This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk05: Hello, everyone. I'd like to thank you all for joining our 2021 Full Year Financial Results Conference Call. I'm here with Roger Mills, our Chief Medical Officer, and Robert Lugins, 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 IIa clinical trial of Dibrogluron for blepharospasm, a type of dystonia characterized by involuntary contractions or spasms of the eyelid muscles resulting in sustained eyelid closures. During 2021, we also continued to advance our pivotal program with Dibrogluron in Dyskinesia associated with Parkinson's disease. Our partner Janssen continued to make significant progress in executing their global phase two 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 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-week delay. We also expect our PD-LID study to report data in H1 of 2023 instead of the end of Q4 of 2022, a three to six month delay. 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 GABA-B-PAM with Indivio 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 GABA-B-PAM program for Charcot-Marie-Tooth type 1a neuropathy and entered into a collaboration with the Charcot-Marie-Tooth Association of the United States. This collaboration is to evaluate selected drug candidates in preclinical models for Charcot-Marie-Tooth 1a neuropathy. We are on track to deliver multiple GABA-B-PAM drug candidates ready to start ion enabling studies. We continue to advance our other preclinical programs, in particular, our mGluR7 negative allostatic modulator program for post-traumatic stress disorder, which is progressing through clinical candidate selection funded by the Eurostars and InnoSwiss grant program. We also expect our mGluR2 negative allostatic modulator program for mild neurocognitive disorders associated with Alzheimer's disease, Parkinson's disease, and depression to enter clinical candidate selection phase in the second half of this year. On the financing side, The extension of our collaboration with Inivia 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 20.5 million Swiss francs or the equivalent of 22.5 million US dollars. So now I would like to hand over to Roger. So Roger, the floor is yours.
spk07: Thanks, Tim. Good morning. Good afternoon, everybody. Let's start by speaking about our Dipragluron 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 2 B3 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 of dipreglorin taken three times daily in conjunction with the patient's L-DOPA dose. Duration of the study is 12 weeks. In parallel, we also initiated our 302 study. Patients who complete the 12 weeks of the 301 study are eligible to roll over into the 302 study, which is a 12-month open-label safety study where all patients received dipreglorant 100 milligrams three times daily, irrespective of the study arm they were randomized to in the earlier 301 study. 302 study provides six and 12-month treatment safety data to meet the regulatory requirements for an NDA submission. The primary endpoint to the 301 study is a change from baseline in the Unified Dyskinesia Rating Scale, or UDIS-RS. This scale was developed specifically to assess dyskinesia symptoms in Parkinson's patients. It's a scale recommended by the Movement Disorder Society and has regulatory precedent with the FDA approval of GoCovri for PD-LID. Secondary endpoints include the clinician's global impression of 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 UDIS-RS scale, which is less prone to placebo response than other scales for dyskinesia, the use of the brief psychosocial therapy adapted for dyskinesia to be used in a screening period of the 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 are also using expert reviews of the ratings to ensure quality. In addition, the 12-week duration of the study will be expected to mitigate placebo response. For background, in a previous Phase IIa study, dipreglomerant met its primary endpoint by being generally well tolerated and showing no clinically significant safety issues. In addition, at day one and day 14, dipragorin showed statistically significant benefit on the PD-Lib's clinical symptoms as measured using the Modified Abnormal Involuntary Movement Scale, or MA. However, statistical significance was not achieved at day 28, due in part to an increasing placebo response. The registration or 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 different 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 main state 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 is 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 dipreglorant or matching placebo. Patients received three doses in total over a two-day period. Following baseline assessments, the first doses are administered in the clinic and the severity of the blepharospasm is assessed during dosing. Patients take a further dose at home, returning for a pre- and post-dose assessment 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 this study for blepharospasm in Q2 of this year. And now to ADX 71149 for epilepsy, which is partnered with Janssen Pharmaceuticals, a J&J company. In June, we announced that Janssen had started enrolling into a Phase II epilepsy study, evaluating 149 in treating patients with focal onset seizures. 149 is a selective metabotropic glutamate type II or NGluR2 receptor positive allosteric modulator. This is a Phase II double-blind placebo-controlled proof-of-concept study that is enrolling patients with focal onset seizures. who have suboptimal response to treatment with levotisirazepam or Keppra. Patients will establish a 28-day seizure count over a 56-day baseline period prior to randomization when they'll be randomized to receive either 149 at 50 milligrams BID or matching placebo. The primary endpoint is a time taken to return to their monthly baseline seizure count. The study will have two periods, period one being the four-week acute efficacy phase, and period two is an eight-week maintenance efficacy phase. Period two will include patients who did not return to their baseline monthly seizure rate during the first period of the 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 109 million euros and double-digit royalties on net sales. I'd now like to hand over to Robert, who will provide an update on some of our preclinical programs.
