Good afternoon. My name is Paul and I will be your conference operator today. At this time, I would like to welcome everyone to CohBar's Fourth Quarter 2020 Financial results conference call. All lines have been place on mute to eliminate background noise. A brief question-and-answer session will follow the formal presentation.

[Operator Instructions] As a reminder, this conference is being recorded. Now I would like to turn the call over to Jordyn Tarazi, Director of Investor Relations at CohBar to begin. .

Thank you, Paul, and thank you everyone for joining CohBar's fourth quarter 2020 financial results conference call. Joining me on today's call is Steve Engle, CohBar's Chief Executive Officer; Ken Cundy, CohBar's Chief Scientific Officer; and Jeff Biunno, CohBar's Chief Financial Officer.

CohBar's 10-K filing and financial results press release were issued earlier today and may be downloaded from our website at cohbar.com. If you're having issues joining the Webex, you can access the slide presentation from the homepage of CohBar's website to follow along.

Jeff will begin with an overview of the fourth quarter financial results, followed by a business and R&D update from Steve and Ken. Before we begin, I'd like to 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 lead CB4211 drug candidate program, the therapeutic and commercial potential of the company's lead drug candidate CB4211 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.

Forward-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 CohBar.

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 at cohbar.com sec.gov and sedar.com, as well as in the Safe Harbor statement included with today's press release.

You are cautioned that such statements are not guarantees of future performance and that our actual results may differ materially from those set forth in the forward-looking statements.

CohBar 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 Biunno, CohBar's Chief Financial Officer.

Jeff?.

Thanks so much, Jordyn, and thank you, everyone, for joining us this afternoon. As Jordyn mentioned, if you're having issues with Webex, the slide presentation is posted on the home page of the CohBar website. Next slide, please. As Jordyn noted, I'll begin with a review of the financials, followed by a business overview by Steve.

Ken will then review the recent developments in our clinical and preclinical programs and we'll conclude with Q&A. Next slide, please. I'll now provide you with a summary of our financial results for the fourth quarter ended December 31, 2020, compared to the fourth quarter ended December 31, 2019. Next slide, please.

Total operating expenses in Q4, 2020, were $4.365 million, as compared to $3.570 million in Q4 2019, an increase of approximately $795,000. Operating expenses included non-cash costs of $345,000 for the quarter ended December 31, 2020, and $638,000 for the quarter ended December 31, 2019.

Net of the non-cash costs, total operating expenses in Q4, 2020, were $4.020 million, as compared to $2.932 million in Q4, 2019, an increase of approximately $1.088 million. Non-cash operating expenses include stock-based compensation and depreciation and amortization costs.

Research and development expenses were $2.697 million in Q4, 2020, compared to $1.898 million in the prior year period, an increase of approximately $799,000.

The increase in 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 $1.668 million in Q4, 2020, compared to $1.672 million in the prior year period.

For the quarter ended December 31, 2020, CohBar reported a net loss of $4.708 million, or $0.08 per basic and diluted share, compared to a net loss for the quarter ended December 31, 2019 of $3.717 million or $0.09 per basic and diluted share.

Net loss included non-cash expenses of $603,000 for the quarter ended December 31, 2020 and $743,000 for the quarter ended December 31, 2019. Excluding the non-cash expenses, CohBar's net loss was $4.105 million for the quarter ended December 31, 2020, as compared to $2.974 million for the prior year period.

Total non-cash expenses include stock-based compensation, depreciation and amortization costs, and equity modification costs. Moving to the balance sheet as of December 31, 2020, CohBar had $21 million in cash, cash equivalents and investments, compared to $12.6 million in cash and cash equivalents as of December 31, 2019.

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 converted outstanding amounts due in 2021 and 2022.

We converted approximately $3.8 million in principal and interest issuing approximately 3.2 million units on terms that were substantially the same as those in the public offering that we completed in August 2020.

The completion of the private offering strengthened CohBar's balance sheet by converting 81% of the debt outstanding at the end of the quarter. Notes totaling $352,000 are due and payable in 2021, and $503,000 is due and payable in 2022.

Subsequent to the year-end, December 31, 2020, CohBar received proceeds of $1 million from option and warrant exercises.

