ReNeuron Group PLC (RNUGF) 首席执行官 OlavHellebø在 2019年 第四季度业绩 - 收益电话会议记录

[机器翻译] 电话会议 · 2019年07月12日 · 17 次阅读

ReNeuron Group PLC (OTCPK:RNUGF) Q4 2019 Earnings Conference Call July 11, 2019 5:00 AM ET

ReNeuron Group PLC([OTCPK:RNUGF])2019年第四季度收益电话会议2019年7月11日美国东部时间上午5:00


Olav Hellebø - CEO & Director
Michael Hunt - CFO, Secretary & Executive Director

  • OlavHellebø - 首席执行官兼董事
  • Michael Hunt - 首席财务官,秘书兼执行董事


Andy Smith - Edison Investment Research
Christian Glennie - Stifel, Nicolaus & Company
Julie Simmonds - Panmure Gordon

  • 安迪史密斯 - 爱迪生投资研究
  • Christian Glennie - Stifel,Nicolaus&Company
  • Julie Simmonds - Panmure Gordon


Good morning. Welcome to ReNeuron's preliminary results presentation for the year ended 31st of March 2019. I'm Olav Hellebø, and with me is Michael Hunt, our CFO. And let's just jump into it.
So just a little warm up in case you don't know us. But looking at you, most of you will know this. We are a global leader in cell therapy. What we work on is allogeneic therapies. We have two assets in clinical trials. And we have a very good news flow for the next year or two coming up. So here's a quick overview of the platform.
Human retinal progenitor cells is a cryopreserved formulation that we are using in retinitis pigmentosa. We are in the Phase IIa study currently, and we'll get into more details on that. CTX is an immortalized neural progenitor stem cell line. Again, cryopreserved. Enables us to conduct clinical trials in a more reasonable fashion, being able to ship and store these products. There are pretty good shipping containers available now so you can actually get it anywhere you want, really, in the world.
These two programs are partnered with Fosun Pharma for China and unencumbered in the rest of the world. Exosomes is our up and coming platform, so these are vesicles derived from our CTX cells that we are working on, mainly for the moment as a drug delivery vehicle for other therapeutics based on demand in the marketplace out there for that. So here is the pipeline. The initial indications are retinitis pigmentosa for the retinal program and stroke disability for the CTX program. Both these programs are in a Phase II study, Phase IIa for the RP and Phase IIb for CTX. And this is part of our strategy over the last few years is to push our programs from being single arm studies in the U.K. to get into controlled clinical trials in the U.S. So we're on that journey.
The last year was a very big year for us, both in terms of pipeline progress as well as deals. For hRPC, we were able to get into, after many years of hard work, both on quality, manufacturing, et cetera, we were able to finish our Phase I part where we did dose escalation and we also developed a cryopreserved formulation. We were able to get into patients who have some remaining vision potential, meaning the retinal architecture is intact enough for a potential efficacy. The first new patients in that study we announced earlier in the year. Normally, we wouldn't want to announce such a small cohort out of a study, but since there were very surprisingly large efficacy gains on those new patients, that was a material event that we were forced to send a press release out on. And we are very excited about the progress on those patients, and so it's very motivating, thus, to listen to their description of changes to their vision.
The Phase IIa is continuing. We will -- it allows us to treat up to 12 patients in total in the Phase IIa cohort. So we're working on finishing those patients over the summer. And we will present then the full data at whatever the time point is that we will have those patients at the American Academy of Ophthalmology, which is the big American ophthalmology meeting. It's in October, in San Francisco, and we have a presentation slot reserved for us for that, so we're looking forward to sharing the data with you at that time. For CTX, we have started the Phase IIb trial, PISCES III, and we expect then top line data from that late next year.

早上好。欢迎来到ReNeuron在2019年3月31日结束的一年中的初步结果演示。我是OlavHellebø,我的是我们的首席财务官Michael Hunt。让我们跳进去吧。


人视网膜祖细胞是我们在色素性视网膜炎中使用的冷冻保存制剂。我们目前正在进行IIa期研究,我们将详细介绍这一点。 CTX是永生化的神经祖细胞干细胞系。再次,冷冻保存。使我们能够以更合理的方式进行临床试验,能够运输和储存这些产品。现在有很好的运输容器,所以你可以在世界各地随时随地获得它。



IIa阶段仍在继续。我们将 - 它允许我们在IIa期队列中共治疗多达12名患者。因此,我们正在努力在夏季完成这些患者。然后,我们将在美国眼科学会(美国眼科学大会)上提供完整的数据。这是在十月,在旧金山,我们为此保留了一个演示位置,所以我们期待在那时与您共享数据。对于CTX,我们已经开始进行IIb期试验,PISCES III,我们期待明年晚些时候的顶线数据。

In terms of CTX, I mentioned that we will have very much focused on CTX-derived exosomes, I'm sorry. We focus very much on the muscle drug delivery vehicle. Talking to a large number of biotech companies out there, there is a need in the marketplace from alternative to viral vectors. Some of the companies are struggling with -- in terms of antibodies and also where -- the targeting where these drugs -- where these viral vectors go. One issue is that they don't go into the brain. So we have been focusing on that part of our exosome program. And we signed a deal during the last year as well with an American company to use their gene program to see if we can deliver it with our exosome as a vehicle. So very much think about it as a truck delivering cargo for another company. Last on this page is business development.
We signed an agreement with Fosun Pharma for China, for hRPC and CTX, earlier this year. The total program is about GBP 80 million milestones. The royalties are double digit, which is very good when you compare to other deals in China. There is a GBP 6 million upfront payment that was received post period. And there is another GBP 6 million in their terms, milestones, meaning the next 12 to 18 months or so that are related to tech transfer and those kind of things. And there's also further milestones, regulatory milestones and profit share milestones. Fosun Pharma is a great partner for us. It's one of the Top 3 pharma companies in China, so, for us, it's a great validation of what we're working on.
And with that, we'll go to the numbers, which is what this is really supposed to be about. Michael?

