Addex Therapeutics Limited (NASDAQ:ADXN) Q4 2021 Earnings Conference Call March 10, 2022 10:00 AM ET

Company Participants

Tim Dyer - CEO
Roger Mills - Chief Medical Officer
Robert Lutjens - Head of Discovery Biology

Conference Call Participants

Raghuram Selvaraju - HC Wainwright
Bob Pooler - valuationLAB AG
Charles Duncan - Cantor Fitzgerald

Tim Dyer

Hello, everyone. I would like to thank you all for joining our 2020 full year financial results conference call. I am here with Roger Mills, our Chief Medical Officer, and Robert Lutjens, our Head of Discovery Biology. I draw your attention to the press release and the financial statements issued earlier today which are available on our website.

I also draw your attention to our disclaimer. We will be making certain forward-looking statements that are based on the knowledge we have today.

I will start this conference call by giving a quick overview of our recent achievements, before handing over to Roger and Robert, who will review our clinical and preclinical pipeline. I will then review our 2021 full year financial results. Following that, we will open the call for Q&A.

During 2021, we have continued to make excellent progress towards achieving our strategic objectives, and now have three clinical programs dosing patients, which is a significant achievement. In September, we started dosing patients in our Phase 2a clinical trial of Dipraglurant for blepharospasm, a type of dystonia characterized by involuntary contractions or spasms of the eyelid muscles resulting in substained eyelid closures.

During 2021, we also continued to advance our pivotal program with Dipraglurant in Dyskinesia associated with Parkinson's Disease. Our partner Janssen continued to make significant progress in executing their global Phase 2 study in epilepsy patients.

Due to the continued disruption caused by the global Coronavirus pandemic, and in particular its impact on clinical research, we have revised our guidance for reporting data from our Dipraglurant clinical studies. We now expect to report data from our blepharospasm study in Q2 of this year instead of the end of Q1, a six weeks delay. We also expect our PD-LID study to report data in H1 of 2023 instead of the end of Q4 2022, a three to six months today.

While these delays are disappointing, we are focused on maintaining the integrity and quality of the study. We continue to expect our partner, Janssen to report data from their epilepsy study in Q3 of 2022. We're also very excited by our preclinical pipeline, which has made spectacular progress with multiple clinical candidates rapidly advancing towards IND-enabling studies.

In 2021, we announced the extension of our strategic collaboration on GABAB PAM with Indivior and their commitment of an additional $4 million of research funding to advance drug candidates through to the start of IND-enabling studies.

We continue to make progress with an independent GABAB PAM program for Charcot Marie Tooth Type 1A neuropathy, and entered into a collaboration with Charcot Marie Tooth Association in the United States. This collaboration is to evaluate selective drug candidates in preclinical models for Charcot Marie Tooth 1A neuropathy. We are on track to deliver multiple GABAB PAM drug candidates ready to IND enabling studies.

We continue to advance our other preclinical programs, in particular our mGlu7 Negative Allosteric Modulator program for post-traumatic stress disorder which is progressing through clinical candidate selection funded by the Eurostars/Innosuisse grant program. We also expect our mGluR2 negative allosteric modulator program for mild neurocognitive disorders associated with Alzheimer’s and Parkinson's Disease depression to enter clinical candidate selection Phase in the second half of this year.

On the financing side, the extension of our collaboration with the Indivior and the additional $4 million of funding as well as the $10 million financing from Armistice Capital contributed to our completing the year with a cash position of CHF20.5 million, or the equivalent of $22.5 million

So now I would like to hand over to Roger. Roger, the floor is yours.

Roger Mills

Thanks, Tim. Good morning, good afternoon, everybody. Let’s start by speaking about our Dipraglurant program for dyskinesia associated with Parkinson's Disease. This indication represents a multi-billion dollar market opportunity. We announced the initiation of our 301 Pivotal Phase 2b/3 Study during the second quarter of 2021.

The study is intended to enroll 140 Parkinson's patients who are experiencing moderate to severe dyskinesia and includes around 50 sites based in the United States. Let me remind you of the study design. This is a one to one randomized, placebo-controlled study of 100 milligrams Dipraglurant taken three times daily, in conjunction with the patient's levodopa dose. Duration of the study is 12 weeks.

