BioTime, Inc. (NYSEMKT:BTX) Q4 2018 Results Earnings Conference Call March 14, 2019 4:30 PM ET
Ioana Hone - Investor Relations
Brian Culley - Chief Executive Officer
Brandi Robert - Chief Financial Officer
Edward Wirth - CMO
Gary Hogge - Senior Vice President of Clinical and Medical Affairs
Conference Call Participants
Naureen Quibria - Maxim Group
Joseph Pantginis - H.C. Wainwright
Reni Benjamin - Raymond James
Keay Nakae - Chardan
Welcome to the BioTime, Inc. Fourth Quarter and Full Year 2018 Conference Call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available on the Investors section of BioTime's website at www.biotimeinc.com. This call is subject to copyright property of BioTime, Inc. and recording, reproduction or transmission of this call without the expressed written concert of BioTime is strictly prohibited. As a reminder, today’s call is being recorded.
I would now like to introduce your host for today's conference, Ioana Hone, Director of Investor Relations at BioTime. Ms. Hone, please go ahead.
Thank you, Jonathan. Good afternoon and thank you for joining us. A press release reporting our fourth quarter and full year 2018 financial results was issued earlier today March 14, 2019 and can be found on the Investors section of our website.
Please note that today's conference call and webcast will contain forward-looking statements within the meaning of federal securities laws including statements regarding our strategy, goals, product candidates and clinical trials, expected synergies and benefits of the Asterias acquisition and financing matters. Such statements are subject to significant risks and uncertainties, including those described in our press release issued on March 14, 2019 and our recent SEC filings on Form 8-K, Form 10-K, and Form 10-Q.
Actual results or performance may differ materially from the expectations indicated by our forward-looking statements, due to these risks and uncertainties. We caution you not to place undue reliance on any of the forward looking statement, which speak only as of today.
Joining us today are our Chief Executive Officer, Brian Culley; our Chief Financial Officer, Brandi Roberts; our Chief Medical Officer, Ed Wirth; and our Senior Vice President of Clinical and Medical Affairs, Gary Hogge. The executives will provide prepared remarks, then take questions from analysts and institutional holders.
With that, I'd like to turn the call over to Brian Culley, our CEO.
Thank you, Ioana. And good morning, everyone. We have been extremely busy since my first earnings call just five months ago with significant advancements made on the corporate development, clinical and operational fronts. BioTime is a very different company than when I joined as CEO in September of last year and we will continue to pave the way toward our objective of becoming a leading cell therapy company.
On our last call we outlined our plans to simplify BioTime’s corporate structure and focus on our most compelling clinical opportunities. We intended to accomplish this in part through targeted transactions with our affiliated companies. We have executed on these near-term promises and I would like to highlight those recent accomplishments briefly before going into greater detail on each one.
First at the beginning of this week we announced that we completed our acquisition of Asterias Biotherapeutics, broadening our pipeline with the addition of two synergistic and compelling clinical stage cell therapy assets.
In January, we entered into exclusive agreement with Orbit Biomedical and we will collaborate with Orbit on the use of their proprietary injection technology to deliver OpRegen for the treatment of dry age related macular degeneration in our ongoing clinical study.
We also made some recent changes to our executive team. In January, we announced the appointment of Brandi Roberts as our Chief Financial Officer and Senior Vice President of Finance; and more recently, as a result of the acquisition of Asterias, we also added Dr. Ed Wirth as our Chief Medical Officer. Ed will oversee the clinical development of the OPC1 and VAC2 programs.
As a reminder, BioTime owns a large portfolio of cell therapy technologies and patents. The actual and potential product candidates continued within this platform exceed our ability to fully develop them. As a result, from time-to-time we look to strategically convert some of these earlier stage or non-core research programs into new businesses from which cash or equity can be utilized to support are more clinically advanced and internally held programs.
For evidence of this effective strategy, I can point to the fact that we now have successfully launched two public companies, OrthoCyte Corporation and AgeX Therapeutics, each value today of more than $150 million and each one launched with assets that originated from within BioTime.
In the first example, OrthoCyte recently reported positive results from an R&D validation study of DetermaVu in non-invasive liquid biopsy test intended to facilitate clinical decision making in lunch cancer diagnosis. BioTime owns approximately 28% of OrthoCyte’s common stock. And as of yesterday, OrthoCyte was trading at $3.81 per share. So the value of BioTime’s equity position in OrthoCyte was approximately $55.9 million.
