CohBar Inc (CWBR) 2020 Q1 法說會逐字稿

Good afternoon. My name is Sherry, I will be your conference operator today. At this time, I would like to welcome everyone to CohBar's First Quarter 2020 Financial Results Conference Call. (Operator Instructions) I would like to turn the conference over to Jordyn Tarazi, Director of Investor Relations at CohBar. Thank you. You may begin.

Thank you, Sherry, and thank you, everyone, for joining CohBar's First Quarter 2020 Financial Results Conference Call. Joining me on today's call is Steven Engle, CohBar's Chief Executive Officer; Ken Cundy, CohBar's Chief Scientific Officer; and Jeff Biunno, CohBar's Chief Financial Officer.

CohBar's 10-Q 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 also access the slide presentation from the homepage of CohBar's website to follow along. Jeff will begin with an overview of the first 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 company's plans and expectations regarding pipeline expansion; 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?

Thank you, Jordyn, and thank you, everyone, for joining us this afternoon. As Jordyn mentioned, if you're having issues joining the Webex, this slide presentation is posted on the homepage of the CohBar website. Next slide, please. As Jordyn noted, I will 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 will conclude with Q&A. Next slide, please.

I will now provide you with a summary of our financial results for the first quarter ended March 31, 2020, compared to the first quarter ended March 31, 2019. Total operating expenses in Q1 2020 were $3,281,000 as compared to $2,828,000 in Q1 2019, an increase of approximately $453,000. Operating expenses included noncash expenses of $927,000 for the quarter ended March 31, 2020, compared to $798,000 in the prior year period. Net of the noncash expenses, total operating expenses in Q1 2020 were $2,354,000 as compared to $2,030,000 in Q1 2019, an increase of approximately $324,000. Noncash operating expenses include stock-based compensation and depreciation and amortization costs.

Research and development expenses were $1,450,000 in Q1 2020 compared to $1,372,000 in the prior year period, an increase of approximately $78,000. The increase in research and development expenses was primarily due to an increase in expenses related to our continuing development of peptides, partially offset by a decrease in bonus and stock-based compensation costs.

General and administrative expenses were $1,832,000 in Q1 2020 compared to $1,456,000 in the prior year period, an increase of approximately $376,000. The increase in general and administrative expenses was primarily due to an increase in stock-based compensation costs, directors' fees and D&O insurance premiums incurred in the current year period.

During the quarter ended March 31, 2020, CohBar recognized a noncash expense of $802,000 in other expenses, which related to the modification of warrants that took place during the quarter. For the quarter ended March 31, 2020, CohBar reported a net loss of $4,218,000 or $0.10 per basic and diluted share compared to a net loss for the quarter ended March 31, 2019, of $2,921,000 or $0.07 per basic and diluted share.

Net loss included noncash expenses of $1,816,000 for the quarter ended March 31, 2020, and $903,000 for the quarter ended March 31, 2019. Excluding noncash expenses, which include stock-based compensation, depreciation and amortization costs and other expenses, CohBar's net loss was $2,402,000 for the quarter ended March 31, 2020, as compared to $2,018,000 for the prior year period.

Moving to the balance sheet, as of March 31, 2020, CohBar had $10.2 million in cash and cash equivalents compared to $12.6 million in cash and cash equivalents as of December 31, 2019. The cash burn for the quarter ended March 31, 2020, was approximately $2.5 million. We estimate that based on our cash and investments balance as of March 31, 2020, we have sufficient capital to finance our operations into the second quarter of 2021.

Subsequent to the quarter end, the company extended the expiration date of the remaining warrants that were issued as part of the company's private offering completed in July 2017. The expiration date of these warrants was extended from June 30, 2020 to September 30, 2021, with the remaining terms and conditions of the warrants unchanged. The company has now extended the expiration dates of the warrants to purchase a total of 3.2 million shares with a strike price of $2.25 from the July 2017 private offering.

I'll now turn the call over to Steve. Steve?

Thanks, Jeff. Welcome, everyone, to our Q1 2020 call. Next slide. Before I talk about the new program news, let me review CohBar's vision and the basis for our technology. This is a cornerstone slide for CohBar summarizing the company and maybe a review for some of you who know our story well.

Beginning with the first bullet, the discovery behind CohBar's technology is the finding that mitochondria, more than the powerhouses of the cell that we learned in biology class, can generate signals that affect cells, organs and systems across the body. Based on the last decade of research, mitochondria dysfunction underlies multiple chronic and age-related diseases, like NASH and obesity, cancer, diabetes and cardiovascular. CohBar has discovered over 100 peptides encoded in the mitochondria genome and has generated over 1,000 analogs. As a result, we believe we have a platform technology capable of providing multiple shots on goal.