We estimate that based on our cash and investments balance as of December 31, 2020 plus the proceeds from the equity exercise in 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. Welcome everyone to our fourth quarter 2020 call. We believe that mitochondria-based therapeutics will provide a treasure trove of potential therapeutic agents for treating multiple diseases. CohBar is elucidating the function of multiple peptides, defined by sequences found in 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 therapies in multiple chronic and age-related diseases. This represents a rare opportunity in biotech. So let's start our review of the quarter with four key points.

Number one, yesterday we announced completion the enrollment in the Phase 1b study. Next, we plan to announce when the last subject has completed their last visit. Ken will speak more about the importance of this step in his section.

Currently, we are expecting top line results at the end of the second quarter of 2021 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 CohBar as we advance our clinical programs towards the clinical stage. For example, we announced CB5138-3 as our next clinical candidate for the potential treatment of IPF and other fibrotic diseases.

We have chosen IPF 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 US government's National Institute of Allergy and Infectious Diseases, signing an agreement called an NCEA to evaluate our CB5064 Analogs in models of COVID-19 ARDS.

As a reminder, we will be providing our Apelin agonist peptides to NIAID for them to administer the preclinical COVID-19 studies at their expense. CohBar will continue to develop and evaluate compounds in this program in parallel with the activity being conducted at NIAID.

And four, Wall Street analysts covering CohBar have increased from four to five. Next slide? What is the CohBar opportunity, we believe that we are the leaders in developing a new class of therapeutics based on our founders discovery, the mitochondrial-generated peptides, regulate multiple systems in the body. Think about that. Prior to 2001, in Dr.

Cohen and Dr. Barzilai discovery, people thought mitochondria were just the powerhouses of the cell and not a key player in regulating some of the body's key functions. Because it is a new class of drug, we believe mitochondria-based therapeutics represent a large, untapped and exciting group of potential therapeutics.

Amazingly, our CSO, Ken Cundy and his scientists have discovered over 100 peptides in the mitochondria genome and developed over 1,000 analogs. It is like we have 100 keys on the wall and we are taking them down one-by-one to discover which biological lock they open.

Based on our research results, we believe that some keys may even open multiple locks 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 therapeutics 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 have therapeutic limitations and side effects. In doing so, we are taking advantage of a mitochondrial derived system of peptides that the body has evolved over 1 billion years. In developing our compounds, we are surfing on the wave of evolutionary biology behind the mitochondrial peptides.

For this reason, we believe, they represent a better starting point for developing therapeutic agents with less side effects. As a result, our peptide medicines may have a higher probability of technical success compared to the traditional discovery approach. In the last year, the company's portfolio has grown from two programs to five programs.

We are no longer just a NASH focused company and now the program is targeting ARDS, fibrosis and oncology. It is a really exciting time. We continue to learn new things about this class of potential therapeutics that is new indications, new targeted organs and new mechanisms of action.

We expect to have a number of near-term milestones demonstrating our continued growth into a company with multiple clinical assets. And as a leader in the development of mitochondrial-based therapeutics, we are committed to strengthening our comprehensive intellectual property position. We have benefited greatly from having a first-mover advantage.

Next slide? Now I would like to discuss our accomplishments from last year. On our investor call in November, we announced the continued advancement of our lead program, evaluating CB4211 for NASH and obesity. In our anti-fibrotic program, we identified multiple peptides with both antifibrotic and anti-inflammatory activity in IPF models.

In our Apelin agonist program, we generated confirmatory results in a preclinical model of ARDS and are moving the program forward to a candidate identification. We did this only a few months after announcing the program. In order to finance our pipeline, we significantly strengthened our finances and had four analysts initiate coverage in 2020.

Based on our current plans, we believe our funds can take us through the first quarter of 2022, as Jeff said. We plan to raise additional funds to support moving CB4211 into Phase II and accelerating our other programs. We are planning to move forward such that we may have multiple programs in the clinic next year.

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-based peptide platform and portfolio.

And lastly, we continue to significantly increase our visibility by presenting at 15 conferences in advance 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 BioSpace, Longevity Technology and Chief Executive Magazine. Next slide.

These are the near-term milestones for 2021 through 2022. We expect to have the top-line results from the Phase Ib study at the end of Q2 2021 dependent on a number of factors, including the timing of the last patient visit, last subject visit.

Based on additional funding, we expect to select a third candidate in the second half of the year and initiate activities to support the next CB4211 clinical study. In 2022, we plan to file a new IND for CB5138-3 and begin a first-in-human clinical trial.

