track a visual stimulus as detected by moving their eye, head or body to follow images. This just brings back to the data presented at ARVO.

On Slide 4, the column on the left shows that images of a human trial patient before, on the top, and after, the middle, OpRegen treatment. The bottom image in the left column is one of a pig that was treated with OpRegen as part of our extensive testing prior to the beginning of the current Phase I/IIa trial.

The green boxes within the images in the column on the left represent the area that was scanned using optical coherence tomography, or OCT, a noninvasive method that uses light waves to take cross-sectional pictures of the retina. The horizontal green line shows the exact area of the images on the right column. As seen in the middle right picture on Slide 4, the images of the patient's treated eye 4 months following OpRegen administration, which looks very similar to the image of the minipig at 3 months as shown in the bottom right of the slide. The yellow arrows indicate areas of potential RPE engraftment in the human. However, those areas indicated by yellow arrows in the pig were conclusively demonstrated to be OpRegen because we could stain from the cells at the end of the experiment. The red arrows indicate the limit of the surgical bleb created a transplant OpRegen in the pig and the red dashed lines represent the area of geographic atrophy, or GA, in the patient.

Turning now to Slide 5. The column on the left shows fundus autofluorescence images of the geographic atrophy and surrounding areas of baseline in month 4.5. The orange dotted line in images in the middle and right columns show the areas where OpRegen was transplanted into the surgically created subretinal bleb we previously discussed.

The horizontal green lines in the image in the top left shows where the OCT images were obtained. Consistent with what we saw in the animal models, where we were able to demonstrate structural and functional improvement, the data from our ongoing clinical study presented at ARVO showed several encouraging signs. First, within the area of the OpRegen cell transplant, there are signs of a reduction and change in drusen material over time. This can be seen in the image as referenced by the yellow arrows. At baseline, you may note that there are numerous soft and confluent drusen, hallmarks of advanced dry-AMD. However, over time, as noted in the month 1, month 3 and month 4.5 images, there's an apparent change and a clear reduction of the size and quantity of these drusen with only a few cuticular-like drusen -- please note the area beneath the red arrow at the bottom lower right -- remain in areas of transition zone where OpRegen was administered.

Second, we observed an improvement or possible restoration in the RPE layer in areas where OpRegen was delivered, similar to what we just discussed in the previous slide. Third, the outer nuclear photoreceptor layer, illustrated by the blue arrows, and the ellipsoid zone areas indicated by the brown arrows, assume a more regular appearance. In both recent cases, improvement in the RPE layer can be clearly seen along with a more regular appearance in the area where OpRegen was administered. These changes are even more evident when comparing the images over time of the treated area versus the area of the eye distant from where OpRegen was transplanted.

At baseline, it is very difficult to make out these layers because of return to drusen and damage to layers of RPE cells and photoreceptors. However, if you look closely at the images at 4.5 months, in particular areas between the blue and brown arrows, you'll see an improvement and/or possible restoration of these layers. Overall, the 4.5-month image on Slide 5 suggests potential structural restoration in the retina, which is consistent with what we saw in the animals.

Our ARVO data, along with the presentation of the Cell and Gene Therapy Summit (inaudible) ARVO were well received by those in attendance. During the conference, we were approached by several therapeutic area experts who complimented us on the exciting data. The main takeaway from these interactions was that there is a high level of excitement for and anticipation of the functional assessments and measurements of Cohort 4 we may see before year-end.

Additionally, we were pleased to report that following subretinal subreplacement with OpRegen, there's rapid healing of injection sites, and digital acuity has remained stable throughout the study with follow-up of greater than 24 months in several patients.

In summary, data presented at ARVO suggested positive signals with structural improvements in the retina, namely a reduction and change in drusen material, an improvement or possible restoration of the RPE layer, and the photoreceptor layer and ellipsoid zone assuming a more regular appearance. We believe these data and signs of structural improvements are a prerequisite for functional improvement, and they're consistent with our preclinical animal models, which showed an improvement in actual vision.

Dry-AMD is a progressive disease that leads to blindness over time. Although functional recovery is an ambitious and hypothetical goal, any treatment that can result in a slowdown or halt in the progression of the disease would make a meaningful difference in the lives of these patients. This is an objective that regulatory agencies have allowed as an endpoint for other trials in this space. We look forward to future discussions as more OpRegen data become available.

Now let me turn the call over to Mike West to discuss AgeX. Mike?