CB4211 is the first mitochondria-based therapeutic to be evaluated in a clinical study in humans. We believe that CB4211 is the first of a number of candidates that our technology platform will identify for advancement into the clinic. Our Chief Science Officer, Ken Cundy, will discuss this further in his section. In parallel, we have generated 4 preclinical programs. We plan to nominate one of these programs for IND-enabling studies in 2020. Ken will speak to that more in a moment.

We are the leaders in the development of mitochondria-based therapeutics. Our IP portfolio is significant and continues to expand. We have an experienced management team that's well leveraged by preclinical and clinical research organizations, outside medical and other experts and world-class founders. This provides strong talent and breadth on a timely basis and with financial efficiency.

As Jeff stated, we had $10.2 million as of the end of the first quarter. We have been spending less than about $900,000 monthly in the last quarter and expect our runway to take this into 2Q 2021. We think it is prudent to plan to maintain our burn rate at the same level until we raise additional funds. We continue to prioritize our spending on the platform, which we will discuss later. Next slide, please.

We believe mitochondrial medicine is a rapidly evolving science in the lead to breakthrough drugs. What is mitochondrial medicine? Mitochondrial medicine focuses on the broad role of mitochondria and mitochondria dysfunction in people's health, aging and disease. Recent research supports a much broader role for mitochondria, including signaling within and between cells and organs, and orchestrating multiple biological systems like the metabolic and immune systems. Mitochondrial dysfunction occurs when the mitochondria fail, either due to environmental or genetic causes. Based on public studies, mitochondrial dysfunction may lead to multiple diseases, metabolic diseases like NASH and neurological diseases like Alzheimer's. We also note that when mitochondria do not function properly, diseases can become increasingly systemic, another aspect of mitochondrial medicine. Next slide.

CohBar's mitochondrial peptide has demonstrated potential to address a wide range of therapeutic needs. We've seen evidence of this in our own research and development activities. Early research from our founders demonstrated therapeutic potential for metabolic diseases, inflammation and cancer. Our own CB4211 peptide has demonstrated potential to treat NASH and obesity, both metabolic diseases, by targeting the fat that leads to inflammation and fibrosis.

More recently, we have demonstrated in animal models the potential of our peptides to act as CXCR4 pathway inhibitors, anti-fibrotic agents and apelin agonists. As you can see, these target a diverse set of diseases. This further supports our belief in the potential of our library of mitochondrial peptides to address the therapeutic needs of a wide range of diseases. We also believe it continues to position CohBar as a first mover and leader in this important new arena of mitochondrial medicine. Next slide.

I am pleased to share with you that since my arrival at CohBar last May, we have expanded the number of programs from 2 to 5. Most recently, we announced that we have a new target for our CB5064 apelin agonist program, which is COVID-19-associated acute respiratory distress syndrome, or ARDS, a life-threatening condition that lacks adequate therapies. We are excited because published preclinical studies have shown that apelin can reduce the severity of acute lung injury. We are also excited because we believe this program will have beneficial effects in ARDS of the non-COVID kind, where it is estimated that there are over 3 million patients around the world annually.

We have already shown that our apelin agonists have positive effects in obese mouse model, a commonly used model for type 2 diabetes. We believe by harnessing the potential of mitochondrially encoded peptides, our apelin agonist may represent a unique approach to this potentially deadly condition. Ken's section will focus on this new target.

This past quarter, in a brand-new program, we demonstrated that our recently discovered CXCR4 agonist reduced the growth of tumors in a model of melanoma when used with chemotherapeutic agents over the use of the agent by itself. We also made significant progress with our anti-fibrotic program by generating new results in a therapeutic model of idiopathic pulmonary fibrosis. Finally, like many biotech companies, we paused our Phase Ib study in NASH and obesity, which we hope to continue once the COVID-19-associated conditions impacting our study sites have improved.

With this quarter's accomplishments, CohBar continues to expand its portfolio of mitochondrial-encoded peptides and maintain our leadership in mitochondrial medicine.

So what is the story behind this most recent news? Given the challenging COVID-19 pandemic, you probably wouldn't be surprised that over the last 2 months, we have also been looking for ways to potentially use the unique property of our existing mitochondrial peptides to help in the COVID fight. We believe mitochondrial-encoded peptides are key regulators of many functions in the body. The mitochondria themselves are found in thousands, in most cells of the body, which include the immune cells, the lungs and other organs. As a result, we thought we might find a mitochondria-based therapeutic in our ongoing programs that would affect organs, such as the lungs.

