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spk03: Good morning and welcome to the NCISE Biosciences, Inc. Corporate Update Call. As a reminder, this conference is being recorded. Your hosts today are Dr. Lynn Kirkpatrick, Chief Executive Officer, Dr. Nylee Osman, Chief Medical Officer, and Dave Humphrey, Chief Financial Officer. Before we begin the formal presentation, I would like to remind everyone that statements made on the call and webcast may include predictions, estimates, or other information that might be considered forward-looking. While these forward-looking statements represent our current judgment on what the future holds, they are subject to risks and uncertainties that could cause actual results to differ materially. You are cautioned not to place undue reliance on these forward-looking statements, which reflect our opinions only as of the date of this presentation. Please keep in mind that we are not obligating ourselves to revise or publicly release the results of any revision to these forward-looking statements in light of new information or future events. Throughout today's discussion, we will attempt to present some important factors relating to our business that may affect our predictions. You should also review our most recent forms, 10Q and 10K, for a more complete discussion of these factors and other risks, particularly under the heading Risk Factors. At this time, I would like to turn the call over to our Chief Executive Officer, Dr. Lynn Kirkpatrick. Lynn, you may begin.
spk02: Thank you, Operator, and good morning, everyone. Thank you for joining us. I am pleased to welcome you to our Corporate Update Conference Call. Before I begin, I want to direct your attention to the slide deck posted and accessible on our Investor Relations website at irncise.com. This slide deck is our latest investor presentation, inclusive of the recently released clinical data from the PF614-102 and PF614 MPAR 101 studies, which we're very eager to review with you in detail this morning. Additionally, we posted our second quarter financial results and filed our 10-2, both of which are also available on our website. Now, some of you are familiar with NCIS, but as I have historically kicked off these calls, I would like to spend just a few minutes reviewing our technical platforms and overall company for those of you new to our event. First, we are a clinical stage biotech company using sophisticated chemistry to improve drug safety and performance. Our technologies, TAP and MPAR, are designed to improve delivery and reduce abuse and overdose of prescription drugs with a goal of creating new classes of prescription medicines that are intended to be powerful and safe. Our focus is to initially utilize our transformative technologies to address the ongoing opioid crisis. We have applied our chemical approach to a number of opioid therapies, and our lead program is an oxycodone product to replace OxyContin in the marketplace. Our lead agent, PF614, has received fast-track status from the FDA, and we have pursued bioequivalence data for PF614. Importantly, we believe... Bioequivalence provides a shortened path to registration through the 505 regulatory process. For those of unfamiliar, bioequivalence is the comparison of two dosage forms or active ingredients showing that they provide similar blood concentration levels, therefore resulting in the same therapeutic effect. Our technologies have over 100 patents issued in 25 countries, are supported by over $100 million in investment since our inception, and we have been advancing our lead products through clinical development and exploring other means of applying our technologies, including for ADHD and opioid use disorder indications. Additionally, we've built a strong team to assist in our clinical and development progress. Before I turn the call over to Dr. Osman to run through our recently reported clinical data, I want to review our two technology platforms in detail. This will be helpful background as we review the clinical trial results. For those following along in the slide deck, I would like to turn your attention to slide five. The first technology, TAP, stands for Trypsin-Activated Abuse Protection. TAP is a chemical modification creating what is called a prodrug that inactivates the drug in NCISIS products until they reach the small intestine, including our lead agent, PF614. Trypsin is a digestive enzyme that is only active in the small intestine. trypsin activates or turns on the release of the active ingredient in our drug products. Therefore, we believe our chemical modification protects from types of abuse such as snorting or injecting, provides resistance to manipulation of our products, commonly called kitchen chemistry, and is meant to reduce other forms of recreational drug abuse. Our second technology platform, MPAR, stands for Multi-Pill Abuse Resistance. MPAR is a smart overdose protection designed to be combined with our top pro drugs to prevent patients or abusers from overdosing. MPAR turns off the release of the active ingredients in an overdose situation. This protection from oral overdose is designed to activate only when more than the prescribed dose is taken. Importantly, we believe that applying our technologies to opioids does not limit the ability of our products to provide a high degree of pain relief for those in severe pain. Now for the primary purpose of our call today. While later we will touch on financial results from the week's earnings release, I now turn the call over to Nylee to allow her to take this opportunity to review the recently reported data from our PF614-102 clinical study. Dr. Osman is our chief medical officer. She is a highly versatile board-certified neurologist, migraine and pain specialist with over 10 years of experience in both R&D and medical affairs, within the pharmaceutical, CRO, and medical device industries. Nylee, the floor is yours.
