Addex Therapeutics Ltd. Q4 FY2020 Earnings Call

Ladies and gentlemen, welcome to the Webex Conference of Addex Therapeutics for the announcement of the Full Year 2020 Financial Results. At our customer's request, this conference will be recorded. All participants will be in a listen-only mode. After the presentation, there will be an opportunity to ask questions. I now hand you over to Tim Dyer, who will lead you for this conference. Please go ahead.

Hello, everyone. I would like to thank you all for joining our 2020 full year financial results webcast. I am here with Roger Mills, our Chief Medical Officer, and Robert Lutjens, our Head of Discovery Biology. I draw your attention to the disclaimer; we will be making certain forward-looking statements that are based on the knowledge we have today. I will start by giving a quick overview of the company and reviewing our 2020 financial results. I will then hand over to Roger and Robert, who will provide an update on our clinical and preclinical programs. Despite the global pandemic, we have made solid progress in 2020 and now have three clinical stage programs, which are all scheduled to start clinical studies in the first half of this year. The company was founded based on a leading drug discovery technology platform, which is focused on our allosteric modulated drug discovery. It is this platform that has generated the deep pipeline of in-house discovered programs focused on unmet medical needs in neurology. We have active partnerships with Indivior and Johnson & Johnson, which were entered into at the discovery phase and provide significant validation of our technology platform. These partnerships are providing significant funding for our GABAB PAM and epilepsy program. Under these agreements, we are eligible for more than 400 million in success-based milestones, in addition to royalties. We're a Swiss company founded in 2002, with operations in Geneva and San Francisco. We're listed on the Swiss Stock Exchange since 2007, and in January last year, we successfully listed an American depository share representing six ordinary shares on the NASDAQ capital market. And in January this year, we completed our first offering of new shares in the form of ADSs on the NASDAQ and raised $11.5 million in gross proceeds. Now to our pipeline. As mentioned, our pipeline has been discovered in-house from our discovery platform and comprises nine small molecule allosteric modulator programs focused on neurological disorders. In addition to our lead program for PD-LID, we are developing a long-acting formulation of dipraglurant for dystonia, and expect to start a Phase 2 study in blepharospasm patients using the immediate release formulation in the coming months. Our partner Janssen is on track to start a Phase 2 POC study in epilepsy, with dosing of patients expected in the second quarter of this year. We have made solid progress in our GABAB PAM program and expect to deliver clinical candidates by the end of 2021 for both Indivior and for our independent CMT1A program. Our mGlu7 NAM and mGlu2 NAM programs have also made significant progress and are advancing towards the clinical candidate selection phase. I remind you that the mGlu7 NAM program for PTSD is funded by a Eurostars and a Swiss grant of €4.85 million. Now to the key activities that drove our 2020 financial results. In January last year, we completed one of our long-term objectives, which was the listing of American Depository receipts on the NASDAQ capital markets. This January, we completed a small capital increase of $11.5 million through the issue of shares in the form of ADSs. Despite the constraints imposed by the COVID-19 situation, we have continued to advance our PD-LID registration program with the completion of several non-clinical activities. We also made good progress in our dystonia program with the preparation of a Phase 2 study with dipraglurant for blepharospasm. Our partner Jansen took the decision to advance ADX71149 into a Phase 2 epilepsy study, which is expected to start dosing patients in the coming months. We recognize CHF3.6 million of revenue in 2020 under our funded research partnership with Indivior and in October, extended the research term with $2.8 million of additional research funding. We have continued to invest in our early-stage pipeline and advanced our mGlu2 NAM and mGlu7 NAM programs into late lead optimization during 2020. Swiss awarded us and our academic partner SIB a CHF600,000 grant to deploy a computational approach to identify novel therapeutic areas for ADX10061, a highly selective D1 antagonist. ADX10061 is a clinical stage asset which we de-prioritized in 2008. Depending on the outcome of the SIB collaboration, we may consider restarting this program. Now, I would like to briefly review our financial results. Now on to the income statement, we recognize CHF3.6 million of revenue from Indivior in 2020 compared to CHF2.8 million in 2019. Revenue is recognized based on the costs incurred, and the increase in 2020 is primarily due to the progress of the program to more expensive activities as molecules advance towards clinical candidates. We also recognize CHF266,000 of revenue under our Eurostars/Innosuisse Grant, which is partially funded out just mGlu7 NAM PTSD program. R&D expenses of CHF10.4 million are primarily related to dipraglurant PD-LID and blepharospasm programs, and to a lesser extent, our GABAB PAM program for addiction and Charcot-Marie-Tooth 1A neuropathy. The reduction in R&D expense is primarily due to us suspending certain clinical activities due to the global pandemic. G&A expenses have increased significantly in 2020, mainly due to costs associated with the listing of American Depository shares on the NASDAQ, and certain other costs associated with operating as a U.S.-listed company. So the financial result is characterized primarily due to foreign losses on the U.S. balance, U.S. dollar cash balances due to the strengthening of the Swiss franc. Now to the balance sheet, our assets are primarily held in cash, and we completed the year with CHF18.7 million of cash held in Swiss franc and U.S. dollars. On the liability side of the balance sheet, the main item is payables and accruals related to clinical and preclinical research organizations. These amounts decreased significantly in 2020 due to the lower clinical related supply payables at the year-end. Contract liabilities and deferred income relate to amounts received from Indivior and Eurostars in Swiss, which have not yet been recognized as income. Now for the cash flow statement, we started the year with CHF31.5 million, consumed CHF15.4 million in our operations and received CHF3.1 million in research funding from Indivior. We have a paper loss of CHF0.6 million in Forex when U.S. dollar cash balances are converted to Swiss francs for the end of the year financial reporting purposes, resulting in CHF18.7 million at the end of the year. I will now hand over to Roger, who will provide an update on our clinical programs.

