Q4 2020 Matinas BioPharma Holdings Inc Earnings Call
Hello, and welcome to the mid teens, Biopharma fourth quarter and full year 2020 results conference call. At this time, all participants are in a listen only mode.
And answer session will follow the formal presentation. As a reminder, this conference is being recorded I would now like to turn the conference over to Peter Bozzo Investor Relations representative from Athena as Biopharma, Peter you may begin.
Thank you Kevin Good morning, everyone and thank you for joining the <unk> Biopharma fourth quarter and full year 2020 results Conference call earlier. This morning, we issued a press release with our financial results along with business updates. The release is available on the but he and his biopharma website under the investors section speaking on today's call will be Jerry G bore.
Chief Executive Officer, who will discuss the company's corporate progress and key milestones and Dr. Terry Ferguson, Chief Medical Officer, who will discuss on the diesel and Dr. Raphael Mannino, Chief Scientific officer, who will provide an overview of our LNC platform delivery technology and Dr. Terry Mcevoy, Chief Development Officer, who will provide an.
And on our LNC platform programs with map 22, both rate and 22, and and Matt 20, 501, and Keith Kucinski, Chief Financial Officer will then review, our fourth quarter and full year 2020 financial results. We also we also have Doctor Kuwait Lu Chief Technology officer available to answer questions during the Q&A.
At this time I would like to remind our listeners that remarks made during this call may state management's intentions hopes beliefs expectations or projections of the future. These are forward looking statements and providing and involve risks and uncertainties forward looking statements on this call or me.
Pursuant to the Safe Harbor provisions of Federal Securities Laws. These forward looking statements are based on <unk> Biopharma is current expectations and actual results could differ materially as a result, you should place under it and you should not place undue reliance on a day forward looking statements.
Some of the factors that could cause actual results to differ materially on and those contemplated by such forward looking statements are discussed and the periodic reports and the Chinas Biopharma files with the SEC. These documents are available on the investors section of the company's website and on the SEC's website and archive of this call will be posted on the company's website.
And the Investor Relations section following the company's prepared remarks, we will open the call for question and answer session I will now turn the call over here.
Thank you Peter Good morning, everyone and thank you for taking the time to join US today as we provide a business update and discuss our 2020 fourth quarter and full year results.
2020 was a year of significant progress and timely execution from a teen us despite the ongoing global pandemic.
Under the most challenging of circumstances, our company remained focused on our strategic objectives and took all necessary and appropriate steps to place patient and caregiver safety and wellbeing above all else, while ensuring that we were able to advance our clinical stage assets in multiple clinical trials.
And looking back across 'twenty, and 'twenty I could not be prouder of our accomplishments and with key results now in hand, and several key upcoming catalysts and milestones in 2020. One we are excited and for what lies ahead.
The completion of our head to head enhance it trial of lip diesel versus Vascepa was a major milestone and form a teen us and we believe that the results support the potential for lip DSO to demonstrate a superior cardio protective effect to vascepa.
Following a close review of the data and discussion with our valued scientific Advisory Board, we believe that securing a global partner for the continued development uplift day. So represents the best course of action for this promising next generation prescription Omega three we are formally launched a process with a well respected firm and we will take.
The opportunity over the next few months to identify and potentially secure the right partner for lip diesel moving forward.
This process now provides us the opportunity as we move forward to refocus our internal expertise and resources on our LNC platform delivery technology.
We believe that the unique ability of our LNC formulations to mimic envelope to viruses and efficiently deliver small and larger molecules intracellular really without causing adverse immune responses or damage to cellular membranes.
Th our technology from any other available intracellular delivery technology being applied today Dr.
Dr. Mannino will have more on this and a few minutes.
Although lip DSO had taken center stage from the past few years, we have made significant progress, especially over the last year with our LNC platform, both with our own drug candidates and with promising collaborations with some of the world's leading pharmaceutical companies.
Cause of this progress we believe that our LNC platform will provide important additional preclinical and clinical data during 2020, one and clearly demonstrate how it can be and important and potentially superior solution for delivery challenges that other technologies like lipid nanoparticles and viral vectors cannot.
And <unk>.
There are three key areas, which highlight the tangible progress of the LNC platform first.
First.
Data safety monitoring review and cohort progression and the enact study of map 22, or three and Cryptococcal meningitis is anticipated in the third quarter of 2021 and provides a near term opportunity to further validate the LNC platform and highlight its ability to facilitate oral bioavailability.
