Q4 2021 Athira Pharma Inc Earnings Call
Yeah.
Welcome to TheraPharma's conference call to discuss its full year 2021 financial results and business update. At this time, all participants are
Welcome to the reformers conference call to discuss its full year 2021 financial results and business update.
At this time all participants are in a listen only mode.
Following the conclusion of the prepared remarks, we will conduct a question and answer session, and instructions will follow at that time.
The conclusion of the prepared remarks, we will conduct a question and answer session and instructions will follow at that time.
This conference call is being recorded today, March 24, 2022.
This conference call is being recorded today March 24th 2022 .
I would like to turn the conference call over to Julie Rathbun head of Investor and public relations at their format.
I would like to turn the conference call over to Julie Rathbun, Head of Investor and Public Relations at Athera Pharma.
Thank you operator.
Julie Rathbun: Thank you, operator. Following the close of the U.S. financial markets today, we issued full year 2021 financial results and recent business updates. This press release can be found on the investor section of our website.
Following the close of the U S financial markets today, we issued full year 2021 financial results and recent business update. This press release can be found on the investors section of our website before we begin I'd like to remind you that during this call management will make forward looking statements, which may include statements about research and clinical development plans and time.
Julie Rathbun: Before we begin, I'd like to remind you that during this call, management will make four looking statements, which may include statements about research and clinical development plans and timelines and results of operations, the timing of and results from clinical trials and preclinical development activities, the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our product candidates.
Wine and results of operations, the timing of and results from clinical trials and preclinical development activities.
Essential efficacy safety profile future development plans addressable market regulatory success and commercial potential of our product candidates.
Julie Rathbun: The anticipated timing of IND or IND equivalent submission, and the initiation of future clinical trials for our product candidate.
Anticipated timing of IMD or IND equivalent submissions and the initiation of future clinical trials for our product candidates the efficacy of our clinical trial designs our ability to.
Julie Rathbun: The efficacy of our clinical trial design, our ability to successfully develop our proprietary development program, the timing and results of our interactions with regulators, the timing and anticipated enrollment in our clinical trials, and the timing of potential publication, a presentation of future clinical data.
Successfully develop our proprietary development program, the timing and results of our interactions with regulators the timing and anticipated enrollment in our clinical trials and the timing of potential publication or presentation of future clinical data forward looking statements are subject to numerous risks and uncertainties many of which are beyond our control.
Julie Rathbun: Forward looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings.
Including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected on today's call are serious not under any obligation to update statements regarding the future or to conform. These statements in relation to actual results unless required by law.
Julie Rathbun: Our results may differ materially from those projected on today's call. The theory is not under any obligation to update statements regarding the future or to conform these statements in relation to actual results unless required by law.
Speaker Change: On today's call, we are joined by Mark Litton, Ph.D., Athera's President and Chief Executive Officer, Hans Mobius, MD, Ph.D., Athera's Chief Medical Officer, Rachel Lennington, Athera's Chief Operating Officer, Glenna Mileson, Athera's Chief Financial Officer, and Kevin Church, Ph.D., Athera's Executive Vice President of Research.
On today's call. We are joined by Mark Litton Ph D. S series, President and Chief Executive Officer.
Lobbyists M D ph D. S series, Chief Medical Officer, Rachel Lenington, <unk>, Chief operating Officer, Glenn Mileson, <unk>, Chief Financial Officer, and Kevin Church, Phd experienced executive Vice President of research.
My prepared remarks, well open the call to your questions I'll now turn the call over to Dr. Mark Litton.
Mark Litton: When prepared to remark, we'll open the call to your questions. I'll now turn the call over to Dr. Mark Linton.
Mark Linton: Thanks, Julie, and thank you all for joining us this afternoon.
Thanks, Julie and thank you all for joining us this afternoon.
Mark Linton: 2022 has gotten off to an exciting start with progress across a number of our key clinical programs.
2022 has gotten off to an exciting start with progress of cost across a number of our key clinical programs.
Mark Linton: Our achievements throughout 2021, including the completion of the Phase II ACT-AD enrollment, laid the groundwork for us to pursue our clinical and corporate strategy, and we are looking forward to the results of these efforts.
Our achievements throughout 2021, including the completion of the phase II at a D enrollment laid the groundwork for us to pursue our clinical and corporate strategy and we are looking forward to the results of these efforts.
Mark Linton: To date, the new year has been highlighted by.
The new year has been highlighted by.
Mark Linton: The dosing of the first patient in our shape phase two study of Fosco-Menten or Fosco in Parkinson's disease dementia and dementia with Lewy body.
The dosing of the first patient in our phase II study of Costco and maintain our fosco in parkinsons disease, dementia, and dementia with lewy bodies.
The peer reviewed publication of our phase one study results with Posco.
Mark Linton: the peer-reviewed publication of our Phase 1 study results with FOSGO, and
And.
Mark Linton: the presentation of preclinical evidence supporting our novel, innovative approach to restoring neuronal health and slowing neurodegeneration across our lead program with FOSGO, and our first oral candidate, ATH1020.
The presentation of preclinical evidence supporting our novel innovative approach to restoring neuronal health and slowing neuro degeneration across our lead program with Posco and our first oral candidate Ath 10 20.
In addition to our considerable clinical progress we expanded our board of directors with the addition of two talented industry leaders.
Mark Linton: In addition to our considerable clinical progress, we expanded our board of directors with the addition of two talented industry leaders.
Mark Linton: Dr. Michael Panzara, an industry veteran with more than 20 years of CNS drug development and commercialization experience.
Dr. Marc Michael Penn's Ara and industry veteran with more than 20 years of CNS drug development and commercialization experience and grant Pickering, our proven life Sciences leader with considerable experience across all stages of corporate and clinical development.
Speaker Change: and Grant Pickering, a proven life sciences leader with considerable experience across all stages of corporate and clinical development.
Our growing body of scientific and clinical evidence is compelling.
Speaker Change: Our growing body of scientific and clinical evidence is compelling and gives us further confidence in our clinical development program.