Thank you, Tim. Good afternoon to those of you in Europe, and good morning to those in the United States. Together with Robert, I would like to give an update on how dipraglurant and clinical programs for Parkinson's disease levodopa-induced dyskinesia, or PD-LID and blepharospasm, as well as an introduction to the epilepsy program being started by our partner, Janssen. The development of LID in PD represents a therapeutic challenge for both patients and their doctors. This is a large underserved market in need of improved treatment options and represents a significant commercial opportunity with limited competition. Dipraglurant has an ideal PK profile to treat the condition. And the program is supported by strong preclinical data, together with our previous Phase 2 proof-of-concept study and is underpinned by a mechanism of action. And I'll pass you to Robert to give you more detail.

Thank you, Roger, and hello everyone. This is a rather complex slide describing different neurons' modes of action. There is a wide body of experimental data pointing to mechanisms underlying LID indications and several lines of evidence explaining the role of mGlu5 receptors in healthy and diseased brains. I'd be happy to go into the details of the science behind this, but in the interest of time I'll summarize here. This slide shows the main take-home messages and why we believe dipraglurant by inhibiting mGlu5 receptors presents a strong rationale for addressing PD-LID. It is characterized by several physiological symptoms of which three are believed to play an essential role. Firstly, is the D1 receptor priming which is a direct result of synaptic changes occurring while limpid and which leads to an abnormal overactivation of downstream effectors collectively called maladaptive changes. Secondly, is excessive glutamatergic transmission, a phenomenon that is indirectly validated by amantadine, reformulated in Gocovri, marketed by Adamas. Indeed, it is believed that the anti-dyskinetic effects seen with amantadine and Gocovri come from its weak inhibition of NMDA, which results in a reduction of glutamatergic transmission. And thirdly, a process that is believed to be at the basis of bidirectional synaptic plasticity, called LTP depotentiation, a mechanism important for signal pruning. This phenomenon is believed to play a crucial role in movement control. mGlu5 receptors are expressed on the post-synaptic side of synapses and modulate glutamatergic transmission, and blocking mGlu5 leads to a decrease of excessive glutamatergic transmission. In addition, mGlu5 inhibition stops the maladaptive changes and restores LTP depotentiation. Dipraglurant is a highly potent and selective inhibitor of mGlu5, and thus, we strongly believe we can efficiently address these key physiological symptoms.