Our overall goal then for the pipeline is to continue generating programs, which could lead to multiple clinical studies over the next few years. Next slide. Recently we have experienced a transformation in the development of our portfolio as stated earlier we are going into a company with the potential to have multiple programs in the clinic.

Note that each one of these compounds represents a different family of peptide structures. They are not the same and each program is targeting multiple indications. So this is a true portfolio with potential to provide multiple shots on goal. Next slide. Interest in the development of therapies for NASH and obesity remains high.

There have been a number of NASH companies that went public in the last year. These companies received funding from some of the largest biotech funds and pharmaceutical companies. Sail of the NASH field 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 in response to FDA communications. For several other companies this year is described as an execution year, a relatively quiet year as many of their later 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 our unique mechanism of action we believe there is plenty of room for our novel mitochondria-based therapeutic CB4211. Finally what do we expect from the top-line data from our four-week Phase Ib clinical study of CB4211.

We initiated our study in order to obtain initial safety data and pharmacokinetics in humans and to begin exploring the activity through MRI-PDFF measures and multiple biomarkers. Ken will explain this further in his section. Next slide.

Turning to our second clinical candidate IPF remains a major unmet medical need with few available treatment options. Drugs currently approved for IPF can slow the progression of the disease, but can also cause significant side effects that limit their use. One of the world's foremost medical experts and a consultant to the company Dr.

Toby Maher detailed the difficulties these patients experience with shortened life expectancies on our recent KOL call. Most companies working in the antifibrotic disease area focused on IPF first as it is a chronic, progressive and usually fatal disease that will likely need multiple therapies.

IPF is an orphan indication which provides other advantages in the development process. Beyond IPF, we are targeting a potential broader opportunity in a range of fibrotic diseases affecting different organs, including the liver, kidney, lungs and heart. These diseases account for 45% of all cause mortality in the developed world. Next slide.

I'm often asked, why target COVID-19 ARDS if everyone is being vaccinated. There are three million patients worldwide suffering from ARDS. Even without counting the COVID-19 ARDS patients, acute respiratory distress syndrome remains a major unmet medical need.

And finally, we continue to develop our CXCR4 inhibitor peptides, which were also derived from sequences of peptides found in the mitochondrial genome. Next slide.

Now I will turn the call over to Ken?.

Thanks, Steve. I'll now give a brief update on recent progress in our key research and development programs. Next slide please. So let's start with the clinical program. CB4211 is currently in Phase Ia/Ib clinical testing as a potential treatment for NASH and obesity.

The Phase Ia stage of the study is completed and we recently announced that we have also completed the enrollment of the Phase Ib stage of the study.

Now as a reminder, this Phase Ib stage of the study is a double-blind placebo-controlled study with a target enrollment of 20 obese subjects with NAFLD in order to provide 10 on placebo and 10 on one active dose level of CB4211 given once-daily by injection.

The Phase Ib stage is designed to assess the potential effects of CB4211 on liver fat, body weight and various biomarkers that are relevant to NASH obesity and metabolic disease. Changes in liver fat are measured by MRI-PDFF 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 II study, so we will be looking for trends in the data. We were able to complete enrollment in this study despite the earlier issues, which have included COVID-19 related impacts on the study pause, on slower enrolment, dropouts due to positive COVID-19 tests at one of our sites.

And even more recently, we've had to deal with ice storms in Texas that impacted even routine lab testing across many regions of the state.

We currently expect to have the top line results at 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 has 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 a rolling enrollment. As shown in this simplified diagram, each new subject was enrolled dosed and followed up for safety. When each subject receives their last dose, there's still a follow-up period for safety observation to ensure there are no issues.

This process continues until the last subject has completed the final study follow-up as shown by diamond. Now 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 CB4211 and who received placebo.

When all subjects have completed, the final follow-up visit and after all required data for safety pharmacokinetics, liver fat, body weight and biomarker levels have all been collected, the data are then cleaned, checked for errors, the errors are systematically resolved and then the database is locked.

Only then will the data finally be unblinded and the analysis of the data will begin. Next slide please. So what can we expect out of this Phase Ib study? Well, there are multiple possible outcomes. The primary endpoints of the study are the safety and the tolerability. 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? What have they shown? While there have been several other published studies that have looked at trends in these same types of activity outcomes in either NAFLD or NASH subjects after a similar four-week treatment period.