spk08: 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 GIB-positive out-of-state modulator program. As a reminder, this program is partnered with Indivio, who is funding the research at ADDx, and their primary interest is substance use disorder. GIB receptor activation is a well-validated approach. benefiting from the wealth of scientific and clinical data generated with Baclofen, the FDA-approved Gabi 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 effect, 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 US dollars of funding committed by Endivio to advance development of the drug candidates discovered by ELIX. 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 in Divio will progress into the clinic for substance use. In parallel, we are progressing multiple differentiated drug candidates for our independent Charcot-Marie-Tooth 1A program. We announced in September 2021 a collaboration with the American Charcot-Marie-Tooth Association. This collaboration will provide us access to significant resources and expertise in the field of CMT1A. As mentioned earlier, there is strong data supporting the GERB receptor activation mechanism coming from clinical studies that reported the beneficial effect of baclofen in patients with CMT1A. In addition, we have robust preclinical data with our own drug candidates in highly translational models of CMT1A. 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 CMT1A models and other non-GLP preparatory studies as we get ready to select a candidate to enter IND-enabling studies by the end of 2022. The second program I want to highlight today is the MV7 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 allostatic 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 Eurostar's industries grant of 4.85 million euros, which is financing a 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, Indivio, and additional funding is a further validation of the quality and productivity of ADDx's drug discovery platform and the significant achievements made in our GERB-EPAM program. This concludes my prepared remarks, and I hand back to Tim.
spk05: Thanks, Robert. I'll now switch to an overview of the financials. Starting with the income statement, we recognize 3.2 million in revenue and income in 2021 compared to 3.9 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 Dipakuron and GABA-B PAM programs, and to a lesser extent on our MGLAR-7 NAM and MGLAR-2 negative allostate modulator programs. R&D expenses have increased by 2.5 million compared to 2020, primarily due to the increased activities in our DIP grant 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 strengthened 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 US dollar cash deposits due to the strengthening of the US dollar. Now to the balance sheet. Our assets are primarily held in cash, and we completed the year with 20.5 million Swiss francs of 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 Indivio. Pre-payments are related to insurance and retirement benefits. Current liabilities of 4.1 million are consistent with prior years and relate primarily to R&D payables and accruals. Non-current 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 our operations, and received 2 million in research funding from Indivio. We have a pay-for-profit of 0.1 million in Forex when US dollar cash balances are converted to Swiss francs for the year financial reporting purposes, for the year-end financial reporting purposes. resulting in 20.5 million at the end of the year. So in summary, ADDx 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 in-house discovered programs and partnerships. We have an experienced team of drug developers in the company, partnerships with industry and the support of top tier investors. We have 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 Alex 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 for questions.
spk02: Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound hash key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Bram Selvaraju from HC Wainwright. Please go ahead. Your line is open.
spk04: Hello to the team. This is Maz representing Bram 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 DIPLA-GLURON study hastening as the Omicron wave proceeds?
spk05: Yeah, maybe, Roger, you'd like to take this one.
