Q3 2019 Earnings Call
<unk>.
Operator: BF-WATCH TV 2021
Operator: Good afternoon, ladies and gentlemen, and welcome to the Syndax Third Quarter 2019 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star and then zero on your touchtone telephone. And as a reminder, this conference call may be recorded. I would now like to turn the conference over to your host today, Ms. Melissa Force, with Argo Partners. Thank you, Operator.
Melissa Force: Welcome and thank you to those of you joining us on the line for the webcast this afternoon for a review of Syndax's third quarter 2019 financial and operational results. I'm Melissa Forrest with Argo Partners, and with me this afternoon to discuss the results and provide an update on the company's progress are Dr. Briggs Morrison, Chief Executive Officer, and Rick Shea, Chief Financial Officer. Also joining us on the call today for the question and answer session is Michael Metzger, President and Chief Operating Officer, and Dr. Michael Myers, Chief Medical Officer. This call is being accompanied by a slide deck that has been posted on the company's website. So I would ask you to please turn to our forward-looking statements on slide two. Before we begin, I would like to remind you that any statements made during this call that are not historical...
Welcome to this index third quarter 2019 financial results Conference call.
At this time all participants are in the listen only mode. Later, we will conduct a question answer session and instructions will follow with that.
If anyone should requires a century to conference. Please press Star then zero under Touchtone telephones.
And as a reminder, this conference call may be recorded.
I would know what could turn the conference over to your host city, It's Melissa force with Argos partners.
Melissa Force: within the meaning of the Private Securities Litigation Reform Act of 1995. However, actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors. This includes those discussed in the risk factors section of the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the FCC. Any forward-looking statements represent the company's views as of today, November 7th, 2019 only. A replay of this call will be available on the company's website following the call. And with that, I'm pleased to turn the call over to Dr. Briggs Morrison, Chief Executive Officer of Syndax.
I.
Thank you operator, welcome and thank you for those of you joining us on the line and the webcast. This afternoon purview us indexes third quarter 2019 financial and operational results.
Most of course with our new partners and with me. This afternoon to discuss the results and provide updates on the Companys progress are Dr. Briggs Morrison.
If executive officer, and Rick Shea Chief Financial Officer.
Also joining us in the call today for the question answer session is Michael Metzger, President and Chief operating Officer, and Dr., Michael Myers, Chief Medical Officer.
This call is being accompanied by a slide deck that has been posted on the Companys website <unk> Peter Please turn to our forward looking statements on slides too.
Dr. Briggs Morrison: Thank you, Melissa, and thank you to everyone for joining us on today's call and webcast. Slide three provides a high-level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before. We recently announced two significant updates for our LEAD program. First, the ECOG Data Safety and Monitoring Board has communicated to us that E2112 has passed its last interim analysis and will proceed to its final analysis at 410 events. This brings us closer to a potential near-term FDA filing, approval, and launch for hormone-receptor-positive metastatic breast cancer. The second important event is that we have begun dosing patients in our Phase 1 Augment 101 trial of our highly selective, rationally designed, menin inhibitor, SNDX5613. As a result of this accomplishment, we are now entering a new and exciting chapter in the evolution of Syndax.
Before we begin I would like termites and he sees they call not historical considered to be for working within the meaning of the private Securities Litigation Reform Act of 99 different.
I.
Actual results may differ materially from those indicated by these statements as a result of various important factors.
[laughter] skus in the risk factor section in the Companys receive quarterly reports on Form 10-Q , that's all those other reports filed with the FCC.
Any forward looking statements represent the company's views as of today November 720, 19 Oh.
A replay of this call will be available.
Company's website following the call and with that I'm pleased to turn the call LIBOR to Dr. Briggs Morrison, Chief Executive Officer Cinda.
Thank you Melissa and take you to everyone for joining us on today's call and webcast.
Slide three provides a high level summary of our current corporate priorities as we strive to realize a future in which people with cancer live longer and better than ever before.
We recently announced two significant updates for our lead program first the E. Cogs data safety monitoring board has communicated to us that he 20 112 has passed its last interim analysis and will proceed to its final analysis at 410 event.
Dr. Briggs Morrison: The SNDX 5613 program takes us into the treatment of genetically defined acute leukemias and importantly broadens our portfolio. Both programs have the potential to become important new medicines. We expect to know much more about the future prospects of both Intenestat and S&DX5613 over the next 6-12 months. Let's review these opportunities in some greater detail.
This brings us closer to a potential near term ft, a filing approval and launch in hormone receptor positive metastatic breast cancer.
Second important event is that we had began dosing patients in our phase one augment won a one trial of our highly selective rationally designed men isn't anywhere else in Dx 56 13.
Dr. Briggs Morrison: Slide 4 summarizes the design of the Phase 3 trial of antinostat in hormone receptor-positive HER2-negative breast cancer. The trial randomized 608 patients to eczemastine plus placebo versus eczemastine plus antennastat, and the focus of this trial is now clearly on the final overall survival analysis. However, final analysis will be conducted once there are 410 events.
As a result of this accomplishment we are now entering a new and exciting chapter in the evolution of Syndax. Yes Index 56, 13 program takes us into the treatment of genetically defined acute leukemias and importantly, broadens our portfolio.
Both programs have the potential to become important new medicine.
We expect to know much more about the future prospects of both antenna stat and acid Dx 56, 13 over the next 612 months.
Dr. Briggs Morrison: Based upon our modeling, we believe that the final readout of E2112, based on the full 410 events, will occur sometime in the second quarter of next year. A positive outcome would allow us to file for regulatory approval in the U.S. based upon the terms of our breakthrough therapy designation for hormone receptor positive metastatic breast cancer and our special protocol assessment with the FDA. Our team is prepared to submit a regulatory filing, should the trial be positive, within about six months of receiving the data from ECOG, which would set us up to launch Antenistat in 2021. As we have now successfully passed five futility analyses and are poised for the final readout of the trial, I'd like to take a moment to remind everyone of the assumptions that were used in the design of the E2112 study.
Let's review these opportunities and some greater detail.
Slide four summarizes the design of the phase three trial of antenna sat in hormone receptor positive hertwo negative breast cancer.
The trial randomized 608 patients to exit methane placebo <unk> versus ex the Mustang plus antenna staff and the focus of this trial is now clearly on the final overall survival analysis.