It gives us further confidence in our clinical development programs.
Speaker Change: Importantly, we are on track to have top-line data from our Phase 2 AD study in the second quarter and expect to complete enrollment in our potentially pivotal Phase 3 LISP AD study in the third quarter.
Importantly, we are on track to have top line data from our phase II <unk> study.
Study in the second quarter and expect to complete enrollment in our potentially pivotal phase III <unk> study in the third quarter.
These are exciting inflection points for the euro and were gearing up for an especially active year ahead.
Speaker Change: These are exciting inflection points for Athera, and we are gearing up for an especially active year ahead.
With that let me turn the call over to our Chief Medical Officer, Dr. Hans <unk> for a review of our clinical development pipeline.
Speaker Change: With that, let me turn the call over to our chief medical officer, Dr. Hans Mobius for a review of our clinical development pipeline.
Speaker Change: For those of you who don't know Hans, Hans is an internationally recognized expert in neuropsychiatry, drug development, and regulatory strategy.
For those of you who don't know hogs hogs is an internationally recognized expert in neuropsychiatry drug development and regulatory strategy.
Is led the development and approval of several drugs, including amendment team and has been instrumental in shaping the development strategy for Costco.
Speaker Change: He has led the development and approval of several drugs, including Mementine, and has been instrumental in shaping the development strategy for Fosco.
Hans has taken the lessons learned and his decades of drug development to increase the probability of technical and regulatory success for our lead clinical program.
Speaker Change: Hans has taken the lessons learned in his decades of drug development to increase the probability of technical and regulatory success for our lead clinical program. With that, Hans.
With that funds the floor is yours.
Thank you mark for that generous introduction.
Hans Mobius: Thank you, Mark, for that generous introduction. As many of you know, in the past 20 years of Alzheimer's disease research and development,
As many of you know in the past 20 years.
MS disease research and development.
Spent trying to replicate the effects seen in transgenic animal models into humans.
Hans Mobius: were spent trying to replicate effects seen in transgenic animal models into humans.
Hans Mobius: namely by monoclonal antibodies in order to achieve disease modification.
<unk> bye.
Antibodies in order to achieve disease modification.
Hans Mobius: This approach requires to treat early pre-dementia stage Alzheimer's disease and there was far less attention to mild to moderate.
This approach requires us to treat early pre dementia states on some of this disease and there was far less attention to minus two motor with states on some of this disease.
Hans Mobius: At Athera, we have undertaken a novel mechanistic approach that does not follow this search for the holy grail of disease alteration, but rather focuses on the symptomatic stage as a first step.
We have undertaken a novel mechanistic approach that does not from them.
Search for the Holy Grail of disease alteration, but rather focuses on the symptomatic stage as a firm.
Step.
Our approach is to develop small molecule therapeutics for a broad range of neurodegenerative diseases, including Alzheimer's disease by promoting the H D Smith system.
Hans Mobius: Our approach is to develop small molecule therapeutics for a broad range of neurodegenerative diseases, including Alzheimer's.
Hans Mobius: by promoting the HGF-MED system, a naturally occurring mechanism to repair and restore neuronal health.
Naturally occurring mechanism to repair and restore new house.
H D. Smith is critical for healthy brain function.
Hans Mobius: HCF med is critical for healthy brain function.
Hans Mobius: Metreceptor expression is reduced in Alzheimer's disease and other neurological conditions.
Met receptor expression is reduced in this disease and other neurological diseases.
Our late stage product candidate is a small molecule product with.
Hans Mobius: Our late-stage product candidate is a small molecule product with an active metabolite that can be used as a protein.
With an active metabolites brain penetrant.
And positively modulates the activity of the HCA system with high specificity.
Hans Mobius: It positively modulates the activity of the HCF med system with high specificity.
Hans Mobius: We have demonstrated this extensively in pre-clinical models and have used electrophysiology, both quantitative EEGs.
We have demonstrated this extensively in preclinical models and diffused electrophysiology.
Both quantitative EEG.
Hans Mobius: and the objective task-related measure of event-related potential P300 latency to determine an active dose range.
And the objective cask related.
Event related potential P 300, latencies to determine an active dose range.
The compelling pharmacodynamic results from a small cohort.
Hans Mobius: compelling pharmacodynamic results from a small cohort of Alzheimer's disease subjects in our Phase 1B study, as well as supportive long-term toxicology results, gave us confidence to initiate a Phase 2 and 3 clinical development program. The study design was to
Subjects in our phase one study as.
As well as supportive long term toxicology results.
Give us confidence to initiate a phase two.
And Sui clinical development program.
The study design was discussed with the FDA.
<unk> and.
Hans Mobius: in order to gain agreement that the Phase III LIFT-AD study
That's a game agreement that the phase three lift studies.
Could potentially serve as a pivotal trial if successful.
Hans Mobius: could potentially serve as a pivotal trial if successful.
The phase two trial with <unk> and the phase three trial. This study.
Hans Mobius: phase 2 trial was branded ACT-AD and the phase 3 trial LIFT-AD. Their design is largely
Their design is largely mirroring.
Hans Mobius: For example, diagnostics, severity range, doses, double-blind duration, and
For example, diagnostics severity range doses.
Double blind duration and more.
Most outcomes.
Both trials started in parallel so just smaller phase two trial.
Hans Mobius: Both trials started in parallel, so the smaller Phase II trial will read out first, allowing us to
We don't first.
Owing us to leverage insights from the <unk>.
Hans Mobius: from the ACT-AD results for the optimization of the LIFT-AD statistical analysis.
Results for the optimization of the lift a statistical analysis plan.
Importantly, we are able to do this without a formal interim analysis in the phase three trial.
Hans Mobius: Importantly, we are able to do this without a formal interim analysis in the phase 3 trial, which carries statistical penalties and inevitably brings operational delays.
Each carries statistical penalties.
Hesitantly brings operational delays.
In short both.
Hans Mobius: In short, both ACT-AD and LIFT-AD are randomized, double-blind, placebo-controlled trials evaluating 40 and 70 mg Fosco daily for the treatment of mild to moderate AD.