A number of companies including Merck, NGM, Metacrine, Hepion and DURECT have released data from four-week studies in either NAFLD or NASH subjects. In some cases, they looked at liver fat changes. In others, they looked at biomarkers and sometimes both.

There was a wide range of outcomes in these studies from statistically significant changes to smaller trends and in 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 in other indications, meaning 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 CohBar's Phase 1b.

Our study is a double-blind placebo controlled study, while some of the published studies were 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.

CB4211 has a unique mechanism of action compared to the agents assessed in 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 CB4211, we will obviously need to wait for the top line data. Next slide, please.

Now let's talk about what's next with CB4211. We plan to complete the ongoing Phase 1a/1b study with readouts for NASH and obesity and prepare for the next clinical study in NASH, including seeking a corporate partner.

Now based on positive clinical results and additional funding from potential partnerships and general fundraising, we then plan to initiate preparations for Phase 2 in 2021 and then initiate a Phase 2 study in 2022.

Our plans for another clinical study for NASH will depend on what we see from the Phase 1b data in terms of trends in liver fat reduction by MRI-PDFF and trends in the biomarkers.

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 larger Phase 2 studies that have a longer duration of 12 or 16 weeks. In planning for another clinical study, there are a number of factors that normally must be considered.

Based on the Phase 1b 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 to study and carefully consider the potential contribution of diabetes and other comorbidities in the NASH study population.

It may be advantageous to use a diabetic population on a GLP-1 agonist to take full advantage of potential synergy with CB4211 mechanism and help differentiate our product. Now we also need to conclude all necessary Phase 2 preparations, including any remaining manufacturing toxicology, et cetera.

And as we progress in development, we will continue to refine our formulation towards a final commercial form. And then independent of the NASH outcome, we will continue to look at the potential for CB4211 in obesity and possibly other alternative indications.

Now ultimately NASH is a complex disease involving a progression from fat accumulation in the liver to inflammation to fibrosis, cirrhosis and eventually liver failure or cancer. There will continue to be a need for multiple treatment options that can be used in combination to address the different stages of the disease.

And as we previously described the mechanism of CB4211 is synergistic with some of these other mechanisms like GLP-1 agonists and that suggests potential utility in that combination treatment setting. Next slide please.

Now let's move on to our preclinical program, with the antifibrotic peptides or CB5138 analogs, these are a family of novel molecules related to mitochondria coated peptide that showed strong antifibrotic and anti-inflammatory properties in multiple in vitro and in vivo models of idiopathic pulmonary fibrosis or IPF.

Now based on studies conducted in cultured human lung cells, these peptides appear to work by reducing the production of key proteins involved in fibrosis and by inhibiting the pathological fibrotic process of cell transformation from healthy lung cells to fibrotic cells.

We've built on those initial discoveries with improved analogs, demonstrating clear antifibrotic, and anti-inflammatory effects in vivo, in prophylactic and therapeutic animal models of IPF.

In the therapeutic model, we showed the treatment of animals beginning one week after induction of fibrosis with bleomycin had positive effects on all study outcomes, reducing the long fibrosis, the levels of collagen, cytokine secretion and inflammation. We further demonstrated the efficacy of multiple CB5138 analogs in this therapeutic model.

And then using the same therapeutic model, we showed that a combination of CB5138 analog with nintedanib one of the two approved IPF drugs and the current standard of care produced greater effects than dosing nintedanib alone. Additional combination studies are ongoing. However, we will likely use monotherapy for the initial clinical proof-of-concept.

Most importantly, we recently announced the nomination of a new clinical candidate CB5138-3 as a potential treatment for idiopathic pulmonary fibrosis. We have initiated IND-enabling activities, and we plan to potentially file an IND and start clinical studies in 2022.

At the same time, the broad anti-fibrotic and anti-inflammatory effects of CB5138 analog suggests, there is a potential for using them to treat other fibrotic diseases. We're exploring that potential now in the preclinical setting in models such as NASH, systemic sclerosis, and kidney fibrosis. Next slide please.

On this slide, we see some of the data for that final CB5138-3 candidate that were released last year at the American Thoracic Society Virtual Annual Meeting. This is looking at efficacy of the peptide as monotherapy, using the mouse therapeutic model of IPF.