And the second example, last year, we sold a portion of our ownership of AgeX Therapeutics to a private company called Juvenescence for a total of $43.2 million. We also distributed approximately 12.7 million shares of AgeX common stock to BioTime’s shareholders and launched AgeX as a newly listed public company.
AgeX has performed well as a public company and as of yesterday was trading at $4.19 per share. The value of BioTime’s nearly 5% equity position in AgeX as of yesterday was approximately $7.2 million and we are still owed $21.6 million from Juvenescence which is due to us no later than August 2020, which represents yet another source of opportunistic capital for us.
We’re pleased with the performance of our subsidiaries and affiliates and believe further value may be extracted from their success.
In addition to the $23.6 million in cash we had at year end and the Juvenescence note with a face amount of $21.6 million, we hold approximately 14.7 million shares of common stock in OrthoCyte and 1.7 million shares of common stock in AgeX. Although no assurances can be given as to the value of Juvenescence note or of those shares I described if and when we were to dispose of them, but those assets together with our cash, represent more than $100 million of assets that could be used to help fund our operations.
Looking forward, 2019 will be an important year with significant planning and execution required on clinical and operational fronts. Our first order of business will be fully integrating the Asterias assets into our pipeline and doing this quickly and successfully so that the financial synergies we anticipated, primarily related to personnel, can be realized.
To that end, we plan to apply our OpRegen process development and scale up teams onto these various programs so that they can contribute learnings and success they had with OpRegen manufacturing to our two new cell therapy assets.
With that brief introduction complete, I next will review each of our programs and plans for the year in a bit more detail as this will be the first time we are discussing the plans for the newly combined company.
I will begin with our lead program OpRegen. OpRegen is an allogeneic or off-the-shelf cell therapy treatment in development for dry-AMD, the leading cause of adult blindness in the developed world. There currently are no FDA approved treatments for dry-AMD.
Our planed approach with OpRegen is to manufacture and deliver healthy RPE cells to the back of the eye to replace dead, dying or dysfunctional RPE cells. We believe this approach can slow the loss of vision and possibly improve vision in effected patients. OpRegen has been granted Fast Track designation by the FDA and currently is the subject of a Phase I/IIa multi-center clinical study.
This study is designed to evaluate the safety and tolerability of different doses of OpRegen but we also are collecting markers of efficacy which will help inform our decisions and strategy for the next trial.
The current study is expected to enroll a total of 24 subjects divided into four cohorts according to disease stage and visual acuity. Of the 24 subjects, 12 legally blind subjects with best corrected visual acuity of no better than 20/200 have been enrolled and we now are enrolling patients with best corrected visual acuity as good as 20/64. We have dosed three of these better vision patients so far with nine better vision patients remaining to be enrolled and dosed, which we expect to be completed this year.
Data reported to-date from the study indicate the treatment with OpRegen is well tolerated with signs of structural improvement in the retina and reductions in drusen density observed in some patients.
In particular, early data collected from better vision patients appears encouraging. We can identify evidence of the continued presence of transplanted cells, signs of structural improvement within the retina. And although the data are preliminary and the number of treated patients is small with limited follow-up, there are early suggestions of improvements in visual acuity. Additional treatments and longer follow-ups will be important to us because better vision patients with earlier stage AMD more closely represent the patient population we ultimately hope to treat.
I next want to explain the significance of the exclusive partnership we announced in January with Orbit Biomedical in which we will assess their recently approved sub-retinal delivery system which is vitrectomy-free delivery device for targeted administration of whole cells to the eye.
Delivery of cells to the sub-retinal space is a well-known challenge for ophthalmology companies. Traditionally, the sub-retinal space is accessed first by a vitrectomy or removal of the gel like substance that fill the eye, followed by an injection through the front of the eye and all the way back into and under the retina itself, puncturing the retina as necessary as a part of the process.
As you can imagine this procedure involves some risk to the patients and furthermore removal of the needle is associated with efflux of cells away from the injection site, leading to dose variability as well as the potential for delayed complications.
Orbit’s sub-retinal delivery system which recently received 510(k) clearance from the FDA is designed to precisely and consistently deliver therapeutics to the sub-retinal space via a super suprachoroidal route, avoiding the need for both a vitrectomy and perforation of the retina from the vitreous base.
We’re excited to deploy the Orbit device into our ongoing trial as soon as possible. Because we believe that if successful the use of this device could not only decrease the number of adverse events we might otherwise observe but also may provide superior dose control of our cells in our clinical trials, which may lead to smaller and more well controlled data collection.
