Member Info for Alquemie

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No immediate implications, but it's a fairly safe prediction that the high-margin but under-invested rare diseases business will be split from the "traditional" pharma business, which is set to decline as generic competition bites. Recordati did a grand job of preserving sales through regional expansion, but have reached the point of diminishing return.

Will be interesting to see if the current geographical reach is maintained, or as with CVC's other majority owned pharma, Alvogen, they will look to sell regional operations prior to exit.

While not much in the way of consolation, this may not be the end of the utrophin saga.

Up for debate, but SUMM was able to establish clinical proof of concept, although unwisely (but perhaps through necessity) romped ahead with a candidate with borderline bioavailability.

It's no secret that SUMM were quietly beavering away to identify next generation candidates with more promising pharmacokinetics and, depending on progress and whatever the SUMM core intellectual property encompasses, the bundle might still have value in the hands of Sarepta or another well-heeled developer.

SUMM is almost certainly now out of the DMD game, and while there is still cash enough to keep the lights on and maintain Mr Edwards in customary style, it's a long ,steep path to the monetization of antibiotic assets.

Pomander, I've never relied on Mr Mellon for my mess of potage, but as a self-proclaimed biotech investment guru, he hasn't half made some risible predictions and recommendations (PLE, DBC, which should really be renamed, "WTF", Arrowhead, the gone and forgotten Burnbrae investments. I share your ambivalence regarding SUMM). The jolly wheeze that is Juvenesence also gives off a strong whiff of oversell, but I'm sure that they'll be no shortage of Mellonanists queuing up to support an IPO. JG is an easy target, but he was handed a hard row to hoe, made harder by the expectation created by unfeasible revenue projections. I think it reasonable to suppose that his background has not equipped him to deal with issues which would tax any pharma old hand (scant intellectual property/commercial protection, undefined regulatory paths, an inadequate clinical dossier, manufacturing issues with cost overruns, positioning of an Rx product in what is essentially and OTC market). True, plenty of people around capable of advising on any and all of these issues, but unless you fully grasp how it all fits together, damned difficult to know what you don't know. What is inexcusable is, whether through naivety or cupidity, his history of miscommunication, although I guess total silence is technically not "miscommunication". This has been covered before, but the canister size has made no difference to the NDA submission timeline. The rate-limiting step has always been securing FDA agreement over definition, capture and measurement of subjective endpoints. Everything now rides on successful clinical validation in the (still to be registered) two part Phase III study, although there are several other critical boxes to be ticked. Bunion: for the record (and it's in my posting history), having bought in large at sub-2p (on the back of a very strong acquisition rumour and with a large, unanticipated, bonus burning a hole in my pocket) and sold at around 18p on EMA approval, PLE, my one and only AIM investment, paid handsomely, thank you. My only regret, one almost certainly shared by many, is that I did not dump the lot back in November 2013. The remainder was dribbled out on spikes, last tranche going at around 5p on the back of the RP acquisition rise.

Oh, I dunno- I thought Ken Dodd's tax arrears alone were in the same ballpark?

This JM quote from a FT article earlier this week made me laugh out loud: Juvenescence aims to tap longevity ‘money fountain’ https://www.ft.com/content/30bb0752-6d5e-11e8-92d3-6c13e5c92914 Every comedian needs a catchphrase.......

Gents, I can appreciate the desire for any hint of positive news on the horizon, but worth keeping a little perspective. To repeat, a batch size of 50K is snack-sized for metered -dose manufacturing and hardly taxing on fill capacity (a single shift for a double line fill/closure set up). It's also expensive but serves as a compromise until likely demand can be established. The first true "tell" that decent demand is anticipated for Fortacin will be notice of batch scale-up to a minimum of 500l, even better if the intention is to (semi)automate the mix and fill process. Pharmaserve, as a contract manufacturer, may or may not need another fill line, but if so, this may not necessarily be driven by Fortacin. At 8 million cans a year, capacity does not appear to have changed that much since the facility was acquired from INYX and they might be struggling to compete with larger capacity CMOs. Installation of an additional line, even within an existing facility, will require planning permission, so easy enough to check with the corresponding authority (Halton Borough Council. Last Pharmaserve application was May 2013). Six month demand data for the core territories will not be available until year end and realistically, it will probably be mid-2019 before first guess at market requirement can be made, with subsequent announcement on scale-up if warranted. As for any "additional licensee" fantasies and extra demand, think of the timelines. So, stock up Hob-Nobs, dig out the box-sets and sit back for 12 months....