So one week after bleomycin induction of fibrosis, animals were treated with placebo vehicle in the red bars, nintedanib in the green bars, our CB5138-3 shown in the orange bars. Now nintedanib, as I said is one of the two approved IPF drugs.

It's a tyrosine kinase inhibitor that blocks several different targets leading to slowing of the progression of IPF. But nintedanib also has significant off-target effects, including nausea vomiting and diarrhea.

And here you see CB5138 has consistent anti-fibrotic and anti-inflammatory effects across the board, including reductions in fibrosis, lung weight, inflammation in terms of lymphocytes in the lung and levels of collagen both in the lung tissue and secreted into lung fluid. Next slide please.

And here, we see some photomicrographs of the lung tissue from these mice. Top left, you see an example of healthy lung tissue from an animal that did not receive bleomycin.

Top right, is the lung tissue of an animal given the bleomycin to induce fibrosis and then treat it for two weeks with vehicle control, it shows significant fibrosis and infiltration of inflammatory cells. On the bottom left, is the lung of an animal given bleomycin followed by nintedanib the standard of care. There is less fibrosis and inflammation.

But on the bottom right, we see the lung of an animal given bleomycin followed by CB5138-3 even more significant reduction in the fibrosis and the inflammation. Next slide please. Here we see another study in the therapeutic mouse model of IPF.

In 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 treating for 14 days with either vehicle nintedanib or CB5138-3. Treatment with nintedanib had no effect on the levels of these pro-inflammatory cytokines.

In contrast, treatment with CB5138 reduced the levels of all of these cytokines. Next slide please. 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 nintedanib for 14 days reduced the levels of cell infiltration, but treatment with CB5138-3 produced a greater reduction in the levels of macrophages lymphocytes and neutrophils in the lungs. Next slide please. So now let's talk a little bit about the candidate selection process.

Obviously, we can't go into this specific way in which we design new analogs or how we go about changing their structures to improve their properties. That's part of our proprietary optimization approach. But we generate analogs in an iterative process that incorporates improvements into their design.

There are many factors that need to be considered in selecting the final clinical candidate. We evaluate the analogs in various in vitro and in vivo models. We look at efficacy in animal models of the target indication.

We look at 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 or 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 CB5138-3 as the lead candidate. But there are other peptides that are still useful as potential backups.

The next step for CB5138-3 is to complete the necessary IND-enabling activities and the IND submission to FDA that will potentially support a first-in-human clinical study. Next slide please. Well, lastly, I'll briefly give an update on the CB5064 analog program.

This is our family of Apelin agonist peptides under development as a potential treatment for acute respiratory distress syndrome, ARDS and COVID-19 related ARDS. We previously announced that we've signed a non-clinical evaluation agreement with the National Institute for Allergy and Infectious Diseases, NIAID.

And under this agreement, NIAID will evaluate the efficacy of our CB5064 analog in their model of COVID-19 at their expense and the model could be something such as the hamster model of SARS-CoV-2 infection. That model has been reported to reproduce some of the acute lung changes that are seen in the lungs of COVID-19 patients with ARDS.

The conduct and the timing of that study is now in the hands of NIH, so we cannot provide guidance on when the data may be available. However, we do look forward to that opportunity to assess the protective effects of CB5064 analogs in the model of COVID-19 related ARDS.

And in the meantime, we'll continue to move this program forward for ARDS in general subject to available resources. Next slide please. Now, in this slide, we present some recent data from a follow-on efficacy study of the CB5064 analogs in a mouse model of ARDS. This involves using lipopolysaccharide or LPS-induced acute lung injury.

The animals received a single dose of these peptide analogs one hour before the LPS administration and then bronchoalveolar lavage fluid was collected from the lungs at four hours after the LPS induction. And here we're looking at the levels of key inflammatory cytokines that are found in the bronchoalveolar lavage fluid.

We see that CB5064 analogs reduced the levels of pro-inflammatory cytokines and these are the same cytokines that are part of the cytokine storm that is characteristic of severe COVID-19 ARDS. So, we're continuing to move this program forward as I mentioned and further development after candidate selection will depend on availability of resources.

So, with that, I'll turn the call back to Steve..

Excellent Ken. Next slide. In closing, I would like to speak about our priorities and why we see this as a transformational year for CohBar. Our priorities are to generate topline results from the Phase Ia/Ib study. And number two to conduct the IND-enabling studies to bring CB5138-3 into first-in-human trials next year.