We believe this ultimate anatomical route of delivery could become a new standard-of-care in ophthalmology, which is why we have obtained the exclusive right to negotiate commercial supply terms with Orbit for the delivery of sales in the field of dry-AMD.
Looking ahead on the data front, we expect to present updated results from the ongoing OpRegen clinical study, including additional data on the better vision patients at the ARVO Annual Meeting on May 2nd of this year.
Moreover, we are working toward initiating dosing of the first patient with both the Orbit device and a new thaw and inject formulation of OpRegen in the second quarter of 2019. We anticipate completion of patient enrollment in this study will occur by the end of the year.
Moving now to Asterias, just a few days ago we announced the closing of the acquisition of Asterias, with that company now becoming a wholly-owned subsidiary of BioTime. Notably, 98% of BioTime vote casts and 96% of Asterias vote casts were in favor of this merger which we believe reflect strong support from stockholders for the advancement of the combined company and product candidate pipeline. We expect this acquisition to be synergistic in a number of ways.
First, we believe Asterias’ cell therapy product candidates fit naturally and operationally within BioTime’s existing business and serve our objective of creating a dominant cell therapy company.
Moreover, we expect to benefit from substantial financial synergies and enjoy other advantages from our critical mass, which collectively supported our decision to acquire Asterias. We also will look to strengthen and broaden the existing collaborations with Asterias’ notable and relevant partners, including the California Institute for Regenerative Medicine or CIRM and Cancer Research UK.
From a general management perspective, two members of the former Asterias Board of Directors will serve on the BioTime Board and we anticipate a smooth transition and integration process.
Importantly, we believe BioTime’s shareholders will benefit from the current and future value of a broader and more innovative pipeline as well as the opportunity to address the lead areas that are in need of groundbreaking approaches and which seem like suitable if not superior targets for whole cell approaches compared to small module or antibody-based techniques.
I now would like to spend a moment to introduce you to OPC1 one of the two clinical programs we acquired from Asterias. OPC1 is similar to OpRegen insofar as the basic approaches to manufacture and deliver to the body a very specific kind of cell.
In the case of OPC1 the approach is to manufacture and deliver an oligodendrocyte progenitor cell which is a type of glial cells found in the central nervous system. Oligodendrocyte progenitor cells are naturally occurring precursors to the cells which provide electrical insulation for axons. Their application to spinal cord injury or SCI is because severe functional impairment including limb paralysis, aberrant pain signaling and loss of bladder control and other body functions can occur when spinal cord cells are subjected to and damaged by a crush or contusion injury.
Based on the reparative properties associative with oligodendrocyte we believe the delivery of healthy new spinal cord cells is ideally suited to treating neurological conditions such as SCI and potentially other disorders of demyelination. The OPC1 cells also have been shown to have additional functions such as the secretion of neurotrophic factors and stimulation of new blood vessel formation which we believe provides further support to the process of tissue repair in the injured spinal cord.
The OPC1 program currently is in a Phase I/IIa multi-center clinical trial in SCiStar for treating acute spinal cord injuries, and which recently completed enrollment. Clinical development of OPC1 has been partially funded by a $14.3 million grant from CIRM and we intend to seek additional non-dilutive funding from CIRM later this year.
OPC1 has received Regenerative Medicine Advanced Therapy or RMAT designation for the treatment of acute SCI and has been granted orphan drug designation by the FDA. In January of this year top-line data was announced from the OPC1 trial. The primary goal of this study was to observe the safety of OPC1 in cervical spinal cord injury patients and to accumulate data on dosing, timing and engraftment to aid the design of later stage trials.
The key findings from the study included positive safety profile, specifically MRI scans at 12 months post injection showed no evidence of adverse changes in any of the 25 subjects treated with OPC1 and to-date there have been no unexpected serious adverse events related to the OPC1 cells.
All three subjects in the cohort 1 and 95% of subjects in cohort 2 through 5 have MRI scans at 12 months, consistent with the formation of a tissue matrix at the injury site which is encouraging evidence that OPC1 cells have engrafted and help to prevent cavitation, a destruction process that occurs following injury and which typically results in permanent loss of motor and sensory function and which can lead to serious additional complications.