--------------------------------------------------------------------------------

Michael D. West, BioTime, Inc. - Co-CEO & Director [5]

--------------------------------------------------------------------------------

Thank you, Gary. Well, the formation of AgeX reflects the breadth and the depth of BioTime's technology platform as well as the vision and entrepreneurship of our scientists. So let me expand on each of these points for a moment.

We frequently pointed out the power of our pluripotent stem cell platform. The ability to manufacture young cells of any kind, for example, young heart, muscle, brain, lungs, retina, as we've just discussed, cartilage, or any of the other hundreds of cell types in the body, give us an incredible number of exciting product opportunities, but we cannot develop all or even a majority of these products in the near term.

Focus is key to our success. AgeX helps us do that. Then in addition, our scientists are incredibly inventive. They've discovered a novel state-of-the-art platform called induced Tissue Regenerator, or iTR, which could, in our opinion, be the basis of an entire new industry. So the question is how do we create value from these assets for BioTime shareholders while maintaining support and focus.

Our plan has been to consolidate certain assets not currently being developed at BioTime into AgeX Therapeutics, a subsidiary focused on human aging. The merits of this strategy can be outlined as follows: First, the field of aging biotechnology is particularly timely. Several companies in this sector are planning IPOs with relatively high market caps. For example, in the last week, Unity Biotechnology, a company focused on cellular aging, successfully completed an IPO with a market capitalization of approximately $800 million. We believe that the AgeX technology platform will be highly competitive compared to companies like Unity.

Second, the strong interest in this sector has made it possible for us to raise capital for these otherwise unfunded product development programs. To-date, we've raised $10 million from the sale of common stock and over $4 million from the sale of noncore assets and warrants. In addition, we recently announced award of a $386,000 Phase I NIH grant to advance our technology, the latter, of course, being nondiluted to our shareholders.

Third, we plan to distribute AgeX shares to BioTime shareholders of record allowing you, a BioTime shareholder, to directly participate in AgeX. In this regard, we plan to file the spinoff prospectus called a Form 10 Registration Statement, with the SEC this month. We will then at the appropriate time announce the record date that will determine the BioTime shareholders that will receive the distributed shares. You will receive a certain number of shares of AgeX common stock based on the number of common shares of BioTime you owned as of the record date. Other than maintaining your ownership of BioTime shares, no further action will be required for you to participate in the distribution.

In the coming weeks, we plan to update you on details related to the distribution of AgeX shares as well as updates on business and product development. In particular, we'll be discussing progress relating to our products: AGEX-BAT1, AGEX-VASC1 and iTR in upcoming scientific and business meetings.

To remind you, AGEX-BAT1 is composed of young regenerative cells designed to rebalance metabolism during aging, particularly type 2 diabetes, coronary disease and obesity. These indications may have significant market potential. We'll also be updating you on AGEX-VASC1, a product designed to regenerate vascular support for ischemic tissues, such as in the case of myocardial infarction. And lastly, we'll roll out more data on induced Tissue Regeneration, or as we say iTR. ITR is, in our opinion, a revolutionary technology, unlocking an innate capacity of the body to regenerate with important implications for cancer diagnosis and therapy as well.

So in summary, we plan to supply you with updates in the coming weeks on both the share distribution as well as our product development. So stay tuned.

I'll now turn the call over to Russell Skibsted to review our financials for the first quarter. Russell?

--------------------------------------------------------------------------------

Russell L. Skibsted, BioTime, Inc. - CFO [6]

--------------------------------------------------------------------------------

Thanks, Mike. I would now like to review the financial highlights for the quarter. BioTime's consolidated cash, cash equivalents and marketable securities totaled approximately $31 million as of March 31, which compared to approximately $38 million as of the end of 2017. In addition, we own common stock in our publicly traded affiliates, Asterias and OncoCyte, which represented aggregate market value of approximately $59 million based on yesterday's closing stock price.

As we've done over the past couple of years, we've included at the end of our earnings press release, a non-GAAP table that details noncash expenses and operating expenses by entity. We believe this will help investors better understand BioTime's financials. Please keep in mind when reviewing this table that the table is not a cash flow by entity because grants and other revenues are not included in the operating expenses in the table.