Thank you, Robert. Our pivotal clinical program consists of two efficacy and safety studies together with a 12-month open-label safety study. The first pivotal study is our 301 trial; it's a one-to-one randomized placebo-controlled study of 100 milligrams of dipraglurant taken three times daily in conjunction with the patient's levodopa dose. The study duration is 12 weeks, patients who complete the 12-week 301 study then will be able to roll over into the 12-month open-label safety study, after which all patients who received dipraglurant will take 100 milligrams three times daily. The 301 study will recruit PD patients with moderate to severe dyskinesia, recruited in the United States. You'll recall that we’ve delayed starting the study due to the impact of the COVID-19 pandemic and the potential risk to patients and the restrictions that were in force across the country. With the changing situation and the availability of effective vaccines against COVID, we're working together with clinical study sites under our CRO to start the 301 study in the first half of this year. The primary endpoints of the 301 study are a unified dyskinesia rating scale, or UDysRS. This scale was developed specifically to address dyskinesia symptoms in Parkinson's patients. It is the scale recommended by the Movement Disorder Society and has regulatory precedent with the FDA approval of Gocovri for PD-LID. Importantly, we have included several measures to manage the placebo response. These include the use of the UDysRS scale, which is less prone to placebo response compared to other scales used for dyskinesia. The use of brief psychosocial therapy adapted for dyskinesia will be used in a screening period of the study, and patients are required to have moderate to severe symptoms both at the screening visit and the baseline visit of the study. We'll also be using expert reviews of the ratings to ensure quality. Additionally, the 12-week duration study would be expected to mitigate the placebo response. The second clinical program we're initiating this year is our program for dipraglurant in blepharospasm. Blepharospasm, or BSP, is a type of dystonia affecting the muscles of the eyelids, which can lead to sustained eyelid closure, resulting in substantial visual disturbance or functional blindness. It can also involve other craniofacial muscles in over half of the patients. There are at least 50,000 BSP patients in the U.S., and about 2,000 new cases are reported each year. The mainstay of treatment involves injecting botulinum toxin, and this is the only treatment approved by the 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's a clear need to improve therapy with an oral therapeutic. I'll ask Robert to summarize the preclinical support for pursuing dipraglurant to treat BSP under the dystonia.

Thank you, Roger. Firstly, it is important to note that blepharospasm is a neuro-functional rather than a neurodegenerative disease. The pictures on the right illustrate the brain neurocircuitry involved in the control of muscles responsible for eye blinking and closure. Without going into too much detail, blepharospasm seems to be the result of an imbalance in signals within this neural circuitry, leading to an over-activation of muscles involved in the eye-blinking reflex. Several connections between brain structures in this circuitry are glutamatergic, and neurons in these structures express mGlu5 receptors. Therefore, the hypothesis is that by inhibiting mGlu5, we can reduce the hyper-glutamatergic signaling and correct the over-activation of the eye muscles observed in blepharospasm. Supporting this hypothesis, we have accumulated robust data in preclinical dystonia models with different neurons. Firstly, in the MPTP-lesioned monkey model, we measured dose-dependent effects on the dystonia components observed in the model. Secondly, in a genetic rodent model called the tottering mouse model, which shows an early onset generalized dystonia phenotype, dipraglurant was able to reverse this phenotype. Finally, in two genetic models of dystonia, the DYT1 mouse model and the DYT25 rat model, we demonstrated that dipraglurant could restore some central mechanisms in neuronal transmission that are lost in dystonia. We also have indications of an anti-dystonic effect of dipraglurant from the Phase 2 clinical trial, although a small number of patients did not allow for statistical analysis of the data. Taken together, our data strongly suggests that dipraglurant is effective on some of the core dysfunctions identified in dystonia, which may be common to several forms of dystonia, including blepharospasm. I'll hand it back to Roger for the blepharospasm's Phase 2 study design.

Thank you, Robert. We intend to start a Phase 2 feasibility study in BSP with dipraglurant in the first half of 2021. The study will enroll patients with benign essential BSP, who experience moderate to severe symptoms prior to their regular doses of botulinum toxin. This will be a single-center, double-blind, placebo-controlled study with approximately 15 patients randomized to dipraglurant immediate release 50 milligrams, 100 milligrams, or matching placebo taken over a two-day period. Efficacy endpoints will include the computational motor objective rater or CMOR, clinician rating scales, and patient-reported outcomes. In parallel, we are developing an extended-release formulation of dipraglurant with the intention of performing a Phase 2 proof-of-concept study in BSP in 2022. Our third clinical program will also be initiated by mid-year 2021. Our partner Janssen, a subsidiary of Johnson & Johnson, is planning to initiate a placebo-controlled Phase 2a proof-of-concept clinical trial of mGlu2 PAM compound ADX71149 in epilepsy patients in the second quarter of 2021. The epilepsy market is projected to reach $20 billion by 2026, with a high proportion of patients considered to be refractory. Today, combination treatments have shown limited therapeutic benefit. The market leader is Keppra, but there remains a large underserved patient population in need of improved treatment options. ADX71149, a positive allosteric modulator of the mGlu2 receptor, exhibits true synergy with Keppra, offering the potential for the first rational combination therapy for epilepsy. There is already extensive preclinical and clinical data for ADX71149, with previous Phase 1 studies and two Phase 2 studies, the latter in other indications. The synergistic effect with Keppra can be seen in the pharmacoresistant mouse epilepsy model. Over to Robert for this slide.