And then Carrie molecules effectively across the blood brain barrier and combating deadly invasive fungal infections.
Second with the financial support up and validation from the cystic fibrosis Foundation, we are rapidly advancing our second LNC platform drug Matt twenty-five all want oral amikacin into preclinical toxicology and efficacy studies with the ultimate goal of developing the first oral aminoglycoside.
For the treatment of non tuberculous mycobacteria lung infections as well as Gram negative bacterial infections and finally, we continue to make important progress and expanding the utilization of the LNG platform through our collaborations with Genentech and with the National Institute of allergy and infectious diseases and Cree.
<unk> and oral formulation of Gilead Ramdev severe in fact genentech extended its collaboration with mid teen S. For another two years. This past November and we recently sent and I D multiple potential oral formulations of room debt severe to begin evaluation and various COVID-19 in vitro.
Models.
We are also evaluating additional opportunities to expand application of our LNC platform and other innovative areas, such as messenger RNA and gene therapy and.
As I look back on 2020 I am pleased with all that we were able to accomplish and law.
Looking forward to 2021 and beyond I see a more focused organization centering our attention and resources on our LNC platform.
Unlike lipid nanoparticles and viral vectors, where multiple companies are working and crowded competitive environments. No. Other company is working with phospholipid based lipid nano crystals, we have taken significant additional steps to protect and grow the intellectual property estate surrounding the LNC platform.
With 24 patents issued within the last five years.
And we look forward to continuing to advance our LNC based drug candidates and expanding the utilization of this exciting technology to innovative areas of medicine during 2021 and beyond I would now like to turn the call over to Dr. Terry Ferguson to provide comments on lip DSO, including a review of the data from enhance it and.
And next steps for this potential best in class prescription Omega three therapy.
Thanks, Gerry and good morning, everyone.
In February of 2021, we announced top line results from enhanced it a second randomized parallel group crossover head to head study of diesel versus vascepa directly comparing their effectiveness and reducing triglycerides and their effects on other important lipid markers.
And their effects on blood levels of Iqos, depending on what gas for EPA and other Omega three fatty acids.
And it included 100 adult men and women with triglycerides between 150, and 499 milligrams per deciliter, approximately 58% of study subjects had triglycerides greater than or equal to 200 milligrams per deciliter.
The study protocol involves 228 day treatment periods with a washout period of at least 28 days between treatments and was conducted at eight sites in the U S.
With DSO and Vascepa were each given is two grams twice daily with food.
In accordance with currently approved Vascepa labeling.
The primary endpoint and enhance it was the percent change from baseline to end of treatment and plasma triglycerides.
A key secondary endpoint with plasma EPA levels.
Two analysis populations were pre specified and the statistical analysis plan.
P D. Pharmacodynamic population of 94 patients and a P. P per protocol population of 82 patients.
The PD population included all subjects for whom estimation of Pharmacodynamic parameters was possible for both treatment periods, regardless of study drug compliance.
The per protocol population included patients from the PD population with the added stipulation of at least 80% compliance with study medications verified by pill counts with no clinically important protocol violations or deviations.
The P. P population was expected to have less variability due to better study drug compliance and to provide a more accurate representation of how study drugs would perform when taken as directed.
Top line results from enhance it included.
The primary endpoint.
Cent change and triglycerides from baseline was numerically greater with diesel 21, 9% versus 15, 7%.
This did not meet statistical significance and the pre specified P. D population, but was significant in the P. P population.
Secondly, plasma EPA concentrations absolute change and EPA from baseline and percent change and the EPA from baseline were all significantly higher with DSO than with Vascepa and both PD and P. P populations.
Thirdly, there were significant reductions in the Hs CRP with lip DSO compared with vascepa, suggesting potential superior anti inflammatory impact of with diesel.
Finally, there were no serious adverse events reported and no drop outs related to study drug adverse events.
Putting these and context, while the primary endpoint of percent change and triglycerides from baseline to end of treatment did not meet statistical significance and the pre specified P. D population.
And now assist from the per protocol population demonstrated statistically significant improvement.
And superiority of lip diesel over Vascepa, and reducing triglycerides total cholesterol and LDL cholesterol.
EPA blood levels were a key secondary endpoint and as noted the final plasma EPA and the absolute and relative changes in the EPA were all significantly higher which would be so then with vascepa.