As previously noted, BioTime's consolidated cash, cash equivalents and marketable securities totaled approximately $31 million at the end of Q1. During the first quarter, BioTime's consolidated GAAP operating expenses were $12.8 million, which is comprised of $9.1 million for BioTime and $3.7 million for AgeX. During the quarter, BioTime's consolidated non-GAAP operating expenses were $9.8 million, which is comprised of $7.3 million for BioTime and $2.5 million for AgeX.

The difference in consolidated operating expenses and total non-GAAP operating expenses is about $3 million in noncash expenses. Non-GAAP operating expenses were higher for both BioTime and AgeX in the first quarter due to some nonrecurring costs associated with preparing for the AgeX distribution, which included legal, audit and tax-related costs. These nonrecurring costs plus nonrecurring costs related to our CE Mark filing preparation, along with certain seasonal cash flow items like annual bonus payments and seasonal grant receipt timing, our Q1 cash burn is higher than we expect for the remainder of the year, just as it was last year when Q1 cash usage was higher in the first quarter than was quarterly cash usage during the second half of the year.

Based on our current 2018 plans, we reiterate that BioTime's quarterly operating cash burn rate over the course of 2018 to be a little over $6 million per quarter. Provided we maintain our planned level of expenditure and receipts, we expect to have sufficient cash to get us well into 2019.

And with that, I will turn the call back to Adi.

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [7]

--------------------------------------------------------------------------------

Thank you, Russell. So we continue to have multiple shots on goal that are progressing well with assets in multibillion dollar opportunities in multiple geographies having commercialization and partnering potential across the globe. The overall partnering environment has improved as most large companies are looking to add to their pipeline. Along with large deals, they have also become comfortable with deals on early-stage products. That along with the growing understanding and acceptance of cell therapies in general bodes well for us.

So 2018 is shaping up to be a significant and transformative year for BioTime. We have seen good progress with OpRegen, where we've seen engraftment and survival of transplanted cells even beyond 2 years for some patients. We're seeing signs of structural and biological effect, and we're getting functional data now and in the coming months.

We expect to have Renevia approval later this year as well as other additional data from Renevia. We monetized the value of some noncore assets with the sale of Ascendance and are working on other similar opportunities. Also, we look forward to unlocking value with impending spinoff distribution of AgeX.

Now operator, we're ready for questions.

================================================================================

Questions and Answers

--------------------------------------------------------------------------------

Operator [1]

--------------------------------------------------------------------------------

(Operator Instructions) Our first question comes from Kevin DeGeeter with Ladenburg.

--------------------------------------------------------------------------------

Kevin M. DeGeeter, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research [2]

--------------------------------------------------------------------------------

Maybe just a couple housekeeping questions on AgeX to begin. Can you clarify that you'll be distributing 100% of your ownership stake in AgeX?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [3]

--------------------------------------------------------------------------------

Kevin, this is Adi. So as you know, we're waiting for the IRS ruling, and we're pretty close, but we're not there yet. We've had the interaction with the IRS. We've got all the filing done. As soon as we have the answer from them, that will influence if it's a 100% or not because if we're able to do this as tax free, certainly that's an opportunity for us to do a 100% distribution. However, if you don't have that, there are other plans that we have. So we'll have a more definitive answer in a very short order here.

--------------------------------------------------------------------------------

Kevin M. DeGeeter, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research [4]

--------------------------------------------------------------------------------

Okay, terrific. And then just with regards to the comments on cash burn, particularly for the balance of the year. Do those assume -- what do they assume with regard to distribution of AgeX and how that sort of impacts that number?

--------------------------------------------------------------------------------

Russell L. Skibsted, BioTime, Inc. - CFO [5]

--------------------------------------------------------------------------------

The -- during cash burn, the distribution of AgeX really doesn't have any impact on the cash burn over the remainder of the year. I'm just trying to think through other -- how it might impact it.

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [6]

--------------------------------------------------------------------------------

No, I think the way to look at the cash burn for the rest of the year is -- our expectation is to be able to complete the distribution and going public of AgeX. Most of the spending related to that was in Q1 kind of as Russell mentioned. So we've done a lot of that work, the legal work, the filing work. So we've paid for a lot of that. Going forward, we do have plans to execute that, but then along with that, it's OpRegen, the trial as laid out. It's Renevia. So it's all the things that we have talked about are included in that expected cash burn, AgeX pays for itself already, and it'll continue to pay for itself.

