RedHill Biopharma Ltd. (RDHL) Q4 2021 Earnings Report, Transcript and Summary

Good day and welcome to the RedHill Biopharma’s Fourth Quarter and Full Year 2021 Financial Results Conference Call. All participants are in a listen-only mode. After the speakers’ presentation, there’ll be a question-and-answer session. [Operator Instructions] At this time, I would like to introduce the conference call, RedHill’s CEO, Dror Ben-Asher; Guy Goldberg, Chief Business Officer; Gilead Raday, Chief Operating Officer; Rob Jackson, Senior VP Sales & Marketing; Rick Scruggs, Chief Commercial Officer; and Micha Ben Chorin, Chief Financial Officer. We have additional senior management team members available to answer questions during the Q&A session, including; Dr. June Almenoff, Chief Medical Officer; and Dr. Mark Levitt, Chief Scientific Officer. Before we begin, we will read from RedHill’s Safe Harbor statement. Please go ahead.

Thank you, Sharon. This conference call may contain projections or other forward-looking statements regarding future events or the future performance of RedHill, including statements with respect to the business financial results, promotion and other efforts related to RedHill’s commercialization activities and the initiation planning, progress and results of RedHill’s research, manufacturing, preclinical studies, clinical trials, marketing applications and approvals, if any, including the clinical trials of opaganib and RHB-107 for the treatment of COVID-19 and RHB-204 for NTM disease. These statements are only predictions and RedHill cannot guarantee that they will, in fact, occur. RedHill does not assume any obligation to update that information. Actual events, performance, timing, results or commercialization activities may differ materially from what RedHill projects today. Additional information concerning factors that could cause actual events, performance, timing, results or commercialization activities to materially differ from those contained in the forward-looking statements can be found in the company’s annual report on Form 20-F filed with the SEC on March 17th, 2022, and in its other filings with the Securities and Exchange Commission. I will now turn the call to Dror Ben-Asher, RedHill’s CEO.

Thank you, Alexandra. Good day, everyone and thank you for joining our fourth quarter and full year 2021 earnings call, during which we’ll be presenting R&D commercial and financial highlights. First and foremost, we’d like to thank the entire RedHill team for their remarkable achievements in the last year. Against the pandemic backdrop, the RedHill team delivered the record revenue and first positive commercial operations contribution in the fourth quarter of 2021. A strong fourth quarter for both Talicia and Movantik coupled with disciplined cost efficiency measures and intensive out-licensing and in-licensing activities, set us up for rapid organic and non-organic growth in 2022 and beyond. Rob Jackson, who is heading our Marketing & Sales will further elaborate shortly. Turning to R&D. RedHill remains at the forefront of the global search for much needed novel oral COVID-19 therapies, particularly so given the frequent emergence of new variants such as Omicron and most recently, BA.2. Our highly capable R&D team has delivered exciting efficacy data with both opaganib and RHB-107, our variant-agnostic investigational oral novel oral candidates for the treatment of hospitalized and non-hospitalized COVID-19 patients. At the same time, our ongoing Phase 3 study with RHB-204 is the most advanced first-line standalone potential treatment for NTM infection is being accelerated. Gilead Raday, our Chief Operating Officer will elaborate about our R&D programs shortly. I will now be turning to Chief – to our Chief Business Officer, Guy Goldberg and the team for our presentation to be followed by a Q&A session.