From an efficacy perspective, at 12 months 95% of subjects recovered at least one motor level on at least one SCI and 32% of these subjects recovered two or more motor levels on at least one SCI according to the ISNCSCI scale, the International Standards for Neurological Classification of Spinal Cord Injury, the exam that’s used to determine motor score.
Notably, no subjects experienced decreased motor function following administration of OPC1 and subjects consistently retained the motor function recovery seen through six months or saw further motor function recovery from six to 12 months.
We now are in the process of analyzing the full dataset from the SCiStar trial to inform how best to proceed with this promising program. We expect to propose the clinical plan to the FDA later that year and to share the outcome of those discussions when they are available.
In the meantime, we will be leveraging our manufacturing capabilities and process development expertise from the OpRegen program to try and accelerate OPC1 product development. We also plan to submit for further grant support from CIRM around the middle of this year.
The second clinical program we acquired from Asterias is VAC2 is an allogeneic or off-the-shelf cancer immunotherapy consisting of antigen presenting dendritic cells and is currently in a phase I clinical trial in subjects with non-small cell lung cancer.
VAC2 is designed to stimulate a patient’s immune responses to its tumor antigen commonly expressed in cancerous cells but rarely found in normal adult cells. Similar to OpRegen and OPC1, VAC2 is produced from pluripotent cell technology but uses a different lineage differentiation protocol to generate a population of mature dendritic cells. We use dendritic cells because they are potent antigen presenting cells which instruct the body’s immune system to attack and eliminate harmful pathogens and unwanted cells.
To target cancerous cells VAC2 is engineered to express a tumor selected antigen found in over 85% of all cancers. Because the tumor antigen is loaded exogenously into the dendritic cell before treatment VAC is actually a platform technology that can be modified to carry essentially any antigen including patient specific tumor neo-antigens. VAC2 represents just one promising foray from this platform.
In the VAC2 program four patients have been enrolled to-date in the Phase I clinical trial and enrollment will continue throughout 2019. We are fortunate that the VAC2 trial is being fully funded and conducted by Cancer Research UK, the world's largest independent cancer research charity.
Upon completion of the Phase I trial BioTime has an exclusive option to acquire the data generated in the trial from Cancer Research UK for approximately $1.6 million. Still though we don't currently have operational control over the VAC2 critical trial, we provide input to Cancer Research UK and the arrangement offers us tremendous optionality at an attractive price.
Turning next to Renevia, our medical aesthetics program targeting an HIV lipoatrophy induction, we submitted our CE Mark application for Renevia in 2018 to BSI, the independent accredited body in the UK responsible for reviewing such applications and their review is ongoing.
It is important to note that this regulatory review process does not come with a statutory clause, meaning BSI can take as long as it deems necessary to review our application. Our best estimate at this time for a response is some time in the second half of this year.
If our application is approved, we intend to identify an external partner for commercialization of Renevia in Europe and as shared previously the US market is no longer part of our commercial plan, because the FDA indicated it would designate Renevia as a drug device combination. So the shorter regulatory path afforded to devices is not available for Renevia in the US.
Lastly, I want to bring attention to one of our core competencies whole cell manufacturing which is a foundation of cell therapy. I believe manufacturing is an underappreciated competitive advantage for BioTime based on our commercially viable GMP manufacturing facility and experienced staff of more than 30 professionals located in Jerusalem, Israel. They’ve done an exceptional job with our OpRegen clinical program.
Driving the lineage of whole cells and controlling their manufacture up to commercially viable scale is a difficult task but our team has made significant improvements with the process development and commercial viability of our OpRegen product candidate.
Our facility manages storage, clinical supply manufacturing, scale up production and stem cell banking and handling. And we now have successfully produced enough OpRegen clinical trial material to conduct our next study. And we will focus our efforts on optimizing process development and scale up activities for the assets we have acquired from Asterias.
I will now take a break and turn the call over to Ed Wirth to introduce himself. He then can pass the call over to Brandi to introduce herself and provide the financial overview. Ed?
Thanks, Brian. I’m very pleased to transition from the role of Chief Medical Officer of Asterias directly into the role of CMO of BioTime. Nearly my entire career over the past 25 plus years in academia and industry has focused on the translational and clinical development of cell-based therapies for neurological indications, and more recently, cancer.
As a faculty member of the University of Florida I planned and conducted the first Phase I clinical study in the USA of neural tissue transplantation in the human subjects with spinal cord injuries.
In 2004 I transitioned from academia to industry and served as the Medical Director of Regenerative Medicine at Geron Corporation where I planned and led the world's first clinical trial of human embryonic stems cell-derived product GRNOPC1 now known as AST-OPC1 in patients with acute SCI.