spk07: Yeah, I mean, quite clearly, as with so many programs, the COVID has had impacts and the obviously omicron um really sort of hit everybody at the end of last year but we've actually seen um some some good momentum and uh across and actually activity across a broad variety of sites which is um which is really encouraging so uh we are you know we are seeing a um sort of beginning of that sort of post uh covid surge so um fingers crossed we keep working and uh moving forward.
spk04: All right, excellent. I look forward to a catalyst, Rich, here. Thanks for the update.
spk02: Thank you. Your next question also comes from the line of Bronze Silver Raju from HC Wainwright. Please go ahead. Your line is open.
spk03: 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 differing 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 flam dunk outcome versus a merely positive outcome from the blepharospasm clinical readout. Thank you.
spk05: That's an interesting question, Ram. Thank you very much. Roger, do you want to have a first stab at this one?
spk07: Okay, thanks. First of all, in terms of positioning, we need to see the data from the blepharospasm study to really then start to think about the further elements of how we exploit the compound. In terms of results, this is an exploratory study. So this is really the first time we have put the drug into this indication, these patients. What I'd be really, really excited to see 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 two 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.
spk03: As a follow-up to that, I think, Tim, you know, what I would also be interested in learning more about is, you know, how you folks are thinking about the possibility of indication splitting for Dipraglorant 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?
spk05: 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 mGluR5 negative allosteric modulators in PD-LID, that there's a very strong rationale for developing an immediate release. formulation of dipreglorant 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 dipreglorant, and we believe that that will probably be the formulation that we would pursue in other indications, including blepharospasm. 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 diproglurant for PD-LID ahead of the 301 readout. Now, if somebody on the back of the blepharospasm data wanted to partner diproglurant for blepharospasm, we would be partnering the partner an extended release formulation of diproclorant. 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.
spk03: 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 ADDx under the scope of that arrangement. And also, if you could speak a little bit about prospect for non-deductive 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.
spk05: Yeah, so... So the first, sorry, the first question you had, can you just repeat that?
spk03: Yes, it was with respect to the Indivior collaboration, you know, what do you expect the timing to be 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 ADDx post mid-2022?
spk05: 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 are starting to take more and more control over the the operational implementation of the development so we will 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 and it's not clear whether we would need, whether ADHICS would need to extend the research collaboration or not. But we will, as soon as any decisions in that area are made, we will be updating the markets. Now, regarding the mGluR7 negative allosteric modulator program, as you know, we're leading a consortium that managed to secure a 4.85 million Euro grant from the Eurostars. We are currently executing on that. We have managed to identify a clinical candidate or 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 series through late lead optimization. The collaboration and the consortium is working extremely efficiently and 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, of course, in addition to, of course, discussing with farmer partners as well.
spk03: Thank you.
spk02: Thank you. Your next question comes from the line of Bob Tuller from Valuation App. Please go ahead. Your line is open.
spk06: Thank you. Hello, gentlemen. A few questions from my side. Just on the cash, could you provide some guides on your cash earn and also your cash reach?
spk05: Yeah, so we've reported having 20.5 million Swiss francs at the end of the year. As you can see from last year, we were burning about 1.5 million a month on average. And so we're basically guiding cash through into the first half of 2023. First half of 2023.
spk06: Okay, great. Just on the background on blepharospasm, they're Any implication if you have a strong readout there for other dystonias, maybe even for the PD-LID trial? And then also, what is the market potential for this indication?
spk05: Yeah, so maybe, Robert, do you want to take the first bit of that around all the preclinical data for the dystonia? Sure, yeah.
spk08: Hi, Bob. Yeah, I think this, you know, blocking MGLU5, you know, has been tested in several models, you know, of different dystonias, and so demonstrated, again, at the behavioral level that we were able to reduce or having an anti-dystonic effect with an MP5 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 a very specific phenomenon is being restored when you add diproglurant, which is an indication that possibly this is a common mechanism of, you know, all sorts of different forms of dystonias. And therefore, you know, it could be helpful So showing or providing some support for Dipragluron 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 dipragluron. 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.
spk05: 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. 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 focal 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.