In parallel, we also initiated our 302 study. Patients who complete the 12 weeks of 301 study are eligible to rollover into the 302 study, which is a 12 month open label safety study where all patients receive Dipraglurant 100 milligrams three times daily, irrespective of the study arm they were randomized to in the earlier 301 study. 302 study provides 6 and 12 month treatment safety data to meet the regulatory requirements for an NDA submission. The primary endpoint of the 301 study is a change from baseline in the Unified Dyskinesia Rating Scale or UDysRS. This scale was developed specifically to assess dyskinesia symptoms in Parkinson's patients. It's a scale recommended by Movement Disorder Society, and has regulatory precedent with the FDA approval of Gocovri, to PD world.

Secondary endpoints include the Clinician’s Global Impression Severity, and standardized patients diary based assessments of on time, without troublesome dyskinesia, and off time. Importantly, we have included a number of measures to manage placebo response. These include the use of the UDysRS scale, which is less prone to perceive the responsibility scales for dyskinesia. The use of the brief psychosocial therapy adapted for dyskinesia to be used in a screening period of study, and the requirement that patients have moderate to severe symptoms both at the screening visit, as well as at the study baseline visit.

We're also using expert reviews of the ratings to ensure quality. In addition the 12 week durational study will be expected to mitigate placebo response. For background, in a previous Phase 2a study, Dipraglurant met its primary endpoint by being generally well-tolerated and showing no clinically significant safety issues.

In addition, at day 1, and day 14 Dipraglurant shows statistically significant benefit on the PD-LID clinical symptoms, as measured using the Modified Abnormal Involuntary Movement Scale or M AIMS. However, statistical significance was not achieved at day 28 due in part to an increasing placebo response. The Registrational 301 study has an improved design cooperating multiple methods to mitigate placebo response. We expect this study to read out top line data in the first half of 2023.

In addition, we've initiated our second Dipraglurant clinical program. This is for the treatment of blepharospasm. Blepharospasm or BSP is a type of dystonia, which affects the muscles of the eyelids and can lead to sustained eyelid closure, resulting in substantial visual disturbance and functional blindness and can involve other cranial or facial muscles in over half the patients. There are at least 50,000 BSP patients in the United States. About 2,000 new cases occurring every year.

The mainstay of treatment is by injecting Botulinum Toxin and this is the only treatment approved by FDA for BSP. With waning benefit or in more severe cases, patients may undergo surgical interventions, often with limited benefit or resulting in poor cosmetic outcomes. There was a clear need for an improved therapy with an oral therapeutic. Study 203 is an exploratory placebo-controlled trial involving about 15 patients with moderate to severe blepharospasm randomized equally to either 50 milligrams or 100 milligrams of Dipraglurant or matching placebo. Patients receive three doses in total over a two day period.

Following baseline assessments, the first dose is administered in the clinic, and the severity of the blepharospasm is assessed during dosing. Patients take a further dose at home, returning for pre and post assessments in the clinic the following day. The outcome measures in this study include Computerized Motor Objective Rater, Or CMOR as well as standard efficacy scales of blepharospasm. We expect to report data from the study for blepharospasm in Q2 of this year.

And now to ADX71149, for epilepsy, which is partnered with Janssen Pharmaceuticals, a J&J company. In June, we announced that Janssen had started enrolling into Phase 2 Epilepsy Study evaluating 149 in treating patients with focal onset seizures. 149 is a selective metabotropic glutamate type 2 or mGluR2 receptor positive allosteric modulator.

This is a Phase 2 double blind placebo-controlled proof-of-concept study that’s enrolling patients with focal onset seizures, who have suboptimal response to treatment with levetiracetam or Keppra. Patients will establish a 28 day seizure count over 56 day baseline period, prior to randomization, when they will be randomized to receive either 149 at 50 milligrams BID, or matching placebo.

The primary endpoint is the time taken to return to their monthly baseline seizure count. So they will have two periods, period one being the four week acute efficacy phase and period two is an eight weeks maintenance efficacy phase. Period two will include patients who did not return to their baseline monthly seizure rate during the first period of study, and they will continue on their randomized drug or placebo. Data from this study is expected in Q3 2022. This study illustrates a continued commitment to our long term collaboration partner, Janssen Pharmaceuticals, to this program and to pioneering novel ways to help epilepsy patients.

As a reminder, Janssen is covering all the costs of development, and we have significant pre-launch milestones of EUR109 million and double digit royalties on net sales.

And now I like to hand over to Robert, who will provide an update on some of our preclinical programs.

Robert Lutjens

Thanks, Roger. Good morning, and good afternoon to everyone. We have made significant progress over the year and today I will highlight three programs starting with our GABAB positive allosteric modulator program. As a reminder, this program is partnered with Indivior who is funding the research at Addex and their primary interest is substance use disorder.