This is the compelling data obtained by Nance and colleagues in the 6Hz model, which is a highly predictive model of epilepsy, showing that the combination of ADX71149 and Keppra produces a 35-fold shift in efficacy. The important point here is that one can achieve the same anti-epileptic effects with a 30 times smaller dose of Keppra when combined with ADX71149. The results obtained when the paradigm was reversed, where a low dose of Keppra enhances the efficacy of ADX71149 by a 14-fold increase, indicates a true synergistic effect rather than a simple pharmacokinetic effect. If this translates into patients, this approach could result in a paradigm shift, allowing patients to receive a much smaller dose of Keppra in combination with ADX71149, achieving high efficacy comparable to high doses of Keppra, but potentially without any of the side effects linked to higher doses. This novel approach could be the first polypharmacy strategy to treat epilepsy. Back to you, Roger.

The Phase 2a clinical trial will enroll patients who have partial onset seizures and a suboptimal response to Keppra. A 28-day seizure count will be established prior to receiving the drug, and patients will be randomized at baseline to either continue on their Keppra dose plus placebo or to add 50 milligrams of ADX71149 to their Keppra regimen. The primary endpoint will be the time to return to their baseline seizure count. The study will have two periods: the first is a four-week efficacy phase, followed by an eight-week maintenance phase for those who do not meet or exceed their baseline 28-day seizure count during the first period of therapy. The advent of COVID in 2020 posed numerous challenges, and we reacted appropriately to contain the spread of the virus to limit mortality and morbidity. It was appropriate for us to pause the start of our dipraglurant clinical program in response. However, with the current availability of effective vaccines, we are now pleased to start clinical studies involving three separate indications this year. We feel that 2021 will be a transformative year for Addex, and we look forward to advancing these clinical programs. I'll now hand back to Robert, who will provide an update on our preclinical programs.

Let me now share with you an overview of our discovery activities and focus on some exciting progress we made during year 2020 in the GABAB program. As mentioned by Tim, we're conducting research fully funded by our partner Indivior, who has repeatedly committed additional support as we announced at the end of last year, totaling now $8.4 million. We have now reached the clinical candidate selection stage and aim to identify the molecule that will enter IND enabling studies by H1 2021. It is important to note that GABAB activation is validated through the use of baclofen, a GABAB orthostatic agonist that is FDA approved for specificity in certain spinal cord injuries. However, it’s also used off-label for several other disorders, including alcohol use disorder. Baclofen is efficacious, but shows dose-limiting side effects that hamper its wider use. One of the key advantages of a positive allosteric modulator approach compared to an agonist approach is the lack of tolerance observed in a chronic administration paradigm. When a receptor gets constantly activated in the presence of an agonist, gradual tolerance is observed mainly due to receptor desensitization. Conversely, because it respects the natural physiological rhythm of receptor activation, it does not induce tolerance. We have been able to demonstrate this in our preclinical studies. Hence, this lack of tolerance over the long term should result in potential advantages in safety and efficacy compared to baclofen. The program is now in clinical candidate selection, and we aim to bring candidates into IND enabling studies in H1 2022. An important aspect of this collaboration is that while Indivior is funding the research of Addex, Addex actually has the right to select clinical candidates from the research and independently develop them in a selection of reserved indications where we have exclusivity, including Charcot-Marie-Tooth 1A. CMT1A is a peripheral neuropathy affecting approximately one in 5,000 people worldwide and qualifies for orphan drug designation. It is the most common inherited neurological disease, resulting from the duplication of the gene encoding PMP-22, a protein playing a central role in myelination of axons. Currently, there is no drug treatment available for patients. With baclofen being used off-label providing some significant validation, we have demonstrated with a positive allosteric modulator in preclinical models of CMT1A that we are as effective as baclofen in normalizing the expression of the duplicated PMP-22 gene and significantly reduce the symptoms observed in the disease. Another important point for our program is that the regulatory path is paved by a French company developing a fixed dose combination of baclofen, naltrexone, and sorbitol. While this combination is not approved, the FDA has set up a path for NDA submission. To recap where we currently stand in the program, we have now entered the clinical candidate selection stage, aiming to bring a clinical candidate into IND enabling studies in the first half of 2022. I'll now hand it over to Tim for his closing remarks.