Thank you, Dror. We’ve started off the year strongly and are poised for successful 2022 with our seasoned commercial team leading the way, we’re expecting commercial operational profitability in 2022. This would mark a major milestone for the company. We will get to this important milestone by growing revenues through our strengthened salesforce, being cost efficient and maintaining disciplined cost-control measures. We look back on 2021 with a lot of pride that what we were able to accomplish. Our commercial operations had a net positive contribution in Q4 for the first time and recorded annual and quarterly revenues of $85.8 million and $22.1 million. This success was driven by our two main revenue generating products. First, Talicia for H. pylori infection. Talicia became the most prescribed branded H. pylori therapy in December. And already, we are seeing a nice growth trajectory this year. Talicia has enormous potential for patients and is a value driver for RedHill as a company. As with almost all launches we continue to advise that it takes time to build awareness and acceptance, both with payers and also with physicians. Second, Movantik for opioid-induced constipation. Movantik prescriptions are up as well as we saw quarter-over-quarter growth. We continue to maintain a market leadership position and that PAMORA class of drugs as a whole continued to rebound. Movantik is well liked by physicians, it has great reimbursement, great efficacy and safety and great brand recognition and satisfaction. There’s still a very large and underserved OIC patient population. RedHill continues to improve Movantik’s status as best unrestricted coverage in the PAMORA class. Our cash position as of the end of 2021 was $54.2 million. We also have had successful transactions and expect to see continued success on this front in 2022. There are two recent transactions to note here. First, with Kukbo, a South Korean company we announced the two-part transaction. The first part is a strategic investment of up to $10 million by Kukbo in RedHill. The second part is the licensing agreement for opaganib for COVID-19 in South Korea, with upfront and milestone payments of up to $7.1 million plus royalties. The second transaction we announced was a licensing agreement for Talicia with Gaelan Medical in the United Arab Emirates. The agreement included a $2 million upfront payment to RedHill and milestone payments and tiered royalties up to mid-teens on net sales. We are in active discussions for potential future licensing deals for our therapeutic products, as we’re seeing an increase in interest in our pipeline. We also see interest in our commercial products and – we also have discussions ongoing to add new commercial products that would be synergistic with the products we currently promote. This would enable us to leverage the great commercial operation we have built and benefit from economies of scale. This slide shows our R&D highlights. Gilead will go into detail on the data. One point I want to emphasize is that, despite some of the infection rate declines seen in the US and elsewhere recently, COVID continues to be an important field of drug development for two reasons. First, it is an ongoing and future public health threat with a huge unmet medical need. And also second, it has shown to be a very large, relatively undeveloped market opportunity. On the first point, we should remember this pandemic is not over. And it’s one of the biggest public health crisis the world has faced in the last 100 years, and it is still here, not just with the threat of future numerous mutations that can overcome and overwhelm vaccine and natural immunity. But also with the strain circulating now. There have been over 11 million newly reported COVID-19 cases globally in just the last seven days, predominantly from Asia and Europe, and there have been over half a million deaths globally since Omicron is detected according to the World Health Organization. Public health officials have been saying loud and clear that a simple, scalable, effective and safe therapeutic is desperately needed. On the second part, COVID therapeutic market continues to prove that it is very large. Pfizer said in its earning announcement last month that expects Paxlovid sales to be worth an enormous $22 billion for 2022. And just last month, Eli Lilly announced a supply agreement with the US government for its COVID-19 antibody for $720 million. We are firm believers in our COVID program and we think their unique mechanism of action puts us at the forefront of development in this field. To remind our audiences of our two novel oral COVID-19 programs for opaganib, our novel orally-administered first-in-class SK2 inhibitor, addressing moderately severe inpatient hospitalization, with its method of action targeting the host cell rather than working on the virus directly, we believe we can cast a wider net of efficacy against emerging variants, and Gilead will go into the details of this data later. Second, we have RHB-107, an orally-administered inhibitor of S1 family of trypsin like serine proteases being developed as a treatment for non-hospitalized COVID-19 patients. Importantly, RHB-107 is also once-daily oral pill and it’s also host-mediated, which means, that it should also potentially work against various mutations. Our recent data has shown 100% reduction in COVID-19 related hospitalization and an 88% reduction in reported new severe COVID-19 symptoms after treatment initiation. As mentioned previously, we’re seeing growing interests from potential partners for our R&D products, especially opaganib, RHB-107 and RHB-204. This slide shows our full commercial and R&D pipeline, a brief overview of RedHill for those new to the story who may be on the call today. At the top of the slide, you see the 3 FDA approved products we promote, Movantik for opioid-induced constipation, Talicia for H. pylori infection and Aemcolo for travelers’ diarrhea caused by non-invasive strains of E. coli. Our commercial products are a mix of products we develop in-house like Talicia and products brought in externally like Movantik which we got from AstraZeneca and Aemcolo which we got from Cosmo. I would note that with the pandemic receding for now in the US, we will put renewed vigor into our Aemcolo product which we think is a great product. The second part of the slide shows the multiple late-stage programs in development, addressing important unmet medical needs. We have generated lots of data with many different drug candidates in many therapeutic areas, other than the ones we’re discussing today on the call. These products include RHB-104 for Crohn’s, BEKINDA for gastroenteritis and IBS-D, and RHB-106 for bowel prep candidates. I will now turn it over to Gilead for a discussion of R&D.

