Q4 2020 CohBar Inc Earnings Call
[music].
Good afternoon. My name is Paul and I will be your conference operator today at this time I would like to welcome everyone to co bars fourth quarter, 2020 financial results Conference call. All lines have been placed on mute to eliminate background noise. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference.
Please press star zero on your telephone keypad other.
The reminder, this conference is being recorded now I would like to turn the call over to Jordan Turabi director of Investor Relations of co bar to begin.
Thank you Paul and thank you everyone for joining called by the fourth quarter of 2020 Financial results Conference call. Joining me on today's call is Steve Engle, <unk>, Chief Executive Officer, Ken Cundy, Chief Scientific Officer, and Jetblue and Al Khobar, Chief Financial Officer, Cobalt and 10-K filing and the financial results press.
And these were issued earlier today and may be downloaded from our website and go buy of dot com and they're having issues joining the wide back you can access the slide presentation from the homepage of cobalt the website to follow a lot GAAP.
We will begin with an overview of the fourth quarter financial results, followed by a business and R&D update from Steven Kent.
Before we begin I'd like to take like the take a moment to remind listeners that the remarks on today's conference call May include forward looking statements within the meaning of the securities laws. These forward looking statements include but are not limited to statements regarding the company's plans and expectations for its needs to be 42, 11 drug candidate program.
The therapeutic and commercial potential of the company the lead drug candidate CB 42, 11, and other mitochondria based therapeutics statements regarding ongoing and planned research and development activities potential partnerships and our capital resources and ability to fund our operations.
Looking statements are based on current expectations projections and interpretations that involve a number of risks and uncertainties that could cause actual results to differ materially from those anticipated by Cobra and.
These risks and uncertainties are described in our registration statements reports and other filings with the Securities and Exchange Commission and applicable Canadian Securities regulators, which are available on our website and Colbert dot com and C. C dot Gov, and SEDAR dot com as well as in the Safe Harbor statement included with today's press release, you are of course.
And that such statements are not guarantees of future performance and that our actual results may differ materially from those set forth and the forward looking statements.
The board does not undertake any obligation to update publicly or revise any forward looking statements or information, whether as a result of new information future events or otherwise now I'd like to turn the call over to Jeff you know called Bis Chief Financial Officer, Jeff.
Thanks, So much Jordan and thank you everyone for joining us this afternoon.
As Jordan mentioned, if you're having issues with Webex. The slide presentation is posted on the homepage of the Khobar website next slide please.
And as Jordi noted ill begin with a review of the financial followed by a business overview by Steve Ken will then review the recent developments and our clinical and preclinical programs and will conclude with Q&A next slide please.
I will now provide you with the summary of our financial results for the fourth quarter ended December 31, and 2020 compared to the fourth quarter ended December 31 and 2019.
Next slide please.
Total operating expenses in Q4, 2020 were 4 million of $365000 as compared to $3 million $570000 and Q4 2019.
And increase of approximately $795000.
Operating expenses included non cash costs of $345000 for the quarter ended December 31, 2020 and.
$638000 for the quarter ended December 31 2019.
Net of the noncash cost total operating expenses in Q4, 2020 were $4 million $20000 as compared to $2.932 million and Q4, 2019 and increase of approximately $1 million $88000.
Non cash operating expenses include stock based compensation and depreciation and amortization costs.
Research and development expenses were 2 million of $697000 and Q4 2020.
Compared to $1 $898000 and the prior year period and increase of approximately $799000. The.
The increase and research and development expenses was primarily due to higher clinical trial costs due to the timing of those expenses, partially offset by lower stock based compensation costs.
General and administrative expenses were 1 million of $668000 from Q4, 2020, compared to 1 million of $672000 from the prior year period.
For the quarter ended December 31, 2020, cobalt reported a net loss of 4 million and some of our $8000 or eight cents per basic and diluted share compared to a net loss for the quarter and December 31, 2019 of $3.717 million or <unk> <unk> cents per basic and diluted share net.
Loss included noncash expenses of $603000 for the quarter ended December 31 2020.
$743000 for the quarter ended December 31 2019.
Excluding the noncash expenses Cobalts net loss was 4 million and $105000 for the quarter ended December 31 2020 of.
As compared to $2.974 million from the prior year period.
Total non cash expenses include stock based compensation, depreciation and amortization cost and equity modification costs.
Moving to the balance sheet as of December 31, 2020, cobalt had $21 million and cash cash equivalents and investments.
Compared to $12 6 million of cash and cash equivalents as of December 31, 2019.
And the cash burn for the quarter ended December 31, 2020 was approximately $2 $4 million.
During the quarter, we completed a private offering with certain promissory note holders, where we've converted outstanding amounts due in 2021 and 2022.
We converted approximately $3 $8 million and principal and interest issuing approximately $3 2 million units on terms that were substantially the same as those and the public offering that we completed in August 2020.
The completion of the private offerings strength in cobalt is balance sheet by converting 81% of the debt outstanding at the end of the quarter.
Notes totaling $352000 of due and payable in 2021 and.
500 of 3000 is due and payable in 2022.
Subsequent to the yearend December 31 2020.
Cobalt received proceeds of $1 million from option and warrant exercises.
We estimate the based on our cash and investments of balance as of December 31, 2020, plus the proceeds from the equity exercises and the first quarter of 2021, we have sufficient capital to finance our operations through the first quarter of 2022.