Pomander, other than some fun with numbers type speculation on this BB, there's nothing to indicate that current scale-up is any more than getting a better margin out of small-scale manual production. Perhaps I did not make myself clear, but labour and QA/QC for either a 200l or 380l batch would be around the same (say �7000-8000), so upping batch size does significantly bring down unit cost. Fortacin manufacture is, by pharmaceutical standards, a very simple batch process (mixing vessel, two blokes, nitrogen for purging, plug in to an existing fill line, rinse and repeat), and even for a space and resource constrained contract manufacturer like PSNW, easy to run batches as required (the need to hold canisters for a couple of weeks in a controlled environment is probably the rate limiting factor). The surprisingly short shelf-life also mitigates against stockpiling so early in the roll-out. JG's confusion over process aside, the outcome is that the deal terms reflect Recordati's perception of potential as being in the Euro 10m to Euro 30m range. Given the low cost of acquisition and the term of the agreement, Fortacin will, in all probability, wash its own face, even if it takes a decade, but it first needs to gain traction in a very small treatment population served by a small number of secondary care prescribers. Simple arithmetic dictates an initially flat sales curve. Loss of exclusivity might normally be a concern, but niche, non-reimbursed products do not make for attractive generic opportunities and I see Fortacin as being at very little direct threat. Generic dapoxetine might exert some pricing pressure, but it too is non-reimbursed. Interestingly, generic dapoxetine is already approved in Europe, but goes out branded as Priligy via Menarini.

Gents, you are reading way to much into something that's a workaday part of commercial production. Scale-up, as RP themselves have stated, is to reduce transfer price. As a batch process, labour and QA/QC costs are about the same for a 200l or 380l fill size: bigger batches mean lower unit cost. Automation is rarely feasible below 500l. Let's consider early demand requirements. To repeat an oft-made point, the ramp-up curve of non-reimbursed Rx products is very different from that of reimbursed products, with no stocking by national or regional health systems and with a low incentive for wholesalers to risk their own cash. The very low population currently under pharmacotherapy of any form for PE and very low levels of treatment seeking makes for a very flat line. Launch has been devolved to national subsidiaries and the initial product requirement is primarily to meet sampling demand. There are some differences between the core territories but all more or less follow Bertrand Law: samples can only be provided on written request are strictly limited (maximum of 2 per year per prescriber in Germany, up to a maximum of 10 per year in Spain). Prescribing urologist numbers vary between the core territories, but even in the most richly endowed (Germany), rep access will be to no more than a couple of thousand potential prescribers , with sample requirements across all core territories being in the low tens of thousands. Pomander, your "two to three years to peak" is overly optimistic, even for a reimbursed product. Sales curves for Rx products have been studied to death and are remarkably similar, peaking in year 6. There's little in the way of quantitative analysis around non-reimbursed Rx products, but since they do not benefit from "normal" market drivers, it's not difficult to predict that time to peak will be greatly extended, if ever reached. And, coming up for 25 years in licensing, I've yet to experience a potential licensee pitch numbers (nor offer an initial term sheet). Being only months into a staggered, nationally-focused launch, I doubt that there any measurable sales and confirmation that early prescriber interest is actually converting into use might be two or more years away. The planned drug utilisation study should help sharpen sales strategy. Frustrating, if you are relying on near horizon sales to invigorate the share price, but that's the nature of the beast.

SOTRR, I sincerely hope I'm not the only one to appreciate the irony of your observation.

Pomander, "not typical" in the context that there was no co-development cost provision in the Recordati agreement. There's no mystery around the scale-up. The restated licence agreement contained a rider attached to cost of goods, with milestones payments being reduced by Euro 1 m in the absence of successful scale-up by RP and consequent lower transfer price. Fortacin production is a relatively simple batch process, with batch size being determined by mixing vessel volume. The move from 300l to 380l might be dictated by a need to further reduce cost of goods, but more likely that PSNW had a 380l vessel going spare. The practical limits on batch size are the need to store filled but unfinished canisters for about two weeks to check leakage and shelf-life, which is short for Fortacin at only 18 months. The last thing you want in early launch with unpredictable demand are pallets of expensively warehoused finished product with the clock ticking towards the use by date.

Pomander, sincere apologies! I'd forgotten that not everyone has TMS on the whole time. Enjoy!

Sorry, that should read "Wildly wrong approval timeline estimates or misleading communication by biopharma companies (yes, looking at you Northwest Biotherapeutics....) are not unknown..... Distracted by England actually taking wickets at Headingley.....

Wildly wrong approval timeline estimates or misleading communication by biopharma companies (yes, looking at you Northwest Biotherapeutics....), but it is staggering that minimal progress has been made with the FDA since they delivered a thumbs down to the Phase III study data back in 2010 or thereabouts. It's also worth remembering that the bare bones RP disclosure is just that and that other study and non-study boxes require ticking beyond PRO validation and achieving subjective improvement over placebo. A realistic timeline and relative risk will become more apparent when the details of the study protocol are released, although this is not something RP have ever volunteered. Right now, I'll stand by my minimum 52 month estimate from first dosing. Time for angry LTHs waving flaming torches and pitchforks to advance on Castle Gibsonstein?

