Member Info for RMM3383

HBD - Interesting read. The last para really chimes with me in that you can't continually boost the immunity system. Reminds me of the debate within the sports endurance sector over carb loading. You can't do it all the time and in fact the effectiveness drops off after each regime (where you deprive the body of carbs and then reintroduce whereby the body 'gorges' itself). The body actually learns and anticipates what's coming and as a consequence the anticipated boost gets moderated. We still have a lot to learn in this area.

I’ve been looking at the Covid Infections curve and its not this summer that worries me. In the last 15 months the damage was done in the initial phase when the vaccines weren’t available and treatment was rudimentary. Summer last year was actually quite a low point until autumn set in and the infection rate rocketed before the vaccination programme got underway. My expectation is that we won’t see a ramping of the infection rate during the Summer months due mainly to the fact that people will socialise outdoors and borders will on the whole remain closed. However, if we have a wet summer followed by an early autumn things could change dramatically. October '21 onwards will be a sensitive time even if we have all adults vaccinated as much depends on which variants emerge. Then there’s the whole issue of Long Covid the symptoms of which are wide and varied. In reality its not much different to what was previously known as Post Viral Fatigue (everything gets re-labelled these days, no one is diagnosed with depression anymore, nowadays its Bi-Polar Disorder). The vaccines are not going to completely stop infection neither do they address ‘Long Covid’. I suspect that going into winter this year the medical profession is going to be in a quandary. How do you protect people against both the Flu and Covid? We’re already talking about boosters to tackle the Covid variants but because there was no flu this year the pharmas don’t have a clue as to what to put in the flu vaccine. In fact I wonder how many people will not get the flu vaccine because of 'vaccine fatigue'? there’s the whole non-covid backlog that the NHS is gearing up to tackle. Potentially this leaves SAR in a sweet spot should it get PoC. A therapeutic that deals with those who are unfortunate enough to catch Covid and one that could moderate the Long Covid symptoms. Furthermore, if it works against Covid it could also be part of the flu arsenal. Add on the implications of getting a fast track for 1801 and potentially 1802 and the Government would be unwise not to back such options. At which point the big pharmas will wade in. Whilst PoC can’t be guaranteed, if SAR is successful then I’ll need to re-write my model. June therefore remains a pivotal month for me! GLA

Interesting article for the insomniacs while we wait on news. Not all cytokines are the same....
https://endpts.com/exclusive-carl-junes-tmunity-encounters-a-lethal-roadblock-as-2-patient-deaths-derail-lead-trial-raise-red-flag-forcing-a-rethink-of-car-t-for-solid-tumors/
Note the comment 'IL-6 was the smoking gun for blood cancers', but needed Tocilizumab to tame the storm. However, it doesn't work for solid tumours and the thinking is that it may be because its not well absorbed by the brain 'or some other explanation may apply'.... Taming the cytokine storm is not just about Covid. GLA

Very happy to be wrong and have missed the premium! That’s part two ticked(part 1 was delay the cta). Now we wait on part 3, the POC results....

Been catching up on the posts from the last two days. In respect of a valuation I’m going to stick to my timetable of reviewing everything at the end of June. From my perspective June is the pivotal month simply because we should find out whether 1801 is effective against Covid. A while back I posed the question as to whether it was sensible to put in a CTA for 1801 before we had news on the Covid PoC. From a strategic point of view I couldn’t see the sense in doing this. Why not wait and if PoC for Covid is successful then it changes the whole basis upon which both 1801 and 1802 are valued and funded. If I was In the BoD’s shoes I’d delay the CTA (which they have done blaming the delay on the pandemic?) and focus on getting the data for the Covid PoC processed. I’d raise a small amount of money while the SP is riding strongly in order to keep the lights on but mainly to demonstrate to any potential buyers/partners etc that we can quite easily fund the next steps and to secure the negotiating platform. No need for a hefty dilution if you can afford to wait a little longer and raise money from other sources. And then there’s 737. It’s annoying that Dilly isn’t being completely transparent but then he’s got institutions breathing down his neck. He’s given clear signals that Momo is not going to be the only asset in the future pipeline and he’s had every opportunity to hand 737 back. Once we know what his plans are then I have further data to put into the valuation model. My view is that he will announce in June/July once he can say that recruitment for the Momo trials is complete and thereby justify a change in focus. The biggest risk in the short term is that 1801 doesn’t work against Covid. My view is that 1801 will go into trials, 737 will be taken forward and 1802 should follow suit. The Covid PoC, even if it fails, will not stop the original plans. Covid was always a sideshow but it has become a very useful sideshow that could fundamentally change the funding options and overall value of SAR’s IP and that’s why I don’t want to hang my hat on a valuation at this point in time. During June I will wait, watch and then review. Until then GLA.