The final analysis will be conducted once there are 410 event.
Based upon our modeling we believed that the final read out of each 20 112 based on the full 410 events will occur sometime in the second quarter of next year.
Positive outcome would allow us to file for regulatory approval in the U.S., but.
Based upon the terms of our breakthrough therapy designation in hormone receptor positive metastatic breast cancer and our special protocol assessment with the FDA.
Our team is prepared to submit a regulatory filing should the trial be positive within about six months of receiving the data from ECOG, which would set us up to launch in tennis that 2021.
Dr. Briggs Morrison: The trial has 80% power to detect a hazard ratio of 0.75, and the maximum hazard ratio that would yield a statistically significant positive trial is 0.82. Based upon the design assumptions, if E2112 reached a hazard ratio of 0.82, that would indicate that patients receiving the combination had about a five-month improvement in median overall survival, from about 22 months in the control arm to about 27 months in the combination. Our market research indicates that this magnitude of benefit in overall survival is perceived by prescribing physicians to be important and clinically meaningful. We remain confident in the potential for E2112 to be a positive trial. Slide five emphasizes the potential for the atenostat-examestane regimen to be the preferred agent after a first-line aromatase inhibitor, which is typically given either as a single agent or in combination with CDK-461.
As you have now successfully passed five futility analyses and are poised for the final read out of the trial I'd take a moment to remind everyone of the assumptions that reuse in the design of the 20 112 study.
Trod, 80% power to detect a hazard ratio of <unk> 0.75, the Maxim hazard ratio that would yield a statistically significant positive trial 0.82.
Based upon the design assumptions, if he 21 called reached a hazard ratio of pointing to that would indicate that patients receiving the combination had about a five month improvement in median overall survival from about 22 month median overall survival in the control arm to about 27 months median overall survival in the combination arm.
Our market research indicates that this magnitude of benefit in overall survival is perceived by prescribing physicians to be important and clinically meaningful.
We remain confident and the potential for Etwenty 112 to be a positive trial.
Slide five emphasizes the potential for the attendance that exit methane regimen to be the preferred agent. After a first line care imitates inhibitor, which is typically given either at single agent or in combination with a CDK for six inhibitor.
Dr. Briggs Morrison: Our current estimate is that between a third and half of the patients in A2112 will have received a CDK4-6 inhibitor prior to entering our trial. Thus, we should have a highly relevant data set in the post-CDK4-6 patient population. In our opinion, the rapid adoption of CDK4-6 inhibitors, such as Ibrance, in the first-line setting underscores the desire of physicians and patients to improve the outcomes associated with anti-estrogen therapy. In the setting of a positive E2112 result, we would expect Antennastat to achieve similar widespread use.
Current estimates that between third and half of the patients in each one of my 12, well have received a CDK for six inhibitor prior to entering our trial. Thus we should have a highly relevant data set in the post CDK for six patient population.
In our opinion the rapid adoption of CDK for six inhibitors, such as high brands in the first line setting underscores the desire of physicians and patients to improve the outcomes associated with anti estrogen therapy.
And the setting of a positive Etwenty 112 result, we would expect intend to stack to achieve similar widespread use.
Dr. Briggs Morrison: This population of patients is substantial, with an estimated 34,000 patients each year who go on to receive hormone therapy after failing first-line therapy and who could therefore be eligible to receive Intinistat. Importantly, we will be prepared to launch Intinistat in the U.S. on our own, and we are actively building out our internal commercial team to ensure we are well-positioned for the potential launch of Intinistat in 2021. Let me now turn to SNDX5613, our genetically targeted agent. Yesterday, we announced the exciting news that the first patient has been dosed in the Augment 101 trial. I'll review that trial shortly, but first, we'd like to provide a brief overview of SNDX5613. Slide 6 summarizes the biology that underlies the development of SNDX5613. Mixed lineage leukemias are driven by a fusion protein known as MLLR. This fusion protein is half derived from MLL1 and half derived from a variety of fusion protein partners. For fans of Greek mythology, you can think of the fusion protein as a centaur, a mythological creature that is half human and half horse.
This population of patients is substantial with an estimated 34000 patients each year, who go on to receive hormone therapy. After failing first line therapy and it would therefore be eligible to receive the antenna sat regimen.
Accordingly, we will be prepared to launch in tennis that in the U.S. on our own and we are actively building out our internal commercial team to ensure we are well positioned for the potential launch of antennas that in 2021.
Let me now turn to Essen Dx 56, 13 are genetically targeted agent yesterday, we announced the exciting news at the first patient has been dosed in the augment one or one trial I'll review that trial, shortly but first I'd like to provide a brief overview of Essen Dxi 630.
Slide six summarizes the biology that underlies the development of Essen Dx 56 30.
Mixed lineage leukemia are driven by fusion protein known it's MLL R. This fusion protein is half derived from MLL, one and half derived from a variety of fusion protein protein partners.
For the fans of Greek mythology, you can think of the fusion protein as a sentara mythological creature that is half human and half port.
Dr. Briggs Morrison: The MLL half of the fusion protein binds to menin, a scaffolding protein involved in activating transcription, while the other half is responsible for recruiting a cancer-producing transcription program. This interaction between menin and the MLL1 half of the fusion protein has been defined at the molecular level, and as illustrated on slide 7, SNDX5613 has been rationally designed to block this interaction. SNDX5613 is a potent and specific orally available small molecule. Slide 8 is an illustration of how the fusion protein causes cancer and how SNDX5613 should work. In the left panel, we see the MLL1 portion of the fusion protein bound to menin and the fusion partner half of the protein, attracting a multi-protein complex to DNA. This results in the activation of a family of genes that cause cancer. In the panel on the right, you can see that SNDX5613 binds to menin, displacing the fusion protein and its accompanying multi-protein complex. The genes that were activated are turned off, and the cancer cell differentiates and dies.
Yeah, well half of the fusion protein binds to men in scaffolding protein involved in activating transcription while the other half is responsible for recruiting cancer producing transcription program.
Interaction between men and the MLL one half of the fusion protein has been defined at the molecular level and as illustrated on slide seven Essen Dx 56, 13 has been rationally designed to block this interaction.
Yes, and Dx 56, 13, as a potent and specific orally available small molecule.