I suspect that JG is always sent to get the first round in, as it's likely to be last orders by the time he makes it back with the beers. Regulatory issues aside, OTC is not an easy market (Alquemie looks at his hand, remembers fingers getting burned.....), being highly promotion sensitive, price constrained and channel dependent. In developed markets, you are absolutely at the mercy of the retail pharmacies and supermarkets- and boy, don't they know it. On principle, I never shop in a certain high street chemist that rhymes with "daisy roots", as payback for the months of my time spent wrangling over transfer pricing and shelf placement. China is a big country and does not (yet) have national or regional retail pharmacies, making for piecemeal distribution. Internet sales are possible, but these largely piggyback off pharmacy presence and promotion. Never say never, but I don't believe that the infrastructure to support OTC sales is in place.

Pomander, if you are referring to China, you would still have the "foreign drug" issue with an OTC application. And since Fortacin is not OTC in any jurisdiction, the CFDA would not simply accept a submission without consideration of the prilocaine-related safety issues. Conversely, while Fortacin requires a full submission and regulatory review in HK, lidocaine-prilocaine products are classified as "pharmacy only medicines", meaning that they can be bought from a registered pharmacist without prescription. OTC in Europe and the US is many years away, if ever. There's a current FDA review of amide local anaesthetic (benzocaine, lidocaine) OTC products, which began with the withdrawal of teething pain products few years back, but has now extended to products for adult use. Risk is significantly lower with delay sprays and wipes but it would not surprise me if they eventually slap warnings on monograph products.

It's pretty obvious that time required to develop an acceptable PRO was grossly underestimated. I have some sympathy for Dr Mike and his advisors in that they were working in essentially a regulatory wilderness, and without the benefit of being a member of a pre-competitive consortia, as is the case for the majority of PROs/COAs. That the FDA appears to have finally accepted the PEBEQ as being worth clinical validation is a small triumph, although this, and the subsequent pivotal study are far from being slam-dunks. At corporate level, the only thing consistent regarding the FDA process is that RP statements and timelines were consistently inconsistent: naivety or disingenuity? As for the "focus on China", HK and Macau, to mix metaphors. are the low hanging fruit right on the doorstep, and represent the only jurisdictions with a high probablity of approval on the back of the existing dossier. Despite recent reforms, there is still no easy route to approval in mainland China even for high need drugs, let alone willy sprays. There may eventually be a couple of less forms to complete, but it's still a minimum of two local clinical studies and five plus years.

Well, on one hand there does appear to be a plan in place, on the other, everything is riding on clinical validation of an untested PRO measure. As always, the devil is in the detail, and, as always, detail is not something RP ever volunteer. In the absence of a study protocol, and with some doodling around with historical response and dropout rates and assuming 2:1 randomisation, I estimate necessary recruitment at around 400 subjects/couples, split 150 and 250 between the validation and pivotal study. I'd allow 24 months for the pivotal, so a minimum of 54 months from dosing of the first subject.

Pomander, link below: http://www.regentpac.com/ICMServlet/download/15-2175-3547/EAnnualReport-RPGL(31Dec2017).pdf Launch estimate on page 23: "The Group will continue to dedicate the necessary resource, with the assistance of its US regulatory consultant, to pursue approval from the FDA in the US as quickly as possible by diligently working through the various regulatory steps, next being the submission of a NDA with the FDA. In this respect, it is expected that the NDA will be filed with the FDA in 2020, and in accordance with mandates set forth by the Prescription Drug User Fee Act (PDUFA date), the FDA will be required to respond to the dossier within a 10-month timescale, which would facilitate approval in the US by the end of 2021 with a commercial launch shortly thereafter". "

Pomander, no study means that there is no clinical readout to enquire about. I'd missed it first time around, but RP did provide an update in the 2017 AR (March 2018, bottom of page 11): ".... Following on from the Company�s meeting with the FDA on 9 August 2017, a pathway has been developed for submitting the NDA. This will involve, among other things, a double blinded placebo pilot study clinical trial that is designed to support the measurement properties of the Premature Ejaculation Bothersome Evaluation Questionnaire (�PEBEQTM�) (i.e. the validation and reliability assessments for the PEBEQTM), which is being developed per FDA Guidance and with FDA input. The pilot study will take approximately 12 months to complete". "Following a positive completion of this pilot study and receiving input from the FDA, Plethora will undertake a phase III double blinded placebo clinical trial and on completion the data will be submitted to the FDA. It is estimated that the clinical trial will take approximately 12 months to complete" RP's US launch estimate is now early 2022. This strikes me as being more than a tad optimistic, with no study currently registered and a with only 12 months stated for completion of the pivotal study. The timeline could reasonably be expected to stretch by another 12-18 months.

Pomander, sadly it�s just not possible to hide a pivotal clinical study, and until such a study is registered and screening underway, it�s impossible for RP to offer a credible estimated approval date or timeline. The mystery is why RP have elected not to update the market, given that the root cause(s) of delay may well be factors over which they have no control.