And number three, continue to execute on the rest of our preclinical pipeline programs. From this plan, you can see why we believe 2021 represents a year of progress from conducting preclinical studies in multiple indications to potentially enable multiple clinical studies in 2022.

I am pleased with our advancements across the board and look forward to the continued change in 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 a 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 by thanking the many people who participate in our clinical studies, including the healthy volunteers, patients and physicians.

We also would like to thank the great team at CohBar for working hard every day to make this vision a reality. Lastly, I'd like to thank our loyal shareholders for believing in our vision. Next slide. Now we'll 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. [Operator Instructions] Thank you. Our first question comes from Michael Morabito with Chardan Capital Markets. Please proceed with your question..

Hi, Steve. Thanks for taking the questions. So I just wanted to try to touch on a little bit of your expectations for 4211, specifically regarding the liver fat. We've seen a lot of NASH compounds come out and report liver fat data, especially from early trials. And the numbers can be all over the place as far as how much liver fat is impacted.

So based on the mechanism of action, roughly I'm not looking to get a number for me or anything, but roughly what kind of impact would you expect on liver fat reduction from 4211 that we should be looking for? And I also wanted to find out if the delays in the trial are due to more COVID impacts and the ice storms in Texas.

I know that they involve -- they affected enrollment, but did they also affect patient visits for patients that had already been enrolled. And finally, you mentioned that you'd like nominate a new third candidate by the end of the year.

Do you think that would be likely to be ARDS or CXCR4 something that you've talked about before, or is this something that maybe is something new that maybe we haven't heard about before?.

Ken?.

Yeah. Let me take those one at a time Michael. Thanks for the question. So the first one about 4211 and the liver fat expectations. What I said and as you're aware several four week studies have been conducted. Some are in NAFLD some are in NASH or presume NASH and the liver fact changes as you said have been quite varied.

I think it's very difficult for us to predict a number that we would expect to see, but we would hope to be able to see a trend in liver fat out of the four week setting based on prior observations over that period. It is possible to impact liver fat significantly in that duration of treatment.

But again, we're not necessarily looking for a powered significant change so much as a trend in liver fat. As for a number, 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 that's pretty clear from what's been published from those other studies, but that's as far as we can go I think. On your second question which was about the COVID-19 ice storms and the other impacts of COVID-19.

Yeah, as 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 unrelated to their time on the study became infected after the fact that hasn't impacted their ability to generate data as far as them having completed their dosing.

So that's a minor component as opposed to subjects that have to drop out of the study because they are positively tested. But as we said, we've now completed enrolment, achieved our target and awaiting this less couple of subjects to get through the process and complete their last follow up visit.

And then your third question was about our third candidate. So yes, I think the likelihood is that would come from the ARDS program, based on the progress we have there and the fact that we are now moving towards a candidate selection.

We've demonstrated in multiple models the activity that we expect to see for something that is stimulating the Apelin agonist pathway, that's clear from these acute lung injury models.

The next step there of course is select a candidate and move through the same process that we've just started with CB5138-3, but of course in the case of ARDS will also be dependent on available resources.

So let me know, have I hit on the three things you brought out there Michael?.

Yes, you have. Thank you very much for the thought..

Thanks Michael..

Thank you. Our next question comes from Elemer Piros with ROTH Capital Partners. Please proceed with your question..

Yes, thank you so much. Maybe if I could pre-empt a housekeeping question with Jeff. Jeff, I think you mentioned that the fourth quarter R&D expense was confluence of events that made it a onetime higher than previous quarters.

Looking forward if you were to look at 2021 estimated expenses, would the $6.5 million to $7 million would be the right range, based on previous trends, or do you expect that to increase higher than that range?.

Hi Elemer, thanks for the call. It will probably be that as a base 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 cost now that sort of pushed through to this year.

So, we'll probably be around that to a bit higher than that as we invest more in the R&D, as well in the other programs. .

So north of $7 million and some... .

I didn't hear what you said I'm sorry?.

North of $7 million that's what you're referring to?.

Right. Yes. .

Okay. Okay. Thank you. And Ken if you could just come back to the 4211 study. You listed a number of safety and efficacy biomarkers and biomarker information that you're collecting in the top line release.

Which of those would you focus on or concentrate on?.