Since joining Asterias Biotherapeutics at its inception in 2013 I had led the continued development of AST-OPC1 via the SCiStar trial and worked closely with my former experienced colleagues on the VAC2 program. I look forward to working with the BioTime team to continue advancing the OPC1, VAC2 and OpRegen programs into later stage clinical trials. Brandi?
Thank you, Ed. I would like to start off by saying that I’m really happy that I joined the BioTime team. I believe that my strong leadership skills in finance and operational areas such as clinical development and manufacturing will be helpful as we continue on our mission to becoming a leading cell therapy company.
I bring over 20 years of experience to my position. I’m a CPA and started off my career at PricewaterhouseCoopers, so I have a strong foundation of accounting and financial knowledge. I worked at Pfizer for seven years, so I also have a strong foundation in pharmaceutical research and development. When I was a CFO at Mast, I helped to run the largest sickle-cell clinical trial ever completed. It encompassed 388 patients at 75 sites in 12 countries. I provided operational oversight including significant project management as we worked to complete data lock in a timely manner and finished our study within budget.
I understand the needs of clinical stage companies and I look forward to working with the team here to create shareholder value as we work to deliver clinical data on our three cell therapy programs.
I will start off the financial discussion with some balance sheet highlights. At December 31, 2018 BioTime’s cash and cash equivalents totaled $23.6 million. Our marketable securities, which include our investment in AgeX, totaled $7.2 million. Our investment in OrthoCyte was value at $20.3 million as of December 31, 2018. But as Brian mentioned previously, OrthoCyte released positive data recently and has seen a significant increase in its stock price. Accordingly, our investment in OrthoCyte was worth $55.9 million as of yesterday.
Our promissory note from Juvenescence is valued at $22.1 million as of December 31, 2018. If Juvenescence completes an IPO prior to note maturity then the note will convert into Juvenescence stock. The conversion is subject to an upward adjustment if the 20 day VWAP of AgeX stock is above 3%. Based on yesterday’s closing price, the 20 day VWAP of AgeX is $4.43.
If the conversion were to take place now, the number of shares to be issued would be adjusted upward by roughly 1.5 times and the shares would potentially be worth more than $30 million. If the promissory note is converted, our Juvenescence stock will be a marketable security that we may use to supplement our liquidity needs. If the promissory note is not converted, it is payable in cash, plus accrued interest of 7% per year which is roughly $1.5 million per year at maturity in August 2020.
And looking at our statement of operations it’s important to remember that we deconsolidated AgeX as of August 30, 2018. So when looking at the entire year, AgeX revenue and expenses were only included for eight months. To make this easier to understand, we have included a non-GAAP table in our earnings release as well as our GAAP financial statements. The non-GAAP table breaks out BioTime versus AgeX operating expenses as well as non-cash and non-recurring charges.
Please keep in mind when reviewing this table it does not represent a cash flow by entity because grants and other revenues are not included in the total.
Revenues for 2018 were $5 million, an increase of $1.5 million compared to the prior year. The increase was primarily related to an increase of $1.9 million in grant revenues, offset by a reduction of $400,000 in subscription and research related revenues due to the deconsolidation of AgeX. Our grant revenues for 2018 were from the Israeli Innovation Authority and the NIH.
Operating expenses are comprised of R&D expenses and G&A expenses. Total operating expenses for 2018 were $46.5 million as reported, which is comprised of $38.8 million for BioTime and $7.7 million for AgeX.
Total operating expenses for 2018 were $37 million, as adjusted, which is comprised of $31 million for BioTime and $6 million for AgeX. R&D expenses for 2018 were $21.8 million, a decrease of $2.2 million compared to prior year. The decrease was mainly attributable to reductions in AgeX related program, LifeMap Solutions expenses, Renevia program expenses and the absence of OrthoCyte R&D expenses in 2018 that were incurred in 2017. The decreases were partially offset by an $800,000 write-off of certain acquired IP R&D assets by AgeX in March 2018.
G&A expenses for 2018 were $24.7 million, an increase of $4.8 million compared to prior year. The net increase was primarily attributable to increases in management transition and compensation costs, legal audit and compliance costs related to the AgeX distribution and share-based compensation expense due to new equity award grants. The increases were offset by reduced G&A expenses for OrthoCyte, LifeMap Solutions and AgeX.