就CTX而言,我提到我们将非常关注CTX衍生的外泌体,对不起。我们非常关注肌肉给药载体。与那里的大量生物技术公司交谈,市场上需要替代病毒载体。一些公司正在努力 - 在抗体方面以及这些药物的靶向位置 - 这些病毒载体的位置。一个问题是他们没有进入大脑。所以我们一直专注于我们的外泌体计划的那一部分。我们去年和一家美国公司签署了一项协议,使用他们的基因程序,看看我们是否可以用我们的外泌体作为载体进行交付。因此,将其视为为另一家公司运送货物的卡车。最后这个页面是业务开发。



Michael Hunt

Thanks, Olav. So, yes, we're announcing full year results today for the year ended 31 March this year. As you can see on the slide, we had slightly reduced loss this year compared to the prior period. The numbers are being flattered by a couple of items, a couple of one-off items that have helped, although the actual underlying cost base is also slightly down over the equivalent period last year as well.
The top line revenue number includes an exclusivity fee from a potential U.S. partner that we didn't ultimately consummate a deal with. That was announced and discussed last year. But, obviously, we kept that exclusivity fee, so that's why the top line number has gone up over the prior period. Accounts for most of the increase. And in addition to that, in the finance income costs line, we had benefits in the financial year from FX gains on foreign currencies that we hold to hedge the increasing amount of spend that we have in foreign currencies, notably the U.S. dollar and the euro. So, overall, that's given us a reasonable reduction in overall loss for the year, and that's flowed through to the cash flow statement as well, giving us an end of cash balance at the end of March of around GBP 26.5 million. And as Olav mentioned, subsequent to the end of the period, we'll receive the upfront payment from Fosun Pharma as well, so that's bolstered our cash balances, and of course, we expect to receive further near-term milestones from that deal, as Olav described it, as we move forward over the next year or so.




Thank you. So let's dive into the program a little bit. So let's start on the retinal side. So hRPC is a unique cell-based therapy. It is allogeneic and it's gene independent. So we are not fixing the gene defect that's underlying. We are attempting to restore the lost vision instead. So that means we could very much be used in tandem with or subsequent to a gene therapy if they become available.
We see that the hRPCs differentiate into functional photoreceptors and integrate into the retinal layers in preclinical models, so that's obviously what we're hoping for in terms of going forward in the clinic. So it has a broad therapeutic range. You are born with all the photoreceptors you'll ever have. So when photoreceptors are lost due to disease, the eye will not generate new ones. So this is a fantastic opportunity for a cell therapy to actually do that. And so if we're able to prove that we can do that, then there is a lot of opportunities there outside RP as well. We have a long time collaboration with Schepens Eye Research Institute, which is part of Harvard in Boston, as well as UCL. We worked a long time on making sure we can produce this correctly and in the right quantities, and we've gotten there. And the cryopreserved formulation is now allowing us to shipping this worldwide, being able to conduct clinical trials anywhere we want and as well for commercial applications. So a little bit about RP.
So it's an inherited degenerative eye disease. It starts with loss of night vision and peripheral vision. And then, over time, the central vision is lost as well. So these patients typically will have kind of complete tunnel vision, very, very small area visual field left. It can still be quite sharp vision right in the middle, but nothing left in the periphery.
Typically starts in the teens to the early 20s, even into the 30s as a starting point. They are diagnosed quickly. Very often, they kind of are expecting that this might happen because they have an uncle or someone already with the disease. And, yes, there is nothing that can be done. So these patients start losing their vision and they know that they will end up completely blind at some stage. That's obviously a terrible diagnosis to receive.
The incidence is 1 in 4,000, so close to 100,000 patients in the U.S. It is a gene defect that's causing this disease, but there are a lot of different genes involved, so over 100 different genes involved, so it's not a great place for gene therapy. You just have to invent a lot of gene therapy products in order to treat all of these patients. Luxturna is approved for one particular gene defect, RPE65, and that's about 1% of the patient population, that means the rest do not have anything treatment options for the moment.
So just a little bit on the preclinical data we have supporting before we went into the clinic. And then relatively quickly, we can see in the dystrophic RAC model that there are -- the retinal progenitor cells integrate into the retina. You can see that they provide trophic support. And we can see that the vision is preserved in this model. This is a model where rats lose vision over time, and you need to show that you could stop that loss.





发病率为4,000分之一,在美国接近100,000名患者。这是导致这种疾病的基因缺陷,但是涉及许多不同的基因,因此涉及100多种不同的基因,因此它不是基因的好地方治疗。您只需要发明许多基因治疗产品,以便治疗所有这些患者。 Luxturna被批准用于一种特定的基因缺陷RPE65,约占患者人数的1%,这意味着其余部分暂时没有任何治疗选择。

因此,在我们进入诊所之前,我们已经支持了一些临床前数据。然后相对较快,我们可以在营养不良的RAC模型中看到 - 视网膜祖细胞整合到视网膜中。你可以看到它们提供了营养支持。我们可以看到该模型中保留了愿景。这是一个老鼠随着时间的推移失去视力的模型,你需要表明你可以阻止这种损失。