We believe that the results from enhanced it strongly support the potential role for <unk> as the best in class prescription only Omega three drug for cardiovascular risk reduction given its unique composition of Omega three free fatty acids.
It's high bioavailability.
It's increased plasma concentrations of EPA compared to Vascepa.
Potential for once a day dosing without regard to meals.
It's documented potency and reducing triglycerides and the new observation of a favorable effect on Hs CRP.
And additional discussions of the enhanced results with our scientific advisers and they have unanimously reiterated how strongly these results point towards a potential role of lip DSO for cardiovascular risk reduction.
We are therefore currently pursuing external partnership opportunities to continue further development of lip DSO toward a cardiovascular outcomes indication.
With sites on this much larger addressable population and recognizing the importance of maximizing and period of exclusivity for this larger indication <unk> is not currently planning to pursue and indication for the treatment of severe hyper triglyceride email, although that could also be.
And option for a potential partner.
And with that I'll turn the call over to Dr. Raphael Mannino, who will be providing some background on our LNC platform.
Thank you Terry and good morning, everyone.
You'll be hearing shortly from Doctor Moskovitz.
And the progress we have made with that 22 O three our oral amphotericin b product.
And Matt twenty-five O one our oral amikacin product.
Both of which utilize the LNC platform.
With App amphotericin and amikacin and the challenges are similar.
Cheating and high levels at the site of infection.
Without this sort of treatment and limiting toxicities.
And it's both amikacin and amphotericin art and fitness.
At this point I'd like to provide a little bit more background on our lipid nano crystal or LNC delivery system that has made the delivery of these drugs possible.
Fundamentally our LNC platform is the next step and efficient safe.
Targeted intracellular delivery.
While amphotericin and amikacin have always had toxicity issues and new.
Who are more biologically complex treatment and have a different problem.
And how to get these sophisticated new drugs like oligonucleotides Messenger RNA.
<unk> therapy, new Antivirals, and even CRISPR Cas nine into cells.
Intracellular delivery is becoming increasingly important.
Medical Sciences to take full advantage of our growing understanding of cell biology.
Unfortunately at this point, the one and two real options on lipid nanoparticles or L M P's and viral vectors.
Both of these delivery systems have significant challenges that they are just not able to overcome.
So there is a need for much more stable formulations for greatly improved delivery efficiency and for less of the toxicity and immunogenicity.
Currently seen with Ellen peas, and viral vectors.
Moreover, there are size limitation patients on what Alan peas, and viral vectors can deliver.
Which can make delivery of large bathroom journey protein complex for example, problematic.
Even with these challenges and then pes and viral vectors are widely used.
Simple reason that up until now there have been no good alternatives.
Our and lipid nano Crystal technology has the potential to overcome most if not all of these limitations.
And he added advantage of potential oral delivery.
As with map 22, O theory, and that 20 501.
Moving down on crystals are primarily composed of two naturally occurring materials.
Total serine or P S and calcium.
And they can deliver a wide range of therapeutic compounds, including small molecules proteins.
Quake assets, such as antisense, Oligos Dsos and messenger RNA.
And small interfering RNA.
And nucleotide polymers as large as 11 kilo basis, including DNA plasmids and potentially CRISPR Cas line.
Partially it'll serene is especially important in our on lipid nano crystal delivery platform.
Because of the role <unk> plays in many important and cellular processes.
For example, the most widely studied has total sir independent process is a pop ptosis.
And the natural mechanism whereby debt cells are removed without inducing a major inflammatory response.
Boston, It'll serene is a natural phospholipid president and virtually all sales.
And then as an integral part of the cell membrane.
Yeah.
And as normally localized to the inner part of the cell membrane bilayer.
By active cellular mechanisms.
However, with cell death, these active mechanisms and no longer function and.
And self serve and moves to the outer layer of the membrane.
And as fast with title serene on the surfaces of cells that initiate the removal of dead cells by macro five without creating and inflammatory response.
Our first title Syrian Lncs are actively taken up by macrophages as.
As well as by a variety of other cells that are known to express plus total serene receptors.
Such as lung epithelium cells that are and the presence of and infection.
Once taken up by the cell efficiency of successful drug delivery into the interior of the cell is substantially better than with lipid nanoparticles.
Which are taken up by endocytosis, but only about 1% to 2% of the drug payload actually escapes from the end of zone.
In addition, there are also circumstances of cellular activation.
Where sales do not have to die to move hostile share into the outer layer, such as infection inflammation and injury immune stimulation and even oncogenesis.