--------------------------------------------------------------------------------

Kevin M. DeGeeter, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research [7]

--------------------------------------------------------------------------------

Great. And then just one operating question, then I'll get back into queue. With regard to Renevia, can you comment as to when you hope to go to FDA sort of is this likely 2Q event or later in the year? And what are the rate-limiting steps to beginning that discussion with the agency?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [8]

--------------------------------------------------------------------------------

Yes. So we -- first, we've already begun the conversation with the agency. We've done the pre-IDE kind of submission. That's the package that you submit. So we've submitted data to them to have a formal conversation. We've had informal conversations. The rate-limiting steps are just FDA processes are long. So we're waiting to have a more substantiative discussion with the package that we've submitted. That could take a month, 2 months. Those are hard to predict. Once that is done, then we can go back with a more formal protocol and have that submitted and approved. So the soon -- as soon as we have more information, which could be in 1 month or 2, we will provide those to you. Everything that we've seen so far gives us decent indication that, look, this year, we'll be able to go through that initial conversation, then go to protocol approval, get that approved and still be able to start a trial by the end of the year.

--------------------------------------------------------------------------------

Operator [9]

--------------------------------------------------------------------------------

Our next question comes from Ren Benjamin, Raymond James.

--------------------------------------------------------------------------------

Reni John Benjamin, Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst [10]

--------------------------------------------------------------------------------

Maybe if you can start off -- it's 2 buckets of questions for me, but starting off with Renevia. Adi, can you tell us what is the ideal sort of label for you guys to get from Europe? And switching gears to the U.S., can you give us any sort of color in how the investigator-sponsored study's going, maybe how many patients? What types of patients are currently being evaluated? And when we might see some results from that study?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [11]

--------------------------------------------------------------------------------

Ren, so now you're asking me for what would be essentially my dream label for Renevia. That's a bit -- yes.

--------------------------------------------------------------------------------

Reni John Benjamin, Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst [12]

--------------------------------------------------------------------------------

That's it. That's exactly what I'm asking you for.

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [13]

--------------------------------------------------------------------------------

Well -- so as you know, we can dream, but we also have a plan to get to that dream label. If the dream happens early, that dream would allow us to have Renevia made available to a large patient population as soon as we hear back from the European agencies. However, our planning is to say we will start with -- if we get HIV-related patient lipoatrophy approval, we have a plan to then file additional data from non-HIV patients and continue to expand that label fairly quickly to make that label broader. So we're trying not to speculate on the dream label, which is have Renevia available for use by most patients that want to have a increase in facial fat volume. So that's kind of where I would say where we are with the Europeans. Things are going fine. We're having these interactions. That's all part of normal process. What we -- with the U.S. study, because it's an investigator-initiated trial, we have less control over the execution of that trial because it's run by, as you know, Dr. Aronowitz in Beverly Hills. He has treated a few patients. And so our hope and our planning and working with him is to try and get him to present that data somewhere in the later part of this year in a conference or podium presentation of some sort to share that data. So he's making decent progress. He's treated a few patients. The types of patients, though, that's important. So these are any patients, so any comers. Anyone who wants or -- to have more mid-face facial volume. Those are the kind of patients he's treating.

--------------------------------------------------------------------------------

Reni John Benjamin, Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst [14]

--------------------------------------------------------------------------------

Okay. And do you need or is it beneficial for you to have this patient data when going to the FDA for more sort of formal protocol discussions? Or frankly, you don't need it?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [15]

--------------------------------------------------------------------------------

Yes. So we don't think we need it. It's not a requirement. I think it definitely helps. So as you know, when you go to the FDA, the more data you take in, it always helps. We don't need it. And so what we are trying to do is go through the FDA process, the way I mentioned before, and along the way, as data comes in, the more data we can take to that final formal meeting, certainly, that will be helpful, especially when it comes to the larger the safety database. As you know, that's what they really care about, right. If you can provide a large safety database from multitude of different patients, that's always helpful. In this space, people have run trials as device fillers. For example, JUVÉDERM and others have run device trials, and basically, they compare it to a nontreated arm. So the size of response and the efficacy is a lot easier for conversation. And because our data so far looks pretty good, I don't think we're worried about efficacy and size of response. So I think for us, having the additional data is good, but it's not a must-have.