Thanks, Robert. I will now review the milestones. We expect to start the PD-LID Phase 2b/3 study in the coming months and report data in Q4 2022. Our blepharospasm Phase 2a study should also start in this half and report data by the end of this year. The epilepsy Phase 2a proof-of-concept being run by J&J is expected to start in Q2 2021, reporting data in the first half of 2022. We also expect to deliver clinical candidates in our GABAB PAM program by the end of the year and start IND enabling studies shortly thereafter. Now, I'd like to conclude our prepared remarks. As you can see, 2021 will be an important year for Addex, with three programs starting clinical studies and one of them reporting data. We have a leading technology platform, which has delivered a deep pipeline of in-house discovered proprietary programs, and an experienced team of drug developers capable of driving these programs to their next value inflection points. We have managed to secure significant industry partnerships that are providing substantial funding for two of our programs. We have top-tier U.S. investors backing the company and a rich pipeline of news flow in 2021. Thank you for your attention, and we will now open the call for questions.

Thank you. The first question is from Ram Selvaraju. Your line is now open.

Hey, this is Ram. Congratulations on the progress. My first question is about the off-time indication. Gocovri received its second indication in February. I understand that you have not met both the primary and secondary objectives in your patient diaries.

Sorry, we can't really hear you.

Okay. How about now?

Yes, it's much better.

I was curious about the off-time secondary objectives. I know Gocovri gained an indication for the off-time endpoint in February. Does this hold more significance, and could this be a consideration for future developments?

So Roger, would you like to take that question?

Yes. Sure. So, obviously I'm assuming, it was hard to hear. So I'm assuming you're asking about the off-time with Gocovri. Yes, we were measuring off-time. We actually did see some benefit on that in the Phase 2. So we’ll measure it in the first obviously include that as an assessment in the upcoming 301 study. And we'll see what the results show. If it's positive, then certainly, we will look at how best to address that in the second pivotal study that we do. So, that is actually good advantage as being able to do the study sequentially. But we get a benefit; we just don't confidently have the data as we run through, but we would expect to see a benefit in the upcoming two pivotal studies.

Okay, that makes sense. Regarding COVID, I know you've mentioned having a COVID appendix in the study protocol for the dipraglurant study. Are you at all worried about some of the reported neurological impacts in relation to the study population? Will you consider excluding infected patients?

So COVID obviously poses a number of challenges in terms of running studies. The key things in terms of the appendix is actually just helping; it's primarily to help sites understand how to manage the study if there are situations where, for example, a patient can't come for a visit, how is that addressed? So, it’s really providing guidance to the sites to help them manage through the pandemic with the study and study visits. In terms of vaccinations, we're not requiring patients to be vaccinated to enter the study. Obviously, across the U.S., there are different criteria for people getting vaccines. Clearly, we would expect PD patients to be at the forefront of priority to receive vaccines. But we're not requiring vaccination for study entry. Likewise, however, if the patient hasn't been vaccinated and is in the study and has the option to get a vaccine, that’s really important. We believe that patients should get vaccinated. We don’t believe there's any rationale why that would interfere with the treatment for the dyskinesia. So, we clearly allow patients to get that vaccine during the course of the study. In terms of complications from COVID, patients who developed COVID during the study will be terminated. The most important thing is for patients to manage their COVID effectively and appropriately. So certainly, patients diagnosed with COVID will be dropped from the study. During the screening period, in terms of prior COVID, which I am assuming you're alluding to, patients who have neurological conditions from COVID or any other illness will not meet the entry criteria to come into the study.

Okay. That's great color. And next, I was wondering about whether you guys have ever done this before, but is it feasible or possible to model how much the levodopa therapeutic window could be increased with dipraglurant in terms of years of disease post-diagnosis? Could the therapeutic window be activated for the duration of the entire PD disease course?

We haven't considered that at this moment. We also haven't fully examined how that could be accomplished. However, we will conduct a series of large efficacy studies in our pivotal program, which will provide us with a better understanding of the therapy's implications during that time.

Okay. Thanks. And then just finally, I wanted to get a developmental update on your in-house discovered molecules, four of which you've mentioned are slated to deliver at the end of the year, beginning of 2022. Are any of them going to be progressing faster than others as a result of possible partnership deals, or in response to some of the competitive landscape?