Further, we know the conditions like ARDS are intensified by cellular processes such as up-regulation of inflammatory agents, including cytokines. We also know that cytokine levels can be affected by half-life downstream from the activity of some of our peptides. This led us to review the possible impacts of apelin signaling on downstream processes that contribute to both ARDS and the global effect of COVID-19 on other organs. This was a breakthrough that expanded our view of the potential of apelin agonist peptides, which had already shown promise in affecting both glucose tolerance and fat levels in animal model of type 2 diabetes. As a result, we focused on this family of active apelin antagonists that were effective and well tolerated in these initial animal studies.

As you also might imagine, we have reviewed the science and our plans with world-class medical experts in the fields of lung diseases and ARDS. Based on their support for this approach, we decided to move forward with targeting the apelin program at ARDS and, more specifically, COVID-19-associated ARDS.

We know some people have asked what happens if COVID-19 is cured suddenly, not likely at this point, but a question we have discussed. We believe that if our peptides have positive effects in COVID-19 ARDS, that we would expect to see a positive impact on other types of ARDS. We also believe that some of these potential effects of our peptides could protect other organs. This has had a very productive and been a very exciting 2 months as a company. We've not only continued progress on our other preclinical programs, which Ken will summarize, but we have developed a new indication for an existing compound in our preclinical programs. We are planning additional preclinical studies now, which we expect will generate more data in the near future. With this quarter's accomplishments, CohBar continues to expand its portfolio.

It has also been a very productive time in sharing our study -- our story with investors, both at the major conferences like JPMorgan and BIO CEO as well as in one-on-one meetings in New York, Boston and San Francisco. It is important to note that since the shelter-in-place process started, we really have not slowed down in holding conversations with both investors and analysts.

Before Ken speaks on our clinical and preclinical programs, I would like to thank Jon Stern, a long-term company executive who is stepping down from his day-to-day management role. As noted in the press release issued earlier, Jon has been a critical player in helping the company grow from the small, early-stage research company to where it is today. We appreciate all of his contributions to CohBar, and we look forward to continuing our close working relationship with him as a Director. Thanks, Jon.

With that, I will turn it over to Ken. Ken?

Thanks, Steve. I'll now give a brief update on our R&D programs, beginning with our CB4211 clinical program. Next slide, please.

CB4211 is our novel enhanced analog of MOTS-c, a naturally occurring mitochondrially encoded peptide discovered by our Co-Founder, Dr. Hassy Cohen & his colleagues. 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 complete and involved a double-blind, placebo-controlled, single ascending dose, multiple ascending dose assessment of safety, tolerability and pharmacokinetics in healthy adults to select the most appropriate dose for the Phase Ib stage. No significant safety or tolerability issues were observed in the Phase Ia after restarting the study.

The Phase Ib part of the study is a double-blind, placebo-controlled evaluation of 1 dose level of CB4211 given once daily in obese subjects with NAFLD. This phase 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 will be assessed by MRI-PDFF, and all subjects must have a minimum of 10% liver fat at baseline.

As we announced in March, the Phase Ib stage of the study is currently paused due to COVID-19. This pause is not unique to CohBar, as more than 1,000 clinical studies have been affected globally by the pandemic, and many of them have paused enrollment. As we mentioned on the last quarterly call, we added 3 new clinical sites to the study earlier this year in order to accelerate enrollment. We're continuing to monitor the situation and expect to provide an update once there's a change in status. But as previously stated, we will not be providing subject-by-subject details on enrollment.

As a result of the COVID-19 pause, we are unable to provide guidance on the time line for availability of top line activity data at this time. In the event that the COVID-19 pause is lifted, the timing of the study will be a function of the post COVID-19 enrollment rate, and we will have more clarity on that when the study resumes. We plan to update on the progress on the next investor call. Next slide, please.

Turning to the rest of our pipeline, we expect additional data from several programs over the next 3 to 6 months. On the last quarterly call, we shared information on 4 programs in the preclinical peptide optimization stage. The first of these was announced in January, our MBT5 analogs for cancer and other indications. MBT5 analogs are a family of peptides that are highly potent in selected inhibitors of the CXC chemokine receptor type 4, or CXCR4, a key chemokine receptor that regulates the growth and metastasis of tumors as well as the localization of immune cells within the bone marrow.

On the last call, we shared data on the in vitro activity of this family of peptides in cell-based assays and successful translation to the in vivo setting in a mouse model of aggressive melanoma, where an MBT5 analog enhanced the efficacy of chemotherapy. We plan to advance this program now into additional preclinical models, including potentially models of hematological cancer and stem cell mobilization with the goal of identifying a candidate for advancement.

