The latest Investing Matters Podcast episode featuring Jeremy Skillington, CEO of Poolbeg Pharma has just been released. Listen here.
Since Boris unveiled a new antiviral taskforce, I thought I'd brush up on where we're at in terms of competition with other oral treatments. Just going to go on a tangent here and say that for the record I don't like to think of the other drugs as competition because I'd like to think we're all in this together and need as many treatments as possible so we can overcome this dreadful virus once and for all. Oral treatments of course have its advantages over injectable treatments (such as monoclonal antibodies, convalescent plasma, and Tocilizumab), and logistically could prove to be a much more convenient treatment option. So how many are there, and what are the chances that the UK government have their eyes on us and we are the 'magic pill' they're talking about? Lets get into the treatments currently being trialled:
1) Upamostat (RHB-107). This serine protease inhibitor with both anti-viral and anti-inflammatory actions is being studied to see if either its low dose or its high dose is effective in clearing SARS-CoV-2. It's already showed effectiveness and apparently a very good safety profile, and was cleared by the FDA to start an outpatient-based P2/3 this year. Lots more work to do with this one so my thoughts are that Upamostat's not really in the running for now.
2) Atea & Roche's AT-527. The companies have recently confirmed positive P1 results of this oral anti-viral and therefore it's progressed into P2, with a specific dose being shown to be effective in clearing SARS-CoV-2. Trials are still obviously ongoing with an outpatient trial being done currently in the UK, Ireland, and Bulgaria. I couldn't find any information to support NIHR involvement of the trials in the UK but admittedly it was late when I looked into this one, but AT-527 is some way off from getting the numbers that are needed.
3) Lopinavir/Ritonavir. These are oral protease inhibitors and inhibitors of cytochrome P450 3A, and it was studied in trials against the SARS-CoV-2 virus and as of last year were shown to not be beneficial in hospitalised patients with Covid-19. The Darunavir/Cobicistat treatment, although tolerated well by patients in the study done early last year, didn't show much of a significant result either as far as I know. Both of these are old news and I haven't paid much attention to them since last year.
4) Favipiravir is an RNA polymerase inhibitor that's been used to treat influenza viruses in Japan, and was granted EUA in Japan as well as in some European countries. It's currently in a P2 trial in the U.S., and as far as I can tell the objective of the study is to see whether viral load decreases when given within the first 72 hours after a positive diagnosis of Covid-19 in an outpatient setting. I think Japan have progressed this into P3 while it remains in it's P2 over in the U.S. until it progresses further. Nevertheless, it was apparently shown to be more effective than the Lopinavir/Ritonavir combination.
(Post 1/3)
Thanks all.
White-rabbit, I completely agree with your post. The knock-on repercussions on healthcare systems after initial infections of all of those people are indeed often overlooked - a good result regarding PACS would be ideal for us. What you said there is key - a drug that could potentially lighten the load off of those systems could very well be valuable.
Maver1k, I suspect there'll still be a thorough reviewing of even that last patient's 90-day arc but as Matml quite rightly said it's anyone's guess. Slotting in the final patient's data into a pre-determined RNS sounds a bit too straightforward to be true as they like to take their time with releases and rightly so. For what it's worth I think it'll be May but don't quote me on that.
With the 90 day follow-up of the last patient dosed being upon us, I thought it'd be prudent to remind everyone why it's worth waiting for this particular endpoint of the trial and why it'd be in our best interests to have the data up until the 90 day point when trial results are released. Lets go over PACS first of all.
Post-Acute Covid-19 Syndrome, or PACS, is a multi-system affliction upon the body. A nightmare for GPs and potentially an inevitably common presentation for speciality physicians and rehabilitation specialists around the world. Imagine a practice where an all-too-common presentation is the patient that turns up complaining of relentless fatigue, sporadic fevers, intermittent sweats, recurrent headaches, a tight chest, and an unremitting need to take that deep breath in to fill the entire lung but just not being able to - all weeks or months after that positive swab result and with all of the other potential differential diagnoses already excluded.
It's not fully understood why it occurs in some and not in others. Weak immune responses leading to a prolonged viraemia, exaggerated inflammatory responses, mental decompensation, all theories that could lead to this syndrome. Studies have been done which have found predictive risk factors for PACS such as females, the older population and people with multi-system disease/more varied early-onset symptoms from the start. Therefore just considering these, it's clear to see that a significant population of the public are automatically at a higher risk of going on to developing Long Covid.
Lets continue thinking about this from the perspective of primary care physicians. Investigations such as blood tests, cultures and scans aside, many follow-ups may need to be arranged with potential referrals to secondary services being required for things such as pulmonary rehabilitation, cardiac investigations for things like ventricular dysfunction, chest pains and the now all-too-common 'lung-burns', mental health referrals, and a multitude of neurological illnesses such as the common cognitive clouding, or the rarer encephalitises or neuropathies. Those of you privy to the costs of investigations and referrals that the NHS or even healthcare systems around the world like in America demand will start to see just how much of an impact PACS could have on healthcare costs.