Thank you, Guy. In the following slides, I will provide a brief update on some of our leading R&D programs. Opaganib is our oral pill which is a first-in-class proprietary selective sphingosine kinase 2 inhibitor. Through inhibiting this host enzyme, opaganib exerts a dual action against COVID-19, inhibiting viral replication on the one hand, and reducing the body’s excess immune response to the infection on the other hand. Given its unique mechanism of action, opaganib is currently positioned to target advanced COVID-19 infection in hospitalized patients with moderate to severe COVID-19 pneumonia. Following the promising data from the global Phase 2/3 study in hospitalized patients, we are in ongoing regulatory discussion about the path forward in multiple territories worldwide. Opaganib development is also being continued in oncology indications with cholangiocarcinoma Phase 2 top line data expected in Q2 2022. RHB-107 is our second advancing COVID-19 oral pill candidate. RHB-107 is positioned to treat early-stage mild to moderate COVID-19 infection through targeting serine proteases, which are host enzymes involved in viral replication. We recently announced positive and promising results from part A of a Phase 2/3 study in non-hospitalized symptomatic COVID-19 patients that show [technical difficulty] potential capacity to prevent deterioration with excellent safety and tolerability. Together, opaganib and RHB-107 cover the broad spectrum of COVID-19 patients from early-stage mild patients to advanced severely ill hospitalized patients. Both products are oral pills and are not affected by viral mutations to the spike protein. As such, they are both highly promising products for tackling and merging variants of concern. The importance of our products’ capacity to address new variants of concern via our mechanism of action, which is independent of the spike protein is highlighted by a recent publication in nature which claims that the lower severity of Omicron is coincidence, and that ongoing rapid antigenic evolution is likely to produce new variants that may escape immunity and be more severe. RedHill is holding two promising products that could serve as important tools in responding to future pandemic waves. RHB-204 is the most clinically-advanced standalone oral therapy in development for first-line treatment of Pulmonary tuberculous Mycobacteria – Nontuberculous Mycobacteria. The ongoing Phase 3 study is progressing and we expect enrollment in the study to pick up with the current waning in COVID-19 infections in the US. Overall, we see strong interest from the industry and potential partners in these promising R&D programs. I will highlight further details regarding each program in the next few slides. Opaganib’s clinical data package has been submitted to several regulatory agencies. Initial guidance requiring confirmatory data on past to potential approval has been received from the EU’s EMA, the US FDA and UK’s MHRA. Communication with these agencies continues. Various types of regulatory submissions and regulatory interactions are also ongoing in several additional countries worldwide. The type of regulatory submission depends on the relevant and often significantly varying regulations in each country. As a reminder, the global Phase 2/3 study met part of this pre-specified endpoints. The study showed a 70% reduction in mortality for opaganib when given on top of remdesivir and corticosteroids. Less than 7% mortality in the opaganib arm versus over 23% mortality in the placebo control arm with a p value of 0.034. Opaganib also provided a 34% benefit in time to recovery by Day 14 with a p value of 0.013. Additionally, opaganib improved the median time to viral RNA clearance by at least 4 days with a hazard ratio of 1.34 and nominal p value of 0.043. Further post hoc analyses showed a marked benefit in reducing mortality with a 62% reduction in a large subpopulation of over half of the study participants, which consisted of moderately severe hospitalized COVID-19 patients. This promising overall data in advanced hospitalized patients underscores our plans to advance developments of opaganib for treating the appropriate patient population. The accumulated data with opaganib for COVID-19 from both the US Phase 2 study and the global Phase 2/3 study point towards the moderately severe patients as an underserved patient population with high unmet need that could potentially benefit greatly from