spk05: Thank you, Lynn.
spk06: It's wonderful to be here this morning to discuss the progress we have achieved against our goals. I will begin with slide 13 that illustrates the 102 study for PF614, which we recently reported positive results for. This was a two-part study. The initial multi-ascending dose or MAD study evaluated the pharmacokinetics and safety of twice daily oral dosing of PS614 compared to similar doses of OxyContin in healthy subjects. The second part of the study examined single oral doses of PS614 compared to OxyContin for bioequivalent, again, in healthy adult subjects. In the initial part of the MAD study, Groups of healthy male and female subjects were randomized three to one to receive either PF614 or OxyContin, twice daily for five days at three different dose levels. The PF614 doses which were selected were 50 mg, 100 mg, and 200 mg. These doses of PF614 have been determined from our Phase I work to correspond to equivalent OxyContin doses of 20 mg, 40 mg, and 80 mg. The endpoints of the mass study were safety and the pharmacokinetics of released oxycodone or PF614. Most importantly, in any clinical trial, the safety signal was excellent in that there were limited treatment emergent adverse events, meaning potential side effects from the administration of either PF614 or OxyContin. These events were similar in both treatment groups at each dose level. Mainly, we observed opioid-related events such as nausea, vomiting, headaches, dizziness, and constipation. The pharmacokinetic data confirmed what we had observed in our Phase I single ascending dose study and provided support for the dosing for Part II, which was the bioequivalent study. As reported in July, the bioequivalent study compared the pharmacokinetic release of oxycodone from PF614 compared to OxyContin ER. which proved positive under both fasted and fed conditions. This study enrolled 60 healthy male and female subjects with 57 completers who were administered PF614, 100 mg, or our test article, or OxyContin, 40 mg, the reference article, orally under both fasted conditions and after high-fat meal. The analysis for bioequivalency was based on the FDA regulations of a 90% confidence interval for the geometric mean ratio for the area under the curve of blood concentration versus time and Cmax or maximal blood concentration of the oxycodone concentrations. These measures must be contained entirely within the common bioequivalency range of 80% to 125%. The following conditions were evaluated. PF614 fasted versus oxycontin fasted and PF614-FED versus OxyContin-FED. Both these conditions were shown to fall within this 80 to 125% limit of bioequivalence. The comparison of CMAX and the area under the curve are illustrated here on slides 18 and 19. The food effects evaluation between PF614-FED and FASFED was also compared in the bioequivalency study. and the area under the curve was also found to fall within the confidence interval for bioequivalence. This finding suggests no statistical difference in the oxycodone level when PF614 is taken with or without food. This could be clinically meaningful, since many individuals in severe pain may be required to be fasted for surgical procedures or may lack an appetite, so thus making it difficult to effectively take oral medications with food. It is important to note that this study also compared safety and pharmacokinetic properties of PF614 and OxyContin. We believe this data may allow us to substitute PF614 directly for OxyContin to provide exquisite pain relief, but PF614 also has a number of advantages over OxyContin. These advantages include PF614's robust chemical stability, PF614 does not convert to Oxycodone if injected, Chewing or crushing of PS614 does not increase exposure to oxycodone, and PS614 abuse deterrent properties are retained even if it's dissolved in water, which can allow for easier oral administration for individuals who may be experiencing symptoms of dysphagia. In summary, we have explored how PS614 delivers oxycodone and compared it to the marketed product OxyContin in healthy subjects. In the first part of the study, we were able to determine dose levels of PF614 that are essentially equivalent to OxyContin. And in the second part of the study, we used a larger group of healthy volunteers to show that both PF614 and OxyContin had no difference in the safety profile or the amounts of Oxycodone delivered. Hence, we believe the pain relief experienced by patients in the two products will be very similar. While at the same time, PF614 has the potential for superior abuse deterrent properties than currently marketed products. These positive results also allow us to pursue the 505B2 pathway for FDA approval, which is meant to be shorter and less costly. I will now turn the call back over to Lynn. Thank you.
