"Today is a milestone day for Paradigm" Paul Rennie 10/10/2023
Possibly one of the better Question and Answer sessions we have seen for some time...
For those that are newer to us, PAR used to have the briefest of Q&A...nowadays they are longer and cover more material and in my view they have a fresh view on trying to be more open with their answers.This will only put them in higher stead. As I always think...if a company has nothing to hide and are confident that their product works and they are working as hard as they can to have a genuine long term profile with as much raw potential as they do, why would you EVER be scared of questions?
There should be NO question we can't throw at them that they can't give some sort of answer.
Having said that there are some they just can't answer, some that might be sensitive, some that might have commercial ramifications, I get and understand that.I wouldn't want any of MY competition knowing anything that could be used against me or to put them ahead of us. Not on.
Look, PR and staff are so busy! They have all the Reg stuff...they have parties they are potentially formulating deals with...they have consultants, they have the day to day staff work...two huge programs and a stack of data to contend with. Conferences all over the place...presentations too. It's still nice of PR to publically welcome questions. This is always a good sign.
The below is my interpretation of the Q&A session. It's good to take the time and read what Donna and Paul covered.
Thanks to @Kiwinvestor and a couple of others for the suggestion, I wasn't really going to write this one up, but glad I did, was worthwhile.
Usual caveats - Do not rely/depend on any of the below.
DYOR
QUESTION 1
Why was the original 2 x 2 dose not included in the original study design?
Donna - We had a lot of experience with the 2 x 2 dosing when we went to the FDA. There was some discussion around whether we were working with the lowest effective dose and whether we were willing to add some lower doses into the study. Not including the 2 x 2 dosing was due to negotiations with the FDA around the findings of a single non clinical program involving some rats and adrenal effects. For that reason we had to reduce the dose while we were conducting studies to resolve those questions around that single rat study.
Now those studies have been conducted and we have resolved that the additional information that the FDA needed to see is now available showing that those rat findings were not relevant in any way. This opens the door for us to reintroduce the 2 x 2 dosing back into our program.
QUESTION 2
Given the FDA did not sanction the 2 x 2 dose originally, in your opinion does it allow PAR to use this dose in the 002 Stage 2 and 003 confirmatory study or will PAR need to conduct a separate stage 1 dosing arm for this dose before proceeding?
Donna - Well now that the optimal dose has been identified for proceeding, a further dosing arm will not be needed in our studies so going forward. Our task will be to introduce this dose into our Phase 3 program and we will come back to the market when we have worked out the details of exactly how that will be done.
QUESTION 3
What impact does the company believe that this will have on the current timelines of the P3 program?
Donna - As you are aware of the initially planned dose selection procedure was scheduled for Q1 of 2024. By requesting this earlier interim analysis from the DMC we have sufficient information to make that decision around dosing now, and that is further supported by the findings that we've seen with 008 with the once weekly -v- the twice weekly performance. So therefore we will be able to move forward with introducing the twice weekly dose into our Phase 3 program now.
We do not believe that we this will have significant impact on the timelines, however we will come back to the market when we've worked out the further details of the next step for this program which is the clinical activity for Phase 3 involving the twice weekly dose.
QUESTION 4
What are the next steps and indicative timeline for the company's TGA Provisional Approval Application?
Paul - These are indicative timelines and are not be taken as confirmed at this time. From talking to the head of our Regulatory department, Dr Karla Knower, we need to firstly provide a notice to the TGA of our intention to seek provisional approval by way of a determination statement to the TGA.
We think that the determination statement could take between one to two months now that we have the durability of effect data. We think if all goes well before Christmas we hope to have that submission made to the TGA. The TGA then have 30 working days to respond to our determination submission. Assuming that they now have all the answers to the questions that we have discussed with them previously. particular the durability effect, the TGA then will ask us to proceed with a dossier providing all of the background info, the safety data, the pre-clinical, the toxicology, all the previous clinical data, cmc sections etc.