We also saw very good dose-dependent efficacy. So the higher the dose was, the better efficacy we saw, until a certain plateau. And there was a plateau after that, there was no change. That plateau converged to about 1 million cells in a human-sized eye. So that was always our target dose for humans and that is the dose that we are using in the human trials.
One other point to make from the preclinical models is that we did not use any immunosuppression. Actually, in the pig model, we had better efficacy data without immunosuppression that we had with or rather integration data rather than efficacy, and so immunosuppression is not used in our clinical trials. One of the questions about our early data is -- that we'll get to in a second is how durable will it be. And, obviously, time will tell. What we can say is that in the animal models that we've run, at the end of the animal study when the animals are sacrificed, we do dissect the eyes to see if we still find cells there. And in a good percentage of animals, we do see still remaining cells at the end of the period. And we're talking here about human cells in rats and mice, so it's not a great environment for them. So that gives us some hope that the durability will be good. So let's jump into the clinical development.
So we completed the Phase I portion. So this is where we went from -- we had different cohorts. We went from 250,000 cells as a starting dose to 0.5 million cells, and we ended up with 1 million cells as our target dose. We also went from fresh cells to cryopreserved cells in that Phase I study. So that was 12 subjects, and that's done. We've now moved into the Phase IIa portion. The protocol calls for 6 to 12 additional subjects, all of them with some visual potential. That means that they need to be able to read some letters on an eye chart. Counting fingers or light perception is not good enough to be in the Phase IIa portion. Primary endpoint is still safety, but obviously, now, we're also looking at efficacy measures as well.
The two clinical trial sites, you can see them here, is Mass Eye & Ear in Boston and Retinal Research Institute in Phoenix. And these are two prominent retinal surgeons that we are working with. So here we go to the efficacy results of cohort 5, which is these three first patients that we have presented. These are the same data you saw from the ARVO Conference at the end of April. The -- what's so remarkable about these three subjects is that the vision gain were much stronger than anyone would expect. When you look at different clinical trials, you expect single-digit gains if you're lucky. You're quite happy with that. And so going to double digits is amazing. And here, we're talking about, in 20 to 25 letters, that's a really remarkable vision gain.
To explain the chart a little bit more. The -- we treat only one eye in these patients. You always treat the worst eye because you don't -- for safety reasons, you don't want to mess with their good eye. And so you treat the worse affected eye. You measure both. And then, over time, you obviously follow to see how this goes. You expect a bit of a loss of vision right in the beginning because the injection is actually a retinal detachment. I mean you create a bled where you put the cells in, so that actually will impact their vision for the first few days and then that will settle down, and then, hopefully, you start seeing improvement over time. And, yes, we're obviously extremely excited about this. And the feedback from the patients here is all three of them saying, "Everything looks brighter, I can see better." Patient 1, she said, "I can see food on my plate again." So it's fun. It's really amazing. And we'll just have to keep pushing this program forward to see that we can replicate this in more patients and we can have a longer duration.


临床前模型的另一个要点是我们没有使用任何免疫抑制。实际上,在猪模型中,我们有更好的疗效数据,没有免疫抑制,我们使用或更确切地说是整合数据而非疗效,因此我们的临床试验中没有使用免疫抑制。关于我们早期数据的一个问题是 - 我们将在一秒钟内得到它的持久性。显然,时间会证明。我们可以说的是,在我们运行的动物模型中,在动物研究结束时,当动物被处死时,我们会解剖眼睛,看看我们是否仍然在那里找到细胞。在很大比例的动物中,我们确实看到了在这个时期结束时仍然存在的细胞。我们在这里谈论的是老鼠和老鼠的人体细胞,所以这对他们来说不是一个好的环境。所以这给了我们一些希望耐久性会很好的希望。让我们跳进临床开发。

所以我们完成了第一阶段的部分。所以这就是我们去的地方 - 我们有不同的队列。我们从250,000个细胞作为起始剂量到达50万个细胞,我们最终得到100万个细胞作为我们的目标剂量。在第一阶段的研究中,我们也从新鲜细胞进入冷冻保存的细胞。这就是12个科目,而且已经完成了。我们现在已进入IIa阶段。该协议需要6到12个额外的科目,所有科目都有一些视觉潜力。这意味着他们需要能够在视力表上阅读一些字母。计数手指或光感不足以处于IIa阶段。主要终点仍然是安全的,但显然,现在,我们也在考虑疗效指标。

您可以在这里看到的两个临床试验点是波士顿的Mass Eye&Ear和凤凰城的视网膜研究所。这些是我们正在合作的两位着名的视网膜外科医生。所以我们在这里讨论第5组的疗效结果,这是我们提出的这三个第一批患者。这些是您在4月底从ARVO会议上看到的相同数据。 - 这三个主题的显着之处在于视力增益比任何人预期的要强得多。当您查看不同的临床试验时,如果幸运的话,您可以获得一位数的收益。你很满意。所以两位数是惊人的。在这里,我们用20到25个字母来谈论这是一个非常了不起的愿景。

更多地解释图表。 - 我们只治疗这些患者的一只眼睛。你总是对待最坏的眼睛,因为你没有 - 出于安全考虑,你不想惹他们好眼睛。所以你治疗受影响较严重的眼睛。你测量两者。然后,随着时间的推移,你显然会跟着看看这是怎么回事。你期望在开始时有一点视力丧失,因为注射实际上是视网膜脱离。我的意思是你创造了一个放入细胞的地方,这样实际上会影响他们前几天的视力,然后就会安定下来,然后,希望你开始看到随着时间的推移而改善。而且,是的,我们显然对此感到非常兴奋。来自这里的患者的反馈是他们三个人都在说,“一切看起来都更明亮,我看得更清楚。”患者1,她说,“我可以再次在盘子上看到食物。”所以很有趣。这太棒了。而且我们必须继续推进这个计划,看看我们可以在更多患者中复制这个,我们可以有更长的持续时间。

In terms of what are we looking for. The FDA guidance is -- they consider three lines to be -- so 50 letters, so three lines of this vision chart. And here is an illustration of the charts that's used in all clinical trials. It's called an ETDRS chart. And patients, if you can read every letter on that chart, you can read 100 letters. If you read 85 letters, you have a 20/20 vision. If you read 35 letters, you're legally blind. So just to put in perspective. So 35, legally blind, 85 letters, perfect vision. So a few letters makes a real difference. FDA's opinion is that one line, so five letters, is that's variation. So three lines, so 15 letters, that's a significant clinical responder. So in terms of primary endpoint for future studies, the proportion of patients reaching 15 letters will be the most logical primary endpoint. You -- the guidance also calls for both eyes to be treated. In the treated patients -- and the control patients are untreated controls. So you cannot mask this surgery, so the placebo patients are actually not placebo, they're just untreated controls. And data on untreated controls from other indications and products is zero. I mean people don't -- there is no placebo effect when you don't -- when you didn't get anything. So that's kind of what we're looking at going forward.
We are -- jump on the next page. So in terms of next steps is to build further safety data on RP using this commercial formulation. Treating further patients, so treating this up to 12 patients in the Phase IIa so that we will have that ready for the readout at American Academy of Ophthalmology in October. So we'll have somewhere between nine months in the longest patient down to probably just a few weeks of the last treated patient for that meeting. In terms of duration of efficacy that's probably needed here, I would say 12 months. So I think the dataset in October won't be quite at 12 months, but it will give us a pretty good picture of duration as well as magnitude of response across these 12 patients.
Following that, the plan would be to do a Phase IIb control study, that should start early next year. And I already described a little bit how that would look like, so treat both eyes in a patient versus observational control is the most logical, but we will have a lot of discussions with the FDA and EMA before we decide on exactly how to do that. There is obviously other indications as potential here. RP is a very attractive market. We obviously have very, very strong early data. So, clearly, this is where we're going to put our efforts in for the moment, and we'll come back to further indication later on.
So with that, I'm going to move into CTX. So CTX is, again, allogeneic, cryopreserved as well and it promotes anatomical plasticity in the brain. It got a great safety profile, we never had any immunogenicity issues or any other cell-related issues here. And we have a 12-month shelf life for this product. It can be -- it's commercially attractive. It kind of goes without saying, both in terms of being able to deliver good cost of goods here because we are able to have high quantities of production as well as being able to ship worldwide from any manufacturing site.