opaganib. This chart illustrates qualitatively who these moderately severe patients are. The horizontal axis shows the WHO Ordinal Disease Severity categories for hospitalized patients, and the Y axis is a Qualitative Continuous Severity Spectrum. Looking at the WHO Ordinal Scale categories, moving from category 3, which is hospitalized with no supporting oxygen to category 4, which is hospitalized with low flow oxygen support devices, to category 5 patients who are hospitalized and receiving high flow oxygen support over to category 6, which have been incubated and are mechanically ventilated. There is some overlap in actual disease severity across the disease different categories. The patients who have the potential to benefit most from opaganib those moderately severe patients who are in need of oxygen support due to the deteriorating condition, whether they are connected to low flow or high flow oxygen devices, up to a certain disease severity beyond which the benefit is likely diminished. We have identified that the fraction of inspired oxygen administered to patients, FiO2 in short, is closely related to underlying disease severity. And this measure enables us to identify the target population likely to benefit most, highlight in the chart in the light blue area. These category four or five patients have a high unmet medical need, and there is still no highly effective therapeutic treating them and represent the majority of hospitalized COVID-19 patients. Milder hospitalized patients are also likely to benefit from opaganib as a result of its antiviral activity. Given opaganib’s potential broad antiviral activity, opaganib is continuing to be developed pre-clinically in collaboration with NIH for also treating additional viral infections such as Chikungunya virus, RSV and Ebola. Previous data has indicated opaganib’s capacity to inhibit Ebola virus replication, and also Chikungunya virus replication. We are also continuing to advance opaganib’s development program in oncology and inflammatory indications with Cholangiocarcinoma Phase 2 study top line analysis expected in Q2 2022. As recently announced, RHB-107 or upamostat as we call it, provided positive top line results from Part A of the Phase 2/3 study in outpatients in the US. Part A met the primary endpoint of safety and tolerability. Moreover, Part A provided highly promising efficacy results despite its small sample size of 61 subjects. We saw a 100% reduction in COVID-19 related hospitalizations with zero out of 41 patients who were treated with RHB-107 versus 15% of patients on the placebo control arm requiring hospitalization. There was also an 88% reduction in reported new severe COVID-19 symptoms after treatment initiation. Only one RHB-107 patients out of 41 equating to 2.4% reported new severe COVID-19 symptoms. This versus 20% of patients reporting new severe COVID symptoms in the placebo control arms. Importantly, for early-stage COVID-19 infected patients RHB-107 presents a highly favorable profile. It is taken orally once a day as a standalone treatment with excellent safety and tolerability and with no major drug-drug interactions limiting its potential use. Given the promising outcomes, work is underway to complete data analysis and submit to regulatory agencies for moving into Phase 3 study. RHB-204 is the only first-line standalone oral treatment in late-stage clinical development for pulmonary NTM disease caused by Mycobacterium avium complex or MAC. A rare condition with no FDA approved first-line therapy. This underscores our focus on this program, advancing the ongoing US Phase 3 study in NTM towards potential NDA. We are expecting enrollment to pick up with the waning of COVID-19 in the US and the expansion of study participating sites. As a reminder, the study is randomized, placebo controlled and has a six months co-primary endpoint of sputum culture conversion, abbreviated SCC, and clinical benefit using patient reported outcomes. After the first six months, study subjects crossover to open label active treatment with RHB-204 for an additional 12 months from conversion in accordance with clinical practice. Of note, RHB-204 has been granted Orphan Drug designation and QIDP status, providing for expedited development, priority review of the NDA and 12 years market exclusivity from approval, underscoring significant market potential for the program. I will now turn it to Rob Jackson for an update on our commercial program.