Flight team did an illustration of how that fusion protein causes cancer and how Essen Dx 56, 13 should work in the left panel, we see the MLL one portion of the fusion protein bound to men.
Infusion partner half of the protein attracting a multi protein complex to DNA.
This results in activation of a family of genes that cause cancer.
In the panel on the right you can see that Essen Dx 56, 13 binds to mention displacing the fusion protein and its accompanying multi protein complex.
The genes that were activated our turned off and the cancer cell differentiates and die.
Dr. Briggs Morrison: We've presented extensive preclinical data showing that this mechanism has potent and sustained anti-cancer effects in numerous in vivo models of both MLLR leukemias and NPM1 mutant leukemias. On slide nine, we summarize the first in human trial in what we call the Accelerated Understanding of Menin Inhibition, or AUGMENT, program. The first in-human clinical trial is a combined Phase I-Phase II trial. The Phase I portion is a dose escalation trial designed to identify the maximum tolerated dose and a recommended Phase II dose of SNDX5613. Patients with relapse or refractory acute leukemia will be enrolled and will take SNDX5613 daily by mouth until they experience either progressive disease or unacceptable toxicity. The first 28 days of dosing will serve as the period in which safety is evaluated for determining dose escalation.
Be presented extensive preclinical data showing that this mechanism has potent and sustained anticancer effects in numerous invivo models adult MLL R leukemias and NPM one immune leukemia.
On slide nine we summarize the first in human trial in what we call the accelerated understanding of men inhibition or augment program.
The first in human clinical trial is combined phase one phase two trial a phase one portion is a dose escalation trial designed to identify the maximum tolerated dose handy recommended phase two dose of Essen Dx 56 13.
Patients with relapsed or refractory acute leukemia will be enrolled and we'll take Essen Dx 56, 13 daily by mouth until they experienced either progressive disease or unacceptable toxicity.
The first 28 days of dosing will serve as the appeared in which safety is evaluated for determining dose escalation.
Dr. Briggs Morrison: Patients are not required to have specific genetic abnormalities in order to enroll in the Phase 1 portion of the study. The first cohorts follow an accelerated dose titration with only one patient required per cohort. Upon entering a pre-specified label, or encountering a pre-specified label of toxicity, the trial will convert to a standard 3 plus 3 design.
Patients are not required to how specific genetic abnormalities in order to enroll in the phase one portion of the study.
The first cohorts follow accelerated dose titration with only one page required per cohort upon entering a pre specified label upon encountering a pre specified labeled up toxicity and trial will convert to a standard three plus three design.
Dr. Briggs Morrison: We will carefully assess pharmacokinetics, safety, and efficacy. It is anticipated that upwards of 30 patients may be enrolled in the Phase I portion, with a precise number dependent on the number of cohorts that need to be explored and the toxicities that are encountered. We announced this week that enrollment in the Augment 101 trial has commenced with our first patient in the first single patient cohort. I want to emphasize that PK analysis is a key component of the phase one trial. Our preclinical data indicate that the Menin-MLLR interaction needs to be continuously inhibited in order to achieve optimal efficacy.
We will carefully assess pharmacokinetics safety and efficacy.
As anticipated upwards of 30 patients maybe enrolled into phase one portion with a precise number dependent on the number of cohorts that need to be explored and the toxicities that are encountered.
We announced this week that enrollment the augment one on one trial has commenced with our first patient in the first single patient cohort.
I want to emphasize it the PK analysis is a key component of the phase one trial, our preclinical indicate data indicates that the men in MLL R interaction needs to be continuously inhibit in order to achieve optimal advocacy and so we will be carefully examining the drug exposures in patients to assess whether we are de indeed.
Dr. Briggs Morrison: So we will be carefully examining the drug exposures in patients to assess whether we are indeed achieving adequate target coverage. We look forward to seeing these initial PK data in the first-dose cohorts, as those data will significantly inform the likelihood and timing of single-agent efficacy in the MLLR rearranged and NPM1 mutant leukemic population. Given that patients are not required to have specific genetic abnormalities in order to enroll in the phase 1 portion of the trial, we believe that PK data from the phase 1 portion could be more informative than the efficacy assessments, with efficacy being an exploratory objective. Furthermore, we believe that safely achieving adequate target coverage in the Phase I trials could bode well for establishing efficacy in the Phase II trials. Once a recommended Phase 2 dose is established, the Phase 2 trial will proceed to enroll three distinct expansion cohorts, each of which consists of a specific, genetically defined, relapsed, or refractory acute leukemia. The three cohorts are adults with MLLR acute lymphoid leukemia, ALL, adults with MLLR acute myeloid leukemia, AML, and adults with NPM1 mutant.
Achieving adequate target coverage.
We look forward to seeing these initial <unk> PK data in the first dose cohorts as those data will significantly in formed a likelihood and timing of single agent efficacy in the MLL R rearranged and PMN, one mute leukemic population.
Given that patients are not required to have specific genetic abnormalities in order to enroll in the phase one portion of the trial, we believe that PK data from the phase one portion could be more informative Andy efficacy assessments with efficacy being an exploratory objective.
Furthermore, we believe that safely achieving adequate target coverage in the phase one trial could bode well for establishing efficacy in the phase two portion.
Once a recommended phase two dose is established the phase two trial will proceed to enroll three distinct expansion cohorts each of which consists of a specific genetically defined relapsed or refractory acute leukemia.
The three cohorts are adults with MLL R acute lymphocytic leukemia halo adults with MLL R acute myeloid leukemia, and email and adults with NPM want to mute email.
Dr. Briggs Morrison: The Phase 2 portion will further characterize the safety of SNDX5613 and will provide an initial estimate of the complete response rate as the primary measure of therapeutic benefit. We know that a lot of people, patients, physicians, and investors are eager to see initial data from the first Augment trial. Given that we are just getting the trial up and running, it's not possible to provide specific guidance as to when we will present data.
The phase two portion will further characterize the safety of Essen Dx 56, 13 and will provide an initial estimate of the complete response rate as the primary measure of therapeutic benefit.
We know that a lot of people patients physicians and investors are eager to see initial data from the first augment trial.
Given that we're just getting the trial up and running it's not possible possible to provide specific guidance as to when we will present data.