Lift.
Brendan mines double blind placebo controlled trials.
Relating 40, 70 milligram first go daily for the treatment of mild to moderate.
Hans Mobius: participants are randomized evenly to those groups.
Participants are randomized evenly to the two dose groups in the placebo group to receive subcutaneous injection of <unk> or placebo once daily for a double blind period of 26 weeks.
Hans Mobius: placebo group to receive a subcutaneous injection of Fosco or placebo once daily over a double-blind period of two weeks.
The primary endpoint.
Hans Mobius: The primary endpoint of ACT-AD is change in event-related potential P300 latency, a functional objective measure of working memory processing speed. Secondary endpoints in ACT-AD?
This change in event related potential petrie on that latency.
Functional objective measure of working memory processing speed.
Secondary endpoints.
E.
Include Adas Coke 11 measure of cognition.
Hans Mobius: ADC-S Cedric, a measure of global clinical change, and ADC-S ADL23, a measure of functional ability.
Citric measure of global change and Adcs ADL twenty-three measure functional abilities.
In addition, we are assessing the plasma pharmacokinetics for school in this patient population.
Hans Mobius: In addition, we are assessing the plasma pharmacokinetics of phosgo in this.
Hans Mobius: Enrollment of ACT-AD was completed last October with 77 participants enrolled, and as Mark noted earlier, we are on track to report top-line data in the second quarter of 2022.
Enrollment.
He was completed last October .
102000 participants enrolled and as Mark noted earlier, we are on track to report topline data in the second quarter of.
2022.
The phase three study.
Study is currently enrolling up to 420 subjects in the U S. In contrast.
Hans Mobius: currently enrolling up to 420 subjects in the U.S.
Hans Mobius: In contrast to ACT-AD, LIFT-AD has a composite primary endpoint, the Global Statistical Test.
This is.
Here's a composite primary endpoint the global statistical test.
Hans Mobius: which is an unweighted and unbiased mathematical algorithm that combines the scores from ADAScope 11.
Unweighted unbiased mathematical algorithm that combines the scores from 811.
Hans Mobius: and either ADCS-CYGIC or ADCS-ADL23, which are amongst the secondary.
And either Adcs.
Adcs <unk> suite, which are amongst the secondary endpoints.
Hans Mobius: You may recall that earlier this year we opportunistically expanded the target recruitment number.
I recall that earlier this year the opex.
Opportunistically expanded the target recruitment number for the study by approximately 120 patients.
Hans Mobius: for the study by approximately 120 patients in order to strengthen the statistical.
Order.
Train from the statistical power of these secondary endpoints.
Hans Mobius: We believe this will enhance the potential for filing a new drug application based on a single pivotal clinical study.
This will enhance the potential for filing.
You broke application based on the singles.
I need to study.
The increased sample size and resulted in power.
Hans Mobius: The increased sample size and resulting power for ADASCOG11
Hans Mobius: based on our unchanged original statistical modeling and is consistent with the design of previous phase three trials in the treatment.
Based on the unchanged original statistical modeling and is consistent with the design of previous phase three trial in the treatment of mild to moderate disease as well.
Hans Mobius: As noted earlier, we will leverage insights from the ACT-AD trial analysis in the second quarter to optimize and refine the statistical analysis plan for LIFT-AD.
Noted earlier, even leverage insights from the <unk>.
Analysis in the second quarter to optimize and refine the statistical analysis plan for Lyft.
Hans Mobius: Moving forward, we anticipate completing enrollment in LISP-AD in the third quarter.
Moving forward.
Fifth completing enrollment list.
In the third quarter of 2022, resulting in top line data in the first half of 'twenty 'twenty suite.
Hans Mobius: 2022, resulting in top-line data in the first half of 2020.
Hans Mobius: There's a growing body of preclinical and clinical evidence in support of targeting the HTF-Met neurotrophic system. The encouraging results from the phase one AB study
There is a growing body of preclinical and clinical evidence in support of targeting the HTS.
Traffic system.
The encouraging results from the phase one study of <unk>.
Over a recently published in the peer review Journal.
Yes.
To summarize first gold was well tolerated across the white those rooms pharmacokinetics of dose linear and pharmacodynamics suggest human blood brain barrier penetration.
Hans Mobius: To summarize, FOSCO was well-tolerated across a wide dose range, pharmacokinetics are dose linear, and pharmacodynamics suggest human blood-brain barrier penetration. The statistically significant
Statistically significant lots reduction.
Hans Mobius: ERP P300 latency seen in the Alzheimer's disease cohort on active drug versus placebo treatment
P P 300 latencies.
So Ms disease cohort on active drug versus placebo treatment.
May be suggestive of enhanced syn <unk> function and ultimately the potential properties for school.
Hans Mobius: of enhanced synaptic function and ultimately the potential pro-cognitive properties.
Second.
Hans Mobius: baseline demographics of ACT-AD presented last week at the ADPV Annual Meeting demonstrate a well-balanced trial population.
Baseline demographics.
He presented last week at the <unk> annual meeting demonstrate a balanced population appropriate to replicate these initial phase one findings on ERP net neutral.
Hans Mobius: appropriate to replicate these emission phase 1b findings on ERP P300, which is a functional measure.
Just a functional measure off working memory processing speed.
Hans Mobius: Finally, in this type of population, one would expect to see about 20% to 35% of discontinuation.
Finally in this type of population one would expect to see.
About 2000% to 35% of discontinuation.
Hans Mobius: largely due to treatment emergent adverse events.
Largely due to treatment emergent.
Adverse events.
Our models assumed 20% dropout rate and we can now report that the discontinuation rate for.
Hans Mobius: a 20% dropout rate, and we can now report
Hans Mobius: The discontinuation rate for ACT-AD was considerably below that rate, coming in at approximately 40%.
Most considerably below that rate coming in at approximately 14%.
Hans Mobius: This effect and the absence of target organ toxicity is a favorable result.
This effect in the absence of targets, Oregon toxicity is a favorable result.