GABAB receptor activation is a well-validated approach, benefiting from the wealth of scientific and clinical data generated with baclofen, the FDA approved GABAB agonist. The aim of this program is to use the differentiated pharmacology of allosteric modulation to discover novel drug candidates with the efficacy of baclofen without its side effects. In other words, a better baclofen. We're well on our way to meeting this objective with multiple novel drug candidates rapidly advancing through clinical candidate selection phase.

We announced in 2021, the extension of our research collaboration with an additional $4 million of funding committed by Indivior to advance development of the drug candidates discovered by Addex. We are currently profiling several candidates in non-GLP studies, with the aim to nominate drug candidates for IND-enabling studies this year. In addition, candidates are being profiled in alcohol use disorder models in order to identify one candidate that Indivior will progress into the clinic for substance use.

In parallel, we are progressing multiple different sets of drug candidates for our independent Charcot Marie 1A program. We announced in September 2021, a collaboration with the American Charcot Marie Association. This collaboration will provide us access to significant resources and expertise in the field of CMT 1A. As mentioned earlier, there is strong data supporting the GABAB receptor activation mechanism coming from clinical studies that reported the beneficial effects of baclofen in patients with CMT 1A.

In addition, we have robust preclinical data with our own drug candidates in highly translational models of CMT 1A. In these studies, we have demonstrated a robust effect both on biomarkers and behavioral measures, suggesting we can slow and possibly stop the progression of the disease with this approach. Our candidates are completing studies in CMT 1A models and other non-GLP preparatory studies, as we get ready to select the candidate to enter IND-enabling studies by the end of 2022.

The second program I want to highlight today is the mGlu7 negative allosteric modulator program for post-traumatic stress disorder, or PTSD. PTSD is a psychiatric disorder that may occur in people who have experienced or witnessed a traumatic event such as a serious accident, natural disaster or war. Current treatments are mostly relying on behavioral therapy, as most pharmacological treatments show poor or insufficient benefit.

We're developing mGlu7 negative allosteric modulators as a novel approach to addressing fear memory consolidation and retrieval. We have generated robust preclinical data in multiple in vivo models of the disease. The program is supported by Eurostars/Innosuisse grant of EUR4.85 million, which is financing consortium led by us. We are advancing drug candidates through clinical candidate selection and expect to enter IND-enabling studies in H2 2022.

And finally, a few words on our mGlu2 negative allosteric modulator program for mild neurocognitive disorders or MCI. MCI is the stage between expected cognitive decline of normal aging and the more serious decline of dementia. Besides being potentially the early sign of Alzheimer's Disease, MCI is also often experienced by patients suffering from depression. Developing mGlu2 NAM offers the exciting opportunity to address cognitive impairment, while also providing an antidepressant effect. Both these effects have been demonstrated in relevant preclinical models with our mGlu2 NAM candidate compounds.

We are now progressing through the final stages of lead optimization and expect to enter clinical candidate selection phase with multiple compounds in the second half of the year. In summary, we have made spectacular progress in our preclinical portfolio, with multiple drug candidates rapidly advancing towards IND-enabling studies. The renewed commitment of our partner Indivior, and additional funding is a further validation of the quality and productivity of Addex’s drug discovery platform, and the significant achievements made in our GABAB PAM program.

This concludes my prepared remarks. And I'll hand back to Tim.

Tim Dyer

Thanks, Robert. I'll now switch to an overview of the financials. Starting with the income statement, we recognized $3.2 million in revenue and income in 2021, compared to $2.9 million in 2020. The primary source of revenue is research funding from our collaboration with Indivior, which we expect to reduce in 2022 as drug candidates move to late stage clinical candidate selection and our partner takes more takes over more of the operational execution of the development.

In terms of expenses, R&D expenses of $12.8 million are primarily related to research and development activities on our Dipraglurant and GABAB PAM programs and to a lesser extent on our mGlu7 NAM and mGlu2 negative allosteric modulator program. R&D expenses have increased by $2.5 million compared to 2020, primarily due to the increased activities, in our Dipraglurant on PD-LID program and blepharospasm programs as they start to actively recruit patients.

G&A expenses were $5.8 million in 2021 compared to $5.7 million in 2020. This modest increase is due to higher insurance premiums as we strengthen our insurance coverage following the company's listing on the NASDAQ stock market.

Finance results of $0.2 million in 2021 relates primarily to exchange rate gains on U.S. dollar cash deposits due to the strengthening of the US dollar.