In addition to be taken up.
Taken up by macrophages.
It appears that lipid nano crystal can also directly target and fuse with cells that have fast that'll series on their out of surface.
There are many other kinds of cells that are known to express first total sitting on their surface incur.
Including bone marrow drive and that'll poetic cells such as monocytes.
In fact itself injured cells tumor cells and epithelium cells.
In addition, and very interesting is that in nature envelope viruses Express hospital sitting on their surface as a way to trick macrophage to take them up and then to maximize membrane fusion with targets out target cells, and therefore enhance intracellular delivery.
Lipid nano crystal is have a unique multi layered structure consisting of continuous solid lipid bilayer sheets, either rolled up and a spiral or stacked up on top of one another.
With no internal aqueous space.
When administered physiological levels of calcium.
Which is which are present and gastro intestinal secretions plasma and interstitial fluids.
And paying the solid three dimensional crystal and structure of the lipid nano crystal.
This protects molecules trap in or between the lipid crystal bilayers from degradation.
In addition, keeping potentially toxic medications like amphotericin and amikacin sequestered within the lipid crystal particles priority intracellular delivery.
Our results and low drug plasma levels, and therefore low toxicity.
As noted because of their stability lipid nano crystal is can be administered in a variety of ways, including orally intramuscularly intravenously and via inhalation.
In summary, we believe that lipid nano crystal and provide a unique opportunity to move far beyond the current and limited options for intracellular drug delivery.
And potentially set completely new standards for safe and efficient targeted delivery of a broad range of therapeutic molecules.
And now I'd like to turn it over to Dr. <unk> to discuss more of the specifics of our net 22 or three and that 20 501 products.
Thanks, Raphael and good morning, everyone I will provide a few key highlights on net $22 three and discuss and act are studied to treat HIV infected patients with Cryptococcal meningitis.
Then follow with an update on net 25 O one.
2020 was the significant progress from Matt 22, or three and we were able to advance this important LNC drug candidate and our next study and Uganda, which explores the use of mid 'twenty, two or three for both induction and maintenance of consolidation treatment of Cryptococcal.
Meningitis and HIV infected patients.
Data from part one of the next study, which was completed early in 2020 were published and the antimicrobial agents and chemotherapy or ACC, a journal of the American Society of Microbiology.
And the manuscript entitled Safety, and Tolerability of the novel oral formulation of Amphotericin B phase, one and that trial.
In the published manuscript trial investigators concluded that mid 'twenty, two or three was well tolerated when administered in Florida six divided daily doses without the toxicities, commonly seen with IV amphotericin b with nearly 100% of patients expressing a preference.
And for oral net 22 or three relative to amphotericin B delivered intravenously.
The second part of and Act, which is designed to assess the safety and efficacy of net 22, three and HIV patients with an active cryptococcal meningitis infection was initiated early in 2020, and only began enrolling patients in July of 2020 due to the global P.
Dominic.
The second part of the net is divided into four distinct patient cohorts with subsequent adjustments to the timing of map 22 or three and.
And the duration of exposure to intravenous amphotericin b the existing standard of care for patients with Cryptococcal meningitis.
In October of 2020, the independent data safety monitoring board completed a pre specified review of the first cohort and unanimously recommended progression to the second cohort of patients.
And as a reminder, in cohort one patient and the active arm received five days and intravenous amphotericin B followed by nine days of oral net 22 or three or the 14 day induction period.
And then continued and net 22 or three four and additional four week maintenance period.
Data from cohort, one and confirms the treatment with oral mid 'twenty, two or three was over on safe and generally well tolerated and did not indicate any potential safety signals, which has been a significant challenge and risk associated with intravenous amphotericin treatment.
All patients and the mid 'twenty, two or three group with positive central nervous system cultures that baseline became scale during the induction and maintenance phases of the study.
Colbert to shorten the lead and treatment with intravenous amphotericin to two day and increases the duration of treatment with net 22 or three and the induction phase to 12 days.
Cohort two includes 40 patients and the active arm and 16 and control therapy, which is an intravenous amphotericin b.
Following the induction phase.
And if patients continue on or on net 22 O suite for the four week maintenance a consolidation period.
We are pleased to report that we have recently reached 50% and a patient enrollment, which is 28 or 56 patients in cohort two.
And we anticipate the data safety monitoring board evaluation of full safety and efficacy data from this cohort.