--------------------------------------------------------------------------------

Reni John Benjamin, Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst [16]

--------------------------------------------------------------------------------

Got it. And then just kind of switching gears to OpRegen. I guess, this is more sort of philosophical, but I'm curious does drusen cause dry-AMD? Or is it a result of the dry-AMD? And do we know either way for sure?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [17]

--------------------------------------------------------------------------------

I'll take a crack at it, and then I'll let Gary answer because he knows a lot more about this. He's spending a lot of time on drusen. Or maybe Gary, why don't you talk about drusen, and we'll try to round out the answer.

--------------------------------------------------------------------------------

Gary S. Hogge, BioTime, Inc. - SVP of Clinical & Medical Affairs [18]

--------------------------------------------------------------------------------

Yes, sure. So thanks for the question. In general, it is thought that the process that leads to drusen then leads to dry-AMD, and that ultimately leads to geographic atrophy and/or even the wet form as the disease progresses. So the drusen are the leading indicator of the dry-AMD is likely to occur.

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [19]

--------------------------------------------------------------------------------

Which, Ren, when you ask a philosophical question, the reason I said that is, I don't know that there's enough experts who have said one causes the other, but it is an indicator of the other. So that's the subtle difference. And so it is important. And treating drusen is a pretty big deal. There are actually, if you look up products or companies who have thought of approaching just reduction of drusen as a way of treating dry-AMD. But we have told you many times that because it's a multifactorial disease, we believe that having an effect on drusen is important, but having an effect on the photoreceptor layer is going to be important, having an effect on actually having RPE cells is going to be important. And all of those things are the reasons why we're pretty excited about what Gary just talked about earlier in this call.

--------------------------------------------------------------------------------

Reni John Benjamin, Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst [20]

--------------------------------------------------------------------------------

Right. And then as I kind of stare at Slide 5 more and more, I guess I keep wrestling between this idea of the cells kind of finding a home and preventing further deterioration because it is multifactorial and they're probably factors being secreted as well as drusen clearance as opposed to these cells eventually repopulating the RPE cells that have already died. But I guess, both mechanisms of actions are plausible. But what are you guys -- how are you guys thinking that this is working?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [21]

--------------------------------------------------------------------------------

Yes. So we think that it's a little early to make any of those claims, but we think that a little of both is happening. There is -- there are some other data and images that we have presented. We talk about some of the RPE cells that go and phagocytose the wound and RPE cells that were in the body, and we see some repopulation with the new cells being available. So there's a combination of both things happening with OpRegen. But again, all very early, hard to make conclusions. Just really exciting to see it early on enough and that dramatic in some of these patients.

--------------------------------------------------------------------------------

Reni John Benjamin, Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst [22]

--------------------------------------------------------------------------------

Fair enough. And just one final question. How do we think about sort of, I guess, what happens with Cohort 4 -- well, so what happens after Cohort 4? How -- do we think about, based on the results, the potential for a pivotal study, going right into a pivotal study. What's the most likely outcome? Or do we wind up choosing to go to a Cohort 5?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [23]

--------------------------------------------------------------------------------

Yes. So that is a really good question. I would say, as you know, most of it depends on the kind of data you get in Cohort 4. There are others, right. Roche's trial, we can point to lampalizumab, where their primary endpoint was just rate of reduction -- or rate -- reduction of the rate of progression of the atrophy. Now the FDA accepts that as a meaningful enough benefit for dry-AMD, which I agree with, right. If you can slow down the disease, that's a big benefit to these patients. If we show anything better than that, meaning, if we can show even further slowing or stopping the progression, that could be meaningful enough. If we show more than stopping, actually recovering even a portion of the atrophy, that would be even more meaningful. So the reason I bring those up is, in one scenario, where you have a very small benefit, we think that it's likely to go to like a Phase IIb or a full-blown Phase II. If we show more benefit than that, then either one of those more benefits could lead us to have a different conversation with the agency about faster pathways. And right now, the signs are good.

--------------------------------------------------------------------------------

Reni John Benjamin, Raymond James & Associates, Inc., Research Division - Senior Biotechnology Analyst [24]

--------------------------------------------------------------------------------

And just so I'm correct on this, the earlier cohorts, cohorts 1 through 3, did you guys ever measure the geographic atrophy that was occurring? Or you really can't because of the status of those patients?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [25]

--------------------------------------------------------------------------------

Yes -- no, we can measure it, not as accurately because of the size -- I mean, there's -- these are essentially giant atrophy sizes. So they're harder to measure more accurately because they're that big. And there are kind of what you call terminal, in some sense, size atrophies in some of them. So it's less appropriate and accurate in terms of measurement and trying to create a baseline and then looking at progression. So we have some of those images. We're going to -- we're learning something from it, but that's not the appropriate measurement at this time. So we are doing a lot more of those in the patients that we're treating now.