Yes, so I'll take that one. So on the GABAB is a very active program and it's making great progress. The mGlu7 is just ahead, but the CMT program, which is part of the GABAB program is actually unpartnered. The mGlu7 is also unpartnered. And the mGlu2, which is also looking to deliver clinical candidates around the end of the year, early 2022, is also unpartnered. Then we've got two early-stage programs, and Addex continues to discuss openly with potential partners. We’re not promising anything, but our strategy is to be open in dialogue with potential partners. We have a track record for forming partnerships at the preclinical late lead optimization, early clinical candidate selection phase. So it’s certainly something that we continue to work at.

Okay. Thanks so much for the update, Tim, Roger, and Robert. We look forward to the coming year with Addex. Thanks so much.

Thank you.

The next question is from Vakhija of ValuationLAB. Your line is now open.

Good afternoon, gentlemen. Thank you for the excellent presentation. A few questions, if I may. Just coming back to the PD-LID trial, I was actually expecting that you would include vaccination as a criterion. Why not include vaccination as a criterion for the patients? Because then you could probably limit the exclusion if patients develop COVID-19?

So, Roger, one for you, I think.

I believe that most patients entering the study will be vaccinated. The study will continue throughout this year and into next year. We are uncertain about the impact of including a vaccination criterion, as the vaccine rollout is unpredictable. For example, there may be booster vaccinations required either later this year or early next year. This makes it difficult to foresee what will happen. We are collaborating closely with the study sites, which are located across different states in the U.S., each with their own regulations. I trust that the investigators will prioritize patient safety in our study. If we require vaccination at this point, we could potentially exclude many patients due to the changing COVID situation.

Okay. And then I get it that probably across the U.S. might be like a staggered approach. If there are places where the infection rates are quite high, you would delay the start of the trial sites there and go to those where the infection rates are currently low.

Yes. We’re working very closely with the sites. We've had these protocols ready to go last year. So the protocol itself is well documented for us with each site. The work with the sites has been around the risk of COVID both across the U.S., but also importantly down to not just state level, but actually site-specific to the conditions. We’ve been working closely, continuing interaction, to ensure that each site has the best start in terms of safety. It may be that certain sites start later than others; we’ll begin with sites that are more comfortable and confident with the COVID situation locally. Once we get a broader spread of people taking the vaccine, the COVID situation should improve significantly, allowing more flexibility to operate.

I hope you can soon start the trials and that it can be in a safe environment. We've been waiting for this quite long and also for the patients here as well. So good luck with that. Just on the pricing strategy as dipraglurant for PD-LID versus BSP, could you maybe give us some feedback on that? How do you see that progressing?

Yes, so dipraglurant is going to be the immediate release formulation in PD-LID. We'll be using a different formulation in dystonia indications, including blepharospasm. At the moment, we haven't done any specific analysis or modeling for pricing. Many dystonias are orphan drugs qualifying for orphan drug designation, and PD-LID is currently priced at $34,000 a year for Gocovri. We would expect to see similar pricing. However, we will likely launch dipraglurant in about four to five years, so the environment will certainly change.

Okay. And also probably the dystonias will be the extended release formulation, most of them are or all of them?

Yes. The dystonias will utilize the extended release formulation. Absolutely.

Okay. Then on ADX71149 for epilepsy. What's the patent life? Do you feel there is room for combination patents for you with Keppra still possible?

Yes. So there is a patent that lasts through 2027 without extensions. The combination with Keppra patent is much longer, potentially going to 2035 without extensions.

Okay. Then my final question just on your financials. Your cash burn for this year, what do you expect? I assume that the G&A is going to decrease that probably more extensively and more to the second half compared to the first half?

Yes, G&A should decrease. We're not guiding cash burn at the moment for this year because it very much depends on how the studies start and how quickly the sites come on board. It’s currently very difficult to estimate. What we're guiding is that we have cash through mid-2022 on a very conservative basis.

Okay. Yes, that excludes any partner, so you have a lot of assets that might be parked in the meantime as well?

Yes, that excludes any partnership income.

Okay. Well, thank you for answering the questions. I wish you successful 2021 with all the trials going on.

Thanks so much.

As there are no further questions, I hand back to the speakers for the conclusion.

Okay. Thank you very much, everybody, for attending our call. We wish you a very nice day and evening. We look forward to the next opportunity to update you. Goodbye, everyone.

Ladies and gentlemen, thank you for your attendance. This call has been concluded. You may disconnect now.