I'll now turn the call over to Steve Steve.
Thanks, Jeff and welcome everyone to our fourth quarter 2020 call.
We believe the mitochondria based therapeutics will provide a treasure trove of.
The potential therapeutic agents or trading multiple diseases.
Co bar is elucidating the function multiple pep side the.
And by sequences found and the human mitochondrial genome.
We are reading the language of the mitochondria speaking to the rest of the body.
Based on our progress to date, we expect this will enable us to develop healing therapy and multiple chronic and.
And the age related diseases.
This represents a rare opportunity and biotech.
And let's start our review of the quarter with four key points of it.
The one yesterday, we announced completion of enrollment and the phase <unk> study.
Next we plan to announce when the last subject is.
The completed their last visit.
Ken will speak more about the importance of the step in his section.
Currently we are expecting top line results at the end of the second quarter of 2020, one based on a number of factors, including the timing of the last clinical study.
Subjects visit.
We made significant progress with our preclinical projects and expect 2021 to be a transformative year for co bar as we advance our clinical programs towards the clinical stage.
For example, we announce it.
The $51 38 cash three as our next clinical candidate for the.
Dental treatment of IPF and other fibrotic diseases.
We have chosen ICF as our initial indication due to a combination of factors both commercial and technical.
Number three we announced the initiation of the collaboration with the U S government National Institute of allergy and infectious diseases, signing an agreement called and in the Hay.
To evaluate our CB 50, 60 core analogs and mouse models of COVID-19.
Yes.
And as a reminder, we will be providing our apple and agonist peptides dunaj and for them to administer the preclinical and COVID-19 studies at their expense.
Co bar will continue to develop and evaluate compounds from this program in parallel with the activity and Doug.
Yeah.
And four wall Street analysts covering co bar of increase from four to five.
Hello.
What is the co bar opportunity. We believe that we are the leaders and developed a new class of therapeutics based on our founder's discovery the mitochondrial generated peptide regulate multiple systems from the body.
Think about the prior to 2001 and doctors Cowen and bars lies discovery people thought mitochondria, where just the powerhouse the cell and not a key player and regulating and some of the bodies key functions.
Because it is the new class of drugs, we believe mitochondria based therapeutics represent a large untapped and exciting group of potential therapeutics.
Amazingly, our CSO and candy and the scientists have discovered over 100 peptides and the mitochondria genome and developed over 1000 analogs.
It is likely of 100 keys on the wall and we are taking them down and one by one to discover which biological walk.
The open.
Based on our research results, we believe that some case.
And even opened multiple walks such as Nash and obesity.
We are targeting a wide range of diseases that are associated with mitochondrial dysfunction and because we are targeting the problem at the cellular level. We believe mitochondrial peptides will work on the cause rather than just the symptoms.
Mitochondria based therapeutic benefit from over 1 billion years of evolution and may generate entirely new approaches to treating diseases, we need new and different approaches many of the older therapies therapeutic limitation and side effects.
And doing so we are taking advantage of a mitochondrial derived peptides.
Peptides that the body has evolved over 1 billion years and developing our compounds we are surfing on the way.
Of evolutionary biology behind the mitochondrial peptides for this reason we believe they represent a better starting point of developing therapeutic agents with less side effects and as a result of our peptide medicine may have a higher probability of technical success compared to the.
Traditional discovery approach and the.
The last year, the company's portfolio has grown from two programs to five programs. We are no longer just the NASS focused company and now of the programs targeting <unk>.
Fibrosis and oncology it is.
The really exciting time.
We continue to learn new things about this class of potential therapeutics.
And that is new indications, new targeted Oregon, and new mechanisms of action.
We expect out of a number of near term milestones demonstrating our continued growth and.
The company with multiple clinical assets and.
And as the leader and the developer of mitochondrial based therapeutics, we are committed to strengthening our comprehensive <unk> been intellectually intellectual property position.
And it greatly from having a first mover advantage.
Thanks Bye.
Now I would like to discuss our accomplishments from last year.
All of our Investor call in November we announced the continued advancement of our lead program evaluating <unk> 40 to <unk> 11 per Nash and obesity.
And our anti Fibrotic program, we identified multiple peptides with both anti fibrotic and the anti inflammatory activity and.
ICF model.
And our Apple and agonist program, we generated confirmatory results and a preclinical model of hard and are moving the program forward two of candidate.
<unk>, we did the only a few months after announcing the program.
And in order to finance, our pipeline, we significantly strengthened our finances.
And had four analysts initiated coverage in 2020.
And based on our current plans, we believe our funds can take us through the first quarter of 2022.
Ted.
And we plan to raise additional funds to support moving seed. The 4200 11 in the phase two and accelerating our other programs. We are planning to move forward such that we may have multiple programs in the clinic next year and.
And subject to successful progress we have the potential to be conducting three clinical stage programs.
We continued meeting with and educating pharmaceutical companies and investors about our mitochondria day.
Upside platform and portfolio.
And lastly, we continue to significantly increase our visibility by presenting at 15 conferences and events in 2020, which is multiples of the prior year and.
Since then we have significantly increased our media presence.
Being featured in publications, such as bio space longevity technology and.
And Chief Executive magazine.
Next slide.
These are the near term milestones for 2020, one through 'twenty 'twenty two we expect to have the topline results from the phase one B study at the end of Q2 2021 dependent on the number of factors, including the timing of the lab.
Patient visits.
Last subject visit.
Based on additional funding, we expect to select the third candidate and the second half of the year and initiate activities to support the next maybe 42 of 11 clinical study and.
And 2022, we plan to file a new R&D of.
Of course, CB $51 38, three and began the first in human clinical trial.
Our overall goal then for the pipeline just to continue generating programs, which could lead to multiple clinical studies over the next few years.
Next slide.
Recently, we have experienced the transformation of the development of our portfolio of stated earlier.
To accompany with the potential of the multiple programs from the clinic.
Note that each one of the compounds and represents a different family of peptides structures. They are not the same and each program is targeting multiple indications.
So this is the true portfolio with potential to provide multiple shots on goal.
Next slide.
Interest and the development of therapies for Nash and obesity remain high.
And a number of SaaS companies.
Is that.
Went public and the last year.
These companies received funding from some of the largest biotech.
And pharmaceutical companies.
Sales of Nashville continues to be a bumpy ride for some of the later stage companies.
One of the first Nash leaders has shifted its focus away from Nash and response to FDA communications.
For several other companies this year as described and.
And the execution year, a relatively quiet here is many of their later.
Nickel trial and stage clinical trials are ongoing and few data readouts are expected.
So given the potential size of the market the need for multiple therapies to manage this complex disease and.
And our unique mechanism of action. We believe there is plenty of room for our novel mitochondria based therapeutics CB 42 of 11.
Finally, what do we expect from the topline data from our four week phase <unk> clinical study of the 42 11.
And we initiated our study in order to obtain initial safety data and pharmacokinetics and humans and to begin exploring the activity.
The <unk> MRI PDF measures and multiple Biomarkers, Ken will explain this further in his section.
Hello.
Turning to our second clinical candidate and IPF remains the major unmet medical need the few available treatment options drugs currently approved for IPF and slow the progression of the disease, but can also cause significant side effects that limit their use.
And of the world's foremost medical experts and a consultant to of the company Dr. Toby Mayer detailed the difficulties these patients.
Experience with shortened life expectancies.
And our recent Kols and call.
Most companies working and the anti fibrotic disease area of focused on Ikea first or is it is the chronic progressive and usually fatal disease.
The likely need multiple therapies.
IPF is and.
Orphan indication, which provides other advantages and the development process the.
And the idea we are targeting of potential broader opportunity and a range of fibrotic diseases affecting different organs, including the liver kidney lung and the heart.
These diseases of the count of 45% of all cause mortality in the developed world.
Next slide.
Hi, I'm often asked why target COVID-19 are everyone is being vaccinated.
There are 3 million patients worldwide suffering from Ards.
Even without counting the COVID-19 are patients acute respiratory distress syndrome remains a major unmet medical need.
And finally, we continue to develop our <unk> four inhibitor peptides.
Which were also derived from sequences of peptides bound and the mitochondrial genome.
Next slide.
And I will turn the call over to Ken.
Yeah.
Thanks, Steve I'll now give a brief update on recent progress and our key research and development programs next slide please.
So let's start with the clinical program. The B 42, 11 is currently in phase <unk> clinical testing as a potential treatment for Nash and obesity. The phase one day stays of the study is completed and we recently announced the we have also completed the enrollment of the phase <unk> stage of the study and it was.
As a reminder, this phase one stage of the study is a double blind placebo controlled study with the target enrollment of 20 obese subjects with N. S. O D. In order to provide 10 on placebo and 10 on one active dose level of <unk> 42, 11, given once daily by injection the fee.
Phase one of these stage is designed to assess the potential effects of C. B 42, 11 on liver fat body weight and various biomarkers that are relevant to Nash and obesity and metabolic disease.
Changes in liver fat and measured by MRI at P. D. S. S and all subjects were required to have a minimum of 10% liver fat at baseline during screening.
This is a short study not a pivotal phase two study so we will be looking for trends and the data.
Well, we were able to complete enrollment in the study. Despite the early of issues, which are included COVID-19 related impacts on the study pause on slower enrollment dropouts due to positive COVID-19 tests at one of our sites and even more recently with types of deal with ice storms in Texas that impacted even routine.
The lab testing across many regions of the state.
We currently expect to have the topline results of the end of the second quarter of 2021 subject to any further unpredictable factors and we expect to update the status of the study again when the last subject is completed their final follow up safety visit.
Next slide please.
So as we discussed on the last call. The clinical trial process for this study has been of rolling enrollment of shown in the simplified diagram, each new subject was enrolled dosed and followed up for safety.
And when each subject receives their last dose theres still a follow up period for safety observation to ensure there are no issues. This process continues until the last subject is completed the final study follow up as shown by the Diamond.
The data are collected throughout this entire process and entered into a database and at this stage. All data are still blinded, meaning we do not yet know who received C. V 42, 11, and who received placebo when all subjects have completed the final follow up visit and after all required data for safety pharmacokinetics the liver.
And that body weight and biomarker levels of all being collected the data or the and cleaned checked for errors. The errors of systematically resolved and then the database is locked and only then will the day to finally be unblinded and the analysis of the data we will begin next slide please.
So what can we expect out of the phase one B study, where there are multiple possible outcomes. The primary endpoints of the study of the safety and the Tolerability.
And the secondary endpoint will be the pharmacokinetics.
The exploratory endpoints include the changes in liver fat body weight and Biomarkers. After four weeks of dosing that we will be analyzing for trends.
And what about historical precedent for four week studies with other Nash compounds.
They shown well there have been and several other published studies that have looked at trends in the same types of activity outcomes and either and the S. O D. R. R Nash subjects and.
After a similar four week treatment period and up.
Other companies, including Merck and G M and that's of Corinne happy on and direct have released data from the four week studies and either and the F L D or Nash subjects.
And in some cases, they looked at the liver fat changes and all of those they looked at Biomarkers and sometimes both.
There was a wide range of outcomes and these studies from statistically significant changes to smaller trends and and at least one study the positive effects were only detected using a subgroup of the study subjects. So this range of outcomes may be the result of testing drugs with completely different mechanisms of action and some of which have already been validated.
<unk> and other indications.
There was already a sense of their clinical potency and some knowledge about the best way to give the drug.
There are also some important differences between these prior studies and cobalt was phase one B L.
And our study is a double blind placebo controlled study while some of the published studies are open label designs, meaning there was no attempt to conceal the identity of the treatment from the subjects or the investigators and there was no control group to demonstrate the underlying placebo effect.
C. B 42 of 11 has a unique mechanism of action compared to the agents assessed and those prior studies and also unlike those earlier studies our subjects were confined for the duration of their treatment.
As this is the first in human study of C. D 42, 11, and we will obviously need to wait for the topline data.
Next slide please.
And let's talk about what's next for C. D 42, 11, and we plan to complete the ongoing phase one a one b study with Readouts for Nash and obesity and prepare for the next clinical study in Nash, including seeking of corporate partner now based on positive clinical results and additional funding from potential partners.
Ships and General fund raising we then plan to initiate preparations for phase two and see it.
And the 2021 and then initiate a phase two study in 2020 two.
Our plans for another clinical study for Nash will depend on what we see from the phase one data in terms of trends and liver fat reduction by MRI of P. D F S and trends and the Biomarkers.
And this is a small study involving four weeks treatment. So we will not be looking for the same outcomes such as biopsy driven outcomes of the largest phase two studies that have a longer duration of 12 or 16 weeks.
And planning for another clinical study there are a number of factors that normally must be considered.
Based on the phase one of the outcome, we need to select the optimum dose regimen or regimens to take forward. The study design and duration and we need to understand how the regulatory landscape is evolving around the most appropriate primary and secondary endpoints.
We will need to select the most appropriate patient population for our drug the right stage of fibrosis. The study and carefully considered the potential contribution of diabetes and other comorbidities and the Nash study population.
It may be advantageous to use the diabetic population on the G. L. P. One agonist to take full advantage of potential synergy with C. D 42, 11 mechanism and help differentiate our product.
And we also need to conclude all necessary phase II preparations, including any remaining manufacturing toxicology et cetera, and as we progress and development. We will continue to refine our formulation towards the final commercial form.
And then independent of the Nash outcome, we will continue to look at the potential for CD 42, 11 in obesity and possibly other alternative indications and.
And ultimately Nash is a complex disease involving of progression from fat accumulation and the liver inflammation to fibrosis cirrhosis, and eventually liver failure or cancer.
They will continue to be a need from multiple treatment options that can be used in combination to address the different stages of the disease and.
And as we've previously described the mechanism of the C. V. 42, 11 is synergistic with some of these other mechanisms like G. O P. One agonists and that suggest potential for utility and that combination treatment setting net.
Slide please.
Yeah.
Now, let's move on to a preclinical program.
With the anti fibrotic peptides or see the 50 138 analogs.
These are of family of novel molecules related to mitochondrial encoded peptide the showed strong anti fibrotic and anti inflammatory properties and multiple in vitro and in vivo models of idiopathic pulmonary fibrosis or I P. S.
Now based on the studies conducted and cultured human lung cells. These peptides of pits of work by reducing the production of key proteins involved and fibrosis and by inhibiting the pathological fibrotic process of cell transformation from healthy long sales to fibrotic cells.
And with built on those initial discoveries with improved analogs, demonstrating clear anti fibrotic and anti inflammatory effects in vivo and prophylactic and therapeutic animal models of I P. S.
And the therapeutic model, we showed the treatment of animals, beginning one week after the induction of fibrosis with bleomycin and had positive effects on all study outcomes, reducing the lung fibrosis of the levels of collagen cytokines secretion and inflammation.
We further demonstrated the efficacy of multiple C. B 51, and 38 analogs in this therapeutic model and then using the same therapeutic model. We showed that the combination of a C. P 50, 138 analog wisdom and Ted and at one of the two approved IPF drugs and the current standard of care produced greater affects the dosing.
Ted and it alone.
Additional combination studies are ongoing however, we will likely use of monotherapy for the initial clinical proof of concept most.
Most importantly, we recently announced the nomination of the New clinical candidate CB 51, and 38 dash three as a potential treatment for idiopathic pulmonary fibrosis.
We have initiated IND, enabling activities and we plan to potentially fall and R&D and start clinical studies in 2020 two.
At the same time, the broad anti fibrotic and anti inflammatory effects of C. B 50, 138, and logs suggest there is the potential for using them to treat other fibrotic diseases.
We're exploring the potential now in the preclinical setting and models such as Nash systemic sclerosis, and kidney fibrosis net.
Slide please.
On this slide we see some of the data flow. That's final C. B 50, 138 desk III candidate that were released last year at the American Thoracic Society virtual annual meeting. This is looking at efficacy of the peptide as mono therapy, using the mouse a therapeutic model of IPF.
So one week after the bleomycin induction of fibrosis animals were treated with placebo vehicle and the red bars.
And then Ted the nib in the green bars or see the 50 138 dash three shown and the Orange bars, now and intently as I said is one of the two approved IPF drugs. It's of tyrosine kinase inhibitor the blocks several different targets, leading to slowing of the progression of IPF.
But and in terms of and it also has significant off target effects, including nausea, and vomiting, and diarrhea and.
And here you see C. B 51, and 38 has consistent anti fibrotic and anti inflammatory of frac effects across the board, including reductions in fibrosis lung weight inflammation in terms of lymphocytes and the lung and.
And the levels of college and both in the lung tissue and secreted into lot of of fluid.
Next slide please.
And here, we see some photo micrographs of the lung tissue from these mice.
Top left you see and example of healthy lung tissue from and animal that did not receive bleomycin top right is the lung tissue of and animal given the bleomycin to induce fibrosis and then treated for two weeks with vehicle control. It shows significant fibrosis and infiltration of the inflammatory cells.
And the bottom left is the lung of and animal given the bleomycin, followed by it and then Ted and it the standard of care.
There is less fibrosis and inflammation, but on the bottom right. We see the long of an animal given the bleomycin and followed by C. B 50, 138, the three even more significant reduction in the fibrosis and the inflammation.
Next slide please.
And here, we see another study in the therapeutic mouse model of IPF.
And this case, we're looking at levels of pro inflammatory cytokines secreted into the lung lavage fluid after induction of fibrosis again waiting a week before trading for 14 days with either vehicle and then Ted and it or <unk> 50, 138 gosh three.
Treatment with Nintendo and they've had no effect on the levels of these pro inflammatory cytokines.
In contrast treatment with <unk> 50, 138 reduce the levels of all of these cytokines.
Next slide please.
Yeah.
And from the same study here, we're looking at infiltration of inflammatory cells into the lung.
By the end of the treatment and treatment with Nintendo and for 14 days and reduce the levels of cell infiltration.
Treatment with <unk> 50, 138 S. Three produced a greater reduction and the levels of macrophages lymphocytes and neutrophils and the lungs.
Next slide please.
So now let's talk a little bit about the candidate selection process of.
Obviously, we can't go into the specific way in which we design new analogues of how we go about changing the structure is to improve the properties. That's part of our proprietary optimization approach but.
But we generate out of logs in an iterative process that incorporates the improvements into their design.
There are many factors that need to be considered and selecting the final clinical candidate.
We evaluate the analogs excuse me and various in vitro and in vivo models we.
And we look at efficacy in animal models of the target indication.
We look of drug like properties, which include things like physical properties chemical and metabolic stability pharmacokinetics and suitability for the intended route of administration.
We also need to consider how easy they are to synthesize and scale up for eventual clinical of commercial use we need to look at preliminary safety data and beyond that there are several other factors involved out of this process. We have identified C. V 50, 138 S. Three.
As the lead candidate.
But there are other peptides that are still useful as potential backups the net.
Next step for <unk> 50, 138, three is to complete the necessary and D, enabling activities and the R&D submission to F D. A.
And with potentially support of first in human clinical study.
Next slide please.
Well lastly, I'll briefly give an update.
On the C V 50, and 64 envelope program. This is our family of Apple and agonist peptides under development as a potential treatment for acute respiratory distress syndrome, a R. D S and COVID-19 related to our D. S.
We previously announced that we signed a non clinical evaluation agreement with the National Institute for allergy and infectious diseases and I D.
And the under this agreement and.
And I I T will evaluate the efficacy of F. C. B 50, and 64 analogs and their model of COVID-19 at their expense.
And the model could be sucked something such as the hamster model of Sars Covid two infection.
That model has been reported to reproduce some of the acute lung changes that are seen and the lungs of COVID-19 patients with a R. D S. The cause.
Non doctor and the timing of that study is now in the hands of NIH. So we cannot provide guidance on when the day that may be available. However, we do look forward to that opportunity to assess the protective effects of <unk> 50, and 64 analogs in the model of COVID-19 related a R. D S and in the meantime, we will continue to move the.
Program forward for a O D S and general subject to available resources.
Next slide please.
Now and this slide we present some recent data from the follow on efficacy study of the C. B 50, and 64 and logs in a mouse model of a R. D S.
This involves using lipopolysaccharide or L. P S induced acute lung injury.
The animals received a single dose of these peptide analogs one of the Arab before the L. P. S administration, and then Bronchoalveolar lavage fluid was collected from the lungs at four hours after the L. P. S induction.
And here we are looking at.
Excuse me.
And here, we're looking at are the levels of key inflammatory cytokines that are found in the Bronchoalveolar lavage fluid and we see the C. B 50, and 64 and logs reduced the levels of pro inflammatory cytokines and these are the same cytokines that are part of the cytokine storm that is characteristic.
Dick of severe COVID-19, a a.
A R D S.
So we're continuing to move this program forward as I mentioned and further development after of candidate selection will depend on the availability of resources.
With that I'll turn the call back to Steve.
Excellent and Ken.
Next slide.
In closing I would like to speak about our priorities and why we see this as a transformational year for co bar.
Our priorities are to generate top line results from the phase one a one b study.
And number two to conduct the IND.
And the enabling studies to bring C. The $51 38, three and.
To first in human trials next year.
And number three to continue to execute on the rest of our preclinical pipeline programs.
From the plan you can see why we believe 2021 represents a year of progress from conducting preclinical studies multiple indications to potentially enable multiple clinical studies and 'twenty 'twenty two.
I am pleased with our advancements across the board and look forward to the continued change and our pipeline.
Given the potential impact of last year's pandemic.
I'm also pleased with the pace of execution.
We know that we have of special opportunity with mitochondria based therapeutics.
We remain committed to delivering on the promise of our science to bring forward a new class of medicines for patients.
Finally, I would like to end my remarks and <unk>.
Thanking the many people participate and our clinical studies, including the healthy volunteers and patients and physicians.
We also would like to thank the great team and co bar of working hard every day to make this vision of real.
<unk>.
Lastly, I'd like to thank our loyal shareholders for believing in our vision.
Next slide.
Now I will turn the line over to the operator to open the line for questions and answers.
Thank you we will now be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad. The confirmation tone will indicate your line is and the question queue. You May press star two if he would like to remove your question from the queue.
For participants using speaker equipment and may be necessary to pick up your handset before pressing the star kids.
One moment, please while we poll for questions.
Thank you. Our first question comes from Michael Morabito with Chardan capital markets. Please proceed with your question.
Hi team. Thanks for taking the questions. So I just wanted to try to touch on the little bit of your expectations for 42 of 11.
And specifically regarding the liver fat, we've seen a lot of Nash.
Compounds come out and reported liver fat data, especially from early trials and.
And the numbers can be all over the place of as far as how much that liver fat and the patents. So based on the mechanism of action roughly and I'm not looking to get a number from you or anything but roughly you know what kind of impact would you expect on liver fat reduction from 42 of weapon that we should be looking for and.
And I also wanted it and find out if the delays in the trial due to multiple COVID-19 impacts and on the ice storms in Texas, and Texas I know that the involved the effect of new enrollments, but did they also affect patient visits for patients that they had already been enrolled and finally.
You mentioned that you'd like the nominated and new third candidate.
By the end of the year do you think that would be likely to be a <unk> C or for something that you've talked about before or is it something that maybe is something new that you know.
Maybe we haven't heard about the floor.
Ken.
Yeah, Let me take those wanted to try and Michael and thanks for the questions. So the first one of about 42 of 11, and the liver fat expectations and so as I said and as you were aware of right. The several of our full week studies have been conducted a summer and end of F. L. D summer and Nash of presumed ash and the liver fat changes and she said have been the Cui.
Varied you know I think it's very difficult for us to predict and it.
The number that we would expect to see but we would hope to be able to see a trend and liver fat out of the four week setting based on our prior observations over that period of it is possible to impact of liver fat significantly in that the duration of treatment.
But again, we're not necessarily looking for of powered significant change so much as a trend and liver fat and asked for a number of your guess is as good as mine, we can't directly predict from the animal studies, what the number will be at the end of a four week study in humans and Thats pretty clear from what's been published from those other studies.
But that's the that's as far as we can go I think.
On your second question.
Which was about the of the COVID-19, and ice storms, yeah, and the other impacts of COVID-19, yeah, whereas we mentioned we did have dropouts related to COVID-19 positive clinical testing. We've had subjects that came back later for safety visits and an unrelated to their time on the study became infected after the fact.
And that hasn't impacted their ability to generate data as far as them having completed their dosing. So that's the minor component of as opposed to you know subjects that have to drop out of the study because they are positively test it but as we said with now completed enrollment of achieve.
The target and are awaiting this less.
Couple of subjects to get through the process and complete the last follow up visit.
And then your third question was about our our third candidate.
And so yeah I think the likelihood is that would come from the E. R. D. S program based on the progress we have there and the fact that we're now moving towards the candidate selection, we've demonstrated and multiple models of the activity that we expect to see for something that is stimulating the apple and agonist pathway. That's clear from these acute lung injury.
Remodels are the next step there of course is select a candidate and moved through the same process that we've just started with CB 50, 138, three but of course are in the case of they are the US will also be dependent on the available resources. So let me know hopefully if I hit on the three things you brought up there Michael.
Yes, you have thank you very much of the color.
Thanks, Michael.
Thank you. Our next question comes from element of Paris with Roth Capital Partners. Please proceed with your question.
Yes. Thank you so much maybe if I could the preempt a housekeeping question the Jeff.
Jeff and I think you mentioned that the fourth quarter R&D expense was.
Comprehensive events that made it a one time and the higher than previous quarters of la.
Looking forward and see where to look at tiny tiny one.
Estimated expenses with the 6.5 to 7 million and all that would be the right range base.
Based on the previous trends might be and.
We expect that to increase higher than that range.
And.
Hi, Omar and thanks, and thanks for the call would probably be that as a base and an and.
Slightly higher than that as we get through.
As we get through the programs and the clinical trial, we're going to start incurring the costs now that you know sort of pushed through to the the this year. So it will probably be around that to a bit higher than that as we invest more on the R&D as well and the other programs.
From the $7 million somewhat.
I didn't hear what you said I'm, sorry, and north of $7 million, that's what you're thinking right. Yes, okay. Okay. Thank you and and Ken If you could if you could just come back the debt 42, 11 study you listed a number of and.
Safety and efficacy Biomarkers, and and biomarker and information that you are collecting in the topline and release Mitra of dose would you focus on or concentrate aren't we.
We would definitely have by the time, we have of topline data and information on all of the ones listed. So you know, we'll certainly have and initial sense of trends across those that the entire list, but as you know when you get data are of that magnitude as far as that money and outcomes. There's a lot of follow.
One of the analysis you need to do so we would expect to be able to tell us when we first put out top line data towards the end of the second quarter, you know what was that our impact specifically on each of those biomarkers.
Right and of course collection of these biomarkers at multiple time points in the 20 patients what kind of subjects.
You have a fairly good sense that there is good.
The completion rate or or or and they do you have the number of data points that you need for the analysis, yeah on the part of that and all of a is because we are the subjects are confined for the duration of treatment. So by definition, we are pretty much assured of having access.
And to to biomarker Readouts and many of these are taken on the weekly basis right.
So you know we'll have a we'll have quite a lot of data out of this the readout.
And if you could just lastly, remind us that how many doses in the Acton and or are you testing.
There's one the one dose level of active versus placebo head to head and the one b. So it's a dose that was selected out of the one of any stage of the study and that's the.
The the same dose being used yep.
But as you know.
To clarify it is once a day dosing for the four week duration of.
By subcutaneous injection.
Got it.
Thank you so much when you're not.
Sure, Thanks, gentlemen, and thanks.
Thanks, Tom.
Thank you. Our next question comes from Steve Brozak with W. B B Securities. Please proceed with your question.
Hey, good afternoon, gentlemen, and thanks for taking the question just just one can you give as much detail as possible on your programs, specifically around COVID-19 and and the the the focus I guess the cause.
There's a lot of people are just simply looking at Covid is a it's a single issue, but the area of that I'm interested in asking about specifically is what I guess ill now turn the long haulers and where the critical importance of cobalt and its programs would be for them and I'll hop back in the queue. Thank you.
Yeah. Thanks, Steve Yeah, I'll take the wants likes the effects of the question Yeah, you're absolutely right Covid is is and evolving our situation.
The situation as far as the secondly, the downstream effects of the the infection. It's not just what happens when you're hospitalized and you recover and you. You think you are returning to a healthy life. There are many people that have long term consequences of the infection and some of these are manifesting and different ways and <unk>.
Terms of things like persistence thrombotic issues, there's evidence of lung fibrosis as a result of the initial injury caused locally and the lungs by Covid as well so there will be continuing our need for ways to treat COVID-19 subjects, even after we have that.
And the need as many people as we can and not just because of these long haul the issues, but because of the emergence of new strains as I'm sure you you're very familiar with the.
The possibility of a new strains emerging when you are unable to vaccinate, everyone. Obviously, there have been pockets, where continuous infection and reinfection occurs and.
And will occur. So we we see you know the possibilities for treatment with Apple and the agonist. So not just in the setting of the acute current a vision of what Covid is but are the longer term issues related to COVID-19.
And which go in many directions related to the downstream damage that the COVID-19 infection has caused and actually overlap somewhat with our other indications. So if you think about it fibrosis now we have and anti fibrotic peptide that is known and our current ethylene the agonist program targeted to Covid, but may very well b and ask.
And that could be used in the setting of the long hole is for COVID-19 as fibrosis becomes more apparent.
Great. Thank you for detailing that because it was one of those things and obviously a lot of people just don't grasp of the totality of it but thank you again.
Yeah. Thanks, a lot of actually effects of the question.
As a reminder, if you would like to ask a question. Please press star one on your telephone keypad. The confirmation tone will indicate that your lineup and the question queue.
Our next question comes from Steuben do Sandra with Brookline. Please proceed with your question.
And thank you the pumps of the business update.
Hum on.
And on behalf of Kumar from Brooklyn, and I had a quick question I really like the word Steve was the guard.
And the studies with the C V fibrosis score of Covid really get the Arts program and this.
Was wondering if you could throw some light on how you plan to move with it and.
So the clinical studies do you expect the partnership's debt.
And possibly big pharma.
Maybe and the odds are dropping in the space.
Yeah. That's the good question as far as the near term setting so.
And we would progress towards you know a healthy subject initial clinical entry and Dennis for the E. R. D. S. Non COVID-19 related population debt would be obviously of a longer and longer term.
Design, probably looking at the same readouts that we're demonstrating are affected by the Apple and signaling pathway. So what affects that having all of those circulating cytokines in the setting of a R. D. S. So driven more by the mechanistic retail and a proof of concept kind of studies is all of it.
I think we with the take that forward initially and to a R. D. S. A and now that May of course change. If the results are we see in the Sars Covid two a L. D. S setting of convincing there may be added momentum if if we get interest from the U S government and that program.
Based on those outcomes.
Okay. Yeah. Thank you by the way if Steve wants to add to that but.
Okay No no that's great can I think of the only other thing I'd add is the.
There's two sides of this right there's the acute disease situation and there is the chronic so thats another piece and thinking about partnering and so forth.
Alright, thank you so much.
Okay. Thank you. Thank you.
Thank you.
Thank you. Our next question comes from Nathan Weinstein with Aegis capital. Please proceed with your question.
Hey, good afternoon, and thanks for the update and for taking my question. So.
Of course, we could just start perhaps you wouldn't mind talking a little bit about the mitochondrial derived peptide the platform itself. The potential you see and all you've discovered over 100 and and the peptides and the thousand analog so perhaps you could speak about the variance and you've seen and those peptides and and maybe the range of indications that they could address perhaps even beyond what's the clinical.
Stage.
Yeah, Yeah, Yeah, let me take that one so it's the great question and it you know the kind of points to what is it that you think mitochondria are right. Obviously, they're not just organelles that are they're generating a T. P. A we know that now from a not just the work of our founders when they first uncovered the of.
Original M D P lists of things like human in and the slips and let's see.
But there is definitely a broad range of possible interactions here from these mitochondrial derived signaling peptides that we're just scratching the surface all of it. So now we have as we said uncovered over 100 sequences and moving from those outwards in terms of.
The improved analogs what are they doing what are they capable of doing again, we're scratching the surface. There, we're using things like target screening of phenotypic screening.
To guess and go and try and find their target sometimes that's very clear as in the case of the CXC are four antagonists, which have minimal of the potency. So by definition highly evolved to a purpose.
And and other cases the effects of the more clear then the target that.
And that would be the case are you know in some of the other settings that we're looking at but the effects of still very you know strong and protective and useful. So we think there's going to be many opportunities here, where we'll find indications we weren't even aware we're involved with the mitochondria as we test.
Of these across a larger range of things initially we focused on metabolic indications because of the paradigm in the mitochondria are of metabolically related but the answer is no there more than that they control the immune system. The control cell proliferation, the control things like Oh, ptosis and defer.
Setting. So there is a broad possibility that these regulatory peptides that we've uncovered could it be used in many different indications and some of which we don't yet appreciate.
Thank you I really appreciate that the answer its very interesting and and I suppose I just from one follow up it's.
Sort of of thematic question around <unk>.
The Gemini Yes go ahead of it.
No. It was exactly that you're headed in that direction. So the the work by Cowen and bars Elias spoke of.
Other collaborators and the appeal besides the metabolic and oncology Theres also indications of an increase.
The around longevity as well as other areas and so you know.
And the work that's been published out there.
You can go through it and you can see there's a broad range of indicators of what might be possible and.
And so and I do think the.
And you know.
As you help people with their health span and that is avoiding some of these diseases you will probably have a big impact on there.
<unk>, a time period in terms of longevity and.
And so we think that will be of possible outcome at some point as well, obviously with the situation with the way drugs get approved and the United States.
Theres a targeted here on specific diseases, but I think most people recognize the.
Some of these diseases of key reasons, whether the cardiovascular or otherwise.
The people aren't living longer and certainly aren't living well longer.
And so I think that there's that opportunity as well.
Great. Thank you pretty much saw my question coming from always more transparent and I think I am and you anticipated that very nicely. So I appreciate the color.
Oh, well, thank you and and I just want to say you know the other day of.
Other you.
You know of few suddenly discovered five new hormones in the body.
People would be you know signed typically you'd be jumping up and down.
And if you knew they were another.
And 95 of those it.
And it would be pretty mind boggling and.
So far we've got five programs moving forward and do I think there are more yes, absolutely and we don't know what they all do by any means yet that's really part of the discovery process. The Ken and his team are executing on but it is a matter of executing on and as we've shown this last year, it's a matter of them.
Time and money to figure out what the different compounds too and we've made big progress and our clinical program as we approach the results as well as and staging the preclinical programs and beginning to move those towards the clinic. So I think the machine is working and the right direction. So we're.
And we're very excited about that.
Okay.
Yeah.
Thank you. Our next question comes from Greg Van Koski with private Investor. Please proceed with your question.
Yes, Hello, gentlemen, and thank you for taking my call.
See here on your accomplishments in 2021 of them is.
And your financing and raising 19 and Mount Milligan and you were added to the Russell 2000, and my question is how it being removed from the Russell 2000 effect of your abilities to finance your operations going forward and the second half.
And I appreciate the question and.
And yet we're not going to really be able to say anything about that on this call.
So sorry, we can speak more about it having directly.
Because of the directly and balls and stock price and so forth. So, but we are well aware of all the possibilities.
Ooh.
Okay, well that was more across the country.
Thank you.
Thank you there are no further questions at this time I would like to turn the floor back over to Stephen angle for any closing comments.
Well Ed.
Investors and I Hope you have appeal debt, we have and moving forward consistently over the last 12 months, we've been doing it within the kinds of resources and funds and in fact, we probably delivered on many promises more than usual or biotech company and.
We are looking forward to continuing the record and in particular to the phase <unk> results soon.
Stay tuned thank you very much.
This concludes today's conference you may disconnect. Your lines at this time. Thank you for your participation and have a wonderful evening.
Yeah.
Okay.