We would definitely have -- by the time we have our top line data information on all the ones listed. So we will certainly have an initial sense of trends across those -- that entire list. But as you know when you get data of that magnitude as far as that many outcomes there's a lot of follow-on analysis you need to do.

So we would expect to be able to tell when we first put out top line data towards the end of the second quarter what was our impact specifically on each of those biomarkers. .

Right.

And as far as collection of these biomarkers at multiple time points in the 20 patients or 20 subjects you have a fairly good sense that there is good completion rate or that you have the number of data points that you need for the analysis?.

Yes. And part of that Elemer is because we are -- these subjects are confined for the duration of treatment. So by definition, we are pretty much assured of having access to biomarker readouts. And many of these are taken on a weekly basis. So we'll have quite a lot of data out of this readout. .

And if you could just lastly remind us that how many doses in the active arm are you testing?.

There's one dose level of active versus placebo head-to-head in the Ib. So it's a dose that was selected out of the Ia Stage of the study and that's the same dose being used. Yes. But just to clarify it is once-a-day dosing for the 4-week duration by subcutaneous injection. .

Got it. Thank you so much for your help..

Sure, thanks Elemer..

Thank you. Our next question comes from Steve Brozak with WBB Securities. Please proceed with your question..

Hey, good afternoon gentlemen. And thanks for taking questions. Just one, can you give as much detail as possible on your programs, specifically around COVID? And the focus I guess, because a lot of people are just simply looking at COVID as a single issue.

But the area that I'm interested in asking about specifically is, what I guess is now turned long haulers. And where the critical importance of CohBar and its programs would be for them? And I'll hop back in the queue. Thank you..

Ken?.

Yeah. Thanks, Steve. Yeah, I'll take that one. Thanks, Steve. Thanks for the question. Yeah, you're absolutely right. COVID is an evolving situation as far as the squally the downstream effects of the infection. It's not just what happens when you're hospitalized and you recover and you think you're returning to a healthy life.

There are many people that have long-term consequences or infection. Some of these are manifesting in different ways in terms of things like, persistent thrombotic issues. There's evidence of lung fibrosis, as a result of the initial injury caused locally in the lungs by COVID as well.

So, there will be continuing need for ways to treat COVID subjects even after we have vaccinated as many people as we can. And not just because of these long-haul issues, but because of the emergence of new strains, as I'm sure you're very familiar with the possibility of new strains emerging.

When you are unable to vaccinate everyone obviously there are then pockets where continuous infection and re-infection occurs and mutation will occur.

So we see the possibilities for treatment with Apelin agonists are not just in the setting of the acute current vision of what COVID is, but the longer-term issues related to COVID which go in many directions related to the downstream damage that the COVID infection has caused. And actually overlaps somewhat with our other indications.

So if you think about it fibrosis now we have an antifibrotic peptide. That is not our current Apelin agonist program targeted to COVID, but may very well be an asset that could be used in the setting of the long haulers for COVID, as fibrosis becomes more apparent..

Great. Thank you for detailing, that because it was one of those things that obviously a lot of people just don't grasp the totality of it. Thank you again..

Yeah. Thanks a lot Steve….

Thanks..

Thanks for the question..

[Operator Instructions] Our next question comes from [Indiscernible] with Brookline. Please proceed with your question..

Hi. Thank you. Thanks for the business update. I'm on behalf of Kumar from Brookline. And I had a quick question related to what Steve asked, regarding the studies with CB5064, your COVID-related ARDS program. I was just wondering if you could throw some light on how you plan to move with it.

In terms of the clinical studies do you expect to have partnership with possibly big Pharma, maybe in the ARDS or diabetes space?.

Yeah, that's a good question. As far as the near-term setting, so we would progress towards healthy subject initial clinical entry. Then for the ARDS, non-COVID-related population that would be obviously a longer-term design probably looking at the same readouts that we're demonstrating or affected by the Apelin and signaling pathways.

So, what effects are we having on those circulating cytokines in the setting of ARDS? So driven more by the mechanistic readout in a proof-of-concept kind of study is how I think we would take that forward initially into ARDS.

And now that may of course change, if the results we see in the SARS-CoV-2 ARDS setting are convincing there may be added momentum if we get interest from the U.S. government in that program based on those outcomes..

Okay. Yeah. Thank you..

Steve wants to add to that, but....

Okay..