就我们在​​寻找什么而言。美国食品和药物管理局的指导是 - 他们认为三条线是 - 所以50个字母,所以三个视线图。以下是所有临床试验中使用的图表的说明。它被称为ETDRS图表。而患者,如果你能阅读该图表上的每一个字母,你可以阅读100个字母。如果您阅读85个字母,则视力为20/20。如果你读了35封信,那你就是合法的盲人。所以只是为了透视。所以35,法律盲,85个字母,完美的视野。所以一些字母会产生真正的不同。 FDA的观点是,一行,即五个字母,就是这种变化。所以三行,所以15个字母,这是一个重要的临床反应者。因此,就未来研究的主要终点而言,达到15个字母的患者比例将是最合乎逻辑的主要终点。你 - 指导也要求对待双眼。在治疗的患者中 - 对照患者是未治疗的对照。所以你不能掩盖这种手术,所以安慰剂患者实际上不是安慰剂,他们只是未经治疗的对照组。其他适应症和产品的未经处理的对照数据为零。我的意思是人们没有 - 没有安慰剂效果 - 当你没有得到任何东西时。所以这就是我们未来的目标。

我们是 - 跳到下一页。因此,就后续步骤而言,使用该商业配方建立关于RP的进一步安全性数据。治疗更多患者,在IIa期对多达12名患者进行治疗,以便我们在10月份为美国眼科学会的读数做好准备。因此,对于那次会议,我们将在最长患者中度过9个月至最后一位接受治疗的患者的几周。就这里可能需要的疗效持续时间而言,我会说12个月。因此,我认为10月份的数据集将不会在12个月时完成,但它会让我们对这12位患者的持续时间和反应幅度有很好的了解。

之后,该计划将进行一项IIb期对照研究,该研究应于明年初开始。我已经描述了一下这会是什么样子,所以对待病人和观察对照的双眼是最符合逻辑的,但在我们决定如何做到这一点之前,我们会与FDA和EMA进行大量讨论。 。这里有明显的其他迹象。 RP是一个非常有吸引力的市场。我们显然有非常非常强大的早期数据。所以,显然,这是我们暂时努力的地方,我们稍后会再回过头来说明。

因此,我将进入CTX。因此,CTX同样是同种异体的,也是冷冻保存的,它可以促进大脑的解剖学可塑性。它有一个很好的安全性,我们从来没有任何免疫原性问题或任何其他细胞相关的问题。此产品的保质期为12个月。它可以 - 它具有商业吸引力。不言而喻,无论是在能否在这里提供良好的商品成本,因为我们能够进行大量生产以及能够从任何制造地点运往世界各地。

I'm not going to bore you with the mechanism of action. It's probably multifold, but the most important bit there I think is the stimulation of synaptic activities. So every neuron is connected to hundreds of thousands or millions of other neurons. So you put 20 million neuro stem cells in there, you create neural growth, you create new blood vessels. And it's a real kickstart of activity in the brain. And it mimics the natural healing. When someone has had a stroke, there is a dead space in the brain and the brain is looking for new ways to get to wherever the information lies. That happens over the first month or two after a stroke, and then patients kind of stabilize and are left, still, with chronic issues, and this is where CTX can give them another shot.
Now the medical need is obviously very, very large. 1 in 6 people will have a stroke in their lifetime. So, clearly, a huge financial burden as well. Very few treatment options. There is alteplase, has to be used very quickly, so it's kind of a ambulance drug. And after that, there is really no therapeutic agents. Clot removal is what's used in hospitals and that's effective. So a lot of people survive strokes these days if they get treatment fast enough. But a portion of patients are left with chronic disabilities, so they're not completely healed by natural healing.
Now the severity in stroke is measured by this modified Rankin scale. That's how alteplase from Genentech was approved. It's a scale that shows dependency on others. So somebody on the modified Rankin 5, they are bedridden, they require a constant help from somebody. If you go down to the four, they need help. They need help to walk. They'll be in the wheelchair. They need assistance for walking, need assistance for using the toilet, et cetera. You go down to the three, you could get around with an appliance, like Zimmer frame or something. You still need some help at home, but not as intensely. And 0 to 2, you have either no disability or slight disability, but you can live independently. The goal is to get people one step down on this ladder. We are including patients with modified Rankin 3 and 4, and the goal is to get them one step down to a 3 or 2 on that scale.
In terms of our clinical trial results in PISCES II. So PISCES II had 23 patients included. It was a single arm study in 8 centers in the U.K. The number of responders was 7 out of 20, so 35% in the total population. However, the population -- total population was in two different groups. The group that we started a trial with was a group that were able to shrug their shoulder on the affected side, which is called an NIH SS upper limb score of less than four, to be technical about it. But that's what it means. So we always thought, in order to be able to show effect, the patient needs to have a functioning corticospinal tract, and a measure of that is that there is some kind of mobility on the affected side.
And the study actually started like that. We did add a group of patients that were not able to shrug their shoulder kind of at the later stage in the study. And we always thought they're probably not going to have the same kind of efficacy rate, and they didn't. We have a 50% efficacy rate when we look at only the patients who have an intact corticospinal tract. So that was one of the learnings from PISCES II that we took into PISCES III, was to make sure that we take patients who have some movement on the affected side as a patient population. So that's one of the things that we've done.