Will occur in the third quarter of this year.
We view cohort two is extremely important for a number of reasons.
First increasing the duration of oral net 22, three during the induction phase to 12 days.
Should provide more detailed insight.
And the efficacy of net 20 tools to me and this vulnerable patient population.
We would expect to see continued improvement and reduction of CSF possible counts and the achievement of stability during the induction without rebound during maintenance.
This would be further validation that it met 22 or three is effectively crossing the blood brain barrier and treating this deadly invasive infection.
Second.
And D S and be evaluation of the data from cohort two and our own internal review.
And we anticipate meeting with the FDA to allow them to we view all data generated to date and and act and to discuss opportunities to potentially accelerate development of mid 'twenty two or three.
Through the limited population pathway for antibacterial and antifungal drugs more cash.
And we refer to as the L pad pathway.
This pathway was created to encourage and facilitate the development and approval of certain antibacterial and antifungal drugs to treat serious or life, threatening infections and limited populations of patients with unmet needs.
Austin development program for drugs eligible for approval under the <unk> pathway.
And we'll follow streamlined approaches to clinical development.
And may involve smaller shorter or fewer clinical trials.
Hmm.
We believe mid 'twenty, two or three is an ideal candidate for the pad pathway and look forward to discussing the data from and act with FDA later, this year and an effort to further streamlines the development and regulatory path toward and initial approval for the treatment of Cryptococcal meningitis.
<unk>.
We also anticipate discussing the way forward for additional indications for <unk> 22, or three and treating other invasive fungal infections, such as aspergillosis and invasive candidiasis.
Ultimately, we believe mid 'twenty, two or three has the potential to become the therapy of choice for the treatment of the most invasive fungal infection, given the broad spectrum nature of amphotericin B and the unique ability of our LNC platform to facilitate world.
<unk> ability and also mitigate issues related to the severe renal toxicity toxicity historically seen with IV administered amphotericin b.
Yeah.
I'll turn next to and update on net 25, and one our LNC formulation of the broad spectrum and potent aminoglycoside amikacin, commonly used to treat both chronic and acute bacterial infections.
We continue to progress the development of net 25 O one.
With the financial support from the cystic fibrosis Foundation.
And the extensive preclinical toxicology and efficacy studies with the goal of completing a single ascending dose pharmacokinetic study in healthy volunteers later this year.
Amikacin is the mainstay of the treatment of severe N T M infections.
Lilly given the increasing prevalence of antibiotic resistant micro bacteria.
Mechanistically and.
On the case and works by binding to the bacterial ribosome and inhibiting bacterial protein synthesis.
Its effects are highly dependent on interest cellular concentrations achieved.
Therefore, our orally administered LNC formulation of amikacin.
And with potentially more efficient and better targeted intracellular deliberately.
As previously described by Dr. Menino.
Could represent a significant breakthrough for these difficult to treat infections.
Moreover, resistance to amikacin and micro bacteria is caused by genetic mutation that reduces the binding affinity of amikacin and toward the bacterial ribosome again, emphasizing the importance of effective intracellular delivery.
Theoretically with higher interest cellular concentrations the reduced binding affinity seen with them a case and resistance could be at least partially compensated for.
We remain particularly enthusiastic about the opportunities for this first portal M. A case and formulation, which takes full advantage of our LNC platform to achieve potentially better intracellular delivery with less toxicity and and area of major unmet.
Medical needs.
We have already seen pre clinically that math 25, and one has demonstrated antibiotic activity and.
Against both sensitive and multi drug resistant strains of and avian and and obsesses, which differentiates met 20 fives on one from other formulations of M. A case and.
We look forward to advancing through preclinical and phase. One studies later this year and also beginning to expand the development program format 25 on one beyond MTN and into more acute bacterial infections, including gram negative bacterial infections.
I would now like to turn the call over to Keith Kucinski, Our CFO, who will discuss our financial results.
Thanks, Terry and good morning, everyone.
Turning now to our financial results for.
For the fourth quarter of 2020, the company reported a net loss attributable to common shareholders of approximately $6 $6 million or three cents per basic and diluted share compared.
Compared to a net loss attributable to common shareholders of approximately $5 $8 million or four cents per basic and diluted share for the same quarter of 2019.
For full year 2020, the company reported a net loss attributable to common shareholders of approximately $23 $2 million or 12 cents per basic and diluted share.
Compared to a net loss attributable to common shareholders of approximately $18 $3 million.
