Hi Guys here are the responses from the great man himself. May I just add superb by him to get back to all these questions on the same day with such detail. Very impressed. Enjoy.
Hi Tom,
Hope you are well.
Ive had discussions with a group of investors and we decided instead of bombarding you with questions of a similar nature we have decided to compile a list of questions from all of us for you to hopefully assist us with (we will post the answers on Hotcopper(an investment site) so all investors a part of forming this list get their answers satisfied).
Questions:
About Announcement1. Why would you give notice of a conference call within 30 minutes of the conference call commencing? Why not announce something like that on Friday?This was not the plan, unfortunately the ASX decides at what point to release the stock from a halt and hence the primary release. I was expecting this to be much earlier in the morning (and this drove the subsequent presentation disclosure and call details). Completely out of Invex’s control. Typically, it is preferable to hold a call as close as practicable to a major disclosure like this so as the market can get access to the call and the information from the horse’s mouth, so to speak, rather than have the stock trade for an extended period and then have a call. This has and will always be my preference having done hundreds of earnings call etc over the years.
2. Why didn’t Dr Baldwin or Loveridge participate in the conference? When will we get a chance to be able to ask them questions directly?Dr Baldwin is a non-executive director of the company. It is not appropriate for her to join executive management calls like these in that capacity with investors. I can assure you she was an attentive participant on the call. Dr Loveridge is based in the UK, hence the time zone didn’t work this time. However, once we have finalised our clin/reg strategy in early Q4 2021 we do plan more of a group event for investors. Stay tuned for details through the ASX once the announcement is made.
About Drug
3. If Presendin has been dropped, what protection against off-label use of generics does Invex have?It is important to note what Presendin really is. Presendin is the trademark owned by Invex, for an Exenatide formulation that we plan to take to Phase 3 and market. The Phase 2 study was using Byetta (exenatide - AstraZeneca) on a 2x per day basis. This drug is impractical for IIH patients, but proved our scientific thesis that Exenatide lowers pressure in the brain of IIH patients, resulting in a strong clinical improvement in headache and vision over 10 weeks. After those results, we spent time developing a 1x per day formulation. We then held discussions with Contract Manufacturing Organisations (CMOs) to assist in its production. This strategy meant we would have need to then test this 1x day formulation in animals and humans to examine the pharmacokinetics (PK) – i.e. how the drug behaves. With Peptron – we will be using theirexistinglong acting exenatide for 1x week administration PT-320, which will be labelled “Presendin” for our IIH studies and for commercial scale orders. This is a very well characterised formulation and Peptron have used in in numerous animal and human studies. I made mention of this on slides, but basically it offers sustained therapeutic levels of Exenatide over 1 week. Exenatide in a naked form – i.e. not encapsulated in a microsphere has a half life of 2.4 hours, So you need to administer 2x per day to keep levels up (not good for patient compliance). SO, our detailed scientific and commercial analysis gave us comfort this Peptron formulation will beIDEALfor an IIH patient and we can use all of Peptrons data to show that We just need to prove Presendin is effective (and safe) in a Phase 3 study of IIH. So don’t think of us having to re-invent the wheel – this path with Peptron lowers risk, saves money and time – and they have a manufacturing plant designed to produce Exenatide. They are developing these formulations for neurological disease – Parkinson’s. We have no patents on that (they do), but we have patents on neurological conditions related to pressure (they don’t) and orphan designations. Great complementarity.
Is it only an orphan drug designation?In my view, an orphan designation offers superior, legislative protection than a patent ever will (which can be potentially litigated and objected as to its validity). So, from the day Presendin is approved in Europe, we have 10 YEARS market exclusivity and for the US we have SEVEN years – which prevents any competitor from using Exenatide in ANY FORMULATION for treatment of IIH. In other words, AstraZeneca who have Exenatide in form of Byetta and Bydureon can’t market and sell in IIH. Our patents cover the use of GLP-1 receptor agonists in the treatment of pressure related disorders of the brain. They are issued in Europe, US and Japan and provide protection until at least 2035. SO this covers exenatide and a whole heap of other drugs that may be considered for use. These patents are pretty broad in my view, and fortunately are issued.
4. Can you contrast the expected PK for Peptron's sustained Exenatide vs. Byetta vs. Daily Presendin or Exenatide vs. Bydureon vs. Daily Presendin
Our clinical, quality and reg consultants agreed the data Peptron hold is suitable for EMA and FDA purpose as a 1x per week. Therapeutic delivery from microspheres is unique as, over time, the exenatide dose in a given week is derived from multiple previous injections undergoing different phases of microsphere breakdown. With simultaneous release from multiple microspheres at different stages of breakdown, exenatide is released at a constant rate, without peaks or troughs in drug concentration – so you get nice even levels of exenatide. This is why we entered into a deal with Peptron (among other reasons too). We can’t control what the EMA / FDA may or may not say about this data, but the advice says it’s fit for purpose. Here is a snapshot of PT320 (Peptron) v Bydureon studied by Peptron and published. You can also go to:https://www.bydureonhcp.com/efficacy-pk-data/pk-profile.html AZ might have done a head to head of Byetta v Bydureon that has been published, but I haven’t got it. The attached paper might be of interest? – more skewed to Diabetes, which is the approved label for Exenatide (which we hope to change to IIH, of course)
5. Why is Invex comfortable in proceeding straight to a P3 without repeating the P2 with Peptron's formulation?No need per above, also we sought regulatory advice from EMA and FDA. Also running another Phase 2 would only likely show what we’ve seen and it would take time and money and it wouldn’t be adequately powered (statistically). The planned Phase 3 would be statistically powered to show a clinical effect. The Phase 2 we ran was a proof of concept in 16 pts. This is the benefit of a re-purposed drug and an orphan disease – you get to bypass a lot of the traditional biotech stage gates.