spk07: Okay. Thanks, Tim. So dystonia is a broad constellation of different manifestations, and dystonia is almost like an umbrella indication with lots of sub-indications beneath it. The rationale around blepharospasm was that we could 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 determine the response across those patients, whereas blepharospasm, we were able to do that. It's a very impactful condition to patients. You can get functional blindness. It's very disfiguring. It's 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 pursue blepharospasm is that we are able, using the thymol, to be able to get an objective readout. And 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 a more homogenous group of patients. And we have the opportunity to utilize an objective criteria. So it really was a very much a sort of sweet spot within the sort of broad constellation of dystonias.
spk06: Okay. Then maybe moving on to the GABA-B PAM program there. You were indicating then on interview, wouldn't you expect them maybe to start with a leaf candidate in clinical trials?
spk05: 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, you know, we're looking forward to Indivi or 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 you know, a good three to nine months, depending on how long they decide they want to run those regulatory ID-enabling studies, and then moving into phase one. So I think moving into phase one is, best guess is, you know, late in 23 at the earliest.
spk06: Okay. How's the C&T program proceeding?
spk08: 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 CMT1A model. And so we expect to complete those 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.
spk06: Okay. Then just moving on, ADX 71149 on epilepsy. Just with the readout of the results expected in Q3 2022, will positive results trigger a milestone payment? I believe not. that Roger said there were 190 million pre-launch milestones?
spk05: No, the results will not read out, will not trigger a milestone. Okay. The trial is being run by, the last milestone we received was when the program entered into a phase two proof of concept study. And we're not able to guide any more detail Um, but there are, they're all development or I would say pre sales milestones. And then there is the, uh, the double digit, uh, royalties on, on first net sale. The study is going, it's going well and it's on track.
spk06: That's great. Also, uh, considering, um, the pandemic. Do you know if there's any potential for a combination formulation of Keppram ADX78749 that would substantially extend the patent life?
spk05: Well, Janssen have taken a patent on the mechanism of the combination. So there is a new patent combining the molecule with SV2A antagonists. So there is a new patent, but we can't comment. I mean, we're a very passive partner here. Janssen is leading the development, and we're not privy to any strategies around co-formulation of the two compounds.
spk06: Okay, and then just my final question here, as you also mentioned in the presentation, making good progress with the pre-committal candidates. What new value inflection points do you expect to reach this year, and any potential partner agreements in the offing?
spk05: Yeah, so, I mean, we're making good progress on the clinical portfolio. As we pointed out, you know, we've got Dipraglon in two Phase II and Phase IIb studies reporting out data. We're not expecting partnerships on those programs until there's more data. Janssen, of course, that clinical program is already partnered with Janssen. We are making a lot of progress in the GABA-B and the part of the GABA-B which is not partnered with Indivio. 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 autosteric agonist, which is now a generic. And we've got the mGlar7 and the mGlar2, 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, and we are starting to get some traction from potential partners who are interested in looking at some of these programs. But as you know, you know when you start the discussion, it's very difficult to predict where you finish them. But certainly it's one of our strategic objectives is to try and do more deals around the portfolio in order to generate cash inflows to take the pressure off the balance sheet. Mm-hmm.
spk06: Okay, yeah, because also with your scientific board, also you have some people there that have direct connections with pharma. So it's great to hear that pharma is looking at some of the candidates as well.
spk05: Yeah.
spk06: Okay, thank you for answering my questions.
spk05: Thank you.
spk02: Thank you. Ladies and gentlemen, as a reminder, if you'd like to ask a question, please press star and one on your telephone keypad. Your next question comes from the line of Charles Duncan from Cantor Fitzgerald. Please go ahead. Your line is open.
spk09: 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 you know, 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 rollover into the OLE. I think that was a few.
spk07: Yeah, so Cheryl's happy to comment on that. So we obviously, I think 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 are progressing through a good number of months in that study. And it's a really nice study because it really, a 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. And 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 six- and 12-month data. So we're actually very pleased with the 302, and that, as well as the 301, is progressing well.
