Protalix BioTherapeutics, Inc. (PLX) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and welcome to the Protalix BioTherapeutics Conference Call regarding the clinical development of PRX-102 for the treatment of Fabry disease. As a reminder, this conference call is being recorded. I will now turn the conference over to our host, Mr. Chuck Padala of LifeSci Advisors, Investor Relations. You may begin your conference.

All right. Thank you, Rob. Welcome to the Protalix Conference Call regarding the clinical development of PRX-102 for the treatment of Fabry disease. With me today are Dror Bashan, President and CEO of Protalix; and Eyal Rubin, Chief Financial Officer. Mr. Bashan and Mr. Rubin are joined today by Mr. Ulrich Granzer, PhD, of Granzer Regulatory Consulting & Services. The agency provides Protalix and Chiesi with consulting services related to drug development and regulatory affairs. Dr. Granzer is a founding member of the German Association of Regulatory Affairs, where he is the current President of the Board and Co-Founder of the European Union Regulatory Affairs Group and a member of the Drug Information Association. He also has long-standing relationships with industry associations and senior colleagues within the pharmaceutical industry. A press release providing a regulatory update and announce of the top line results from the interim analysis of the Phase III BALANCE clinical trial was issued this morning and is available now on the Protalix website. Please take a moment to read the disclaimer about forward-looking statements in the press release. The press release and the teleconference include forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially from these statements made. Factors that could cause the actual results to differ are described in the disclaimer and Protalix' filing with the U.S. Securities and Exchange Commission. I will now turn the call over to Mr. Dror Bashan. Dror?

Thank you, Chuck, and thank you, everybody, for joining today's clinical development update call for PRX-102 and a special thanks to Dr. Ulrich Granzer, who is joining us today. As a reminder to everyone on this call, we currently have 3 ongoing clinical studies. The pivotal Phase III BALANCE trial and 2 long-term extension studies, which are part of the overall clinical development of PRX-102 for the proposed treatment of Fabry disease. Our BALANCE study is a 24-month randomized, double-blind, active control study of PRX-102 in Fabry patients with impaired renal function designed to evaluate the safety and efficacy of 1 milligram per kilogram of PRX-102 dosed every 2 weeks compared to agalsidase beta, and the study enrolled 78 patients who were randomized on a 2:1 scheme. The BALANCE study is ongoing and assignment to treat arm remains blinded. Unblinded final data is anticipated to be released in the second quarter of 2022, after all remaining patients have completed the 24-month treatment period. The primary endpoint of the interim analysis is the comparison of mean annualized changes, which is the slope of the eGFR after completion of at least 12 months of treatment between the 2 treatment arms. The interim efficacy analysis was conducted on 2 pre-defined analysis set. The first set is Intention to Treat, ITT, which consists of all randomized patients who received at least one dose, in this case, 77 patients. The Intent to Treat analysis is the primary analysis for this interim review. The second set, the Per Protocol, PP, consists of all patients who completed at least 12 months of treatment with no major protocol violations, and in this case, 74 patients. The patient's population, the ITT analysis set of the study is comprised of 47 males, which is 61% and 30 females, 39%, with a mean age of 44.3 years. The initial top line results show that the lower boundary of the confidence interval for the mean difference between the 2 treatments was below the noninferiority margins pre-specified for this interim analysis in the ITT analysis set. The main difference between the 2 treatments was above such limit in the PP analysis set. At the time of this analysis, 2 patients discontinued participation due to treatment-emergent adverse events. One of those 2 patients was discontinued participation due to related adverse events. No deaths were registered. Overall, safety data appears favorable and consistent with what was observed in previous clinical study with PRX-102. Based on the interim analysis of the 12-month data generated from the BALANCE study, and in combination with the previously reported positive data from the Phase III BRIGHT and BRIDGE clinical trials of PRX-102, we, together with our development and commercialization partner, Chiesi Global Rare Diseases, intend to submit a marketing authorization application to the European Medicine agency for the review of PRX-102 for the proposed treatment of Fabry disease. We will be taking questions at the end of this call. However, if the BALANCE study is a double-blind, we are unable to provide more information regarding the unblinded. Final data, which is expected in the second quarter of 2022, after all remaining patients have completed the full 24 months treatment. I would now would like to introduce Dr. Ulrich Granzer of Granzer Regulatory Consulting & Services, consultants to Protalix. Dr. Granzer has founded the agency close to 2 decades ago, and he currently employs 40 people with focus of all aspects of drug development and regulatory affairs and with a special consideration of orphan drugs. Prior to founding the agency, Dr. Ulrich held various roles at Glaxo Wellcome, BASF Pharma, Knoll including as Vice President, Global Regulatory Centres and Bayer as a VP Global Regulatory Affairs. Granzer has worked on more than 250 new molecular entities, performed more than 300 Orphan Drug Designation in the U.S. and EU and are involved in more than 200 scientific advice meetings with the EMA, FDA and other regulatory authorities every year. Please.