spk02: Thank you, Nylee. I want to reiterate how pleased we are with the positive bioequivalence data. I would now like to outline the additional clinical data we reported in May about our overdose protection product, PF614-MPAR. This data is from the Phase I PF614-MPAR-101 study, which is evaluating our MPAR oral overdose protection technology. PF614-MPAR is a combination of PF614 and nifamistat, a trypsin inhibitor, a combination designed to provide both abuse and overdose protection. We believe our approach is unique in the industry. The pharmacokinetic data reported has been obtained from groups of six to eight healthy male and female subjects receiving PF614 or a combination of PF614 and nifamistat, in what we believe would be a simulated overdose combination. The initial pharmacokinetic data which had been reported for this study is shown on slide 25. On the left, the blood levels of oxycodone released from PF614 when administered alone are shown in blue. When PF614 and nifamistat are combined to simulate an overdose situation where Nephamistat should block the trypsin activation of PF614 resulting in less oxycodone release. The oxycodone blood levels are shown in green. This data demonstrates a 47% reduction in the oxycodone maximal blood concentration due to Nephamistat inhibition of the trypsin activation of PF614. This confirms the approach to prevent overdose is feasible. The figure on the right shows the corresponding blood concentrations of PF614 itself. When administered alone, the majority of PF614 is converted to oxycodone with little parent prodrug absorbed into the blood unchanged, which is shown on the right-hand side, the blue line. While in the overdose simulation, the nifamistat prevents activation of PF614, and more unchanged drug is absorbed, as illustrated with the green line. It's important to note from this that PF614 absorbed directly into the blood is not converted to oxycodone, showing that attempts to abuse PF614 by direct injection will be unsuccessful. We are continuing to examine various combinations of PF614 with Nifamistat prepared with different release profiles in this study. The final data from this part of the study is expected in the fourth quarter of this year and will allow us to define a drug product and test the concept of increasing doses of PF614 MPAR in the final part three of the study through 2023. designed to show how MPAR can control oxycodone release and provide overdose protection. We're extremely pleased with this data, as the MPAR combination technology is the first approach that we expect may prevent all four forms of abuse, injecting, chewing, inhaling or snorting, and oral overdose. As mentioned, additional data is expected by fourth quarter of this year that will aid the design of continued studies for PF614 MPAR into 2023. Along with our current clinical study of PF614, our TAP opioid with abuse protection, this study of PF614 MPAR with added oral overdose protection will enhance our dual-pronged approach to provide safer solutions to patients and prescribers. A federal grant from the National Institute on Drug Abuse supports completion of this clinical study. We were recently awarded $2.8 million for a fourth year of funding under this grant, bringing the total award to over $10 million. Finally, a Human Abuse Potential or HAP study to evaluate PF614 for potential abuse by the nasal route, in other words, snorting, has completed the clinical portion and we are awaiting final results. We are also initiating an oral HAP study to begin in September of this year. These HAP studies will be key for our gaining abuse deterrent labeling for PF614. The studies will help us understand the tendencies for drug abusers to like the effects achieved after taking PF614 either orally or nasally as compared to that of similar products, for example, crushed OxyContin. Looking ahead, the milestones for the remainder of the year are summarized as follows. Human abuse potential nasal study data of the PF614-103 trial are expected by the end of third quarter. We also expect to begin the oral HAP study, PF614-104, in the third quarter and provide data by late first quarter in 2023. We expect full data from the PF614 MPAR 101 Part 2 to be reported in the fourth quarter of 2022 and data from the final Part 3 of the study in the first half of next year. I now welcome our CFO, Dave Humphrey for a short financial summary. Dave?
spk01: Thanks, Lynn. Before we take questions, I want to briefly summarize our financial status. As we reported last week, we recently closed on a financing of $8 million before fees, which adds to the $15 million in financing we completed at the end of 2021. We have approximately $3 million in non-dilutive government grant funding left to support our OUD research program. And as Lynn mentioned, in July, we were awarded another $2.8 million of non-diluted grant funding to support completion of the MPAR clinical study. With our June 30th cash balance of $3.7 million, the recently completed $8 million financing, and continuing grant funding, we are on track to advance the clinical development of our highly unique TAP and MPAR technologies through the end of the year. I will now turn the call back to Lynn for closing remarks and questions.