Now to the balance sheet, our assets primary held in cash and we completed the year with CHF20.5 million, cash held in Swiss francs and US dollars. Our current assets just below $1.5 million in 2021 relate primarily to research funding receivable from our collaboration partner, Indivior, prepayments are related to insurance and retirement benefits. Current liability of $4.1 million are consistent with prior years and relate primarily to R&D payables and accruals. Noncurrent liabilities of $1.5 million relate to retirement benefit obligations calculated under International Financial Reporting Standards.

Now to the cash flow statement, we started the year with $18.7 million, raised net proceeds of $16 million from offerings, executed in 2021, consumed $6.7 million in operations and received $2 million in research funding from Indivior. We have a paper profit of $0.1 million in ForEx when US dollar cash balances are converted to Swiss francs, for financial reporting purposes -- for the yearend financial reporting purposes, resulting in $20.5 million at the end of the year. So in summary, Addex has made notable clinical development progress in 2021. We have three clinical programs that are actively treating patients in difficult to treat indications where we are first in class.

We look forward to updating you on all these studies, when they begin to read out, the first of which is blepharospasm, which we'll read out next quarter. The company is built based on a leading technology platform, which has delivered an exciting portfolio of enhanced discovery programs and partnerships. We have an experienced team of drug developers in the company partnership with industry and the support of top tier investors, with a rich news flow coming for the rest of 2022 and beyond, in addition to the three upcoming clinical data readouts, we have four preclinical programs that are expected to enter IND-enabling studies in the coming 12 months. Taken together, I believe Addex has a very promising outlook, and perhaps undervalued equity story. We look forward to providing you with updates on our progress soon. This concludes the presentation and we will now open the call questions.

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Your first question comes from the line of Ram Selvaraju from HC Wainwright. Please go ahead. Your line is open.

Unidentified Analyst

Hello for the team. This is Mansa [ph] representing Ram Selvaraju at HC Wainwright. Thanks for the update. Very comprehensive. You effectively answered all of our questions. Just one is the enrollment for the PD-LID Dipraglurant study hastening as the Omicron wave recedes?

Tim Dyer

Yeah, maybe Roger, you'd like to take this one?

Roger Mills

Yeah, I mean, actually quite clearly, as with so many programs, the COVID has had impacts and obviously Omicron really sort of hit everybody at the end of last year. But we've actually seen some good momentum across -- and actually activity across a broad variety of sites, which is, which is really encouraging. So we are seeing a sort of beginning of that sort of post-COVID surge. So fingers crossed, we keep working and we'll be moving forward.

Unidentified Analyst

All right, excellent. I look forward to a catalyst rich year. Thanks for the update.

Operator

Thank you. Your next question also comes from the line of Ram Selvaraju from HC Wainwright. Please go ahead. Your line is open.

Raghuram Selvaraju

Hi, thanks very much for taking our follow-up questions as well. I wanted to ask about the overall strategic positioning for Dipraglurant in terms of, the different indications being pursued in the context of PD-LID as well as blepharospasm. And how you're thinking about that, from a partnering perspective, should the blepharospasm study data prove to be positive? And if you can also give us a sense of what you would consider to be a slam dunk outcome versus a merely positive outcome from the blepharospasm clinical readout? Thank you.

Tim Dyer

That's an interesting question. Ram. Thank you very much. Roger, do you want to have a first stab at this one?

Roger Mills

Okay, thanks. So first of all, in terms of pre-positioning, we need to see the data from the blepharospasm study to really start to think about the further elements of how we exploit the compound. In terms of our result, this is an exploratory study. So this is really the first time we have put the drug into this indication, these patients and such. It's you know, what I'm really what I'd be really, really excited to see is, is obviously a strong signal. If it's a slam dunk, then I would be even more pleased.

It's a relatively small study, 15 patients. We've got two active doses versus placebo. So a number of factors in terms of looking at the data from this study. That will then inform the program as we then decide how to sort of prosecute the next phase of the development, which obviously would be a much larger Phase 2 proof-of-concept study. And the data from this first study, this exploratory study will obviously inform such as dosing, get a real feel for the clinical outcomes in the study how the drug is manifest on those. And then we'll build that into the program moving forward.

Raghuram Selvaraju

As a follow up to that, I think, Tim, you know, what I would also be interested in learning more about is, how you folks are thinking about the possibility of indication splitting for Dipraglurant? And if that's really something that you consider feasible, or if when you think about the prospect of partnering, you're looking at it more as a package deal as it were.

Tim Dyer

Yeah, okay. So well, the first thing is that we believe, based on the data we've generated, based on the MOA, based on data generated with other mGlu5 negative allosteric modulators in PD-LID, that there's a very strong rationale for developing an immediate release formulation of Dipraglurant for PD-LID. Now, while we are developing, we are currently running a study in blepharospasm, using the immediate release formulation. We are also developing an extended release formulation of Dipraglurant and we believe that, that will probably be the formulation that we would pursue in other indications, including blepharospasm.

