The next focusIR Investor Webinar takes places on 14th May with guest speakers from Blue Whale Growth Fund, Taseko Mines, Kavango Resources and CQS Natural Resources fund. Please register here.
I got my question into MH about intravitreal injection and he confirmed RENE will now be testing this as well as proceeding with subretinal. It makes perfect sense for them to compete in both types of procedures. RENE's cryopreserved formula offers a real competitive advantage against jCyte's fresh formulation in widespread distribution to ophthalmologist offices.
Shame we didn't get to learn more about the number of patients treated so far in the phase 2a extension. I did ask but he didn't read out the question..
50% efficacy in the 6M cell group seems pretty impressive to me. Clearly, they will be dosing at that level in their Ph3.
The fact that intravitreal injection procedure can be performed by a regular ophthalmologist rather that a highly skilled (and expensive) retinal surgeon in a specialist centre is significant. Rene has stated that sub-retinal injection confers other benefits, new photoreceptors may develop/integrate and longevity of effect may be significantly better, but this has to be balanced with ease of administration and cost. IMHO Rene need to be agnostic to the method of treatment and play to their strengths in lower cost of goods as a result of their Cryopreservation techniques.
At the end of the day, I suspect the decision on strategy will be down to the commercialisation partner who licenses the hRPC cells for the indication.
Rene made a big point about the Ph2a being an open-label study which allows them to report whenever they wish so I wouldn't take too much notice of those dates. In the Ph2a, they reported results at two months follow-up for one subject, and at 18 days for the other two. They are required to report any "material" events they are aware of to the market.
For the extension study, they announced dosing had started a month ago so It's probable that further patients are being treated by now - hence the update to the clinical trials register.
Based on the Phase 2a results, it seems that efficacy becomes evident a short time after treatment so they should have a good idea of vision improvement early on. The longevity of effect is the other concern in these studies but they now have the previous Ph2a patients results - out to 18 months in one patient in their latest update .
https://clinicaltrials.gov/ct2/show/NCT02464436?cond=Retinitis+Pigmentosa&draw=2&rank=33
Sorry if this question has already been asked, but has anyone done the math on the best case CVR values?
I would watch Michael Hunt's latest interview rather than Olav. Hunt was somewhat guarded regarding exosomes development prospects and also stated that RENE did not have the same level of expertise as some of the pure-play, start-ups such as Codiak. However, he did say that RENE would still have a place in the market if the platform was validated. His main emphasis was still RP and the "exciting" prospects of further positive data.
If you look back at the RNS history for the PH2a, an RNS was released regarding efficacy "at two months follow-up for one subject, and at 18 days for the other two". I would expect a similar timeline if the PH2a results are "material" because the company would be obliged to release the news for regulatory reasons. RENE recently confirmed that the first patient has been treated so we could be looking at news mid to late October.
If RENE were to "go it alone", a pivotal PH3 is likely to require a larger number of participants than the Ph2a ext and take around 2 years. Assuming it starts in 2022 and If successful, RENE could submit an NDA (or BLA) late 2024. They would need to recruit a small sales force and incur launch costs in 2025. So, that's 4-5 years from now. I can see them needing at least £50million to get to that point.
As we all know, the RENE share price moves on Newsflow so another interesting quote of interest..."There are also earlier stem cell projects (in immunotherapy and diabetes) which could generate preclinical data in 2020".
In the prelim results presentation on July 20, the CMO stated that they expect to start the ph2a extension study in August/early September. They have two sites ready (Oxford and Boston) but it sounded like they were still scoping out two additional sites (Pheonix has probably been dropped because Pravin Dugel seems to have moved on). Hopefully, Jason Commander and Robert MacLaren will move forward fairly quickly. We must also hope that RENE has secured the two new locations (Barcelona was mentioned as one) and has kicked off recruitment by now. Allowing for the DSMB delay between each treatment, quarter1 next year seems reasonable for completion. They have the PH2a data on duration of effect and if the one-month extension study results are equal or better than the original ph2a then this could be enough for a US institutional investor. It's also possible that they have partners heavily engaged (as suggested by the CMO) who are willing to cut a deal on early data. All supposition though - I'd much rather hear something from RENE's management ream!