--------------------------------------------------------------------------------

Operator [26]

--------------------------------------------------------------------------------

Our next question comes from Bruce Jackson with LSCM.

--------------------------------------------------------------------------------

Bruce David Jackson, Lake Street Capital Markets, LLC, Research Division - Senior Healthcare Research Analyst [27]

--------------------------------------------------------------------------------

So first a quick housekeeping question on AgeX. At the fourth quarter, the share count was 28.8 million and the BioTime ownership interest was 85%. Is that still the case?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [28]

--------------------------------------------------------------------------------

Russell?

--------------------------------------------------------------------------------

Russell L. Skibsted, BioTime, Inc. - CFO [29]

--------------------------------------------------------------------------------

Yes, that is still the case. Although the total shares of AgeX is larger than that, our ownership, BioTime owns 28.8 million shares of AgeX, which represents 85%.

--------------------------------------------------------------------------------

Bruce David Jackson, Lake Street Capital Markets, LLC, Research Division - Senior Healthcare Research Analyst [30]

--------------------------------------------------------------------------------

Okay, okay. And then a question for Dr. Hogge. Taking a look at the ARVO poster, I wanted to ask about the epiretinal membrane. So it says that in some of the patients, there was some progression. My question just broadly is how many of the patients came into the trial with epiretinal membrane. Can you tell us what it is? Is this kind of standard in this particular type of patient population? And what should we be expecting to see in this particular aspect of the trial?

--------------------------------------------------------------------------------

Gary S. Hogge, BioTime, Inc. - SVP of Clinical & Medical Affairs [31]

--------------------------------------------------------------------------------

Yes, Bruce. So the majority of the patients came in with epiretinal membranes because, as you would expect, in older patients that have had ocular problems, it's not uncommon to have epiretinal membranes. And even the general population, if they're older than 75 years of age, about 30% are walking around with an epiretinal membrane in some capacity. So it's not unexpected that they've had them. And so it's also known that in a vitrectomy, that a surgical procedure can also exacerbate an epiretinal membrane. And so we're monitoring those patients, and we know they're Cohort 4 because they're typically younger and less advanced disease who will likely have less of an issue with an ERM.

--------------------------------------------------------------------------------

Bruce David Jackson, Lake Street Capital Markets, LLC, Research Division - Senior Healthcare Research Analyst [32]

--------------------------------------------------------------------------------

Okay. Super. And then just one also kind of broad question in terms of the response rate that you're expecting to see and the time to response with Asterias, for example. They're doing the trial with the spinal cord injury patients, and they believe that it takes about 12 months for the patients to really show a response to the cellular therapy. What's your experience right now in the eye? And when do you think that you should be seeing some response from the patients in the trial?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [33]

--------------------------------------------------------------------------------

Yes. Bruce, this is Adi. So one of the things we can point you to on the slides that were presented today, as you can see, as soon as the first couple, 3 months, we are seeing response in terms of the structural changes. And given that going forward, we'll be able to do a lot more of those measurements that we care about reporting in the future. We can add those also. So we think that this response is happening fairly quick in terms of structural change, drusen change. You've seen data at 3 months. You've seen data at 4.5 months looking really good. And multiple patients is what we have in these first 3 cohorts. So we think a few months is enough to start seeing atrophy size over other data.

--------------------------------------------------------------------------------

Operator [34]

--------------------------------------------------------------------------------

Our next question comes from Patrick Dolezal with LifeSci Capital.

--------------------------------------------------------------------------------

Patrick Edward Dolezal, LifeSci Capital, LLC, Research Division - Associate [35]

--------------------------------------------------------------------------------

So just as it relates to OpRegen, can you just remind us of the ultimate goal of therapies for dry-AMD, the approval endpoints for this indication? And then kind of how you see the data that you guys have to-date translating in the future?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [36]

--------------------------------------------------------------------------------

So Patrick, I think this is kind of like the question we answered before about what happens to the next steps. Is that what you're asking is...?