So we're not -- we will from a partnering point of view, we don't believe it's likely that anybody is going to step in and want to buy that Dipraglurant PD-LID, ahead of the 301 readouts. Now if somebody on the back of the blepharospasm data, wanted to partner Dipraglurant, and for blepharospasm, we would be partnering an extended release formulation of Dipraglurant.

However, I think we will cross that bridge when it comes. But we're certainly not looking to -- I don't think it's feasible to split indications with the same formulation of the same pharmaceutical entity. It makes it extremely complicated. So the only split we would do, if it came to that would be around different formulations.

Raghuram Selvaraju

Thank you. Very helpful. And then just two other very quick ones. I was wondering if you had a sense of timing with regard to Indivior’s decision making process in terms of extending the collaboration and determining how much additional funding would be provided to add under the scope of that arrangement. And also, if you could speak a little bit about prospects for non-dilutive funding in the context of the PTSD indication which our understanding is appears to be of significant interest to multiple governmental entities, including, for example, the Department of Defense in the United States.

Tim Dyer

Yes, so sorry, the first question you had. Can you just repeat that?

Raghuram Selvaraju

Yes, it was with respect to the Indivior collaboration, what do you the timing for Indivior to reach a decision regarding what's going to happen to the collaboration and its scope and the extent of the funding that would be provided to Addex post mid-2022?

Tim Dyer

Yeah. So as you say -- as you point out, we extended the collaboration last year, with an additional $4 million of commitment from Indivior through till the end of July 2022. At the moment, we are delivering on our part of the collaboration the program is reaching advanced stages of clinical candidate selection. And so there are a number of molecules which are reaching a stage where Indivior is starting to take more and more control over the operational implementation of the development.

So we will be having a discussion with Indivior as to whether it's necessary to extend the research collaboration beyond July 2022. But at the moment, the program is doing extremely well. And it's not clear whether we would need -- whether Addex would need to extend the research collaboration or not. But as soon as any decisions in that area are made, we will be updating, dating the markets.

Now regarding the mGluR7, negative allosteric modulator program, as you know, we were leading a consortium that managed to secure a EUR4.85 million grant from the Eurostars. We are currently executing on that. We have managed to identify a clinical candidate or lead a lead that's entered clinical candidate selection phase from that program. So we are currently profiling that molecule. And we are also in parallel, driving forward multiple theories through lately the optimization, the collaboration and the consortium is working extremely efficiently, extremely well.

We will start to pursue other funding sources. As you rightly point out, there are a number of government organizations which are offering support to run clinical studies. And we have started to look into those, in addition to in addition to of course, discussing with pharma partners as well.

Raghuram Selvaraju

Thank you.

Operator

Thank you. Your next question comes from the line of Bob Pooler from valuationLAB. Please go ahead. Your line is open. Thank you.

Bob Pooler

Thank you. Hello, gentlemen. A few questions from my side. Just on the cash, could you provide some guidance on your cash burn? And how’s your cash reach?

Tim Dyer

Yeah, so we've reported having CHF20.5 million at the end of the year. Last year, we were burning about CHF1.5 million a month on average. And so we're basically guiding cash through into the first half of 2023.

Bob Pooler

First half 2023. Okay, great. Just on the grant on blepharospasm, there any implication if you have a strong lead out there for other dystonias, maybe even for the PD-LID trial? And then also what is the market potential for this indication?

Tim Dyer

So maybe, Robert, do you want to take the first bit of that around all the preclinical data for the dystonia?

Robert Lutjens

Sure, yeah. Hi, Bob. Yeah, I think this, talking mGlu5, has been tested in several models of different dystonias. And so demonstrated, again at the behavioral level, that we were able to reduce or having an anti-dystonic effect with mGlu5 chronic treatment. We've also been exploring the mechanism at the cellular level, looking at electrophysiology to measure the effect. And we've shown basically, that very specific phenomenon is being restored when you add Dipraglurant, which is an indication that possibly this is a common mechanism of all sorts of different forms of dystonias. And therefore could be helpful. So showing or providing some support for Dipraglurant being effective in several forms of dystonia. And then, in the PD-LID study, there were seven patients who had dystonia and three of them were on placebo and four were on Dipraglurant. And we observed there some effect, obviously the size of the number of patients was not sufficient to actually being able to do some statistical analysis. But nevertheless, this was a very positive signal that we observed.