Hans Mobius: Consequently, the majority of subjects completing Act 80 have opted to participate in the 26-week opening.
Consequently, the majority of subjects completing.
Yes.
To participate in the 26 week open label extension study.
Hans Mobius: Remember, two-thirds of subjects have been on active drug during the double-blind period.
Remember two thirds of subjects.
Active drug during the double blind portion of the study.
Hans Mobius: We think this speaks to the tolerability of this novel intervention.
We think this speaks to the Tolerability of this novel intervention.
Particular.
Hans Mobius: in an elderly, frail, polypharmacy population.
Italy Trail Polypharmacy population.
Hans Mobius: with increased susceptibility to adverse.
Increased susceptibility to Atlas.
<unk>.
Hans Mobius: Because positive modulation of HGF-MED is not dependent or based on a specific performance.
Because positive modulation of HTS, that's not dependent.
Based on our specific pathology.
Part of this.
Hans Mobius: we expanded in parallel into other neurodegenerative indications.
Expanded in parallel.
Or the degenerative indications.
Earlier this year.
Hans Mobius: our SHAPE study, a randomized, double-blind, placebo-controlled,
<unk>, our shaped study a randomized double blind placebo controlled trial.
Phase two trial.
Hans Mobius: Parallel Group Phase 2 Trial Evaluating Phospho in Subjects with Parkinson's Disease.
Relating firstgroup.
Subject to Parkinson's disease, dementia, or dementia with lewy bodies.
This proof of concept study will enroll approximately 75 individuals in the U S utilizing the same dose regimen.
Hans Mobius: This proof-of-concept study will enroll approximately 75 individuals in the U.S.
Hans Mobius: utilizing the same dose regimen as ACT-AD and LIFT-AD over the same double-blind treatment course of 26 weeks. The primary endpoint for SHAPE is also the composite global statistical test utilizing cognitive change and P300 latency, which has also been shown to be affected in Parkinson's disease dementia.
And lift.
Over the same double blind treatment course of 26 weeks.
The primary endpoint for shape.
So the composite global statistical test utilizing proptosis change.
And P 300 latency.
It's also been shown to be effective in Parkinson's disease dementia.
Secondary endpoints.
10 points.
And automotive space.
Since most Parkinson's disease patients develop dementia. This is an area of high end, maybe could meet with only one approved drug on the market.
Hans Mobius: In addition to expanding the indications for FOSCO, we are advancing another compound from our discovery group, ATP.
In addition to expanding indications for school.
Advancing another compound from our discovery group.
Th 10 20.
Compelling preclinical results were presented at the recent American Society for extra mental.
Hans Mobius: Preclinical results were presented at the recent American Society for Experimental Neurotherapeutics annual meeting.
<unk> Therapeutics, Inc.
It showed.
It's 10 20 demonstrated in vitro and in <unk>.
Hans Mobius: demonstrated in-vitro and in-vivo efficacy, including its effect.
Secrecy.
Including its ability to implement mitigation promote activation of downstream signaling pathways.
Hans Mobius: activation of downstream signaling pathways and in distinct animal models, address depression-like behaviors, and normalize and address depression-like behaviors.
And distinct animal models to address personal behaviors normalize.
Normalized and is published electrophysiological hallmark of schizophrenia.
Following Cleveland.
Our investigational new drug application with the FDA in January .
Hans Mobius: our investigation on new drug application with the FDA in January . The study is now underway.
Buddy is now underway.
Dosing for the first subject with its been 20 into phase one human from oncology trial is no imminent.
Hans Mobius: Phase I Human Pharmacology trial is now imminent.
In summary.
Hans Mobius: FIRA is pursuing a diverse clinical development pipeline, both in terms of target indication.
<unk> is pursuing a diverse clinical development pipeline both in terms of target indications.
And development stages.
Hans Mobius: We believe that our work will provide a bonus of data for presentation and public.
Our Brooklyn provides a bolus of data for presentation and publication in the years ahead that will hopefully translate into new medicines for patients in need.
Hans Mobius: will hopefully translate into new medicines for patients in need.
And at the same time, we will create shareholder value.
Hans Mobius: and at the same time will create shareholder value.
That overview.
Ill turn the call back to Mark.
Thanks for that detailed review of our clinical programs.
Speaker Change: Thanks, Hans, for that detailed review of our clinical program.
Given how closely are the topline data from our phase II study. We are still frequently asked so what does success look like for <unk>.
Speaker Change: Given how close we are to top line data from our phase two study, we are still frequently asked, so what does success look like for ACT-AD?
Speaker Change: Obviously, achieving statistical significance on the primary P300 endpoint would be a success.
Obviously, achieving statistical significance on the primary P 300 endpoint would be a success.
Speaker Change: In addition, should we see trends in some of the key secondary endpoints, we would also see that as a big win.
In addition, should we see treat trends and some of the key secondary end points. We would also see that as a big win.
We say trends because this study was not powered to show statistical significance in these cognitive clinical and functional endpoints.
Speaker Change: We say trends because this study was not powered to show statistical significance in these cognitive, clinical, and functional endpoints.
Speaker Change: That said, we are hopeful that we will see some trends towards clinical benefit, as this would corroborate our thesis and further support our confidence in a favorable outcome in our Phase III LISP-A-B studies.
That said, we are hopeful that we will see some trends towards clinical benefit as this would corroborate our thesis and further support our confidence in a favorable outcome in our phase III lift.
Eddie.
Our goal with Posco is to bring clinical benefit to patients suffering with neuro degenerative diseases and to provide tangible rapid and lasted lasting cognitive improvement with our novel approach.
Speaker Change: Our goal with FOSGO is to bring clinical benefit to patients suffering with neurodegenerative diseases and to provide tangible, rapid, and lasting cognitive improvement with our novel approach.
We want to provide patients with what is most important to them memory improvement and extended independent.
Speaker Change: We want to provide patients with what is most important to them, memory improvement and extended independence.
This is most critical in the mild to moderate patients or the rate of cognitive and behavioral declines it seemed most dramatically.