The effects of early administration of interferon beta on viral load has been observed already and the vehicle of the home trial to show both short and long term effects after this very early administration could be a stroke of genius. With the cohort being patients that aren't hospitalised and with one of the risk factors for PACS that I know of being patients who'd received hospitalised care already, I'm rather hopeful. Like we've all heard before - data is king. Even if initial endpoints don't impress, a larger dataset is a stronger dataset.
All just my humble opinion. Happy Monday everyone!
Thank you everyone, Happy Easter to all!
Yes I agree. The inclusion criteria alone in trials are a headache let alone the red tape that follows. With a trial being done in different trusts in the UK as well as different health authorities around the world which are headaches in themselves to navigate, it's reassuring that we're being fast-tracked and recruiting as fast as we are and this surely can't be without good reason from those who've fast-tracked us. Looking forward to the home trials coming through as nebs seem to be very effective in a lot of situations. In my opinion if they're not just as or even more effective than anything else being trialled at the moment including the monoclonal antibodies then I'll be very surprised.
I took a hiatus from here for a while and it's done me the world of good, but I felt the time was right to come back before news starts coming in waves.
The situation at the hospital's improved over the past couple of weeks both in ICU, admissions via A&E and the ambulatory unit, and on the wards. ICU treatments have been effective but the need for something more has been felt every step of the way. Dex, Toc, and Remdes have all been useful but they've only been able to do so much - particularly when the exacerbations and infections have truly taken hold of a patient's lungs on admission.
Vaccinations have been successful but herd immunity hasn't been reached and won't be for a while to come, meaning we'll still be under the shadow of the very tangible prospect of another wave that's threatening to offset the UK's roadmap out of lockdown. Our opinion is that the European wave will hit us and cases will inevitably rise again, but hopefully the numbers of the severely sick will be lower than they have been previously due to the vaccination efforts. However this still leaves us open to new infections in the voluntarily unvaccinated, the contraindicated, the exempt, the undiagnosed, and also reinfections (particularly in the elderly). It also leaves us open to the group vulnerable to respiratory infections, asthma and COPD exacerbations, the immunocompromised, pregnant women, children, and dare I say it - long Covid and PASC.
Vaccines may well be the answer to overcoming the pandemic but they will not be how we truly get ahold of this virus. Plan B was always and will always be needed. To the people on here expressing concerns that we need to be hearing news and we need to be kept informed and we're missing out on this pandemic, your concerns are valid and understable. But I will say this - if you knew what conducting trials in a hospital setting entailed and how much time they usually take, you'd know that we're in the right place, at the right time, we're still on track, and we're actually moving at lightning speed.
News is probably around the corner and if it isn't then I'm not worried in the slightest either way. But as always do your own research and all that.
Ah my post was aimed more not at the regulars but to everyone else. I've no doubt the regulars don't get shaken like some others do on here. And Ghia, absolutely right. I'm expecting that too. We may have had conditional pre-order news already depending on results or early results.
I've sensed that the overall sentiment on this board has drifted over the past couple of days with this SP drop. Some people clearly haven't grasped that this is the stock market and share prices do drop every now and then. What those same people need to realise is that nothing has changed with this company. Being announced onto the Activ-2 trial is bigger than some people can comprehend. I'm as disappointed as the next person that we didn't get the coverage that we deserved but I'm over it, and looking ahead to what's to come over the next few weeks.
If Remdesivir, Hydroxychloroquine and Dettol can make airwaves in America like they did all those months ago then so can we and I'm confident we will. There's a reason we've been fast-tracked and given this much priority Stateside. Biden's Science Team will be itching to announce some the first piece of good news since their induction and my bet is on an inhaled treatment that's already known to be safe and effective. I feel like we're close to a name-drop.
RM's interview on Fox Business was a class act once again. From not wanting to give any concrete numbers of treatments and not elaborating on the prices of treatments seems like him keeping his cards close to his chest. Our US partners and EU partners helping us gear up production, the UK's P3 arm underway, Activ-2 along with an FDA fast-tracked P3 all screams that something has already happened behind the scenes. I'm feeling sure that an agreement has already been made and they're just waiting on results for any major announcements. We may have a slow couple of weeks or so ahead of us if we don't get name-dropped but once we enter the thick of February 2021 then things will start getting serious in my opinion.
Nothing's changed. Do your own research and remind yourselves why you invested.
All of the above purely speculation of course.
It'll soon dawn on people Oak won't it. Very soon in my opinion too. One of three indeed but I struggle to think of one that can be utilised in the way ours can, and the sheer relief it'll provide to a country being rocked by case numbers and death at the moment. The value is being realised and I'm looking forward to extremely good days ahead starting from right now. I'm so proud of how far we've come and where we're clearly going.