Tim Dyer

So with regard to the market, we believe there's about 50,000 patients in the United States suffering from blepharospasm. And there's about 2,000 new blepharospasm patients being identified annually. I mean, maybe Roger, you'd like to talk through how we took the decision to move into blepharospasm as opposed to other forms of dystonia, because vocal cervical dystonia is clearly a very interesting area as well. But we decided on blepharospasm and I'll leave Roger to explain how we took that decision.

Roger Mills

Thanks, Tim. So dystonias cover a broad sort of broad constellation of different manifestations. Dystonia is almost like an umbrella indication with lots of sub indications beneath it. The rationale around blepharospasm was that we can actually get a more homogenous population of patients. Obviously, with a more heterogeneous group of patients, it gets harder in a small study to be able to be to determine the response across those patients, where blepharospasm, we were able to do that.

It's very impactful condition to patients. You get functional blindness. It's very disfiguring, it's very -- pretty impactful with really what is a limited treatment with recurrent botulinum toxin. The other key factor that really figured into the decision to look at, and to see blepharospasm is that we are able using the CNS [ph] to be able to get an objective readout. One of the great challenges in doing CNS studies is always the subjectivity of endpoints.

So being able to utilize an objective assessment is particularly attractive. So we have a disease, which is impactful. We have the ability to have more homogenous group of patients. We have the opportunity to utilize an objective criteria. So it really was a very, very much a sort of sweet spot within sort of broad constellation of dystonias.

Bob Pooler

Okay, then maybe moving on to GABAB PAM program there. You are indicating then when you expect them maybe to start with a lead candidate in clinical trials?

Tim Dyer

Well, we're currently scaling up a number of compounds, running them through secondary in vivo assays. We’re looking very closely at substance use disorder. And we're looking forward to Indivior taking a decision on which compound they want to then move into the IND-enabling studies. We're expecting that to happen around the end of the year, potentially early in 2023. And then of course, that's going to take a good three to nine months, depending on how long they decide they want to run those regulatory IND-enabling studies. And then moving into Phase 1. So I think moving into Phase 1 is best guess is late in ‘23, at the earliest.

Bob Pooler

How's the CMT program proceeding?

Roger Mills

Yeah, so I can take that Tim. So very well, again, we've identified several compounds that we're currently profiling in different preclinical studies, including in CMT 1A model. And so we expect to complete those by the by the end of Q2 this year, and in parallel, we're running additional studies. So that we are gearing up the preparation to enter IND-enabling studies by the end of this year.

Bob Pooler

Then just moving on ADX71149 epilepsy, just with the readout of the results expected in Q3 2022. Will positive results trigger a milestone payment, and I believe that Roger said there were $109 million pre-launch milestones.

Tim Dyer

No, the results were not read out, will not trigger a milestone.

Bob Pooler

Okay.

Tim Dyer

The trial is being run by -- the last milestone we received was when the program entered into a Phase 2 proof-of-concept study. And we were not able `to guide any more detail. But they are all development or I would say pre-sales milestones. And then there is the double digit royalties on first net sale. The study is well, and it's on track.

Bob Pooler

That's great, also, we're considering the pandemic. Do you know if there's any potential for combination of Kaprun ADX 71149? That would substantially extend the patent life?

Tim Dyer

Well, Janssen have taken a patent on the mechanism of the combination. So there is a new patent combining the molecule with SB 2A antagonists. So there is a new patent. But we can't comment. I mean, Janssen -- we're very passive partner here. Janssen is leading the development. We're not privy to any strategies around co-formulation of the two compounds.

Bob Pooler

Okay, then just my final question, as you also mentioned in the presentation, you’re making good progress with your preclinical candidates. What new value inflection points do you expect to reach this year? And any potential partner agreements in the offing?

Tim Dyer

Yeah, so I mean, we're making good progress on the clinical portfolio. As we pointed out, you know, we've got Dipraglurant in two Phase 2 or Phase 2b studies, reporting out data. We're not expecting partners -- partnerships on those programs until there's more data. And Janssen of course, that clinical program is already partnered with Janssen. We are making a lot of progress in the GABAB, and the part of the GABAB, which is not partnered with Indivior.

So there's certainly some opportunities. There we've got some very well-characterized compounds. It's a highly validated mechanism of action, due to all the work that's been done with baclofen, which is the allosteric agonist, which is now a generic. And we've got the mGlu7, and the mGlu2, which also are now programs which have delivered some well characterized drug candidates, which are marching through clinical candidate selection phase.