As we turn to 2019, one of our major goals will be to realize synergies from the Asterias acquisition. At this point in time, we’re working on the transition of manufacturing activities from Fremont to Jerusalem and evaluating our plans for the next clinical trial of OPC1. We’re still working out the final details of our 2019 budget but we do anticipate our 2019 cash spend will be significantly less than the prior year.
Even with taking into consideration one-time expenses related to Asterias acquisition and the evaluation of the Orbit device in 2019, we still intend to spend less than the combined company in the prior year.
In connection with the Asterias acquisition we expect to make extensive reductions in headcount and non-clinical related spend. We will also continue to evaluate our existing operations for additional cost efficiencies as we progress our clinical programs in the best way possible.
We plan to provide more detail on financial guidance at our first quarter earnings call that is anticipated to take place in May.
And with that, I will turn the call back to Brian.
Thanks, Brandi. As you can tell we’ve been rapidly transforming BioTime into a leading cell therapy company through strategic transactions on the corporate development, clinical and operational fronts and we have no plans to slow our pace of progress.
We will remain focused on advancing our clinical programs in a thoughtful and cost effective manner throughout 2019 and will update investors frequently on our timelines, achievements and regulatory plans.
Some things we look forward to this year include: A new corporate brand focused on clinical stage cell therapy programs which we expect to be launched in the second quarter; Updated results from our Phase I/II clinical study of OpRegen for the treatment of dry AMD at the 2019 ARVO Annual Meeting in May; Initiation of dosing with the Orbit device and the new thaw and inject formulation in our ongoing clinical study of OpRegen anticipated in the second quarter; Advancing the OPC1 program including manufacturing improvements and plans to meet with the FDA to discuss next steps in the clinical development of the program; Strengthen partnerships with CIRM and Cancer Research UK for the ongoing support of the OPC1 and VAC2 programs; Completion of the patient enrollment in our Phase I/II clinical study of OpRegen anticipated by the end of this year; Evaluating the development of OPC1 as a candidate for multiple sclerosis and ischemic stroke through ongoing research collaborations we have with major universities; And increase presence in the patient, physician and advocacy communities; And lastly, decision on BioTime’s CE Mark application for Renevia which is expected in the second half of 2019.
I believe in the past six months following my hire, we have delivered on promises to take BioTime in an exciting new direction and we will continue to increase visibility of the company in our attempt to build institutional and retail support through continuous communication and engagement. Our goal is to build awareness and support for a reinvigorated and repositioned BioTime that will be this management team’s priority and focus in 2019 and beyond.
And with that, operator, we are ready for questions.
[Operator Instructions] Our first question comes from the line of Jason McCarthy from Maxim Group. Your question please.
This is actually Naureen calling on behalf of Jason. Congratulations on the quarter. We were just wondering one question really with regards to the spinal cord asset that you acquired with the Asterias acquisition. You mentioned that you have a meeting coming up with the regulatory authorities later on in the year. Where do you think the path forward is with regards to this asset and is that advancing in the setting of spinal cord injury?
Hey, Naureen, thanks for joining. So because it's a new asset to BioTime, we are just going to be evaluating the existing path. At present we don't have any reason to think that the path that Asterias had discussed with the FDA has any flaws or deficiencies or problems, it's just a matter that we want to go through and make sure that we’re comfortable with it as well. If there are any changes whether those are to regulatory strategy or on CMC side or anything like that, that is something that we would update accordingly. But at that time we know that Asterias has done a lot of work and had very promising interactions with the agency on a proposed next study. And so until and unless something changes, it does grow with that program.
And just a quick question on what you could be presenting at ARVO with regards to OpRegen. Can you talk about how many patients have been enrolled and what we are missing there? Any cohorts or …?
Yes. I'll hand that question to Gary Hogge, who can provide you with some more information.
Yes, thanks for the question, Naureen. So as Brian said there are 12 patients that were involved in Cohorts 1 through 3, additional 3 patients with better vision in Cohort 4 and those data will be updated and presented at ARVO. So a total of 15 patients will be presented.
Thank you. Our next question comes from the line of Joe Pantginis from H.C. Wainwright. Your question please.
Thanks for taking the question. And congratulations on getting Asterias done. Also starting with OPC1, just curious, you did mention Brian that you will obviously be doing some internal analysis of the data, so was curious about what your public disclosure plan might be especially with regard to granularity on the patient populations in the study to-date and differences between say the AIS-A and the AIS-B populations as an example?