Speaker Change: This is most critical in the mild to moderate patients, where the rate of cognitive and behavioral declines is seen most dramatically.
It is also important as the mild to moderate <unk> segment accounts for nearly 80% of all all alzheimers patients.
Speaker Change: It is also important as the mild to moderate AD segment accounts for nearly 80% of all Alzheimer's patients.
Speaker Change: And 78% of these patients are currently on marketed drugs.
78% of these patients are currently on marketed drugs.
There is a real need for innovation in this space and we believe our unique HTS met approach can help fill this void.
Speaker Change: There is a real need for innovation in this space, and we believe our unique HGF-Med approach can help fill this void.
Speaker Change: As we move closer to a potentially pivotal phase 3 data readout next year, we have spent considerable time evaluating the market opportunity and market access.
As we move closer to a potentially pivotal phase III data readout next year.
We have spent considerable time evaluating the market opportunity and market access.
Speaker Change: Currently, there are 55 million people suffering with Alzheimer's disease worldwide. And that number is expected to grow to 100 million by 2050, given the aging population and other dynamics.
Currently there are 55 million people suffering with all timers disease worldwide.
And that number is expected to grow to $100 million by 2050, given the aging population and other dynamics.
Speaker Change: Currently, there are only three to four drugs available to treat mild to moderate Alzheimer's disease. And as we've noted, there's considerable room for improvement.
Currently there are only three to four drugs available to treat mild to moderate alzheimers disease and as we've noted there is considerable room for improvement.
Speaker Change: contrast that with cancer drugs, which have a multitude of treatment options across a variety of targets, and it underscores how woefully underdeveloped Alzheimer's disease treatment options are today.
Contrast that with cancer drugs, which have a multitude of treatment options across a variety of targets and it underscores how woefully underdeveloped alzheimers disease treatment options are today.
Speaker Change: Importantly, given this gap, we see there is room for a lot more success for any number of players in the sector. Now let me turn to…
Importantly, given the gap, we see there is room for a lot more success for any number of players in the sector.
Now, let me turn to a brief review of our financials.
We continue to invest in our clinical development programs with a focus on advancing fosco towards approval with an overarching goal to benefit patients worldwide.
Speaker Change: We continue to invest in our clinical development programs with a focus on advancing FOSGO towards approval with an overarching goal to benefit patients worldwide.
We are prudently building our team in order to deliver on the potential of our novel HTS met platform.
Speaker Change: We are prudently building our team in order to deliver on the potential of our novel HDFMAT platform.
Speaker Change: We are keenly aware of the trust put in us by you, our shareholders, and we work diligently to be good stewards of those resources by balancing our investments with disciplined financial management. Now, let's look at the details of our plan.
We are keenly aware of the trust put in us by you our shareholders and we work diligently to be good stewards of those resources by balancing our investments disciplined financial management.
Now, let's look at the details of our financial results.
Our research and development expenses were $42 8 million for the year ended December 31, 2021, as compared to $13 3 million for the full year ended December 31 2020.
Speaker Change: Our research and development expenses were $42.8 million for the year ended December 31st, 2021, as compared to $13.3 million for the full year ended December 31st, 2020.
The increase was driven primarily by costs related to an increased clinical trial activities expanded personnel and increased preclinical research and development expenses.
Speaker Change: The increase was driven primarily by costs related to an increased clinical trial activity.
Speaker Change: expanded personnel, and increased preclinical research and development expenses.
General and administrative expenses were $21 2 million for the year ended December 31, 2021, as compared to $6 7 million for the same quarter in 2020.
Speaker Change: General and administrative expenses were $21.2 million for the year ended December 31, 2021, as compared to $6.7 million for the same quarter in 2020.
Speaker Change: These were primarily due to an increased personnel expense as we expanded headcount and infrastructure, and it includes insurance, legal, facilities, new product planning, and investor-relation costs.
These were primarily due to an increased personnel expense as we expanded headcount and infrastructure and it includes insurance legal facilities, new products product planning and investor relation costs.
Speaker Change: We had a net loss of $54.9 million, or $1.49 per share basic and diluted, for the year ended December 31, 2021 compared to a net loss of $19.9 million, or $1.67 per share basic and diluted, for the year ended December 31, 2020.
We had a net loss of $54 9 million or $1 49 per share basic and diluted for the year ended December 31 2021.
<unk> to a net loss of $19 9 million or $1 67 per share basic and diluted for the year ended December 31 2021.
Importantly, we ended 2021 with cash cash equivalents and investments of $319 7 million compared to $268 2 million as of December 31, 2020.
Speaker Change: Importantly, we ended 2021 with cash equivalents and investments of $319.7 million compared to $268.2 million as of December 31, 2020.
This puts us in a strong position to support our lead clinical programs through important potentially value, creating data readouts and beyond.
Speaker Change: This puts us in a strong position to support our lead clinical programs to important, potentially value creating data readouts and beyond.
Speaker Change: Before we open the call to your questions, I'd like to remind you that we're joined by Rachel Linnington, our Chief Operating Officer, Kevin Church, our EVP of Research, and Glenna Myleson, our CFO .
Before we open the call to your questions I'd like to remind you that we are joined by Rachel Lenington, Our Chief operating officer.
Kevin Church, our EVP of research and good a milestone our CFO .
Speaker Change: Collectively, our team has presided over the development, approvals, and successful launches of many meaningful drugs.
Collectively our team has presided over the development approvals and successful launches of many meaningful drugs.
In closing I am.
Speaker Change: In closing, I want to take a moment to thank the talented and dedicated Athera team who are all working tirelessly in pursuit of our goals.
I want to take a moment to thank the talented and dedicated <unk> team, who are all working tirelessly in pursuit of our goals.
The energy and excitement at Sierra is very high as we truly believe we have a unique opportunity to reshape the course of neuro degenerative diseases.
Speaker Change: The energy and excitement of the era is very high, as we truly believe we have a unique opportunity to reshape the course of neurodegenerative diseases. We look forward to making our vision a reality.
We look forward to making our vision a reality for these patients.