Thank you, Gilead and good morning. Over the next few minutes, I’m going to summarize the progress we made during the fourth quarter with our sales, marketing and market access activities, so that you can all better understand why we feel increasingly confident about where our business is heading in 2022. Before I begin, I’d like to recognize the efforts of our RedHill colleagues, especially the Field Sales Team, as we all strive to deliver consistent profitable growth. Thank you everybody at RedHill for all of your contributions. During the fourth quarter, RedHill achieved record quarterly prescription volume for both Talicia and Movantik. RedHill grew Talicia prescription volume by 25.5% over third quarter, delivering 10 point improvement in quarter-on-quarter growth. Additionally, Talicia prescription volume has now surpassed [pylori] [ph] establishing Talicia the most prescribed branded H. pylori therapy in the United States. This is strong and growing evidence that payers and prescribers increasingly recognize Talicia’s ability to overcome the combined challenges of clarithromycin resistance, H. pylori regimen tolerability and diminishing efficacy, issues that first rated prescribers and patients every day, while consuming valuable healthcare resources. Simultaneously RedHill grew Movantik prescription volume by 2.4% over the third quarter, and our fourth quarter results represented our best quarterly performance with Movantik since we acquired commercial rights from AstraZeneca in first quarter of 2020. We continue to maintain overwhelming market share with Movantik and clear market leadership of the PAMORA class. Our two lead brands are well positioned to continue these performance trends into 2022. And additionally, we continue to explore opportunities to expand our portfolio and add synergistic products that complement our current salesforce focus in the Pain and GI segments. During the fourth quarter, RedHill grew Movantik volume by 2.4% over third quarter, and that fourth quarter volume represented a 9% improvement over what we achieved in first quarter of last year. We achieved this growth by continuing to take a disciplined approach in focusing on target prescribers in the Pain Specialty segment. In tandem, we also executed marketing strategies focused on growing the PAMORA market. This is a key objective for Movantik as the established market leader and we invested to raise OIC awareness with patients and prescribers and also to educate potential customers about how Movantik can provide relief from the symptoms of opioid-induced constipation. During the fourth quarter, we continue to achieve significant market access – success with key payers and we believe this will yield additional growth for Movantik during 2022. As I just mentioned, RedHill has invested to grow the PAMORA market and looking at the 12-month moving annual total of PAMORA prescriptions, the clear trend of market growth has emerged over the past two quarters. This is a significant change for the PAMORA class and it reflects RedHill’s investment in building awareness of opioid-induced constipation, an encouraging provider-patient conversations. Movantik is the clear market leader and Movantik will disproportionately benefit from more patients being treated with PAMORA agents. Recently, CDC announced draft revisions to their 2016 opioid prescribing guideline. This new guideline is expected to provide further support for opioid use in patients experiencing chronic pain. In fact, one of the reported intents of the revised guideline is to address the misapplication of the 2016 guideline. The proposed CDC guideline is currently open for public comment and CDC expects to publish their final guidance by the end of this year. It remains to be seen but the new guideline may relax some portions of the 2016 guideline resulting in a potential increase in responsible opioid prescribing and a subsequent increase in demand for PAMORA agents. So to summarize for Movantik, we continue to achieve new milestones with this brand. We had close to 115,000 prescriptions in fourth quarter of 2021. This was our best quarterly performance since we acquired the rights to this product. Movantik also maintains its competitive advantage of having best-in-class payer coverage close to 90% of insurance plans provide access for Movantik today, and since launch more than 3 million Movantik prescriptions have been dispensed. Simultaneously, Talicia continue to achieve new milestones and in fourth quarter, Talicia achieved its best ever performance in terms of prescription volume and market share. RedHill also achieved further improvements in customer access, which in turn enabled greater trial and usage of Talicia. With solid field execution, we believe these trends will continue and accelerate in 2022. In the fourth quarter, Talicia achieved 25.5% prescription growth and we’re optimistic this growth will continue into this year as recent payer wins take effect, new payer wins come to fruition and field execution continues to strengthen. Antimicrobial stewardship is a very important issue. And when the most effective antibiotics are used first-line, they provide the best chance for cure, while eliminating the need for second, third and even fourth lines of treatment. And these growing realizations are enabling Talicia to achieve record performance for weekly, monthly and quarterly volume. On the payer front, our Market Access team has continued to improve our already competitive position with commercial payers, and it’s covered in our third quarter call effective January 1st of this year, Talicia has now become available to 14 million Medi-Cal beneficiaries as a preferred brand with no restrictions. We believe this will help RedHill accelerate Talicia uptake in what is the second largest individual state for H. pylori infections and treatments. This is another sign that healthcare experts increasingly recognized, first, the challenges of clarithromycin resistance that are currently outlined by the American College of Gastroenterology’s 2017 guidelines. And second, the pitfalls of continuing to persist with using clarithromycin-based therapy as a first-line treatment choice. To summarize, Talicia continues to achieve new milestones, we had record prescription volume again driven by 25.5% growth in the fourth quarter, we surpassed pylori for the first time to become the most prescribed H. pylori agent in the United States and our coverage continues to improve including the addition of Medi-Cal Rx coverage which became effective in January of this year. We also continue to promote Aemcolo to consumers, primary care physicians in – gastroenterologists and our mid-term expectations are optimistic as international travel begins to return and we continue to explore new avenues for success with this brand. In closing, we finished the fourth quarter with a consistent trend of delivering growth for both Talicia and Movantik. As the market leader in the PAMORA class, we demonstrate our ability to continue to grow new Movantik prescriptions, prescription volume in the PAMORA class and further improve on our already strong Movantik payer coverage. We also achieved 25.5% quarter-on-quarter growth in Talicia prescription volume and became the leading branded H. pylori agent in US market. And Talicia also achieved a preferred unrestricted position on the Medi-Cal Rx formulary, which covers 14 million beneficiaries. We look forward to further growing our business during 2022. Thank you, and I’ll turn the call back to our CFO, Micha Ben Chorin.