Thank you very much, Dror. We have been involved with Protalix and its PRX-102 clinical development program for a number of years and have been involved in each of the BRIDGE, BRIGHT and BALANCE studies, including with respect to regulatory interactions for the programs such as applications for Orphan Drug Designation, amendments to the Pediatric Investigation Plan and others. Our primary role in the PRX-102 program relates to regulatory affairs. Currently, we are participating in the preparation of the marketing authorization application filed for submission to the European Medicines Agency. In addition, we are participating in the preparation of materials for the anticipated Type-A meeting with the U.S. Food and Drug Administration. When reviewing MAA, the EMA generally looks not only for the primary endpoint, but more importantly, the EMA looks at the totality of the data and the totality of the evidence presented in the application, including those generated from additional relevant clinical studies. For rare diseases, this is of particular importance. We, therefore, can expect the EMA to take a holistic view on the data taking into full consideration all relevant endpoints such as safety, immunogenicity and secondary efficacy parameters as well as endpoints of both the BRIDGE and the BRIGHT clinical studies. With this approach, the regulators ensure that in their review or relevant clinical data is fully taken into account. Dror, please?

Thank you, Ulrich. Protalix look forward to submission of the MAA to the EMA for the European Union anticipated towards the end of 2021 and to continuing to work with the FDA towards approval in the United States. These regulatory milestones are currently our primary focus. The BALANCE study continues as planned through its 24-month treatment duration to support its final analysis. Based on the entire clinical development program, which includes the BRIGHT and the BRIDGE studies, we believe that PRX-102 has the potential to become an important treatment option for both male and female Fabry patients and that the BRIGHT and the BRIDGE studies have been completed, and these studies met the defined endpoints. In addition to the BALANCE study, the PRX-102 clinical program currently includes extension study for patients who completed the BRIDGE, BRIGHT and BALANCE studies, as well as the Phase I/II clinical trial of PRX-102. Currently, more than 100 patients who participated in such studies continue to be treated in the extension studies, and additional patients completing the BALANCE study are expected to join the extension study. Also, Chiesi is providing PRX-102 to Fabry patients in the United States through the U.S. expanded access program. Regarding the regulatory process in the U.S., Protalix and Chiesi plan to submit a Type-A meeting request with the FDA to discuss the path for approval of PRX-102 in the United States. We expect that this meeting will take place in the third quarter of 2021. We remain focused on advancing PRX-102 through the clinical development process in hope to provide additional treatment options to the Fabry patients. Once again, I would like to emphasize that the BALANCE study is a double-blind trial and as per an agreement with the FDA, there are limitations on the disclosure of specific details regarding the BALANCE study beyond those shared with you in the press release and on this call. In addition, and very importantly, I ask to emphasize that following the last fundraising, Protalix has sufficient means to repay the debt in full and continue to working, maturing the potential of PRX-102. I would like to turn the call over the operator and see if there are any questions from the audience.

[Operator Instructions] Our first question is from the line of John Vandermosten with Zacks.

On the -- regarding the Type-A meeting, what's left to complete before you make that request with the FDA to get that set up?

So John, thank you for the question. Actually, what we are doing now. We are working on the briefing book, we are now putting together all the analysis in order to be prepared for the Type-A meeting.

Okay. I guess I was just wondering if there's any consultants that need to be consulted to put together specific analyses or any other work that has to be done. Is there anything specific like that, that needs to be accomplished?

We do what is -- what we think together with Chiesi and Granzer to be as ready as possible and be -- conduct the Type-A meeting successfully.

Okay. Yes, we're keeping an eye on for that. And second question is on the results. So when you're doing your initial statistical analysis or assessment of how to design the trial. So relative to those expectations, where did that fall below the non-inferiority line come from? Was it number of participants in the trial? Or was it, I guess, the mean -- the expected mean difference between the two populations?

John, as we mentioned earlier, it was not just to make a view on the check box. We cannot -- we are -- this study is blinded. So we cannot reveal anything more than what we have said so far. Once the study will be completed, 24 months of all patients will be completed, we will share the full analysis and outcomes, of course.

[Operator Instructions] At this time, we will hand the call back to management for closing remarks.

Thank you, Rob. So thank you all for joining our clinical update call today. We look forward to working closely with the regulatory agencies in the U.S. and Europe to advance PRX-102 for adult Fabry patients and bring this important product to commercialization. We are excited about continuing to advance our pipeline and build shareholders value in the company for the long-term success, and we look forward to updating you as developments evolve. Thank you.

Thank you to everyone joining us today. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.