Or a 13 cents per basic and diluted share for 2019.
The increase loss for each period was due primarily to an increase in operating expenses.
Research and development expenses were approximately $3 $5 million and the fourth quarter of 2020 compared to approximately $3 $4 million and the same quarter of 2019.
For full year 2020.
R&D expenses were $14 $4 million compared to $11 $2 million for full year 2019.
The increase for full year 2020 was due primarily to higher preclinical and clinical development expenses and employee compensation related to the development of lip DSO and had 22 or three.
And that 20 501.
General and administrative expenses were approximately $3 million and the fourth quarter of 2020 compared to the previous year's fourth quarter G&A expenses of approximately $2.3 million.
For full year 2020, G&A expenses were $10 million compared to seven $8 million for full year 2019.
The increase in both periods was due primarily to increased head count head count and professional fees.
Cash cash equivalents and marketable securities at December 31st 2020 were approximately $58 $7 million compared to 27 $8 million and.
At December 31st 2019.
The year over year increase was due primarily to the sale of approximately $32 3 million shares of the company's common stock at a price of $1 55 per share.
During January 2020.
Generating net proceeds of approximately $46 $7 million.
And July 2020, the company entered into and at the market sales agreement with B T I G.
Pursuant to which the company and they offer and sell from time to time through P. T I G.
Shares of its common stock, having an aggregate offering price of up to $50 million subject to certain limitations.
As of December 31, 2020, the company did not sell any shares of its common stock.
Under the sales agreement.
However, during January 2021, the company sold approximately 3 million shares of its common stock under the sales agreement generating net proceeds of approximately $5.6 million.
Based on current projections management believes that cash on hand is sufficient to fund operations into 2024.
I will now turn the call back over to Gerry.
Thanks, Keith and summary, 2020 was a year of significant accomplishment from a teen us as we look forward now to the balance of 2021, our focus is and on is on improving the intracellular delivery of critical therapeutics through our paradigm changing LNC platform delivery technology.
We believe our technology can be differentiated from any other intracellular drug delivery technology being applied today and has the potential to solve some of the challenges presented by the use of lipid nanoparticles and viral vectors are proprietary foster total serine based lncs and enter cells and a variety of ways without unintended adverse.
And consequences and without cell based toxicity or debt and we have the flexibility with both route of administration and with the types and sizes of molecules that can be formulated inside our lnc's cohort two from the enact study continues enrollment and represents a great opportunity for further validation of map 22 or three.
And our LNG platform and a highly vulnerable patient suffering from a deadly fungal infection, which requires drug transport across the blood brain barrier and about 25, and one is poised to advance rapidly during 2021 and position that drug for a phase II program next year and we are excited to see our relationship with Genentech to continue and expand.
As well as how our initial formulations of Gilead from death severe perform and and I D. Preclinical studies over the next few months. We also remain confident that we will find the right partner to continue development of lip DSO and maximize the opportunity presented by a differentiator and Omega three with the capability of achieving elevated.
Levels of EPA and the fight against cardiovascular risk.
And with a cash runway into 2024 and with sole control over and potentially disruptive delivery platform. We believe this is a very exciting time for our company and our stockholders and we look forward to keeping you apprised as to our progress throughout the year.
With that we have reached the conclusion of our prepared remarks, and I will turn the call over to our operator for our question and answer session.
Thank you and I'll be conducting a question and answer session, if you'd like to be placed and the question queue. Please press star one on your telephone keypad, a confirmation tone will indicate your line is and the question queue and he may.
Press Star two and we'd like to remove your question from the queue for participants using speaker equipment may be necessary to pick up your handset before pressing star one one moment. Please while we poll for questions.
Our first question today is coming from Yasmin Rahimi from Piper Sandler Your line is now live.
Hi team. Thank you for taking the questions and for the really thoughtful and detailed updates.
Two questions for you and maybe the first wanted to and just walk me through why why what the reason for the decision and that's we're not pursuing that triglyceride EMEA, but.
And I'd, rather focus into the broader population and and then the second question is I would like to understand a little bit more and the opportunities on using the LNC platform, specifically for mrna construct and gene therapy and thank you again for taking my questions.
Great. Thanks, Thanks, guys me and so in terms of sort of not deciding not to move forward.
With the amplify trial, which was the phase III trial. The global trial that was to be conducted and severe hepatic triglycerides EMEA a lot of it came from the review very close review of the enhanced data and ultimately if you look at what the strengths are.