If they agree and advise us to submit the dossier, it will take us somewhere in the region of around 6 months to prepare the dossier and then once the dossier is submitted the TGA has a maximum of 12 months to respond to that dossier. So we would hope that in terms of indicative timing a determination submission to the TGA before Christmas 2023.
Assuming we get feedback from the TGA before December 2023 or Jan 2024 we should then have our full dossier submitted to the TGA by June/July 2024 and assuming the full 12 months from the TGA then that would see provisional approval being awarded being to the company in June/July 2025, 12 months from the submission of the dossier. These are indicative times. We will work on those times and narrow them where we can and we will advise the market accordingly once we have a very clear timeline for TGA provisional approval.
Now bear in mind that we do know that there are some other jurisdictions that also have a similar provisional approval process and we are investigating simultaneous applications to those additional jurisdictions so where we can get provisional approval we will be making every effort to get provisional approval in other jurisdictions. We will outline that in our communication to shareholders, it may well extend beyond the Australian Market.
QUESTION 5
What are the negative effects of the once weekly results for the P3 program in terms of time and program costs. Do the results allow a decision to drop further work and resources applied to the once weekly study monitoring?
Donna - The second half of the question is YES. The information that we have recently acquired both from 002 and 008 allow us to make a decision about the appropriate and optimal dose to move forward.
In terms of the negative effects of the 1.5 mg dose, it's not a negative effect but not seeing the performance that we see with the 2 mg/kg twice weekly dose. As we continue to work through the data further, I think we will determine whether or not any dose from stage 1 will move forward but that will have to be based on seeing performance that is as good as what we have seen with the twice weekly dosing in 008 and well as our other programs.
Certainly at this point we feel confident making a decision moving forward with 2mg/kg twice weekly dosing being introduced into our P3 program and as we make decisions about how to do that we can come back to the market about any other further information about the other doses study.
QUESTION 6
Based on your last question/answer if you got TGA provisional approval in mid 2025 would you require a domestic partner or would you proceed to domestic sales on your own?
Paul - We are currently preparing plans to look at the possibility for PAR to building out it's own sales and marketing organisation to manage the drug in Australia. Equally we are interested in discussing the marketing and distribution rights with any commercial partner. Just to remind investors the Aus market is not insignificant. We know that there is roughly 3 million OA sufferers in Australia who are largely dissatisfied with current medications.
(Arthritis Australia)
If you think about the price point of $2500 by a percentage of those 3 million sufferers it turns out to be quite a large number and so therefore it's a very attractive opportunity for a partner to do the sales and distribution for Paradigm. But equally, we're not going to wait for a commercial transaction when we have the opportunity to market ourselves because the market in Australia is much more manageable than say a market like United States where the reach and the number of primary care physicians is best severed by a big pharma company.
QUESTION 7
Can you please enlighten us on some of the conversations regarding partnerships for OA and MPS?
Paul - So let's start with MPS. I should also let investors know that given the likelihood, and again we don't know at this stage because it's double blinded placebo control, but the likely positive outcome for MPS VI in Brazil will also be a adequately sized well-controlled clinical study phase 2 study which meets the criteria for provisional approval in Australia so we will be concurrently trying to get provisional approval for PPS for treating MPS VI patients in Australia and that most certainly can be managed by Paradigm because the number of sufferers in Australia is much smaller market than the osteoarthritis market.
But in terms of discussions, in relation to MPS, we have been targeting companies in three geographic hotspots. So it's ultra rare but in some countries there are higher proportions of these subjects relative to the rest of the world, areas such as Latin America particularly Brazil, which is why we did that phase 2 study there, also the Middle East and North Africa is a considerable hotspot and also Turkey and Germany is the third area.