Well said Ghia. I have a feeling this climb on the back of Activ-2 inclusion news isn't done yet and as soon as we're name-dropped we could be flung north even further. It seems like we're picking up momentum quickly now.
If it doesn't happen tomorrow pmjh then nobody will be holding you to anything, don't worry. You've done more than enough to reassure us that good news is on its way this month and that's enough for me. But yes if it happens tomorrow then I'd love that too.
Jaffjoon, interesting question. You have to think of both SNG001 and the vaccines in terms of their purposes and the timing of their administration.
So for vaccines, you're giving them to people to prepare for the eventuality of contracting the virus and being able to deal with it if and when they ever contract it. The active immunity acquired would cause a disease less severe in someone who hadn't been vaccinated, if at all. In theory.
For SNG001, you're giving this therapeutic to somebody to give someone back their antiviral response molecules that were inactivated by SARS-CoV-2 infection - interferon. This interferon is involved in the body's response to a virus via an increase in cell to cell signalling. They message the rest of the immune system to alert it to an active infection and activate cells like macrophages which target the invading antigens.
In an unvaccinated person, the interferon would be used to give a person back this interferon to make sure their bodies are primed enough to fight the virus. In a vaccinated person, they already have another mechanism to fight the virus by way of antibodies to the virus which now exist due to the vaccine. So two entirely different mechanisms to fight the virus.
However, vaccinated patients, like unvaccinated patients, can still catch the virus. Viral exacerbations, viral pneumonias, pneumonitis, can all still occur, particularly in those susceptible to it. In vaccinated patients, it's hard to say how severe the infection would be but exacerbations can still occur and difficulties can still be encountered. By giving inhaled interferon to a vaccinated patient you're just giving them something extra to help fight the virus which they should have had in the first place. Being vaccinated or unvaccinated makes no difference in terms of SNG001's use. SNG001 is there for both vaccinated and unvaccinated people to bolster their immune responses, whether they have other existing mechanisms to fight or not.
Hope that helps.
Thanks Oak.
I saw a post yesterday that suggested we were missing the boat with the second wave and I'm afraid people just don't seem to grasp that the second wave hasn't even peaked yet with a few weeks left for that to apparently happen. That's a lot of exponential spread until that point.
Rumours of new variants evading vaccines, rumours of data needing to be looked at more closely as per Vallance's recent comments, and rumours of families being allowed to mingle over Easter, could all be catalysts to send this even further past the peak. I hope it doesn't happen but we're on track to being a therapeutic waiting on the other side to those that need it.
So starting with some science again from when a patient spikes a fever. Fevers generate large amounts of heat and this is owed largely to the action of certain chemicals called pyrogens which travel through the blood from sites of higher immunological activity where certain threats have been identified. These pyrogens trigger the hypothalamus to generate a higher temperature as a self-defence mechanism to kill off the offending pathogens. The body's oxygen consumption increases, but in patients who've been badly affected by Sars-CoV-2, the supply and demand ratio can sometimes be affected by lung damage such as inflammation and scarring. The lungs are unable to keep up with the demand of oxygen from the body, and this in turn causes oxygen desaturation. In severely deteriorating patients, oxygen isn't enough and further breathing support's required and then possibly ventilation. In ICU, flipping patients over to improve oxygen saturation is often seen but sometimes isn't effective enough, and so general supportive measures are often explored to ensure everything else can be done to support patients as much as possible. I started from the scenario of spiking a fever through to ending up on ventilatory support in ICU as I wanted to take you through the likely journey of somebody who continues to deteriorate with Sars-CoV-2 in hospital.
According to my ICU colleagues the space available has now reached critical point. Spaces for patients in ICU need to be huge to accommodate for oxygen units, CPAP machines, ventilator machines, dialysis machines, infusion machines, ECMOs, among other things. Space is running out and the makeshift ICU wards that were created on other levels of the hospital are the next best thing but some just aren't big enough. Over-spillages are occurring into neighbouring wards, and around a third of patients needing ICU care aren't making it. Dexamethasone is thought to prevent one in three deaths of patients already on a ventilator, yet would those patients even need to be on a ventilator if interferon had played a bigger role in their immunological response at any point before the deterioration had led them to ICU?
With the recent short-ACE2 study now helping us understand our role amongst a cytokine storm, vast amounts of safety data, as well as P2 efficacy data and now a filled home trial, I feel like we're tantalisingly close to getting the EUAs we need. There are many points during a patient's deterioration that I feel inhaled interferon could be given to re-ignite a patient's antiviral response and immunological fight. The apparent Activ-2 announcement (different setting I know) in the coming days could be more welcome than you think in terms of the quick data it could provide, and I could be forgiven for suggesting that preliminary data in Activ-2 could pave the way for early EUAs. We're still in the eye of the storm, and people could do with it right about now.
All of the above purely speculation of course. DYO