spk02: Thanks, Dave. Before I turn the call back over to the operator for Q&A, I want to take a moment and acknowledge all our public company constituents as we forge ahead on our mission. The clinical progress we highlighted today are the building blocks that enable our platforms to fully support our mission of developing a unique pipeline of safer pain products and helping millions who experience severe pain. Operator, we will now take questions.
spk03: At this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation symbol will indicate your line is in the question queue. You may press star 2 to remove your question from the queue. For participants using speaker equipment, it may be necessary for you to pick up your handset before pressing the star keys. One moment while we poll for questions. Our first question comes from the line of Thomas Lattin with Lake Street Capital Markets. You may proceed with your question.
spk00: Hey, everybody. Thanks for taking the questions. Just a quick one on the bioequivalence data. I was just curious to get – I know TMAX isn't typically included in the bioequivalence measures, but just curious if you could comment on the delta between Oxy and PF614. Nylee?
spk06: My apologies, I was speaking while the line was muted. I'm sorry, Thomas, could you please repeat your question for a second?
spk00: Sure. I know TMAX isn't typically included in a bioequivalence analysis for approval, but there was a pretty substantial delta between 614 and Oxy. I was curious if you could comment on that, whether that's purely from design or if there was something else playing a part in that in the longer TMAX for 614.
spk06: Thank you so much. That's a very good question. You're absolutely right. It's not included in the bioequivalency. There was a TMAX, and we will look at this a bit more closely in follow-up studies, and we are still analyzing that. But as it stands right now, the bioequivalency data, as Lynn and I both discussed, meets the FDA requirements and falls within the range. Lynn, did you want to add anything more to that?
spk02: Yeah, Thomas, your comment that there's a big delta, I think you might mean the half-life. Our Tmax for both PF614 and OxyContin, meeting the time to reach the maximum concentration, were approximately four to six hours. Our half-life, however, is much longer, which is why we believe PF614 can be prescribed twice a day, while OxyContin, although it's prescribed twice a day, it doesn't last twice a day. Our half-life was 12 hours in OxyContin. Generally, in our studies, we've measured that between four and seven hours.
spk00: And as you kind of look ahead through the milestones, obviously the upcoming meeting with the FDA to clarify a number of things Do you have a sense of when that meeting might actually take place other than kind of more broadly next year? Because you'll still have data coming out in the first quarter, right, which I'm assuming you're going to wait for on the human abuse liability or potential study.
spk06: Yes, we have. Sorry, it's Nyle again. Lynn, did you want to take that or would you like me to speak to it?
spk02: I was just going to comment that we are gearing for a meeting in probably the early second half of next year. as defined as our end of phase two study. And obviously, by that time, we will have both of our human abuse liability studies defined, and we're working towards that goal, both with not only our clinical data, but obviously our manufacturing will need to be included with that.
spk00: And then finally, I was wondering if you could share some thoughts on what you think a design of a pivotal study might look like at this point, number of patients, et cetera.
spk06: Yes, so we are exploring options for a pivotal study. It would be a larger study, as I'm sure you would know, and the indication within the pain space that we would pursue, whether it be chronic or acute, that's something that's part of our ongoing discussions with the FDA. So I cannot comment at this point on the specifics because we have reached out to the FDA with questions, and we will discuss those with them. to design the study, but it would be a very, a much larger study than the current studies that we have, and indicated to a specific pain indication, acute versus chronic. Lynn, did you want to add anything additional to that?
spk02: Yeah, the only direction we've had from the agency to date, and as Nyle indicated, we are still awaiting feedback from our initial questions that we provided earlier this year. For a longer study, we would anticipate up to 1,500 subjects. And for chronic use, we'd have approximately 100 individuals on. But as Nylee indicated, we're in discussions as to what indication we'll go forward with. So we can't really give you direct answers. Thomas, sorry.
spk00: No, no, no worries. I appreciate you taking the questions. Thank you.
spk03: Ladies and gentlemen, we have reached the end of today's question and answer session. I would like to turn this call back over to Dr. Lynn Kirkpatrick for closing remarks.
spk02: Thanks, operator, and thanks, Thomas, for your questions. As we progress, there is increasingly more to discuss on our corporate update calls, and we look forward to this cadence continuing as we close out the second half of 2022. I wish everyone a lovely remainder of the summer. and look forward to speaking with and updating you on our additional progress very soon. Thank you.
spk03: This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. Enjoy the rest of your day.
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