现在,通过这种改良的Rankin量表测量中风的严重程度。这就是基因泰克的阿替普拉药获得批准的方式。这是一个表示依赖他人的量表。所以改名Rankin 5的人,他们卧床不起,他们需要一个人的不断帮助。如果你下到四,他们需要帮助。他们需要帮助才能走路。他们会坐在轮椅上。他们需要步行辅助,需要协助使用厕所等等。你下到三,你可以使用一个设备,如齐默帧或其他东西。你在家里仍然需要一些帮助,但不是那么强烈。 0到2岁,你既没有残疾,也没有轻微的残疾,但你可以独立生活。目标是让人们在这个阶梯上迈出一步。我们将患有改良Rankin 3和4的患者纳入其中,目标是让他们在一定程度上将其降低到3或2。

就我们在​​PISCES II中的临床试验结果而言。因此,PISCES II包括23名患者。这是英国8个中心的单臂研究。响应者的数量是20个中的7个,因此占总人口的35%。然而,人口 - 总人口分为两个不同的群体。我们开始试验的那个小组是一个能够在受影响的一侧耸肩的小组,这被称为NIH SS上肢评分低于4分,是关于它的技术。但这就是它的含义。所以我们一直认为,为了能够显示效果,患者需要有一个功能正常的皮质脊髓束,其中一个衡量标准是受影响的一侧有某种活动能力。


And if you go to the PISCES III study. We're treating 110 subjects. It's randomized between CTX and placebo surgery. So a placebo surgery means that the patient is actually sedated. The surgeon will make an incision. It will not penetrate, but the patient will not know if they have been treated or not and neither will the assessment center because they are sent back to the assessment center after the surgical site.
The primary endpoint is one point improvement from baseline at modified Rankin, 6 months post treatment. There is a host of secondary endpoints as well, of course. And the study is ongoing, it's a U.S.-only study, and we are expecting the readout late next year. And a couple of words on exosomes before we open up for questions.
So there is more and more activity on the exosome field. So these are nanoscale vesicles that are released by all cells, really, in the body, and they are important when it comes to communication between cells. And the -- I mentioned a little bit about the advantages of exosomes versus viral vectors and other type of delivery vehicles, particularly the low immunogenicity, is the key. There is also probably some advantages in the ability to produce enough in terms of quantities at high quality.
In terms of ExoPrOs or our exosome that is particular we probably focus more on quality manufacturing than most other companies out there, so we are very proud of our -- the stability that we have in our manufacturing. We have established excellent analytics, which is very, very important. And we have shown that we're able to get our exosomes across the blood brain barrier, and that is unique to our exosome. So that's really the focus for us now is to develop it as a delivery vehicle for a payload that wants to get into the brain. And with that, we come to the summary.
So we're a global leader in cell-based therapeutics. We're based in the U.K. We also have a team in Boston, our CMO is there and our clinical -- most of our clinical team is there. Everything we do is allogeneic, which means it's scalable, cost-effective. The diseases that we're targeting have very high unmet medical need, so there's no doubt there is a market there should we be successful in making -- getting the drugs all the way through. We have significant clinical milestones, both in stroke and the retinal program, over the next 18 months. And we will definitely be looking at business development opportunities as the data is maturing, particularly in the RP program.
With that, I say thank you, and open up for questions.

如果你去参加PISCES III研究。我们正在治疗110个科目。它在CTX和安慰剂手术之间随机化。因此,安慰剂手术意味着患者实际上是镇静剂。外科医生会做一个切口。它不会穿透,但患者不会知道他们是否得到了治疗,评估中心也不会,因为他们会在手术部位之后被送回评估中心。


因此,外泌体领域的活动越来越多。因此,这些都是纳米级囊泡,所有细胞都是在体内释放出来的,它们在细胞间通讯时非常重要。并且 - 我提到了一点关于外泌体与病毒载体和其他类型的递送载体的优点,特别是低免疫原性,是关键。在高质量的数量方面生产足够的能力也可能具有一些优势。

就ExoPrOs或我们的外泌体而言,我们可能比其他大多数公司更注重质量制造,因此我们为我们 - 我们在制造业中的稳定性感到自豪。我们已经建立了非常非常重要的优秀分析。我们已经证明,我们能够将我们的外泌体穿过血脑屏障,这对我们的外泌体来说是独一无二的。因此,现在我们真正关注的是将其作为有效载荷的运载工具进行开发,以便进入大脑。有了这个,我们来总结一下。

因此,我们是细胞疗法的全球领导者。我们的总部设在英国。我们在波士顿也有一个团队,我们的CMO就在那里,我们的临床 - 我们的大多数临床团队都在那里。我们所做的一切都是同种异体的,这意味着它具有可扩展性和成本效益。我们所针对的疾病具有非常高的未满足的医疗需求,因此毫无疑问,我们应该成功制造一个市场 - 让药物一路走来。在接下来的18个月中,我们在中风和视网膜计划方面都有重要的临床里程碑。随着数据的成熟,我们肯定会关注业务发展机会,特别是在RP计划中。



Andy Smith from Edison. If the presentation is any guide, I get the idea there's a promotion, a pipeline promotion for the RP program over CTX. Is that because the data has been so good today or the CTX product leads results later next year? Or perhaps even that might be quicker for the RP program to get to the market over CTX?

来自爱迪生的安迪史密斯。 如果演示文稿是任何指南,我认为这是一个促销,RPX计划的管道推广。 那是因为今天的数据如此之好还是明年晚些时候CTX产品的结果如何? 或者甚至可能更快的RP程序通过CTX进入市场?


It's kind of yes to probably all of those things. In terms of time to market, RP is likely to be fast, faster than CTX. But, obviously, we'll have to see how the programs go, but it could be very fast. So that's one part of your question. The other one is that there is a lot more news flow on the RP program over the next 18 months, because, for CTX, we'll have to just wait until the trial reads out. There's no interim readout or anything like that, so it's kind of one of those things where we just have to wait for the study to complete.