Speaker Change: With that, operator, let's open the call up for questions.
With that operator, let's open the call up for questions.
Speaker Change: Certainly. Ladies and gentlemen, if you have a question at this time, please press star one on your telephone.
Certainly ladies and gentlemen, if you have a question at this time. Please press star one on your telephone.
Speaker Change: If your question has been answered or you wish to remove yourself from the queue, please press the pound key.
My question has been answered or you wish to remove yourself from the queue. Please press the pound key.
Our first question comes from the line of Andrew Tsai with Jefferies.
Speaker Change: Our first question comes from the line of Andrew Cy with Jeffrey.
Andrew Cy: Thanks, and good afternoon. Thanks for all the updates. First question is just a high-level one on Act 80. Can you remind us how you're thinking about sharing the top-line release in Q2? There's a lot you could share in terms of the number of endpoints that you have. So how much are you planning to share? You know, will we see efficacy curves out to six months? I guess, what should we be expecting?
Thanks, and good afternoon. Thanks for all the updates first question is just a high level. One on <unk> can you remind us how youre thinking about sharing the topline released in Q2, there's a lot you could share in terms of the number of endpoints that you have so how much are you planning a share.
We see efficacy efficacy curves out to six months.
Guess, what should we be expecting thanks.
Speaker Change: Thank you, Andrew, so just to expect.
Thank you Andrew.
So just to expect.
Speaker Change: The primary endpoint is P300, and we will show, hopefully, statistically significant data throughout six months for P300.
The primary endpoint is P 300, and we will show hopefully statistically significant data throughout six months for P 300.
Speaker Change: And then the plan is to show ADIS-CoV-11 and we're hopeful to see trends because ADIS-CoV-11, as you know, is not powered to be statistically significant. So those would be the colors that we will show. We do plan to give more color in an upcoming scientific conference.
And then the plan is to show Adas Cog 11.
And we're hopeful to see trends because Adas cog 11, as you know is not powered to be statistically significant so those would be the colors that we will show.
We do plan to.
Give more color in upcoming scientific conference.
Speaker Change: So, to be clear in your things, we probably will not show the graphs over time.
So to be clear in your things, we'd probably will not show the graphs overtime.
Got it and.
Speaker Change: Got it. And just a reference point would be helpful on these harder endpoints on AS-COSCEGIC, ADL. You know, what do the approved drugs for moderate Alzheimer's show at six months for these three efficacy endpoints?
Just a reference point might be helpful. On these harder endpoints on anti Scott Seajack ADL.
What do the approved drugs for mild to moderate Alzheimers show at six months for these.
Three efficacy endpoints.
Sure so.
Speaker Change: Sure, so now we're talking historically. I think I'm gonna hand that over to Hans to answer on that. Yeah, in a mild to moderate Alzheimer's disease population in a 26-week or six-month trial, you would historically expect to see two to three points
So now we're talking historically, I think I'm going to hand that over to Hans.
To answer on that.
In the mild to moderate some of the student population.
26.
Six months trial.
Europe is historically expect.
To see two to three poems.
Benefits plus.
Placebo.
That is behind.
The highly dependent.
Setting and the placebo decline.
That has been observed.
A number of points.
So.
Literally placebo decline.
In the past.
Yes.
Okay.
And then.
My last question is.
Hans Mobius: You know, you shared some interesting ADPD kind of data update on ACT-AD. I think 50 to 60% of your patients in this study are on acetylcholinesterase inhibitor. So 40% are, I believe, treatment naive. I believe that, you know, naturally the old studies in the past probably were done in naive patients.
You shared some interesting ADP D data update on activity.
$50 to 60% of your patients in this study are on a single client aspiration inhibitor. So 40% are I believe treatment naive I believe that.
Naturally that the old.
Studies and the <unk>.
Probably we're done in naive patients so.
Hans Mobius: So here, if 50% to 60% of the patients are on a combo therapy, how does that dynamic affect?
Here.
50% to 60% of patients are on a combo therapy, how does that dynamic affect both the placebo and the drug arm on Adas cog.
Hans Mobius: both the placebo and the drug arm on ADAS-CoG. Thanks.
Thanks.
Okay.
When you go pumps.
Okay.
Hans Mobius: So, you're correct, I reported on average, quite precisely, 60% currently taking.
So.
Youre correct.
Got it.
Quite precisely 60%.
Currency taking.
Medication.
Hans Mobius: In the historical trials, indeed, the number was smaller. I will remind that also in phase 1B, we had drug-naive subjects, as always, in phase 1 trials. We believe that it can only be helpful to support the traffic.
And you just told us look twice.
The number was smaller.
Remind us also.
<unk>.
Subjects.
As always.
Phase one trials.
We believe that.
It can only be helpful to support.
The traffic situation of cutting edge it runs.
That are.
Of course together.
Uh huh.
<unk> transmitter.
Addressed.
Rooms.
Key areas in the brain.
They're all responsible for memory.
And language.
So.
So rather than advantaged and potential disadvantage.
Thanks, very good thanks for all the color.
Thanks, Andrew.
Speaker Change: Thank you. And our next question comes from the line of Paul Matias with Stiefel.
Thank you and our next question comes from the line of Paul <unk> with Stifel.
Great. Thanks, so much for the detail you're offering I wanted to clarify a couple of things if I might so one is I.
Paul Matias: Great. Thanks so much for the detail you're offering. I wanted to clarify a couple things if I might. So one is, I guess, for Lyft.
I guess for Lyft.
Paul Matias: The hope here is that you hit on both cognition and function, is that right, right? Is that so your assumption that 8S-COG alone would not be enough to get registered? And if that's right, how much flexibility do you see on which?
The hope here is that you'd hit on both cognition and function is that right right is that so your assumption that Adas cog alone would not be enough to get registered.
And if that's right.
How much flexibility do you see on which functional scale you'd need to succeed on.
Paul Matias: functional scale you need to succeed on? And how much time do you have, I guess, to pre-specify which you're using in the global statistical test? And then the one last thing I just wanted to ask out of curiosity, not sure if you're willing to disclose, but just when you look at the baseline data in ACT, right, you did a number of different baseline data cuts.