spk09: Okay, very good. That's helpful, and I appreciate the color. My second question was on the PTSD. 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 neuroinnovators. There are programs with MDMA. There's also an NMDA positive allosteric modulator program, and so I guess I'm wondering how you feel the 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.
spk05: Yeah, thanks, Charles, for that question. I'll hand that over to Robert, who can give you a good answer.
spk08: Yeah, hi, Charles. Thanks, very good question. I mean, clearly, So there's a lot of data around MBlu7, you know, either from knockout animals or from knockdown animals, which show an anxiolytic profile. So there's clearly an effect of blocking or not having MBlu7 to treat anxiety. And what we've gone into is really looking at mechanisms, again, at the cellular level, with electrophysiology showing that, you know, we do have an effect with NMP7NAM on LTP, which is one of the measures that is taken, you know, 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, you know, into fear learning, fear memory recall, but also, you know, so that we get this, we open this window in the memory formation, which is called, you know, memory consolidation or reconsolidation, depending on who you're talking to. And then later on, so at a later time point, 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 they have experienced their trauma and when they're going to see their doctor, that a treatment together of, you know, mGlu7-Nam or mGlu7-Nam and the behavioral therapy will be actually be able to address the symptoms much better than, you know, with any other approach. But as you say, it's still very speculative, obviously. It's all based on animal data. But again, you know, everything fits pretty well. And just, you know, on your remark that There are other compounds out there that are being progressed in PTSD trials. I think, you know, especially the NMDA compound, for example, you know, is an indirect proof that, you know, if you are able to modulate the glutamatergic transmission, which you're doing obviously by binding to the NMDA 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, but it's expressed very specifically within the synapse. And this is a receptor which is a bit standing out from the rest of the family of the mGlu receptors the EC50 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 receptor is expressed within the synapse. 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, you know, there's a panic or, you know, some kind of behavior that is really leading to a very strong glutamate release.
spk09: And let me ask you a follow-up. Do you know if those receptors become overexpressed within a long-term potentiation model and therefore reinforce, it would seem like that might be the case. And in that case, a negative allosteric modulator may be particularly useful.
spk08: Yeah, I mean, I really don't, I mean, it's difficult. I mean, again, it's, you know, I can only give you an answer that, you know, could be quite speculative. But again, I'm not sure about the expression. I don't think that the receptor gets, you know, 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, you know, certain synapses rather than others. And this is really what is probably the basis of, you know, the memory formation.
spk09: 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 been 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?
spk05: 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. So I'm sorry about that.
spk09: Okay. 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?
spk05: Correct. But again, I can leave you to therefore speculate when the next milestone could be. That's what I'm allowed to do.
spk00: Yeah.
spk05: Okay. Okay. No, 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.
spk09: No worries. I understand. Thanks for taking my questions. Thanks. Thank you.
spk02: Thank you. Your next question comes from the line of Peter Alick from Accontralt. Please go ahead. Your line is open.
spk01: Thank you, and good afternoon to everybody. My question relates also to the expected milestone payment. I understand now it's not at 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 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 €109 million, and on the second discussion, it sounded more like €190 190 million. So can you explain, please?
spk05: Yes, so the total number of milestones is 109, so 109 million. And 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 on 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 royalty is payable on the first sale of the product anywhere in the world.
spk01: Okay, and then I suppose on all subsequent sales also?
spk05: Yeah, yeah, sure.
spk01: Yeah, okay. And that could be a few years out yet, likely.
spk05: Yeah, 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.
spk01: Okay. Thank you.
spk02: 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.
spk05: Thank you. So 2022 looks like it will be an exceptional year for addicts 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 preclinical programs advancing rapidly through clinical candidate selection. And these are novel programs, so lots of novel IP that's being generated at ADDx to cover these programs. And we would 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. And we look forward to updating you on 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.
spk02: Thank you. That does conclude today's conference call. Thank you for participating. You may all disconnect.
Disclaimer