Yes. That’s something I think that -- I’m going to have Ed join in just a second. I think Asterias didn’t provide let’s say patient level data yet and so Ed can provide a quick review of what’s currently known. And then what are things that we will be doing as we continue to analyze this data is provide greater granularity because that will help it form our strategy, such as our inclusion-exclusion criteria in the next study.
Yes. Thanks, Brian. So yes, you may recall Asterias didn’t provide, as Brian mentioned top-line data earlier this year for the 12 month primary readout in the study and the plan as Brian mentioned is underway right now to deeply analyze this data. We believe that the data we have thus far are very informative as it relates to later stage trials with respect to patient inclusion, dosing-- dose level, dose timing and so forth. So again we’re evaluating all of those variables right now and those will factor into our plans going forward and our coming meetings release with the FDA.
But with regard to say public disclosure of any of these analysis?
Joe there is nothing on the calendar right now. But as we have summaries available whether those are in the form of peer reviewed publications or abstracts or presentations, I imagine that would be something that we would be sharing this year.
No, that’s helpful and then just one quick question hopefully. So as you are looking to get patients on the OpRegen study going under the Orbit delivery system, just curious what the outstanding punch-list might look like with regard to getting a patient to that stage?
Look, you're probably familiar just that there's a 30-day waiting period for any protocol amendment that goes in and then prior to that there is a little bit of qualification of the Orbit device that gets done. So those two things together we anticipate that our first Orbit patient will occur in the second quarter.
Thank you. Our next question comes from the line of Reni Benjamin from Raymond James. Your question please.
Can you talk a little bit about enrollments in the OpRegen program right now, are you finding any sort of difficulty in obtaining these patients and identifying the patient's? I guess where I’m going with this is I would have expected the next six patients in that study to be enrolled a lot quicker than kind of by the end of the year.
Yes, Ed please?
Hey, Reni. As we’ve gone to the better vision cohort, the Data Safety Monitoring Group as well as the FDA put in mandatory stagger periods where they wanted to evaluate the safety in those individual patients. Also as those evaluations were ongoing we began the discussions with Orbit and as Brian alluded to earlier we certainly believe that Orbit may represent a superior way to administer OpRegen. And so in a way we’re hoping now for the OpRegen to be received by the agency.
And just to clarify the nine remaining patients to be dosed in Cohort 4, they are not going to be with the Orbit injection technology, they'll be dosed the classic way and then you will have an additional x number of patients with the Orbit technology?
No, our goal would be to treat the next six patients using the Orbit device at least the next six patients.
And then I know that you guys mentioned on the call and on the press release about looking at the cell therapies as a potential treatment in multiple sclerosis and ischemic stroke. I think it was the OPC1 candidate. Can you talk a little bit about, what's driving your thought process there? Have you done work with OPC1 in these indications or is it more from work that's been done externally that makes you think that this might be a great area to go into?
Yes, I mean absolutely we're always looking for ways that existing programs may have a broader application, so rather than thinking of OPC1 as limited only to spinal cord injury, maybe it is appropriate to look at it in terms of conditions at a demyelination. So Ed if you could comment about some of the work that Asterias has done with some of the academics looking at other areas that OPC1 could potentially go into in the future?
Yes, so on the MS front we have had prior collaborations with academic institutions and also we had an ongoing collaboration with investigated obviously line actually that developed unique animal model of MS where the immune attack is directly against the myelin forming cells but it wouldn’t be necessarily reject our cells. So we’re looking at that model, potentially to help us evaluate the ability of OPC1 to re-myelinate axon in a very good MS animal model.
With regard to stroke, stroke actually -- about one-third of all strokes are predominantly in the white matter which is targeting OPC1 but even major strokes have a significant white matter component to them. And so we have a collaboration in progress as we speak right now, a preclinical efficacy study in the leading animal model of stroke which is the middle surgical artery inclusion model with an investigator at University of South Florida who has done quite of few of these studies, and there the in line phase of that applicable collaboration should be completed in the second quarter and then once the data are analyzed and so forth I would imagine slightly later year we would have -- be able to provide an update from that work.
And just switching gears to Renevia real quick. Has there been any sort of back and forth with the European agency Brain? I mean typically during this phase there is both a question-and-answer period, sometimes the clock stops. Can you just give us a little bit more color there? And you mentioned a distribution agreement, what would be ideal sort of a distribution agreement look like?