And of that data suggest and the fact that the profile of lip DSO.
Is designed to achieve elevated blood levels of EPA and ultimately appears that the ceiling for liberty. So is higher than perhaps we thought it was before the enhance it trial came out the ability.
To generate that level of EPA and the blood suggests that even as against Vascepa and we have the potential if diesel is the potential for a superior cardio protective effect that suggested and in consultation with our S. D that a cardiovascular outcomes trial and made the most sense.
And when you thought about continuing down both paths you didn't want to have a situation where you continue to get.
And and went for approval and a smaller indication and S. H T G.
And even if you got approval in 2020 four all you'd be doing much starting your exclusivity clause. So given the profile of lift do you. So the opportunity. We believe we have to find a partner to develop it toward a broader indication you wanted to put yourself and the position to maximize the opportunity and to maximize the opportunity it's about positioning.
For a reduction of cardiovascular risk and <unk>.
Preserves your exclusivity it positions you to then be able to take advantage of a much broader label and it also puts you and position of not necessarily just spending $30 million to $40 million to get an approval as quick as you can because of some of the challenges we've seen.
And with Amarin.
And and what happened to it with skinny labeling and and other things whether it's drugs. So overall, we believe that finding a partner and obviously you know raising this sort of money in order to be able to run a cardiovascular outcomes trial I think would be challenging for a company like between us and our at our current position today and the.
Data suggests that there will be you know a partnership interest in and sort of helping to take on debt burden and really driving this towards the cbot outcome. So that ultimately was was what the decision was based on I don't know if Terry Ferguson and if theres anything else you would add to that.
No no jewelry on thank you you hit the high points and I think that that again, depending on the partner that could remain and opportunity.
And thinking about this and thinking about the very clear signal that this appeared to be you know a very good drug for cardiovascular risk reduction.
And not to jeopardize that period of exclusivity for that much larger opportunity seem to make the most sense for right now.
And then you guys I mean these decisions are never made and the vacuum so.
They're always made with an idea of what technology or what expertise and and what products are within your company. What is the best allocation of resources and as we evaluated the entire company, particularly with the emergence of the LNC platform.
And the opportunity presenting itself that liberty so.
Has the potential to become a superior cardio protective drug and it made sense to line things up this way.
Does that answer your first question.
Yeah. Thank you Jerry that's helpful. Thank you every day and color.
Sure and.
And so now to turn to your second question on the LNG platform, particularly how it may apply to things like messenger RNA and gene therapy.
There's no question that drug delivery continues to be one of the greatest challenges and and the development of medicine today, and and the ability to get specifically complex new play that nucleic acid polymers inside itself is really hard.
And you can tell by how long it's taken some companies look at on the island and how long. It took them you know working with lipid nanoparticles to get their first drug approved.
And in that then in that area was on Todd trial, what we've seen with Lnc's historically has the ability to formulate these complex nucleic acid polymers and so as we sit here today and yes, we're working on important drugs like amphotericin and amikacin <unk> helped them.
Chief results that would not be possible without that technology, but we do recognize that there's a lot of attention today, particularly because of COVID-19, and the emergence of the vaccines, which are mrna based and do use lipid nanoparticles to deliver we know that they can.
And be effective, but we also know that there's limitations that can't be used chronically there are issues with toxicity and other things and we've seen the ability and have formulated DNA plasmids as large as 11 kilo basis, we've gotten.
Formulations of messenger RNA stable at room temperature.
For four weeks and a refrigerator for up to six months. So we know we have the ability to formulate these drugs and we expect to have the opportunity to work with some of these companies to demonstrate our ability to sort of move forward and that area, but maybe Rafael could you just talk about you know the.
Alert effect.
And that we could have and formulating.
Gene therapy, or a messenger RNA and and the unique way, which we could deliver it.
Inside of the cell and the multitude of cells that we're talking about here and and maybe focus again on faster total theory.
Sure. Thank you.
I think one of the first things is just to go back to our ability number one to debt.
And up and expressed in a macro fashion macrophage or one of the major antigen presenting cells.
And the immune system and.
And the second thing is that although people tend to focus on antibodies for things like influenza virus and Corona virus. We also know that cell mediated immunity killer T cells are probably much more effective and protecting a person from lung destruction or lung disease and the antibodies.
And.
And the third is that although we give most of these vaccines and from muscular Lee.