Given that "Cells communicate via exosomes, nano-sized packages of information released by cells and absorbed by other cells in a functionally relevant manner", then I guess is it true to say CTX expressed exosomes would have been present in the CTX trials. However, this is presumably not quite the same as where they have been loaded with a particular payload. That's what is being worked on at present, I believe.
Completely agree Grizzlyb.
The main point is perhaps that the whole hRPC story has now been validated by a decent-sized PH2b study. OK - jCyte uses intravitreal rather than subretinal injection but the latter technique is already used in approved treatments so I don't believe that this represents an undue risk and it could well have significant benefits. As an investor, I feel happier about the risk-reward proposition after today's news. Hopefully, some of the larger partners in discussion with RENE regarding the PH2a extension study also feel the same way. It's worth remembering that jCyte did their $250m deal with Santen a month before making their Ph2b data public.
Thanks Haplo.
"A total of 84 patients were randomized of which 74 met criteria for the per protocol analysis. The mean change in BCVA from baseline to month 12 were +2.81, +2.96, and +7.43 letters in the sham (N=26), 3.0x106 hRPC (N=25), and 6.0x106 hRPC (N=23) treatment arms, respectively. In a post hoc exploratory analysis of the target subgroup (n=37), mean change in BCVA from baseline to month 12 were +1.85, -0.15, and +16.27 letters in the sham (N=13), 3.0x106 hRPC (N=13), and 6.0x106 hRPC (N=11) treatment arms, respectively (p=0.003 for 6.0x106 hRPC vs sham). Supportive improvements in the 6.0x106 hRPC target subgroup compared to the control (sham) group were also observed in all secondary endpoints which further support the BCVA findings in this subpopulation.."
I'm no expert but this seems like good news for RENE. The results across the whole population at month 12 were +2.81, +2.96, and +7.43 - the last being the highest dose of 6million cells. jCyte have then looked at a specific subpopulation and achieved +1.85, -0.15, and +16.27. A few things to note: (i) JCyte's efficacy appears dose dependant (ii) RENE's 2b results are comparable to the 6Million dose jCyte subpopulation figure, I believe (ii) RENE have improved the PH2a extension study design in several ways - - doubling cell count, changing the bleb location to avoid potential damage to functioning photoreceptors and using more sophisticated techniques for measuring efficacy (as used in Gene Therapy trials that lead to product approvals). These steps should further improve efficacy.
I'm sure we will hear from RENE's management team in due course on their thoughts.
It's worth listening to what RENE's CMO says about the RP PH2a extension in the presentation. In the final minute, he mentioned that they expect to have efficacy data this time next year, however, if there is something material then they will be announce before then. Looking back at the RNS dated 20 February 2019 "ReNeuron Group plc - Positive preliminary data in US retinal", this was, I assume, deemed to relate to a "material" event. The RNS was based upon data from the first Phase II cohort, at two months follow-up for one subject, and at 18 days for the other two. Assuming the Ph2a extension starts in August, then it might be that we see a similar announcement of a subset of the nine patients in Q4.
jCyte announced their Ph2b trial results at a conference this weekend. I believe this will be made public soon but if anyone is aware of this, please share. Given the similarities with RENE, the increase in Cell Count used in their latest study is of great interest.
Hi Chester
I think you will see more research collaborations over the next few months - as Michael Hunt pointed out, not all will be a "hit" but signing more agreements increases the odds of a commercial arrangement with at least one partner. If the RP PH2a extension begins in August/September and finishes late 2020/early 2021 then they are likely to release 3 -month data in Q1/Q2 next year.
I think you are pretty much spot on in your assessment. My main concern when investing is the amount of risk to capital that I am prepared to accept. I bought in above the current share price but having listened to the analyst presentation yesterday, I am reasonably comfortable that I will see a premium in the next 12 months. The RP study results, reported by independent investigators at multiple sites, plus the progress made by their competitor jCyte, gives a level of confidence that results will be positive in the next cohort of the Ph2a. For the exosomes program, the commercial deals that competitors have secured also bodes well. Olav stated that the main difference between Rene and the pure-play exosomes competition was that they have yet to produce data in an animal model - something Rene are working furiously on. I certainly do not take what company directors say as gospel but his expectation that one or more of the research agreements will result in a commercial deal seems plausable. The Fosun continuation of the CTX program for stroke is a bonus as far as I am concerned. If Rene do pull in a high value partnering deal at some point, they could chose to restart the stroke trial by funding themselves.