对所有这些事情都是肯定的。 就上市时间而言,RP可能比CTX更快,更快。 但是,显然,我们必须看看程序是如何进行的,但它可能非常快。 这是你问题的一部分。 另一个是在接下来的18个月里RP计划上有更多的新闻流,因为对于CTX,我们必须等到试验读出来。 没有临时读数或类似的东西,所以这是我们必须等待研究完成的那些事情之一。

Christian Glennie

Christian Glennie with Stifel. A couple on the retinal program then. Just to set some expectations around that data that we're going to see in October at the medical conference. So far, you've had 100% hit rate and a very high response rate, so 100% response rate at a very high bar in terms of that improvement in the visual acuity. What is your expectation around sort of -- I think you've talked about sort of a percentage response that gets that 15 letters. Is that what you're thinking about in terms of that data from all 12 patients, so albeit there will be a range of duration?

Christian Glennie与Stifel。 一对夫妇在视网膜计划然后。 只是为了对我们将在10月的医学会议上看到的数据做出一些预期。 到目前为止,你已经有100%的命中率和非常高的响应率,因此在视力提高方面,100%的响应率非常高。 您对此类期望的期望是什么 - 我认为您已经谈到了获得15个字母的百分比响应。 就所有12名患者的数据而言,这是您正在考虑的问题,所以虽然会有一段持续时间吗?


Yes. I mean what would great data look like? Great data would look like if you can hit double digit on average vision gain would be complete -- fantastic. If you can reach, I don't know, 1/4 to 1/3 of patients as responders, that's fantastic compared to any other drug out there. So if you look at statistics for running a pivotal trial, when you know that the control group is 0, that's what has been in other trials, if you have a, let's call it -- if you have a 30% efficacy rate for hRPC, you don't [indiscernible] study.

是。 我的意思是伟大的数据会是什么样子? 伟大的数据看起来如果你可以达到平均视力增益的两位数就会很完美 - 太棒了。 如果你能够达到,我不知道,作为应答者的1/4到1/3的患者,与那里的任何其他药物相比,这是非常好的。 因此,如果您查看运行关键试验的统计数据,当您知道对照组为0时,那就是其他试验中的情况,如果您有,请让我们称之为 - 如果您对hRPC的有效率为30% ,你没有[音频不清晰]学习。

Christian Glennie

The 15 letters? What's that bar?

15个字母? 那是什么酒吧?


Yes. The bar is 15 letters, that is the FDA's bar. So 15 letters, that is their definition of responder. If we can get -- if, hypothetically, throwing out a number, so if you put that down as 30%, you don't need a very large study to be successful. You can run a stats program on Google and find that out, right? So that's what success looks like. Yes, I'd be very happy with 100% response rate, don't get me wrong, but it's probably unrealistic to expect that.
And the other bit that we want to see is 12 months' worth of efficacy. I think that's what it takes for that to be a successful program. You can repeat sub-retinal injections, but it's an invasive procedure, so it's not something you want to do very often. In our discussions with key opinion leaders, they feel quite comfortable doing that once a year. So that's kind of part of their thinking there as well. We don't see any reason why efficacy would disappear. These are -- if we are creating new functional photo receptors, they will be disease-free. They will not have a gene defect. They'll be healthy. There is no reason why they will disappear as long as the retinal structure is still there. So we're not worried about the duration, but it has to be proven.

是。酒吧是15个字母,这是FDA的酒吧。所以15个字母,就是他们对响应者的定义。如果我们可以得到 - 如果假设丢弃一个数字,那么如果你把它降低到30%,你就不需要一个非常大的研究才能获得成功。您可以在Google上运行统计程序并找到它,对吗?这就是成功的样子。是的,我对100%的回复率感到非常满意,不要误会我的意思,但是期待它可能是不现实的。

我们希望看到的另一点是12个月的功效。我认为这是一个成功的计划所需要的。您可以重复进行视网膜下注射,但这是一种侵入性手术,所以这不是您经常要做的事情。在我们与主要意见领袖的讨论中,他们每年做一次这样做感觉很舒服。所以这也是他们思考的一部分。我们认为没有任何理由可以消除功效。这些 - 如果我们正在创造新的功能性光感受器,它们将是无病的。他们不会有基因缺陷。他们会健康的。只要视网膜结构仍然存在,它们就没有理由消失。所以我们并不担心持续时间,但必须要证明。

Christian Glennie

And then on -- and in terms of other aspects of the data so far, so being focused on acuity. But clearly, it's a, as you described it, a peripheral vision primary, that's the gradual degradation of that peripheral vision. Will there be more data around some more of these other visual assessments like peripheral vision and [indiscernible]?

然后 - 就目前的数据的其他方面而言,所以专注于敏锐度。 但很明显,正如你所描述的那样,这是一个周边视觉初级视觉,即周边视觉的逐渐退化。 是否会有更多关于其他视觉评估的更多数据,如周边视觉和[音频不清晰]?


Yes. I mean there are other assessments being done in these patients. Exactly what will be presented in October, I don't know. That will be up to [indiscernible] whose presentation it will be. So yes, so I don't know. But, yes, we do assess other things. I mean in most clinical trials in RP, there's a lot of focus on other endpoints because they don't see much of visual acuity, right? So then you have to look at all other ways to eke out efficacy. And it's clearly meaningful to have an expanded field of vision, for example. But yes, that's not FDA's guidance, though, in terms of what they are looking for.

是。 我的意思是这些患者还有其他评估。 我不知道将在十月份呈现的具体内容。 这将是[音频不清晰]的表现形式。 是的,所以我不知道。 但是,是的,我们会评估其他事情。 我的意思是在RP的大多数临床试验中,有很多关注其他终点,因为它们看不到很多视力,对吗? 那么你必须看看所有其他方法来提高效率。 例如,拥有扩大的视野显然是有意义的。 但是,就他们所寻求的而言,这不是FDA的指导。

Christian Glennie

And then just finally, in terms of those two sites, is that it will stay with just the two sites? There won't be any others? And what -- and do you expect sort of rough even distribution between those two sites?

最后,就这两个网站而言,它只会留在这两个网站吗? 不会有其他人吗? 什么 - 你是否期望在这两个网站之间进行粗略均匀的分配?


I haven't thought about the distribution between them, but they seem to be kind of coming back and forth between them. The -- in the Phase IIa, that will be those two sites that patients look on a schedule already throughout the summer. The -- in a future Phase IIb study, we might go to more sites, we haven't decided that yet.