Dr. Briggs Morrison: As of now, we expect to report initial clinical data from the trial in 2020. We should be able to give you a better sense of the data timing as the trial progresses. In addition, we are eager to advance this molecule into the pediatric population. It is a key component of our overall strategy, and we will have more to say about the details of the pediatric timing and approach on a future call. We know pediatric leukemias with MLLR rearrangements represent a significant unmet medical need, and we are eager to work with the pediatric oncology community to bring SNDX5613 to their patients. Based upon preclinical data and the underlying biology of the pathway, we are expecting evidence of single-agent activity. As a result, there could be a rapid and straightforward clinical development path for 5613, perhaps similar to the path taken for agents addressing patients with split 3 or IDH mutations. As we continue to learn more about the potential of SNDX5613 in acute leukemia, we see this molecule becoming an additional and important value driver for syndicates.
As of now we expect to report initial clinical data from the trial in 2020, we should be able to give you a better sense of the data timing as a trial progress.
In addition, we are eager to advance this molecule into the pediatric population. It is a key component of our overall strategy and we will have more to say about the details of the pediatric timing and approach on a future call.
We know pediatric leukemias with MLL R. Rearrangements represents a significant unmet medical need and were eager to work with the pediatric oncology community to bring Essen Dx 56 13 to their patients.
Based upon preclinical data and the underlying biology of the pathway. We are expecting evidence of single agent activity. As a result, there could be a rapid and straight forward clinical development path for 56, 13, perhaps similar to the path taken for agents addressing patients with what three or IDH mutation.
As you continue to learn more about the potential of Essen Dx 56, 13 in acute leukemia, we see this molecule, becoming an additional and important value driver for Cindy.
Dr. Briggs Morrison: Let me now turn to slide 10, and SNDX6352, our potential best-in-class monoclonal antibody therapy targeting the CSF1 receptor. We are conducting a trial testing 6352 as monotherapy in chronic graft-versus-host disease. Chronic graft-versus-host disease is a frequent complication of hematopoietic stem cell transplantation wherein the donor-derived immune cells contribute to the initiation and development of fibrosis and manifestation of many of the advanced disease symptoms. In preclinical models, blockade of the CSF1-CSF1R axis with an antibody can result in the depletion of donor macrophages, thereby I mentioned on our last call that when our IND was cleared for this study, the FDA required that we limit enrollment to patients whose disease had progressed after both steroids and ibrutinib therapy. However, as ibrutinib is not currently frequently used to treat this population, enrollment has been a bit slower than anticipated.
Let me now turn to slide 10, and Essen Dx 60, 352, our potential best in class monoclonal antibody therapy targeting the CSF one receptor [laughter], we're conducting a trial testing 60 352 as monotherapy in chronic graft versus host disease.
Graft versus host disease is a frequent complication of a matter of what extent cell transplantation, whereas the donor derived immune cells contribute to the initiation and development of fibrosis and manifestation of many of the advanced disease symptoms.
Preclinical models blockade of the CSF, one CSF one our axis within antibody you can result in depletion of donor MACRA macrophages, their pipe, preventing and reducing chronic graft versus host.
We believe that chronic graft versus host disease represents an important clinical opportunities.
I mentioned last call that when our eye in D. was cleared for this study yeah FDA required that we limit enrollment to patients whose disease had progressed after both steroids and I Bruton IV therapy.
However, as I brewed and it was not currently frequently used to treat this population enrollment has been slower than anticipated.
Dr. Briggs Morrison: We've now worked with the FDA to modify the enrollment criteria, so we are now in a position to enroll a broader set of patients. We hope to provide an update on this program in the second half of next year. Finally, slide 11 summarizes the transactions that led to the acquisition of the Mennon MLR program and the SNDX 6352 program. We believe that we will be able to continue to expand our pipeline through the acquisition or in-licensing of quality, differentiated assets. We believe that we have the necessary clinical development expertise to bring these compounds through valuable inflection points and expect to remain among preferred partners in such transactions. I will now turn the call over to Rick, who will review our financial results.
I work with the FDA to modify the enrollment criteria. We're now in a position to enroll a broader set of patients.
We hope to provide an update on this program in the second half of next year.
Finally side 11 summarizes transactions that led to the acquisition of the men and while our program Andy SMB X 60, 352 program. We believe that we will be able to continue to expand our pipeline through the acquisition or in licensing quality differentiated assets.
I'll leave that we have the necessary clinical development expertise to bring these compounds through valuable inflection points and expect to remain among preferred partner such transaction.
I'll now turn the call over to Rick who will review our financial results.
Rick Shea: Thank you, Briggs. The results of our operations for the third quarter of 2019 and the comparison to the prior year periods are included in our press release, so I won't repeat them in these remarks. Additional financial details are available in our quarterly report on Form 10-Q, which we filed today. Turning to slide 12, we ended the third quarter of 2019 with $72.2 million in cash and 31.6 million shares and pre-funded warrants outstanding. The net change in cash for Q3 was a decrease of $8.3 million. The net loss for the quarter of $12.8 million was offset by non-cash items of $1.6 million and a net favorable balance sheet change of just under $3 million.
Thank you breaks.
Results of our operations for the third quarter of 2019 in the comparison to the prior year periods are included in our press release, So I won't repeat them in these remarks additional financial details are available on our quarterly report on Form 10-Q , which we have filed today.
Turning to slide 12, we ended the third quarter of 2019 with $72.2 million in cash and 31.6 million shares and pre funded warrants outstanding.
And that changing cash for Q3 was a decrease of $8.3 million.
The net loss for the quarter of $12.8 million was offset by noncash items of $1.6 million and a net favorable balance sheet change of just under $3 million.
Rick Shea: Looking ahead, I'd like to provide updated financial guidance for both Q4 and for full year 2019. For the fourth quarter of 2019, we expect R&D expenses to be $11-12 million and total operating expenses to be $15-16 million, including approximately $1.5 million of non-cash stock compensation expenses. For the full year 2019, we expect R&D expenses of $45 to $46 million and total operating expenses of $60 to $62 million. Operating expenses for 2019 are expected to include non-cash stock compensation expense of $6 million. And our interest income is approximately $2 million. So our net cash burn for 2019 is expected to be between $52 and $54 million. Cash at year-end 2019 is expected to be approximately $57 million, and this current cash will allow us to operate the company to achieve key milestones for our prioritized programs. Specifically, O.S. Results for the E2112 study are anticipated in Q2 of 2020, and early proof of concept for our targeted menin inhibitor, SNDX5613. I'll now turn the call back over to Briggs.