I rasied a question at the Investor Meet session along the lines that surely it would be better to get the results of the Covid PoC on 1801 before putting 1801/2 into CTA. Tim avoided the question but now it seems that's exactly what they are doing! Apart from the delay its far from bad news. In fact on 737 and Covid it seems to be just the opposite! GLA.

I thought that the Edison report was done to death yesterday. Couldn’t understand the bit about SAR de-prioritising 737. Clearly wrong as Sierra control it! The whole EQS thing this morning is a storm in a tea cup. Nothing has changed. Everything to play for in terms of 1801 POC and beyond.

John R mentioned CAR-T last week in the context that a number of therapies have side effects that 1801 could address. Our interest would be in combo therapies to address over reaction of the immune system.

As expected the BoD presented as much as they could given stockmarket rules and confidentialities. What helped me was the clarity around the indications being considered - Psoriasis, Psoriatic Arthritis, Lupus, Ovarian and Breast Cancers, Covid, Flu, CAR-T side effects. My biggest problem has been in identifying which markets the molecules could address. I think we've now had some clear pointers. Whilst 1801/2 could have much broader applications there has to be a starting point. I would not expect SAR to take the company beyond P1 for 1801/2 but 737 could go all the way (100% regression??? how can someone ignore that....) and then there's Covid/Flu/CAR-T etc. Bottom line is that Thoth's 28p on just 737 could be an underestimate and for 1801/2 we definitely go beyond £1. Not going to reveal my workings this time, that will be in June when I expect an update on the Covid PoC. In Tim's position I wouldn't rush negotations. GLA

Looks to me as if the MM's are allowing a drift upwards in anticipation of tomorrow's session. I wouldn't be at all surprised if they dont engineer a drop as Tim makes his opening remarks. However, the current rise is IMHO totally sustainable as SAR have not hyped the SP to high heaven and we have a highly promising pipeline going forward that is not reliant purely on a single indication. I've been watching the carnage over at Hemo where the SP spiked in November to 12p and now lies down at 2.7p. The dangers of not having a long term strategy that doesn't rely on Covid. For me the next few months are pivotal for two reasons. If we get PoC with 1801 for Covid (not guaranteed) then this opens up much more than just the treatment for the current pandemic. It puts 1801 firmly into the arena for respiratory diseases. If we don't get POC for Covid then the focus reverts to the CTA for other indications, of which there are many to choose from. We are not reliant on Covid but it could change the pace at which we progress. For once I'd like to see SAR take a measured approach to timelines. If we don't get results until the end of June then waiting 2 months is a sensible delay. Tomorrow should be interesting but not ground breaking. GLA

It’s pretty obvious the delay was to include a statement after the Government announced the Antivirals task force. Should the task force mention TYK2 then it’s a big headline for us. Especially given the situation in India.

Article in the Telegraph regarding the second wave of Covid sweeping India. ‘We’re seeing many more people with a cytokine storm’. Therapeutics urgently needed.

We are now halfway through April and the BoD have told us that there will be a trading update by the end of the month. Let’s start with Sierra. Last year they moved their Head Office, recruitment has been underway for some time, institutions hold the majority of shares and have invested large sums and in Stephen Dilly they have a credible operator. These are all signs that Sierra is not a short term investment. Furthermore they are not signs consistent with a one product pipeline pharma. He clearly has a strategy. What this strategy is depends on who you are. If you are an institution he’s probably let you in on his plans, under strict confidence etc. For the likes of ICR/SAR we remain a ‘supplier’ and will be told of developments as and when appropriate. I suspect that we will know more by the end of April. In the meantime the SAR BoD have plenty to be getting on with. We are now just over halfway through PoC on 1801 for Covid. I doubt very much that they have enough data to make a statement but what they do have is probably shaping their thoughts. If the data is looking good then I’d be re-thinking my strategy for getting 1801 and 1802 into the clinic for immune/cancer. Currently SAR does not have the money to get one let alone both into the clinic but I don’t believe that is the key issue. I suspect that money is available but there’s a very big issue hanging in the balance. If 1801 looks good for Covid then funding and timelines change dramatically as does the value of the company. In this position I would ideally postpone any trading statement until the 1801 Covid PoC is resolved. However, they can’t do this. My expectation is that the update we will get at the end of the month will be highly dependent on what happens over the next two weeks. Sierra milestones would be useful cashflow but the main impact will be on the SP. How they go about raising the money for putting 1801 into the clinic will be indicative of how confident they are that 1801 will prove effective against Covid and the fast track that could follow. Furthermore I don’t rule out an institution putting in the money. With the Covid global fallout getting worse by the day (side effects, political posturing, media propagated misinformation, manufacturing bottlenecks, new variants etc etc) there isn’t a single pharma out there that is probably having to change its plans on a weekly basis. For our two executive directors that’s a real problem in terms of the day to day tasks and the longer term strategy. I’m expecting an update but it will have to be heavily caveated until there’s some certainty around 1801 PoC and Covid. Should 1801 not prove effective against Covid the only thing that changes is the timescale for getting it into the clinic. April will be important but June/July could be pivotal. In the overall scheme of things that’s not long to wait. GLA

Hi Working - Thoth has mentioned the next pandemic a few times and I seem to recall he was the first to say that based on Spanish Flu it wouldn't be the first wave that did the damage. On a different tack I met someone in Cornwall last September who had been in regular touch with a researcher from Oxford. His view was not to stock up on loo rolls and tinned food just yet as this wasn't the biggee in terms of pandemics. Apparently that is yet to come.......