我没有想过它们之间的分布,但它们似乎在它们之间来回传播。 - 在IIa阶段,这将是整个夏季患者按计划查看的两个地点。 - 在未来的IIb期研究中,我们可能会去更多的地方,我们还没有决定。


Robyn Davison [ph]. I was just wondering, if -- in the light of the Fosun deal and perhaps also the -- perhaps more the best situation for the company to finance itself with the share price or more realistic share valuation, whether you have opportunities to accelerate the RPC program. I mean, obviously, thinking of the FDA, you had a breakthrough therapy designation, all this sort of thing. I mean could you spend more money and get this to market faster? Is that an option that you're looking at, for example?

罗宾戴维森[ph]。 我只是想知道,如果 - 根据复星的交易,也许还有 - 或许是公司用股价或更实际的股票估值来融资自己的最佳情况,无论你是否有机会加速RPC 程序。 我的意思是,显然,考虑到FDA,你有一个突破性的治疗指定,所有这些事情。 我的意思是你可以花更多钱并将其推向市场吗? 例如,这是您正在考虑的选项吗?


We're going as fast as we can. If I got another GBP 50 million from Michael here, I couldn't go any faster. So -- and that's true for now. When we get into the next phase, at Phase IIb, yes, it can maybe do two studies at once, one in Europe, one in U.S., and so there are probably things you can do at that point. But this is pioneering, you learn as you move forward as well, so you don't want to -- you want to take the appropriate time. There is safety, still, paramount there where you are. You don't want to mess with people's vision. So I think there is a balance there as well. But, yes, we can't go faster than what we are for the moment.

我们尽可能快地去。 如果我从迈克尔那里得到另外5000万英镑,我就不能再快了。 所以 - 现在也是如此。 当我们进入下一阶段时,在阶段IIb,是的,它可以同时进行两项研究,一项在欧洲,一项在美国,因此可能在那时你可以做些什么。 但这是开拓性的,你在学习的同时也要学习,所以你不想 - 你想要适当的时间。 那里有安全,仍然是最重要的。 你不想搞乱人们的愿景。 所以我认为那里也存在平衡。 但是,是的,我们现在不能比现在更快。

Michael Hunt

I mean just to add to that. I mean I think we took a fairly cautious stance on what we believe the future clinical development pathway might look like. So for RP, that's orphan status condition and we have fast tracked the rest of that. Our underlying assumption is that we need to do a IIb, followed by another study. As Olav said, there might be ways of combining that and doing it in parallel, all that kind of stuff, but the underlying assumption is still quite cautious I think in terms of what would be required. And I think the Phase I, IIa data will inform that to a degree. The better the data is, obviously, the more leverage one has in terms of what we'd need to do to get the program through, but we're reasonably cautious in terms of our own expectations on this.

我的意思是加入那个。 我的意思是,我认为我们对未来临床发展路径的看法采取了相当谨慎的立场。 因此对于RP来说,这是孤儿状态,我们已经快速跟踪其余部分。 我们的基本假设是我们需要做一个IIb,然后是另一项研究。 正如奥拉夫所说的那样,可能有一些方法可以将这种方法并行地组合起来,所有这些东西,但我认为根据所需要的内容,基本假设仍然非常谨慎。 我认为第一阶段,第二阶段的数据将在一定程度上提供信息。 数据越好,显然,就我们需要做的事情而言,获得该计划的杠杆越多,但我们对此的期望值相当谨慎。


Right, okay. Just on exosomes, I mean, are you sort of -- well, I mean, you sort of give us the impression that you're looking less to invest in this technology yourself now more. That would be -- it would more likely be licensed to third parties for their own development programs and you have an economic interest in that than perhaps what was the case last year when you did the R&D day, exosomes.

对,好的 对于外泌体,我的意思是,你有点 - 好吧,我的意思是,你给我们的印象是你现在更少投资这项技术。 那将是 - 它更有可能被许可给第三方用于他们自己的开发计划,并且你对此有经济利益,而不是去年当你做研发日时的情况,即外泌体。


Yes. So we've signed one deal, and that deal is a deal where we are trying to deliver the gene therapy of the unnamed American company to different target sites. They carry their costs. We carry our costs for doing that. And if we produce a product that is -- if a product comes out of that collaboration, we own that 50-50, then we'll have a discussion who does what. At that point, we might very well say that they go ahead with it and we get the royalty, that's possible. But we haven't actually gotten to that point yet. But in terms of strategy, as very much, we are -- this is all about collaborations with others. We are investing in exosomes, but we -- it's not a very large budget because we're not a big clinic.

是。 所以我们签了一笔交易,这笔交易是我们试图将这家未具名的美国公司的基因疗法送到不同目标地点的交易。 他们承担他们的费用。 我们承担这样做的成本。 如果我们生产的产品是 - 如果产品来自合作,我们拥有50-50,那么我们将讨论谁做了什么。 那时,我们可能会说他们继续这样做,我们获得版税,这是可能的。 但我们实际上还没有达到这一点。 但就战略而言,我们非常关注 - 这完全是与其他人的合作。 我们正在投资外泌体,但我们 - 这不是一个非常大的预算,因为我们不是一个大诊所。


I suppose sort of finally, I was trying to think. I mean, obviously, last year, when you entered into that option arrangement, it's sort of like dragged out rather a long time and they didn't ultimately resolved it other than it was money coming in. Given the situation that the company finds itself in now, which is presumably a lot better financially, would you enter that sort of agreement now or do you -- would you be looking for much better terms?

我想最后,我试图思考。 我的意思是,很明显,去年,当你进入这个期权安排时,它有点像被拖出相当长的时间,除了钱进来之外他们最终没有解决它。鉴于公司发现自己的情况 在现在,这可能在经济上要好得多,你现在或者你也会签订这种协议 - 你会想要更好的条款吗?


I would have to admit that we were quite happy that we didn't sign the agreement, although it was a good agreement. But yes, in the end, we didn't come to terms, and that was obviously before we had the data, right? So after the data, it's looking a lot more interesting. We will have discussions after, I will say, in Q4 this year, we will have discussions with a number of companies who have overly expressed an interest. We want to have kind of the data set, a proper data set, so it's a sensible discussion. And then we will have to make decisions about how much -- get the balance right between how much rights to give away, how much risk to reduce and how much of our future upside to retain. And that is kind of a balance that we'll look at coming Q4. And if we sign away rights for everything, then we don't have a reason to exist. So we definitely would like to have a continued interest in the program even if we do the [indiscernible].