Thank you, Rob. Good morning, good afternoon everybody. RedHill is executing on consistent growth and value creation strategy, which facilitate achieving positive contribution of our commercial operations segment for the first time in Q4, and which is expected to continue to grow in 2022 and reach profitability. We have achieved another quarterly and annual record of net revenues accompanied by reduction in cash burn, which resulted in cash balance of $54.2 million as of December 31st, 2021. All these against pandemic headwind. Net revenues were $22.1 million for the fourth quarter of 2021. The third consecutive quarter of record net revenues, attributable to an increase in revenues from both Talicia, 132% growth over previous year and Movantik. We generated an annual record of $85.8 million in net revenues for 2021. The record net revenues also contributed to an annual record of non-GAAP gross margin of 53% coupled with disciplined cost control measures across the business which we are committed to continue in 2022 resulted in quarterly reduction of $6.4 million in operating expenses in Q4, following previous reduction of $5.9 million from Q2 to Q3, signaling a path towards commercial operations profitability this year. We have signed a strategic investment agreement of up to $10 million with our South Korean Partner, Kukbo, which comes on top of the recently announced $1.5 million upfront opaganib license fee and the $2 million upfront Talicia license fee from our Emirates partner, GAG. Importantly, we are in intensive discussions for additional licensing and other business transaction – transactions, potentially totaling dozens of million dollars, which together with our continued organic and non-organic growth expected in 2022 set the stage for our financial independence in the near future. I will turn our discussion back to Dror to questions.