Hi Citizen. Nothing wrong in publishing research that doesn't project our molecules as guaranteed blockbusters! Taking the two pieces together there is some interesting overlap. The first article seems to suggest that toxicity is an issue but that this could be overcome by adminstering lower doses more frequently, something that 737 is good at as it is the only oral inhibitor of the 3 tested. The second article then seems to suggest that TNBC drug resistance was established through gradually building up the dosing levels. If 737 can be administered orally at low doses along with something like Gemcitibane then toxicity and resistance are not an issue. What we need is for 737 to go back into the clinic with suitable partners for combo trials.

I've been looking at the data behind Chile's 3rd wave which is hitting the headlines in some journals (as a wake up call to the UK). My conclusions are that SAR's Covid play could be bigger than we think, assuming 1801 is effective. Chile is ahead of the UK in terms of its vaccination program but that creates a false perception of how protected the vaccinated population is. The majority of the population were vaccinated using the Sinovac vaccine because the Government in Chile got in very quickly with an order (its almost the reverse of what the EU has done). The Sinovac vaccine has an efficacy rate of around 50% vs Pfizer/Moderna's 95%. Whilst almost a quarter of Chile's population have had both doses and a third have had one dose, with the majority having Sinovac the reality is that probably only 5% of the population are fully Covid resistant. That's a long way off having a community that can re-open. Hardly surprising therefore that despite the number vaccinated the third wave is so bad. For Chile the options are to go for vaccine boosters, further lockdowns or a means of reducing severity through therapeutics thereby easing the pressure on the hospitals. The Daily Terrorgraph recently published an article saying 'we may never get back to normality'. Depends what you mean by normality because lifestyles have irreversibly changed under lockdown and the better hygiene practices will probably reduce the impact of colds and flu for many years to come. However, the world cannot operate under lockdown forever, vaccines are not 100% effective and who knows where the next variant will take the virus. Should 1801 prove effective in the PoC against Covid then it becomes a major component in the arsenal against the current pandemic as well as against other respiratory conditions. It's going to be an interesting race in terms of what goes forward first - 1801 into the Clinic as promised or the results of PoC for 1801 against Covid? I still think it's too early for results on PoC however, I think it will be a neck and neck race. Meanwhile I wait on 737.

b_t - Prepping the figures IMHO is not the issue. They are waiting on something. Could be news on 737, funding or a research update, or all 3. We'll know by the end of April at the latest. My view is that something pivotal is in the pipeline and it will kick off a cascade of activities. I'm not banging the T/O gong here but these are unprecedented times in terms of the pandemic and its effect on the sector. One way or another I think we're going into the clinic and that raises the bar in terms of SP.

Just reviewed the weekend 'board' and as far as I'm concerned nothing has changed in respect of TYK2. We wouldn't be going into the clinic without patent protection, MTD resolved in the eyes of the regulators and above all else, faith in the science. My money remains on John Reader. As to other interests, quite clearly something is brewing in the US with Sierra (whether its 737 is yet to be revealed). In respect of 1801 and Covid the clock continues to tick but we're not late yet. For all the scientific debate the fact is that only John and Tim really know what 1801 and 1802 are capable of and they only joined the Covid bandwagon when it was clear there was a potential role for 1801. My view remains that the key benefit of PoC for Covid is acceleration and that's probably for both 1801 and 1802. Like most LTH's I'll look to the MM's to raise their game and SP before parting with any shares. GLA

https://endpts.com/roche-claims-key-win-in-the-12b-early-stage-checkpoint-race/

Just wondering if Merck will rise to the challenge and combo with a certain company we have an interest in.

Furthermore with POC the Pharma’s are going to look at us differently because our value overall just went into a different league. I’m not expecting a pre-clinical licence quite simply because I think we’re now beyond that. What has held them back will be the lack of data but that game could literally change overnight. I always thought 2021 would be a pivotal year but that was without Covid. The pandemic has simply underpinned my expectation. I’m not making any SP predictions because sentiment will play as big a part as the science. So far nothing has undermined the science this year, even Aurora still has potential in the right hands. So, in conclusion I’m waiting on Sierra and then the BoD. Patience is a virtue but a good red makes the waiting bearable! Hope that helps. GLA