Looking ahead I'd like to provide updated financial guidance for both Q4 and for full year 2019.
For the fourth quarter 2019, we expect R&D expenses.
To be $11 million to $12 million and total operating expenses to be $15 million to $16 million.
Including approximately one and a half million dollars of non cash stock compensation expense.
For the full year 2019, we expect R&D expenses of $45 million to $46 million and total operating expenses of $60 million to $62 million.
Operating expenses for 2019 are expected to include noncash stock compensation expense of $6 million.
And our interest income is approximately $2 million. So our net cash burn for 2019 is expected to be $52 million to $54 million.
Cash at year end 2019 is expected to be approximately $57 million.
And this current cash will allow us to operate the company to achieve key milestones for our prioritize programs, specifically or Wes results for the 20 112 study results anticipated in Q2 2020 and early proof of concept for.
Targeted men inhibitor Sdx 56 13.
I'll now turn the call back over to bricks.
Dr. Briggs Morrison: Thanks very much, Rick. I'd like to close our call with a clear summary of our company priorities and important near-term milestones. We believe that a positive OS result in E2112 would be transformative for Syndax and create significant shareholder value, and we anticipate a final readout in the second quarter of 2020. We also believe that SNDX5613, our Menin MLLR inhibitor, is well-poised for near-term proof-of-concept data. We believe that safely achieving adequate target coverage in the phase one trial could de-risk this program with single-agent activity in patients with either MLLR or NPM1 mutant leukemia, providing clinical proof-of-concept and enabling early regulatory clarity in planning for next steps. For 6352, we are expecting initial efficacy data for chronic GVHD in the second half of next year.
Thanks, very much Rick I like to close our call with a clear summary of our company priorities an important near term milestones.
We believe that a positive west result in 20, 112 would be transformative for syntax and create significant shareholder value and we anticipate a final read out in the second quarter of 2020.
We also believe that SMB expertise 613, our men in MLL R inhibitor is well poised for near term proof of concept data, we believe that safely achieving adequate target coverage in the phase one trial could de risk. This program with senior single agent activity in patients with either MLL R core NPM, one meeting leukemia, providing.
Clinical proof of concept and enabling early regulatory clay clarity and planning for next step.
For 60 352, we are expecting initial efficacy data in chronic gvhd in the second half of next year.
Dr. Briggs Morrison: Finally, we are optimistic that we will continue to identify and bring in novel molecules to deepen our portfolio. We have a proven track record of delivering on this pillar of our strategy, and I believe this remains a core strength of our company. As always, I would like to thank the team here at Syndax, our collaborators, and, most importantly, the patients, trial sites, and investigators involved with our clinical program. With that, I'd like to open the call to questions.
Finally, we are optimistic that we will continue to identify and bring in novel molecules to deepen our portfolio.
Proven track record of delivering on this pillar of our strategy and I believe this remains a core strength of our company.
As always I would like to thank the team here its index, our collaborators and most importantly, importantly, the patient trial sites and investigators involved with our clinical program.
With that I'd like to open the call for questions.
Thank you if you have a question at this time, please first start and the number one on your Touchtone telephone and if your question, it's been answered or you wish to removes yourself from the Q.
Operator: Thank you. If you have a question at this time, please press star and the number one on your touchtone telephone, and if your question has been answered or you wish to remove yourself from the queue, please press the pound button. And your first question comes from the line of Chris Shibutani of Cowen. Chris, your line is now open. Great.
Please press the pound.
And your first question comes from the line of Chris Shibutani of Cowen Chris. Your line is now open.
Great. Thank you very much Briggs and team appreciate all the update on the programs a lot to look forward to certainly the next 12 months, it's like I, just ask for a little bit more background to help us understand what we can expect from the augment trial. It sounds as if in terms of patient selection standpoint, you're not going to be requiring any.
Chris Shibutani: Thank you very much, Briggs and team. Appreciate all the updates on the programs. A lot to look forward to, certainly, in the next 12 months.
Chris Shibutani: If I could just ask for a little bit more background to help us understand what we can expect from the AUGMENT trial. It sounds as if, in terms of patient selection, you're not going to be requiring any specific genetic profile. Therefore, what should we contemplate might be the mix of patients in that study? And then can you also help us with giving us a sense for at what time point you'll be looking to measure? Efficacy, particularly in the Phase 1 study, and in particular, also, you have the CR, which I believe is kind of the gold standard from a regulatory standpoint. I think in leukemia, there's a lot of discussion about different aspects of complete response rate, CRI, CRH, and, as well now, minimal residual disease. So can you help us understand, you know, any additional parameters that you think would be helpful to help us understand the efficacy profile?
Specific genetic profile, therefore, what should be contemplate might be the mix of patients in that study and then can you also help us with giving us a sense for at what time point, you'll be looking to measure.
Africa.
So in the phase one study.
And in particular also you have the CR, which I believe it's kind of gold standard from a regulatory standpoint, I think in leukemia, there's a lot of discussion about different aspects of complete response rate.
Yes, I see our age and as well now minimal residual disease. So can you help us understand any additional parameters that you think would be helpful to help us understand the efficacy profile.
Dr. Briggs Morrison: Great. Thanks so much, Chris, for your question. So, the first point on a mix of patients. You're correct that we do not require that there be either MLLR or NPM1 mutations in the Phase I portion. Having said that, I think as we've talked with investigators to get the trial up and running, they're particularly interested in enrolling those types of patients. So, we would not be surprised to see even the Phase I portion enriched for patients who have either MLLR or NPM1. I can't tell you exactly what that mix will be, but we would not be surprised to see a pretty good enrichment.
Great. Thanks, so much Chris for your question. So I first the first point on the mix of patients. So you're correct that we do not require that there be either MLL R and PMO mutations in the phase one portion.
Having said that I think as we've talked with investigators to get the trial up and running there, particularly interested in the enrolling those types of patients. So we would not be surprised to see the even the phase one portion enriched for patients who have either MLL R. NPM one I can't tell you exactly what that mix will be but we would we would not be.