我不得不承认,我们很高兴我们没有签署协议,尽管这是一个很好的协议。 但是,是的,最后,我们没有达成协议,这显然是在我们获得数据之前,对吗? 因此,在数据之后,它看起来更有趣。 我将在今年第四季度讨论之后,我们将与一些过度表达兴趣的公司进行讨论。 我们希望拥有一种数据集,一个合适的数据集,因此这是一个明智的讨论。 然后我们将不得不做出多少决定 - 在给予多少权利,减少多少风险以及保留多少未来上行空间之间取得平衡。 这是一种平衡,我们将关注即将到来的第四季度。 如果我们签署一切权利,那么我们就没有理由存在。 因此,即使我们做[音频不清晰],我们也一定希望对该计划持续感兴趣。


Julie Simmonds, Panmure Gordon. Just going back to what you're saying, Michael, about the sort of next phases of the trial. Is there any sort of precedent for something similar where the FDA have sort of -- where there is a sort of more guidance on what might be likely for a Phase IIb or further trial?

Julie Simmonds,Panmure Gordon。 回到你所说的迈克尔,关于试验的下一阶段。 在美国食品药品管理局(FDA)有哪些类似的情况下,是否存在任何类型的先例 - 对于IIb期或进一步试验的可能性有哪些更多的指导?

Michael Hunt

Difficult one for me to answer. I don't know if you've gotten...

我很难回答。 我不知道你是不是......


Yes. No. I mean, actually, the guidance are pretty clear. The guidance is actually gene therapy guideline, but the FDA told us we should expect to follow the same. So the guidelines ask for a 15-letter gain as an endpoint. It asked for both eyes to be treated in the treated subject, not necessarily simultaneously, most probably not because if something is wrong, you don't want to be wrong in both eyes at the same time. And they ask for the control group to be an observational control group. There is also some talk in that guidance about going -- having a target dose group and a low-dose group. It's kind of your payment for not having a proper placebo control, so that there are two doses being tested versus observational control. So there is pretty good guidelines there. In terms of speed to market versus kind of learning as you go, I think we are in a rush to produce great data. It's not necessarily rush to kind of have your pivotal study ready. I think if you start a big pivotal study, you go into a very -- a period with very little news for a long period of time. I think it might be better to kind of keep working on it and learn as we go. So a 2-trial strategy is what we're planning on for the moment. So a Phase IIb followed by a Phase III.

是。不,我的意思是,实际上,指导非常明确。该指南实际上是基因治疗指南,但FDA告诉我们,我们应该遵循同样的原则。因此,指南要求将15个字母的增益作为端点。它要求在受治疗的受试者中治疗双眼,不一定同时进行治疗,很可能不是因为如果出现问题,您不希望同时出现双眼错误。他们要求对照组成为一个观察对照组。关于去的指导也有一些话题 - 有一个目标剂量组和一个低剂量组。这是因为没有适当的安慰剂控制而付出的代价,因此有两种剂量被测试而不是观察控制。所以那里有很好的指导方针。就目前的市场速度与学习方式而言,我认为我们急于提供出色的数据。不一定急于准备你的关键研究。我想如果你开始一项重要的关键性研究,你会进入一个很长一段时间内很少有新闻的时期。我认为继续努力并随时学习可能会更好。因此,目前我们正计划采用2试策略。因此,阶段IIb接着是阶段III。


And just on that sort of where they want sort of both eyes treated in the patients. Have you spoken to any or is it possible to treat the other eye of the patients in the study you are doing at the moment or does that go against the protocol?

就在那种他们想要在患者身上治疗双眼的地方。 您是否曾与任何人交谈,或者是否有可能在您正在进行的研究中治疗患者的另一只眼睛,或者这是否违反了协议?


Yes. No. That goes against the protocol. So there will be a subsequent study. But yes, it's something that we did think about. But I think we'll finish this study and then we'll start the next.

是。 不,这违反了协议。 因此将会有一项后续研究。 但是,是的,这是我们考虑过的事情。 但我想我们将完成这项研究,然后我们将开始下一个研究。


Just a follow-up, I should have a question on CTX in stroke. Just your -- a bit more insight in terms of where you're at with recruitment in that trial, confidence around delivering that data in towards the end of 2020. How is the recruitment going? Do you have any sense for rates and time? How you'd expect it to presumably accelerate at some point, if an inflection point was needed for inflection recruitment?

只是一个后续行动,我应该对中风CTX有疑问。 只是你的 - 就你在该试验中招聘的位置而言更有洞察力,对于在2020年底提供这些数据的信心。招聘如何进行? 对速度和时间有什么看法吗? 如果拐点招募需要一个拐点,你怎么能指望它在某些时候加速?


Yes. No. Recruitment is fine. It was -- I would say very heavy-lifting to get started. It took us longer to get sites up and running than we expected, so -- but now we have a really good number of sites running. So we have kind of a critical mass, the -- because we really prefer patients to go to a local site rather than being -- having to be shipped around the country because there's quite a lot of follow-up visits, et cetera. So if you have to fly somewhere every time, it gets quite cumbersome for them and expensive for us. So we rather have a local site open. If there's really nothing kind of coming up close, then we'll transport the patient. So yes, so it's -- we're confident on our guidance of having data late next year.

是。 不,招聘很好。 这是 - 我会说非常繁重的开始。 我们花了比我们预期更多的时间来启动和运行网站,所以 - 但现在我们有非常多的网站正在运行。 所以我们有一个临界质量,因为我们真的更喜欢患者去当地的一个地方而不是 - 不得不在全国各地运送,因为有很多的后续访问,等等。 因此,如果你每次都必须飞到某个地方,那对它们来说会非常麻烦,对我们来说也很昂贵。 所以我们宁愿打开一个本地网站。 如果真的没有什么可以接近,那么我们将运送病人。 是的,所以它是 - 我们对明年晚些时候提供数据的指导有信心。


Any more questions? If not, I say thank you again for your support and interest, and looking forward to catching you next time. Thank you.

还有其他问题吗? 如果没有,我再次感谢您的支持和兴趣,并期待下次再次接待您。 谢谢。


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