How much time do you have I guess to pre specify which you're using in the global Statistical Test and then the one last thing I just wanted to ask out of curiosity not sure if youre, if youre willing to disclose but just when you look at the baseline data in act right. You did have a number of different baseline data cuts.
Paul Matias: Which, which is appreciated when you look at patients across disease severity at baseline. Do you see any association with their baseline P 300 latency? Thanks so much.
Which is appreciated when you look at patients across disease severity at baseline do you see any association with their baseline P 300 latency. Thanks, so much.
Let me answer the last question first we have not.
Speaker Change: Yeah, let me answer the last question first. We have not specifically looked in that difference of P300.
Specifically.
That difference.
Baseline.
Speaker Change: We have been looking into the baseline of the entire group, and what we found was that the...
And looking into the base.
I'm of the entire group and what we found was that.
Mean baseline and equitable.
Speaker Change: 381 milliseconds, plus minus 4.1, which is very well in keeping with published data in the same target population.
81 <unk>.
Seconds, plus or minus 4.1.
Rich.
Very well in keeping with published data in the same target population.
I think.
Second question related to the selection and to time the selection for the.
Okay.
Speaker Change: and the time we have, the answer is we have plenty of time.
Enlist and the times you have the answer.
We have plenty of time.
Speaker Change: Because in quarter two, we will have unblinded results from ACT, which allows us, irrespective of an effect size that we may or may not see, we will see the sources of variance. And that is particularly very important.
Of course.
In quarter two.
Within the quarter tools, you will have unblinded results from <unk>, which allows us irrespective of the fact that you may or may not see.
You can see the sources of variance and that is particularly valuable for us because it really allows us to optimize the statistical analysis plan for Lyft.
Speaker Change: because it really allows us to optimize the statistical analysis plan for LIFT. And on that occasion, we will then also define...
On that occasion, you will then also defined.
<unk>.
Speaker Change: which additional co-key secondary endpoint, in addition to ADASCOT11, will be defined.
Rich addition of key.
Key secondary endpoints in addition to English.
We'll be defined.
And.
Usually.
<unk>.
Last moment.
Speaker Change: file the statistical analysis plan is before unblinding, but I think we have plenty of time to do that way before.
File the statistical analysis plan is before on blinding.
We have plenty of time to do that way before.
And the first question you would quickly get to me.
Speaker Change: quickly give me a reminder of what.
Remind us.
Yes, no. Thanks Todd.
Speaker Change: Yeah, no, thanks Hans. Yeah, I was just kind of making sure that you agree with the premise that
Just kind of making sure that you agree with the premise that.
Hans Mobius: you likely need to hit cleanly on both a cognitive and functional endpoint for registration. And the only reason why I'm asking is Mark's prepared remarks surrounding sharing ADAS COG in the top line, but it doesn't sound like you're gonna share any functional scales. And I'm honestly a little bit sure why that is, but yeah, maybe you can just give any more color would be great.
You would likely need to hit cleanly on both the cognitive and functional end point for a registration and the only reason why I'm asking is Mark's prepared remarks surrounding sharing Adas cog in the topline, but it doesn't sound like you're going to share any functional scales.
I'm honestly, a little bit sure why that is but maybe you can just give any more color would be great.
Speaker Change: Yeah, look, I think in keeping with the philosophy of the FDA, it is really important to look at the totality of the data.
Look I think.
In keeping with our philosophy of <unk>.
Yeah.
It is really important to look at the totality of the data.
Speaker Change: And that requires a bit of time and it will also require a good.
And that.
That requires a bit of time and it will also.
Good discussion.
Speaker Change: And so beyond the initial publication via press release, we are obviously aiming to discuss this totality of the findings in the context of a scientific conference.
So beyond the initial.
Publications on our press release.
Aiming.
To discuss this totality of it.
Findings in the context of a scientific conference.
Tricky as possible.
Speaker Change: I think that is, in any event, a better place for such an in-depth analysis, which, by the way, let me add that to what was said before, also has to include, then, of course, the data.
I think that is.
In any event to pick up.
Place for such an in depth analysis, which by the way.
To set before.
And of course safety and Tolerability data.
And let's also just make Brian .
Speaker Change: And just to remind you that this is only 77 patients, right? So, it's just going to be exploratory on these co-secondary endpoints.
To remind you that this is only 77 patients right. So it's just going to be exploratory on these co secondary endpoints.
Correct, yes.
Yes, yes totally understood. Thanks.
Speaker Change: Yeah, for that. Yep. Yeah. Totally understood. Thanks. Thanks very much.
Thanks very much.
Thanks, Bob.
Thank you.
Speaker Change: Thank you. And our next question comes from the line of Corrine Jenkins with Goldman Sachs.
Our next question comes from the line of Corinne Jenkins with Goldman Sachs.
Corrine Jenkins: Hey, good afternoon, everyone. I just have one quick follow-up. In terms of the ACT-AD study, have you taken a blinded look at the data, and if so, is there any color that you could provide on that?
Good afternoon, everyone.
I just have one quick follow up.
<unk> study have you taken a blinded lock at the date on it.
Any color that you can provide on that.
Yes.
Yeah.
Corrine Jenkins: We are very careful in this type of approach.
We are very.
Carefully.
And this type of approach.
The trial.
I cannot comment on.
And such.
Behind its findings.
Okay, and then I think maybe just an enrollment update on less than and now an expansion I am just curious.
Corrine Jenkins: And then I think maybe just an enrollment update on Lyft, since you announced the expansion. I'm just curious if there's, I know part of that was you saw really good enrollment, and then we had Omicron, so I'm curious if you could provide any color on kind of the pace of enrollment in Lyft and updated.
Apparently that was huge.
<unk> got enrollment and then we had undergrounds I'm curious if you could provide any color on kind of the pace of enrollment.
Okay. That's all from the data timing there.
Speaker Change: Yeah, yeah, Karen, we're still shooting for getting complete enrollment in Q by the end of Q3, so that's what we're pushing for.
Yes, Karin we are still shooting for getting.
Getting complete enrollment in <unk> by the end of Q3, so that's what we're pushing for.
Karen: And will you announce that when you hit an enrollment completion, or is that something that you won't disclose?
And where you announced that when you hit.
Inflation.
Is that something that you won't disclose.
No no we will definitely we will announce that we've completed enrollment.
Speaker Change: No, no, we'll definitely, we'll, we'll announce that, that we've, we've completed enrollment.
Great. Thank you so much.
Thanks, Greg.
Speaker Change: Thank you. And our next question comes from the line of Jason Butler with JMP Securities.
Thank you and our next question comes from the line of Jason Butler with JMP Securities.
Hi, Thanks for taking the questions just one on the.
Jason Butler: Hi, thanks for taking the questions. Just one on the cognition trends, you'll look for an act. Mark, I think you said you're not going to show the graphs, but just.
Cognition trends, you'll look for an act.
Mark I think you said youre not going to show the graphs, but just.
Jason Butler: How should we think about the potential time course of impact on cognition here versus the relatively rapid effects you see on P300 or SORM P300 in the phase one trial? You know, do other, you know, the correlation there between P300 and cognition timelines for other drugs, is that relevant here?
How should we think about the potential time course of impact on on cognition here versus the relatively rapid effects you see on P. 300, <unk> 300 in the phase one trial or the other.
The correlation there between.
P 300 called mission timelines for other drugs is that relevant here.
Speaker Change: Yeah, so let me let me answer it first question about timing, right? So we're looking for what happens over six months.
Yes, So let me let me answer it first Jason Good question about timing right. So we're looking for what happened over six months.
Speaker Change: So we will, at the end of six months, we will announce that there was a difference of X, Y, and Z for P300, right, and ADIS-CoG 11, just to show a difference. Because truly, the ADIS-CoG 11 is really, really important.
So we will at the end of six months, we will announce that there was a difference of X Y and Z four P 300, right and Adas Cog 11, just to show a difference because truly the Adas Cog 11 is really really important.
Speaker Change: But Hans, do you want to enlighten any of that? Oh, Hans, can you mention when the placebo effect goes away over time?
But how do you want to.
Enlighten any of that.
Can you mentioned when the placebo effect goes away over time.
Yes.
Hans Mobius: Yeah, well, in this type of trial, you would expect a placebo response anywhere between 6 and 12 weeks.
And this type of trial, you would expect placebo response.
We were between six and 12 weeks.
But.
Hans Mobius: this is then disappearing and that's why we are running 26-week trials to really escape any potential placebo effect.
This has been disappearing and that's why we are running 26 week trial. It's.
Two really escape.
Any potential placebo effect.
I wanted to add to that.
Hans Mobius: After entry of the baseline, we have the first assessment of both P300 and ADASCOG 11 after two weeks.
After after entry of the baseline.
The first assessment of both pizza.
11 after two weeks and then we have multiple visits.
Hans Mobius: And then we have multiple visits ending with visit eight after 26 weeks.
And then.
Visit eight after 26 weeks so of course.
Hans Mobius: So, of course, we are, at all these time points, looking at the development of P300 and ADASCOG11.
It's all these time points looking at the development.
Of the 308.
11.
Hans Mobius: I'm hoping to show that their development goes hand-in-hand in replication of the data, you know, from the...
Hoping to show that their development goes hand in hand.
Replication of the data as you know from the literature.
Got it and then just a couple quick questions on the shape trials.
Hans Mobius: And then just a couple quick questions on the SHAPE trial.
Hans Mobius: Could you just maybe remind us of the mechanistic rationale in PDD and DLB? Do you see the same kind of...
Could you just maybe remind us of the.
The mechanistic rationale and PDD and B do you see the same kind of.
Hans Mobius: dysfunction in the HGF-Met system that you see in Alzheimer's patients. And then I think it's pretty clear what, you know, the potential impacts of the ACT results on the LIFT trial, but are there any changes that you would consider making to the SHAPE trial based on the results you get from ACT?
Dysfunction in the H, Jeff met system that you see in Alzheimer's patients and then I think it's pretty clear what.
The potential impacts of the of the act results from a lift trial, but are there any changes that you would consider making to the shape trial based on the results you get from <unk>.
Speaker Change: The answer is no. So this is really opening up a quite different type of dementia investigation.
Yes.
No.
So this is really opening up.
Right different type of dementia investigation.
Speaker Change: And we are indeed in a situation where...
And we are indeed in a situation where.
Speaker Change: P300 latency extension has been described also for Parkinson's disease dementia, and the underlying mode of action rationale is very much in keeping with what we have been presenting.
P 300 latency extension has been described also for Parkinson's disease dementia.
And the underlying.
Russia.
It's very much in keeping with what we have.
And presenting.
And after setting before.
Speaker Change: publicizing before, mainly it's the whole cascade of...
It's the whole cascade.
Perfect perfect.
Speaker Change: that do not stop at the microstriatal system. So, the specific neuronal population that is affected in Parkinson's disease, at least in the beginning before it is spreading out,
Do not stop.
The Iqos triathlon system. So it will be specific <unk> population that is affected in Parkinson's disease at least at the beginning before is it spreading out.
<unk>.
Speaker Change: could theoretically benefit from positive modulation of the HDF-MED system. And that's what we are leveraging.
Theoretically.
Benefits from positive modulation of the HTS system.
And Thats, what we are leveraging.
Okay, Great. That's helpful. Thanks for taking the questions.
Thanks, Jason.
Thank you I'll now turn the call back over to Dr. Mark Litton for any closing remarks.
Speaker Change: Thank you. I'll now turn the call back over to Dr. Mark Litton for any closing remarks. Thank you everyone for taking the time today and we're really looking forward to an exciting 2022.
Thank you everyone for taking the time today.
And we're really looking forward to an exciting 2022.
Thanks, so much.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating and you may now disconnect.
[music].
Mark Litton: Thank you.