The second program is our MBT2 analog peptides for fibrotic diseases. We previously shared data on the efficacy of MBT2 in prophylactic and therapeutic mouse models of idiopathic pulmonary fibrosis, or IPF. In April, we announced acceptance of our late-breaking abstract on this program at the American Thoracic Society, ATS, National Meeting. The ATS in-person meeting originally planned for May was eventually canceled due to concerns around COVID-19, but the abstract has been published by ATS, and they are now considering a virtual meeting later this year. This family of peptides has been further expanded, and we're now running additional studies with the goal of identifying a candidate for advancement towards IND-enabling studies.

The third program, also discussed on previous calls, is the MBT3 peptide analogs with potential for cancer immunotherapy, enhancing the killing of cancer cells by human immune cells in vitro. That program will be advancing into in vivo studies to look at translation of these in vitro effects.

The final program on the list is the CB5064 analogs. This is a family of novel apelin agonists that have already shown positive results in a mouse model of type 2 diabetes. This program has now been expanded to include a new target indication, acute respiratory distress syndrome, or ARDS, including specifically ARDS associated with COVID-19. On today's call, I will focus on this newest indication. Next slide, please.

So this is now a new target for our CB5064 analogs, the acute respiratory distress syndrome, or ARDS, and specifically, COVID-19-associated ARDS.

Next slide, please. Well, let's start with understanding what ARDS is. So ARDS is a much bigger problem than just what we are now seeing in the setting of COVID-19. ARDS can be triggered by a variety of injuries to the lungs such as viral or bacterial infection, including influenza viral infections, sepsis, traumatic injury, inhalation of smoke or chemicals and other sources. ARDS presents most commonly as a sudden shortness of breath, accompanied by rapid breathing, a fast heart rate, mental confusion, low blood oxygen and extreme tiredness.

As shown on the right of this slide, ARDS involves damage to the thin lining of the lungs that separates the capillary blood flow from the alveoli or air sacs, where the exchange of oxygen and carbon dioxide occurs. When that thin layer of lung cells is damaged, there is a leakage of fluid, blood cells and proteins from the blood that gradually fills the air sacs and blocks the ability of the lungs to absorb oxygen. Blood cells entering the damaged alveoli send out a cascade of signals that start an intense inflammatory response.

Now ARDS is a major cause of morbidity and mortality among patients who are hospitalized for other reasons, and usually occurs within about 7 to 10 days of the initial injury. There are no effective drugs for prevention or management of ARDS, and instead, ARDS patients with low blood oxygen levels are treated with mechanical ventilation and supportive care in attempt to support breathing, reduce infection, reduce inflammation, pain and anxiety.

The resulting need for intensive care, convalescence and rehabilitation leads to long hospital stays that are a major contributor to expensive and rising health care costs. There's a huge unmet need for a safe and effective treatment to reduce time spent on ventilators, reduce mortality and to improve the quality of life. Even without COVID-19, ARDS is a major unmet medical need affecting about 3 million people globally. Next slide, please.

In the setting of COVID-19, ARDS has emerged as one of the most lethal consequences of the coronavirus infection, and this is why so many people end up on ventilators. In severe cases, the virus infects the cells lining the lungs, leading to pneumonia, inflammation, cellular destruction, resulting in that loss of the thin capillary alveola membrane that separates the blood from the air spaces. The local damage leads to vascular leakage and accumulation of fluid in the alveoli. As the lungs fill with fluid, the blood cannot absorb enough oxygen and the heart must pump harder to force blood through the saturated lungs.

Another potentially devastating effect of the virus is a disregulated release of inflammatory signals called a cytokine storm. This results in intense local inflammation, but the storm also reaches other organs like the heart, the kidneys, the liver and the brain, where inflammation and cellular damage can eventually result in multi-organ failure. Next slide, please.

Now recent evidence shows that metabolic dysfunction is a major underlying factor contributing to the severity of COVID-19. The presence of comorbidities like obesity, hypertension and diabetes all increase the chances of severe disease and lethal consequences. As an example, a recent publication took a retrospective look at the fate of 7,000 patients with COVID-19. The presence of type 2 diabetes prior to infection increased the overall need for medical intervention, including ventilation, and had a significant impact on overall survival. In fact, 7.8% of COVID patients with diabetes died, while only 2.7% of those without this comorbidity died. And looking just at the subpopulation of patients with diabetes, as shown in the diagram on the left, those with poor glucose control had a much greater chance of dying, 11% versus closer to 1% for those who had well-controlled glucose levels. Next slide, please.