So we have a commercial partner in Europe who is looking to transact with the company on the asset for Turkey/Europe. We also put out non confidential information to companies involved in the rare disease market in the middle east and we have a short list of those companies who have expressed interest in participating in our business development process which is to have a non-confidential information received, they then sign an nondisclosure that then goes into the data room. They then develop a binding offer and submit that to the company. So that process is well underway in the Middle East and we do have a number of companies that we've met through by a partner and meetings that have requested more information from us so we have sent them a copy of under confidentiality agreement the manuscript for the MPS I study and when we finished the MPS VI [study] those discussions will really ramp up and they are aware of this Phase 2 data coming out in December.
In relation to OA, I mean it's a Global opportunity. We have for sometime explained to shareholders that our focus is on the regional deal. China remains a very key focus for us. It is a rapidly progressing market, the healthcare system does allow for reimbursement of some medications so it is a market heavily dominated at the moment by long-acting hyaluronic acid medication which we know 'long acting' means between 3 and 6 months so our new data is going to be very very well received by those companies who are looking for an extended duration and also disease-modifying or structural improvements of the joint also keenly sought after in the Chinese market.
So we have a number of companies, we have a very good partner in China we are working with we have gone through that same process of where we have sent out non confidential information to these companies, we have asked them if they're interested in participating in the process and if they're interested in participating they sign a CDA and we let them into our data room so that they can confirm the data or ask any questions from the company as they see fit.
So we are well progressed we have had renewed interest from Latin America. We did have a low ball offer which the company didn't proceed with but investors would have been highly critical if we would've accepted that offer. But that same company has expressed interest in OA and we have explained that we won't accept a low ball offer.We are working as hard as we can on a commercial transaction. We feel a regional deal is the way to fill our funding to execute our P3.
If we see a deal in China the quantum will be sufficient large enough to see us funded through the P3 program. China is a key market. Today's data is a blessing for us and we believe we have the necessary assets to go to those companies and say that we have the answer for you and we hope something will precipitate from those discussions in the near future.
QUESTION 8
No mention of DMOAD, is it still on the table?
Donna - Yes it certainly is on the table (Mozz Note: Good to hear Donna have half a giggle here as she was bemused), we are eager to complete the review of the quantitative MRI data and present this to you in the coming days/week. These data will be much more relevant to the DMOAD discussions.We have been working with a team in terms of the DMOAD biomarker aspects of DMOAD so we can have that regulatory discussion.
Paul - In terms of DMOAD and the announcement around those data, they are clearly important for discussions in China.Our goal is to get the product on the market, if we need to go for pain and function label initially then that will be our objective and we can do P4 studies after we become revenue generating to fund DMOAD studies. We are not planning on doing pain and function and delay registration waiting for a DM label,
QUESTION 9
What are the immediate capital requirements to continue the P3 program?
Paul - Next few quarters will be relatively light [in terms of spending] as we aren't recruiting subjects for Stage 1 and we are winding down our activities as that's been concluded and as we work out how to get that 2x2 into the P3 Program. So our capital requirements will reduce in the upcoming months.
But suffice to say it is a question we get asked regularly, do we have enough cash in the bank to see through out P3. I think the answer is that we don't want to go into partnering discussions with a balance sheet that looks like a commercial company could wait us out....We want to move forward with non dilutive funding by way of a transaction with a regional deal with Latin America or China or both and we hope that combo of transactions is sufficient to fund us well into the P3 trials, certainly to the discussions that we are having with the Pharma companies in the US because they are well aware of our quarterly we are on their watchlist, they do track our cash so we want to be well prepared for those discussions and we don't want to be doing a transaction purely because we are running out of cash.
WRAP UP
Paul - We want every investor to feel listened to and we want every investor to feel they can ask questions to the company.
Today is a milestone day for Paradigm. The data clearly shows 2mg/kg twice weekly in moderate to severe OA now really has changed in terms of the available communications going forward.
The data is very compelling.
These data are critical for the OA market.
We feel very privileged to be working with Bene's product.
(20min delay)