So there's really something for pharma to look at. We are starting to get some traction from potential partners who are interested in looking at some of these programs. So but as you know, when you start a discussion, it's very difficult to predict where you finish them. But we're certainly -- it's one of our strategic objectives is to is to try and do more deals around the portfolio in order to generate cash inflows to take the pressure off the balance sheet.

Bob Pooler

Okay, yeah. Because also with your Scientific Board also, yeah, some people there that have direct connections with pharma. So it's great here that pharma is looking at some of the candidates as well. Okay, thank you for answering my question.

Tim Dyer

Thank you.

Operator

Thank you [Operator Instructions]. Your next question comes from the line of Charles Duncan from Cantor Fitzgerald. Please go ahead. Your line is open.

Charles Duncan

Yeah, good morning, Tim and team. Thanks for taking my question despite not covering the stock and therefore not being able to recommend it. I had a few questions, because I'm intrigued with the pipeline. I'm wondering if, first of all, Roger could help us understand a little bit about not only the pace of enrollment for the ongoing PD-LID study, but also, perhaps whether or not there's been any participation in the open label extension study. It would seem to me that since the time that this study opened, that there would be patients through the 12-week dosing period and I'm wondering if there is participation and roll over into the OLE.

Roger Mills

So happy to comment on that. So we obviously, as I mentioned earlier, we are seeing momentum building in the study. I'm not giving specific guidance on enrollment throughout. But I think you hit on an important point there, which is our 302 study. We have got patients who rolled over into 302, and then progressing through like a number of months in that study. It's a really nice study, because it really -- the couple of things. It allows freedom in terms of background medication change.

So it's much more of a real world sort of management study in that respect. It really reflects that sort of longer maintenance of patients on the drug, as well as importantly, providing formal safety data for long term administration for the requirements for putting an NDA together with 6 and 12 month data. So we were actually very pleased with the 302 and that as well as the 301 is progressing well.

Charles Duncan

Okay, very good. That's helpful, and I appreciate the color. My second question was on the PTSD program. And I'm going to ask you to speculate, so don't really expect any definitive answers. But I'm just kind of wondering about mechanism. And PTSD being very often looked at by lots of neuro innovators, there are programs with MDMA. There's also an NMDA [ph], positive allosteric modulator programming. So I guess I'm wondering how you feel, mGlu7 negative allosteric modulator mechanism fits in, and what gives you confidence for it being useful in PTSD?

You mentioned memory consolidation and retrieval. So I'm particularly intrigued with that.

Tim Dyer

Yeah, thanks, Charles, for that question. I'll hand that over to Robert. He can answer that.

Roger Mills

Yeah. Hi, Charles. Thanks. Very good question. I mean, clearly. So there's a lot of data around mGlu7, either from knockout animals, or from knockdown animals, which show an anxiolytic profile. So there's clearly an effect of blocking or not having mGlu7 to treat anxiety. And what we've gone into is really looking at that mechanism again, at the cellular level, with electrophysiology showing that no we do have an effect with an mGlu7 on LTP, which is one of the measure that is taking -- which is seen as a phenomenon happening in memory.

And so then we link that to animal models. And so we've been doing some fear conditioning models, specifically to instill like a PTSD-type of response in animals. And we've been able to look at different phases of -- into fear learning, fear, memory recall, but also so that we get this, -- we open this window in the memory formation, which is called memory consolidation or reconsolidation, depending on who you're talking to.

And then later on, so at a later time point, we're looking at memory retrieval, and we show specifically with our compounds that we can modulate that. So this gives us confidence that maybe together with a behavioral therapy, where patients after have experienced their trauma, and when they're going to see that doctor, that that a treatment together of mGlu7 NAM or mGlu7 and the behavioral therapy will be actually be able to address the symptoms, much better than with any other approach.

But as you say, it's still very speculative, obviously. It's all based on animal data, but again everything fits pretty well and just on your remark that there are other compounds out there that are being progressed in PTSD trials, I think especially in MDA compound, for example is an indirect proof that if you are able to modulate the dramaturgic transmission, which you're doing obviously by binding to the MDA receptors, but also to the mGlu7 receptors, you can actually achieve, a beneficial effect.

So we see it also as a kind of indirect validation of our approach. Now mGlu7 is expressed quite widely in the brain. It’s expressed very specifically in within the synapses. And this is a receptor, which is a bit standing out from the rest of the family of the mGlu receptors, because the [indiscernible] of glutamate is very high. So basically, you need very high levels of glutamate to activate the receptor, which makes sense if you think that the receptors expressed within the synapses.