Now let's look at how apelin signaling figures into this picture. Apelin is a naturally occurring adipokine. It's a cell-signaling peptide secreted by fat cells or adipocytes to regulate a variety of biological functions, including fluid homeostasis, metabolic homeostasis, cardiovascular function, inflammation and other processes. It works by activating a cell surface receptor called the apelin receptor, or APJ, found broadly in most tissues but particularly abundant in lung and heart.

On the right of this slide, you see a stimulation of the receptor on the surface of cells leads to activation of several different intracellular signaling pathways that in turn regulate the expression and control of other proteins. These include pathways involving important regulators like RAS, AMPK, ERK 1/2, eNOS and others. Apelin is, therefore, a key regulator of multiple regulatory pathways, leading to pleiotropic or broad system effects. Apelin has been shown to have broad protective effects in animal models of ARDS, including prevention of the pulmonary edema or fluid accumulation in rodent models of acute lung injury, and reduction of acute lung damage caused by chemical insults like oleic acid, or bacterial toxins like lipopolysaccharide or LPS.

Importantly, apelin signaling also decreases pro-inflammatory cytokine levels in these and -- in these cells and protects other organs such as the liver from similar damage. Apelin has also shown beneficial metabolic effects by decreasing body weight and fat deposits in obese mice. However, apelin itself is rapidly metabolized, and the in vivo half-life is only about 8 minutes. So this is too short for effective use of the peptide itself in the clinic. Next slide, please.

Now CohBar's CB5064 analogs are a family of novel peptides based on a natural human peptide encoded within the mitochondrial genome. We've confirmed that a number of them display agonist activity at the apelin receptor in vitro using different assay formats, in some cases, stimulating a signal of the same magnitude as that produced by apelin itself. Metabolic stability of the peptides has also been demonstrated in human plasma in vitro. We've previously shared data for this family of novel apelin agonists in the setting of type 2 diabetes at the American Diabetes Association meeting last year.

In that poster presentation, we showed that administration of CB5064 analogs to obese mice led to improved glucose tolerance in diet-induced obese mice and reduced body weight and fat mass. No safety issues have been observed to date in multiple 10- to 14-day rodent studies of these molecules. Based on their ability to engage the apelin signaling pathway, we now believe that the CB5064 analogs could potentially have similar effects to apelin on acute lung injury. Let's go to the next slide.

So the rationale for potentially using a CB5064 analog to treat ARDS associated with COVID-19 lies in the demonstrated ability of the apelin signaling pathway in animals to regulate many of the damaging processes that are also induced by COVID-19 injury. On the left here, you see COVID-19, coronavirus infection, producing the same array of damaging effects that we've already described: pneumonia, vascular leakage, fluid accumulation, low blood oxygen and the cytokine storm, leading to multi-organ failure. Next slide, please.

And there you see the effect that a CB5064 analog could potentially have by engaging the apelin receptor, initiating a series of protective events to potentially block many of the damaging processes shown here. By decreasing fluid accumulation and vascular leakage, a CB5064 analog can potentially reduce fluid accumulation and improve oxygen absorption, raise the levels of oxygen in the blood. By blocking the cytokine storm, our peptides could potentially protect other organs from failure, and thereby reduce mortality and the long-term health consequences after recovery from COVID-19. Since the effects of apelin signaling are independent of the cause of the lung injury, this approach could equally be applicable to other forms of ARDS, including even ARDS resulting from infections by future novel strains of viruses or bacteria. So now let's look at some of the underlying data that support this approach. Next slide, please.

In this slide, we see just one example of the published data on the protective effects of stimulating the apelin receptor in the setting of acute lung injury. In this case, in animals injured by introducing a bacterial toxin into the lungs, apelin injection reduced the infiltration of inflammatory cells into lung tissue and preserve the lung structure, as you can see in the Figure A. Apelin also reduced the accumulation of fluid in the lungs as measured by the difference in the water content in Figure B. Capillary leakage was also decreased by apelin based on the measurement of protein leaking into the bronchoalveolar lavage fluid in Figure C. And finally, in the bottom 3 figures, apelin also reduced the secretion of pro-inflammatory cytokines, such as TNF-alpha, IL-6 and IL-1beta, important components of the cytokine storm. Next slide, please.