So I'll do the second part of it before the first part. So we don’t currently have the infrastructure to establish a European commercial business. So I think what would be ideal for us would be to find an entity that has those capabilities and structures something where we can enjoy the potential upside, essentially shift the risk -- shift the commercial risk onto somebody else. With respect to the process, Gary, you can provide -- I mean we have been going back and forth, there’s different divisions within that group that we interact with.
Yes, so we’ve interacted with a number of other groups on the CMC side from the animal component aspect and we’re still awaiting clinical questions. So we know that they are actually reviewing it but at this time we have no deadline and to your question as to the stop clock, particularly if there is no clock and no stop clock, so it’s entirely we respond when we receive questions but thus far no positive interactions.
And one final one if you will let me. Regarding manufacturing you spent some a little bit time talking about it on the call. What are your thoughts in terms of keeping it in-house versus working with the CMO at later stages of development?
Cell therapy is not like making Aspirin as everyone knows, and I feel strongly that owning manufacturing, controlling manufacturing has tremendous value. These cells can diverge through the process and I think throwing it over the wall to a CRO, especially one that hasn’t been doing it for years and years, is a big gamble. There in some cases maybe some cost savings. Although frankly I think what we -- what our expense structure looks like is, is really attractive. So you never know what may happen in the future if a partner wants to come in and buy commercial right, some or all of the commercial rights and demand to absorb manufacturing, obviously we’re open to having that conversation. But we’re pretty happy with our very new facility there and the work that's been done.
Working towards getting a close system, growing these cells in bioreactors, these are things that I think are perhaps underappreciated and meaningful differentiating characteristics for that program vis-à-vis some of the other things that are happening out there in the space.
The next question comes from the line of Keay Nakae from Chardan. Your question please.
A couple of question about the collaboration with Orbit. First of all, trying to understand how quickly a practitioner becomes [facile] using this device? Maybe to start, what kind of clinical data did Orbit have in getting the 510(NYSE:K)?
Yes. Hi, Keay that’s a good question for Gary.
So the data for 510(K) clearance was granted at the end of November. They had extensive process, human developments, there was a paper published by Allen Ho out of Philadelphia area looking at some patients using the Janssen cell line. Janssen decided not to pursue that and then Orbit was an option of that. They conducted device improvement and undergone extensive human and animal testing as part of that filing with agency and so based on those data and the FDA clearance we feel comfortable beginning patients with -- OpRegen patients with Orbit.
So is it straight forward for the surgeon to utilize the device or what kind of training or even in some sort of non-human model do they need to undergo before they feel comfortable putting into a human eye, especially in somebody with less savior vision impairment.
Right. So there is training process -- physical training process, it is suprachoroidal route, so it’s not something that a typical retinal surgical specialist undergoes training and so they have an extensive training program involving online aspects, dendritic lectures and wet lab experience in preparation for that.
And our investigators undergo those before they began treating any subjects.
And in terms of the exclusivity of the collaboration, is this exclusive only to cells administer to the eye from dry-AMD or those include potentially other therapies?
Orbit’s business model if I could speak for them would be to partner with various companies in different parts of the eye and different approaches. We feel extremely satisfied that we have whole cell delivery to the back of the eye for the field that dry-AMD. It's not limited in some way. But we would imagine as that company is going to also approach some of the gene therapy companies or others that work in the eye that may have other diseases or indications, as long as we have the right to lock-up the space that we are working in that’s sort of primary interest to us.
Two more questions. One, have you explored the potential to get on that designation for dry- AMD indication?
This is something we will definitely engage with the agency when we interact with them presenting some of our Phase I/IIa data.
Okay, and just the final question on the manufacturing and moving to Israel, if you could just maybe quickly describe what it is that they are able to do much better than what you've been able to do in three months?
I wish I could, certainly components of these are proprietary illustrated part of competitive intelligence. I did allude to some of them in a general way working towards having a closed system, growing cell in bioreactor, so we think about more three-dimensional cell growth in production rather than two dimensional. The COGS improvement that you have their, the scale improvements you have there and the control improvements you have there without going any further, those are sort of the categories of advantages that we think are relevant to that program.
Thank you. This concludes the question-and-answer session. I'd like to hand the program back to you Brian Culley for any further remarks.
Alright, I appreciate everyone joining us this afternoon. I'm obviously excited about our plans and thank you for your interest in our business, and I hope we will be able to keep this positive momentum going for a long-time. Thank you very much.
Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.