And so you need to have conditions where you get really a very high level of glutamate that gets released in the synaptic cleft in order to activate the receptor. And one could speculate that these are conditions that are reached in moments where there's a panic, or some kind of behavior that is really leading to a very strong glutamate release.

Charles Duncan

And let me ask you a follow up. Do you do you know if those receptors become overexpressed within a long term potentiation model and therefore reinforced? It would seem like that might be the case. And in that case, a negative allosteric modulator may be particularly useful?

Roger Mills

Yeah, I mean, I really don't -- I mean, it's difficult. I mean, again, I can only give you an answer that could be quite speculative. But again, I'm not sure about the expression. I don't think that the receptor gets -- the expression of the receptor gets upregulated in LTP. I think it's more linked to strengthening of synapses, and so that you have mechanisms that will activate, certain synapses rather than others. This is really what is probably the basis of the memory formation.

Charles Duncan

Makes sense? Last question, probably a lot easier, maybe for Tim, and appreciate you taking all my questions, that is relative to the J&J program. I understand that you're very much a passive partner in that program. So do you think you'll be able to press release top line data from the focal seizure study? And then there was a question about milestone payments, being triggered with the results. But could you see a milestone payment, say in the next 12 months or so? Should J&J take that data and decide to move forward with that particular candidate?

Tim Dyer

Yeah, so the first question around, would we press release the top line data from the part one of the study? The answer is yes. And they will let us press release that. With regard to the milestone we are not allowed to give any granularity around the milestones, unfortunately. Okay, so I’m sorry about that.

Charles Duncan

That's no worries. That's fair. I appreciate it. But you did say that the last milestone received was with the start of a clinical study. Correct?

Tim Dyer

Correct. But again, I can leave you to therefore speculate when the next milestone could be. That's what I'm allowed to do.

Charles Duncan

Yeah, okay, okay.

Tim Dyer

I know it’s not very helpful. But we’ve been through this a lot with our partner Janssen. And they're quite clear on what we're allowed to communicate around the milestones.

Charles Duncan

No worries. I understand. Thanks for taking my questions. Thanks.

Tim Dyer

Thanks, thank you.

Operator

Thank you. Your next question comes from the line of Peter Alec from Acontrove [ph]. Please go ahead. Your line is open.

Unidentified Analyst

Thank you, and good afternoon to everybody. My question relates also to the expected milestone payment. I understand now it's not with the completion of the current study. And also, Roger mentioned there is a royalty payment expected in a double digit figure. Now royalty payments, I suppose would only be expected when the product is in the market, which may take quite a few years yet. But any indication, a bit a bit closer indication about the milestone payment when that is expected. And also, I'm not quite sure whether I understood the amount correctly. I understood first EUR109 million. And on the second discussion, it sounded more like EUR190 million, 1-9-0. So can you explain please?

Tim Dyer

Yeah, so the total number of milestones is 1-0-9. EUR109 million. And we're not -- the only thing we're allowed to say about them is that they are pre-launch milestones, which means that they are linked to stages in the development and stages in the regulatory approval process, as opposed to being a milestone or launch or first sale or meeting certain sales targets. So none of the 109 are linked to sales targets.

Now the royalty is a double digit royalty. It's flat, it's low double digit. That's what we're allowed to say. So as opposed to being tiered, so that low double digit royalties payable on the first sale of the product anywhere in the world.

Unidentified Analyst

Okay. And then I suppose on all subsequently sales also.

Tim Dyer

Yeah, so.

Unidentified Analyst

Yeah. Okay. And that could be a few years out yet, likely?

Tim Dyer

Yes, Janssen is running a phase two study. And then there will be further studies. Further pivotal studies could be expected prior to filing for a marketing authorization. So yes, some years out. Correct.

Unidentified Analyst

Okay. Thank you.

Operator

Thank you. Ladies and gentlemen, this brings the main part of our conference to a close and I would like to hand back to Tim Dyer for closing remarks.

Tim Dyer

Thank you. So 2022 looks like it will be an exceptional year for Addex, with the three ongoing clinical trials and data starting to report out as early as Q2 this year, which is only a couple of months. In addition, we have multiple clinical preclinical programs advancing rapidly through clinical candidate selection. And these are novel programs. So lots of novel IP that's being generated at Addex to cover these programs. And we'd like to thank our shareholders for their continued support, especially New Enterprise Associates, New Leaf ventures and CAM Capital, as well as Armistice Capital for supporting the recent 10 million financing. We look forward to updating you on all the progress we are making in the coming months. So thank you very much for attending this call. I wish you all a very nice day.

Operator

Thank you. That does conclude today's conference call. Thank you for participating. You may all disconnect.