It has been shown and we have shown with the lipid nano crystal and living them orally allows you to express both antibody and cell mediated immune responses on the mucosal surface, which is the which is the way that these viruses enter the body. So just focusing on respiratory viruses.
And the ability to make a vaccine that is safer because you can give it intramuscularly and you can boost you don't get side effects. When you do that you can give it or at least so that you can or intranasal leased so that you can immunized and get better strong mucosal immunity as well as systemic immunity.
It gives the lipid nano crystal a K a.
A large advantage over anything like a lipid nanoparticle or viral vector.
When you have stemmed from there and you go to and you looked at other yourselves like finally infected cells cell inflamed cells on.
Chronic.
Inflammation and inflammatory disease.
On to let's say and and and cancer yourself all of these cells. They start as normal sales when they convert or are converted into pathogenic cells by virus infection by oncogenesis by inflammation. So fast on assuming pops from the inside of the cell membrane to the outside that and fast titles shearing receptors.
And in some cases are seem to appear on the outside of the cell surface. So both of those things.
Maximize and enables the targeting delivery.
<unk> lipid nano crystal formulated drugs as well as the uptake either by fact with psychosis or through fusion and that's important and just to get into a little bit more immunology and that if you want and antibody response, and you want delivery, let's say into and into something but if you want cell mediated immunity you need to have the <unk>.
Antigen directly and the cytoplasm, so our ability to enter as sell and both ways.
Maximizes our ability to it to enhance the efficacy of the drug that we're delivering.
Thanks, that's helpful.
Yeah.
Very much thank you.
Thank you as a reminder, that star one to be placed and the question queue. Our next question today is coming from Gregg Gilbert from true and Securities. Your line is now live.
Good morning folks, it's Greg Fraser on for Gregg Gilbert.
A couple of questions on net 22 or three assuming the results from the second cohort are supportive of moving forward can you just walk us through the timeline for the third and the fourth cohorts and you mentioned meeting with the agency.
Following completion of the second cohort to discuss and accelerated approval pathway what would be a best case scenario in terms of timing, if you're able to pursue an accelerated pathway and and if that route is not available how should we think of that as a likely regulatory path.
Thanks, Greg.
So first just to kind of I'll take your questions and can sort of reverse so in terms of speculating on how quick the pathway could be under el pad without getting in there and reviewing the data with FDA, it's hard to speculate we have seen.
There are obviously, a very few companies that have been able to take advantage of this pathway to date. We know are case was the first drug that was approved pursuant to the <unk> pathway.
But when youre talking about Cryptococcal meningitis, and Youre talking about and drugs like amphotericin.
We do think it's it's an ideal circumstance to be able to leverage the <unk> pathway, but how quickly that that can turn into and approval.
It's just too difficult to foresee at this time, but you can't you could envision a scenario in which you looked at the back half.
And act and found a way either to expand the size of that study perhaps include an arm and the U S and a scenario in which enact in and of itself could become a registration trial that would probably be the ideal circumstance, but until we get in and see the data and then have that discussion.
And with the FDA, it's too difficult to forecast that in terms of what cohort three and cohort four looked like.
Terry Mcevoy, it's do you want to walk through both the size of those cohorts and then the projected sort of timelines for the full completion of and act.
Sure Jerry so the enrollment in the enact trial of course is it dependent on largely when the patients will present since its and acute bacterial and fungal.
Hung on section, but our current estimated timing.
Timing for the cohort progression as we discussed in the third quarter on this year, we anticipate to have a read out at the stage two data.
Which we believe will be pivotal to the discussion on the potential for the hour pad, we view with S. P. A.
Stage to me will be initiated and a third quarter of this year, we see read out by the early fourth quarter. This year and that is a smaller cohort of patients where we're looking at the.
14 day, 14 cohort, a and <unk> patients stage, four which is really the critical cohort looking at an all oral treatment of patients with penta Taco meningitis will be initiated in the fourth quarter and this year based on our enrollment projections with a read out on.
The initial stage of the study by the first half of 2020 two.
Thanks Terry.
Yeah.
Thank you we've reached end of our question and answer session I'd like to turn the floor back over to management for any further or closing comments.
Thanks, Kevin and thank you all for joining US today. We appreciate your continued interest and between us and the team here looks forward to providing you with updates on our future progress have a great day.
Thank you that does conclude today's teleconference and webcast you may disconnect. Your line at this time and have a wonderful day, we thank you for your participation today.
Yes.