In this slide, we summarize published results of studies of stimulating the apelin signaling pathway in obese mice. Here, injection of apelin had multiple beneficial effects on metabolic dysfunction, increasing glucose uptake and storage into muscle, reducing circulating levels of insulin, triglycerides and fatty acids. These effects also led to a reduction in body weight and fat deposits. So in this animal model, apelin signaling had clear protective effects on what is a significant comorbidity of ARDS. Next slide, please.

So now let's look at the data we have previously shared for CohBar's own novel apelin agonist, the CB5064 analogs. Our ADA poster in 2019 included data on the mechanism of action of this new family of peptides, exploration of the interaction between CB5064 analogs and a broad range of cell surface receptors revealed a very selective activation of one specific receptor, the apelin receptor, or APJ. As shown in the figure on the left, some of our novel CB5064 analogs produced a maximum response at the apelin receptor, the blue bars, that were similar to the maximum effect of the natural peptide, in the black bar. On the right, we see in a second assay that CB5064 analogs decreased the production of cyclic AMP in cells overexpressing the APJ receptor, a characteristic of apelin signaling. Next slide, please.

Now the CB5064 analogs were also shown to have beneficial effects in vivo in diet induced obese, or DIO mice, a model of human type 2 diabetes. As shown on the left here, at the top, analogs of CB5064 dosed once daily for 10 days produced significant body weight loss and reduced fat mass compared to vehicle-treated animals. Below that, the administration of several CB5064 peptide analogs in another study in obese mice also reduced the decreased -- and decreased peak glucose levels following a challenge with a glucose bolus injection, indicating an improved glucose tolerance. Now that effect was also reflected in significantly lower blood glucose levels 2 hours after the glucose challenge shown on the bottom right. So these results demonstrate similar effects in obese mice to those produced by apelin injection. Next slide, please.

So now let's cycle back to summarize how we believe CB5064 analogs could have the potential to treat ARDS, and more specifically, ARDS in the setting of COVID-19. Here, once again, is the array of damaging processes that COVID-19 produces. And let's go to the next slide, please.

And here is the potential impact of CB5064 analogs, engaging the apelin receptor and shutting down these damaging effects. Other drugs now being evaluated in COVID-19 target individual cytokines or only a subset of these issues. We now know that apelin signaling can protect animals from acute lung injury, whether the injury is caused by chemical, bacterial, viral or other insults. We know apelin signaling reduces the fluid accumulation and the vascular leakage and cytokine release in animal models. So based on these observations, CohBar's novel CB5064 apelin agonist could potentially block the same range of damaging effects seen with COVID-19-associated ARDS.

It's important to note that this signaling pathway is completely independent of the source of the injury. So CB5064 analogs could have potential utility in COVID-19-associated ARDS and other forms of ARDS. And this can include future viral or bacterial infections. We're now moving forward with evaluation of our CB5064 analogs in preclinical models of ARDS. Let's move to the next slide.

This final slide shows a high-level overview of our current R&D programs for mitochondria-based therapeutics. CB4211, our first clinical candidate, currently in Phase Ib clinical testing for potential use in treating NASH and obesity. The study is currently paused, awaiting the resolution of the COVID-19-related delay. And we have 4 preclinical programs moving forward in various animal models of cancer, idiopathic pulmonary fibrosis and acute respiratory distress syndrome with the goal of identifying our next clinical candidate this year for advancement to IND-enabling activities. We expect to see additional preclinical data emerging on these programs in the next 3 to 6 months, and we plan to provide an update on our next call.

And with that, I'll return the call back to Steve.

Thanks, Ken. Before we move to the next slide, let me summarize all this a little bit. I want to make sure you understand. First of all, we're extremely excited to have these new targets, and you can see why now, because we're talking about affecting multiple downstream pathways that are causing multiple problems. And you now begin to get a sense of the power of these mitochondrial-derived peptides.

But I wanted to say, we believe we have a very large platform that we're working on. We have over 100 of the peptides encoded that are within the DNA. And it's like they're up on the wall and we're pulling them down one at a time like keys and looking for what locks they open. But it's a very large platform, and it's also targeting some very large, well-known opportunities. Most of you already know, virtually everything in terms of the disease areas, whether it's oncology or some of the others, we all know these are very large areas and with high unmet need, any one of which would be enough to make a big difference, both with patients and with the company itself.

And we are the leader in this area. Our patents are already filed and being filed, creating a huge hedge around the original discoveries. And we believe we have multiple shots on goal. And when you think about what that means, this is not one drug that happens to work in 5 different indications. Every one of these preclinical programs and the clinical program are different compounds and families of compounds. So this is a very solid situation. If one gets in trouble, the others are still free to move forward. So that greatly diminishes the risk and increases the potential of these programs.

So I think with that, we can move forward. But I want you to understand, we really think there are quite a few opportunities here and that at some point, we'll run into an inflection point, much like some of the other companies in biotech do. And we think as a result of that, this is a great time to be involved with the company. Next slide.

So here are the goals for 2020. Obviously, we're moving forward with the NASH and obesity clinical program, but it has been placed on pause. And we'll continue to move forward as soon as the sites themselves are able to operate that we expect we'll be able to push the program forward, and we'll give you more update on that as we get to that point. On the preclinical programs, the key for this year is to identify the next clinical candidate. In addition to which, we want to continue to make progress on our preclinical programs. And we can certainly say based on the retargeting of the program towards ARDS and also the advent of the new program, CXCR4, in the oncology area, that we are making significant progress in that particular goal.

And then as always, we're continuing to evaluate our options, both in the financing area. And as we do that, we're looking at a number of factors, and we'll -- and are doing that, monitoring the market and so forth. As you can imagine, we've been very closely monitoring what's going on. And then in parallel, we're also continuing to expand the relationships with the investor community. And we've been having 2 or 3 meetings a day, even under the conditions we've been on recently with the shelter-in-place.

Regarding partnering, I wanted to make sure it was clear that we continue to look for [walls] to move those conversations forward. You may remember, right after I joined last year, we were at the BIO 2019 meeting. We had 10 meetings with corporate partners, very large pharmaceutical companies, mostly. And we're about to hit that same point again. BIO 2020 meeting is coming up the first week of June, and we will be there. There, in this case, of course, is virtual, but we will be having meetings with folks and expect to, again, keep moving forward in this area. And finally, in the intellectual property area. As leaders in mitochondrial-derived peptide development, we will continue to expand our IP portfolio to maintain our leadership. Next slide.

So we continue to realize the CohBar vision. Recent academic research on mitochondria continues to expand the list of impacts of mitochondria dysfunction on multiple systems in the body, such as the immune system and the metabolic systems. Further, new research is illuminating the multiple connections between the mitochondria and these systems. They're showing that mitochondrial-derived peptides are a key component of regulation and modulation. And we believe CohBar is uniquely positioned to capitalize on these new scientific findings.

In the last year, CohBar has made substantial progress, increasing our clinical, preclinical programs from 2 to 5, showing the therapeutic breadth and potential of the peptides and the potential of the platform to generate multiple shots on goal. CohBar's technology and opportunity has been well received. The company's fundamentals have strengthened significantly, and the management team is increasingly enthusiastic about its prospects. And you can see why. We continue to be on the front lines of mitochondrial medicine, and step by step, we are realizing the potential of the CohBar vision.

Thank you. We'd like to go to Q&A now.

(Operator Instructions) Our first question is from Edward Nash with Canaccord Genuity.

This is [Adam] on for Edward. Just a few questions from us. First off, Ken, thank you very much for that great description provided in your prepared remarks regarding ARDS and CB5064. Maybe I missed it, but could you expand on the time line for CB5064? How many additional preclinical studies do you need to be -- need to completed to advance this program? And what other additional information will you get out of these trials? And I have another follow-up.

Right. Thanks, Ed, for the question. And let me give you some feeling on that. Obviously, we're just getting into now preclinical studies in the setting of ARDS. These are acute lung injury models, and we will be looking at the data emerging from those in the next 3 to 6 months. That -- those data are what's going to define how much additional work there needs to be done in this setting. It may be a case that we don't have too much more to do before selecting a candidate and moving rapidly to IND-enabling work. And that will be something we will know more about as soon as we see the data emerging from these studies.

Adam, before you go, first, can I just add a couple of things on to that. One thing you well understand is that -- and it's good to talk with you again. You well understand these are acute indications. So although you still have to set up the studies for the preclinical work, the reality is the time it actually takes to evaluate -- to conduct the experiment and evaluate it is much shorter than it might be for a chronic type disease. So as compared with some of the other areas that we're working in, this is a very different situation in terms of the time it might take to actually run the experiments themselves.

And the second thing about this is we're very fortunate. We know some of our friends in other biotech companies that are struggling with the fact that they're in the clinic -- or trying to get in the clinic and they're stuck, and we certainly understand and commiserate. But in our case, we expect these programs to continue to provide additional results and news flow over the next 6 to 9 months. So I know you were focused mostly on the one program, but I did want to point out that we expect to see additional results coming out of several of these programs. And we're fortunate in the sense that our preclinical research partners, people like Charles River and so forth, they're still very much open and running. So we plan to continue to move forward in that direction.

Yes, that's great to hear. And I'm going to pivot now to one of those -- the other indication that you're probably referring to, which is NASH. So I thought that you stated, you're adding a Phase Ib study in a diabetic population on a GLP-1 agonist to evaluate synergies and show the results of CB4211 in liraglutide. Could you speculate on why there might be a synergistic effect there?

Yes. The synergy that you're referring to is actually information we shared earlier from preclinical studies, clearly showing that if you add a small amount of our peptide, CB4211, onto a liraglutide treatment in an obese animal, you greatly increased the potency of the combination to decrease liver fat, to decrease body weight as well. So that synergy's established in a preclinical setting.

Now the reason is our mechanism is very different from a GLP-1 agonist, which is obviously acting very specifically at one receptor, regulating the management of glucose. Our mechanism involves an enhancement of the way that insulin itself interacts with the insulin receptor, and the downstream signaling effects of that on lipolysis, in the setting of adipocytes, regulating how much free fatty acid is flowing into the portal circulation and accumulating in the liver. So these are 2 different mechanisms that, by definition, are attacking different components of NASH. So it's not really a big surprise that there's an opportunity there that the 2 together are greater than the individual parts.

We also see that with other mechanisms like PPAR-gamma combination with ours, there's 2 different mechanisms going on there, very different mechanisms. So I hope that answers your question.

Yes. No...

And if I could -- sorry, just one more add on. Sorry about that. But I think we're seeing several things here and what Ken's pointing at. One is that the MOA is different virtually from anybody else. And we believe that NASH -- you probably do, too, will be treated eventually by a combination of compounds. And so we know right now that Intercept is going to be reviewed, both at the AdCom level and for approval by the FDA, probably by the end of June based on what they've said. And you just have to understand, from our point of view, that's great because it means it's -- and I'm sure you feel the same way -- it's a validation that you can actually get a drug approved.

But in addition to that, we see it as -- even people like Intercept may become people who need -- companies who need to fill out the pipeline in order to treat the patients. And because we're working upstream in the process, not only is the mechanism different, but the reduction in fatty acids going into the liver should result in a reduction in the problems downstream.

Obviously, we have to run the studies and so forth. So we've got a unique MOA. We think it makes sense in terms of combination, as Ken said, with GLP-1s and so forth, so you can imagine the companies that might be interested. And then it's upstream from what people are doing. And I think that most people believe that this will be a situation where more than one drug will be used to treat these patients. So for all those reasons, from a partnering point of view, we think that this is a very good candidate for a number of potential partners and unique in the way that it's positioned.

(Operator Instructions) Our next question is from Steve Brozak with WBB Securities.

Just one quick question. In your approach to ARDS, you're showing and you're explaining how you're shutting down the cytokine cascade. But I'd like to know in terms of how you're approaching it because obviously, what's coming out a lot now on the COVID side is that this is a global attack on the body. So what can you tell us, and as much color you can get on what you would look at in terms of being able to stop that hyper expression of -- the hyperinflammatory expression throughout the body because I'd like to know how that would be viewed. And I'll just hop back in the queue after that.

Yes. Thanks for the question. Thanks for getting on the call. The effect that you're going to have if you're able to decrease cytokine expression in the level of the lung is that circulation from there to other organs, which is what's going on in the cytokine storm, is going to be also decreased. So you can have direct effects in each organ by the apelin signaling because that's already been shown preclinically, too. You can go in directly in your liver and protect it with apelin signaling. You could also theoretically block the cytokines from ever being able to circulate and reach the liver and lead to the inflammation.

So there's multiple ways in which apelin signaling could be effective here. I think it's important to also compare this to what other approaches are. If you go and you block something like a single cytokine, you're really just allowing other cytokines to do the job, right? So you want something that's going to down-regulate generally cytokine levels but also be applicable in organs elsewhere. So if you give an apelin agonist like ours systemically, potentially you would directly protect organs in addition to reducing the lung production of the cytokines.

We have reached the end of our question-and-answer session. I would like to turn the conference back over to Steve for closing remarks.

Thanks, everyone, for listening today. I think Ken has really done a great job of lining this up for us so that we can understand it. I realize for some of us, it's a lot of science at once. But as we presented it to some of the world-class outside experts in lung disease and particularly in the ARDS area, we've gotten very positive responses. In addition, as we've talked to our own founders and other medical and scientists on the Board and so forth, similar kinds of responses. So I think it's a very exciting new program. And when you combine it with the others, I think, again, you get the sense of just what's possible. So we're very excited, and we'll look forward to talking to you on the next call. Thank you.

Thank you. This does conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.