Price to see a pretty good enrichment the time point at which you measure efficacy. So again I think if we if we think about the analogs of IDH inhibitors in foot three inhibitors.
Dr. Briggs Morrison: The time point at which you measure efficacy. So, again, I think if we think about the analogs of IDH inhibitors and FLT3 inhibitors, oral agents for targeted mutations in leukemia, the time to response can be anywhere from a month to six months. So, you know, we'll be monitoring that on an ongoing basis as the patients continue to get treated. You're correct that the gold standard in leukemia is complete response. There are other intermediates, I guess we would call them that.
Oral agents were targeted mutations in leukemia.
Time to response can be anywhere from a month to six month.
So we'll be monitoring that an ongoing basis.
As the patients could you get treated youre correct that the gold standard in leukemia is complete response there are other.
Intermediate I guess, we would call them.
Dr. Briggs Morrison: CRI is basically a complete response with incomplete bone marrow recovery. CRH is basically you have half the normal amounts of platelets and neutrophils. But CR, just straight flat CR, tends to be the end point, at least as we've talked with leukemia docs, that is the best predictor of eventually showing overall survival. So in the phase two portion, we do have CR or CRH. CRH seems to be, by many people, a good marker of efficacy. And then there is your last question about MRD. As you know, there's a lot of work going on with MRD and what is, from a regulatory point of view and from a clinical point of view, validated assays to assess MRD both in ALL and AML. We're continuing to monitor that. Thus far, I don't think from a regulatory point of view that it's been acceptable to simply take patients and make them MRD positive to negative. They really want to see pathologic CRs from patients who have frank leukemia, but that's an evolving area of the science, and we'll sort of see how it progresses.
CR I would is basically complete response with incomplete bone marrow recovery CR H is essentially you have half normal amounts of platelets and neutrophils, but do you see our just straight flat CR tends to be the the endpoint at least as we've talked with leukemia docs that is the best predictor of eventually.
Showing overall survival so in that in the phase two portion, we do have CR or see our age it seems to be.
By many people a good marker of efficacy, but and then your last question about MRT. So.
As you know there's a lot of work going on with MRT and what is from a regulatory point of view and from a clinical point of view validated assay is to assess MRT both in AOL in AML.
We're continuing to monitor that.
Thus far I don't think from a regulatory point of view, it's been acceptable to simply take patients and make them MRT positive to negative they really want to see pathlogic see ours for patients who have Frank leukemia, but that's it an evolving area of the of the science and we'll sort of see how it how it progressed.
Dr. Briggs Morrison: Great. And then there is one last aspect. With the Phase I, you mentioned potentially 30 patients is what you might be aiming for, ultimately then taking it into Phase II and III subgroups of subtypes of leukemia. Should we expect that you will be able to, maybe with some intention, try to get a relatively balanced number of the different types of leukemia from the Phase I, or is that not how you're going to be designing or executing the trial?
Great and then one last aspect with assays one dimension potentially 30 patients is what you might be aiming for ultimately then taking it into phase two and three sub groups Oh some types of leukemia.
We expect that you'll be able to to maybe with some intention tried to get a relatively balanced number of the different types of looking there from the phase one or is that the way you're going to be design, you're executing the trial.
Dr. Briggs Morrison: So I think phase one is really focused on safety and rapid execution of enrolling patients and assessing safety. So we're not trying to guide physicians or investigators as to enriching one versus the other and trying to slow down one arm or increase another arm. It's really just trying to get through quickly so we can get to the recommended phase two dose and then do a detailed assessment of each genetic lesion in phase two. So phase one is, as I said earlier, I think it will be enriched for MLLR and NPM1, but it won't be 100%. But I can't really give you a breakdown of those three different arms in phase two and how much of each of those we'll see in phase one.
In the phase one is really focused on safety and rapid execution of enrolling patients in assessing safety. So we're not trying to guide physicians, our investigators as to enriching one versus the other and trying to slow down one arm or increase in other arm. It's really just try to get through quickly. So we can get to recommended phase two.
Dose and then do detailed assessment of each snack lesion in phase II. So.
Phase one is as I said earlier I think it'll be enriched for MLL R. And then PMN, one not not 100%.
And but I can't really give you a breakdown of of those three different harms in phase two how much of each of those we'll see in phase one.
Chris Shibutani: Okay, great. Thank you very much for the clarification.
Okay, great. Thank you very much the classification.
Operator: Thank you.
Thank you.
Next question comes from the line of David Lebowitz of Morgan Stanley David Your line is now open.
David Lebowitz: This next question comes from the line of David Lebowitz of Morgan Stanley. David, your line is now open.
Dr. Briggs Morrison: Thank you very much for taking my question. With the final analysis from E-2012 coming up, assuming that a positive analysis would come through, what type of preparations would you have to put into play, I guess given where your organization stands now, to be able to... Prepare for, I mean the submission sounds like it's far along, but to prepare now for a potential launch downstream.
Thank you very much for taking my question.
With the final analysis from eat two on two coming up.
Assuming that a positive analysis would come through what type of preparations what do you have to put into play I guess, given where your organization stands now.
To be able to.
Prepare for I mean, the submission sounds like it's how far along like repair now for a potential launch downstream.
Yeah, So you're right that the regulatory submission piece, where it really in good shape for and I'll, let Michael Metzger comment on the commercial preparation.
Michael A. Metzger: Yeah, so you're right that the regulatory submission piece we're really in good shape for, and I'll let Michael Metzger comment on the commercial preparation.
Dr. Briggs Morrison: Thanks, David. So, yes, I think there's always quite a bit of work to do before you're able to launch a drug, and I think we're planning to launch this product in the U.S. on our own, and so we'll be prepared to do that, and we're taking necessary steps now to put necessary infrastructure, specifically internal commercial team together that could be in position to launch that drug, and so we're preparing to do that now, how we actually ultimately launch the drug Ex-US will look to partner most likely and will be prepared in the US to do it on our own.
Thanks, David So, yes, I think there's there's always quite a bit of work to do before you're able to launch a drug and I think.
We're planning to launch this product to the U.S. on our own and so we'll be prepared to do that and we're taking necessary steps now.
To put but necessary infrastructure.
Specifically internal.
Commercial team together that could could be in position to launch that drug and so we're we're preparing to do that now.