No, no, that was great, Ken. I think the only other thing I'd add is that, there's two sides of this right? There's the acute disease situation and there's the chronic. So that's another piece in thinking about partnering and so forth..

Correct. Thank you so much..

Thank you..

Thank you..

Thank you. Our next question comes from Nathan Weinstein with Aegis Capital. Please proceed with your question..

Hey, good afternoon. Thanks for the update and for taking my question. So I suppose we could just start perhaps you wouldn't mind talking a little bit about the mitochondria derived peptide the platform itself, the potential you see I know you've discovered over 100 of the peptide and 1,000 analogs.

So perhaps you could speak about the variance you've seen in those peptides and maybe the range of indications they could address perhaps even beyond what's the clinical stage?.

Ken?.

Yeah. Let me take that one. So it's a great question and it points to what is it that you think mitochondria are, right? Obviously they're not just organ ALS that are there generating ATP.

We know that now from not just the work of our founders when they first uncovered the original MDP list so things like humanin and the SHLPs and MOTS-c, but there is definitely a broad range of possible interactions here from these mitochondrial derived signaling peptides that we are just scratching the surface of.

We have as we said uncovered over hundred sequences and moving from those outwards in terms of 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 and phenotypic screening to guess and go and try and find their targets.

Sometimes that's very clear as in the case of the CXCR4 antagonist, which have nanomolar potency. So by definition highly evolved to a purpose. And in other cases the effects are more clear than the target. That would be the case in some of the other settings that we're looking at. But the effects are still very 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 mitochondria as we test these across a larger range of things. Initially we focused on metabolic indications because of the paradigm that mitochondria are metabolically related, but the answer is no they're more than that.

They control the immune system. They control cell proliferation. They control things like apoptosis in different settings. So there is a broad possibility that these regulatory peptides that we've uncovered could be used in many different indications, some of which we don't yet appreciate..

Thank you. I really appreciate that -- the answer. It's very interesting. And I suppose I just have one follow-up. It's, sort of, a thematic question around longevity. Yes go ahead..

No, it was exactly that. You're headed in that direction. So the work by Cohen and Barzilai as well as other collaborators in the field, besides metabolic and oncology there's also indications of an increase around longevity as well as other areas. And so in 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 so -- and I do think that as you help people with their health span that is avoiding some of these diseases, you will probably have a big impact on their total time period in terms of longevity. And so we think that will be a possible outcome at some point as well.

Obviously with the situation with the way drugs get approved in the United States there's a target here on specific diseases, but I think most people recognize that some of these diseases are the key reasons whether it's cardiovascular or otherwise that people aren't living longer and certainly aren't living well longer.

And so I think that there is that opportunity as well..

Yeah, thank you. You pretty much saw my question coming, so I'm always more transparent than I think I am and you've anticipated that very nicely. So I appreciate the color..

Well, thank you. And I just want to say the other day, I was there with someone if you suddenly discovered five new hormones in the body, people would be scientifically be jumping up and down. And if you knew there were another 95 of those, 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. It's really part of the discovery process that Ken and his team are executing on. But it is a matter of executing on it. As we've shown this last year, it's a matter of time and money to figure out what these different compounds do.

And we've made big progress, both in our clinical program, as we approach the results, as well as in staging the preclinical programs and beginning to move those towards the clinic. So, I think the machine is working in the right direction. So, we're very excited about that..

Thank you. Our next question comes from Greg Wan Cowski [ph] with Private Investor. Please proceed with your question..

Yes. Hello gentlemen. Thank you for taking my call. I see here on your accomplishments in 2020, one of them is your financing, raising $19.5 million and you were added to the Russell 2000.

My question is, how it being removed from the Russell 2000 affect your abilities to finance your operations going forward in the second half?.

I appreciate the question. And yes, we're not going to really be able to say anything about that on this call. So sorry, we can't speak more about it. I mean directly. Because it directly involves stock price and so forth. So -- but we are well aware of all the possibilities..

Okay. Well, that was my question. Thank you..

Thank you..

Thank you. There are no further questions at this time. I would like to turn the floor back over to Steve Engle for any closing comments..

Well, as investors, I hope you have a feel that, we have been moving forward consistently over the last 12 months. We've been doing it within the kinds of resources and funds. And in fact, we've probably delivered on many promises more than usual for a biotech company.

And we are looking forward to continuing that record and in particular to the Phase Ib results soon. So 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..