Happy to take questions. Thank you.

Thank you. [Operator Instructions] Your first question today comes from the line of Brandon Folkes from Cantor Fitzgerald. Please go ahead. Your line is open.

Hi, thanks for taking my question. Dan, congratulations on all the progress. Maybe just firstly on opaganib. Can you just help us characterize the size of the South Korea opportunity currently? And whether yourself or your partner is going to be required to run additional trials there? And then maybe along the similar lines you know should we expect potentially more partnerships on opaganib before running any additional trials? I’d love to just get your thoughts there. And then maybe the other side of business development. In terms of bringing in additional assets, should we think of these as commercial assets? Or would you look at earlier-stage assets as well? Thank you very much.

Thank you, Brandon. I’ll answer the last question first and then refer to Gilead. So, we are looking at commercial assets. FDA approved our focus to the US, we have 120 customer-facing salespeople and we can handle additional products and capitalize on economies of scale. So the short answer is, we are looking at commercial assets that are synergistic to our commercial basket our existing one. And we are very well positioned to complete such transactions, in-licensing transaction in the coming months. We have several ongoing, we are cautiously optimistic.

Thank you, Dror. With regards to opaganib and future regulatory approaches, we are working in multiple territories worldwide, and some of them as you mentioned in Korea, there is a partner involved and we are working collaboratively to advance regulatory approaches there. In other territories, different regulations and requirements, require different approaches and we are adjusting to each territory in order to – and approaching each territory with the required dossier and plans in order to move forward as effectively as possible in every territory.

I might add about the market in South Korea, you asked about that. We have received the market analysis from our partners, we are not authorized to share unfortunately, but it’s public information that in March alone, approximately 4 million new infections happened in South Korea and we are in mid-March. So, half a month with 4 million infections. That’s a big market and a big concern. Regarding the regulatory part, the same thing, our partner has analyzed that, they will get closely with the regulatory consultants. We are supporting that we are not authorized to see their regulatory analysis, but Kukbo, our partner are optimistic. I hope this helps.

It is very helpful. Thank you very much and congratulations on all the progress.

Thank you. [Operator Instructions] Your next question comes from the line of David Hoang from SMBC. Please go ahead. Your line is open.

Hi, thanks so much for taking the questions. I had mostly a few on the commercial portfolio. So just first you know in terms of Talicia, it’s great to see the – you know the growth in quarter-over-quarter scripts. I’m just wondering, though, in terms of translation to the bottom line, I think you know it’s about 2% quarter-over-quarter revenue growth if I – you know if I did the math correctly there. And so is that – you know, do you, I guess a few questions here. Is there any change to gross to net for the product? And then do you expect sort of this – you know this relationship to persist into 20 – you know through the bulk of 2022?

Thank you, David. This is Dror, I’ll refer this to Micha, our CFO.

Thank you, David. So Talicia is growing in increased pace, which we are very happy with. So, we set up in penetration into new prescribers all the time. And we believe that this growth that you currently see, we will continue to see and even more.

Okay, great. Maybe just you know a related follow-up question. So I know you’re not – you don’t give guidance, but in terms of you know full year 2022 and you know maybe next few years just in terms of the cadence of Talicia growth? You – you know do you expect kind of a continued linear trend? Or should we expect more you know of I guess you know an inflection as we enter the second full year of Talicia sales?

Yeah it’s a good question. A lot has to do with a pandemic, because until very recently, the pandemic’s impact on prescriptions in GI generally and specifically, H. pylori has been very negative and consistent for the last two years. We are seeing a rapid improvement in access to clinics, both for patients and also for on field sales. So we do expect rapid increase and rapid improvements that will be constant. That said, perhaps our Chief Commercial Officer, Rick Scruggs would like to add some color.

Thanks, Dror. It’s a good question. We have seen in the past you know the effects of the pandemic and our ability to see healthcare providers, we have addressed that, we have initiated and created a new department in our company, it’s Customer Engagement Specialist, and they reach out to physicians who now like to be seen via video, maybe not necessarily in person. So this group is out there working with physicians in the new modality they like to be called upon. And as you’ve seen by our nice growth in fourth quarter, we’re now the number one prescribe branded product in the category and we’re moving to teach physicians, to teach healthcare providers that Talicia is the best choice. It’s better than anything that’s available to treat H. pylori. So we’re going to see that, we’ve seen the growth now in first quarter and we anticipate to have a really good year with Talicia in 2022 and beyond.

Okay, I appreciate that. And then maybe you know one last one if I may and changing the topic here to the NTM RHB-204 study. In terms of the – you know the endpoint there, I know it’s the six month sputum culture conversion. Is that – you know is that sufficient to gain a full approval there or do you expect accelerated approval with the need to do a confirmatory study down the line?

Thanks, David. We would like to add a couple of sentences about the previous question. And then I’ll refer to Gilead for the question about 204 for NTM. Micha, please.

Hi, David this is again, Micha here. Just wanted to add with respect to your previous question, that we saw a growth of 17% on Talicia revenues between Q4 and Q3 of this year, which is substantial.

Thank you. Regarding NTM and the study, yes, you’re correct, we expect the primary endpoint at six months, where we’re looking at sputum culture conversion and a co-primary of patient reported outcomes to potentially support accelerated approval. We’ve continued evaluation of the longer-term treatment of up to 12 months post-conversion to eventually support the full dossier.

Okay. Thanks for taking the questions.

Thank you.

Thank you. [Operator Instructions] Your next question comes from the line of Boobalan Pachaiyappa [sic - Boobalan Pachaiyappan] from H.C. Wainwright. Please go ahead. Your line is open.

Hi, this is Boobalan. Thanks for taking my questions and congrats on all the great progress. So few from us. Firstly, with respect to opaganib for COVID-19, have you conducted any European-based market research study regarding potential positioning of opaganib?

Thank you. We see COVID-19 as a global evolving pandemic highly dynamic. And we’re doing market research and evaluations across the various territories. Our Phase 2/3 study was global and we are approaching markets and regulators on a global basis. We do expect the market for COVID-19 worldwide to continue to be highly requiring new therapies. And as we see the emerging expected revenues of products that have been used and received emergency uses or approvals in this market, we see these very, very high and growing and we anticipate that to continue.

Might add, Boobalan and thank you for the question. That if we look at the data from the last couple of weeks, we’re seeing very high numbers and rapidly increasing actually in Germany, in France, in the UK, many other countries. So, this is not going away unfortunately. And with BA.2 and future variants, this is likely to remain a very significant medical need and the resulting commercial market.

Thanks for the color. With respect to RHB-107 for COVID obviously. So the Phase 2 data is pretty intriguing. So, what are your preliminary thoughts regarding the Phase 3 study design? And will you consider including an active comparator drug in your future Phase 3?

Thank you. Yes, we are still in the process of completing the analysis of Part A, which as you mentioned and we disclosed, provided highly promising results despite being a small study in terms of the efficacy that is obtained. We are planning next steps and evaluating the next steps with FDA. We will approach FDA, present the full data and agree with them on next steps. We see the next steps to continue studying the product in a large study in non-hospitalized patients with mild-to-moderate symptoms. And we expect to be able to replicate the very promising results. And given the very attractive profile of upamostat we think this could be a very important tool in treating the mild-to-moderate patients with COVID-19.

As an add-on on the same topic. Are you open to partner – partnering for the Phase 3 trial or future Phase 3 trial? Are you planning to go solo?

Yes, we are having discussions. The strong results that were achieved in the study attracted a lot of attention. And this is not only from potential pharma partners, this is also government and other grants. So, when it comes to a large Phase 3, which we are confident about, we are confident it will be funded by external sources, be it industry or other.

Switching gears a little bit. Can you help frame the expectations for your upcoming cholangiocarcinoma study readout which is expected in second quarter and what kind of efficacy signals would generate investor confidence in this program?

Thank you. We have already disclosed that we have observed a signal of activity with patients which are very advanced after two lines of failing therapy in cholangiocarcinoma with nothing available to them. And this is a very promising signal of activity. We will complete analysis over the coming months and present the data and based on that, we will consider next steps – possibly refining the patient population targets using biomarkers is a very possible path. But again, overall, the clinicians who are very familiar with these dire condition of patients are optimistic that the signal is an important one for continuing developments of the program.

Right. One final from me if I may. How do you expect the R&D cost evolve for the remaining – for the year 2022?

So as can be seen in our press release from today, we are targeting a cost reduction program, in which, we will enhance contribution and profitability to the maximum extent possible. So, we are expecting relatively a low investment in research and development during this year 2022.

All right. Thanks so much for taking my questions.

Thank you. I will now hand the call back to you.

Thank you, Sharon and thanks everybody for joining the call. Please reach out to us if you have any additional questions. Keep safe and have a pleasant day.

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