In terms of.
How we actually ultimately launched the drug ex US, we'll look to partner most likely.
And we'll be prepared in the us to do it on our.
Thank you for that and as far as a SNB X 65 to <unk>.
David Lebowitz: Thank you for that. And as far as SNDX 6352 is concerned, does GVHD manifest itself similarly in adult and adolescent populations?
Does gvhd manifest itself similarly in adult and adolescent populations.
Dr. Briggs Morrison: To my knowledge, yes. Remember, GVHD can affect multiple different organ systems, but to my knowledge, there's nothing unique about how it presents in adolescents versus adults.
To my knowledge, yes.
Matt I mean, remember gvhd can affect multiple different Oregon systems, but to my knowledge. The theres nothing unique about how how it presents in adolescence versus adults.
Thanks for taking my questions.
Operator: Thanks for taking my questions. Thanks, David. And your next question comes from the line of Christopher Murai of Nomura Instamets. Christopher, your line is now open. This is Jackson Harvey on behalf of Christopher Murai.
Thanks, David.
Your next question comes from the line of Christopher Myride Nomura Instinet Christopher Your line is now.
Okay.
But this is Jackson Harvey on for Chris to Fair MRI. Thank you for taking my questions. The first one is for incentive stat. If if the trial comes up negative well you people to do any subset analysis to tighten suffice to population that might be a good responded.
Christopher Murai: Thank you for taking my questions. The first one is for Intenistat. If the trial comes up negative, will you be able to do any subset analysis to identify a subpopulation that might be a good responder? The next question is about the menin inhibitor. Do you plan on presenting any preclinical data in the first half of 2020? Thank you.
The next question is about the men in inhibitor.
Do you plan on presenting any preclinical data in the first half of 2020. Thank you.
Dr. Briggs Morrison: Right. Thanks, Jackson, for your questions.
Right. Thanks Jackson for your questions. So the first one if the trials negative.
Dr. Briggs Morrison: So the first one, if the trial's negative... One can always go back and look at subsets. But it's generally not possible to rescue a negative trial by saying that you saw efficacy in a subset of patients. That is always perceived to be hypothesis-generating and could be the ground for another trial if you wanted to do another trial. I think our own, as we sit here today, I think if the trial were negative, unless there was something very, very compelling in one of those post hoc subset analyses, I don't think so. We would not necessarily have a strong case to go to a regulatory agency, nor would we necessarily have a strong case to do another trial. So I think if it's negative, it's negative.
One can always go back and look at subset.
It's a generally not possible to rescue a negative trial by saying that you saw efficacy in a subset of patients that is always.
Perceived to be a hypothesis generating and could be the ground for another trial. If you wanted to do another trial I think our own a as we sit here today I think if the trial.
Were negative unless there was something very very compelling in one of those co stocks subset analyses I don't think.
We would have a strong case to go to regulatory agency, nor would we necessarily have a strong case do another trial. So I think if it's negative.
It's.
Dr. Briggs Morrison: Your second question about presenting preclinical data, I don't think we have plans just now. A lot of preclinical data, as I said, on the mechanism has already been put into the public domain with a tool count that we call 469. We're looking for opportunities to present preclinical data on the development candidate itself, but I don't know that we have a defined time frame of when that will be available.
It's negative.
Your second question about presenting preclinical data I don't think we have plans just now a lot of preclinical data as it had on the mechanism has already been put into the public domain with a tool count on that we call for six nine we're looking for opportunities to present preclinical data on the development candidate itself, but I don't.
No that we have a defined timeframe of when that will be available.
Great. Thank you.
Your next question comes from the line of birth has let us be T I.
Dr. Briggs Morrison: Your next question comes from the line of Bert Hazlett of DTIG. Bert, your line is now open.
Hurt your line is you know.
Bert Hazlett: Thanks. Yes, I have two questions. First, on 2112 and that program, could you just remind us what the status is with the rest of the world in terms of regulatory activity? You know, it's clear what might happen in the U.S., but if you had any discussions, OUS.
Thanks, Yes, I've two questions first on the 20 112.
And that program could you just remind us what the status is with the rest of world regulatory ER activity.
Clear what might happen in the U.S., but.
If you had a discussions.
Operator: Did you have a second question, Bert, or just that one?
Yes.
Did you have a second question Burger just that one.
Bert Hazlett: The second question was with regard to Mennon and the Augment program. Would you expect there to be different response rates in the subgroups?
The second question was with regard to men and.
The augment program would you expect there to be different.
Response rates in in the subgroups.
Thanks.
Yes.
Okay. So first let me take the rest of world regulatory activity, we have had regulatory consultation in Europe .
Dr. Briggs Morrison: Okay, so first, let me take a look at the rest of the world's regulatory activity. We had regulatory consultations in Europe with regard to 2112 pretty early on, I think after the end, after the phase two study. We have not gone back to have additional conversations.
With regard to 20 112 pretty early on I think after the end after the phase two study.
We have not gone back to have additional conversations I think our our clinical and regulatory team believes that a positive or west trial.
Dr. Briggs Morrison: I think our clinical and regulatory team believes that a positive OS trial would be something that the European regulatory agencies would be willing to take a look at, but we'd have to have a more contemporaneous conversation about that question. So, that's sort of where that stands, and as Michael has pointed out, we would be looking for a partner outside the US, and so we would, obviously, if we were able to find a partner, rely a little bit on their regulatory insight on that question as well. In terms of men and the response rate in different subgroups, what we've seen pre-clinically is that both in MLLR, AML, and ALL samples and NPM1 samples, we see really quite significant activity. So, there's nothing from the pre-clinical data that would suggest that the response rates would be different by subgroup, but that's something we'll have to figure out. That's why we have split out the three subgroups in the Phase II portion of the trial to answer that question in the clinic. Okay, thank you.
Wouldn't be something that the European regulatory agencies would be willing to take a look at but we'd have to go have that a more contemporaneous conversation about that that question.
So that's sort of where that stands as Michael as pointed out we would be looking for a a partner ex us and so we would obviously if we were able to find a partner rely a little bit on their regulatory insight on that question as well.
In terms of men in the response rate in different subgroups, what we've seen preclinically is both in MLL R.