--------------------------------------------------------------------------------

Patrick Edward Dolezal, LifeSci Capital, LLC, Research Division - Associate [37]

--------------------------------------------------------------------------------

Yes. I mean, more or less, just kind of how the data to-date are going to translate down the line and how you guys see it kind of coming through on the provable endpoints?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [38]

--------------------------------------------------------------------------------

Yes. So I think for us what is great is seeing response from multiple patients and seeing something like change in drusen, which is -- there's a lot of publications on drusen changes. And it is something that is being used now with the FDA. So that's an area that we can explore. Seeing a change in atrophy size. Those are things that we will measure. Seeing not just the markers of structural and biological change but other functional data that we will gather in the next few months will all help us design and define what we would talk to the FDA about. Now knowing that the FDA has accepted rate of progression of disease, that gives us a baseline that we can use. And I think I mentioned before, anything that we see that might be even better than slowing the rate of progression would be things that we would use in our thinking as we approach the FDA for next steps. Is that next step a pivotal trial because the data look so great and there's such a big need? Is that next step a slightly more defined Phase IIb so that we can nail down that primary endpoint. There -- some of that will come. But I think having this kind of data that we see today go for a few more months and some additional data show up in the coming months is what'll help us define those next steps. We think it's encouraging at this point.

--------------------------------------------------------------------------------

Patrick Edward Dolezal, LifeSci Capital, LLC, Research Division - Associate [39]

--------------------------------------------------------------------------------

All right. And then on Renevia, what is the planned timing for product launch in Europe? And can you provide any additional color on how you're currently thinking about commercialization with respect to the 3 potential strategies that you outlined?

--------------------------------------------------------------------------------

Michael D. West, BioTime, Inc. - Co-CEO & Director [40]

--------------------------------------------------------------------------------

Yes, Patrick. It's -- well, I was just looking at this saying, yes, it was only 6 weeks ago we had the last call. So it's still -- we're still getting there. We have done a lot of work in terms of market research and have pretty good understanding of what that market would be. So we still want to keep our options open with those 3 that we have mentioned. But I think the next couple of months or 3 months will tell us a lot as we go through this discussion with the agency, the label structure come through. We have a little more data on our commercialization plan, and then we'll be able to share that.

--------------------------------------------------------------------------------

Operator [41]

--------------------------------------------------------------------------------

Our next question comes from Keay Nakae with Chardan.

--------------------------------------------------------------------------------

Keay Thomas Nakae, Chardan Capital Markets, LLC, Research Division - Senior Research Analyst of Therapeutics, Devices and Diagnostics [42]

--------------------------------------------------------------------------------

Just back to the ARVO data and specifically the drusen. I'm just trying to understand as a follow-up to that prior question about which is the symptom and which is the cause, but is there any possibility that the improvement in drusen is simply due to the administration of the -- of some substance whether [it's your] cells or anything else, the procedure itself and a response to that, a healing response to that disruption that is affecting the drusen reduction. Or is it clearly attributable to your live cells?

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [43]

--------------------------------------------------------------------------------

Yes. Keay, great question. I'm going to let Gary start off and give you his fill on that.

--------------------------------------------------------------------------------

Gary S. Hogge, BioTime, Inc. - SVP of Clinical & Medical Affairs [44]

--------------------------------------------------------------------------------

Yes. So we know from the patients in Cohort 3, Slide 5, when you look at the area below the geographic atrophy, the GA area, that didn't receive OpRegen cells, you do not see these changes, and these data represented at the summit meeting. So there's a clear difference between the area that was treated and the area that was not treated. And so we're confident that in the recent patients that it's more likely attributable to the OpRegen and not the vitrectomy or anything else.

--------------------------------------------------------------------------------

Operator [45]

--------------------------------------------------------------------------------

Ladies and gentlemen, this does conclude the Q&A portion of today's conference. I'd like to turn the call back over to our host for closing comments.

--------------------------------------------------------------------------------

Aditya P. Mohanty, BioTime, Inc. - Co-CEO, President & Director [46]

--------------------------------------------------------------------------------

Yes. Thank you, everyone, for joining us. We're pretty excited about where we are. So look forward to coming back and sharing more. Thank you.

--------------------------------------------------------------------------------

Operator [47]

--------------------------------------------------------------------------------

Ladies and gentlemen, this does conclude today's presentation. You may now disconnect, and have a wonderful day. There will be a telephone replay of this call starting today at 7:30 and available till the 17th at 11:59 p.m. You can access the replay by dialing 1 (800) 585-8367 and entering access code 7797422 or you may also access the replay by dialing (855) 859-2056 by using the same access code 7797422. Everybody have a great day.