6. What exactly has been licensed in/out and to whom (i.e., by how much have we cut potential profits globally by using Peptron's SR-formulation); for what cost (whether it be financial or otherwise); what are the limitations to each party during and post P3.There is no licence. They produce the drug, we label it Presendin and then use it. This is a transaction with NO ROYALTIES and NO COMMERCIAL milestones. We pay a fix price per dose for clinical and commercial scale. The transaction is structured to ensure we (Invex) have enough profit margin when ultimately (if) this gets to market with partners and payers (government/private). As I said on the call, there is no Gross to Net sales effect through royalty payments etc that can be a drag on margins. We’ve left this as a nice, clean opportunity if we get to market. As a team, one balances risk versus opportunity. Peptron is far lower risk, lower road for us and we are important to them. A plain vanilla large CMO might produce a 1x day formulation for us at a lower cost, but it would be unproven (i.e. need to be all of what Peptron has done already), we’d be a minnow of a client (given orphan disease, volumes wouldn’t be enormous versus say a juicy covid vaccine contract). We’ve done the best possible deal for Invex and shareholders in my view and preserved the integrity of the asset value.
7. What has the FDA/EMA seen of PT320? Have they seen any of the pharmacokinetics or tolerability studies? Is the data package ready to go or will it need to be generated? How confident is Invex that the regulators would deem the current preclinical studies for PT320 to be acceptable? No, the Peptron data will be presented as part of our regulatory submission to commence a trial. However, Peptron have run a bunch of studies in Korea under the Korean FDA equivalent and has a GMP plant. Korea is a signatory to a number of global initiatives on drug development, so we feel pretty comfortable on their diligence. AS above, our consultants believe its fit for purpose, but ultimately we can’t predict what a regulator may or may not say.
8. Do you think that the preclinical and clinical data from Peptron about PT320 will change the FDA's mind on the recommended primary endpoint for the phase III trial for Presendin?The FDA response wanted Perimetric Mean Deviation (PMD) as the primary endpoint whereas we submitted a Phase 3 design for ICP and headache. The pre-clinical/CMC package and human safety studies are obviously important, but the overarching consideration is the endpoint request. Wont change anything in other words.
9. What superior aspects does PT320 have over Bydureon apart from the faster steady state?I think the paper attached calls these out nicely. There is no commercial benefit whatsoever in using Bydureon in an IIH study, if that’s what you mean. We’d only be benefiting AstraZeneca and evergreening their franchise. This new formulation allows us to have a proprietary position in IIH. If AZ wished to suddenly use Bydureon in an IIH trial, they still would be prohibited from selling by virtual of our orphan drug designations. It’s an exenatide formulation, after all. We also have issued patents too.
10. Is IXC going to be using a unique formulation of exenatide for IIH treatment? If not then our sale potential must surely decrease if we are just relying on orphan drug designationAS Above, Peptron’s PT-320 is the formulation, branded Presendin and we have an exclusive agreement for that. We areNOTdoingANYformulation work at all, and they’ve done theirs. So why we say “12 months and $3M” reflects the fact that had we appointed another CMO on the same day as Peptron, all of the lead-in studies would need to be done from scratch. i.e. animal tolerability and human PK studies and we would have had to revise our guidance of “1H CY2022” for trial commencement. With Peptron, is all packaged up and in a regulatory friendly manner (given they are running clinical trials in Parkinson’s disease – in Korea). I think it’s a win/win for Invex and shareholders. Orphan drug markets are, in every respect, better than non-orphan markets. Take a cancer drug developer in colorectal cancer. There are (not kidding) >20 approved agents / combinations for a medical oncologist to consider -0 can you imagine taking market share from these entrenched agents?. Take a look below for current guidelines (NCCN).
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Then take a look at ours: NO drug approved. Acetazolomide is not even approved for IIH in any market. Our market is $1.6 Billion of addressable market, growing 3.4% per annum with no drugs approved – and it will be chronically administered – treating clinician – neurologist or neuro ophthalmologist. Indeed Professor Sinclair (Exec Director) actually wrote the US and European IIH treatment guidelines………..
11. Many other ASX listed companies publish the list of members on their Scientific Advisory Board. Can Invex release a list of members on their scientific advisory board?Our clinicians prefer to not be publicly disclosed. There is no Listing Rule that requires disclosure be made. Also, we use different experts for different purposes as required. So it’s not necessarily a static SAB, perhaps more ad hoc.
12. Are management/directors now able to purchase shares on market considering the collaboration deal is over. If yes, will we be seeing purchasing to instill further confidence to shareholders of how undervalued this company is?I won’t speak on the motives of my fellow directors; however, noting the comment below it is not appropriate to acquire shares with a pending strategy as conveyed to the market in the investor deck for Peptron (and shown below). To put any doubt to rest, I bought most of my shares at $1.30, so I have every motivation to grow value for shareholders.
13. What are the next steps for IXC at the moment. What are they focusing on the most at this current stage and whose working in what areas?Q42021 – clinical and regulatory strategy articulated based on FDA feedback and EU feedback received and considered. 1H CY2022 Phase 3 trial starts.
Appreciate your time Tom and looking forward to hearing your answers to the above.Pleasure.
Thanks
Kind regards,