Email and AOL samples and NPM, one samples, we see really quite significant activity. So theres nothing from the preclinical data that would suggest that the response rates would be different by subgroup, but that's something we'll have to figure that that's why we have split out the three sub groups in the phase two portion of the trial is to answer that question in there.
Nick.
Okay. Thank you.
Your last question comes from the line else Madhu Kumar of ours W. Baird.
Madhu Sudhan Kumar: Your last question comes from the line of Madhu Kumar of RW Baird. Marty, your line is now, Hey guys, this is Jennifer on behalf of Madhu. Thanks for taking the question. So I know that you guys discussed the Augment 101 trial and sort of have it as a little bit of a proof of concept, but I'm wondering if you could give us a little bit more detail and sort of maybe let us know how many doses in that trial you would expect to see a signal and then, sort of on the back of that, if you expect to see just primarily PK data or if And then After that, I have one more financial question.
Your line is no.
Hey, guys. This is Jennifer on term I do on thanks for taking the question. So I know that you guys discussed the augment one or one trial and.
I'm sort of having a little bit of a proof of concept, but I'm wondering if you can give us a little bit more detail and sort of maybe let us know how many doses in that trial on you would expect to see a signal and then sort of on the back of that if you expect to see just primarily PK data or if you think there might be an initial therapeutic.
Bob.
And then I have one more financial question after that.
Right. So I think that your question is really about how.
Dr. Briggs Morrison: Right, so I think that your question is really about how many dose escalations do you think we have to go through to get to our recommended phase 2 dose. Obviously, we don't know that as of today.
How many dose Escalations do you think we have to to go through to get to a recommended phase two dose.
Obviously, we don't know that as in your today, we have to the experiment.
Dr. Briggs Morrison: We have to do the experiment. In general, if you look at these phase 1 dose escalations, it's often four or five dose escalations before you get to your therapeutic dose. We're hopeful that we're on the lower end of that. Based upon the projections we've done for PK, we think we will get even at the first dose compared to PK that we think we need for efficacy. We think we're in, again, on the lower end of the number of dose escalations we would need. Whether or not we see an efficacy signal again really depends on the types of patients that are enrolled. If we are fortunate enough to get some of the MLLRs and NPM1s, then there's a potential we'll be able to pick up an efficacy signal as we get to adequate exposures. However, if there are patients who don't have either of those mutations, then from the work we've done so far, we think it would be unlikely to pick up an efficacy signal.
In general if you look at these phase one dose escalations, it's often four or five dose escalations before you get to your therapeutic dose. We're hopeful that we're on the lower end of that based upon the.
Projections, we've done for PK, we think we will get even at the first dose compared to PK that we think we need for efficacy. We think we're in again on the lower end of the number of dose Escalations, we would need.
Whether or not we see an efficacy signal again really depends on the types of patients that are enrolled if we.
Our fortunate enough to get some of the MLL ours and NPM ones, then there's a potential will be able to pick up an efficacy signal as we get to adequate exposures.
If there are patients who don't have either those mutations and it would be from from the work. We've done so far we think it would be unlikely to pick up an efficacy signal.
Dr. Briggs Morrison: And then if you want to ask your financial question,
And then if you want to ask your financial question.
Jennifer: Great, thank you, that was really helpful. So roughly, how do you divide cash firm between AntennaScout 5, 613, and 6352?
Great. Thank you get that was very helpful. So roughly how do you divide cash burn between that's got a five 613.
<unk>.
[laughter].
Rick Shea: As of right now, we don't have a significant cash burn relating to antennastat. It's just the 2012 study and the number of patients that still remain on that study. And 5613, that program is just in phase one, and same thing with 6352. In both of those earlier stage programs, actually, we've had more significant CMC expenses over the past six months or so as we produce material for the clinical studies and get the process squared away on those programs. So you know, I would say our cash burn is spread across the programs. There's no one program that is bearing the brunt of the cash burn.
As of right now.
We don't have a significant cash burn relating.
Two intend to stay out it's just the 2012 study the number of patients, but still remain on that study.
And 56 13.
Program is just in phase one so.
Same thing with 60 352 in both of those earlier stage programs actually we've had more significant.
CMC.
<unk> expenses over the past six months or so as we.
Produce material for the clinical studies and get the process.
Squared away on on those programs so.
No I would say our cash burn to spread across the the programs.
There's no one program that is bearing the brunt of the cash burn.
Great. Thanks, so much.
Jennifer: All right, great. Thanks so much, guys. And we have a follow-up question from the line of Bert Hazlitt. (inaudible)
[noise] then we have a follow up question from the line of Bert Hazlett.
[noise] hurt your line is there going to.
Bert Hazlett: Thank you for taking the follow-up. I was just on the CMC comments. Is there, assuming success with E2112, is there anything in particular that is a gating item, either from the CMC or manufacturing specifically, that might present challenges in terms of a timeline, assuming success in the trial?
Thank you for taking the follow up I was just on the CMC comments.
Are there assuming success with.
20, 112, or there is there anything in particular that is a gating item or either from the CMC or or manufacturing specifically that that that.
Mike White present challenges in terms of a timeline assuming success on trial.
Dr. Briggs Morrison: Yeah, Bert, I'll let Michael Metzger take that question.
Yeah, but I'll, let Michael Metzker take that question.
Michael A. Metzger: However, I think it's safe to say that it has nothing to do with CMC's rate limitation in terms of filing. I think that was your question. And we feel very confident with the process and what we have, so we're in good shape. Okay, thank you.
I've heard that.
I think safe to say that.
Nothing to do is CMC gate rate limiting in terms of filing I think that was your question.
We feel very confident with what with the processes.
What we have so we're in good shape.
Okay. Thank you.
There are no further questions at this time presenters he may continue.
Operator: There are no further questions at this time. Presenters, you may continue.
Dr. Briggs Morrison: So this is Briggs. Thanks everybody for joining in on the call again. We look forward to seeing you at upcoming meetings and thanks again for your time.
So this is Rick thanks, everybody for began joining in on the call.
We look forward to seeing you at upcoming meetings and thanks again for your time.
Thank you so much direct presenter sent to everyone who participated this concludes today's conference call. You may now disconnect have a great team.
Operator: Thank you so much to our presenters and to everyone who participated. This concludes today's conference call. You may now disconnect. Have a great day.
Operator: Copyright 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced